cds algorithms 2005a

Diagnostic Imaging

Evaluation*

Negative

Benign

Suspicious

HighlySuspicious of

Malignancy

Probably

Benign

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2

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w/in 30 days

MassPersists?

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Palpable Mass

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for Primary Care Providers

California Department of Health Services Cancer Detection SectionBreast Expert Workgroup

Third Edition, June, 2005Online at: www.qap.sdsu.edu

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for Primary Care Providers

California Department of Health Services, Cancer Detection SectionBreast Expert Workgroup

Third Edition, June, 2005

Online at: www.qap.sdsu.edu

http://www.sdsu.edu/qap

California Department of Health Services, 2005

Table of Contents

Background and Acknowledgments ..................................................................................................................................................................1

Intended Audience .............................................................................................................................................................................................2

How to Read and Use the Algorithms ................................................................................................................................................................3

Background Information Applicable to All Algorithms .....................................................................................................................................4

Assessment of Risk ............................................................................................................................................................................................8Algorithm 1 ...............................................................................................................................................................................................11

New Palpable Mass .........................................................................................................................................................................................13Algorithm 2 ...............................................................................................................................................................................................15

Abnormal Screening Mammogram with Normal CBE ..................................................................................................................................17Algorithm 3 ...............................................................................................................................................................................................19

Spontaneous Unilateral Nipple Discharge .......................................................................................................................................................20Algorithm 4 ...............................................................................................................................................................................................21

Work-up of Breast Skin Changes/Nipple Retraction .......................................................................................................................................23Algorithm 5 ...............................................................................................................................................................................................25

Breast Pain in a Non-Lactating Woman ...........................................................................................................................................................27Algorithm 6 ...............................................................................................................................................................................................29

Management of Breast Biopsy Results ...........................................................................................................................................................31Algorithm 7 ...............................................................................................................................................................................................33

Appendix A-1: Breast Cancer History And Risk Assessment ........................................................................................................................34

Appendix A-2: Risk Assessment Table ............................................................................................................................................................37

Appendix A-3: Core Compentancies of Clinical Breast Examination .............................................................................................................38

Appendix A-4: CBE Results Documentation Form ........................................................................................................................................39

Appendix A-5: Glossary Of Terms ..................................................................................................................................................................40

Appendix A-6: Bibliography ............................................................................................................................................................................46

Appendix A-7: Previous Edition Acknowledgements .....................................................................................................................................52


PAGE 1Background and Acknowledgments

Breast Cancer Diagnostic Algorithms for Primary Care Providers (Algorithms) is the product of the California Department of Health Services Cancer Detection Section (CDS). The Breast Expert Workgroup, a volunteer panel of California clinicians, provides leadership and consultation to CDS. These algorithms provide guidelines and are based on an informal consensus development process.

CDS administers the state and federally funded Cancer Detection Programs: Every Woman Counts! The program provides free breast and cervical cancer screening and diagnostic services to eligible underserved, low-income women in California. Additionally, CDS provides community outreach and education, quality assurance, professional education and evaluation and research services. The algorithms were originally published in 1997. This third edition incorporates updates on guidelines, research and technologies, especially the use of ultrasound, assessment of risk, and interpretation of pathology. The algorithms, along with other professional education information, is posted to the Internet at www.qap.sdsu.edu

Breast Expert Workgroup Members

Lawrence D. Wagman, MD, Chairman, Division of Surgery, and Director, Department of General Oncologic Surgery, City of Hope National Medical Center, Duarte, CA (Workgroup Chairman)

Lawrence Bassett, MD, Iris Cantor Professor of Breast Imaging, Iris Cantor Center, Los Angeles, CA

Ernie Bodai, MD, Director, Breast Surgical Services, The Breast Health Center Kaiser Permanente, Sacramento, CA

R. James Brenner, MD, Director of Breast Imaging, Eisenberg Keefer Breast Center, St. Johns Hospital, Santa Monica, CA

Barbara Florentine, MD, Medical Director, Department of Pathology, Henry Mayo Hospital, Valencia, CA

Ian Grady, MD, North Valley Breast Center, Redding, CA Patty Hansen, MD, Medical Doctors Imaging, Redding, CA Lydia Howell, MD, Associate Dean, Professor of Pathology, University of

California, Davis, Davis Medical Center, CA George Khoury, MD, Stockton Diagnostic Radiology and Ultrasound,

Stockton, CA

Michael Lagios, MD, Pathologist, St. Mary’s Health Center, San Francisco, CA

Debbie Lawler, FNP, MSN, Santa Ana, CA Britt-Marie Ljung, MD, Professor of Pathology, University of California, San

Francisco, San Francisco, CA Julie Ohnemus, MD, Family Physician, Arcata, CA Linda Olson, MD, Professor of Radiology, University of California, San

Diego, San Diego, CA Maren Scheuner, MD, MPH, FACMG, Visiting Associate Professor, University

of California, LA, School of Public Health, Los Angeles, CA and ATPM Fellow, Office of Genomics and Disease Prevention, CDC, Atlanta, GA

Amy Shaw, MD, Family Physician, Santa Rosa, CA

CDS acknowledges and appreciates the voluntary contributions of these Workgroup members and the many other California-based clinicians who participated in the review phase and/or field-testing of this document.

Project Staff

California Department of Health Services, Cancer Detection Section Marcus Doane, MD, MPH Cathy Hare Joan Hurlock, RN, MS, EdD Kathleen Mintert, LCSW Candace Moorman, MPH (Project Lead) Caroline Peck, MD, MPH, FACOG

San Diego State University Graduate School of Public Health Suzanne Lindsay, PhD, MSW, MPH Sherry Patheal, MPH Marie Falcon, RN, BSN, PHN

Project Consultant

Pro-Health Inc. Nancy Dunn, RN, MS

CDS also acknowledges Liana Lianov, MD, former CDS Chief, for spearheading the development of the 1st and 2nd editions and for serving as a reviewer for this 3rd edition.


PAGE 2Intended Audience

These algorithms were developed for Primary Care Providers (PCPs) who provide breast cancer screening services. These clinicians are the critical providers to ensure that women receive timely and appropriate screening and diagnostic services, including the highest quality initial screening, appropriate referral of abnormal findings, and follow-up with other breast specialists. PCPs are encouraged to use these algorithms to aid clinical decision-making. As with all medical protocols and algorithms, they are intended to serve as an adjunct, not as a replacement for clinical judgment applied to individual cases. Excellent communication must always be maintained among PCPs and radiologists, surgeons, pathologists, and other breast specialists.

Clarifications and Disclaimer Regarding Practice Standards Recommendations in these algorithms are for informational purposes

only. They do not represent the only medically or legally acceptable approach to breast cancer screening and follow-up, but rather are presented with the recognition that there are alternate and acceptable approaches. Deviations do not necessarily represent a breach of a medical standard of care. New knowledge, new technologies, clinical or research data, individual patient needs, and clinical experiences may provide

sound reasons for alternative approaches that may not be described in this document. Use of algorithms or practice guidelines, and careful documentation, are important for continuity of care, risk management and reimbursement.

This document may be copied with full acknowledgment of the source. Please cite: Breast Cancer Diagnostic Algorithms for Primary Care

Providers. Cancer Detection Section, California Department of Health Services, 2005.

Users of the algorithms are requested to direct any written comments or inquiries about updates to:Chief, Professional Education UnitCancer Detection SectionCalifornia Department of Health ServicesMS 7203P.O. Box 997413Sacramento, CA 95899-7413FAX (916) 449-5312E-mail: [email protected]


PAGE 3How to Read and Use the Algorithms

These algorithms graphically describe a logical progression of services designed to facilitate the work-up of a patient presenting with breast symptoms or abnormal breast screening. The graphics provide a visual presentation of decision points throughout the process as well as recommendations or indications for the timing of a referral to a breast specialist for definitive risk assessment, diagnosis, staging and/or treatment. For the purpose of this document, the term “breast specialist” is defined as someone who has special education and/or experience in breast cancer. It is used as a general term because the actual medical discipline of this specialist may vary by community. Thus, a breast specialist may be a risk assessment counselor, radiologist, surgeon, PCP trained in breast disease, etc. PCPs using these algorithms are encouraged to adapt them for each particular patient situation. The special cases or nuances that breast specialists manage are not presented in this document.

The term “concordance” is used to describe agreement between multiple tests or procedures. Concordance implies that a lesion assessed by two or more independent means (i.e., clinical breast examination (CBE) and mammogram), was identified at the same general location in the same breast, and was found to be similar in nature or in degree of suspicion by all assessment techniques. Generally speaking, in the situation of discordance, additional diagnostic work-up is necessary.

The following algorithms are included in this document: Algorithm #1 – Assessment of RiskAlgorithm #2 – New Palpable MassAlgorithm #3 – Abnormal Screening Mammogram with Normal CBEAlgorithm #4 – Spontaneous Unilateral Nipple DischargeAlgorithm #5 – Breast Skin Changes / Nipple RetractionAlgorithm #6 – Breast Pain in a Non-Lactating WomanAlgorithm #7 – Management of Breast Tissue Biopsy Results

Notes for each algorithm provide additional information on the assessment and decision-making guiding principles, including selected terminology, rationales, alternative approaches, and controversies. The Appendices contain additional content related to assessment of risk, clinical, radiologic and pathologic examinations and diagnostic tests. They also provide sample forms for documenting health history and exam findings. A bibliography is included for PCPs who want additional information.

When the algorithm recommends “routine screening” the patient can resume routine (usually annual) breast screening if the most recent examination is normal and there are no new symptoms or complaints. However, if new symptoms or concerns arise in the time interval prior to the next routine screening, it is appropriate to undertake a new diagnostic work-up to address these.


PAGE 4Background Information Applicable to All Algorithms

The American Cancer Society (ACS) 2004 guidelines for early breast cancer detection consist of a clinical breast examination (CBE) every three years in women between the ages of 20 and 39 years, and annually for women aged 40 and older. Women at average risk should begin regular mammography at age 40 years. Annual breast cancer screening for women 40 and older consists of a clinical breast examination and mammographic imaging of both breasts. Women at increased risk for breast cancer may benefit from earlier initiation of screening, screening at shorter intervals, and screening with additional methods such as ultrasound or magnetic resonance imaging (Smith, 2004). The US Preventative Services Task Force (USPTF) 2002 guidelines recommend screening mammography, with or without clinical breast examination every 1-2 years for women aged 40 and older. CDS requires a CBE prior to a mammogram for women being served in the Cancer Detection Programs: Every Woman Counts.

The management of any patient will vary according to age, clinical history and clinical findings. Health history and assessment of risk, physical examination of the breast, mammographic imaging and documentation should be performed routinely for all patients and are defined as follows:

Health History and Assessment of RiskSignificant factors to be elicited in the woman’s health history include current symptoms of nipple discharge, breast mass, axillary mass, skin dimpling, ulceration, inflammation and/or non-cyclical pain. Other factors include current medications (including hormonal therapy), a history of previous breast cancer; any prior breast biopsies; history of breast implants or breast reduction; age at menarche and menopause; pregnancy and lactation history; age at first live birth; exposure to radiation; a history of breast trauma; and a family history (maternal and/or paternal) of breast, ovarian or other associated cancers including age at diagnosis. For more specific information on risk assessment, see Algorithm #1. The history should also include the date and results of the last clinical breast examination, screening mammogram, ultrasound or other diagnostic procedures, and any significant abnormal finding. A sample Breast Cancer History and Risk Assessment form is included in Appendix A-1. Examples of relative risk categories are included in Appendix A-2.

Physical ExaminationAs part of the complete physical examination, the CBE needs to be thorough and should preferably be performed on days 5-10 of the menstrual cycle. CBE and mammographic imaging of the breasts of young premenopausal women can be less diagnostic due to breast nodularity (from the increased glandular-to-fat ratio) when compared to the more homogeneous breasts of postmenopausal women. The Core Competencies of Clinical Breast Examination are included in Appendix A-3.

Documentation of the VisitUpon completion of the woman’s CBE, thorough and standardized documentation will assure appropriate continuity of care, enhance communication between providers, and will serve as a practical risk management strategy. In order to maintain continuity of care, the PCP must coordinate service delivery across settings, multiple providers and time. Breakdowns in the coordination of primary and specialty care have the potential for missed or delayed diagnoses (Institute for Healthcare Improvement, 2000). A sample CBE Results Documentation Form is included in Appendix A-4.

Screening Mammography vs. Diagnostic Imaging EvaluationScreening mammography is specifically designed for asymptomatic women, and consists of two standard views of each breast, the craniocaudal (CC) projection and the mediolateral oblique (MLO) projection. Women who have had breast augmentation can still receive screening mammography (Kopans, 1997). The implants can be manipulated to remove them from the imaging fields, but additional views may still be needed to provide a complete picture of the breast tissue. Women who are breast-feeding should wait at least 3 months post-lactation before having a mammogram (in order to reduce the amount of swelling and achieve a better image), unless a suspicious abnormality is present. For all women, prior mammograms should be used for comparison whenever possible.

Diagnostic imaging evaluation is used for women presenting with a breast finding (usually a palpable mass or a mammographically detected abnormality found on a screening mammogram) or a history of breast cancer. A diagnostic imaging


PAGE 5evaluation will commonly include a diagnostic mammogram and breast ultrasound, but can also include additional ancillary procedures at the Radiologist’s discretion. The radiologist correlates the results of all of these diagnostic procedures into a diagnostic imaging evaluation or final imaging result. The diagnostic mammogram component will include the standard screening views (if not already done) plus additional views. Spot compression views evaluate asymmetrical densities or better define areas of clinical concern. Magnification views determine the morphology of calcifications or improve visibility of masses. A mammogram is not considered diagnostic unless a radiologist reviews all associated images.

American College of Radiology BI-RADS® Assessment Categories

Category 0 Need Additional Imaging Evaluation and/or Mammograms for Comparison. Category 0 is a screening mammogram result indicating that additional imaging evaluation is needed. The additional imaging may include spot compression, magnification, special mammographic views and/or ultrasound. Category 0 may be assigned in situations where the current films need to be compared with prior films, however it should only be used for old film comparisons when such comparison is required to make a final assessment. PCPs should follow-up with radiology facilities for the final diagnostic imaging evaluation result if they receive a report describing a Bi-RADS® 0 result.

Category 1 Negative. There is nothing to comment on. The breasts are symmetric and no masses, architectural distortion or suspicious calcifications are present.

Category 2 Benign Finding(s). Like “negative” this is a “normal” assessment, but the interpreter chooses to describe a benign finding in the report.

Category 3 Probably Benign Finding—Initial Short-Interval Follow-up Suggested. A complete diagnostic imaging evaluation should be made before assigning a Category 3 result, thus it cannot be issued as the result of a screening mammogram alone. The vast majority of patients with Category 3 results are referred for an initial short-term follow-up (6 months) followed by additional clinical and radiographic examinations until longer-term (2 years or longer) stability is demonstrated. A finding placed in this category should have less than a 2% risk of malignancy.

Category 4 Suspicious Abnormality—Biopsy Should Be Considered. This category is reserved for findings that do not have the classic appearance of malignancy but have a probability of malignancy that is greater than those in Category 3.

Category 5 Highly Suggestive of Malignancy—Appropriate Action Should Be Taken. These lesions have a high probability (>95%) of being cancer. This category contains lesions for which one-stage surgical treatment could be considered without preliminary biopsy. However, current oncologic management may require percutaneous tissue sampling as, for example, when sentinal node imaging is included in surgical treatment or when neoadjuvant chemotherapy is administered at the outset.

Category 6 Known Biopsy / Proven Malignancy—Appropriate Action Should Be Taken. This category is reserved for lesions identified on the imaging study with biopsy proof of malignancy prior to definitive therapy. This category has been added for breast findings already known to be malignant by biopsy but prior to definitive therapies such as surgical excision, radiation therapy, chemotherapy or mastectomy. Radiologists use this for giving second opinions on outside films with known cancers or following tumor response in neoadjuvant chemotherapy settings.

Note: Particularly for categories 0, 3, 4, and 6: Refer to the ACR-Guidance Chapter noted in the Bibliography Appendix.

Mammograms should only be performed in facilities certified under the Mammography Quality Standards Act (MQSA) with FDA accreditation. As an MQSA certified facility, all mammographic imaging results are required to be reported using the Breast Imaging Reporting and Data System (BI-RADS®). This is a standardized system for reporting categories of imaging results. The American College of Radiology (ACR) has developed BI-RADS® for Ultrasound and MRI reporting as well (First Editions-2003). The standardized BI-RADS® categories for mammography results are as follows:


PAGE 6The following legend displays the graphic designations and abbreviations used in the algorithms:

Graphic Designations Abbreviations

Starting point for algorithm

Decision point

Process or procedure

Endpoint—decision finished for that algorithm

Direction for further work-up or connector to another algorithm

Flowchart note marker

ADH = Atypical Ductal Hyperplasia

ALH = Atypical Lobular Hyperplasia

BI-RADS® = Breast Imaging Reporting and Data Systems

CBE = Clinical Breast Examination

DCIS = Ductal Carcinoma In Situ

DX = Diagnosis

FNA = Fine Needle Aspiration

F/U = Follow-up

HX = Patient History

LCIS = Lobular Carcinoma In Situ

NCI = National Cancer Institute

US = Ultrasound


PAGE 7


PAGE 8ALGORITHM 1:

Assessment of Risk

Risk assessment for breast cancer effectively engages the PCP and the patient in a discussion about breast cancer prevention, educates a woman about her specific risk factors, and helps guide a personalized plan for risk reduction and early detection. For the woman with high risk determined by a risk assessment algorithm, a referral to a risk assessment counselor can be helpful in further defining the risk, identifying possible genetic risks, and recommending appropriate risk reduction strategies.

Risk is the probability or likelihood that an event will occur. Risk can be expressed in several ways, the most common being relative risk and lifetime risk. Relative risk is the ratio of the risk of disease (in this case breast cancer) among those exposed to a risk factor to the risk of disease among those not exposed to the risk factor. For breast cancer, important risk factors include age, gender, family history, age at menarche, other reproductive factors, use of hormone replacement therapy, radiation exposure, alcohol use, and previous breast biopsies – especially those with abnormal findings. See Appendix A-2 for details on relative risk estimates associated with certain risk factors. Absolute risk describes the risk of disease in the context of time, such as the lifetime risk for a disease or risk by a certain age. The Gail Model estimates the absolute risk of breast cancer for a woman over the next five years and over her lifetime based on certain risk factors for the disease. It is an excellent breast cancer risk assessment tool for most women. However, it may underestimate risk for women with a family history of cancer. The Claus Tables provide a better estimate of absolute risk for women with a family history of cancer. These tables estimate breast cancer risk based on the family history of breast cancer and/or ovarian cancer taking into account the age of onset of the disease.

Algorithm #1 is intended to assist PCPs with the identification of women at increased risk for developing breast cancer. Breast cancer risk assessment should be performed as part of routine screening, and it should be repeated annually since risk factors for breast cancer change over time. Certain breast cancer risk factors are more significant than others, and generally, there are interactions between these major risk factors. The interactions make true risk assessment difficult to calculate. This algorithm attempts to incorporate the risk factors that have epidemiologic evidence of significant risk; it does not include all possible risk factors or assess

absolute risk for combinations of risk factors. Rather, the algorithm provides a qualitative assessment of risk based on personal history, family history, medical/pathological/genetic factors, with the outcome of either normal or increased risk for breast cancer.

Pathological factors: A personal history of breast cancer increases the general risk of a second primary breast cancer either in the contralateral breast or the ipsilateral breast if there is remaining tissue. For most women, this risk is estimated to be 0.7% to 1.0% per year for the first 10 years with a 20-year cumulative risk of 4%-20%. However, the personal risk of another primary breast cancer depends to a great extent on the presence of risk factors. For example, a BRCA1 or BRCA2 mutation is associated with a 10-year cumulative risk of 43% and 34% respectively (Metcalfe et al., 2004).

Ductal carcinoma in situ (DCIS) confers a risk similar to invasive breast cancer (Yen, 2003). Other pathological features that increase breast cancer risk include: lobular carcinoma in situ (LCIS), atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), fibroadenoma with complex features, moderate or florid hyperplasia and solitary papillomas without coexistent hyperplasia.

Genetic and family history risk factors: Inherited mutations in breast cancer susceptibility genes are associated with a very high risk of the occurrence of breast cancer. The breast cancer susceptibility genes identified to date include:

BRCA1/BRCA2, associated with the diagnoses of hereditary breast-ovarian cancer and hereditary site-specific breast cancer.

PTEN, associated with the diagnosis of Cowden syndrome. STK11, associated with the diagnosis of Peutz-Jeghers syndrome. MLH1/MSH2/MSH6, associated with hereditary non-polyposis, colorectal

carcinoma and breast cancer in certain families. ATM, associated with a 4-fold increase in risk among heterozygotes. CHK2, associated with a 2-fold increase in risk among heterozygotes. TP53, 50% risk of breast cancer by age 50.


PAGE 9

A family history of breast cancer significantly increases the risk of breast cancer for the individual if the cancer occurs in first and/or second-degree biological relative(s) – parents, siblings, children, grandparents, aunts, uncles, nieces and nephews. Red flags suggestive of genetic susceptibility to breast cancer include:

One or more first- or second-degree relatives with breast cancer at an early age (less than 40-50 years of age).

Breast cancer and a second primary cancer in a close relative, especially ovarian cancer. (Other cancers that may be associated with an increased genetic risk include: thyroid, colorectal, prostate, endometrial, pancreatic, adrenocortical carcinoma, melanoma, childhood sarcoma, leukemia/lymphoma, and brain tumors.)

Male breast cancer in a close relative. Two or more relatives with breast cancer at any age. If of Ashkenazi Jewish descent, a biological relative with breast cancer

diagnosed before age 50 or ovarian cancer at any age.

Personal factors: Gender is the most obvious and important risk factor for breast cancer.

Females have a 100-fold increase in risk as compared to males. However, the ACS estimates that in 2005 there will be 1,690 new cases of invasive

breast cancer diagnosed among men in the United States. (Male breast cancer is a red flag for a possible genetic susceptibility.)

Age – breast cancer risk increases with age; 96% of breast cancers occur in women age 40 and older (ACS, 2003-2004). Most women face a lifetime risk of 12-13%.

Race – Caucasian women have a greater risk of breast cancer than other racial groups.

Prolonged exposure to endogenous estrogen and progestins (U.S. Preventive Services Task Force, 2005).

Exposure to exogenous combined estrogen and progestin therapy in hormone replacement therapy for postmenopausal women has been shown to slightly increase the risk for breast cancer. It is controversial whether or not exogenous estrogen alone in estrogen replacement therapy for postmenopausal women affects the risk for breast cancer. (U.S. Preventive Services Task Force, 2005.)

Alcohol use – greater than 27 drinks per week. (Gronbaek, 2004.) Obesity – obese women with BMI >30 had estrogen concentrations

between 60% and 219% higher then thin women and the risk of breast cancer increased as BMI increased at an average rate of about 18% per 5-point increase in BMI. (Journal of National Cancer Institute, 2003.)

Radiation exposure to the upper torso (e.g. treatment of Hodgkin’s lymphoma). (Preston, 2002.)

The table below reveals changes in breast cancer risk across a woman’s lifetime, according to age group.

Age-Specific Probabilities of Developing Breast Cancer*

Probability of developing breast If current age is… cancer in the next 10 years is:** Or 1 in: 20 0.05% 2,152 30 0.40% 251 40 1.45% 69 50 2.78% 36 60 3.81% 26 70 4.31% 23

* Among those free of cancer at beginning of age interval. Based on cases diagnosed 1988-2000. Percentages and “1 in” numbers may not be numerically equivalent due to rounding.

** Probability derived using NCE DEVCAN software.

American Cancer Society, Surveillance Research, 2003


PAGE 10FLOWCHART NOTES

NOTE 1A: Gail Model Risk Calculation Instead of continuing with age and others, calculate risk using the National Cancer Institute (NCI) Risk Assessment Tool if possible: http://bcra.nci.nih.gov/brc/

(Gail Model) A five-year risk of 1.7% or greater may be considered Increased Risk After ruling out the presence of Personal Risk Factors and Family History Risk Factors listed in Algorithm #1, assessment of Age and Other Risk Factors will

identify most women at increased risk for breast cancer, but may over-estimate risk for some women.

NOTE 1B: Age and Breast Cancer Risk A Caucasian woman aged 65 with average risk factors has a 2% risk of developing breast cancer within the next 5 years according to the Gail Model. Therefore,

women 65yrs or older should have their personal risk evaluated on an individual basis using the Gail Model if possible. Women with a 5-year risk of >1.7 % meet FDA criteria for receipt of approved chemoprevention (e.g., Tamoxifen). However, the potential benefit of treatment

must be weighed against the associated risk of serious side effects for the individual woman.


PAGE 11ALGORITHM 1

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PAGE 13ALGORITHM 2: New Palpable Mass

Management of the patient with a breast mass varies according to age, history and clinical findings. Detection of a breast mass often creates anxiety for the woman and her family, requiring sensitive provider/patient communication. Important questions to consider when assessing the index of suspicion of a breast mass (lesion) detected on physical examination include:

What is the location and depth (i.e., superficial, medium, deep) Is it an asymmetrical finding in both breasts? Is it a three dimensional discrete palpable mass? Is it mobile or fixed? What is the size and shape? What is the consistency? Is it tender or non-tender?

Normal glandular tissue is generally mirrored in the contralateral breast. A discrete palpable mass is three-dimensional, different from surrounding tissues and usually asymmetric. Clinical signs that are suggestive of benignity, but are not diagnostic, include a mass that is soft, rubbery and mobile. Features suggestive of malignancy include a mass that feels firm or hard, is fixed, has an irregular shape, is solitary, and feels much different from the surrounding breast tissue (Barton, 1999; Goodson, 1996).

CBE is a screening method, not a diagnostic test. Regardless of age, every clinically suspicious lesion requires further evaluation. CBE finds 4% to 7% of cancers that are normal or benign on mammography (Green 2003, Bobo 2000, Beyer 2003, Georgian-Smith 2000). Thus, an abnormal CBE in the presence of a negative mammogram requires further follow-up. The leading cause of physician delay in the diagnosis of breast cancer continues to be inappropriate judgment that a mass is benign without performing a biopsy. Reducing delay in diagnosis requires less reliance on CBE to determine the benignity of a mass as well as less reliance on benign mammographic reports in deciding not to biopsy a mass (Goodson,

2002). Physical exam alone is approximately 70% accurate; mammography alone is approximately 85% accurate; minimally invasive tissue diagnosis alone is approximately 95% accurate. While physical exam and mammogram alone can detect many cancers, no single test by itself allows for detection of all breast cancers. The best clinical approach to the diagnosis and management of patients with a palpable mass is the combination of all three tests – physical exam, radiographic imaging and pathology (biopsy or fine needle aspiration). This diagnostic triad is known as the “triple test.” The diagnostic accuracy of these three tests taken together approaches 100% (Morris, 2002; Vetto, 2003). Clinicians should select the “triple test” method as it helps make an evidence-based decision about clinical management. If one of the “triple test” components is discordant, the entire diagnosis is uncertain and each of the “triple test” findings will need to be reviewed before proceeding.

Pre-menopausal WomenIn patients younger than 30 years of age, or patients who are pregnant, ultrasound may be the first or sole breast imaging modality performed (Mehta, 2003 and Baker, 2000). For patients 30-49 years of age with a new palpable mass, a cyst is the most likely diagnosis and can be confirmed or ruled-out by fine needle aspiration (FNA) or ultrasound (a diagnostic imaging modality). If the degree of suspicion is very low (the palpable mass is a “ridge” and is two-dimensional, rather than three-dimensional), it is acceptable to repeat the screening CBE at a more optimal time of the menstrual cycle. Any palpable mass that persists and has not been proven to be a simple cyst, must receive additional diagnostic work-up until a final diagnostic status is determined.

Postmenopausal WomenSince the risk of breast cancer increases with age, clinicians need to be more suspicious of a dominant mass or asymmetric thickening in the breasts of postmenopausal women. Cystic findings decrease after menopause, although cysts, pain, and discharge can be found in women taking hormone replacement therapy. Diagnostic imaging evaluation is usually the first-line investigation of a palpable breast mass in postmenopausal women.



NOTE 2A: Upon detection of a palpable breast mass, the PCP may suspect a simple cyst. This diagnosis must be confirmed with ultrasound or FNA/biopsy. A breast mass that completely resolves by needle aspiration of non-bloody fluid can be considered insignificant if there are no signs of recurrence four to six weeks post-aspiration (Pruthi, 2001). Ultrasonography depicts the fluid within cysts and can diagnose cysts with a diameter as small as 2-3 mm in small breasts. Ultrasound is less sensitive in large breasts due to the fatty breast tissue. Although multiple cysts commonly occur, a woman with breast cysts needs to be advised to seek medical advice whenever a new mass arises. Neither the clinician nor the woman can automatically assume that a new mass is “just another cyst.” Non-palpable cysts detected by mammography and confirmed by ultrasound do not need to be aspirated unless they are symptomatic and cause pain. A cyst that recurs more than two times within four to six weeks, contains bloody fluid, or leaves a residual palpable mass post-aspiration demands a diagnostic imaging evaluation. In this situation, the radiologist should be informed that an aspiration was undertaken prior to the imaging procedure. Cysts with internal debris or thick material require further follow-up.

NOTE 2B: Clinician confidence level in performing cyst aspiration may vary. Proceed with diagnostic imaging evaluation (e.g., ultrasound) if routine aspiration is not offered in your practice.

NOTE 2C: A clinically suspicious mass may have one or more features consistent with cancer, such as firmness, irregularity, or solitary. Sometimes such masses are fixed and associated with skin retraction. Any asymmetrical finding should be cause for concern (Barton, 1999; Goodson, 1996). Patients with suspicious findings should be referred to a breast surgeon immediately.

NOTE 2D: Patients with a new palpable mass and Negative (BI-RADS® category 1) diagnostic imaging evaluation result should at minimum have a repeat CBE within thirty days. The negative imaging result indicates that there were no radiographically identified lesions, but does not preclude existence of a non-radiographically evident lesion. The follow-up CBE will allow the PCP to determine whether the palpable mass is persistent. If the mass is not persistent, there should be another repeat CBE in 3-6 months. If this confirms that the mass is no longer present, the patient can then return to routine screening intervals. Patients with negative imaging, in whom the mass persists at a follow-up CBE, should be referred to a breast specialist for decisions regarding follow-up interval or need for biopsy.

NOTE 2E: Patients with a Benign finding (BI-RADS® category 2) on mammogram should have a repeat CBE within thirty days. This allows the practitioner to correlate the physical findings with the diagnostic imaging evaluation and assure that the finding is concordant. The imaging finding identifies the anticipatory physical finding as benign; if there is no correlation between the imaged mass and the palpable mass, the patient should be referred to a breast specialist for decisions regarding interval follow-up or tissue biopsy. Mammography should be performed using a radio-opaque marker on the skin over a palpable lesion to assist in determining if the palpable mass corresponds to the mammographically identified lesion. A discordant mammographic finding may represent a separate lesion, which may need further evaluation in addition to a work-up for the original palpable mass. Careful correlation of the physical exam and the diagnostic imaging evaluation is critical to assure appropriate and timely follow-up. If the imaging findings show a simple cyst, it can be aspirated during a follow-up CBE if required to alleviate discomfort.

NOTE 2F: The American College of Radiology does not recommend the assignment of a Probably Benign (BIRADS category 3) result as the final diagnostic imaging evaluation for a patient with a palpable mass. This may occur if the radiologist is unaware of the CBE findings. If the results of your CBE screening indicate a palpable mass and you receive a BIRADS category 3 final diagnostic imaging evaluation, contact the radiologist for further consultation.


PAGE 15ALGORITHM 2

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PAGE 17ALGORITHM 3:

Abnormal Screening Mammogram with Normal CBE

With improved imaging techniques, screening mammograms are enabling detection of earlier breast cancers. If an abnormality is suspected with screening mammography, the radiologist performs additional mammographic views and/or ultrasound. After the imaging work-up is complete, the radiologist assigns a BI-RADS® category 1-6 as the final imaging result.

Final Imaging Results – Negative or Benign (BI-RADS® Categories 1 or 2)Routine clinical follow-up is appropriate for Negative and Benign (BI-RADS®

category 1 and 2) mammographic imaging results.

Final Imaging Result – Probably Benign (BI-RADS® Category 3)A Probably Benign, BI-RADS® category 3 lesion generally will require a repeat CBE in 3-6 months and repeat mammography in six months to ensure concordance between the CBE findings and the radiographic lesion. If the woman is at increased risk for breast cancer, immediate follow-up is recommended with a breast specialist. Women with average risk may be referred for repeat CBE and imaging in six months (short-term follow-up). If the initial six-month short-term follow-up (unilateral mammogram) is stable, another bilateral mammogram in 6 months may be recommended by the radiologist (ACR, 2003 and Kerlikowske, 2003). If there is still no change, the patient should be rescreened at one-year intervals for two years. While a lesion’s radiographic stability over time suggests benignity, a lack of change in features cannot completely reassure the PCP and patient that

a lesion is benign. There have been reports of microcalcifications, which are stable on radiologic exam, yet are later found to be malignant in 8-63 months (Michell, 2003). Some lesions classified mammographically as probably benign may be biopsied depending on the recommendations of the breast specialist and the preferences of the patient.

Final Imaging Results – Suspicious Abnormality or Highly Suggestive of Malignancy (BI-RADS® Categories 4 or 5)All mammograms showing a Suspicious Abnormality or a lesion that is Highly Suggestive of Malignancy (BI-RADS® category 4 or 5) should result in biopsy.

Categories 3, 4, and 5 always require further evaluation despite the normal clinical breast exam. A reasonable percentage (50-90%) of category 4 and 5 lesions will be shown to be cancerous (ACR, 2003). In fact, it is the detection of these small or pre-invasive cancers by mammography that significantly contributes to the reduction in breast cancer mortality.

The false-negative rate for screening mammography is 8% to 10% (Shaw de Paredes, 2000). Breast density can compromise the ability of a mammogram to detect a mass, and lesions located near the sternum can be difficult to visualize (Mandelson, 2000). Over a 10 year period approximately 24% of women getting an annual mammogram will have at least one false positive mammogram.



NOTE 3A: Screening mammogram results of Negative (BI-RADS® category 1) and Benign (BI-RADS® category 2) prompt routine rescreening for women with normal CBE exams.

NOTE 3B: Lesions identified with a screening mammogram require a diagnostic “work-up” (additional views and/or ultrasound) before a final imaging result can be assigned (ACR, 2003). Prior to assigning the final imaging result, a BI-RADS® category 0 may be temporarily assigned to indicate that additional views or tests are needed, or that previous mammographic results need to be reviewed.

NOTE 3C: The American College of Radiology does not recommend the assignment of a BI-RADS® 3 result to a screening mammogram. If you should receive a screening mammogram report with this result, refer the woman for additional diagnostic imaging. If a diagnostic evaluation has already been completed, continue work-up based on that diagnostic imaging result.

NOTE 3D: A patient with a final imaging result of BI-RADS® category 3 who is at increased risk for breast cancer (See Algorithm #1) should be immediately referred to a breast specialist. Referral to a breast specialist can be offered to women who are concerned about their results and do not want to wait six months for further follow-up.

NOTE 3E: For BI-RADS® category 3, the vast majority of findings will be managed with an initial short-term follow-up examination in 3-6 months, followed by additional examinations until stability is demonstrated (2 years or longer). There may be occasions when a biopsy is done (i.e. patient request or clinical concerns). Evidence from all the published studies indicates the need for biopsy if the lesion increases in size or undergoes morphologic change (ACR, 2003).

NOTE 3F: A BI-RADS® category 4 lesion should lead to biopsy, and a BI-RADS® category 5 lesion requires biopsy (ACR, 2003). If the lesion is definitively diagnosed as benign after core biopsy and is consistent (concordant) with the radiological findings, excisional biopsy is not required (See Algorithm #7). The methods of biopsy include stereotactic or ultrasound-guided core biopsy for definitive diagnosis or needle localization followed by excisional biopsy with intraoperative confirmation of negative margins.


PAGE 19ALGORITHM 3

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PAGE 20ALGORITHM 4:

Spontaneous Unilateral Nipple Discharge

Nipple discharge is a common breast problem that has been reported in 10-15% of women with benign breast disease and in 2.5-3% of women with breast cancer (Morrow, 2000). A nipple discharge should be of concern when a woman reports it as unilateral and spontaneous (not in response to stimulation) and staining her bra, bed sheet, or sleeping garment. Directly squeezing the nipple to express fluid promotes discharge and is not a routine part of the screening CBE in asymptomatic women. Using an aspiration pump will elicit a discharge from 50 to 80% of women without breast disease. Women should be advised to avoid checking themselves for discharge since benign discharge may resolve when the nipple is left alone (Morrow, 2000).

A number of conditions result in nipple discharge. Endocrine causes of galactorrhea include pregnancy, hypothyroidism and amenorrehic syndromes. Medications such as antihypertensives, oral contraceptives, phenothiazines, and tranquilizers may also cause nipple discharge. Milky discharge could be due to medications and the provider may want to consider ruling out this etiology prior to referral to a breast specialist.

Bilateral nipple discharge usually has a physiological cause, such as hyperprolactinemia leading to galactorrhea. It can also occur in breast disease that is bilateral, such as mammary duct ectasia. This is a benign condition occurring in postmenopausal women, characterized by dilation of the ducts, nipple secretions and periductal inflammation.

Every woman with a unilateral, spontaneous, clear, watery, serous, or bloody discharge should be referred for diagnostic imaging evaluation. Most mammograms in such instances are normal and should NOT deter surgical referral. Any discharge from a single duct is of concern. Multiple duct discharges are rarely caused by cancer (Florio, 2003). Any mammographic abnormality should correspond with the quadrant of the breast from which the discharge originates for it to be considered relevant to the cause of the discharge. Cytology in the assessment of nipple discharge is controversial and is generally not recommended as a first line investigation due to the high number of false negative results.

FLOWCHART NOTES

NOTE 4A: A non-spontaneous discharge is not usually significant. It is more clinically relevant if a history of a spontaneous discharge is elicited. The patient should be asked whether she has noticed staining of her clothing. A true nipple discharge originates in one or more duct(s) (Apantaku, 2000). Inverted nipples, eczema, infection, etc can cause pseudo-nipple discharges.

NOTE 4B: It is important to determine if the nipple discharge is associated with a palpable mass. Any mass noted within 2 cm of the nipple is considered correlative (Sheen-Chen, 2001). Immediate referral for diagnostic imaging followed by surgical consultation is appropriate.

NOTE 4C: The diagnostic imaging abnormality should correspond with the quadrant from which the discharge originates (i.e. a radiographic abnormality that does not correlate to the discharge quadrant may represent a separate lesion). It is important to realize that a mammographic abnormality that corresponds to a palpable lesion may be a separate lesion that is not associated with the discharge. It may need a separate work-up and referral to a breast specialist.

NOTE 4D: Clinical re-evaluation of a woman with a BI-RADS® category 1 or 2 is recommended at 3 months and is intended to assure that the nipple discharge has resolved.


PAGE 21ALGORITHM 4

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PAGE 23ALGORITHM 5:

Work-up of Breast Skin Changes/Nipple Retraction A thorough history and CBE are important in the assessment of the patient who presents with skin changes (e.g. inflammation, scaling) or skin/nipple retraction. Important questions to consider include:

How long has the change been present? Is there an associated palpable mass or mammographic abnormality? Is it a unilateral finding?

Timing of onset of nipple retraction is of paramount importance; congenital nipple inversion is insignificant, whereas recent nipple retraction has more serious implications. Unilateral nipple retraction, even slight, is also more suspicious than bilateral nipple inversion.

Skin changes that may signify carcinoma include skin erythema, retraction, dimpling, nipple excoriation or crustiness. Asymmetry of the breasts that indicate a recent change should be noted along with other findings, particularly any masses. Inflammatory breast cancer (IBC) symptoms include diffuse erythema, edema involving more than two-thirds of the breast, peau d’orange, tenderness, induration, warmth, enlargement of the breast, and diffuseness (or absence) of a tumor on palpation (Cristofamilli, 2004).

Signs of inflammation can be treated with a 10-day course of antibiotics that cover aerobic and anerobic skin bacteria (typical of those in the mouth and vagina), but if not completely (100%) resolved, inflammatory carcinoma must be suspected and diagnostic imaging is required. A possible treatment regimen could be cephalexin plus metronidazole. Nipple retraction can be managed in the case of suspected periductal mastitis or deep tissue infections. A lack of a complete (100%) response requires further diagnostic imaging work-up.

There are many dermatologic causes of red, oozing and crusted nipples, including psoriasis, seborrheic dermatitis, contact dermatitis, neurodermatitis and atopic dermatitis. Eczema can be localized or can involve the complete nipple-areolar complex and must be distinguished from the non-eczematous conditions of Paget’s disease of the nipple. Because Paget’s disease is a very serious but commonly missed diagnosis, a thorough history and physical examination are important for every patient who presents with skin and/or nipple changes of the breast. Paget’s disease comprises 1-3% of all primary breast cancers (Marcus, 2004). Paget’s disease is manifested by progressive eczematoid changes of the areola with persistent soreness or itching (Lev-Schelouch, 2003). A mass is often associated with Paget’s disease (NCI, 2002) and those patients with a palpable mass have a worse survival rate than do patients with a nonpalpable mass (Fu, 2001).

Eczema Paget’s Disease of the Nipple Usually bilateral Unilateral Intermittent history with rapid evolution Continuous history with slow progression Moist Moist or dry Indefinite edge Irregular but definite edge Nipple may be spared Nipple always involved and disappears in advanced cases Itching common Itching common

From Hughes LE et al. Benign Disorders and Diseases of the Breast: Concepts and Clinical Management. London, Ballière Tindell, 1989.


PAGE 24

Despite some of these clinical differences, it is important to consider Paget’s disease until proven otherwise. Nipple scaling may respond to a short course of topical steroids, but a follow-up appointment is critical to assess responsiveness. Sometimes Paget’s will transiently respond to steroid cream, so if used, a follow-up exam is required. Paget’s disease with a palpable breast mass is likely to be accompanied by an invasive ductal carcinoma and has a poor prognosis (Sun Q, 2003).

Diagnostic imaging is the first line investigation when there are skin or nipple changes, even if no mass is palpable on CBE. However, a negative diagnostic imaging work-up for a clinical abnormality of the breast must not preclude referral to a breast specialist. Patients with any nipple complaint require further evaluation.

FLOWCHART NOTES

NOTE 5A: There is some controversy over the use of a topical steroid cream for nipple symptoms indicative of Paget’s disease. Some surgeons now advocate referral for examination and possible biopsy prior to any use of steroid cream.


PAGE 25ALGORITHM 5

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PAGE 27ALGORITHM 6:

Breast Pain in a Non-Lactating Woman Mastalgia (breast pain) is the most common breast-related complaint at both primary care clinics and breast referral centers. Most of these complaints are cyclic in nature. Cyclic pain usually is normal in menstruating women or in postmenopausal women on hormone replacement therapy. Fibrocystic changes represent the most common cause of cyclic breast pain and symptoms are typically bilateral and described as diffuse, dull, full, achy, and heavy.

Non-cyclic causes include a ruptured cyst, a non-ruptured cyst under tension, fat necrosis, cervical radiculitis, intercostal neuritis, shingles, Tietze’s Syndrome (costochondritis), mastitis/abscess, Mondor’s disease, trauma, post-radiation syndrome and rarely cancer. Non-cyclic pain tends to be unilateral and described as localized, sharp, throbbing, stabbing, or burning.

The differential diagnosis of breast pain requires a CBE and careful assessment:

Is it cyclic or non-cyclic? Is it bilateral or unilateral? Is the pain diffuse or focal? Is it associated with a mass? Is hormone replacement therapy ongoing? Is there a history of trauma?

Non-cyclic pain is initially investigated with diagnostic imaging evaluation. If the patient is a young woman, an ultrasound may be preferred. Additional follow-up

depends on the diagnostic imaging/ultrasound final assessment category. The risk of cancer with a negative evaluation for breast pain is less than 1% (ICSI, 2003).

Mastalgia is reported by up to 15 percent of women diagnosed with breast cancer, and 7 percent present with pain alone (Morrow, 2000). Therefore, a diagnosis of cancer must be considered in patients with well-localized breast pain of recent onset. The pain associated with breast cancer is often unilateral, persistent, and constant in position.

If there are changes consistent with mastitis (such as erythema, fever >102 degrees, skin tenderness, abscess, or pus expressed from the nipple), refer to Algorithm 5 on skin changes/nipple retraction.

Although this algorithm addresses the non-lactating woman, a similar work-up of breast pain in the lactating woman is recommended; however the latter may need referral to a breast specialist.

For most women, treatment consists of relieving symptoms and reassuring the patient that there is no underlying carcinoma or other serious disorder. Non-narcotic analgesics and supportive bras may be helpful. Some women may find relief by using oil of primrose (3 grams a day). Elimination of caffeine, chocolate or salt from the diet has not been scientifically proven to be beneficial. The etiology of breast pain remains unclear, and no satisfactory treatment exists for some women (Khan, 2002).



NOTE 6A: Distinguish between cyclic and non-cyclic breast pain. Cyclic pain is typically bilateral and described as diffuse, dull, full, achy, and heavy. Non-cyclic pain tends to be unilateral and described as localized, sharp, throbbing, stabbing, and burning.

NOTE 6B: As with other algorithms, a BI-RADS® category 3 result requires a differential assessment of risk. See Algorithm #1, Risk Assessment, to determine if the patient is at increased risk for breast cancer. If so, refer to a breast specialist.

NOTE 6C: For BI-RADS® category 3, the vast majority of findings will be managed with an initial short-term follow-up imaging examination in 3-6 months, followed by additional examinations until stability is demonstrated (2 years or longer). There may be occasions where biopsy is done (i.e. patient request or clinical concerns). Evidence from all the published studies indicates the need for biopsy of a lesion that increases in size or undergoes morphologic change (ACR, 2003).


PAGE 29ALGORITHM 6

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PAGE 31ALGORITHM 7:

Management of Breast Biopsy Results Definitive diagnosis of a breast mass can only be established through fine needle aspiration biopsy (FNAB), core needle biopsy, or excisional biopsy. Most experts agree that if a mass persists for three months, a sampling of the lesion is warranted. Further delay in work-up is not prudent unless the diagnostic imaging evaluation shows a concordant benign lesion. Generally speaking, the best option depends on whether the mass is palpable, the availability of resources and expertise, the degree on CBE of suspected invasiveness and patient demand for a rapid diagnosis.

The pathologic findings from a biopsy must fully explain the clinical and/or the imaging findings that prompted the biopsy (“triple test”). Clinical/radiologic/histologic discordance occurs when the CBE and/or imaging findings are not explained by the final pathology. When repeat imaging studies or clinical exam indicate that the original radiographic or clinical finding may not have been adequately sampled (“discordant triple test result”), further biopsy is needed. Clinical/radiologic/histologic discordance carries a rate of malignancy that can be as high as 40-50% (Morris, 2003). Therefore, if the results are discordant, or if the clinician is not sure, the patient must undergo further evaluation by a breast specialist. Various options are available for obtaining concordance. These include radiology consultation, repeat image-guided biopsy, or surgical consultation. For example, a woman with a palpable mass within 2 cm of visual nipple retraction and a pathology result of normal or fibrocystic change represents discordance between the clinical findings and the pathology report (regardless of the diagnostic imaging result). The patient needs a repeat biopsy.

Core Needle BiopsyCore needle biopsy of the breast provides a solid cylinder(s) of tissue for histologic evaluation and when properly done in appropriately selected patients is a safe, well-tolerated and cost-effective alternative to surgical biopsy. Large core needle biopsy specimens do not require subspecialty pathologist expertise for histologic diagnosis. Core biopsy may also have a 7.6% (with a range of 3.3 to 22.2% depending on the gauge of needle employed) risk of false negative diagnosis which is chiefly due to sampling error. Sampling error is reduced with the use of larger gauge needles and by obtaining multiple core biopsy samples (Shah, 2003).

When core biopsy yields a result that is discordant with the clinical or imaging impression, it is incumbent on the provider to pursue the situation with repeat core biopsy or surgical biopsy. Radiologic-guided core biopsy (see below) is useful in the evaluation of the palpable breast mass that is small, deep, mobile, vaguely palpable, or multiple (Liberman, 2000). Core biopsy needle sizes may be 8, 11 or 14 gauge depending on operator preference, usually in a spring-loaded instrument, to extract several cores of tissue through a 3-5mm incision. Core biopsy is a sampling technique and is not intended to remove the lesion.

Radiologically-Guided Percutaneous Core BiopsyA nonpalpable mass detected via imaging study can be percutaneously biopsied by a radiologist or other physician with special skills using ultrasound or mammographic (stereotactic) guidance. Stereotactic core needle biopsy is performed using special mammographic apparatus. A core biopsy needle (either an automated spring-loaded or vacuum-assisted biopsy instrument) is inserted into the lesion. Multiple tissue samples are obtained. In most centers, large core needle biopsy is replacing open surgical biopsy for the diagnosis of nonpalpable mammographic lesions.

Pre-Operative Needle (or wire) Localization BiopsyIn pre-operative needle (or wire) localization biopsy a radiologist inserts a wire through a needle into the breast to mark nonpalpable lesions detected mammographically or by ultrasound. The wire guides the surgeon to the lesion for tissue removal during an excisional biopsy; hence it is a combined radiographic and surgical technique. Today, this technique is mainly therapeutic rather than diagnostic as the majority of breast lesions have had a prior diagnosis by a radiologically guided percutaneous biopsy. For nonpalpable abnormalities the localized biopsy has less than a 2% failure rate (Bassett, 2002).

Excisional Biopsy (Lumpectomy)Surgical removal of a breast lesion is the gold standard against which all other diagnostic techniques are compared. Excisional biopsy surgically removes the entire lesion and should include a zone of normal tissue surrounding it. The procedure requires a sterile operating room setting and leaves a small (2-4 cm) scar.


PAGE 32Fine Needle Aspiration BiopsyFNA biopsy is safe, accurate and better tolerated with less bleeding and infectious complications than either large core or surgical biopsy. However, it is a highly operator-dependent procedure, requires subspecialty expertise for interpretation, and cannot distinguish invasive from non-invasive disease. Compared to other biopsy methods, FNA biopsy has a higher rate of false negative results (chiefly due to sampling error) and suspicious results (chiefly due to interpretative challenges),

(Salami, 1999; Shah, 2003). When FNAB yields a result that is discordant with the clinical or imaging impression, it is incumbent on the provider to pursue the situation with a different diagnostic procedure. The use of FNA biopsy may be limited since the special expertise required to perform and interpret this form of biopsy may not be available in all areas.

FLOWCHART NOTES

NOTE 7A: If physical findings and/or diagnostic imaging results are suspicious for a malignancy then a “negative” biopsy must be considered “discordant” and may represent a false negative result. The patient should be referred to a breast specialist for further evaluation.


PAGE 33ALGORITHM 7

CBE & Hx & Imaging

Breast Biopsy

Algorithm 7: Management of Breast Biopsy Results

Pathology Findings*

Malignantor

Ductal Carcinoma In Situ (DCIS)

All OthersDo findings

from all 3 modalitiesagree?

Yes, Concordant

No,Discordant

DefinitiveTreatment

Routine Clinical F/U& Screening

Refer toSpecialist

Non-Malignant,But Concerning

Atypical Ductal HyperplasiaAtypical Lobular Hyperplasia

Lobular Carcinoma In SituLobular Neoplasia

Radial ScarPhyllodes TumorMucocele LesionPapillary Lesion

Refer toSpecialist

Correlate:

Physical FindingsDiagnostic ImagingPathology Results

7A

*Definitions of pathologic terms can be found in Appendix A-5: Glossary of Terms.

Appendix A

-1: Breast C

ancer History A

nd Risk A

ssessment

Please answer the questions below

about your breast health. Your answers w

ill help us develop a breast health plan that is right for you. F

eel free to ask for help if you don’t understand any of the questions or are not sure how

to answer them

.

1. N

ame __________________________________________________________________________

2. Today’s D

ate ______________________D

ate of birth________________________ A

ge ______

3. W

hat is your current height? ______ feet ______ inches

4. W

hat is your current weight? ______ pounds

5. A

ny recent changes and/or concerns:Right

Left C

yclic

Lump

Nipple discharge

Nipple / skin retraction

Erythema / sw

elling

Rash / scaling / itching

Breast pain

Other: __________________

None

6. H

ave you ever had any of the following exam

inations of your breasts?

Physical exam of the breast by a doctor or nurse:

No

Don’t know

Yes most recent one w

as: ______________________________________________________

Results: ____________________________________________________________________

Mam

mogram

-an x-ray of your breasts (not a chest x-ray) or ultrasound:

No

Don’t know

Yes most recent one w

as _______________________________________________________R

esults: ____________________________________________________________________

Other tests on your breasts (needle biopsy, excisional biopsy):

No

Don’t know

Yes. What w

as done: _________________________________________________________W

hen was it done? ___________________________________________________________

Results: ____________________________________________________________________

Personal and Fam

ily History

Please indicate with a check m

ark whether you or your fam

ily mem

bers listed in the column on the left

have had any of the conditions listed in the top row of the table. If there are other cancers in yourself or

these family m

embers, please w

rite in which type of cancer. Provide inform

ation about your biological (blood) relatives only. This should include your relatives w

ho are living and deceased. If you are adopted, please include inform

ation about your biological (blood) relatives, if known.

B

reast B

reast B

reast

cancer at cancer

cancer in

or before after

a male

Ovarian

Other cancers*

age 50

age 50 relative

cancer

(please specify) Yourself

Your parents

Your brothers & sisters

Your children

Your mother’s parents

Your m

other’s brothers and sisters

Your father’s parents

Your father’s brothers and sisters

* Exam

ple of others cancers include colorectal, thyroid, prostate, endometrial, pancreatic, adrenocortical, m

elanoma, childhood

sarcoma, leukem

ia/lymphom

a, and brain.

If yes to personal history of breast cancer, please respond below:

What treatm

ents did you have for breast cancer?

Surgery: what type? _____________________________________________________________

Radiation: how

long? ____________________________________________________________

Chem

otherapy: how long? ________________________________________________________

Horm

ones: how long? ____________________________________________________________

Other: ________________________________________________________________________

8. H

ave you or a family m

ember tested positive for a m

utation in a breast cancer susceptibility gene (e.g., B

RC

A1, B

RC

A2, ATM

, PTEN

, STK11, M

LH1, M

SH2, TP53 or C

HK

2)?

Do you have A

shkenazi Jewish ancestry (certain form

s of breast and ovarian cancer are more

comm

on in Ashkenazi Jew

ish families)?

Yes

No

Don’t know

/not sure

10. Indicate if you have every had any of the following procedures:

Breast surgery other than for cancer (im

plants, reduction, other)

Radiation treatm

ent to your upper torso (not mam

mography)

11. Did you begin m

enstruation before age 12?

Yes

No

Don’t know

/not sure 12. H

ave you had a full term pregnancy before age 30?

Yes

No

Don’t know

/not sure

13. Have you entered m

enopause (no menstruation for 12 or m

ore months)?

Yes. If yes, at what age did m

enopause begin? ______ years

No

Don’t know

/not sure

14. Have you used horm

one replacement therapy (estrogen alone or com

bined estrogen and progesterone) for m

ore than 5-10 years?

Yes

No

Don’t know

/not sure 15. H

ave you had your ovaries removed?

Yes. If so, one or both? _________________________________________________________

No

16. On average, do you drink m

ore than two alcoholic beverages a day?

Yes

No

17. How

would you rate your lifetim

e risk for developing breast cancer compared to m

ost wom

en?

Low

Medium

High

Don’t know

Thank you for taking the time to com

plete this form

Sample docum

ent courtesy of the California D

epartment of H

ealth Services July 2005


PAGE 37Appendix A-2:

Risk Assessment Table

Adapted from ACS Breast Cancer Facts and Figures 2003-2004

Relative Risk Factor

Relative Risk >4.0 Age (>65 years, although risk increases across all ages until age 80)Certain inherited genetic mutations for breast cancer (i.e., BRCA1, BRCA2)DCIS, LCIS, ADH, ALHTwo or more first-degree relatives with breast cancer diagnosed at an early agePersonal history of breast cancerPostmenopausal breast density

Relative Risk 2.1-4.0 One first-degree relative with breast cancerBiopsy-confirmed atypical hyperplasiaHigh-dose radiation to the chest or torsoHigh bone density (postmenopausal)

Relative Risk 1.1-2.0 Fibroadenoma with complex features, moderate or florid hyperplasia without sclerosing adenosis, solitary papillomas without coexistent atypical hyperplasia Benign lesions

Reproductive Late age at first full-term pregnancy (>30 years)Early menarche (<12 years)Late menopause (>55 years)No full-term pregnanciesNever breast fed a child

Circulating hormones Recent oral contraceptive use

Recent/long-term use of hormone therapyObesity (postmenopausal)

Other Personal history of cancer (endometrium/ovary/pancreas)Alcohol consumption (greater than 27 drinks per week)Tall and/or high socioeconomic status and/or Jewish heritage

Combination Five-year Gail Model risk that exceeds 1.67%



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Appendix A

-4:



Glossary Of Terms

Adenoma: a benign epithelial tumor, which forms glands.

Adenosis: a benign proliferation of glandular acini within a lobule.

Aneuploid: refers to an abnormal amount of DNA per cell. Aneuploid DNA content is commonly found in carcinomas and in particular, it is seen in carcinomas of higher nuclear grade. Of itself, it does not impact outcome.

Apocrine Metaplasia: a benign change in which the epithelium of ducts and lobules change to a cell type similar to those of apocrine sweat glands and is frequently seen in cysts.

Atypical Ductal Hyperplasia (ADH): a proliferation of cells confined to the ductal-lobular space which has some but not all of the features of ductal carcinoma in-situ and is characterized by a population of evenly spaced uniform cells with monotonous hyperchromatic nuclei which form the rigid geometric structures similar to ductal carcinoma in-situ (DCIS), but only involves part of the membrane-bound ductal-lobular space. This finding indicates a moderately increased risk of invasive breast cancer, which is five times above that of the general population.

Atypical/indeterminate: probably benign, but a definitive diagnosis cannot be provided due to either technical difficulties such as limited cellularity or poor preservation, or due to the inherent nature of certain breast lesions such as papilloma vs. papillary carcinoma, fibroadenoma vs. phyllodes tumors, proliferative lesions with atypia vs. in-situ or low-grade infiltrating carcinomas.

Atypical Lobular Hyperplasia (ALH): a proliferation of cells confined to the ductal-lobular space which has some but not all of the features of lobular carcinoma in-situ and is characterized by a population of bland, round cells which are evenly spaced and often of smaller size than those seen in ADH or DCIS. These cells resemble those of lobular carcinoma in-situ, but do not completely fill and distend the glandular acinus leaving intercellular spaces, or involve less than half of the multiple acini in a lobular unit. This finding indicates a moderately increased risk of invasive breast cancer, which is five times above that of the general population.

Benign: no evidence of malignancy; includes fibrocystic change without atypia, fibroadenoma, pregnancy or treatment-associated changes, infectious and inflammatory conditions.

Biopsy: a surgical procedure in which tissue samples are removed for examination under a microscope. The biopsies can include minimally invasive techniques such as core biopsy or larger core procedures guided by mammography or ultrasound (i.e., the Bard gun or vacuum-assisted core biopsies). Biopsies can also refer to open incisional or excisional biopsies.

Breast Self Examination (BSE): a technique in which a methodical examination by a woman is performed of her own breasts to detect palpable changes. Breast self-examination has not been shown to improve survival from breast cancer, but it is an important, easily accessible tool, which can inform a woman of the need for medical attention.

Computer-Aided Detection (CAD) in Mammography: an adjunct to mammography that uses computer programs to mark suspicious areas in breast tissue. It takes the images of breast tissue and does a “second-read,” putting signals on areas where the radiologist should focus attention.

Calcifications: (see microcalcifications): refers to a number of distinct types of calcium phosphate or calcium oxalate deposits in benign and malignant breast epithelium and in periductal stroma. Microcalcifications can be psammomatous, indeterminate, dystrophic, or large coarse tumoral calcification. Microcalcifications do not necessarily indicate a malignant process.

Carcinoma In Situ: a malignant epithelial tumor, in the breast limited to the duct system and ductolobular units, and incapable at this stage of invading beyond the duct wall into the adjacent parenchyma.

Clinical Breast Examination (CBE): a physical breast examination performed by a licensed medical professional, including MD, NP, PA, CNM.


PAGE 41Comedo: a term that refers to the gross appearance of certain duct carcinomas in situ in which central areas of necrotic tumor cells accumulate. These were initially seen to resemble comedones of the skin, hence the term. At present, comedo frequently is used as an adjective to describe certain types of duct carcinoma in situ in which areas of necrosis occur. Computerized Axial Tomography Scan (CAT Scan): a scan procedure in which multiple x-rays are taken of all or part of the body to produce an image of internal organs.

Concordant: agreement in the types of data that occur in natural pairs. For breast diagnostic work-up, all test and procedure results are in agreement with one another.

Core Needle Biopsy: removal of a piece of tissue with a needle, which is examined under a microscope to see if cancer cells are present. The patient is given a local anesthetic before a core biopsy is done.

Cribiform: type of DCIS where the cells filling the duct have punched out areas.

Cumulative Lifetime Risk: a statistically derived number assuming all women live to be a certain age.

Cyst: a fluid-filled structure that is benign if it has no internal echoes, has a smooth wall with no internal masses through enhancement on ultrasound.

Cystosarcoma Phylloides: unusual type of breast tumor.

Cytologist: one who specializes in studying cells.

Diagnostic Workup: any of the follow-up procedures used to establish a final diagnosis (e.g., additional mammogram views such as special views, spot compression or magnification techniques; ultrasound, fine-needle aspiration, core needle biopsy, MRI, or consultation with a breast specialist or surgeon).

Differentiation: in cancer, refers to how mature (developed) the cancer cells are within a tumor: differentiated resemble normal cells and grow at a slower rate than undifferentiated, which lack the structure of normal cells and grow at a more rapid rate.

Digital Mammography: an x-ray mammography system that produces digital images using a computer receptor. Standard mammography produces images on radiographic film.

Discordant: for diagnostic work-up, all test and procedure results are not in agreement, hence further evaluation needs to be done.

Ductal Carcinoma In-Situ (DCIS): non-invasive breast cancer characterized by distended ducts and lobules lined by an increased number of cells. Nuclear grading (I-III), presence of zonal necrosis, architectural sub-type contribute to classification. DCIS is detected by mammography and can appear as fine granular, coarsely granular or micro-calcifications on film.

Duct Ectasia (cysts): a dilatation of medium to large ducts lined by flattened cells, filled with amorphous debris, and associated with periductal inflammation.

Ductal Lavage: a relatively new technique being studied as a potential additional measure for breast cancer screening. Currently being used with high-risk patients.

Ductography (Galactography): radiography of the mammary ducts after injection of a radio-opaque substance into the duct system.

Epithelial Hyperplasia: an increased proliferation of cells lining the ductal-lobular unit, which distend the glandular space. The cells are variable in appearance; maintain their polarity and form irregular, slit-like spaces.

Excisional Biopsy: surgery to remove an entire tumor or mass which is then studied under a microscope to see if cancer cells are present.

False-Positive Result: an initial positive test result that is truly negative after complete evaluation.

False-Negative Result: an initial negative test result that is truly positive after complete evaluation.

Fat Necrosis: area of dead fat usually following some form of trauma or surgery and can be the cause of lumps and/or calcifications on a mammogram.


PAGE 42

Fibroadenoma: a focal well-circumscribed growth of glands and stroma in which proliferating stroma surrounds the growing glands and often compress and distort them.

Fibrocystic Change: a benign condition representing focal, non-uniform changes in the breast tissue representing a wide variety of pathologic changes.

Fibrosis: increased collagen deposition within the breast stroma.

Fine-Needle Aspiration (FNA): biopsy technique used to evaluate palpable masses by placing a small gauge needle into a lesion and extracting cells.

Galactocele: milk cyst sometimes found in a nursing mother’s breast.

Galactography: (see Ductography)

Genetic Counselor: an individual with a masters degree in genetic counseling and eligible for board certification in genetic counseling.

Genetic Risk Counseling and Testing: a method to determine an individual’s risk of disease that passes genetically (such as some breast cancers) by examining the history and genetic material (blood cells) or the family.

Grade: describes how closely a cancer resembles normal tissue of the same type, and the cancer’s probable rate of growth (see differentiation).

Gynecomastia: swollen breast tissue in a man or boy.

HER-2/neu: an oncogene found in some breast and ovarian cancer patients that is associated with a poor prognosis.

Heterozygote: a person possessing two different forms of a particular gene, one inherited from each parent. A heterozygote is also called a carrier.

Histology: study of tissue removed by biopsy or other surgery to determine whether or not cancer is present. Cytology as well as the overall structure of the tissue is examined.

Hormonal Therapy: treatment of postmenopausal women with synthetic hormones.

Hormone Receptor Test: a test to measure the amount of certain proteins, called hormone receptors, in breast cancer tissue. A high level means that the hormones (attached to the protein) probably help the cancer grow.

Hyperplasia: excessive growth of cells.

Imaging: a technology to produce a picture of the inside of the body. Includes mammogram, ultrasound, CAT, MRI, and x-ray.

Incidence: the number of women who get breast cancer in a defined number of women in the population during a given time period.

Infiltrating Ductal Carcinoma: the most common type of invasive breast cancer, accounting for as much as 75-80% of all breast cancers. It is occasionally referred to as carcinoma of no special type. These tumors can vary microscopically in their degree of tubule formation, mitotic rate and nuclear pleomorphism. Grading these features can help determine prognosis. There are several sub-types of ductal carcinoma, all of which are considered to have an improved survival rate over those of no special type.

Infiltrating Lobular Carcinoma: characterized histologically by small cells, which frequently contain a cytoplasmic vacuole, which are classically arranged in a single-file arrangement. The stroma is densely sclerotic giving this tumor a rock-hard feeling to palpation and making the cells difficult to remove by fine needle aspiration. This tumor has an intermediate prognosis in its classic form (variants do exist), and has an increased incidence of multi-focality and bilaterality.

Inflammatory Breast Cancer: a rare type of breast cancer in which cancer cells invade the lymphatic channels of the skin causing a redness and firmness of the breast.

In Situ: the cancer cells are contained within the duct or lobule and have no ability to metastasize.


PAGE 43Intraductal Papilloma: benign tumor which projects like a finger from the lining of the duct.

Invasive (infiltrating) Cancer/Carcinoma: cancer that has spread beyond the layer of tissue in which it developed.

Lobular Neoplasia: a term used to represent the spectrum of changes, which include atypical lobular hyperplasia, and lobular carcinoma in-situ, which some pathologists may prefer due to controversies on criteria for differential diagnosis of the two lesions.

Lobular Carcinoma In-Situ (LCIS): characterized microscopically by distention of at least half of the acini in a lobular unit by a very round uniform population of small cells, which may have clear cytoplasm or nuclear vacuoles. Usually an incidental finding in breast tissue removed for another indication, frequently multi-focal and bilateral, and rarely causes clinical findings or changes on a mammogram. This finding indicates a 10 fold increased risk of invasive breast cancer above that of the general population.

Localized Breast Cancer: cancer that is confined to the breast.

Lumpectomy: surgery to remove a breast tumor and a small margin of normal surrounding tissue. Lumpectomy is usually followed by radiation. May be the first and only surgical excision of a breast lesion if the proper pre-operative diagnosis and work-up is done.

Lymphedema: swelling in the arm caused by excess fluid that collects after lymph nodes and vessels are removed by surgery or treated by radiation.

Macrocalcifications: calcifications typically larger (greater than 2-3 mm) in size than microcalcifications and are considered benign. These coarse calcium deposits are most likely due to aging, old injuries, or inflammation.

Magnetic Resonance Imaging (MRI): an imaging technique that uses a powerful magnet to transmit radio waves through the body to produce an image of the internal structures.

Malignant: cancerous neoplasm that should be further characterized as a specific type such as ductal or lobular carcinoma, either in-situ or invasive.

Malignant Phyllodes Tumor: formerly called cystosarcoma phyllodes. Characterized by a proliferation of glands and malignant stroma with more than 10 mitoses per high field. It may resemble fibrosarcoma or have heterologous elements such as malignant bone cartilage, skeletal muscle or fat. Unlike carcinomas, it can spread along nerves in addition and metastasize hematogenously.

Mammogram: a low dose x-ray technique especially designed to detect breast cancer.

Mammotome®: a minimally invasive alternative to open surgical biopsy, which uses a unique vacuum-assisted technique to provide tissue samples.

Margins: the edge of the tissue removed at a biopsy, a partial mastectomy, or a mastectomy. For optimal control of cancer, the margin of tissue should not have cancer.

Mastalgia: pain in the breast.

Medical Geneticist (or Clinical Geneticist): a physician with specialty training in genetics and eligibility for board certification by the American College of Medical Genetics.

Medullary Carcinoma: characterized histologically by syncytial sheets of large extremely pleomorphic cells with a prominent lymphoid infiltrate. Usually well circumscribed with little fibrous reaction; can feel deceptively soft and benign.

Microcalcifications: tiny deposits of calcium in the breast detected on a mammogram. A cluster of these small specks of calcium may indicate that an early cancer is present.

Mucinous (colloid) Carcinoma: a well-differentiated form of ductal carcinoma, accounts for two percent of all breast cancers, is more common in older women, usually well-circumscribed, and is characterized by the production of abundant pools of mucin making it deceptively soft and benign.


PAGE 44Mucocele Lesion: mucus lakes that may be due to benign reasons (e.g. sometimes seen with ruptured cysts) or may be associated with nearby (un-sampled) DCIS or invasive mucinous carcinoma.

Oncogene: tumor genes present in human cells that can be activated by carcinogens and cause cells to grow uncontrollably and form a tumor.

Open Surgical Excisional Biopsy: surgical removal of a breast lesion, considered the gold standard against which other diagnostic techniques are compared.

Papillary Carcinoma: usually occurs in larger ducts, which can be cystically dilated. Resembles the frond-like branching structure of the benign papilloma, but is lined by atypical cells.

Papillary Neoplasm: a group of neoplasms with a “papillary” growth pattern characterized by epithelial proliferations supported by fibrovascular stalks. They may occur anywhere within the ductal system and may be benign (intraductal papilloma), atypical or malignant (intraductal papillary carcinoma.)

Papilloma: benign frond- or finger-like growth with a fibrovascular core which is always associated with epithelial hyperplasia of varying degrees. Can occur in large or small ducts and can be solitary or multiple.

Papillomatosis: multiple, small papillomas.

Pathologist: doctor who specializes in examining tissue and diagnosing disease.

Phyllodes Tumor: a group of circumscribed biphasic tumors (composed of benign epithelial elements and a cellular, spindle cell stroma) similar to fibroadenoma in appearance but that grow rapidly and have a potential for a sarcoma arising from the stromal component. They are called “phyllodes” (from the Greek term “leaf like” because they have a leaf-like pattern of growth seen by the naked eye and microscopically.)

Poland’s Syndrome: a congenital condition where there is no breast development on one side of the chest.

Polymastia: literally many breasts. Existence of an extra breast or breasts.

Positron Emission Tomography (PET): the PET machine is used to detect the degree to which the different parts of the body use glucose. If glucose is being consumed faster in certain parts of the body, this will be revealed in the PET Scan, and it may indicate the presence of a cancerous tumor by highlighting the area on imaging.

Pre-Operative Needle (or wire) Localization Biopsy: pre-operatively, a radiographic technique used to find small lesions detected by mammography. A radiologist inserts a wire through a needle into the breast to mark non-palpable lesions detected by mammography. The wire guides the surgeon to the lesion for tissue removal, hence is a combined radiography and surgical technique.

Radial Scar: an abnormal mammographic finding that requires a core biopsy to rule out atypia; if atypia is found, excisional biopsy is recommended to rule-out breast cancer.

Relative Risk: a number used to compare the impact of different risk factors associated with the likelihood of developing breast cancer.

Risk Factor: anything that increases a person’s chance of developing disease.

S-Phase: the time during which an individual cell makes new DNA chromosomes in preparation for dividing and becoming two cells. The higher the percentage of cells that are in S-phase, the more dangerous a cancer is.

Scintimammography: a breast imaging technique that tracks radioactive tracers as they concentrate in cancer cells.

Sclerosing Adenosis: A benign proliferation of acini within a lobule associated with fibrosis and distortion of the lobule.

Screening: the search for disease in an asymptomatic population-at-risk with the hope of finding disease at an earlier and more treatable phase. Screening tests for breast cancer include CBE and imaging.

Sentinel Lymph Node Biopsy: the tumor site is injected with a blue dye and /or a radioisotope that flows to the sentinel lymph node. This node is removed and examined by a pathologist. If there are no cancer cells in the sentinel node, no further nodes are removed.


PAGE 45Staging: the method used to determine the extent of a cancer, especially whether it has spread from its original site to other parts of the body.

Stereotactic Core Biopsy: a method using a series of computerized mammograms to identify an abnormality in three dimensions. This more accurately pinpoints a non-palpable lesion in order to collect tissue for pathologic examination. This procedure offers an enhanced ability to sample (biopsy) suspicious clustered calcifications.

Suspicious/Probably Malignant: highly suggestive of malignancy, but a definitive diagnosis cannot be made due either to technical difficulties such as limited cellularity or poor preservation, or due to the inherent similarity of certain breast lesions such as papilloma vs. papillary carcinoma, fibroadenoma vs. phyllodes tumors, proliferative lesions with atypia vs. in-situ or low-grade infiltrating carcinomas.

Tamoxifen: estrogen blocker used in treating breast cancer.

Timeliness: a set of terms used to define the timeliness for follow-up. There is expert consensus in the following terms:

Immediate…as soon as possible Short-term (short interval)…with-in one to three months Short-term (medium interval)…in six months Routine…in one to three years (depending on age category)

Tubular Carcinoma: the most well differentiated form of ductal carcinoma, frequently presenting as small occult lesions discovered by screening mammography, and usually curable. Derives its name from well-defined oval or round tubular structures formed by cells with little atypia.

Ultrasound: an imaging technique that uses high-frequency sound waves to produce an image of the internal structures of the breast.



BibliographyAmerican Cancer Society. (2004, September). California cancer facts and figures 2005. Oakland, Ca: Author.

American College of Radiology (ACR). (2003). Appropriate imaging work-up of palpable breast masses. ACR Appropriateness Criteria. Retrieved Oct. 11, 2003, from http://www.acr.org/ac pda American College of Radiology (ACR). (2003). BI-RADS® - Ultrasound. Reston, VA : Author.

American College of Radiology. (2003). Breast imaging reporting and data system (BI-RADS)‰ (4th ed.). Reston, VA: Author.

Amir, E., Evans, D.G., Shenton, A., Lalloo, F., Moran, A., Boggis, C., et al. (2003). Evaluation of breast cancer risk assessment packages in the family history evaluation and screening program. Journal of Medical Genetics, 40, 807-814.

Apantaku, L. (2000). Breast cancer diagnosis and screening. American Family Physician, 62, 596-602, 605-6.

Baines, C.J. (2000). Screening for breast cancer: how useful are clinical breast examinations. Journal of the National Cancer Institute, 92, 958-959.

Baker, J. A., Soo, M. S. (2000). The evolving role of sonography in evaluating solid breast masses. Semin Ultrasound CT MR, 21(4), 286-96.

Barton, M., Harris, R., Fletcher, S. (1999). Does this patient have breast cancer? The screening clinical breast examination: Should it be done? How? Journal of the American Medical Association, 282 (13), 1270-1280.

Bassett, L., Jackson, V., Jahan, R., Ful, Y., Gold, R. (1997). Diagnosis of diseases of the breast. Philadelphia: W.B. Saunders.

Bassett L.W. (2002, March). Options in breast biopsy. Imaging Economics.

Bassett, L. W., Jackson, V. P., Fu, K. L., Fu, Y. S. (2005). Diagnosis of Diseases of the Breast (2nd ed.). Philadelphia: Elsevier Saunders.

Bates B. (1979). A guide to physical examination (2nd ed.). Philadelphia: JP Lippincott.

Beyer, T., Moonka, R. (2003). Normal mammography and ultrasonography in the setting of palpable breast cancer. American Journal of Surgery, 185 (5), 416-419.

Bobo, J. K., Lee, N. C., Thames, S.F. (2000). Findings from 752,081 clinical breast examinations reported to a national screening program from 1995 through 1998. Journal of the National Cancer Institute, 92(12), 971-976.

Bodai, B. I., Linm, A., Nakata, T., Chesshire, S. (1999). Breast Disease: Clinical Guidelines for Practitioners. (Available from The Breast Health Center, Kaiser Permanente, 1650 Response Road, Sacramento, CA 95815)

Brekelmans, C. T. M., Seynaeve, C., Bartels, C. C. M., Tilanus-Linthorst, M. M. A., Meijers-Heijboer, E. J., Crepin, C. M. G., et al. (2001). Effectiveness of breast cancer surveillance in BRCA1/2 gene mutation carriers and women with high familial risk. Journal of Clinical Oncology, 19, 924-930.

Brenner, R. J., Bassett, L. W., Fajardo, L. L., Dershaw, D. D., Evans, P. W., Hunt, R., et al. (2001). Stereotactic core-needle breast biopsy: a multi-institutional prospective trial. Radiology, 218(3), 866-872.

Brown, E. F., Goldberg, S., Scheuner, M. T., Short, M. P. (2001). Identifying and managing hereditary risk for breast and ovarian cancer. Retrieved from the American Medical Association Web site: http://www.ama-assn.org/cmeselec/mhrboc/index.htm

Burke, W., Daly, M., Garber, J., Botkin, J., Ellis Kahn, M. J., Lynch, P. (1997). Recommendations for follow-up care of individuals with an inherited predisposition to cancer. II. BRCA1 and BRCA2. Cancer Genetics Studies Consortium. Journal of the American Medical Association, 277, 997-1003.

Byrd, B. F. (1985). Standard Breast Examination. New York: American Cancer Society.

Cady, B., Steele, G. D., Jr., Morrow, M., Gardner, B., Smith, B. L., Lee, N. C., et al. (1998). Evaluation of common breast problems: Guidance for primary care providers. CA: A Cancer Journal for Clinicians, 48(1), 49-63.

California Department of Health Services. (1999). Clinical breast examination: proficiency and risk management. (2nd ed.) Davis: University of California.


PAGE 47Claus, E. B., Risch, N., Thompson, W. D. (1994). Autosomal dominant inheritance of early-onset breast cancer. Implications for risk prediction. Cancer, 73(3), 643-651.

Clinical Breast Protocols Workgroup, California Department of Health Services. (2000). Breast diagnostic algorithms for primary care clinicians. (Rev. 2nd ed.). Davis: University of California.

Cristofanilli, M., Singletary, E. S., Hortobagyi, G. N. (2004). Inflammatory breast carcinoma: the sphinx of breast cancer research. Journal of Clinical Oncology, 22, 381-383.

Cummings, S. R., Eckert. S., Krueger, K. A., Grady, D., Powles, T. J., Cauley, J. A., et al. (1999). The effect of raloxifene on risk of breast cancer in postmenopausal women. Results of the MORE randomized trial. Journal of the American Medical Association, 281, 2189-2197.

Endogenous Hormones Breast Cancer Collaborative Group (2003). Body mass index serum sex hormones, and breast cancer risk in postmenopausal women. Journal of the National Cancer Institute, 95, 1218-1226.

Fisher, B., Costantino, J. P., Wickerham, D. L., Redmond, C. K., Kavanah, M., Cronin, W. M., et al. (1998). Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. Journal of the National Cancer Institute, 90, 1371-1388.

Florio, M. A., Fam, F., Giacombbe, G., Pollicino, A., Scarfo, P. (2003). Nipple discharge: personal experience with 2,818 cases. Chirurgia Italiana, 55(3), 357-363. Abstract obtained from PubMed, PMID: 12872570.

Frykberg, E. R. (1999). Lobular carcinoma in situ of the breast. The Breast Journal, 5(5), 296-302.

Fu, W., Mittel, V. K., Young, S. (2001). Paget disease of the breast: analysis of 41 patients. American Journal of Clinical Oncology, 24(4), 397-400.

Gail, M. H., Brinton, L. A., Byar, D. P., Corle, D. K., Green, S. B., Schairer, C., et al. (1989). Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. Journal of the National Cancer Institute, 81(24), 1879-86.

Georgian-Smith, D., Taylor, K. J. W., Madjar, H., Goldberg, B., Merritt, C. R. B., Bokobsa, J., et al. (2000). Sonography of palpable breast cancer. Journal of Clinical Ultrasound, 28(5), 211-216.

Green, B. B., & Taplin, S. H. (2003). Breast cancer screening controversies. The Journal of the American Board of Family Practice, 16, 233-241.

Goodson, W., & Moore, D. H. (2002). Causes of physician delay in the diagnosis of breast cancer. Archives of Internal Medicine, 162(12), 1343-1348.

Goodson, W. H. (1996). Clinical breast examination. Western Journal of Medicine, 164, 355–358.

Haagensen, C. D. (1986). Diseases of the breast (3rd ed.). Philadelphia: Saunders.

Harris, J. R., Lippman, M. E., Morrow, M., Hellman, S. (1996). Diseases of the breast. Philadelphia: Lippincott-Raven.

Hartmann, L. C., Schaid, D. J., Woods, J. E., Crotty, T. P., Myers, J. L., Arnold, P. G., et al. (1999). Efficacy of bilateral prophylactic mastectomy in women with a family history of breast cancer. New England Journal of Medicine,340, 77-84.

Hughes, L. E., Mansel, R. E., Webster, D. T.J. (2000). Benign disorders and diseases of the breast--concepts and clinical management (2nd ed.). New York: WB Saunders. Hill, D. A., Preston-Martin, S., Ross, R., Bernstein, L. (2002). Medical radiation, family history of cancer, and benign breast disease in relation to breast cancer risk in young women, USA. Cancer Causes and Control, 13, 711–718.

Institute for Clinical Systems Improvement. (2003). Breast Disease, Diagnosis of (formerly Breast Cancer Diagnosis). ICSI Healthcare Guideline. Retrieved from http://www.icsi.org/knowledge/detail.asp?catID=29&itemID=168.

Institute for Healthcare Improvement. (2000). Clinical: reference management. Eye on Improvement, VII(20).

Jacobs, T. W., Connolly, J.L., Schnitt, S. J. (2002). Nonmalignant lesions in breast core needle biopsies: to excise or not to excise? American Journal of Surgical Pathology, 26(9), 1095-1110.

Jacobs, T. W., Byrne, C., Colditz, G., Connolly, J. L., Schnitt, S. J. (1999). Radial scars in benign breast-biopsy specimens and the risk of breast cancer. New England Journal of Medicine, 340(6), 430-436.

Jernström, H., Lubinski, J., Lynch, H. T., Ghadirian, P., Neuhausen, S., Isaacs, C., et al. (2004). Breast-feeding and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. Journal of the National Cancer Institute 96, 1094-1098.


PAGE 48Kauff, N. D., Satagopan, J. M., Robson, M. E., Scheuer, L., Hensley, M., Hudis, C. A., et al. (2002). Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation. New England Journal of Medicine, 346, 1609-1615.

Khan, S. A., Apkarian, A. V. (2002). The characteristics of cyclical and non-cyclical mastalgia: a prospective study using a modified McGill pain questionnaire. Breast Cancer Research and Treatment, 5(2), 147-157.

Kerlikowske, K., Grady, D., Barclay, J., Sickles, E. A., Eaton, A., Ernster, V. (1993). Positive predictive value of screening mammography by age and family history of breast cancer. Journal of the American Medical Association, 270, 2444-2450.

Kerlikowske, K., Smith-Bindman, R., Ljung, B., Grady, D. (2003). Evaluation of abnormal mammography results and palpable breast abnormalities. Annals of Internal Medicine, 139(4), 274-284.

King, M-C., Wieand, S., Hale, K., Lee, M., Walsh, T., Owens, K., et al. (2001). Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2: National Surgical Adjuvant Breast and Bowel Project (NSABP-P1) Breast Cancer Prevention Trial . Journal of the American Medical Association,286, 2251-2256.

King, M-C., Marks, J. H., Mandell, J. B. (2003). Breast and ovarian cancer risk due to inherited mutations in BRCA1 and BRCA2. Science, 302(5645), 643-646.

Komenaka, I. K., Ditkoff, B. A., Joseph, K. A., Russo, D., Gorroochurn, P., Ward, M., et al. (2004). The development of interval breast malignancies in patients with BRCA mutations. Cancer, 100(10), 2079-2083.

Kopans, D. B., Moore, R., McCarthy, K., Hall, D., Hulka, C., Whitman, G., et al. (1997). Should women with implants or a history of treatment for breast cancer be excluded from mammography screening programs? American Journal of Roentgenology, 168(1), 29-31.

Kriege, M., Brekelmans, C. T. M., Boetes, C., Besnard, P. E., Zonderland, H. M., Obdeijn, I. M., et al. (2004). Efficacy of MRI and mammography for breast-cancer screening in women with a familial or genetic predisposition. New England Journal of Medicine, 351, 427-437.

Lagios, M. D. (2003). The clinical significance of immunohistochemically detectable epithelial cells in sentinel lymph node and bone marrow in breast cancer. Journal of Surgical Oncology, 83(1), 1-4.

Lev-Schelouch, D., Sperber, F., Gat, A., Klausner, J., Gutman, M. (2003). Paget’s disease of the breast [Electronic Version]. Harefuah, 142(6), 433-437, 485.

Liberman, L. (2002). Percutaneous image-guided core breast biopsy. Radiology Clinics of North America, 40(3), 483-500.

Liberman, L., Drotman, M., Morris, E. A., LaTrenta, L. R. (2000). Imaging-histologic discordance at percutaneous breast biopsy (an indicator of missed cancer). Cancer, 89(12), 2538-2546.

Lucas, J. H., & Cone, D. L. (2003). Breast cyst aspiration. American Family Physician, 68, 1983-1986, 1989.

Mandelson, M. T., Oestreicher, N., Porter, P. L., White, D., Finder, C. A., Taplin, S. H., et al. (2000). Breast density as a predictor of mammographic detection: comparison of interval-and screen-detected cancers. Journal of the National Cancer Institute, 92(13), 1081-1087.

Marcus, E. (2004). The management of Paget’s disease of the breast. Current Treatment Options in Oncology, 5(2), 153-60.

Mehta, T. S. (2003). Current uses of ultrasound in the evaluation of the breast. Radiology Clinics of North America, 41(4), 841-856.

Meijers-Heijboer, H., Van Geel, B., Van Putten, W. L. J., Henzen-Logmans, S. C., Seynaeve, C., Menke-Pluymers, M. B. E., et.al. (2001). Breast cancer after prophylactic bilateral mastectomy in women with a BRCA1 or BRCA2 mutation. New England Journal of Medicine, 345, 159-164.

McDonnell, S. K., Schaid, D. J., Myers, J. L., Grant, C. S., Donohue, J. H., Woods, J. E., et.al. (2001). Efficacy of contralateral prophylactic mastectomy in women with a personal and family history of breast cancer. Journal of Clinical Oncology, 19, 3938-3943.

Meyer, J., Smith, D. N., Lester, S. C., Kaelin, C., DiPiro, P. J., Denison, C. M., et al. (1999). Large-core needle biopsy of nonpalpable breast lesions. Journal of the American Medical Association, 281(17), 1638-1641.

Metcalfe, K., Lynch, H. T., Ghadirian, P., Tung, N., Olivotto, I., Warner, E., et al. (2004). Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. Journal of Clinical Oncology, 22(12), 2328-2335.


PAGE 49Michell, M. J., & Miaad, A-A. (2003). Detection of subtle mammographic signs of malignancy. Applied Radiology, 32(9), 11-16.

Mincey, B. A. (2003). Genetics and the management of women at high risk for breast cancer. Oncologist, 8(5), 466-473.

Modan, B., Hartge, P., Hirsh-Yechezkel, G., Chetrit, A., Lubin, F., Beller, U., et.al. (2001). Parity, oral contraceptives, and the risk of ovarian cancer among carriers and noncarriers of a BRCA1 or BRCA2 mutation. New England Journal of Medicine, 345, 235-240. Morris, A. M., Flowers, C. R., Morris, K. T., Schmidt, W. A., Pommier, R. F., Vetto, J. T. (2003). Comparing the cost-effectiveness of the triple test score to traditional methods for evaluating palpable breast masses. Medical Care, 41, 962-971.

Morris, K. T., Vetto, J. T., Petty, J. K., Lum, S. S., Schmidt, W. A., Toth-Fejel, S., et al. (2002). A new score for the evaluation of palpable breast masses in women under age 40. American Journal of Surgery, 184, 245-247.

Morrison, C. (1998). The significance of nipple discharge. Lippincott’s Primary Care Practice, 2(2), 129-140.

Morrow, M. (2000). Physical examination of the breast. In J. R. Harris, M. E. Lippman, M. Morrow, & C. K. Osborne, (Eds.), Diseases of the breast (2nd ed., pp. 67-70). Philadelphia: Lippincott, Williams and Wilkins.

Morrow, M. (2000). The evaluation of common breast problems. American Family Physician, 61, 2371-2378, 2385.

Moyer, P. (2003, May 2). Breast cancer in younger women calls for flexibility in imaging. Retrieved July 8, 2004, from http://www.auntminnie.com/index.asp?Sec=sup&Sub=wom&Pag=dis&ItemId=58007

Narod, S. A., Risch, H., Moslehi, R., Dorum, A., Neuhausen, S., Olsson, H., et al. (1998). Oral contraceptives and the risk of hereditary ovarian cancer. Hereditary Ovarian Cancer Clinical Study Group. New England Journal of Medicine, 339, 424-428.

Narod, S.A., Brunet, J. S., Ghadirian, P., Robson, M., Heimdal, K., Neuhausen, S. L., et al. (2000). Tamoxifen and risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: a case-control study. Hereditary Breast Cancer Clinical Study Group. Lancet, 356(9245), 1876-1881.

National Cancer Institute. (2002). Cancer Facts. Paget’s disease of the breast: questions and answers. [Brochure]. Author.

Newman, L. A., & Sabel, M. (2003). Advances in breast cancer detection and management. Medical Clinics of North America, 87(5), 997-1028.

Oregon Breast & Cervical Cancer Program. (2003). Breast Cancer Diagnostic & Follow-Up Protocols. Portland.

Orel, S., Kay, N., Reynolds, C., Sullivan, D. (1999). BI-RADS® categorization as a predictor of malignancy. Radiology, 211(3), 845-850.

Piekarski, J., Jeziorski, A., Baklinska, M., Szymczak, W., Zadrozny, M., Berner, J. (2004). Patients with Paget disease of nipple and with palpable mass in breast have unfavorable prognosis. Journal of Experimental & Clinical Cancer Research, 23(1), 33-37.

Preston, D.L., Mattsson, A., Holmberg, E., Shore, R., Hildreth, N. G., Boice, J. D., Jr. (2002). Radiation effects on breast cancer risk: a pooled analysis of eight cohorts. Radiation Research, 158(2), 220-235.

Pruthi, S. (2001). Detection and evaluation of a palpable breast mass, Mayo Clinic Proceedings, 76(6), 641-647.

Rebbeck, T. R., Levin, A. M., Eisen, A., Snyder, C., Watson, P., Cannon-Albright. L., et.al. (1999). Breast cancer risk after bilateral prophylactic oophorectomy in BRCA1 carriers. Journal of the National Cancer Institute, 91, 1475-1479.

Rebbeck, T. R., Lynch, H. T., Neuhausen, S. L., Narod, S. A., van’t Veer, L., Garber, J. E., et.al. (2002). Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. New England Journal of Medicine, 346, 1616-1622.

Rockhill, B., Spiegelman, D., Byrne, C., Hunter, D. J., Colditz, G. A. (2001). Validation of the Gail et al. model of breast cancer risk prediction and implications for chemoprevention. Journal of the National Cancer Institute, 93(5), 358-366.

Rosen, E., Sickles, E., Keating, D. (1999). Ability of mammography to reveal nonpalpable breast cancer in women with palpable breast masses. American Journal of Roentgenology,172(2), 309-312.

Salami, N., Hirschowitz, S., Nieberg, R., Apple, S. (1999). Triple test approach to inadequate fine needle aspiration biopsies of palpable breast lesions. Acta Cytologica, 43(3), 339-343.


PAGE 50Saslow, D., Hannan, J., Osuch, J., Alcati, M.H., Baines, C., et.al. (2004). Clinical breast examination: practical recommendation for optimizing performance and reporting, CA: A Cancer Journal for Clinicians, 54:327-344.

Scheuer, L., Kauff, N., Robson, M., Kelly, B., Barakat, R., Satagopan, J., et al. (2002). Outcome of preventive surgery and screening for breast and ovarian cancer in BRCA mutation carriers. Journal of Clinical Oncology, 20, 1260-1268.

Scheuner, M. T., Karlan, B.Y. (2002). The genetic basis of common diseases (2nd ed.). New York: Oxford University Press.

Seidell, H. M., Ball, J. W., Dains, J. E., Benedict, G. W. (1995). Breasts and axillae. Mosby’s Guide to Physical Examination (3rd ed.) (pp. 444-470). St Louis: C. V. Mosby.

Sellers, T. A., Mink, P. J., Cerhan, J. R., Zheng, W., Anderson, K. E., Kushi, L. H., et.al. (1997). The role of hormone replacement therapy in the risk for breast cancer and the total mortality in women with a family history of breast cancer. Annals of Internal Medicine,127, 973-980.

Shaw de Paredes, E. (2000). Missed breast cancer: avoiding this pitfall. Applied Radiology, 29.

Shaw, V. I., Raju, U., Chitale, D., Deshpande, V., Gregory, N., Strand, V. (2003). False negative core needle biopsies of the breast. Cancer, 97, 1824-1831.

Sheen-Chen, S. M., Chen, H. S., Chen, W. J., Eng, H. L., Sheen, C. W., Chou, F. F. (2001). Paget disease of the breast - an easily overlooked disease? Journal of Surgical Oncology, 76(4), 261-265.

Shetty, M. K., Shah, Y. P., Sharman, R. S. (2003). Prospective evaluation of the value of combined mammographic and sonographic assessment in patients with palpable abnormalities of the breast. Journal of Ultrasound in Medicine, 22, 263-268, 278-297.

Sickles, E. (1997). Radiological diagnosis of breast diseases. New York: Springer Verlag.

Smith, R. A., Cokkinides, V., Eyre, H. J. (2004). American Cancer Society Guidelines for the Early Detection of Cancer, CA: A Cancer Journal for Clinicians,54(1), 41-52.

Smith, R. A., Saslow, D., Sawyer, K. A., Burke, W., Costanza, M. E., Evans, W. P. 3rd, et al. (2003). American Cancer Society guidelines for breast cancer screening; update 2003. CA: A Cancer Journal for Clinicians, 53, 141-169.

Sun, Q., Zhou, Y. D., Huang, H.Y. (2003). Diagnosis and treatment of Paget’s disease of the breast: report of 33 cases. Zhongguo Yi Xue Ke Xue Yuan Xue Bao, 25(1), 93-95.

Steinberg, K. K., Thacker, S. B., Smith, S. J., Stroup, D. F., Zack, M. M., Flanders, D., et.al. (1991). A meta-analysis of the effect of estrogen replacement therapy on the risk of breast cancer. Journal of the American Medical Association, 265, 1985-1990.

Tyrer, J., Duffy, S. W., Cuzick, J. (2004). A breast cancer prediction model incorporating familial and personal risk factors. Statistics in Medicine, 23, 1111–1130.

Ursin, G., Henderson, B. E., Haile, R. W., Pike, M. C., Zhou, N., Diep, A., et al. (1997). Does oral contraceptive use increase the risk of breast cancer in women with BRCA1/BRCA2 mutations more than in other women? Cancer Research, 57, 3678-3681.

U.S. Preventive Services Task Force (2005). Hormone therapy for the prevention of chronic conditions in postmenopausal women: recommendations from the U.S. Preventive Services Task Force. Annals of Internal Medicine, 142(10), 855-860.

Varas, X., Leborgne, J. H., Leborgne, F., Mezzera, J., Jaumandreu, S., Leborgne, F. (2002). Revisiting the mammographic follow-up of BI-RADS® category 3 lesions. American Journal of Roentgenology, 179(3), 691-695.

Vasen, H. F., Haites, N. E., Evans, D. G., Stell, C. M., Moller, P., Hodgson, S., et.al. (1998). Current policies for surveillance and management in women at risk of breast and ovarian cancer: a survey among 16 European family cancer clinics. European Familial Breast Cancer Collaborative Group. European Journal of Cancer, 34, 1922-1926.

Vetto, J., Pommier, R., Schmidt, W., Wachtel, M., DuBois, P., Jones, M., et al. (2003). Use of the “Triple Test” for palpable breast lesions yields high diagnostic accuracy and cost savings. American Journal of Preventative Medicine, 24(2), 128-135.


PAGE 51Williams, R. S. (2002). The relevance of reported symptoms in a breast screening program. Clinical Radiology, 57(8), 725-729.

Yasmeen, S., Pettinger, M., Chlebowski, R. T., Robbins, J. A., et al. (2003). Frequency and predictive value of a mammographic recommendation for short-interval follow-up. Journal of the National Cancer Institute, 95(6), 429-436.

Yen, M. F., Tabar, L., Vitak, B., Smith, R. A., Chen, H. H., Duffy, S. W. (2003). Quantifying the potential problem of over diagnosis of ductal carcinoma in situ in breast cancer screening. European Journal of Cancer, 39(12), 1746-1754.

Yoon, P. W., Scheuner, M. T., Khoury, M. J. (2003). Research priorities for evaluating family history in the prevention of common chronic diseases. American Journal of Preventive Medicine, 24(2), 128-135.



Previous Edition Acknowledgements

2000 Edition Lawrence D. Wagman, MD, Chairman, Division of Surgery, and Director,

Department of General Oncologic Surgery, City of Hope National Medical Center, Duarte, CA (Workgroup Chairman)

Robyn Birdwell, MD, Assistant Professor of Radiology, Stanford University Hospital, Stanford, CA

Charles Elboim, MD, General Surgeon, Sonoma, CA Patricia Ganz, MD, Division of Cancer Control, UCLA School of Medicine

and Public Health, Los Angeles, CA Lydia Howell, MD, Department of Pathology, University of California Davis

Medical Center, Sacramento, CA Julie Ohnemus, MD, Family Practitioner, Arcata, CA Greg Talavera, MD, Family Practitioner, Department of Family and

Preventive Medicine, University of California, San Diego and Graduate School of Public Health, San Diego, CA

1997 Edition Lawrence D. Wagman, MD, Chairman, Division of Surgery, and Director,

Department of General Oncologic Surgery, City of Hope National Medical Center, Duarte, CA (Workgroup Chairman)

Carol Beatty, MD, Department of Radiology, University of California, Davis Medical Center, Sacramento, CA

Patricia Ganz, MD, UCLA School of Medicine and Public Health, Division of Cancer Control, Los Angeles, CA

Lydia Howell, MD, UC Davis Medical Center, Department of Pathology, Sacramento, CA

Joy Melnikow, MD, Department of Family Practice, University of California, Davis Medical Center, Sacramento, CA

Greg Talavera, MD, Family Practitioner, UCSD Department of Family and Preventive Medicine, and SDSU Graduate School of Public Health, San Diego, CA

cds algorithms 2005a

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