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Breast CancerManagementClinical Guidelines

Prepared by the Clinical Guidelines CommitteeRoyal College of Surgeons in Ireland

November 2000

Mr. T. N. WalshProf. N. O’Higgins

Mr. T. N. WalshSenior Lecturer in Surgery

Royal College of Surgeons in IrelandJames Connolly Memorial Hospital, Dublin

Prof. N. O’HigginsProfessor of Surgery, University College Dublin

(St. Vincent’s University Hospital)Member of Council, Royal College of Surgeons in Ireland

Breast Cancer Management Clinical Guidelines 1

Contents

Introduction 2

Role of Individual Services in a Breast Unit 3

General practitioner 3Surgeon 3Breast-care nurse 3Radiologist and radiographer 4Pathologist 4Medical oncologist 5Radiation therapist 5Data management 5

Diagnosis of Breast Disease 6

Mammography 6Surveillance of women at special riskfor breast cancer 6

High risk group 6Moderate risk group 7Low risk group 7

Management of a breast lump 7Triple assessment 7Open surgical biopsy 8

Management of Breast Cancer 9

Treatment planning 9Avoidance of delay in surgical treatment 9Decision-making 9

History and physical examination 9Mammography 11Histology 11Patient preference 11Pre-operative staging tests 11Resection margins 11

Surgery for Primary Operable Breast Cancer 12

Surgery of the breast 12Breast conserving surgery (BCS) 12Contraindications to breast conservation 12Points on surgical technique 12Risk factors for local recurrence 13Further surgery followingconservative resection 13

Surgery of the axilla 13Evaluation of the sentinel lymphnode in breast cancer 14

Management of non-invasive breast cancer 16Ductal carcinoma in situ (DCIS) 16Management of DCIS 16Skin-sparing mastectomy 16Factors favouring mastectomy in DCIS 17Lobular carcinoma in situ (LCIS) 17Treatment of ductal carcinomain situ (DCIS) and Paget’s Disease 18

Breast reconstruction 19Follow-up of the breast cancer patient 19Communication with general practitioners 19

Adjuvant Systemic Therapy in Breast Cancer 20

Chemotherapy 20Endocrine therapy 20Adjuvant therapy in node-negative patients 21Adjuvant therapy in node-positive patients 21Radiotherapy 23

Management of Recurrent Disease 24

Local recurrence 24Contralateral primary breast cancer 24Locally advanced primary breast cancer 24Regional recurrence 24Metastatic breast cancer 25Palliative and terminal care 25

Training and Continuing Education 26

Surgical training 26An estimate of the surgical workloadin a breast unit 26Standards and audit 26

References 27

Table 1 Survival after BCS 10

Table 2 Recurrance after BCS 10

Table 3 Sentinel node data sheet 15

Table 4 DCIS and Paget’s disease 18

Table 5 Risk in node-negative patients 21

Table 6 Node-negative patients 22

Table 7 Node-positive patients 22

Introduction

Guidelines in the management of breast cancershould lead to:

■ a uniformly high standard of surgical treatmentthroughout the country

■ reassurance of patients that surgicalmanagement is standardised

■ standardisation of radiotherapy andchemotherapy

■ identification of resources needed to fulfil theseguidelines in all hospitals treating breast cancer

In Ireland, most patients with breast cancer presentwhen they are symptomatic. The introduction ofscreening will increase the number of asymptomaticlesions. The highest quality of care is required tooptimise the chances of cure with the leastmorbidity for all patients. This is best achieved in amultidisciplinary setting with high-quality surgery,medical oncology and radiotherapy together withthe support provided by a breast care nursingservice.

A team consisting of surgeons, radiologists,pathologists, medical oncologists and nursespecialists, each of whom specialises in breastdisease, should manage breast cancer. A Breast Unitshould treat a minimum of 100 new primary breastcancer patients annually.

A Breast Unit is defined by the staff,multidisciplinary teams and resources that it appliesto the management of breast disease.

Most of the Breast Unit’s work is outpatient-basedand involves ‘reassuring the worried well’. Amultidisciplinary approach is more effective if allclinicians follow guidelines. Standards of treatmentand outcome of breast cancer vary between andwithin countries1. Guidelines can help to reducethese variations and allay public concern.

A breast practice generates a large administrativeworkload and it is essential that the breast team hasadequate clerical support.

Breast Cancer Management Clinical Guidelines2

GENERALPRACTITIONER In Ireland, referral to a breast surgeon is usually viaa general practitioner (GP). It is essential thereforethat the links between GPs and Breast Units be ofthe best quality to facilitate urgent referral. BreastUnits should communicate the diagnosis andproposed treatments to the GP.

Patients who can be managed by thegeneral practitioner include:■ women with minor or moderate degrees of

breast pain who do not have a palpable distinctlump.

■ women under 50 years of age with multiductalnipple discharge, which is not troublesome orblood-stained.

■ asymptomatic women with a negative familyhistory who are at low risk of developing breastcancer.

■ young women with tender nodular breasts andolder women with symmetrical nodularity whohave no focal lesion demonstrable.

When referring patients the term ‘urgent’ should beused only for patients with symptoms or signshighly suggestive of breast cancer.

‘Urgent’ referrals include:

■ discrete lump in a women over 30 years of age.

■ skin ulceration.

■ distortion of breast or nipple-areolar complex

■ an intradermal nodule

■ blood-stained nipple discharge.

This ‘urgent’ list serves as a guide, and does notimply that all other patients should be considerednon-urgent. The decision to refer to the BreastClinic should be at the discretion of the generalpractitioner.2

SURGEONThe primary care of breast cancer is theresponsibility of the surgeon. In the majority ofcases the surgeon establishes the diagnosis andprovides the initial treatment. High quality surgerymaximises the chance of cure and of local control,reduces morbidity, and provides best pathologicalinformation for prognosis and selection of othertherapy. The surgeon should remain the primary co-ordinator of care for patients with breast cancer.

It is the duty of the surgeon to discuss the diagnosisand treatment options with the patient and toensure that the patient has sufficient understandingof the issues to allow her to be an active participantin the decision-making process. The surgeon alsohas responsibility for co-ordinating themultidisciplinary team. Surgeons with specialtraining and expertise should treat patients withbreast cancer because surgical subspecialisation incommon cancers improves the standard of care andoutcome.3-6

Follow-up of breast cancer patients involves thesurgeon as a member of the multidisciplinary team.

The trained surgeon treating patients with breastdisease should demonstrate this interest byparticipating in audit and by his/her continuingmedical education (CME) activity.7

BREAST-CARE NURSEA breast-care nurse should be available for allpatients undergoing treatment for breast disease.Breast Units treating 100 breast cancer patients perannum need two breast-care nurses. It is mandatorythat these nurses attend the multidisciplinary breastmeeting. A suitable room should be available sothat consultations can take place in private. Thepresence of the patient’s husband, other relative orfriend should be encouraged.

The nurse should see patients on the ward beforeand after surgery where the patient’s concerns andpersonal problems can be discussed. She should beoffered advice on bras, swimwear and choice ofpermanent prostheses. Temporary prostheses shouldbe fitted by the nurse before discharge and bookletsgiven on treatment, support groups and continuingcare.

Breast Cancer Management Clinical Guidelines 3Role of Individual Servicesin a Breast Unit

Role of Individual Services in a Breast Unit

Following axillary surgery and/or radiotherapy sheshould advise all patients on arm care. Followingsurgery for breast cancer, she should observe allpatients for signs of anxiety and depression.

The nurse should update herself with knowledge ofbreast disease. She needs to be involved in theeducation of nursing staff on breast disease, both inthe hospital setting and elsewhere.8

RADIOLOGIST ANDRADIOGRAPHERBreast imaging must be performed and reported byradiologists with expertise in breast disease andwho reach the appropriate standards. Theradiologist is an integral member of the Breast Unit.The surgeon and radiologist must consult regularlyabout the diagnostic breast clinic.

Imaging and physics standards are the responsibilityof the radiologist(s) on the Breast Unit. Physicsservices should meet the appropriate guidelines.Each unit should have in place a quality-controlprogramme to monitor and maintain standards.9-13

The radiology service should optimise the qualityobtained in their existing equipment including films,screens, cassettes and processors to achieve imagesof acceptably high quality. Radiological equipment,when due for replacement, should be replaced byequipment which meets internationally acceptedstandards.

Mammography equipment suitable formagnification and localisation procedures must beavailable. Ultrasound equipment suitable for breastexamination is also essential.

Reports should include details of the site, size,extent and nature of any abnormality, a descriptionof any significant associated features, and anopinion as to the most likely diagnosis. Radiologistsshould participate in regular audit of individualperformance.

Radiologists involved in diagnosis shouldparticipate in the imaging of patients followingtreatment and be familiar with imaging changes.Radiologists should be involved in decisions on themost appropriate imaging investigations.

A standardised proforma for reporting byradiologists should be devised.

Radiographers taking mammograms should holdthe appropriate certification of competence.Mammography should be performed only byradiographers with appropriate skills andknowledge. In a centre which has a screening unitthe same radiographers should work in thesymptomatic Breast Unit.

PATHOLOGISTThe Breast Unit must include pathologist(s) withexpertise in breast pathology and cytology.Histopathology laboratories must be accredited.Histopathology departments and surgeons musthave access to specimen radiography.

The diagnosis of breast cancer should be made pre-operatively in over 85% of cases. For palpablelesions the surgeon takes the core biopsy specimenwhile core biopsies of impalpable lesions are carriedout by the radiologist under image-guidance byultrasound or stereotactic methods.

Results of cytology (C) and core biopsyhistology (B) specimens are categorised asfollows:

C1 or B1 = no diagnosis possible

C2 or B2 = benign

C3 or B3 = atypia, probably benign

C4 or B4 = suspicious for malignancy

C5 or B5 = malignant

Histopathology procedures and reporting should bein accordance with international standards using theTNM system.14-16 There is a clear need for a definednationally operated proforma on reporting.Histopathology reports should include informationon the following factors:

■ the maximum diameter of carcinomas inmillimetres (mm)

■ the extent of intraductal and invasive disease


■ whether the tumour contains an in situcomponent and if so the size of the invasivecomponent

■ the size of the whole tumour

■ the distance between the tumour and thesurgical excision margins

■ tumours identified as multicentric should be soreported

■ the histological grade of the cancer

■ the presence or absence of lymphovascularinvasion

■ tumour oestrogen receptor and progesteronereceptor status

■ the number of axillary lymph nodes examined,their location (Level I, II, and III) and the extentof involvement by metastatic carcinoma.

MEDICAL ONCOLOGISTImprovements in recurrence-free survival andoverall survival for breast cancer patients have beendue to the multidisciplinary approach to theproblem of breast disease. The development of thespeciality of medical oncology has lead tosignificant advances in adjuvant therapies. Suchtreatments have undoubtedly improved the survivalof patients with early breast cancer. The medicaloncologist therefore, is an important and intrinsicpart of the Breast Unit and should be involved inthe multidisciplinary meetings of all patients withbreast cancer at a time when treatment is beingplanned. As primary chemotherapy may becomemore widely practiced, it is appropriate that themedical oncologist be involved at the early stages ofthe decision-making process. The input of medicaloncology into locally advanced and metastaticbreast cancer is also most important and combinedclinics with surgeon, medical oncologist andradiotherapist in the follow-up of patients withbreast cancer should be routine.

RADIATION THERAPISTAs with the medical oncologist, the radiotherapistshould be involved at the early stages of treatmentplanning for patients with proven carcinoma of thebreast. Close consultation between the surgeon andradiotherapist in patients undergoing breastconservation surgery permits the radiotherapist toplan post-operative treatment carefully. The opinionof the radiotherapist is also valuable in post-mastectomy patients where the issue of chest wallirradiation is important. Furthermore, liaisonbetween surgeon and radiotherapist becomes ofcritical importance in the area of the axilla asradiotherapy to the axilla which has been surgicallycleared is inappropriate. New techniques inradiotherapy for breast disease are evolving and thescope and application for radiotherapy is increasingfor patients with breast cancer. Therefore, theradiation therapist should be an intrinsic part of theBreast Unit after the primary diagnosis has beenmade. The radiotherapist will also have a keeninterest in follow-up as radiotherapy has animportant palliative role to play in both locallyadvanced and metastatic breast cancer.

DATA MANAGEMENT The Breast Unit must collect patient dataprospectively and requires adequate resources interms of information technology and dataprocessing. This data must be made available to theNational Cancer Registry database for properepidemiological studies. Breast Units should beaudited annually in a similar way to thearrangement for the National Breast ScreeningProgramme, BreastCheck. A National ReferenceCentre is recommended to co-ordinate annual audit.

Breast Cancer Management Clinical Guidelines 5Role of Individual Services in a Breast Unit of Breast Disease

Diagnosis of Breast Disease

Diagnosis of breast cancer should be based on tripleassessment, where clinical examination is followedby imaging and cytology/pathology as required. TheBreast Unit should produce a rapid multidisciplinaryassessment for patients with breast disease. Forpatient convenience diagnostic tests should bearranged to minimise the number of visits.

Patients should receive all the diagnostic testsrequired at the first visit so that they can bereassured as soon as possible that there is noabnormality or that their lesion is benign. If thelesion is likely to be malignant there is a case to bemade for providing time for the patient to adjust tothe realisation of the significance of the diagnosis. Itis often appropriate to discuss the diagnosis ofbreast cancer at one visit and the management at asubsequent visit.

Any symptomatic breast referral may be acarcinoma. Patients should be seen soon afterreferral to identify the problem and to alleviateanxiety. The hospital administration is responsiblefor providing adequate facilities and personnel tomeet these standards.

MAMMOGRAPHYDecisions as to who should have mammographyshould be made only by members of the BreastUnit.

Mammography should not be the sole or initialdiagnostic test for symptomatic breast disease.A negative mammogram does not exclude cancer.The sensitivity of mammography alone is over 80%but is considerably less in young patients.17

A mammogram is not required in all women withbreast symptoms. Palpable breast cancers may notbe visible on a mammogram, particularly in a youngwoman. Mammography is generally inappropriateunder the age of 35 unless there is a specificindication.

Pre-operative mammography is essential forassessment of all patients with operable breastcancer.

There is no evidence that women on hormonereplacement therapy (HRT) require more frequentmammograms than received through the NationalBreast Screening Programme. This also applies towomen who are taking HRT under 50 years of age.

Screening is currently advised for women over 50years of age. Populations of women who are not athigh risk of breast cancer do not benefit fromroutine screening mammography under 50 years ofage. The majority of breast cancers are notgenetically inherited. The assumption thatidentification of cancer gene mutations will reducemortality is unproven. Referral to a Family HistoryClinic provides an opportunity for proper riskassessment, counselling, and the opportunity to takepart in screening or prevention studies and anyother research programme.

SURVEILLANCE OF WOMEN ATSPECIAL RISK FOR BREASTCANCER

The following is a management strategy for womenwith concerns about their family history.

High Risk GroupThe high-risk group is defined as:

■ breast/ovarian cancer families with 4 or moreaffected relatives on the same side of the family

■ breast cancer families with 3 affected relativeswith an age at diagnosis of under 40 years

■ breast/ovarian cancer families with 3 affectedrelatives with breast cancer diagnosed under 60years

■ families with one member with both breast andovarian cancer.

These patients require consultation with aconsultant in human genetics in association with thepatient’s clinician.


Moderate Risk GroupThe moderate risk group includes women with:

■ one first-degree relative with breast cancerdiagnosed under the age of 40 years

■ two first-or second-degree relatives with breastcancer diagnosed under the age of 60 years, orovarian cancer at any age

■ three first-or second-degree relatives with breastor ovarian cancer diagnosed at any age

■ a first-degree relative with bilateral cancer underthe age of 60 years

■ a first-degree male relative with breast cancer atany age.

The relative risk for breast cancer in these women isat least 3 times that of the general population.

A possible age-dependent screening protocol forhigh-risk and moderate-risk groups might be:

■ Over age 50 Mammography every 18 months

■ Age 35-49 Annual mammography (considerscreening from 5 years prior toage at diagnosis in relative if thisis age under 39 years).

■ Below age 35 No mammography.

Low-Risk Group The strategy for these women should be to discussthe difference between familial and non-familialcancer and to explain that that individual’s risk isnot significantly elevated. They should be informedthat the risk of non-familial breast cancer remainsand be encouraged to participate in the breastscreening at an appropriate age. The advice offeredto women should be the same, whether in primarycare or in the Breast Unit.

MANAGEMENT OF A PATIENTWITH A BREAST LUMPPatients should be encouraged to bring somebodywith them when the results are being discussed.Breaking bad news should be done in a professionalway by the surgeon with a breast-care nurse inattendance. The consultation should br conducted

in a sensitive fashion and should not be rushed. Itshould take place in an appropriate environmentwith adequate privacy.

The follow-up arrangements should be clear topatient, doctor and breast-care nurse. The patientmust have a contact telephone number for thebreast-care nurse.

Triple AssessmentAssessment of a patient with a breast lump requiresa careful history and clinical examination by thesurgeon.18 Further assessment of a discrete breastlump is based on Triple Assessment.

If a discrete lump is found fine needle aspiration isperformed.19 If the aspirate contains fluid which isnot blood stained and the lump disappears, the fluidneed not be sent for cytology and no further actionis needed other than an imaging procedure. If theaspirate is blood-stained or the mass remains theaspirate should be sent for cytology.

If the breast lump is solid, fine needle aspirationcytology (FNAC) provides useful information. Theresults of FNAC are variable and are operator - andpathologist - dependent. FNAC is valuable in thatpatients with clinically benign and cytologicallybenign lesions may be reassured. Where thediagnosis is positive on cytology confirmatory testscan be performed.

FNAC cannot distinguish between invasive andin-situ carcinoma. Core biopsy provides tissue forhistological examination and therefore allowsdefinition of whether a tumour is invasive or non-invasive, provided a representative sample of tissuehas been taken. Core biopsy sensitivity variesbetween 67% and 95%.20-21 Advantages of corebiopsy over FNAC are that tissue can be processedas ordinary histology and oestrogen receptor statusdetermined. The use of automated core biopsydevices increases sensitivity of core needle biopsy.

Open surgical biopsy can be performed if corebiopsy is negative or inappropriate. However, over90% of patients should be diagnosed without openbiopsy. The diagnosis of breast cancer should beestablished before definitive treatment isundertaken.

Breast Cancer Management Clinical Guidelines 7Diagnosis of Breast Disease

Diagnosis of Breast Disease

A mammogram should be performed in womenover 35 years of age or if the mass is clinicallymalignant.22 Mammography should be performedbefore FNAC if the mass is suspected to bemalignant as haematoma can interfere withinterpretation. Mammography in this settingassesses the risk of malignancy and screens bothbreasts for non-palpable lesions that may affect thesurgery performed. Mammography has a falsenegative rate of up to 20% in palpable breastcancer.

Open Surgical BiopsyIn the small number of cases in which open surgicalbiopsy is needed for diagnosis (e.g. needlelocalisation for calcification) the surgeon orpathologist should weigh the specimens. Biopsies fordiagnosis of impalpable lesions that prove to bebenign should weigh less than 15 grams in 90% ofcases.

Some breast operations are suitable for day-casesurgery but this is not always so. There must berecognition of the emotional needs and generalhealth of the woman. The decision as to whetherday case surgery is appropriate should be made onan individual basis by the surgeon and not dictatedby a general management policy by hospitaladministration.


TREATMENT PLANNINGTreatment of the primary tumour must followwritten protocols agreed by the Breast Unit.23

Following diagnosis, women must be givenadequate time, information and support in order tomake a fully informed decisions about treatment.This must include discussion of treatment optionswith the surgeon with the breast-care nurse inattendance.

The treatment options offered and the decisionsagreed with the patient must be recorded. In theevent of a patient refusing the treatment optionsrecommended this should also be recorded. Theremust be close communication between the surgeon,the medical oncologist and the radiotherapist toplan primary treatment and facilitate adjuvanttherapy.

A care plan must be drawn up and recorded foreach woman. This must take account of predictivefactors of local or regional recurrence and ofsurvival, of social circumstances and patientpreferences. Planning should also allow discussionof reconstructive surgery options.

Consultants within the Breast Unit (surgery,radiology, pathology, medical oncology, andradiotherapy) must have contractual time forattendance at the multidisciplinary meeting. Breastsurgery trainees, and breast-care nurses must attendmultidisciplinary meeting.

All patients should receive advice on reconstructivebreast surgery where appropriate. There should beadequate facilities for outpatients, inpatients, daypatients and theatre sessions.

AVOIDANCE OF DELAY INSURGICAL TREATMENTWhen a decision has been reached on surgery,patients should be offered a date for operation.Diagnostic or therapeutic surgery is associated witha great deal of patient anxiety. Such surgery shouldtherefore be classified as ‘urgent’.

The date offered for surgery should be within 2 – 3weeks of the diagnosis to minimise patient anxiety.24

There is no evidence, however, that a delay of 4weeks has any effect on survival. Management mustmake resources available to achieve these targets.

DECISION-MAKINGEvidence is available at 18 years follow-up on sixprospective trials comparing mastectomy andaxillary clearance with breast conservation andaxillary clearance.25-31 Whole breast irradiation withdoses of 45 to 50Gy were used in all these trials.(Tables 1 and 2). None of the trials demonstratedsignificant differences in overall or disease-freesurvival with either treatment. In only one trial 29

was a significantly higher risk of local recurrenceidentified in the breast conservation group. In thisstudy, however, only gross tumour removal wasrequired for entry to the trial.

Local recurrence after breast conservation may bethe result of inappropriate patient selection,inadequate surgery or inadequate radiation therapy.The incidence of local recurrence in the treatedbreast varies between 3 and 19%. Most of theserecurrences can be treated by mastectomy andsurvival after such an event is approximately 75%at 5 years. The incidence of chest wall recurrenceafter primary mastectomy ranges between 4 and14%.

The critical elements in selection of patients forbreast conservation are:

■ history and physical examination

■ mammography

■ histology

■ assessment of the patient’s needs andexpectations

History and Physical ExaminationA young age is not a contraindication to breastconservation. In elderly women, the physiologicalrather than the chronological age and the presenceor absence of co-morbidity should be thedetermining factors. A family history of breastcancer, including the age at diagnosis and whetherthe family member had bilateral breast cancer arerelevant. A family history of ovarian, endometrialor other tumours is also taken into account.

On physical examination, the tumour size andlocation are important as is the size of the breast. A3 cm tumour in the periphery of a large breast maybe suitable for breast conservation while a similarlesion in a small breast may make a satisfactoryresult from breast conservation less likely, both in


Management of Breast Cancer

Management of Breast Cancer


Comparison of Survival after Breast Conserving Surgery and Radiotherapywith Mastectomy – Prospective Randomized Trials

Endpoint Overall Survival (%) Disease Free Survival (%)Trial (years) CS & R (P Value) Mastectomy CS & R (P Value) Mastectomy

National CancerInstitute, Milan26 18 65% (NS) 65% N/A N/A

Institut Gustave-Roussy27 15 73% (.19) 65% N/A N/A

NSABP B-0628 12 63% (.12) 59% 50% (.21) 49%

National CancerInstitute, U.S.A.29 10 77% (.89) 75% 72% (.93) 69%

EORTC30 8 54% (NS) 61% N/A N/A

Danish BreastCancer Group31 6 79% (NS) 82% 70% (NS) 66%

CS & R = conservative therapy and radiation: EORTC = European Organization for Research and Treatment of Cancer;N/A = data not available: NS = not significant; NSABP = National Surgical Adjuvant Breast and Bowel Project

Table 1

Comparison of Local Recurrence after Breast Conserving Surgeryand Radiation with Mastectomy – Prospective Randomized Trials

Local Recurrence (%)Trial Endpoint CS & R (P Value) Mastectomy

National CancerInstitute, Milan26 Cumulative incidence at 18 years 7% (NS) 4%

Institut Gustave-Roussy27 Cumulative incidence at 15 years 9% (NS) 14%

NSABP B-0628 Cumulative incidence at 8 years 10% (NS) 8%

National Cancer Crude incidence, median follow-up 19% (.01) 6%Institute, USA29 10.1 years

EORTC30 Crude incidence at 14 years 17% (NS) 4%

Danish Breast Crude incidence, median follow-up 3% (NS) 4%Cancer Group31 3.3 years

CS & R = conservative therapy and radiation: EORTC = European Organization for Research and Treatment of Cancer;N/A = data not available: NS = not significant; NSABP = National Surgical Adjuvant Breast and Bowel Project

Table 2

Winchester, Cox25

Winchester, Cox25

terms or histological clearance and acceptablecosmesis. Patients with multiple primary breasttumours are unlikely to be suitable for breastconservation. If there is evidence of locallyadvanced breast cancer, such as skin ulceration, thepresence of satellite nodules, inflammatorycarcinoma, fixed axillary lymph nodes orlymphoedema, the patient should be considered forprimary systemic therapy. It should be noted thatskin tethering or retraction of the nipple or ofbreast parenchyma are not signs of locally advancedbreast cancer and are not contraindications tobreast conservation.

MammographyMammography is a requirement for patients withbreast cancer and is a prerequisite in determiningsuitability for breast conservation. It defines theextent of the disease and whether the tumour isunicentric or multicentric. It also indicates thepresence and extent of microcalcification and allowsevaluation of the opposite breast.

HistologyThe histological features indicating an increased riskof local recurrence after breast conservation arelisted under ‘Risk Factors for Local Recurrence’ andare taken into account when planning primarysurgery.

Patient PreferenceThe surgeon should discuss with the patient, in thepresence of the breast-care nurse, the benefits andrisks of breast conservation compared with those ofmastectomy. Issues of survival, local recurrence,psychological adjustment, cosmetic outcome,functional capacity and sexuality should be takeninto account.

PRE-OPERATIVE STAGING TESTSAll patients should have a chest x-ray and liverfunction tests. Bone scanning and liver ultrasoundmay be done on a selective basis.32,33 There is goodevidence that a peri-operative search for occultmetastases (e.g. bone scan, liver ultrasound) doesnot yield useful information in a woman withoperable primary breast cancer. These investigationsshould be carried out only if the patient issymptomatic or for the investigation of symptomsin the follow-up clinic or as part of a clinical trial.

The goals of breast cancer surgery are cure ofcancer, local disease control with the provision ofaccurate pathological staging and a satisfactorycosmetic result. This should occur where there isinfrastructure to ensure physical and psychologicalrehabilitation.

Resection marginsAll tumours should be removed with an adequatesurgical margin. If resection margins are not clearfurther surgery should be recommended. Anadequate margin may be defined as that whichresults in a local recurrence of less than 5% at 5years, in the conserved breast. Clear margins of 1cm should be the aim but this is not alwayspossible, particularly for tumours situated close tothe pectoralis major muscle. To minimise thenumber of therapeutic operations in womenundergoing conservation surgery the number ofoperations should be recorded.

To ensure that all necessary data are obtainedhistological node status should have been obtainedin patients with invasive breast cancer. Formalaxillary dissection should be performed. Themorbidity of the procedure can be minimised withmeticulous surgery, physiotherapy and by avoidingirradiation to the surgically cleared axilla.

Appropriate treatment should be given to patientswith ductal carcinoma in situ (DCIS) in the absenceof invasive breast cancer. A local excision is notappropriate for extensive or multifocal DCIS.Patients with previously diagnosed DCIS should notundergo an axillary clearance.

Breast Cancer Management Clinical Guidelines 11Management of Breast Cancer

Surgery for PrimaryOperable Breast Cancer

SURGERY OF THE BREAST

Breast Conserving Surgery (BCS) All patients should be considered, but not allpatients are suitable, for BCS. Conservation of thebreast without compromising the goals of breastcancer surgery is the preferred option. Appropriateconservative surgery to the breast followed byradiotherapy gives similar survival to more radicalsurgery.

Breast conserving surgery (followed by radiationtherapy to the conserved breast) is the treatment ofchoice for unifocal invasive breast cancer providedthat the disease can be excised with histologicallyclear margins of at least 5mm around thetumour.34,35 The use of metallic clips to the tumourbed facilitates subsequent radiotherapy. The tumourbed can be seen on x-ray films taken duringsimulation so that a radiation boost can be given tothis area if indicated. Rigorous histopathologicalassessment of the margins of the excised specimen isrequired. The excised specimen should be orientatedfor the pathologist. This can be done convenientlyby the use of sutures according to the locally agreedprotocol. The specimen should be inked by thepathologist. Oestrogen and progesterone receptorstatus can be measured by ELISA at designatedcentres. Receptor status can also be estimated byimmunohistochemistry on fixed sections.

Some patients who have undergone conservativeresection for invasive breast cancer require furtherexcision or completion mastectomy once the fullhistological report is available as the risk of localrecurrence within the breast is unacceptably high ifthe resection margins are involved by tumour.Studies have found variation in the rates of breastconservation treatments in the United Kingdom.Not all patients are suitable for breast conservationsurgery. Mastectomy is indicated in situations wherethe disease is multifocal or in situations whereradiotherapy is contra-indicated. The possibility ofbreast reconstruction should be offered to allpatients undergoing mastectomy.

Contraindications to Breast ConservationIndications for total mastectomy are:

■ multifocal disease

■ two or more primary tumours in separatequadrants of the breast

■ anticipated poor cosmetic result

■ breast cancer occurring in the 1st and 2nd

trimester of pregnancy

■ inability to obtain histologically clear margins

■ patient preference and

■ contraindications to radiotherapy.

Patients undergoing mastectomy or/and certainpatient after BCS should be considered for breastreconstruction.

Relative contraindications to breast conservationinclude collagen vascular disease as such patientstolerate radiotherapy poorly. Tumour size per se isnot a contraindication to breast conservationalthough adequate resection of a large tumour in asmall breast might result in unacceptable cosmeticdeformity.

Points on Surgical TechniqueThere are several technical considerations which thesurgeon should take into account to minimise risksof local recurrence and to maximise the cosmeticresult.

■ curvilinear incision (radial for large mass inlower quadrants)

■ incision directly over the lesion

■ separate incision for the axillary surgery

■ at least 1cm gross margin (margins must behistologically clear)

■ pectoralis fascia removed in deep lesions

■ metallic clips (titanium) to the tumour bed

■ no drain or deep sutures to the breast arerecommended but drainage of the axilla isadvised.

■ subcuticular suture


Risk Factors for Local RecurrenceRisk factors for local recurrence, following BCSinclude:

■ positive surgical margins for tumour

■ tumour near the margin

■ radiotherapy not given

■ extensive DCIS or extensive intraductcomponent (EIC) associated with an invasivecancer

■ extensive lymph node involvement(more than 4 nodes)

■ young age

■ multiple tumours

■ high grade tumours

■ lymphovascular invasion

■ tumour necrosis.

Further Surgery followingConservative Resection Some patients, having undergone conservativeresection, may require further excision orcompletion mastectomy when the full histologicalreport is available. It should be explained to thepatient in advance that the risk of local recurrenceis unacceptably high if resection margins areinvolved

The risk of local recurrence after breast conservingsurgery, if radiotherapy is not given, is up to 43%at 9 years compared with 12% if radiotherapy isused. Patients having BCS should therefore haveradiotherapy to the residual breast.

SURGERY OF THE AXILLAThe aims of axillary surgery are:

■ to accurately stage the disease

■ to provide prognostic information

■ to provide a rational basis for subsequentsystemic therapy

■ to prevent axillary recurrence

■ to increase the likelihood of cure.

Clinical examination of the axilla is inaccurate withfalse positive and false negative rates of 30% soaxillary surgery is needed to stage the disease. Thechances of axillary involvement is high even whenthe primary tumour is small. The number of nodesinvolved is also important.

Formal axillary clearance involves removal of LevelsI, II, and III nodes. The number of nodes involved isimportant in estimation of prognosis and hence inthe selection of adjuvant therapy.36-44 Lymph nodesampling frequently does not provide sufficientnumber of nodes for accurate staging as no nodesmay be retrieved. Sampling missed nodal metastasesin 14% of patients in one study. The technique ofaxillary lymph node sampling is, therefore, poorlydefined and provides an uncertain yield of nodes.

Level I removal of axillary contents from thelateral border of latissimus dorsi tothe lateral border of pectoralis minorup to the axillary vein; this usuallyinvolves complete dissection of theaxillary vein on its anterior andinferior surfaces for a distance of 6 to8cms.

Level I-II Level I and, in addition, removal ofthe contents posterior to pectoralisminor.

Level I-III Level I-II and contents medial to themedial border of pectoralis minor upto the subclavius muscle (Halsted’sligament)

■ If Level I nodes are involved the chances ofLevel II-III being involved is 41%.

■ Level I clearance will miss the 3% of cases thathave skip lesions - involvement of Level II andIII with negative Level I.

■ If a Level I-II clearance is performed only 0.5%of skip metastases to Level III would be missed

Breast Cancer Management Clinical Guidelines 13Surgery for Primary Operable Breast Cancer

Surgery for Primary Operable Breast Cancer

■ Level I-III provides the best staging information.Although Level I-II will also provide accurateinformation, 22% of patients with positive LevelI-II nodes will have positive nodes at Level III.The average number of lymph nodes in acomplete axillary dissection is around 25.

■ With a full Level I-III clearance the incidence oflocal axillary recurrence is 1%. This contrastswith a relapse rate of 8% with radiotherapyalone and 21% with an expectant policy.

The thoraco-dorsal nerve and vessels and the longthoracic nerve are isolated and protectedthroughout their extent in the axilla and theintercosto-brachial nerve is protected if this isfeasible, unless it is surrounded by tumour. Formalaxillary dissection (Levels I, II and III) provides themost accurate staging information on the axilla. Arelationship exists between the size of the tumourand the likelihood of the axillary lymph nodes beingaffected. If a tumour is more than 5cms in diameter,more than 60% of patients have involved axillarylymph nodes whereas when the tumour is less than0.5cms only 3% of the nodes are affected.

Disadvantages of formal axillary clearance areseroma formation, arm swelling and shoulderstiffness. Significant arm swelling after axillaryclearance or radiotherapy occurs in 2% of cases.This increases to at least 30% if axillaryradiotherapy is added to surgical clearance. Axillaryirradiation should, therefore, generally be avoidedafter axillary clearance.

Evaluation of the Sentinel Lymph Node inBreast CancerPatient with uninvolved axillary lymph nodes donot benefit from axillary dissection andidentification of such patients before the lymphnodes are completely excised, would obviously bedesirable. Evaluation of the first lymph node thatdrains the tumour area (sentinel node) is underinvestigation in an attempt to avoid extensivesurgery on a “negative” axilla. Sentinel lymph nodemapping may identify patients most likely to benefitfrom axillary dissection and avoid the need foraxillary clearance by identifying node-negativepatients. The ideal technique, the extent of thehistopathological examination and the trainingrequired for accurate and reproducible results haveyet to be determined. For this reason the sentinelnode method remains investigational and should becarried out only in the context of a promisingmethod under evaluation.

A multicentre trial has demonstrated markedvariations among surgeons in the performance ofsentinel lymph node dissection.45 The adverseoncological consequences of this surgical procedurebeing poorly performed are serious. The results ofindividual surgeons should be audited before thesentinel node assessment becomes the only axillaryintervention. Because the procedure, whether doneby blue dye, by radio-isotope or by both, remainsunder evaluation, it should be performed only in thecontext of a subsequent verifiable axillary clearanceon each individual patient and the informationrequired for such an evaluation is demonstrated inTable 3. Most studies indicate that the combinationof blue dye and radio-isotope provides the mostaccurate means available at present.


Table 3

SENTINEL NODE DATA SHEET

Side: 1. Right 2. Left 3. Bilateral

Palpable mass: 0. No 1. Yes

Diagnosis: 1. FNA 2. Core 3. Surgical Biopsy

Location: 1. UOQ 2. LOQ 3. UIQ 4. LIQ 5. Central

Clinical size:

Pathological size:

Date of procedure: / /

Surgeon:

Number of nodes seen(approx)

Counts: Background

Injection site

Nodes Level I Nodes Level II Nodes Level III

Location (level) of node

Blue dye 0. No 1. Yes

Counts over skin

Counts in situ

Counts ex vivo

Bed count post excision

OPERATION: 1. Breast Conservation 2. Mastectomy

Number of sentinel nodes excised:

Number of sentinel nodes positive:

Number of axillary nodes excised:

Number of axillary nodes positive:

Total number of nodes excised:

Total number of nodes positive:

1. Dye only 2. Isotope only 3. Dye + Isotope 4. Failure

Comments about procedure:



MANAGEMENT OF NON-INVASIVEBREAST CANCERNon-invasive breast cancer includes ductalcarcinoma in situ (DCIS) and lobular carcinoma insitu (LCIS).

Ductal carcinoma in situ (DCIS)DCIS can present clinically by the presence of alump, Paget’s disease of the nipple or a bloodynipple discharge. DCIS may be detected clinically orby screening mammography. With the widespreaduse of mammography DCIS accounts for up to 30%of breast cancers. DCIS is a spectrum of histologicalsubtypes of diseases of different biologicalbehaviours; comedo, cribiform, micropapillary andsolid.46-48

Pathological reports should include the histologicalsub-type, its extent and margin involvement.Attempts have been made to classify DCISaccording to prognosis. The comedo-type has thegreatest potential for recurrence after localtreatment.49

When excision alone was compared with excisionand radiotherapy for DCIS there was a significantreduction in the local recurrence rates at 5 years inirradiated patients.51

The National Surgical Adjuvant Breast and BowelProject (NSABP B-17) was a prospectiverandomised trial comprising excision alone withexcision and radiotherapy in the treatment of ductalcarcinoma in situ (DCIS). The first report in 1993indicated a significant reduction in the 5-year ratesof local recurrence in the irradiation group ofpatients from 10.4% to 7.5% for non-invasiverecurrences and from 10.5% to 2.9% for invasiverecurrences. The European Organisation forResearch and Treatment of Cancer (EORTC) hasrecently published the results of a trial confirmingthat radiation decreases rates of local recurrence inDCIS patients treated with breast conservation.50

The reduction in invasive recurrence, noted inNSABP B-17, was not confirmed in the EORTCstudy and neither trial provided a subset analysisgiving comparative rates of local recurrence forvarious subgroups of DCIS. Of concern is theobservation in the EORTC study of an increasedrate of contralateral breast cancer in the irradiated

group. At present, the evidence is that radiotherapyto the breast in DCIS patients following breastconservation is beneficial, reducing local recurrencerates but it is not yet known which subgroupsbenefit.

Management of DCIS■ DCIS less than 0.5cm Segmental

mastectomy

■ DCIS 0.5-1.9cm Segmental mastectomy + radiotherapy

■ DCIS more than 2.0cm Total mastectomy

Thirty percent of patients with DCIS treated bybiopsy alone develop invasive breast cancer within10 years.

Total mastectomy had in the past been the standardtreatment for DCIS with a local recurrence of0.75% and an overall cancer-related mortality of1.7%. Wide excision plus radiotherapy gives arecurrence rate at 5 years of 10% versus 21% ifradiotherapy not given.50

Skin-sparing Mastectomy Wide excision alone is indicated for a small focus ofmammography-detected non-comedo DCIS. WhenBCS is performed the margins must be histologicallyfree as for invasive breast cancer. BCS mandatesfrequent follow up as 50% of the recurrences willbe invasive breast cancer. The 7-year disease freesurvival after excision and radiotherapy was 84%compared to 98% for mastectomy.

Skin-sparing mastectomy involves a procedurewhereby the breast tissue is excised whilstpreserving the overlying skin. This procedurecombines the possibility of removing all theunderlying breast tissue and affords the opportunityof placing an implant under the skin to preserve thebreast contour. In some circumstances thisprocedure may be carried out with preservation ofthe nipple-areolar complex but care must be takento ensure that resection margins are clear of DCIS.


Factors Favouring Mastectomyin DCIS include: ■ the presence of comedo necrosis

■ extensive disease on mammography

■ clinically palpable lump greater than 2cm

■ bloody nipple discharge

■ Paget’s disease

■ involved margins after resection

■ biological data indicating poorer prognosis e.g.high nuclear grade, high proliferation index,negative oestrogen receptor status

■ diffuse pattern of growth.

Axillary surgery is unnecessary in patients withDCIS as the risk of nodal involvement is 2%.52 LowLevel I axillary clearance is indicated for extensivedisease or microinvasion. The place of tamoxifen inthe management of DCIS remains to be established.An algorithm for the management of DCIS andPaget’s disease is presented in Table 4.

Lobular Carcinoma in situ (LCIS)LCIS is an incidental finding in pre-menopausalwomen. It has no clinical, mammographic or grosspathological features. LCIS does not requiretreatment. Its significance is that it is a “marker” ofincreased risk for the development of breast cancer.

The risk of breast cancer, equal for both breasts, is1% per annum for 15-20 years.53 This represents a12-fold risk over the general population. Closesurveillance with clinical examination and annualmammography is indicated. In spite of this there isa 7% breast cancer mortality rate in patientsfollowed up for LCIS.



Table 4

TREATMENT OF DUCTAL CARCINOMA IN SITU(DCIS) AND PAGET’S DISEASEEligibility into approved clinical trials should be considered. If not appropriate for a trial, the following schemacan be recommended.


BREAST RECONSTRUCTIONBreast reconstruction should be considered for allpatients who have undergone mastectomy.Consideration of this procedure may take placebefore or after mastectomy depending on thecircumstances. Evidence is accumulating that thelong-term results of immediate breast reconstructionare no worse than in delayed reconstruction.Reconstruction takes the form of synthetic implants,myocutaneous flaps or frequently a combination ofboth.

FOLLOW-UP OF THE BREASTCANCER PATIENTPatients should be supported by a specialist breastcare nurse who is a member of the Breast Unit andwho should have links with the ward nurses toassist in continuity of care. Following surgery, thefitting and supply of breast prostheses should beexplained to patients.

Patients should be informed about the range ofservices available and provided with literatureincluding details of follow-up treatment andinformation about local support groups. Supportgroups should preferably work with patients underthe direction of the breast-care nurse. Clinicalfollow-up involving the surgeon should take placeat regular intervals and annual mammography isrecommended.

On outpatients visits women may receive resultsand further treatment may be discussed. Atelephone contact number to discuss treatment andanswer questions is important. Women with benignconditions need similar opportunities.

Following diagnosis of cancer the patient must begiven adequate time, information and support inorder to make a fully informed decision about theirtreatment. This should include discussion with thesurgeon, in liaison with a breast-care nurse, ofappropriate treatment options. It is often preferableto have this discussion at a separate interview in anappropriately calm setting.

COMMUNICATION WITH GENERALPRACTITIONERSThe Breast Unit should ensure that GPs receivecommunications that gives them a clearunderstanding of the diagnosis, care plan andtoxicity profile of any proposed systemic treatment.Such communications must follow the first post-operative review and any subsequent change oftreatment.

Clinical trialists must ensure that GPs are fullybriefed about any trial that the patient is enteringand any potential side-effects which may ensue.


Adjuvant Systemic Therapyin Breast Cancer

Radiotherapy and chemotherapy should be directedby radiation oncologists and medical oncologistswho specialise in breast cancer. They should beactive members of the Breast Unit.

Treatment should be provided at the Breast Unitwhenever practicable. Standard chemotherapy maybe carried out at the Breast Unit or at anothercentre but arrangements must comply with therequirements for the safe handling of cytotoxicdrugs and has trained supervision.

Radiotherapy has to be provided at a RadiotherapyCentre but the patient should be cared for at thecentre by the radiotherapist attached to her ownBreast Unit.

Many issues in adjuvant therapies remainunresolved and await the outcome of carefullydesigned and rigorously conducted clinical trials.As large numbers of patients are needed for thesestudies, multicentre collaboration is needed.Surgeons, radiotherapists and medical oncologistsare encouraged to seek recruitment of their patientsin ethically approved international clinical trials inEurope and the United States in addition to inter-hospital studies within Ireland. A surgeon should beinvolved as a principal investigator in all trialsinvolving surgery, either as part of diagnostic ortherapeutic intervention.

CHEMOTHERAPYMost patients with breast cancer will require someform of adjuvant therapy. This will depend ontumour pathological characteristics, lymph nodeinvolvement, oestrogen receptor status and age ofthe patient.54-56

The role of chemotherapy is best defined in amultidisciplinary conference when all of thepathology information is available. In cases inwhich adjuvant chemotherapy is required, the timeinterval between the decision to give chemotherapyand the start of treatment should not exceed threeweeks. These target times include any waiting timefor ward or hostel accommodation. Local protocolsmay vary.

Delivery of cytotoxic chemotherapy should becarried out under the supervision of a medicaloncologist who is a member of the Breast Unit andis treating the majority of patients from that unit.There should be adequate pharmacy support. Theremust also be adequate facilities for the managementof complications that may arise.

ENDOCRINE THERAPYThe benefits achievable by endocrine manipulationin ER-positive breast cancer may exceed gains fromcytotoxic therapy for both early and advanceddisease.

The Early Breast Cancer Trialists CollaborativeGroups overview demonstrated that ovarianablation significantly improved the long termsurvival for women under 50 years of age. Theoverview indicated that further trials of the additionof chemotherapy to ovarian ablation were needed.Issues arise about the safety of inducing menopausein young women, particularly in relation toconcerns about delayed side-effects such as skeletaland cardiovascular disease. In patients withadvanced breast cancer similar disease-free survivaland overall survival was noted for those treated byoophorectomy as with the GnRH analogue,goserelin. The value of GnRH analogues in theadjuvant setting is under investigation in clinicaltrials.

Tamoxifen remains an important agent as adjuvanttreatment for patients whose tumours expresssteroid hormone receptor. While initial trialsindicate that the protective effect of tamoxifenagainst relapse lasted for 2 years, more recentstudies indicate that its value extends for at least 5years. The evidence for tamoxifen efficiency forlonger than 5 years remains inconclusive and iscurrently under study.

The use of selective oestrogen-receptor modifier(SERM) drugs and selective aromatase inhibitors arebeing used increasingly both in the adjuvant settingand for locally advanced or metastatic breast cancer.Their precise role in clinical practice remains to beestablished after evaluation in clinical trials.


Breast Cancer Management Clinical Guidelines 21Adjuvant Systemic Therapy in Breast Cancer

ADJUVANT THERAPY IN NODE-NEGATIVE PATIENTSThe following guidelines, supplied by theInternational Consensus Panel 54 are based onclinical trials which indicate that adjuvant systemictherapy can reduce the risk of relapse and increaselength of survival. They should not be taken asdefinitive requirements to be applied to all patientssince individual circumstances vary.

The Consensus Panel divided node-negative patientsinto minimal/low risk, intermediate risk and highrisk as shown below (Table 5).

For node-negative patients considered at high riskof recurrence the choice of treatment follows similarguidelines to that for node-positive disease, afterwhich the prognosis is similar (Table 6).

For high-risk patients with negative hormonereceptors, chemotherapy alone is considered to beappropriate.55,56 The addition of tamoxifen tochemotherapy is suitable for tumours which expressoestrogen or progesterone receptors. Combiningchemotherapy with tamoxifen in ER or PgR-positivetumours is more effective than endocrine therapyalone, irrespective of menopausal status. The use ofanthracyclines for these patients probably results ina small but statistically significant improvementover the oral cyclophosphamide (Days 1 and 14),intravenous methotrexate and 5-fluorouracil (day 1and 8) regimen.

For patients at minimal or low risk, account shouldbe taken of the low relapse rate within 10 yearswithout adjuvant treatment and the potentialreduction of contralateral breast cancer by the use

of tamoxifen. In premenopausal women classified ashaving an intermediate risk, the value of endocrinetherapy other than tamoxifen remainsinvestigational considering the long-term side-effectsof these treatments. This includes ovarian ablationeither by oophorectomy or by gonadotropin-releasing hormone (GnRH) analogue.

ADJUVANT THERAPY IN NODE-POSITIVE PATIENTSFor oestrogen-receptor (ER) or progesterone-receptor (PgR) positive patients with positive nodes,chemotherapy in the form of cyclophosphamide,methotrexate, fluorouracil (CMF) or anthracycline-based chemotherapy in addition to tamoxifen hasbeen demonstrated to be better than tamoxifenalone in terms of prolonging disease-free survival(Table 7). Tamoxifen alone in postmenopausalwomen may be justified when other factors, such asage, co-morbidity, risk of recurrence and patientpreference are taken into account. Anthracycline-based regimens indicate a small but significantadvantage over CMF treatments. The use oftaxanes, dose intensification and more novelcombinations of chemotherapeutic agents are underevaluation.

The International Consensus Panel 54 agreed thatpatients with less than 10% chance of relapsewithin 10 years should not be candidates forroutine adjuvant systemic therapy. The mostrelevant factors involved in estimating the risk ofrelapse are the presence and number of axillarylymph nodes involved and the size of the tumour.

Risk in node-negative patientsMINIMAL/LOW INTERMEDIATE HIGH

FACTORS (has all listed factors) (has at least one listed factor)

Tumour Size <1cm 1-2cm > 2cm

Oestrogen and/orprogesterone receptor status Positive Positive Negative

Grade Grade 1 Grade 1-2 Grade 2-3(uncertain relevance fortumours < 1cm)

Age (years) ≥35 < 35

Table 5

Adjuvant Systemic Therapy in Breast Cancer


Node-Negative PatientsPatient Group Minimal/Low Risk Intermediate Risk High Risk

Premenopausal NONE OR TAMOXIFEN± CHEMOTHERAPY+ER or PgR positive TAMOXIFEN CHEMOTHERAPY▲ TAMOXIFEN▲

Ovarian ablation◆ Ovarian ablation◆

GnRH analogue◆ GnRH analogue◆

Premenopausal not applicable● not applicable● CHEMOTHERAPY■

ER and PgR negative

Postmenopausal NONE OR TAMOXIFEN± TAMOXIFENER or PgR positive TAMOXIFEN CHEMOTHERAPY▲ CHEMOTHERAPY▲

Postmenopausal not applicable● not applicable● CHEMOTHERAPY■

ER or PgR negative

Elderly NONE OR TAMOXIFEN± TAMOXIFEN (If noTAMOXIFEN Chemotherapy ER or PgR expression:

CHEMOTHERAPY)

Node-Positive PatientsPatient Group

Premenopausal CHEMOTHERAPY + TAMOXIFENER or PgR positive OVARIAN ABLATION (or GnRH analogue ± Tamoxifen)◆

Chemotherapy ± ovarian ablation or (GnRH analogue) ± Tamoxifen◆

Premenopausal CHEMOTHERAPY▲

ER and PgR negative

Postmenopausal TAMOXIFEN / CHEMOTHERAPY■

ER or PgR positive

Postmenopausal CHEMOTHERAPY▲

ER or PgR negative

Elderly TAMOXIFEN (If no ER or PgR expression: CHEMOTHERAPY)

Goldhirsch, Glick, Gelber, Senn54

WORDS IN CAPITAL LETTERS Based directly on randomised controlled trials or internationally accepted for routine useGnRH Gonadotropin releasing hormone◆ Still under evaluation■ The addition of Tamoxifen following chemotherapy might be considered for ER and PgR (-) patients who have minimal traces of ER or PgR▲ The addition of chemotherapy is considered an acceptable option based on evidence from clinical trials, considerations based on low relative risk of

relapse are toxicity, socio-economic implications and patient preference might justify use of Tamoxifen alone● ‘Not applicable’ because these patients are, by definition, at high risk

WORDS IN CAPITAL LETTERS Based directly on randomised controlled trials or internationally accepted for routine useGnRH Gonadotropin releasing hormone◆ Therapies under evaluation in clinical trials■ The addition of chemotherapy is considered to be an acceptable option based on evidence from clinical trials. Considerations about the low relative risk

of relapse, age, toxicity, socio-economic implications and patient preference might justify use of Tamoxifen alone.▲ The addition of Tamoxifen following chemotherapy might be considered for patients whose tumours are classified as ER and PgR negative but which

exhibit minimal or trace levels of either ER or PgR.

Goldhirsch, Glick, Gelber, Senn54

Table 6

Table 7

For node-negative patients, differential prognosiscan be defined and therefore selection of adjuvanttherapy should be considered, according to:

■ tumour size■ histological and nuclear grade■ steroid hormone receptor status■ lymphovascular invasion ■ age

New developments may alter the estimation of riskand require validation before they are accepted forroutine practice outside of clinical trials. Surgery ofthe axilla might change if sentinel node biopsy andevaluation replaces formal axillary clearance in‘sentinel node-negative’ patients.

Furthermore the use of primary, or pre-operative,systemic therapy will influence the prognosticinformation available and assessment on thepathological features will depend on analysis of thelimited material obtained from a core biopsy.

Finally, although steroid hormonal receptor status isa most important feature, methodology used toassess receptors varies and correlatingresponsiveness with immunohistochemical cut-offperameters is still under evaluation.

RADIOTHERAPYIn the case of patients with early breast cancertreated by wide local excision and post-operativeradiotherapy, the time interval between the twoshould not exceed 4 weeks. The precise time shouldbe determined by clinical assessment and shouldtake into account any time needed for woundhealing.

Patients should be seen at a combined clinic by thesurgeon and medical oncologist. Wherechemotherapy and radiotherapy are both requiredphasing of treatments is decided for clinical reasonsand the planned interval should be strictly adheredto.

The radiation oncologist who is a member of theBreast Unit should see the majority of breast-cancerpatients from that Unit and should directradiotherapy techniques. Therapeutic radiographersshould be appropriately trained, and staffing shouldbe as recommended by appropriate authorities.Patients should be reviewed by the medicaloncologist regularly throughout their radiationtherapy.

Post-operative breast irradiation after breastconservation is routinely given as it reduces the riskof in-breast recurrence and probably reduces thedisease specific mortality. Previous radiotherapy tothe breast, collagen vascular disease and pregnancyare contraindications.

Chemotherapy and radiotherapy are usually givenin sequence rather than concurrently as increasedtoxicity is seen with concurrent regimens especiallywhen anthracyclines are used. Radiotherapy to thechest wall after mastectomy should be considered inpatients who have a higher risk of local chest wallrecurrence. These include patients in which thedescribed tumour was at or within 3 mms of thepectoral fascia or those who have heavy axillarynodal disease (more than 4 nodes positive).

Breast Cancer Management Clinical Guidelines 23Adjuvant Systemic Therapy in Breast Cancer

Management of Recurrent Disease

Although early diagnosis and new modalitytreatments have improved prognosis, many willhave some form of recurrence and metastases anddie of the disease. Prognostic scores should bedefined at the time of treatment. More than two-thirds of all recurrences occur within the first 5years after treatment, the incidence of eventsdecreasing exponentially with time

LOCAL RECURRENCE Local recurrence after breast conservation is definedas further breast cancer within the skin orparenchyma of the treated breast (whetherconsidered a recurrence or a new primary tumour).

All breast cancer patients should be followed up bythe Breast Unit as recurrence is sometimes difficultto recognise. Recurrence in the conserved breast orin the mastectomy flaps may pose diagnosticdifficulties. Distant recurrence may also presentclinical dilemmas (for example, hypercalcaemia,endobronchial disease, lymphangitis of the lung orbone pain). These are most likely to be recognisedand appropriately treated by a breast cancerspecialist.

The GP will see on average only one new patientwith metastatic breast cancer every 3-4 years. TheGP should refer suspected recurrence back to theBreast Unit so there must be a clear line of contactfor the GP to the Breast Unit.

The surgeon is responsible for patient follow-up in abreast clinic with the co-operation of othermembers of the breast team. They must work tostandards that are the same as for the diagnosis ofprimary breast cancer. It is inappropriate forpatients treated by conservation surgery andradiotherapy to be followed solely by the medicaloncologist, who should have combinedresponsibility with the surgeon and radiotherapistfor patients who have received radiotherapy and/orchemotherapy

Regular clinical follow-up is routine in most centres.The purpose of follow-up is to providepsychological support (especially in the first year)and to detect loco-regional recurrence or distantmetastases. The ideal frequency for mammographicfollow-up is unclear and current practice is variable.At present annual mammography is recommended.Patients’ follow-up after treatment for breast canceris part of the management and facilities must beavailable.

The incidence of local recurrence in mastectomyflaps is influenced by the extent of the operationand by the use of radiotherapy. Local recurrencepresenting as a single lesion within the flap may betreated by simple excision. More extensiverecurrence such as dermal lymphatic invasionreflects more aggressive disease and should bemanaged by a multidisciplinary approach from thesurgeon, medical oncologist and radiationoncologist.

The breast surgeon should be able to advise onreconstructive techniques in managing theseconditions and may have personal operativeexperience. If the breast specialist does not have theprerequisite experience the Breast Unit must workin collaboration with a plastic surgeon withexpertise in breast substitution. Local relapse withinthe conservatively treated breast will usually bemanaged by mastectomy.

CONTRALATERAL PRIMARYBREAST CANCERPrevious breast cancer increases the risk of acontralateral second cancer four-fold. Women whodevelop their first cancer below the age of 40 yearsmay be at much higher risk. The optimal timing ofmammography of the contralateral breast iscurrently unknown. Annual mammography iscurrently recommended. Tamoxifen decreases therisk of contralateral cancer and may slow theappearance the second primary breast cancer.

LOCALLY ADVANCED PRIMARYBREAST CANCEROverall survival is poor although improvement maybe achieved by systemic therapy. Achievement oflocal control of disease and symptomatic relief is ofgreat importance. Treatment of locally advancedbreast cancer must be by a multidisciplinaryapproach. Local control is usually gained bycombined treatments that may include radicalsurgery and/or radiotherapy and systemic treatment.

REGIONAL RECURRENCERegional recurrence reflects both primary treatmentfailure and natural disease aggression. The majorityof women with breast cancer do not developsymptomatic regional recurrence. Formal axillaryclearance at the time of primary surgery reduces the


axillary recurrence rate to less than 1%. Patientswho develop axillary recurrence should haveaxillary clearance if this is technically feasible.Radiotherapy should be considered if the lesion isunresectable.

METASTATIC BREAST CANCERIn metastatic breast cancer the metastases shouldpreferably be proven by biopsy in patients withsolitary lesions or those in whom there is a longinterval between primary treatment and recurrence.

When metastases are proven all patients should beconsidered for eligibility into approved clinicaltrials.

Radiation therapy should be considered for patientswith skeletal metastases and/or impending fractures,those with cerebral metastases, potential spinal cordcompression or other localised deposits. Surgicaltreatment should be considered for recurrent chestwall disease and for solitary metastatic lesions.Orthopaedic surgeons have a crucial role in themanagement of metastatic bone disease and shouldbe consulted with a view to preventing and treatingpathological fractures.57 Orthopaedic referral isalways indicated when plain radiographs showgenuine erosion of weight-bearing bone. In steroidhormone receptor-positive cases, endocrine therapyis recommended and can be expected to bring abouta favourable response in approximately 75% ofcases if both ER and PgR are positive. Multiplesequential trials of hormonal therapy areappropriate for these patients.

If the disease progresses or if the patient is ER andPgR-negative and is a candidate for chemotherapybased or general performance status and ability totolerate potential side-effects, a trial ofchemotherapy, preferably in a prospective studyshould be considered. A variety of newer agentsincluding the taxanes and the evolution of high-dosechemotherapy for metastatic disease require furtherevaluation.

Following the symptomatic presentation of distantmetastases, average life expectancy is around 2years but virtually all patients will ultimately diefrom breast cancer. The aim of treatment is topalliate symptoms and to maintain the best possiblequality of life. Systemic treatments (endocrine orcytotoxic) give some prolongation of life in manypatients

The specialist breast surgeon should help in the

management of women with advanced disease. Thesurgeon should have a good understanding of thenatural history of breast cancer and should take ajoint role with the other oncologists when assessingpatients with recurrent disease.

A variety of treatments may be appropriatedepending on the site of metastases, the likelybenefit versus toxicity and the preferences of thepatient. These include systemic anti-cancertherapies, palliative measures such as radiotherapyfor bone metastases, and bone stabilisation. Apatient with recurrent breast cancer should remainunder the care of the Breast Unit. Treatment mustbe according to protocols agreed within the Unit.

As the disease progresses the focus of care shifts toa more predominant role for the non-surgicaloncologists within the Breast Unit. A patient withmetastatic breast cancer requires considerablesupportive care including relief of nausea and painand acknowledgement of her psychological, socialand spiritual well-being.

The involvement of the palliative care team in thehospital and the community should be sought.

Clinic attendance to assess progress should be at theBreast Unit in order to ensure continuity of care byone team and to minimise travel problems. Thisshould be supported by a clinical nurse specialist.

PALLIATIVE AND TERMINAL CARE Centres offering breast cancer treatment shouldensure that there are adequate terminal carefacilities to support the primary care team.

Palliative care services should be involved at anearly stage rather than at a late stage in the patient’scare. The expertise of palliative care specialists is atpresent sought too late in the disease process.

Early involvement of these specialists ensures hugegains in the quality of life of women with breastcancer.

Breast Cancer Management Clinical Guidelines 25Management of Recurrent Disease

Training and Continuing Education

SURGICAL TRAININGAll consultant surgeons treating patients with breastcancer should have developed a special expertise inthe treatment of breast diseases and all surgeonswho treat patients with breast disease will beexpected to have specific training during theirformal surgical training programme. The level oftraining required for a consultant surgeon with aspecial interest in breast disease depends to someextent on whether the consultant will practice in aUnit in which some 50% of the surgeon’s time isdevoted to this disease or in a Unit where theconsultant will practice almost exclusively in breastdiseases. The training requirements for each maydiffer somewhat.

For a general surgeon expecting to work as aconsultant in a hospital in which some 50% of theconsultant’s time is involved in breast diseases, thefollowing training would be appropriate:-

(a) one year in higher training working 50% of thetime for a consultant with a special interest inbreast diseases in a Breast Unit.

(b) an additional six months full-time in a ReferenceBreast Unit.

(c) one month in a Medical Oncology service andone month in a Radiotherapy Unit.

(d) one month in a Palliative Care Unit.

For a surgeon expecting to work as a consultantpractising almost exclusively in breast diseases, thefollowing training is considered appropriate:-

(a) one year of training spending 50% of time witha consultant with a special interest in breastdisease in a Breast Unit.

(b) one year of training in a Reference Breast Unit.

(c) a flexible year of research related to breastdisease.

(d) at least one month each in a Medical Oncologyand Radiotherapy Unit.

(e) at least one month in a Palliative Care Unit.

Breast Units are encouraged to support clinicalresearch and to participate in multicentre studiesaimed at improving treatments for breast cancer.There is evidence to suggest that patients treated incentres actively involved in research have improvedoutcomes.58

Personnel must be given sufficient encouragementand time to update knowledge and skills.Continuing postgraduate education in breast diseasemay be measured on a points system. Annual studydays for surgeons in breast disease may be part offuture continuing education.

AN ESTIMATE OF THE SURGICALWORKLOAD IN A BREAST UNITIt is suggested that there should be a Breast Unit fora catchment population of 300,000. Up to 40 newsymptomatic breast referrals may be seen eachweek. A minimum of 100 new primary breastcancer patients will be treated in a Unit. Not all thepatients will require surgery, due to age, oradvanced stage, but at least two cases per week mayrequire breast cancer surgery. Some cases willrequire lengthier procedures, e.g. for extensive localdisease or reconstruction.

Locoregional recurrence, mammographic lesions fordiagnostic biopsy and symptomatic benign breastconditions may require surgery. These sessionsshould be carried out by a specialist at consultantlevel or by advanced trainees under specialistguidance.

STANDARDS AND AUDITBreast Units should be required to provide data onthe number of patients treated and type oftreatment received. Units should also be able toreport the long-term outcome measures in treatingwomen with breast cancer. This includes data onlocal and regional recurrence, long-term morbidityof the primary treatment such as lymphoedema,uncontrolled local recurrence, distant metastasesand death.

There should be a nominated surgeon who isultimately responsible for the accuracy of the datacollected. Each Unit should be able to provideresults of its audit on at least an annual basis.

The physical structure, staffing needs, equipmentfacilities and the organisation and trainingrequirements for a Breast Unit are outlined anddiscussed in detail in a report on the Developmentof Services for Symptomatic Breast Disease preparedby a Sub-Group of the National Cancer Forum.61


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2. Austoker J, Mansel R. (1999) Guidelines for Referral of Patientswith Breast Problems, 2nd Edition. NHS Screening Programme andCancer Research Campaign.

3. Provision of breast Services in the UK - The Advantage ofSpecialist Breast Units. Report of a Working Party of the BritishBreast Group, September 1994.

4. Dawson C., Lancashire MJR., Reece-Smith H., et al. BreastDisease and the General Surgeon 1: Referral of Patient with BreastProblems. Ann R Coll Surg Eng 1993; 75: 7-86

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