RADY401 Case Presentation

Elizabeth NeylanJune 2019

Focused patient history and workup

• Ms. P is a pleasant 60 year old female with a history of glaucoma who presented for consultation for a self-detected left breast mass.

• Patient is postmenopausal. Menarche occurred at age 15.

• She is a G2, P2, with first pregnancy was at age 21.

• She sustained breast trauma 5 months ago due to a fall.

List of imaging studies

1. Outside institution bilateral diagnostic mammography

2. Left diagnostic mammography (compression images)

3. Left breast and axilla diagnostic ultrasound

4. Left breast ultrasound guided needle core biopsy

5. Left diagnostic mammography

Bilateral Diagnostic Mammography

Left Diagnostic MammographyFindings?

Left Diagnostic Mammography

On magnification compression of L breast, a partially visualized mass with indistinct margins in posterior depth,

11:00 position. Supplemented by ultrasound. BI-RADS Category: 5 Highly Suggestive of Malignancy (Biopsy

recommended)

Left Diagnostic Ultrasound - BreastFindings?

Left Diagnostic Ultrasound - Breast

Targeted ultrasound of L 10:00 to 11:00 corresponding breast mass, 8 cm from the

nipple. Hypoechoic mass with microlobulatedmargins measuring 1.9 x 1.5 x 1.9 cm.

Left Diagnostic Ultrasound - AxillaFindings?

Left Diagnostic Ultrasound - AxillaProminent lymph node with mild

cortical asymmetry. LN measures 0.8 x 0.6 x 1.0 cm with cortex up to 0.3 cm

.

Ultrasound Guided Core Needle Biopsy

Biopsy needle

Deployment of biopsy marking clip

Left Diagnostic Mammography Post Biopsy Findings?

Left Diagnostic Mammography Post Biopsy

Localizer clip placement in mass in L breast upper inner quadrant

Patient Care Episode: Diagnosis

• Surgical pathology report: • Invasive ductal carcinoma, grade 3

• Defined as a poorly differentiated tumor composed of solid nests of neoplastic cells without evidence of gland formation3

• Triple Negative Breast Cancer (TNBC): ER (less than 1%) negative, PR (less than 1%) negative, HER2 negative

• Referred to UNC Breast Multidisciplinary Conference• Medical Oncology, Surgical Oncology, Radiation Oncology, Radiology, Pathology

specialists meet in the interdisciplinary care approach to patients with newly diagnosed breast cancer

• Next steps: genetics consult, oncology consult, systemic staging with CT and bone scan, echocardiogram, and port placement

Patient Care Episode: Treatment• No clear, proven effective single agent that targets a defining vulnerability in

triple-negative breast cancer2

• Per Genetics consult, pursuing testing of the hereditary breast cancer genes: BRCA1, BRCA2 and PALB2• Positive result may change management and provide important information to at-risk

relatives• Negative result is reassuring, but does not eliminate the increased risk of breast

cancer for immediate female relatives

• Given triple negative status, endocrine therapies and anti-HER2 drugs are not an option

• General approaches do exist• If metastatic disease palliative chemotherapy• If no metastatic disease neoadjuvant chemotherapy, surgery, then radiation

• Dose-dense chemotherapy with doxorubicin, cyclophosphamide followed by weekly paclitaxel

Discussion: Radiologic Workup of a Palpable Breast Mass

• Thorough breast examination, then radiologic imaging

• Diagnostic Mammography:• Sensitivity 87% and specificity 88% in detecting cancer

• PPV 22%

• Ultrasound: detects cystic and solid masses, guide biopsy technique• Sensitivity 89% and specificity 78% for abnormalities in symptomatic women

(Klein, 2005)

Discussion: Radiologic Workup of a Palpable Breast Mass

• Thorough breast examination, then radiologic imaging

(American College of Radiology Appropriateness Criteria, 2016)

Discussion: Radiologic Workup of a Palpable Breast Mass

• FNA: fast, inexpensive, accurate• Can detect solid vs. cystic masses

• May disrupt cyst wall

• But obtaining adequate samples can be tricky

• Core-needle biopsy (as in this case): histologic diagnosis, hormone receptor testing, differentiates between in situ and invasive disease• Produces larger tissue sample for pathology

• Sensitivity 99% in diagnosing malignancy in palpable lesions and 93% in nonpalpable

• Insufficient specimens is quite rare

• Higher PPV and overall cost benefit

(Klein, 2005)

Discussion: Immunohistochemistry and Hormone Receptors

• Recent increased emphasis on IHC and genetic profile of breast tumors

• Three molecular biomarkers used in routine clinical management of patients with IBC• Estrogen Receptor (ER)

• Progesterone Receptor (PR)

• Human Epidermal Growth Factor Receptor (HER2)

• ER, PR, HER2 are targets and/or indicators of highly effective therapies• ER+ and PR+ respond to hormone therapies

• HER+ respond to therapies that specifically target the HERb protein

Discussion: Triple Negative Breast Cancer (TNBC)

• Our patient: ER (less than 1%) negative, PR (less than 1%) negative, HER2 negative

• Typically more aggressively and higher grade

• 15% of breast cancers worldwide

• Higher risk of relapse

• More commonly in women younger than 40 years

• Risk factors include:• Positive BRCA mutation• African American• Premenopausal status

Take Home Points

• Work-up for a breast mass (as in this case):1. Physical exam: dominant, palpable breast mass

2. Ultrasonography to visualize solid mass

3. Diagnostic Mammography (ex. compression images)

4. Ultrasound guided core-needle biopsy

• TNBC: typically females <40 years, less prevalent, more aggressive, higher grade

• No proven effective single agent available that targets triple-negative breast cancer

References

1. “American College of Radiology Appropriateness Criteria - Palpable Breast Mass.” American College of Radiology Appropriateness Criteria, American College of Radiology, 2016, acsearch.acr.org/list?_ga=2.259956362.167462045.1560990840-1422462938.1559840679.

2. Anders CK and Carey LA. “ER/PR Negative, HER2-Negative (Triple-Negative) Breast Cancer.” UpToDate, May 2019, www-uptodate-com.libproxy.lib.unc.edu/contents/er-pr-negative-her2-negative-triple-negative-breast-cancer?search=triple%2Bnegative%2Bbreast%2Bcancer&source=search_result&selectedTitle=1~33&usage_type=default&display_rank=1.

3. Bleiweiss, Ira J. “Pathology of Breast Cancer.” Edited by Anees B Chagpar and Sadhna R Vora, UpToDate, UNC Chapel Hill Libraries, 13 Feb. 2019, www-uptodate-com.libproxy.lib.unc.edu/contents/pathology-of-breast-cancer?search=invasive%2Bductal%2Bcarcinoma&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1#H11.

4. Hudis CA and Gianni L. “Triple-Negative Breast Cancer: an Unmet Medical Need.” The Oncologist, U.S. National Library of Medicine, 2011, www.ncbi.nlm.nih.gov/pubmed/21278435.

5. Klein S. “Evaluation of Palpable Breast Masses.” American Family Physician, 1 May 2005, www.aafp.org/afp/2005/0501/p1731.html.