Jose A Torres, MD 1/12/2017

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1 Jose A Torres, MD 1/12/2017

2 Background Globally leading cause of cancer related death in women ~249,000 Americans diagnosed with invasive breast cancer ~40,890 will die of their disease

3 Breast cancer risk factors Non-modifiable Age Female sex Menstrual factors Early age at menarche (onset before age 12 yrs) Older age at menopause (onset beyond age 55 yrs) Nulliparity Family history of breast cancer Genetic predisposition (BRCA1 and BRCA2 mutation carriers) Personal history of breast CA Race, ethnicity (white females) History of radiation exposure

4 Breast cancer risk factors Modifiable Reproductive factors Age at first live birth Parity Lack of breast feeding Obesity EtOH consumption Smoking HRT Decreased physical activity Histologic Proliferative breast disease Atypical ductal hyperplasia Atypical lobular hyperplasia LCIS

5 Anatomy Axillary borders Superior axillary vein Anterior Pectoralis minor muscle Lateral latissimus dorsi muscle Axillary LN levels I lateral to pectoralis minor II posterior to pectoralis minor III medial to pectoralis minor Innervation Long thoracic nerve serratus anterior Thoracodorsal nerve latissimus dorsi Intercostobrachial nerve sensory to upper inner arm

6 Case 58 yo F G2P2 PMH: nil PSH: hysterectomy (fibroids) FamHx: Mother breast cancer Benign breast exam Undergoing routine surveillance imaging

7 Imaging Mammogram (8/2015): BI-RADS 3 No masses or suspicious microcalcifications. Amorphous microcalcifications along superior posterior aspect of L breast likely vascular calcifications Mammogram (11/2016): BI-RADS 4 Segmental linear pleomorphic microcalcification in upper inner L breast

8 8/ /2016

9 BI-RADS Category Radiologic finding Recommendation 0 Incomplete evaluation Additional imaging 1 Negative Routine screening 2 Benign Routine screening 3 Probably benign (risk 2%) 4 Suspicious (risk 30%) 5 Highly suspicious (risk 95%) 6 Known malignancy - Short term interval follow up Biopsy Treat accordingly

10 Pathology 11/17/2016: Excisional biopsy Invasive ductal carcinoma, poorly differentiated with extensive DCIS ER + PR HER2

11 Indications for excisional biopsy after core biopsy Lack concordance (radiology vs pathology) Non-diagnostic study/specimen Atypical ductal hyperplasia Atypical lobular hyperplasia Radial scar LCIS Columnar cell hyperplasia with atypia Papillary lesions

12 Pathology 12/13/2016: Simple mastectomy, SLNBx Invasive ductal carcinoma, DCIS SLNBx 0/3 LN negative for metastasis T1bN0Mx

13 Staging TX Primary tumor cannot be assessed T0 No evidence of primary tumor Tis Carcinoma in situ T1 Tumor 20 mm or less T1mi 1 mm T1a > 1 mm but 5 mm T1b >5 mm but 10 mm T1c >10 mm but 20 mm T2 >20 mm but 50 mm T3 >50 mm T4 Tumor of any size with direct extension to chest wall and/or skin (ulceration or skin nodules) T4a Extends to chest wall T4b Ulceration and/or ipsilateral satellite nodules and/or edema of skin T4c Both T4a and T4b T4d Inflammatory carcinoma

14 Staging NX Regional LN cannot be assessed N0 No regional LN metastasis N1 1-3 LN, Metastasis to movable ipsilateral level I, II axillary LN N2 4-9 LN N2a Metastasis to ipsilateral level I, II axillary LN fixed to one another (matted) or to other structures N2b Metastasis only in clinically detected ipsilateral internal mammary nodes and in the absence of clinically evident level I, II axillary LN N3 10 LN N3a Metastasis in ipsilateral infraclavicular LN N3b Metastasis in ipsilateral internal mammary LN and axillary LN N3c Metastasis in ipsilateral supraclavicular LN M0 No clinical or radiographic evidence of distant metastasis M1 Distant detectable metastases as determined by classic clinical and radiographic mean and/or histologically proven larger than 0.2mm

15 Anatomic stage T N M 0 Tis N0 M0 IA T1 N0 M0 IB T0 N1mi M0 T1 N1mi M0 IIA T0 N1 M0 T1 N1 M0 T2 N0 M0 IIB T2 N1 M0 T3 N0 M0 Mastectomy + SLNBx Mastectomy + SLNBx + reconstruction BCT + XRT IIIA T0 N2 M0 T1 N2 M0 T2 N2 M0 T3 N1 M0 T3 N2 M0 IIIB T4 N0 M0 T4 N1 M0 Neoadjuvant chemotherapy + MRM + XRT + HRT T4 N2 M0 IIIC Any T N3 M0 IV Any T Any N M1 ChemoXRT + HRT

16 Case 58 yo F s/p L mastectomy and SLNBx Path: Invasive ductal carcinoma, DCIS SLNBx 0/3 LN negative for metastasis T1bN0Mx

17 Noninvasive carcinoma LCIS Marker of increased risk 25% harbor invasive ductal CA Management Observation Tamoxifen Bilateral mastectomy DCIS Anatomic precursor to ipsilateral invasive ductal CA Excisional biopsy < 1mm margin need reexcision Management BCT + XRT Mastectomy ± SLNB ± reconstruction BCT + observation

18 NSABP B-17 Lumpectomy (LO) vs Lumpectomy + XRT (LRT) NSABP B-24 LRT + placebo vs LRT + tamoxifen (LRT +TAM) Endpoints Invasive-IBTR, DCIS-IBTR, contralateral breast cancer Overall survival, breast cancer specific survival, survival after I-IBTR

19 Results LRT reduced I-IBRT by 52% vs LO LRT + TAM reduced I-IBTR by 32% vs LRT + placebo I-IBTR DCIS-IBTR CBC

20 15 yr incidence of I-IBTR 8.5% LRT + TAM 15 yr incidence of CBC 7.3% LRT + TAM I-IBTR DCIS-IBTR CBC

21 Case 58 yo F s/p L mastectomy and SLNBx Path: Invasive ductal carcinoma, DCIS SLNBx 0/3 LN negative for metastasis T1bN0Mx

22 Invasive ductal carcinoma RCT of stage I or II breast CA Mastectomy vs lumpectomy (LO) vs lumpectomy + XRT (LRT) Endpoints IBTR, Disease-free survival, Distant-disease free survival, Overall survival

23 Results 14.3% recurrence of IBTR in LRT vs 39.2% LO No difference in disease-free survival, distant disease free survival, overall survival

24 Z0011 Trail T1-T2 invasive breast CA, no palpable LAD, 1-2 SLN with metastasis Randomized after SLNBx ALND No further axillary treatment

25 Results No difference Overall survival Disease-free survival ALND worse morbidity Wound infection Axillary seromas Paresthesias Lymphedema

26 Hormone receptor status Identify receptor status of excised mass Prognosis: ER/PR+ > ER-/PR+ > ER+/PR- > ER-/PR- Premenopausal ER + Tamoxifen ± ovarian suppression or ablation Postmenopausal AI for 5 yrs Tamoxifen for 2-3 yrs -> AI for 5 yrs AI for 2-3 yrs -> Tamoxifen to complete 5yrs of therapy

27 HER2 status HER 2 + AC (doxorubicin/cyclophosphamide) followed by T (docletaxel) + trastuzumab ± pertuzumab TC +trastuzumab HER2 AC followed by paclitaxel every 2 weeks AC followed by paclitaxel every week TC

28 Inflammatory breast CA Tumor cells in dermal lymphatics Stage IIIB without nodal involvement Management Neoadjuvant chemotherapy anthracycline + taxanes Response MRM + XRT ± HRT No response additional chemotherapy ± HRT

29 51 yo F undergoing lumpectomy for 0.9 cm invasive ductal carcinoma. Axillary exam normal. Proper management of axillary LN consist of which of the following? A Observation B SLNB with permanent pathology C SLNB, frozen section, and completion ALND if node are positive D Partial breast irradiation E Axillary US and no further therapy if no abnormal nodes seen

30 63 yo F with breast mass undergoes lumpectomy and SLNB. Path reports 1.0 cm invasive ductal CA, ER + HER 2+. Which of the following regimens wound be best chemotherapy of choice? A Cyclophosphamide, MTC, 5-FU B Doxorubicin, cyclophosphamide, paclitaxel, trastuzumab C Doxorubicin, cyclophosphamide, paclitaxel D Doxorubicin, cyclophosphamide E Docetaxel, cyclophosphamide

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34 Case 63 yo M with left breast cancer ER+ PR + HER2 Family history Mother and 2 maternal aunts Everted left nipple, mobile periareolar mass No axillary lymphadenopathy

35 Pathology 11/15/2016: Core needle biopsy Invasive ductal carcinoma ER+ PR + HER2 12/28/2016: Simple mastectomy, SLNBx Invasive ductal carcinoma SLNBx 0/3 LN negative for metastasis T2N0Mx

36 Imaging Mammogram (10/2016): BI-RADS 0 Breast US (11/2016): BI-RADS 4 Well-circumscribedlobulated heterogenous echoic lesion in retroareolar region. Hypervascular. 1.8 x 1.7 x2.3cm

37 Case 63 yo M with left breast cancer ER+ PR + HER2 Family history Mother and 2 maternal aunts Everted left nipple, mobile periareolar mass No axillary lymphadenopathy

38 Pathology 1/5/2017: Core needle biopsy Adenocarcinoma, moderately differentiated

39 Imaging Mammogram (12/2016): BI-RADS 5 Irregular lobulated mass. Slightly spiculated. Focal skin thickening under nipple Breast US (12/2016): BI-RADS 5 Lobulated hypoechoic mass in retroareolar region. 1.0 x 1.8 x 2.3 cm

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