Treatment options for the precancerous Atypical Breast lesions. Prof. YOUNG-JIN SUH The Catholic University of Korea

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1 Treatment options for the precancerous Atypical Breast lesions Prof. YOUNG-JIN SUH The Catholic University of Korea

2 Not so benign lesions? Imaging abnormalities(10% recall) lead to diagnostic evaluation, especially suspicious ones subject to CNBX CNBX adoption challenges with pathologic classification: benign vs. atypical Post-biopsy radiologic-pathologic concordancy is required CNBX = core needle biopsy

3 Getting into.. The management of precancerous lesions of the breast has become a matter of debate for the past 20 years, mostly as increasing early detection after mammographic screening. It is un-real to identify with absolute certainty which of those lesions must go on to invasive carcinoma, and tailoring treatment personally remains a challenging problem. This is a particular dilemma for surgeons, who must balance the risk of too-much resection leaving unfavorable cosmetic outcome, or leaving too-much resulting increased risk of recurrence.

4 Precancerous and/or Atypical Precancerous atypical lesions Precancerous lesions Atypical lesions

5 Various lesions after CNBX Atypical ductal hyperplasia, atypical hyperplasia, atypical lobular hyperplasia(alh), cellular fibroepithelial lesions, columnar cell lesions, complex sclerosing lesion, flat epithelial atypia, lobular carcinoma in situ(lcis), lobular neoplasia, mucocele-like lesions, phyllodes tumor, intraductal papilloma, pseudoangiomatous stromal hyperplasia(pash), radial scar

6 Precancerous Breast Lesions MMG increases detection of precancerous lesions (~25% DCIS by MMG screening) These include atypical ductal hyperplasia(adh) and intraductal proliferative lesions with atypia like flat epithelial atypia(fea) and others Phyllodes tumours MMG = mammography

7 Communication/Consultation Radiologic-pathologic concordant case: Reassurance of benign lesion and advice about future risk of developing cancer Radiologic-pathologic discordant case: Surgical consultation

8 When in turmoil! [CNBX with USG guidance] Discordance rate: ~ 6% When discordant, yield rate of carcinoma after excision = 18% (range, 3~63%) [MRI-guided VAB] Discordant rate: ~ 7% Carcinoma after excision = 30% Cancer 2000,89(12):2538~46 AJR 2007,189(4):852~9 VAB = vacuum-assisted biopsy

9 BI-RADS Breast Imaging and Reporting Data System BI-RADS 5 = HIGHLY suggestive BI-RADS 4 = suggestive of malignancy, recommend biopsy 4A = low suspicion 4B = moderate suspicion 4C = high suspicion

10 In the process Discordant = benign pathology BUT BI- RADS 4(preferably B or more) or 5, until proven otherwise Begin discussion with pathologist, especially associated with architectural distortion or mass PLAN: Re-biopsy or further radiologic evaluation

11 Protean histologic feature Proliferative(30%) Proliferative with atypia(5%) BBD NON-proliferative (65%) BBD = benign breast disease

12 Relative breast cancer risk (~20yr) Category (RR: Relative cancer risk) Mammographic findings Non-proliferative (RR, 1.2 ~ 1.4 x) Simple cyst Fibrosis Fibroadenoma (simple) Columnar alteration (simple) Apocrine metaplasia (simple) Mild ductal hyperplasia Circumscribed mass Mass, focal asymmetry Circumscribed mass calcifications Mass, focal asymmetry calcifications Proliferative disease (RR, 1.7 ~ 2.1 x) Usual ductal hyperplasia Sclerosing adenosis calcifications Calcifications, focal asymmetry, architectural distortion Columnar hyperplasia Papilloma Radial scar calcifications Mass, calcifications Architectural distortion Proliferative disease with atypia (RR, 4 x) Atypical lobular hyperplasia Lobular carcinoma is situ Atypical ductal hyperplasia None, calcifications None, calcifications calcifications Unclear risk Mucocele-like tumor / Apocrine atypia Apocrine atypia Calcifications, mass calcifications NEJM 2005, 35393):229-37, Cancer 1985,55(11):2698~708.

13 Atypical Hyperplasia Age: avr. 48~52 yo Ductal and lobular in histology, confer same RR (~ 4x) Possible clonal neoplastic proliferation = NON-obligate precursor to cancer Once affected, 40% of subsequent contralateral affliction risk J Clin Pathol 1995,48(7):611~5 NEJM 2005,353(3):229~37 avr. = average yo = years old

14 ADH Localized intraductal proliferation /w some (low-grade) DCIS DDx /w low-grade cribriform DCIS Cytological atypia!!! Pathologic distinction: size 2 mm or 3 contiguous layers (distribution) 10~20( 62)% up to DCIS or invasive one Ann Surg Oncol 2012,19(10):3264~9 DDx = differential diagnosis

15 ALH/ LCIS Lobular neoplasia by cytology DECREASED expression of E-cadherin ALH vs. LCIS = quantitative distinction Subsequent diagnostic excision -> NO substantial malignancy rate, when in benign imaging NO routine screening breast MRI Rx: SERM or AI should be considered

16 Apocrine proliferative lesions Uncommon with relevant atypia Most often with sclerosing adenosis or complex sclerosing lesions Recommend excisional biopsy to rule out malignancy (difficult to distinguish from low-grade apocrine DCIS in CNBX)

17 Columnar cell lesions (CCL) aka. blunt duct adenosis Subsets: columnar cell change, columnar cell hyperplasia(cch), and flat epithelial atypia ER expression and proliferative rate = early stage of cancer progression??? CCH behave like PD ER = estrogen receptor PD = proliferative disease

18 Flat epithelial atypia A form of CCL AJR 2011,197(3):740~6. ~30% of ALH/ADH after excision 5~15% after excision even to DCIS or invasive carcinoma May be early precursor of low-grade carcinoma J Pathol 2011,223(2): BUT, insufficient evidence-based recommendation

19 Papillary lesion WITH arborescent fibrovascular stalk Mixed with benign intraductal solitary papilloma, atypical papilloma, and multiple papilloma = heterogeneous Problematic benign vs. carcinoma in CNBX IHC (p63, calponin, actin) 15% of ADH from papilloma IHC = immunohistochemical staining

20 Benign solitary intraductal papilloma Typical subareolar lesion /w /w/o nipple discharge Upstaging from benign = ~ 5.9% Ann Surg Oncol 2013;20(6):1900-5

21 Atypical papilloma 67% risk of associated malignancy, therefore should be excised

22 Multiple and/or peripheral papilloma Associated with complex sclerosing lesions and AH Larger than 1.5 cm should be surgically excised. Radiol Clin North Am 2010;48(5):

23 Radial scar/ Complex sclerosing lesion (CSL) CSL= radial scar >1 cm. Difficult to distinguish from low-grade carcinoma Semin Ultrasound CT MR 2011;32(4): When with atypia, ~ 12% upstaging AJR 2012;198(2):W NO increased cancer risk above that of PD /w atypia Eur J Surg Oncol 2011;37(8):709-13

24 Desmoid tumor (Mammary fibromatosis) Rare benign Infiltrative and locally aggressive growth Recur locally, BUT lack metastatic potential MRI evaluation for tumor extent Ann Surg Oncol 2008;15(1): COMPLETE surgical excision /w WIDE margin

25 Mucocele-like lesion 25% - associated with AH 31% - upstaging, when /w AH and/or mass Am J Clin Pathol 2012;138(6):783-8.

26 Summary Breast lesion Management Surveillance Atypical ductal hyperplasia Surgical consultation with excision CBE/ 6~12 mo; annual MMG Lobular neoplasia, ALH/LCIS Surgical consultation CBE/ 6~12 mo; annual MMG Flat epithelial atypia Surgical consultation CBE/ 6~12 mo; annual MMG Papillomas Radial scar/ complex sclerosing lesion Surgical consultation for lesions with atypia, Size > 10mm, multiple or peripheral 10mm: observe if adequately sampled > 10mm: surgical consultation CBE/ 12 mo; annual MMG If excised, annual CBE and MMG Fibroadenoma Surgical consultation if atypia/ growing Annual CBE and MMG Complex fibroadenoma Observe Annual CBE and MMG Sclerosing adenosis Observe Annual CBE and MMG Fat necrosis Observe Annual CBE and MMG Columnar cell hyperplasia Observe Annual CBE and annual MMG PASH Surgical consultation if large/symptomatic Annual CBE and MMG Apocrine metaplasia Surgical consultation if atypia/ discordant Annual CBE and MMG if excised Desmoid tumor/mammary fibromatosis Surgical consultation CBE/ 12 mo Annual MMG Phyllodes tumor Surgical consultation CBE/ 12 mo Annual MMG CBE = clinical breast examination mo=month

27 Benefit vs. Harm Tailoring treatment of precancerous lesions according to 10% recall after screening. Each individual case is a multidisciplinary challenge involving radiologists and pathologists as well as breast surgeons and/or radio-oncologists, in case of DCIS. There must be a particular precaution to balance the risk of causing unnecessary overtreatment or leaving an increased risk of recurrence or progression.

28 Conclusion All CNBX pathology results should be evaluated with imaging for verification ADH by CNBX justify surgical consultation Lobular neoplasia, too Atypical hyperplasia and LCIS further discussion of risk-reducing strategies

29 Conclusion Further knowledge in the field of predictive and prognostic factors together with the development of gene-profiling techniques will, hopefully, provide answers to these questions. Among precancerous lesions of the breast, particular attention should be paid to ductal carcinoma in situ or intraductal carcinoma, appropriate treatment of which is crucial to prevent invasive breast cancer. Nearly all possible combinations of surgery, radiotherapy and medical treatments (anti-estrogens) have been tested in different clinical trials, but the situation is far from satisfactory. We believe that an important contribution can come from oncoplastic surgery, which is the application of plastic and reconstructive surgical techniques to ensure both radical excision of the disease and acceptable cosmetic outcomes.