Lobüler Karsinoma İn Situ Yönetimi
Özet
Lobuler karsinoma in situ (LCIS), memenin atipi içeren benign proliferatif bir lezyonu olup, mutlak bir kanser öncülü (prokürsör) olmaktan ziyade, gelecekte her iki memede de invazif meme kanseri gelişme riskini artıran güçlü bir risk belirtecidir. Oldukça nadir görülen ve benign biyopsilerin %1'inden azını oluşturan LCIS, sıklıkla yüksek östrojen reseptörü (ER) pozitifliği gösterir. Klasik, pleomorfik ve florid olmak üzere üç histolojik alt tipe ayrılır. Radyolojik bulgularla uyumlu klasik tip LCIS olgularında sadece yakın izlem yeterli olabilirken, yüksek invazif odak eşlik etme riski nedeniyle pleomorfik ve florid alt tiplerinde cerrahi eksizyon ve güvenli sınırların sağlanması zorunludur. LCIS varlığı, normal popülasyona göre meme kanseri riskini 8 ila 10 kat artırarak 15 yıllık kümülatif riski %11-26 seviyelerine ulaştırır. Takipte yaşam beklentisi 10 yıldan fazla olan hastalara 6-12 ayda bir muayene, yıllık mamografi ve MR önerilir. Kemoprevensiyonda premenopozal dönemde tamoksifen, postmenopozal dönemde ise tamoksifen, raloksifen veya aromataz inhibitörleri kullanımı riskleri %50-75 oranında azaltır. İlaç istemeyen veya çok yüksek riskli hastalarda bilateral risk azaltıcı mastektomi %90-96 koruma sağlasa da, erken evre tanı avantajı ve yaşam kalitesi dengesi gözetilerek tedavi yönetimi mutlaka hastanın risk algısı ve klinik faktörlerine göre bireyselleştirilmelidir.
Lobular carcinoma in situ (LCIS) is a benign proliferative lesion of the breast characterized by atypia, serving as a potent risk indicator rather than a direct precursor for subsequent invasive breast cancer across both breasts. Accounting for less than 1% of benign breast biopsies, LCIS is quite rare, demonstrates high estrogen receptor positivity, and occurs at a median age of 45. It is categorized into three distinct histological variants: classic, pleomorphic, and florid. While close clinical surveillance may suffice for radiologically concordant classic LCIS, surgical excision with clear margins is strongly recommended for pleomorphic and florid variants due to their high correlation with synchronous invasive foci. The presence of LCIS elevates breast cancer risk 8- to 10-fold compared to the general population, translating to a 15-year cumulative risk of 11% to 26%. Surveillance strategies for patients with a life expectancy exceeding 10 years entail clinical examinations every 6-12 months, annual screening mammography, and breast MRI. Chemoprevention using tamoxifen for premenopausal women, or tamoxifen, raloxifene, and aromatase inhibitors for postmenopausal women, yields a 50% to 75% risk reduction. Alternatively, bilateral risk-reducing mastectomy offers a 90% to 96% risk reduction. However, given that close surveillance ensures early-stage detection with minimal mortality, management strategies must be customized individually, carefully balancing therapeutic efficacy against quality-of-life considerations.
Referanslar
Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, Vogel V, Robidoux A, Dimitrov N, Atkins J: Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. JNCI: Journal of the National Cancer Institute 1998, 90(18):1371-1388.
Tavassoli FA: Breast pathology: rationale for adopting the ductal intraepithelial neoplasia (DIN) classification. Nature Clinical Practice Oncology 2005, 2(3):116-117.
Page DL, Kidd Jr TE, Dupont WD, Simpson JF, Rogers LW: Lobular neoplasia of the breast: higher risk for subsequent invasive cancer predicted by more extensive disease. Human pathology 1991, 22(12):1232-1239.
Akashi-Tanaka S, Fukutomi T, Nanasawa T, Matsuo K, Hasegawa T, Tsuda H: Treatment of noninvasive carcinoma: fifteen-year results at the National Cancer Center Hospital in Tokyo. Breast Cancer 2000, 7(4):341-344.
Middleton LP, Grant S, Stephens T, Stelling CB, Sneige N, Sahin AA: Lobular carcinoma in situ diagnosed by core needle biopsy: when should it be excised? Modern pathology 2003, 16(2):120-129.
Bagaria SP, Shamonki J, Kinnaird M, Ray PS, Giuliano AE: The florid subtype of lobular carcinoma in situ: marker or precursor for invasive lobular carcinoma? Annals of surgical oncology 2011, 18(7):1845-1851.
Morrow M, Schnitt SJ, Norton L: Current management of lesions associated with an increased risk of breast cancer. Nature reviews Clinical oncology 2015, 12(4):227-238.
Simpson PT, Gale T, Fulford LG, Reis-Filho JS, Lakhani SR: The diagnosis and management of pre-invasive breast disease: pathology of atypical lobular hyperplasia and lobular carcinoma in situ. Breast cancer research 2003, 5(5):1-5.
Lopez‐Garcia MA, Geyer FC, Lacroix‐Triki M, Marchió C, Reis‐Filho JS: Breast cancer precursors revisited: molecular features and progression pathways. Histopathology 2010, 57(2):171-192.
King TA, Pilewskie M, Muhsen S, Patil S, Mautner SK, Park A, Oskar S, Guerini-Rocco E, Boafo C, Gooch JC: Lobular carcinoma in situ: a 29-year longitudinal experience evaluating clinicopathologic features and breast cancer risk. Journal of clinical oncology 2015, 33(33):3945.
Martinez V, Azzopardi J: Invasive lobular carcinoma of the breast: incidence and variants. Histopathology 1979, 3(6):467-488.
Reed AEM, Kutasovic JR, Lakhani SR, Simpson PT: Invasive lobular carcinoma of the breast: morphology, biomarkers and’omics. Breast cancer research 2015, 17(1):1-11.
Haagensen C, Lane N, Lattes R, Bodian C: Lobular neoplasia (so‐called lobular carcinoma in situ) of the breast. Cancer 1978, 42(2):737-769.
Chuba PJ, Hamre MR, Yap J, Severson RK, Lucas D, Shamsa F, Aref A: Bilateral risk for subsequent breast cancer after lobular carcinoma-in-situ: analysis of surveillance, epidemiology, and end results data. Journal of Clinical Oncology 2005, 23(24):5534-5541.
Fisher ER, Costantino J, Fisher B, Palekar AS, Paik S, Suarez C, Wolmark N: Pathologic findings from the National Surgical Adjuvant Breast Project (NSABP) protocol B‐17: Five‐year observations concerning lobular carcinoma in situ. Cancer: Interdisciplinary International Journal of the American Cancer Society 1996, 78(7):1403-1416.
Fisher ER, Land SR, Fisher B, Mamounas E, Gilarski L, Wolmark N: Pathologic findings from the National Surgical Adjuvant Breast and Bowel Project: twelve‐year observations concerning lobular carcinoma in situ. Cancer 2004, 100(2):238-244.
Reis-Filho JS, Pinder SE: Non-operative breast pathology: lobular neoplasia. Journal of clinical pathology 2007, 60(12):1321-1327.
Andrade VP, Ostrovnaya I, Seshan VE, Morrogh M, Giri D, Olvera N, De Brot M, Morrow M, Begg CB, King TA: Clonal relatedness between lobular carcinoma in situ and synchronous malignant lesions. Breast cancer research 2012, 14(4):1-14.
Sakr RA, Schizas M, Carniello JVS, Ng CK, Piscuoglio S, Giri D, Andrade VP, De Brot M, Lim RS, Towers R: Targeted capture massively parallel sequencing analysis of LCIS and invasive lobular cancer: Repertoire of somatic genetic alterations and clonal relationships. Molecular oncology 2016, 10(2):360-370.
Begg CB, Ostrovnaya I, Carniello JVS, Sakr RA, Giri D, Towers R, Schizas M, De Brot M, Andrade VP, Mauguen A: Clonal relationships between lobular carcinoma in situ and other breast malignancies. Breast Cancer Research 2016, 18(1):1-11.
Sawyer E, Roylance R, Petridis C, Brook MN, Nowinski S, Papouli E, Fletcher O, Pinder S, Hanby A, Kohut K: Genetic predisposition to in situ and invasive lobular carcinoma of the breast. PLoS genetics 2014, 10(4):e1004285.
Network NCC: NCCN Guidelines Version 1.2022 Breast Cancer Risk Reduction. 2022.
McEvoy MP, Coopey SB, Mazzola E, Buckley J, Belli A, Polubriaginof F, Merrill AL, Tang R, Garber JE, Smith BL: Breast cancer risk and follow-up recommendations for young women diagnosed with atypical hyperplasia and lobular carcinoma in situ (LCIS). Annals of surgical oncology 2015, 22(10):3346-3349.
Network NCC: NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) Breast Cancer Screening and Diagnosis Version 1.2021. 2022.
Wickerham DL, Costantino JP, Vogel VG, Cronin WM, Cecchini RS, Ford LG, Wolmark N: The use of tamoxifen and raloxifene for the prevention of breast cancer. Cancer Prevention II 2009:113-119.
Vogel VG: The NSABP study of tamoxifen and raloxifene (STAR) trial. Expert review of anticancer therapy 2009, 9(1):51-60.
Cuzick J, Sestak I, Thorat MA: Impact of preventive therapy on the risk of breast cancer among women with benign breast disease. The breast 2015, 24:S51-S55.
Valero MG, Zabor EC, Park A, Gilbert E, Newman A, King TA, Pilewskie ML: The Tyrer–Cuzick model inaccurately predicts invasive breast cancer risk in women with LCIS. Annals of surgical oncology 2020, 27(3):736-740.
Lo LL, Milne RL, Liao Y, Cuzick J, Terry MB, Phillips K-A: Validation of the IBIS breast cancer risk evaluator for women with lobular carcinoma in-situ. British journal of cancer 2018, 119(1):36-39.
Euhus DM, Leitch AM, Huth JF, Peters GN: Limitations of the Gail model in the specialized breast cancer risk assessment clinic. The breast journal 2002, 8(1):23-27.
Carbine NE, Lostumbo L, Wallace J, Ko H: Risk‐reducing mastectomy for the prevention of primary breast cancer. Cochrane Database of Systematic Reviews 2018(4).
Wong SM, Stout NK, Punglia RS, Prakash I, Sagara Y, Golshan M: Breast cancer prevention strategies in lobular carcinoma in situ: a decision analysis. Cancer 2017, 123(14):2609-2617.
Hartmann LC, Schaid DJ, Woods JE, Crotty TP, Myers JL, Arnold P, Petty PM, Sellers TA, Johnson JL, McDonnell SK: Efficacy of bilateral prophylactic mastectomy in women with a family history of breast cancer. New England Journal of Medicine 1999, 340(2):77-84.
Foote Jr FW, Stewart FW: Lobular carcinoma in situ: a rare form of mammary cancer. The American journal of pathology 1941, 17(4):491.
