Genomic landscape of small cell carcinoma of the breast contrasted to small cell carcinoma of the lung
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Small cell carcinoma of the breast is a rare, aggressive form of breast cancer that is associated with extremely poor outcomes . In an effort to identify possible targets for treatment, we utilized comprehensive genomic profiling in small cell carcinoma of the breast. Under an IRB approved protocol, we identified patients with small cell carcinoma of the breast and small cell carcinoma of the lung profiled by Caris Life Sciences between 2007 and 2015. Tumors were assessed with up to 25 immunohistochemical stains, in situ hybridization of cMET, EGFR, HER2, PIK3CA, and TOP2A, and next generation sequencing as well as Sanger sequencing of 47 genes. 19 patients with small cell carcinoma of the breast were identified, median age was 58 years (range 37–79) and 42 % had metastatic disease at presentation; for comparison, 58 patients with small cell carcinoma of the lung were identified (66 [36–86], 65 % metastatic). By immunohistochemistry, 31 % of small cell carcinoma of the breast patients expressed ER, 13 % expressed PR, and 16 % expressed AR; small cell carcinoma of the lung patients expressed ER 0 %, PR 2 %, and AR 6 %. Small cell carcinoma of the breast and small cell carcinoma of the lung patients had similar patterns of other immunohistochemical expression (0 v 0 % PDL1, 50 v 42 % PD1, and 77 v 95 % TOP2A, respectively). All small carcinoma of the breast and small cell carcinoma of the lung patients were negative for HER2 and cMET amplification by in situ hybridization. Next generation sequencing revealed TP53 mutations in 75 % of patients both with small cell carcinoma of the breast and small cell carcinoma of the lung and PIK3CA mutations in 33 % of small cell carcinoma of the breast patients but no small cell carcinoma of the lung patients (Fisher’s exact test p = 0.005, OR 0.02 [0.00–0.52]). No other mutations were found in small cell carcinoma of the breast patients and no other mutation occurred in over 10 % of small cell carcinoma of the lung patients except RB1 in 19 % (p = 0.31). Small cell carcinoma of the breast is an aggressive tumor with few therapeutic options. Molecular profiling suggests many similarities between small cell carcinoma of the breast and small cell carcinoma of the lung with the exception an increased incidence of PIK3CA mutations in small cell carcinoma of the breast, which may have therapeutic implications.
Rebecca Feldman works for Caris Life Sciences.
- 9.Arsenic R, Treue D, Lehmann A, Hummel M, Dietel M, Denkert C, Budczies J (2015) Comparison of targeted next-generation sequencing and Sanger sequencing for the detection of PIK3CA mutations in breast cancer. BMC Clin Pathol 15:20. doi: 10.1186/s12907-015-0020-6 CrossRefPubMedPubMedCentralGoogle Scholar
- 11.PolyPhen-2: Prediction of Functional Effects of Human nsSNPs. Available at: http://genetics.bwh.harvard.edu/pph2/. Accessed September 2015
- 16.Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M (2012) Safety, activity, and immune correlates of anti–pd-1 antibody in cancer. N Engl J Med 366(26):2443–2454. doi: 10.1056/NEJMoa1200690 CrossRefPubMedPubMedCentralGoogle Scholar
- 17.Antonia JS, Bendell JC, Taylor MH, Calvo E, Jaeger D, De Braud FG, Ott PA, Pietanza MC, Horn L, Le DT, Morse M, Lopez-Martin JA, Ascierto PA, Christensen O, Grosso J, Simon JS, Lin C, Eder JP (2015) Phase I/II study of nivolumab with or without ipilimumab for treatment of recurrent small cell lung cancer (SCLC). J Clin Oncol 33 suppl; abstr 7503Google Scholar
- 18.Ott PA, Fernandez ME, Hiret S, Kim D, Moss RA, Winser T, Yuan S, Cheng JD, Piperdi B, Mehnert JM (2015) Pembrolizumab (MK-3475) in patients (pts) with extensive-stage small cell lung cancer (SCLC): Preliminary safety and efficacy results. J Clin Oncol 33, suppl; abstr 7502Google Scholar
- 21.Weigelt B, Horlings HM, Kreike B, Hayes MM, Hauptmann M, Wessels LFA, de Jong D, Van de Vijver MJ, Van’t Veer LJ, Peterse JL (2008) Refinement of breast cancer classification by molecular characterization of histological special types. J Pathol 216(2):141–150. doi: 10.1002/path.2407 CrossRefPubMedGoogle Scholar
- 23.Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), Davies C, Goodwin J, Gray R, Clarke M, Cutter D, Darby S, McGale P, Pan HC, Taylor C, Wang YC, Dowsett M, Ingle J, Peto R (2011) Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet 378(9793):771–784. doi: 10.1016/S0140-6736(11)60993-8 CrossRefGoogle Scholar
- 24.BIG 1-98 Collaborative Group, Mouridsen H, Giobbie-Hurder A, Goldhirsch A, Thürlimann B, Paridaens R, Smith I, Mauriac L, Forbes J, Price KN, Regan MM, Gelber RD, Coates AS (2009) Letrozole Therapy Alone or in Sequence with Tamoxifen in Women with Breast Cancer therapy alone or in sequence with tamoxifen in women with breast cancer. N Engl J Med 361(8):766–776. doi: 10.1056/NEJMoa0810818 CrossRefGoogle Scholar