title: Genomic landscape of small cell carcinoma of the breast contrasted to small cell carcinoma of the lung.
abstract: Small cell carcinoma of the breast is a rare, aggressive form of breast cancer that is associated with extremely poor outcomes [1]. 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.
authors.affiliation: University of Tennessee Health Science Center, Memphis, TN, USA. bpalazo@gmail.com.
authors.forename: Brennan
authors.identifier: 0000-0001-8490-4709
authors.initials: B
authors.lastname: McCullar
authors.affiliation: University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Manjari
authors.initials: M
authors.lastname: Pandey
authors.affiliation: University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: George
authors.initials: G
authors.lastname: Yaghmour
authors.affiliation: University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Felicia
authors.initials: F
authors.lastname: Hare
authors.affiliation: University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Kruti
authors.initials: K
authors.lastname: Patel
authors.affiliation: University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Matthew
authors.initials: K
authors.lastname: Stein
authors.affiliation: University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Feldman
authors.affiliation: University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Jason C
authors.initials: JC
authors.lastname: Chandler
authors.affiliation: University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Martin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D018288:Carcinoma, Small Cell / Q000235:genetics* / Q000378:metabolism; D058534:Class I Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D023281:Genomics / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D008875:Middle Aged; D000075223:Poly-ADP-Ribose Binding Proteins / Q000235:genetics / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods; D055752:Small Cell Lung Carcinoma / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D058534:Class I Phosphatidylinositol 3-Kinases; D004250:DNA Topoisomerases, Type II; D066246:ErbB Receptors; D000075223:Poly-ADP-Ribose Binding Proteins; D019859:Proto-Oncogene Proteins c-met; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53; C495901:TP53 protein, human; C484760:PIK3CA protein, human; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C491743:MET protein, human; C000618811:TOP2A protein, human