Abstract 2013: Comprehensive genetic characterization of apocrine lesions of the breast.

Apocrine differentiation occurs in a variety of breast lesions, both benign and malignant. The molecular classification of breast cancer defined an apocrine molecular subtype of breast cancer. In general, apocrine carcinomas do not present clinical behavior distinct from the observed in ductal carcinomas of no special type. However, these carcinomas are frequently triple negative (ER-/PgR-/HER2-) with no targeted therapy and poor prognosis. Still they are unique in the aspect of the expression of a different nuclear receptor - androgen receptor (AR). In this study we thought to perform a comprehensive genetic/molecular characterization of this type of lesions. For that, a series of 44 apocrine lesions were studied. These comprised 9 apocrine metaplasia, 8 apocrine adenosis, 13 apocrine in situ carcinoma and 18 apocrine invasive carcinoma. Importantly four samples contained different lesions in different stages in close proximity. Immunohistochemistry was performed to evaluate the ER, PgR, HER2 and AR status of these lesions. Genomic DNA was microdissected from FFPE slides and used both to identify chromosomal copy number aberrations using aCGH and to monitor 739 mutations from 46 oncogenes and tumor suppressor genes using the Ion PGM system. The aCGH study allowed the identification of recurrent chromosomal aberrations. These were rare in benign apocrine lesions, mostly comprised of small gains and deletions, and dramatically increased in malignant lesions up to complete loss and gain of full chromosome arms. Also the analysis of the different lesions within the same sample indicates a putative existence of an apocrine tumor progression. Moreover the profiling of mutational status of the different tumor suppressor/oncogene allowed the identification of mutations that may provide new avenues for the development of new targetable therapeutically options and also corroborated the putative apocrine tumor progression. The study of apocrine lesions in different differentiation stages allowed a deeper insight on the molecular complexity of these lesions. Although further studies are required to independently validate this work, this study identifies recurrent genomic alteration that may open targeted treatment opportunities that may be used independently or in combination with anti-androgen drugs. Citation Format: Jose L. Costa, Ana Justino, Madalena Gomes, Cesar Augusto Alvarenga, Rene Gerhard, Semir Vranic, Zoran Gatalica, Jose Carlos Machado, Fernando Schmitt. Comprehensive genetic characterization of apocrine lesions of the breast. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2013. doi:10.1158/1538-7445.AM2013-2013