Male breast cancer precursor lesions: Analysis of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program

Shusma C. Doebar, Leen Slaets, Fatima Cardoso, Sharon H. Giordano, John M.S. Bartlett, Konstantinos Tryfonidis, Nizet H. Dijkstra, Caroline P. Schröder, Christi J. Van Asperen, Barbro Linderholm, Kim Benstead, Winan N.M. Dinjens, Ronald Van Marion, Paul J. Van Diest, John W.M. Martens, Carolien H.M. Van Deurzen

Research output: Contribution to journalArticle

Abstract

In men, data regarding breast cancer carcinogenesis are limited. The aim of our study was to describe the presence of precursor lesions adjacent to invasive male breast cancer, in order to increase our understanding of carcinogenesis in these patients. Central pathology review was performed for 1328 male breast cancer patients, registered in the retrospective joint analysis of the International Male Breast Cancer Program, which included the presence and type of breast cancer precursor lesions. In a subset, invasive breast cancer was compared with the adjacent precursor lesion by immunohistochemistry (n=83) or targeted next generation sequencing (n=7). Additionally, we correlated the presence of ductal carcinoma in situ with outcome. A substantial proportion (46.2%) of patients with invasive breast cancer also had an adjacent precursor lesion, mainly ductal carcinoma in situ (97.9%). The presence of lobular carcinoma in situ and columnar cell-like lesions were very low (<1%). In the subset of invasive breast cancer cases with adjacent ductal carcinoma in situ (n=83), a complete concordance was observed between the estrogen receptor, progesterone receptor, and HER2 status of both components. Next generation sequencing on a subset of cases with invasive breast cancer and adjacent ductal carcinoma in situ (n=4) showed identical genomic aberrations, including PIK3CA, GATA3, TP53, and MAP2K4 mutations. Next generation sequencing on a subset of cases with invasive breast cancer and an adjacent columnar cell-like lesion showed genomic concordance in two out of three patients. A multivariate Cox model for survival showed a trend that the presence of ductal carcinoma in situ was associated with a better overall survival, in particular in the Luminal B HER2+ subgroup. In conclusion, ductal carcinoma in situ is the most commonly observed precursor lesion in male breast cancer and its presence seems to be associated with a better outcome, in particular in Luminal B HER2+ cases. The rate of lobular carcinoma in situ and columnar cell-like lesions adjacent to male breast cancer is very low, but our findings support the role of columnar cell-like lesions as a precursor of male breast cancer.

Original languageEnglish (US)
Pages (from-to)509-518
Number of pages10
JournalModern Pathology
Volume30
Issue number4
DOIs
StatePublished - Apr 1 2017

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Doebar, S. C., Slaets, L., Cardoso, F., Giordano, S. H., Bartlett, J. M. S., Tryfonidis, K., Dijkstra, N. H., Schröder, C. P., Van Asperen, C. J., Linderholm, B., Benstead, K., Dinjens, W. N. M., Van Marion, R., Van Diest, P. J., Martens, J. W. M., & Van Deurzen, C. H. M. (2017). Male breast cancer precursor lesions: Analysis of the EORTC 10085/TBCRC/BIG/NABCG International Male Breast Cancer Program. Modern Pathology, 30(4), 509-518. https://doi.org/10.1038/modpathol.2016.229