Gestational breast cancer: distinctive molecular and clinico-epidemiological features

Abstract

Breast cancer; Gene expression; Gestational breast cancer

Càncer de mama; Expressió gènica; Càncer de mama gestacional

Cáncer de mama; Expresión genética; Cáncer de mama gestacional

Gestational breast cancer (GBC), defined as breast cancer (BC) diagnosed during pregnancy or the first-year post-partum, accounts for 6–15% of BC cases in women aged 20–44 years. GBC has worse prognosis than non-GBC, but reasons behind are not clear. The GEICAM/2012–03 Study (Molecular Characterization of Gestational Breast Cancer) is a multicenter prospective/retrospective observational registry of patients diagnosed with GBC. From November 2014 to June 2015 seventy patients diagnosed with GBC were included in the study, 30 diagnosed during pregnancy and 40 after delivery. Our current study was aimed to explore differences in epidemiological, clinico-pathological and gene expression features of GBC tumors, from the GEICAM/2012–03 Study, compared to non-GBC tumors from patients of similar age (< 43 years) from six different GEICAM studies, used as non- GBC control population. As per the main objective, the study found multiple differences showing GBC tumors as a different biological entity. GBC showed a more aggressive biology, with higher Ki67 levels, higher incidence of breast and/or ovarian cancer family history, and germline deleterious BRCA1/2 mutations, and are enriched in basal-like intrinsic subtype. GBC patients showed a lower number of tumor infiltrating lymphocytes, while specific genetic signatures highlight differences in GBC´s distinctive transcriptome. Our study shows that GBC is potentially a clinically and molecularly different entity, with specific epidemiological, clinical, and histological features, as well as a distinctive altered immune state and genetic signature. Nevertheless, further studies are needed to better understand the biology of GBC and to identify new targets against which develop new, more effective, targeted therapies.

This study GEICAM/2012-03 was funded by FSEOM-BUCKLER 0′0 grant and donations from the program “Territorios solidarios BBVA” and the associations of patients “Rosae” and “Santa Águeda”, as well as the “Enquetepuedoayudar. Cocktel Benéfico Córdoba” initiative and the Instituto de Salud Carlos III (Madrid, ES) (research grant FIS—GRANT_NUMBER: Pi18/00817). Federico Rojo is funded by Instituto de Salud Carlos III (Madrid, Spain) (research grant FIS—GRANT_NUMBER: PI21/00142). Pablo Minguez is funded by the Miguel Servet Program from the Instituto de Salud Carlos III (CPII21/00015). Silvia Guil is funded by Universidad de Córdoba-Programa Fondo Europeo de Desarrollo Regional (FEDER Program; 1381156-R). The funding sources played no role in study design, data collection, analysis and interpretation of data or the writing of this manuscript. We thank all the patients included in this study and their families, as well as all the participating investigators and the support staff at each study site and at the GEICAM headquarters.