Linking Pregnancy and the Genomic Landscape of Subsequent Breast Cancer
Posted: Friday, May 3, 2019
Findings presented in Breast Cancer Research may highlight an unprecedented link between reproductive history and the genomic landscape of subsequent breast cancer. Bastien Nguyen, PhD, of the Université Libre de Bruxelles, Brussels, and the Memorial Sloan Kettering Cancer Center, New York, and colleagues hypothesized that TP53-mutant premalignant lesions may be less susceptible to the protective effect of an early parity, which might explain the difference in parity-induced protection according to breast cancer subtypes.
“Our study reveals that age at first pregnancy has a bigger imprint on genomic alterations of breast cancer than parity status alone,” the authors concluded. “Our results, which need to be validated in other studies, support that patients’ reproductive history should be routinely collected in future large-scale genomic studies addressing the biology of female cancers.”
The study, reportedly the first to explore the impact of reproductive history on the genomic landscape and the immune composition of subsequent breast cancer, enrolled 313 patients with primary breast cancer. Researchers used whole-genome, RNA sequencing, and tumor-infiltrating lymphocytes data, and multivariate analysis adjusted for age at diagnosis, pathologic stage, molecular subtype, and histologic subtypes. The authors also compared nulliparous versus parous, late parous versus early parous, and nulliparous versus pregnancy-associated patients with breast cancer.
Dr. Nguyen and colleagues found that genomic alterations of breast cancer were associated with age at first pregnancy—but not with parity status alone. Compared with late-parous patients, early-parous patients developed tumors characterized by a higher number of insertions or deletions, a lower frequency of CDH1 mutations (1.2% in early-parous patients vs. 12.7% in late-parous patients), a higher frequency of TP53 mutations (50% vs. 22.5%, respectively), and MYC amplifications (28% vs. 7%, respectively). Pregnancy-associated breast cancer was associated with increased tumor-infiltrating lymphocyte infiltration.
Disclosure: The study authors reported no conflicts of interest.