Risk of breast cancer after ovarian cancer in germline BRCA1/BRCA2 heterozygotes.

Residual breast cancer penetrance in germline BRCA1/BRCA2 heterozygotes after an ovarian cancer diagnosis.

Breast cancer risk after ovarian cancer in germline BRCA1/BRCA2 heterozygotes remains uncertain, a recent large multicentre international study having reported lower-than-expected incidence in the first decade. The authors re-evaluated their regional cohort of 701 women with ovarian cancer and a germline pathogenic or likely pathogenic BRCA1/BRCA2 variant, restricting the analysis to women tested after ovarian cancer diagnosis and without prior breast cancer, to minimise ascertainment and survivor bias. In this refined cohort of 406 women, 19 breast cancers occurred over 1,340.97 person-years, an annual incidence of 1.42% (1.60% for BRCA1 and 1.14% for BRCA2). Incidence was lowest within the first 5 years (0.88%/year) and rose beyond 10 years (1.89%/year). These estimates align closely with the recent report and support reassurance during early survivorship while leaving room to discuss risk-reducing mastectomy in long-term survivors.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The value of this work is methodological as much as clinical: by keeping only women tested after their ovarian cancer diagnosis and without prior breast cancer, the authors strip out the ascertainment and survivor biases that inflated earlier estimates. The figure worth quoting in clinic is the contrast between 0.88%/year before 5 years and 1.89%/year beyond 10 years, which justifies deferring the risk-reducing mastectomy discussion without abandoning it. That said, 19 events cannot settle gene-specific risk, and the reported BRCA1 versus BRCA2 difference should be read as indicative only.

Analysis by Dr Thibaut Benquey