Breast cancer after ovarian cancer in BRCA1 and BRCA2 pathogenic variant heterozygotes: Lower rates for 5 years post chemotherapy

Genet Med. 2024 Sep;26(9):101172. doi: 10.1016/j.gim.2024.101172. Epub 2024 Jun 3.

Abstract

Purpose: The identification of germline BRCA1/BRCA2 pathogenic variants (PV) infer high remaining lifetime breast/ovarian cancer risks, but there is paucity of studies assessing breast cancer risk after ovarian cancer diagnosis.

Methods: We reviewed the history of breast cancer in 895 PV heterozygotes (BRCA1 = 541). Cumulative annual breast cancer incidence was assessed at 2, 5, 10, and >10 years after ovarian cancer diagnosis date.

Results: Breast cancer annual rates were evaluated in 701 assessable women with no breast cancer at ovarian diagnosis (BRCA1 = 425). Incidence was lower at 2 years (1.18%) and 2 to 5 years (1.13%) but rose thereafter for BRCA1 with incidence post 10 years in excess of 4% annually. Breast cancer pathology in BRCA1 PV heterozygotes showed less high-grade triple-negative breast cancer and more lower-grade hormone-receptor-positive cancer than women with no prior ovarian cancer. In the prospective cohort from ovarian cancer diagnosis, <4% of all deaths were caused by breast cancer, although 50% of deaths in women with breast cancer after ovarian cancer diagnosis were due to breast cancer.

Conclusion: Women can be reassured that incidence of breast cancer after ovarian cancer diagnosis is relatively low. It appears likely that this effect is due to platinum-based chemotherapy. Nonetheless women need to be aware that incidence increases thereafter, especially after 10 years.

Keywords: BRCA1; BRCA2; Breast cancer; Ovarian cancer; Survival.

MeSH terms

  • Adult
  • Aged
  • BRCA1 Protein* / genetics
  • BRCA2 Protein* / genetics
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / epidemiology
  • Breast Neoplasms* / genetics
  • Female
  • Genetic Predisposition to Disease
  • Germ-Line Mutation / genetics
  • Heterozygote*
  • Humans
  • Incidence
  • Middle Aged
  • Ovarian Neoplasms* / drug therapy
  • Ovarian Neoplasms* / epidemiology
  • Ovarian Neoplasms* / genetics
  • Prospective Studies

Substances

  • BRCA2 Protein
  • BRCA1 Protein
  • BRCA2 protein, human
  • BRCA1 protein, human