Incidence of contralateral and ipsilateral breast cancers and prognosis in BRCA1/2 pathogenic variant carriers based on the Japanese HBOC Consortium registration

J Hum Genet. 2021 Apr;66(4):379-387. doi: 10.1038/s10038-020-00850-5. Epub 2020 Oct 9.


This study aimed to clarify the breast cancer prognosis in Japanese patients with BRCA1/2 pathogenic variant. We analyzed 2235 women with breast cancer who underwent BRCA1/2 genetic testing between 1996 and 2018 using data from the Japanese hereditary breast and ovarian cancer syndrome registry. The cumulative risk for contralateral and ipsilateral breast cancers and time to death since the first breast cancer were stratified based on the BRCA1/2 variant status. The median follow-up was 3.0 years (0.1-34.1 years) after the first breast cancer. The annual average risks of contralateral breast cancer in BRCA1 and BRCA2 and non-BRCA1/2 pathogenic variant carriers were 4.0%, 2.9%, and 1.9%, respectively (P = 0.001). The annual average risks of ipsilateral breast cancer in the three groups were 2.7%, 1.4%, and 1.1%, respectively (P = 0.06). BRCA1 pathogenic variant carriers had significantly higher risks of contralateral (hazard ratio 1.91, P < 0.001) and ipsilateral (hazard ratio 2.00, P = 0.02) breast cancers than non-BRCA1/2 pathogenic variant carriers. The time to death by the BRCA1/2 variant status was not significantly difference (P = 0.28). The prognosis of breast cancer patients who received standard treatment was comparable regardless of the BRCA1/2 variant status.

MeSH terms

  • Adult
  • BRCA1 Protein / genetics*
  • BRCA2 Protein / genetics*
  • Breast Neoplasms / classification*
  • Breast Neoplasms / epidemiology*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Female
  • Genetic Testing / methods*
  • Humans
  • Incidence
  • Japan / epidemiology
  • Middle Aged
  • Mutation*
  • Prognosis


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