BACKGROUND AND PURPOSE:

• Carriers of BRCA1 and BRCA2 pathogenic variants are at higher risk of developing breast and ovarian cancer, and these variants have also been associated with increased risk of other cancer types
• Allen et al. (Journal of Clinical Oncology, 2024) estimated relative and absolute risks of second primary cancer (SPC)

METHODS:

• Retrospective cohort study
  • Data from UK National Disease Registration Service and Hospital Episode Statistics
• Population
  • Male and female individuals diagnosed with breast cancer
  • Tested for germline BRCA1/BRCA2 pathogenic variants (between 1995 and 2019)
• Exposures
  • BRCA1/BRCA2 pathogenic variant carriers
  • Non carriers
• Study design
  • Individuals were followed until
    • SPC diagnosis | Death | Migration | Contralateral breast/ovarian surgery plus 1 year | End of 2020
  • Standardized incidence ratios (SIRs) were calculated using English population incidences
  • Hazard ratios (HR) were calculated using Cox regression
• Primary outcome
  • Second primary cancer

RESULTS:

• Females with breast cancer: 25,811 | Males with breast cancer: 480
  • BCRA1 carriers: 1840 | BRCA2 carriers: 1750
• Compared with population incidences, female BRCA1 carriers had elevated incidence of SPCs
  • Contralateral breast cancer: SIR 15.6 (95% CI, 11.8 to 20.2)
  • Ovarian: SIR 44.0 (95% CI, 31.4 to 59.9)
  • Combined nonbreast/ovarian: SIR 2.18 (95% CI, 1.59 to 2.92)
  • Colorectal: SIR 4.80 (95% CI, 2.62 to 8.05)
  • Endometrial: SIR 2.92 (95% CI, 1.07 to 6.35)
• BRCA1 carriers had elevated incidence of SPCs
  • Contralateral breast cancer: SIR 7.70 (95% CI, 5.45 to 10.6)
  • Ovarian: SIR 16.8 (95% CI, 10.3 to 26.0)
  • Pancreatic: SIR 5.42 (95% CI, 2.09 to 12.5)
  • Combined nonbreast/ovarian: SIR 1.68 (95% CI, 1.24 to 2.23)
• Compared with females without BRCA1/BRCA2 pathogenic variants, BRCA1 carriers had higher risk of
  • Contralateral breast cancer: HR 3.60 (95% CI, 2.65 to 4.90)
  • Ovarian: HR 33.0 (95% CI, 19.1 to 57.1)
  • Combined nonbreast/ovarian: HR 1.45 (95% CI, 1.05 to 2.01)
  • Colorectal: HR 2.93 (95% CI, 1.53 to 5.62)
• BRCA2 carriers had higher risk of
  • Contralateral breast cancer: HR 2.40 (95% CI, 1.70 to 3.40)
  • Ovarian: HR 12.0 (95% CI, 6.70 to 21.5)
  • Pancreatic: HR 3.56 (95% CI, 1.34 to 9.48)
• Ten-year cumulative risk for second primary cancers were
  • For BRCA1 carriers
    • Contralateral breast cancer: 16%
    • Ovarian: 6.3%
    • Combined nonbreast/ovarian cancer: 7.8%
  • For BRCA2 carriers
    • Contralateral breast cancer: 12%
    • Ovarian: 3.0%
    • Combined nonbreast/ovarian cancer: 6.2%
  • For noncarriers
    • Contralateral breast cancer: 3.6%
    • Ovarian: 0.4%
    • Combined nonbreast/ovarian cancer: 4.9%
• Compared to noncarriers, male BRCA2 carriers had higher risk of
  • Contralateral breast cancer: HR 13.1 (95% CI, 1.19 to 146)
  • Prostate: HR 5.61 (95% CI, 1.96 to 16.0)

CONCLUSION:

• Breast cancer survivors with BRCA1/BRCA2 pathogenic variants are at increased risk of developing several types of second primary cancer, and increased surveillance may be warranted for this population

Learn More – Primary Sources:

Second Primary Cancer Risks After Breast Cancer in BRCA1 and BRCA2 Pathogenic Variant Carriers