Does Assisted Reproduction Increase Risk of Breast, Ovarian, Uterine Cancer?

BACKGROUND AND PURPOSE:

  • Williams et al. (BMJ, 2018) examined the risk of ovarian, breast, and uterine cancer in women who underwent assisted reproduction

METHODS:

  • Large, population-based, data linkage cohort study of women who underwent ART
    • Cohort records 1991 to September 2009, with those included from October 2009 to December 2010 providing consent
  • ART defined as “treatments or procedures that include in vitro handling of both human oocytes and sperm or embryos, for the purpose of reproduction.”
  • Fertility records for cohort members were linked to national cancer registrations
  • The main outcome measures observed first diagnosis of ovarian, breast, and uterine cancer
  • Potential confounders, such as parity and infertility diagnosis were included in the analysis

RESULTS:

  • 255,786 women contributed 2,257,789 person years’ follow up
  • There was no significant increased risk of
    • Uterine cancer: 164 observed v 146.9 expected; Standardized incidence ratio SIR 1.12 (95% CI, 0.95 to 1.30)
    • Breast cancer (overall): 2,578 observed vs 2,641.2 expected; SIR 0.98 (95% CI, 0.94 to 1.01)
    • Invasive breast cancer: 2272 observed vs 2,371.4 expected; SIR 0.96 (95% CI, 0.92 to 1.00)
  • There was significant increase in risk for
    • In situ breast cancer: 291 observed vs 253.5 expected; SIR 1.15 (95% CI, 1.02 to 1.29)
      • absolute excess risk (AER) 1.7 cases per 100,000 person years, (95% CI, 0.2 to 3.2)
      • associated with an increasing number of treatment cycles (P=0.03)
    • Ovarian cancer overall: 405 observed vs 291.82 expected; SIR 1.39 (95% CI, 1.26 to 1.53)
      • AER 5.0 cases per 100,000 person years (95% CI, 3.3 to 6.9)
    • Invasive ovarian cancer: 264 observed vs 188.1 expected; SIR 1.40 (95% CI, 1.24 to 1.58)
      • AER 3.4 cases per 100 000 person years, (95% CI, 2.0 to 4.9)
    • Borderline ovarian cancer: (141 observed vs 103.7 expected; SIR 1.36 (95% CI, 1.15 to 1.60)
      • AER 1.7 cases per 100,000 person years (95% CI, 0.7 to 2.8)
    • Note: Ovarian cancer risk
      • Increased risks of ovarian cancers limited to women with endometriosis and/or low parity
      • No observed increase in ovarian tumor risk for women treated because of only male factor or unexplained infertility

CONCLUSION:

  • The use of assisted reproduction did not increase risk for invasive breast or uterine cancer
  • In situ breast cancer was increased but not overall cancer
    • Authors suggest that potential explanations may include surveillance bias, chance, and potential confounding by factors such as higher socioeconomic status
  • Ovarian cancer risk was increased
    • Borderline cancer may related to surveillance bias as women in ART programs undergo multiple ultrasound examinations
    • The authors state that “our results suggest that this finding is more likely due to underlying patient characteristics, rather than assisted reproduction itself.”

Learn More – Primary Sources:

Risks of ovarian, breast, and corpus uteri cancer in women treated with assisted reproductive technology in Great Britain, 1991-2010: data linkage study including 2.2 million person years of observation