Hysterectomy, bilateral oophorectomy, and breast cancer risk in a racially diverse prospective cohort study

J Natl Cancer Inst. 2023 Jun 8;115(6):662-670. doi: 10.1093/jnci/djad038.

Abstract

Background: Gynecologic surgery is hypothesized to reduce risk of breast cancer; however, associations may be modified by subsequent hormone use. Our objective was to examine the association between gynecologic surgery and breast cancer incidence considering the use of hormone therapy.

Methods: The Sister Study is a prospective cohort of initially breast cancer-free women aged 35-74 years with a sister who had breast cancer. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between gynecologic surgery (no surgery, hysterectomy only, bilateral oophorectomy with or without hysterectomy) and incident breast cancer among 50 701 women.

Results: History of gynecologic surgery was common, with 13.8% reporting hysterectomy only and 18.1% reporting bilateral oophorectomy with or without hysterectomy. During follow-up (median = 11.4 years), 3948 cases were diagnosed. Compared with no surgery, bilateral oophorectomy was inversely associated with breast cancer (HR = 0.91, 95% CI = 0.83 to 1.00), and hysterectomy alone was positively associated (HR = 1.12, 95% CI = 1.02 to 1.23). Compared with no surgery and no hormone therapy, bilateral oophorectomy combined with estrogen only therapy (HR = 0.83, 95% CI = 0.74 to 0.94) was inversely associated with breast cancer, while hysterectomy combined with estrogen plus progestin therapy was positively associated with breast cancer (HR = 1.25, 95% CI = 1.01 to 1.55).

Conclusions: We observed an inverse association between bilateral oophorectomy and breast cancer risk. The positive association between hysterectomy and breast cancer may be due to concomitant estrogen plus progestin therapy.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Aged
  • Body Mass Index
  • Breast Neoplasms* / epidemiology
  • Breast Neoplasms* / etiology
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • Estrogens / adverse effects
  • Estrogens / therapeutic use
  • Female
  • Hormone Replacement Therapy* / adverse effects
  • Humans
  • Hysterectomy* / adverse effects
  • Incidence
  • Menopause
  • Middle Aged
  • Neoplasm Invasiveness
  • Ovariectomy* / adverse effects
  • Progestins / adverse effects
  • Progestins / therapeutic use
  • Proportional Hazards Models
  • Prospective Studies
  • Racial Groups* / statistics & numerical data
  • Receptors, Estrogen / metabolism
  • Risk Factors

Substances

  • Estrogens
  • Progestins
  • Receptors, Estrogen