BACKGROUND AND PURPOSE:

• Vinogradova et al. (BMJ, 2020) examined the risk of breast cancer associated with different types and durations of hormone replacement therapy (HRT)

METHODS:

• Two nested case-control studies
• Data source
  • 2 of the largest UK primary care databases: QResearch and Clinical Practice Research Datalink (CPRD) GOLD
• Participants
  • Women age 50 to 79
  • Primary diagnosis of breast cancer between 1998 and 2018
  • Female controls: Matched by age, general practice, and index date
• Study design
  • Definitions
    • Recent use: <5 years
    • Long-term use: ≥5 years
    • Short-term use: <4 years
  • Odds ratio (OR) calculated for HRT types, adjusted for personal characteristics, smoking status, alcohol consumption, comorbidities, family history, and other prescribed drugs
• Primary outcome
  • Breast cancer diagnosis from general practice, mortality, hospital or cancer registry records

RESULTS:

• 98,611 women with breast cancer | 457,498 controls
• Use of HRT prior to one year before the index date
  • Women with breast cancer: 34%
  • Control Group: 31%
• Estrogen-only therapy and combined estrogen and progestogen therapy were both associated with increased risks of breast cancer in recent users with long-term use, compared with women who never used HRT
  • Estrogen-only: adjusted OR 1.15 (95% CI, 1.09 to 1.21)
  • Combined: 1.79 (95% CI, 1.73 to 1.85)
• For combined progestogens, the increased risk was highest for norethisterone and lowest for dydrogesterone
  • Norethisterone: aOR 1.88 (95% CI, 1.79 to 1.99)
  • Dydrogesterone: aOR 1.24 (95% CI, 1.03 to 1.48)
• Past use
  • Past long-term use of estrogen-only therapy and past short-term use of estrogen-progestogen were not associated with increased risk
  • Past long-term estrogen-progestogen use was still associated with increased risk
    • Estrogen-progestogen: aOR 1.16 (95% CI, 1.11 to 1.21)
• Extra expected cases in HRT users
  • Recent estrogen-only: Between 3 (in younger women) and 8 (in older women) extra cases per 10,000-person years
  • Recent estrogen-progestogen: Between 9 and 36 extra cases per 10,000-person years
  • Past estrogen-progestogen: Between 2 and 8 extra cases per 10,000-person years

CONCLUSION:

• In this study, women who used combined methods of HRT, and women who used HRT for longer, had an increased risk of breast cancer
• Past long-term use of estrogen-only therapy and past short-term use of estrogen-progestogen were not associated with increased risk
• The authors conclude

Our findings of generally lower increased risks for combined HRT treatments and of more pronounced declines in risk once HRT has stopped, provide some counterbalance to the higher than expected risks reported in a recently published meta-analysis

Learn More – Primary Sources:

Use of hormone replacement therapy and risk of breast cancer: nested case-control studies using the QResearch and CPRD databases

Related ObG Topics:

North American Menopause Society: Hormone Therapy Statement

The WHI Randomized Trials: Is Menopausal Hormone Therapy Associated with Long-Term Mortality?

Prospective Data: Breast Cancer Risk and Menopausal Hormone Therapy

Is There an Association Between Vaginal Estrogen Use and Risk for Cardiovascular Disease and Cancer?