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2020
Br Med J
A large UK study of 98,611 women with breast cancer and 457,498 controls found that long-term hormone replacement therapy (HRT) use (≥5 years) was associated with significantly increased breast cancer risk, with combined estrogen-progestogen therapy showing a 79% increased risk and estrogen-only therapy showing a 15% increased risk. Among combined therapies, norethisterone carried the highest risk (88% increase) while dydrogesterone showed the lowest (24% increase), and importantly, the increased risk from past long-term combined therapy use persisted even after stopping treatment (16% increased risk). In practical terms, recent combined HRT users could expect 9-36 extra breast cancer cases per 10,000 women per year depending on age, while estrogen-only users would see 3-8 extra cases per 10,000 women per year, providing critical information for women and clinicians weighing the benefits and risks of different HRT regimens.
2020
JAMA
This long-term follow-up study of over 27,000 postmenopausal women in the Women’s Health Initiative tracked breast cancer outcomes for more than 20 years after participants were randomized to receive either hormone therapy or placebo. The results showed strikingly different effects depending on the type of hormone therapy: estrogen alone (CEE) in women who had undergone hysterectomy was associated with 22% lower breast cancer incidence and 40% lower breast cancer mortality, while estrogen plus progestin (CEE plus MPA) in women with an intact uterus was associated with 28% higher breast cancer incidence but no significant difference in breast cancer mortality. These findings indicate that the addition of progestin to estrogen therapy substantially changes its impact on breast cancer risk, with estrogen-alone therapy appearing protective and estrogen-plus-progestin therapy increasing risk. The study helps resolve longstanding uncertainty about menopausal hormone therapy and breast cancer by demonstrating that the type of hormone therapy and whether a woman has had a hysterectomy are critical factors in determining breast cancer outcomes.
2020
Breast Cancer Res
A study of 118,760 postmenopausal women in the NIH-AARP cohort found that combined estrogen-progestogen therapy (EPT) was associated with a 54% increased breast cancer risk overall, with risk doubling for women using EPT for 10 or more years and reaching an 80% increased risk for those who continued use through 2004. Importantly, women who discontinued EPT showed no increased risk (14% non-significant increase), suggesting the elevated risk may be reversible after stopping treatment. Estrogen-only therapy (ET) showed no increased risk at baseline, though a 35% increased risk emerged in women who continued use through 2004, and EPT was associated with elevated risk across all breast cancer subtypes including in situ disease, invasive cancers, and tumors of varying hormone receptor status.
2024
Breast Cancer Res Treat
A meta-analysis of 10 randomized controlled trials including 14,282 participants and 591 breast cancers found that estrogen-alone hormone therapy was associated with a significant 23% reduction in breast cancer incidence (3.6% vs 4.7% in estrogen vs placebo groups, RR 0.77, 95% CI 0.65-0.91, P=0.002). This finding was driven primarily by the large Women’s Health Initiative trial but was supported by nine smaller trials showing similar directional effects, with estradiol formulations showing a 37% non-significant risk reduction. These results from randomized trials contradict findings from observational cohort studies and challenge conventional wisdom about hormone therapy and breast cancer, suggesting that estrogen-alone therapy (in women without a uterus) may actually protect against breast cancer rather than increase risk—a finding with important implications for counseling postmenopausal women about menopausal hormone therapy decisions.
2023
Environ Sci Pollut Res
A hospital-based case-control study in Petrópolis, Brazil found that women exposed to pesticides for 10 or more years had elevated but non-significant breast cancer risk after adjusting for confounders (OR = 1.40; 95% CI: 0.85-2.49), while higher education and hormone replacement therapy showed significant positive associations, and having 2+ pregnancies was protective. The authors conclude that further research is needed to clarify pesticide exposure’s contribution to breast cancer development given conflicting findings in the literature.
2022
Int J Epidemiol
A large European prospective study of 150,257 women followed for 14 years found that weight gain of more than 10 kg from age 20 to middle adulthood was associated with a 42% increased postmenopausal breast cancer risk among women who were lean at age 20, with the association present in both HRT users (23% increased risk) and non-users (40% increased risk) and particularly strong for ER+/PR+ breast cancers (46% increased risk). The findings indicate that maintaining stable weight from young adulthood is especially important for women who start out lean, as weight gain appears to negate the protective effect of lower early-life body weight. These results highlight a critical window for breast cancer prevention: while being lean in early adulthood is protective, this benefit is substantially diminished by subsequent weight gain, suggesting that weight management efforts should focus not just on current weight but on preventing long-term weight accumulation from young adulthood through menopause.
2018
Breast Cancer Res Treat
A meta-analysis of 25 epidemiological studies (23 cohort studies and 2 randomized trials) found that hormone replacement therapy (HRT) was associated with a 33% increased breast cancer risk overall, with combined estrogen-progestin therapy (EPT) showing stronger associations than estrogen-only therapy (ET). EPT was associated with both ductal (51% increased risk) and lobular breast cancer (38% increased risk), and all HRT types were linked to ER-positive but not ER-negative breast cancers, consistent with hormone-driven carcinogenesis. Notably, Asian women using HRT showed higher breast cancer risk than Western women, possibly due to differences in baseline hormone levels, genetic susceptibility, body composition, or HRT formulations used—a finding highlighting the importance of considering racial and ethnic differences when counseling women about menopausal hormone therapy risks and benefits.
2018
PLOS One
A case-control study of 399 breast cancer patients with receptor status information and 324 controls found that current menopausal hormone therapy (MHT) use was associated with approximately double the risk of hormone receptor-positive breast cancers, including ER+ (104% increased risk), ER+/PR+ (129% increased risk), and notably ER+/PR+/HER2- subtypes (130% increased risk). Past MHT use showed no elevated risk for any subtype, and current use was not significantly associated with hormone receptor-negative cancers, indicating the effect is specific to hormonally-driven tumors. These findings provide mounting evidence that MHT specifically increases risk of the ER+/PR+/HER2- subtype—the most common breast cancer type—adding to concerns about current hormone therapy use and supporting the need for women and clinicians to carefully weigh the duration of MHT treatment against cardiovascular and quality-of-life benefits versus breast cancer risks.