Why Are Leading Researchers Saying “Enough” to the WHI’s Breast Cancer Claims?
Because, in their view, the Women’s Health Initiative keeps reporting a breast cancer risk from combined hormone therapy that does not survive the statistical adjustments its own protocol required. In this reply letter in Menopause, Avrum Bluming, Howard Hodis and Robert Langer argue that once those adjustments are made, women randomized to estrogen plus progestin (CEE+MPA) showed no increased risk of breast cancer, and that the WHI’s warnings have scared millions of women away from hormone therapy.
Dr. Kumar’s Take
This is a pointed exchange between researchers, not a new study, and it should be read as one side of a long-running debate. Still, the core statistical argument is specific and checkable. The breast cancer signal from the WHI estrogen plus progestin trial has always been borderline, and these authors show how it becomes non-significant with the adjustments the trial’s protocol called for. Even the WHI’s own worst-case estimate is about 1 extra case of non-fatal breast cancer per 1,000 women per year of use. That is a small number to have shaped a generation of fear about hormone therapy.
What the Authors Argue
- Breast cancer was a secondary outcome. Per the WHI protocol, it required statistical adjustment for covariates and multiple outcomes, because participants were randomized for heart disease risk, not breast cancer risk. The authors say WHI investigators instead re-branded it as the primary safety outcome.
- The 2002 result was borderline. The original paper reported that breast cancer “almost reached nominal statistical significance” (95% CI 1.00 to 1.59). With adjustment for multiple comparisons, the interval was 0.83 to 1.92, clearly non-significant.
- The 2003 result lost significance with basic adjustment. Adjusting for repeated looks at the data gave a 95% CI of 0.97 to 1.59.
- The placebo group was unusual. The authors attribute the higher hazard ratio to an unexplained, extremely low breast cancer rate among women with prior hormone therapy use who were assigned to placebo, rather than to increased risk on CEE+MPA.
- No increase in new users. The WHI acknowledges no increased risk among women who had not taken hormone therapy before joining the study, which describes most women who start it.
- Post-trial follow-up does not fix it. The authors say the WHI’s roughly 15 years of observational follow-up also lacked the required adjustments.
The Other Side
This letter is a response to WHI investigators Rowan Chlebowski and Aaron Aragaki, who maintain that estrogen plus progestin increases breast cancer risk. The disagreement is about which statistical analyses are appropriate, not about the raw numbers. One of the letter’s authors, Robert Langer, was himself a WHI principal investigator from 1993 to 2005.
Practical Takeaways
- Understand that researchers, including a former WHI investigator, disagree sharply about the WHI breast cancer findings for estrogen plus progestin
- Recognize that statistical significance, and the adjustments behind it, matter when evaluating medical research claims
- Ask about absolute risk: even the WHI’s worst-case estimate is about 1 extra non-fatal breast cancer per 1,000 women per year
- The debate concerns combined estrogen plus progestin (CEE+MPA), the specific regimen tested in that WHI trial
- Ask for an individualized risk assessment rather than a decision based on headlines
What This Means for Perimenopause and Menopause Care
For women weighing hormone therapy, this letter is a reminder that the breast cancer warning attached to it rests on a contested analysis. The authors describe hormone therapy as the most effective treatment for menopausal symptoms and bone loss when started within 10 years of menopause. Decisions still need to be individual, made with a provider who can explain both sides of the evidence.
Related Studies and Research
- Risks and benefits of hormone therapy: has medical dogma now been overturned?
- Effects of menopause on temperature regulation
- Recurrent Urinary Tract Infection in Older Outpatient Women
- Episode 27: Perimenopause, Menopause, and HRT: What Every Woman Should Know
FAQs
Did the WHI find that hormone therapy causes breast cancer?
The WHI investigators say estrogen plus progestin increased breast cancer risk. These authors counter that the increase was never statistically significant once the protocol-mandated adjustments were applied, and that it was driven by an unusually low rate in one placebo subgroup.
What does this mean for women currently avoiding hormone therapy?
It means the breast cancer risk they have heard about is disputed, and small in absolute terms even at worst. It is worth revisiting the decision with a provider who knows the current evidence.
How can I tell if my doctor understands the current hormone therapy evidence?
Ask about the absolute risk of breast cancer with hormone therapy, whether it differs between women with and without prior use, and whether they distinguish between estrogen-only and combined regimens.
Bottom Line
Three researchers, one a former WHI investigator, argue that the WHI’s breast cancer claim for estrogen plus progestin does not hold up under the statistical adjustments its own protocol required. It is one side of a live debate, but it is a specific, data-based argument that women and their doctors should hear before rejecting hormone therapy out of fear.
