'Tis but a scratch: a critical review of the Women's Health Initiative evidence associating menopausal hormone therapy with the risk of breast cancer

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doi: 10.1097/GME.0000000000002267.


Online ahead of print.

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Avrum Z Bluming et al.


Menopause.


.

Abstract

Use of menopausal hormone therapy (HT) fell precipitously after 2002, largely as a result of the Women’s Health Initiative’s report claiming that the combination of conjugated equine estrogen (CEE) and medroxyprogesterone acetate increased breast cancer risk and did not improve quality of life. More recently, Women’s Health Initiative (WHI) publications acknowledge HT as the most effective treatment for managing menopausal vasomotor symptoms and report that CEE alone reduces the risk of breast cancer by 23% while reducing breast cancer death by 40%. Their sole remaining concern is a small increase in breast cancer incidence with CEE and medroxyprogesterone acetate (1 per 1,000 women per year) but with no increased risk of breast cancer mortality. This article closely examines evidence that calls even this claim of breast cancer risk into serious question, including the WHI’s reporting of nonsignificant results as if they were meaningful, a misinterpretation of its own data, and the misleading assertion that the WHI’s findings have reduced the incidence of breast cancer in the United States. A generation of women has been deprived of HT largely as a result of this widely publicized misinterpretation of the data. This article attempts to rectify this misunderstanding, with the goal of helping patients and physicians make informed joint decisions about the use of HT.

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Conflict of interest statement

Financial disclosure/conflicts of interest: R.D.L. was funded by the National Heart, Lung, and Blood Institute as a principal investigator in the Women’s Health Initiative 1993 to 2005 but has not received funding related to this article from any source for more than 5 years. The other authors have nothing to disclose.

References

    1. Brown S. Shock, terror and controversy: how the media reacted to the Women’s Health Initiative. Climacteric 2012;15:275–280. doi: 10.3109/13697137.2012.660048



      DOI

    1. Rossouw JE, Anderson GL, Prentice RL, et al; Writing Group for the Women’s Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA 2002;288:321–333. doi: 10.1001/jama.288.3.321



      DOI

    1. Chlebowski RT, Aragaki AK. The Women’s Health Initiative randomized trials of menopausal hormone therapy and breast cancer: findings in context. Menopause 2023;30:454–461. doi: 10.1097/GME.0000000000002154



      DOI

    1. Anderson GL, Chlebowski RT, Rossouw JE, et al. Prior hormone therapy and breast cancer risk in the Women’s Health Initiative randomized trial of estrogen plus progestin. Maturitas 2006;55:103–115. doi: 10.1016/j.maturitas.2006.05.004



      DOI

    1. Langer RD, Manson JE, Allison MA. Have we come full circle — or moved forward? The Women’s Health Initiative 10 years on. Climacteric 2012;15:206–212. doi: 10.1016/j.maturitas.2006.05.004



      DOI

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