New evidence on impact of hormones on breast cancer

New evidence on impact of hormones on breast cancer

Use of menopausal hormone therapy decreased dramatically after reports of increased breast cancer risk with oestrogen plus progestin from the WHI randomised clinical trial followed by the Million Women Study observational analysis. Following the initial WHI reports, decreases in both combined oestrogen plus progestin use as well as oestrogen alone use were seen. However, in the WHI randomised trials, while oestrogen plus progestin increased breast cancer incidence and breast cancer deaths, oestrogen alone in women with prior hysterectomy significantly reduced breast cancer incidence and breast cancer deaths. Those results raised questions about the short- and long-term postintervention effects of these two regimens on breast cancer.

Rowan T. Chlebowski, of the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, California, and co-authors examined early and late postintervention effects on breast cancer in the two WHI hormone therapy trials with a current median follow-up of 13 years. Their analysis* of the longer-term influence of menopausal hormone therapy on breast cancer incidence is published online by JAMA Oncology.

A total of 16,608 women with a uterus were assigned to receive oral conjugated equine oestrogens (0.625 mg/d [oestrogen]) plus medroxyprogesterone acetate (2.5 mg/d [progestin]) or placebo with a median intervention of 5.6 years, and 10,739 women with prior hysterectomy were assigned to receive the oestrogen alone or placebo with a median intervention of 7.2 years.

In the oestrogen plus progestin trial, the increasing breast cancer risk seen during the intervention while women were receiving the combined hormones was followed by a substantial drop in risk in the early postintervention period (within 2.75 years from intervention) when hormone therapy was discontinued but a sustained higher breast cancer risk remained during the late postintervention period years after the therapy was stopped, according to the results.

In the oestrogen alone trial, the reduced breast cancer risk seen during the intervention when women were receiving the oestrogen lasted through the early postintervention phase but was lost during the late postintervention follow-up, the results show.

“The ongoing influences on breast cancer after stopping hormone therapy in the WHI trials require recalibration of breast cancer risk and benefit calculation for both regimens, with greater adverse influence for oestrogen and progestin use and somewhat greater benefit for use of oestrogen alone,” the article concludes.

In a related editorial**, Rama Khokha, of the Princess Margaret Cancer Centre, Toronto, Canada, and co-authors write: “Emerging detailed analyses from the WHI trials such as that reported by Chlebowski et al, reveal new compelling evidence for the significance of progesterone in breast cancer where it has traditionally taken a back seat to oestrogen.”

* Rowan T. Chlebowski, et al. Breast Cancer After Use of Estrogen Plus Progestin and Estrogen Alone. Analyses of Data From 2 Women’s Health Initiative Randomized Clinical Trials. JAMA Oncol. Published online April 16, 2015. doi:10.1001/jamaoncol.2015.0494

** Rama Khokha, et al. Progesterone Exposure and Breast Cancer Risk. Understanding the Biological Roots. JAMA Oncol. Published online April 16, 2015. doi:10.1001/jamaoncol.2015.0512






By Jo Carlowe,

OnMedica, Friday 17 April 2015

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