The following article features coverage from the 2019 San Antonio Breast Cancer Symposium. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

Although estrogen alone appeared to decrease the incidence of breast cancer in the long term in postmenopausal women who had undergone hysterectomy, estrogen plus progestin appeared to increase the incidence of breast cancers long-term in postmenopausal women with an intact uterus.

The long-term results from the Women’s Health Initiative (WHI) randomized trials were presented at the 2019 San Antonio Breast Cancer Symposium (SABCS) in Texas.1

Between 1993 and 1998, the WHI trials enrolled women who had no history of breast cancer from 40 sites in the United States. Eligible women were postmenopausal and between the ages of 50 and 79.

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A total of 16,608 women (each with an intact uterus) were randomly assigned to receive conjugated equine estrogens plus medroxyprogesterone acetate or placebo for a median of 5.6 years, and 10,739 women who had undergone a hysterectomy were randomly selected to receive conjugated equine estrogens alone or placebo for a median of 7.2 years.

While receiving conjugated equine estrogens alone, women who had undergone hysterectomy had a significantly lower rate of breast cancer compared with the placebo group (hazard ratio [HR], 0.76 95% CI, 0.58-0.98, P =.04).

In contrast, while receiving conjugated equine estrogens plus medroxyprogesterone acetate, women with an intact uterus had a significantly higher rate of breast cancer compared with the placebo group (HR, 1.26; 95%, CI 1.02-1.56; P =.04).

More than a decade after discontinuing conjugated equine estrogens plus medroxyprogesterone acetate, women with an intact uterus continued to have a significantly higher rate of breast cancer compared with the placebo group (HR, 1.29; 95% CI, 1.14-1.47; P <.001). In addition, these women had a 45% higher risk of dying from breast cancer (HR, 1.45; 95% CI, 0.98-2.15; P =.06) and a 29% higher risk of dying after a breast cancer diagnosis (HR, 1.29; 95% CI, 1.02-1.63; P =.03).

In contrast, more than a decade after discontinuing conjugated equine estrogens alone, women who had undergone a hysterectomy continued to have a significantly lower rate of breast cancer (HR, 0.76; 95% CI, 0.58- 0.98; P =.04), as well as a lower risk of dying from breast cancer (HR, 0.56; 95% CI, 0.34-0.92; P =.02) or after a breast cancer diagnosis (HR, 0.75; 95% CI, 0.56-1.01; P =.06).

Regarding the mortality data, study presenter Rowan T. Chlebowski, MD, PhD, chief of the division of medical oncology and hematology at Harbor-UCLA Medical Center, and an investigator at The Lundquist Institute, cautioned that these analyses were not preplanned — they were exploratory. 

“I should point out that, to our review, this is the only intervention of any kind that has been able to report a reduction in deaths from breast cancer, including the tamoxifen and aromatase inhibitor trials,” said Dr Chlebowski.

He concluded that the use of conjugated equine estrogens alone and conjugated equine estrogens plus medroxyprogesterone acetate have “opposite effects” on breast cancer. “These findings, in conjunction with other hormone therapy effects on clinical outcomes, should inform clinical decision making.”

Disclosure: Dr Chlebowski disclosed financial relationships with Novartis, AstraZeneca, Amgen, Immunomedics, Puma, and Genentech. For a full list of disclosures, please refer to the original abstract.

Read more of Cancer Therapy Advisor‘s coverage of SABCS by visiting the conference page.

Reference

  1. Chlebowski RT, Anderson GL, Aragaki AK, et al. Long-term influence of estrogen plus progestin and estrogen alone use on breast cancer incidence: The Women’s Health Initiative randomized trials. Oral presentation at: 2019 San Antonio Breast Cancer Symposium; December 10-14, 2019; San Antonio, TX. Abstract GS5-00.