Menopausal Hormone Therapy with Estrogen Alone Decreases Breast Cancer Incidence

Women who took estrogen alone as hormone therapy for their menopause experienced decreased rates of breast cancer and death from the disease even after they stopped taking the therapy, while postmenopausal women who took estrogen with progestin experienced increased breast cancer rates, according to long-term follow-up results from two large, randomized, placebo-controlled Women's Health Initiative (WHI) trials.

The new data, presented during a press conference at the San Antonio Breast Cancer Symposium (SABCS), included 27,347 postmenopausal women aged 50 to 79 years with no prior breast cancer, enrolled in one of two randomized clinical trials that took place at 40 different centers in the United States between 1993 and 1998, with follow-up taking place over more than 19 years, through September 2016.

In total, 8,506 postmenopausal women with an intact uterus received conjugated equine estrogens (CEE) with medroxyprogesterone acetate (MPA), while 8,102 women received a placebo treatment. Both groups received their treatment for a median of 5.6 years.

Postmenopausal women who had undergone a hysterectomy received CEE alone (5,310) or placebo (5,429) for a median of 7.2 years.

Among those who only received CEE — the estrogen-only group – 520 cases of breast cancer were diagnosed after 16.1 years of follow-up. These women were 23% less likely to have been diagnosed with breast cancer and 44% less likely to die from the disease when compared with women who had received placebo.

In the group that received both estrogen and progestin (CEE with MPA), there were 1,003 diagnoses of breast cancer after 18.3 years of follow-up, for a 29% increased risk of diagnosis versus those on placebo. This group also saw an increased risk for death from breast cancer in the extended analysis, but this finding did not reach statistical significance.

“Menopausal hormone therapy with estrogen plus progestin (for postmenopausal women with an intact uterus) and estrogen alone (for postmenopausal women with prior hysterectomy) continues to be used by millions of women worldwide,” Dr. Roman Chlebowski, chief of the Division of Medical Oncology and Hematology at Harbor-UCLA Medical Center, and an investigator at The Lundquist Institute, said in a statement. “Nonetheless, after nearly half a century, menopausal hormone therapy influence on breast cancer incidence and mortality remains unsettled, with discordant findings from prospective observational studies compared to findings from randomized clinical trials.”

When asked at the press conference whether the new findings should impact clinical guidelines that doctors use to treat their patients, Chlebowski said he was hopeful that they would, and added that it’s important to consider the weight of his 20-year randomized-controlled trial in a large patient population against a meta-analysis of observational studies, which are not as rigorous.

“Women who are considering estrogen alone should know it’s safer and that there may be a breast cancer benefit associated with its use. I think women considering estrogen plus progestin have a little bit more of a difficult dilemma, because they have to be willing to accept an increased 20-year, and even a lifetime, breast cancer risk,” he said. “Having said that, for a woman with limited symptoms…the absolute risk is very small.”