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Hormone Replacement Therapy’s Effect on Breast Cancer Risk Changes Over Time

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Another analysis of results from the two parts of the Women’s Health Initiative (WHI) trial has found that the influence of hormone replacement therapy (HRT) on breast cancer risk changes as time passes.

The study was published online on April 16, 2015 by JAMA Oncology. Read the abstract of “Breast Cancer After Use of Estrogen Plus Progestin and Estrogen Alone: Analysis of Data From 2 Women’s Health Initiative Randomized Clinical Trials.”

The WHI started in 1993 and included nearly 27,350 postmenopausal women ages 50 to 79. The 16,608 women who had a uterus were randomly assigned to get either:

  • combination HRT (combination HRT contains both estrogen and progesterone)
  • a placebo (a sugar pill that looked just like the combination HRT pill)

for nearly 6 years.

The 10,739 women who had had a hysterectomy and so didn’t have a uterus were randomly assigned to get either:

  • estrogen-only HRT
  • a placebo (a sugar pill that looked just liked estrogen-only HRT)

for about 7 years.

In 2002, the combination HRT part of the WHI was stopped after about 6 years of follow-up because an early analysis showed that the women taking combination HRT were much more likely to be diagnosed with breast cancer compared to women taking the placebo. In 2004, the estrogen-only HRT part of the study also was stopped because of concerns about the women’s risk of breast cancer.

When the two parts of the WHI study ended, more than 12,700 women who had been taking combination HRT and more than 7,640 women who had been taking estrogen-only HRT agreed to be followed for more time. The researchers followed these women through Sept. 30, 2010. Fewer than 4% of the women continued to take HRT (either combination or estrogen-only) after the WHI trial officially ended.

Combination HRT long-term results

The higher breast cancer risk that was seen while the women were taking the combination HRT dropped about 3 years after the women stopped taking the combination HRT. Still, their risk of breast cancer stayed higher than average.

Estrogen-only HRT long-term results

While taking estrogen-only HRT, women were about 20% less likely to be diagnosed with breast cancer compared to women taking the placebo. This decrease in risk lasted for a few years after the women stopped taking estrogen-only HRT. Still, a few years later, this decrease in risk went away.

In an editorial in the same issue of JAMA Oncology, Rama Khokha, Ph.D., of the Princess Margaret Cancer Centre in Toronto wrote, “The contrast between effects of E + P [estrogen plus progesterone] therapy vs estrogen alone is striking – breast cancer risk is persistently elevated with E + P therapy, while risk is persistently decreased with estrogen alone therapy. Thus, an important message underlying the study is that the progesterone inclusion during a median hormone therapy intervention period of 5.6 years not only increases the breast cancer risk during intervention but results in a continued elevated risk for several years after stopping this regimen.”

Many studies have shown a link between higher breast cancer risk and using HRT to treat menopausal symptoms. The results of all the studies aren't exactly the same, but there is good evidence that:

  • HRT increases invasive breast cancer risk
  • breast cancer risk goes up during the first several years of using HRT; risk seems to keep increasing the longer a woman uses HRT
  • high-dose HRT increases risk more than low-dose HRT
  • combination HRT increases risk more than estrogen-only HRT

Menopausal side effects can dramatically reduce quality of life for some women. These women have to weigh the benefits of HRT against the risks. If you're having severe hot flashes or other menopausal side effects and are considering HRT, talk to your doctor about all of your options. Ask how you can minimize your breast cancer risk AND relieve your symptoms. Be sure to discuss the pros and cons of different types and doses of HRT.

If you’ve been diagnosed with breast cancer, you should NOT take any type of HRT.

If you do decide to take HRT, try to take it for the shortest time possible and ask your doctor if estrogen-only HRT is a good option for you. You also may want to ask your doctor about vaginal or transdermal HRT.

Learn more about menopause and ways to manage side effects on the Managing Menopausal Symptoms pages.

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