Combination Hormone Replacement Therapy Linked to Higher Breast Cancer Risk in New WHI Analysis

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In 2002, results from the Women’s Health Initiative (WHI) Study were released showing that women who took combination hormone replacement therapy (HRT) had a higher risk of breast cancer than women who didn’t take HRT. In the years after the WHI study was published, use of HRT dropped dramatically. At the same time, rates of breast cancer dropped and other studies, including the Million Women Study, found a link between HRT use and breast cancer risk.

In January 2012, a group of experts reviewed the Million Women Study and concluded that it wasn’t done properly. More recently, another group of experts has reviewed the three main studies that were used to make the link between HRT use and breast cancer risk and concluded that the data from the studies don’t support the link. The experts’ analysis was published online on March 14, 2013 by the Journal of Family Planning and Reproductive Health Care. Read the abstract of “Does hormone replacement therapy (HRT) cause breast cancer? An application of causal principles to three studies.”

Still, this analysis was very speculative and considered weak by many doctors. Also, the research wasn’t published in a major medical journal.

Now, other researchers have done a longer-term analysis of information collected in the WHI study and found that combination HRT use IS linked to a higher risk of breast cancer.

The study was published online on March 29, 2013 by the Journal of the National Cancer Institute, a major medical journal. Read the abstract of “Estrogen Plus Progestin and Breast Cancer Incidence and Mortality in the Women’s Health Initiative Observational Study.”

When the WHI study started in 1993, about half of the more than 16,000 postmenopausal women in it got combination HRT. The other half got a placebo (a sugar pill that looked just like the combination HRT). This type of study is called a randomized trial because neither the women nor the doctors knew who was taking the combination HRT and who was taking the placebo. After more than 5.5 years, an early analysis showed that the women taking combination HRT were much more likely to be diagnosed with breast cancer compared to the women taking the placebo. So in 2002, ALL the women in the study stopped taking the medicines, both HRT and placebo. Another analysis several years after the medicines were stopped showed that breast cancer risk in women who got HRT decreased some, but that risk was still higher than the risk in women who didn’t take HRT.

In addition to the randomized trial, the WHI also included an observational study of 93,000 women who weren’t eligible or didn’t want to participate in the randomized trial. In the observational study, the researchers kept track of whether or not the women used HRT, what type of HRT they used, as well as other health information, including mammogram results, age, body mass index, and whether the women smoked or drank alcohol.

This new longer-term analysis looked at 41,499 women in the observational study who had a negative mammogram within 2 years of the study’s start and either didn’t use HRT or used combination HRT:

  • 16,121 women used combination HRT
  • 25,328 didn’t use HRT

The women who took combination HRT tended to be younger, have a lower body mass index, and drank alcohol. About half the women were followed for more than 11 years and half were followed for less than 11 years. During follow-up, 2,236 breast cancers were diagnosed in the women.

The researchers found that women who took combination HRT were about 1.5 times more likely to be diagnosed with breast cancer than women who didn’t take HRT. Women who started using combination HRT as soon as menopause started had an even higher risk.

Dr. Rowan Chlebowski, M.D., Ph.D., of the Los Angeles Biomedical Research Institute and who was the lead researcher and author of the study, said, “This study shows that women who begin the hormonal therapy of estrogen plus progestin closer to menopause are at greater risk of breast cancer than those who started the therapy earlier. Because menopause usually is the reason for women to undergo hormonal therapy, this is a very significant finding.

"The study also showed that all categories of breast cancer are increased -- not just those with favorable prognosis -- among women using estrogen plus progestin. This finding suggests higher mortality from breast cancer among women who use this combined hormonal therapy. As always, women should consult with their physicians and consider the potential risks of any hormonal therapy to help relieve the symptoms of menopause."

To add to the confusion surrounding HRT, seven medical societies issued a statement on March 14, 2013 saying that HRT is the most effective treatment available for menopausal symptoms. The statement was published online by the journals Climacteric and Maturitas. Read “Global Consensus Statement on Menopausal Hormone Therapy.”

It’s important to know that the medical societies all agreed that HRT IS NOT recommended for women who’ve been diagnosed with breast cancer.

It’s also important to know that while the societies said that HRT is the most effective treatment for menopausal symptoms, they also said that higher breast cancer risk is seen with HRT use.

The bottom line on 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. Still, all this conflicting information about HRT and breast cancer risk is confusing. While all the results of studies on HRT and breast cancer risk don’t perfectly agree, there is good evidence that:

  • HRT increases the risk of being diagnosed with invasive breast cancer.
  • HRT increases the risk of recurrence (the breast cancer coming back) in women who’ve been diagnosed.
  • Risk increases within the first several years of HRT use; the risk appears to be greater the longer a woman uses HRT.
  • Combination HRT increases breast cancer risk more than estrogen-only HRT.
  • High-dose HRT increases risk more than low-dose HRT.

Here are the important things to keep in mind:

  • If you’ve ever been diagnosed with breast cancer, HRT is NOT RECOMMENDED for you.
  • HRT is known to increase the risk of blood clots and stroke; these risks go down when you stop taking HRT.
  • Using bioidentical hormones is not recommended.
  • If vaginal dryness or discomfort during intercourse is your only menopausal symptom, you may want to ask your doctor if low-dose topical estrogen if a good idea for you.
  • If you’re having severe hot flashes or other menopausal symptoms, talk to your doctor about ALL of your options. Be sure to discuss the pros and cons of different types and doses of HRT, as well as any other health problems you may have.
  • Some complimentary and holistic medicine techniques have been shown to ease hot flashes, including exercise, yoga, cognitive behavioral therapy, and acupuncture.
  • If you decide to take HRT, try to take it for the shortest time possible. 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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