• For women experiencing the symptoms of menopause, HRT can greatly improve quality of life but can also increase the risk of developing breast cancer. Photograph by Dr. Chelsea Mooser. •

According to French physicians in the 1800s, menopause is l'age de retour, a time when women can return to the bliss of their pre-fertile youth. Or according to a bumper sticker I saw the other day, menopause “sucks.” Regardless of one’s perception of menopause, one thing is certain – at around age 50 most women’s ovaries stop pumping out estrogen. Dr. Janet Pregler, director of the UCLA Iris Cantor Women’s Health Center explains, “women who take hormone replacement therapy generally take two hormones: estrogen which is used to treat the menopause symptoms and then progesterone which is used to prevent uterine cancer which will occur if you take estrogen by itself. These are the two hormones that are produced by the ovaries when you go through menstrual cycles, which are much decreased when you go through menopause.”

Although it’s not clear exactly why decreases in these hormones cause the symptoms of menopause, it is clear that supplementing women with estrogen alleviates them. But ever since the inception of HRT in 1942 there were reports on its connection to breast cancer. Although there have been some conflicting studies, “there is really no question now by pretty much anyone who has looked at the data that estrogen plus progesterone promotes breast cancer,” says Dr. Pregler. Her assertion is most strongly supported by two landmark studies.

In the 1990s the National Institutes of Health set up the Women’s Health Initiative (WHI) to study the risks and benefits of hormone replacement therapy. According to a 2002 press release from the NIH, the trial was halted after researchers found an “increased risk of invasive breast cancer” and “increases in coronary heart disease, stroke, and pulmonary embolism in study participants on estrogen plus progestin compared to women taking placebo pills.” A few years later researchers with the UK-based Million Women Study asked over a million women during mammogram appointments to tell them what kind of hormones they were taking. They then followed these women to find out if they got breast cancer or not. “The study confirmed what we saw in the WHI, which is an increased risk for breast cancer,” says Dr. Pregler.

Although the clinical trials are convincing, as a scientist I am always a bit skeptical of their results. In a clinical trial it is often difficult to control for all the variables that can contribute to a disease like breast cancer. I wanted to understand if, on a biological level, estrogen could promote breast cancer.

From my own work I know that cancer arises from a single cell that has undergone a series of genetic mutations that allow it to mutate into a tumor. When a cell divides – or proliferates – it has the potential to pick up these genetic mutations. Therefore, proliferation can lead to mutations, which can lead to cancer.

To understand how estrogen affects cells in the mammary gland, I spoke with Dr. Tim Lane, a senior breast cancer researcher at UCLA. “All throughout life estrogen drives proliferation of cells in the mammary gland,” he explains. This proliferation in the mammary gland is important during development and pregnancy, but proliferation also opens the door for genetic mutations. “Any cell that is being asked to proliferate is at the highest risk of becoming cancerous. The more times proliferation happens during a life, the more times you might get a mutant cell.”

By taking estrogen women essentially cause continued proliferation of cells that normally wouldn’t proliferate after menopause. Although a few extra years of proliferation spurred by HRT won’t guarantee that the cells will get mutated, it does increase the opportunity for mutations.

Of course hormone replacement therapy does have significant benefits. As Dr. Lane confirms, when it comes to treating menopausal symptoms and protecting bones from osteoporosis, “HRT is the only game in town.” So how significant is the breast cancer risk associated with HRT?

According to Dr. Pregler, “hormones probably do have some increased risk but the overall increased risk is small and consistent with other lifestyle choices we make.” She put this risk into perspective with a story from her own life. “I didn’t have my first child until I was 32, that increased my lifetime risk of breast cancer by about one percent, which is well within the realm of taking hormones for a few years.” When her patients ask her about the risks of HRT, Dr. Pregler considers the particular situation of each woman. “Is the risk zero? No. Would I recommend it to a breast cancer survivor or a woman who is high risk? No. On the other hand, a woman who is at normal risk who is having bad symptoms? I think it is certainly a reasonable choice to make.”

And what will I tell someone the next time I am asked about hormone replacement therapy? I will explain that HRT is just one of many factors that causes a small but significant increase in breast cancer risk. For me, since I’ve made other dicey lifestyle choices – still no kids at 32, a smoker when I was young and reckless – it’s not an added risk I want to take.

When I asked my aunt – who has experienced both menopause and breast cancer, which one was worse – she says she’d take a hot flash over chemo any day of the week.



About the Author
Dr. Chelsea Mooser, Ph.D. is scientist and a writer living in Los Angeles. She received her doctorate from the department of Biological Chemistry at UCLA in 2009 for her work on breast cancer. Prior to coming to Los Angeles she was a research assistant studying genetics at the Jackson Laboratory in Maine.

Before becoming a research scientist, Chelsea received her BA from College of the Atlantic in Bar Harbor, Maine and spent a year working with AIDS orphans in Zimbabwe. She hopes to continue to bring science to non-scientists through teaching, writing and building science programs in developing countries. She fills her spare time with flea markets, brunches with friends and traveling.