For women diagnosed with hormone-sensitive breast cancer -- more than 150,000 in the U.S. each year -- five years of tamoxifen treatment can dramatically cut the risk of death or recurrence of the cancer, according to a study published Thursday in the medical journal The Lancet.
Tamoxifen, a mainstay in breast cancer therapy since the early 1980s, blocks estrogen receptors to thwart the sex hormone's tumor-feeding effects. Doctors always knew it worked, but the Lancet study -- which included data from 20 trials and 21,000 women -- confirmed the drug's effects are both profound and long-lasting.
"It is an extraordinary drug in terms of the protection it offers women in the decade after treatment," said Christina Davies, a senior research scientist at the Clinical Trial Service Unit at Oxford University and the study's lead author. "It's off-patent, it's cheap and it's available to women worldwide."
Taking a pill a day for five years reduced annual breast-cancer mortality by 30 percent for 15 years, the study found. And recurrence rates fell 47 percent in the first four years after treatment, and 32 percent over the next five years, according to the study.
But tamoxifen does come with its share of side effects, and some are even life-threatening, such as an increased risk of uterine cancer and blood clots forming in the lungs. In the Lancet study, there were nine deaths from uterine cancer and six deaths from lung blood clots among women taking tamoxifen compared with one death from uterine cancer and no deaths from lung blood clots in women taking a placebo. However, the overall risk of death was small -- 0.1 percent in younger women and 0.6 percent in older women.
Less severe but no less significant for premenopausal women on the fence about tamoxifen is the drug's potential to trigger symptoms of menopause -- hot flashes, mood swings, dryness, leg cramps and joint pain. For some women, those discomforting side effects are enough to make them hesitate when it comes to tamoxifen.
Alicia Staley was 33 when she was diagnosed with breast cancer. Her doctor recommended a lumpectomy, radiation therapy and five years of tamoxifen. Staley, a systems analyst in Boston, said she weighed the drug's benefits against the risks and decided to start taking it. But after 2½ years, the side effects became unbearable.
"My doctor felt tamoxifen was definitely doing its job, but the side effects were just too much," said Staley.
Six months later, her breast cancer came back.
"I think that staying on tamoxifen probably kept it in check," said Staley. "I racked my brain at the time, wondering, 'Did I make the right decision?' But it was a quality of life decision at that point."
Her doctor said she could have another lumpectomy and more radiation, or "bite the bullet and put this to rest" with a double mastectomy. Staley opted for the radical surgery, and credits tamoxifen for buying her time to prepare herself for a much more difficult decision.
"If I hadn't tried it and eventually relapsed, I think I would have always questioned that there was an option on the table that I hadn't taken," she said. "Tamoxifen was sort of a blessing in disguise. It gave me a little distance and the opportunity to make a much better decision for myself."
Staley, who is today cancer-free and with peace of mind she never thought she would get, said she wonders what would have happened had she made it to the "magical five-year" treatment endpoint. Studies have found that even two years on tamoxifen can bring benefits, and ongoing studies are investigating whether a 10-year treatment course is even better than a five-year course.
The study also confirms that women whose tumors are even mildly hormone-sensitive -- as low as 1 percent positive for estrogen receptors in standard lab tests -- can benefit from tamoxifen.
"Recently, we started calling these low-level-expressing tumors positive and have been offering these women tamoxifen," said Dr. Banu Arun, co-director of Clinical Cancer Genetics at the University of Texas MD Anderson Cancer Center in Houston. "This further supports that what we've been doing was correct."
The new study also found that tamoxifen extends survival, even in women who've had chemotherapy, debunking a common misconception that one or the other would do, Arun said.
Tamoxifen is also used to prevent breast cancer in women at high risk for the disease because of their genetic makeup. But only 30 percent of these women opt to take the drug, said Arun, with 70 percent opting for regular screenings instead.
"It's easier for me to tell my patients with invasive breast cancer that they need to take the drug because the benefits far outweigh the risks," said Arun. "But in high-risk women who don't have cancer, it's harder to make that decision. At the end of the day, it's our patients' choice. But it's our job to help them decide."