The first big advance in the fight against recurrent breast cancer was the drug tamoxifen (Nolvadex). In September 1998 a major study demonstrated that breast cancer recurrence could be reduced with tamoxifen. Within one month the FDA had approved the drug. During the intervening years the data have been remarkably consistent: taking tamoxifen for 5 years post diagnosis reduces a woman’s risk of estrogen receptor (ER)-positive breast cancer recurrence by about 50%.
The big unanswered question, however, has been how long should a woman continue to take this drug. Until this week the answer has been 5 years. But new and compelling data suggest that 10 years might be a better target. The study was published in The Lancet (Dec. 5, 2012). Researchers followed nearly 13,000 women who had ER-positive breast cancer for 15 years. One group of women took tamoxifen for five years and then were switched to placebo. Another group received tamoxifen for 10 years. Those who received the drug for 10 years had a 50% relative reduction in breast cancer recurrence compared to those who stopped after five years.
It is always best to translate relative risk into absolute terms so you can actually understand the big picture. Over the 15 years of the study, those taking tamoxifen for five years had a 15 percent chance of dying from breast cancer. Those who took tamoxifen for a decade had a 12.2 percent chance of dying from this disease. That’s significant (an absolute risk reduction of dying of 2.8%) but doesn’t sound as impressive as a 50 percent relative risk reduction.
HOW DOES TAMOXIFEN WORK?
This drug is an anti-estrogen in the breast. Think of it a bit like bubblegum. If you jam a wad of bubblegum into the lock of a door you won’t be able to get the key in to open the door. The door will remained locked and shut.
Tamoxifen fits into estrogen receptors in breast tissue and, like bubblegum, jams the metaphorical locks. The drug thereby prevents estrogen from occupying the receptor sites. Because estrogen cannot activate the receptors, the doors to breast cancer remain closed. Another benefit of tamoxifen is that it acts like estrogen for bone and reduces the risk of osteoporosis.
This sounds like a great story. The only trouble is that tamoxifen also acts like estrogen on the uterine lining. Instead of blocking estrogen there, it activates the tissue as if it were estrogen. Roughly 3 percent of the women who took tamoxifen for 10 years developed endometrial cancer. That was approximately double the rate of those who only took tamoxifen for five years. So, you sort of rob Peter to pay Paul. You can reduce your risk of breast cancer by 50 percent but you double your risk of endometrial cancer.
Some breast cancer experts have called this tamoxifen study a game changer and will recommend that all ER-positive breast cancer patients stay on tamoxifen for 10 years. Others are saying it represents a modest benefit and risks must be taken seriously.
WHAT ARE TAMOXIFEN SIDE EFFECTS?
Many women find this drug hard to handle. You will see in the list below some of the most serious and most uncomfortable complications to tamoxifen therapy:
• Hot flashes, night sweats, menopausal symptoms
• Blood clots, stroke
• Reduced mental clarity, confusion, impaired memory
• Cancer of the uterine lining (endometrial carcinoma), fibroids
• Vaginal bleeding, vaginal dryness, painful intercourse
• Digestive upset, nausea, vomiting, loss of appetite
• Dizziness, lightheadedness, vertigo
• Visual changes, blurriness, difficulty reading, cataracts
• Fluid retention
• Thinning of hair, hair loss
• Sexual side effects, reduced libido
• Blood disorders
• Liver damage
• Skin rash (requires immediate medical attention)
There is no easy answer when it comes to long-term treatment with tamoxifen. For women who can take the drug without experiencing side effects, it is a blessing. Reducing the risk of breast cancer recurrence and death is an important benefit. For those who experience lots of uncomfortable side effects, or something more serious such as a blood clot or endometrial cancer, the risks may be too great. Any decision to continue (or resume) treatment up to 10 years will require thoughtful conversation between a breast cancer expert and the patient.
We hope this information will facilitate this process.