Cancer prevention is built around screening. In screening, the hope is to catch cancer at an earlier stage than it would be found otherwise and increase options for treatment and chances of cure. But what if instead we could prevent cancer from developing altogether?
I met Mrs. TR in clinic for the first time last week. At 72, she looked great. As she bounced from the examining table to the chair next to me, she told me how busy her life was. Though she retired from nursing years ago, she helps out in her church every day of the week except Saturday and has 10 grandchildren and great-grandchildren she spends her evenings with.
Mrs. TR was referred to me by a breast surgeon after her previous primary care doctor passed away. She didn't have a history of breast cancer herself, but had a strong family history. One of her sisters died of metastatic breast cancer, diagnosed at age 58; a second sister passed at age 70 of an unknown cancer. In reviewing her record, I was impressed at how aggressive her screening regimen was. She received a mammogram and a breast MRI every year and was evaluated by a breast surgeon twice per year. "I'm really scared about getting cancer and want to do everything to make sure I don't get it," she explained.
When she said this, my mind immediately jumped to tamoxifen. Unlike screening, which can only detect breast cancer earlier, tamoxifen can actually prevent breast cancer from developing. Used for years for the treatment of breast cancer, tamoxifen has now been tested and approved by the FDA for the breast cancer prevention (called chemoprevention). Remarkably, studies show that in women at increased risk tamoxifen and its cousin raloxifene prevent 50 percent of invasive breast cancers.
Mrs. TR didn't recall ever being counseled about tamoxifen before. Unlike screening, breast cancer chemoprevention has not received widespread attention and usage. If you were to ask a room full of women whether we have a pill that prevents breast cancer, I suspect many would say no; they would be surprised to learn that for well over a decade we have had not one but two medications that taken daily safely cut a woman's risk of developing breast cancer by half. On the other side of equation, primary care doctors have been gun shy about recommending these medications, largely because they don't have much experience prescribing them (this, of course, is a circular argument), despite the fact that counseling women at high risk of breast cancer about tamoxifen is supported by the United States Preventive Services Task Force (USPSTF).
The benefit of tamoxifen varies with a woman's risk of the disease - the greater the risk of breast cancer, the greater the benefit. Similar to the Framingham risk calculator for heart disease, scientists have created "risk calculators" that allow doctors to estimate a woman's risk of developing breast cancer. To calculate Mrs. TR's risk, I went to the the National Cancer Institute website (http://www.cancer.gov/bcrisktool/). After inputting information about her age, race, family history, and menstrual history I found out that she has a 4.8% risk of breast cancer over the next 5 years and a lifetime risk of 11.7%. I told Mrs. TR that she had a 1 in 10 chance of developing breast cancer in her lifetime and that tamoxifen would reduce this risk to 1 in 20. Then I explained the risks of the medication. Because it blocks the effects of estrogen, tamoxifen can cause symptoms of menopause such as hot flashes. More rarely, tamoxifen increases the risk of blood clots similar to oral contraceptives and the risk of uterine cancer. These risks are not small, I noted, and must be balanced against the potential benefits of therapy.
Despite her assertion that she wanted to do everything possible to prevent breast cancer, Mrs. TR balked at tamoxifen. The idea of taking a medication, especially one that had potential for serious side effects, for a disease she might never get was untenable to her. Looking at her other medications - a statin, two blood pressure-lowering medications, and three vitamins - I was caught off guard by this reasoning. Dyslipidemia isn't itself a life-threatening disease; she was taking a cholesterol-lowering medication every day to reduce her risk of heart disease. Statins furthermore are not without side effects; though rare, they have been associated with serious medical conditions such as rhabdomyolysis and liver failure. Likewise, though elevated blood pressures may itself sometimes cause health problems, doctors treat hypertension primarily to reduce cardiovascular disease. And vitamins, except for vitamin D, are largely unproven in her age group, yet they too are a pill one must take every day.
In the end, Mrs. TR agreed to be referred to our high-risk breast cancer clinic for further counseling about chemoprevention. It is certainly not my intent to get her on tamoxifen therapy. It is drug not without cost and harm, and in the end it is her choice to make. However, given her keen desire to prevent breast cancer, I was struck that she would be willing to bear the risk, cost, and inconvenience of cholesterol-lowering medications and antihypertensives to prevent a disease she is at no higher risk of than most women her age and yet not be interested in a medication to prevent breast cancer, a disease she is at increased risk of. Moreover, she is pursuing an aggressive screening regimen for breast cancer, one that is not well proven, carries its own risks, and that at best will identify breast cancer earlier than it would be found otherwise.
Mrs. TR is not alone. Support for tamoxifen in breast cancer prevention is bafflingly low amongst both doctors and patients, though it is routinely used for treatment. There is a pill out there to prevent breast cancer - it's just that most women are finding it hard to swallow.
- Shantanu Nundy, M.D.