Chemoprevention of Breast Cancer

The data showing exemestane’s ability to prevent breast cancer are promising, but the reality is that currently only a very small percentage of women at high risk for breast cancer take tamoxifen for the purposes of primary prevention.

Significant barriers in behavior and practice need to be addressed before more women are going to take medications aimed at preventing breast cancer.

Not the least of the needed changes is for more women to know and understand their risk for developing the disease.

Dr. J. Leonard Lichtenfeld

I have been giving talks on breast cancer screening and prevention to medical professional audiences for years. Three to five years ago, when I asked the audience "who knows their breast cancer risk?" no hands were raised. Today, only a few hands go up. If women who are professionals involved in health care aren’t taking the lead to find out their own risk of breast cancer, you can be sure that even fewer women in the general population do so. It’s just not on their radar screen.

Medical professionals also are not helping them understand that risk. Primary care providers – ob.gyns., family physicians, and internists – are nowhere near routinely providing information about breast cancer risk or asking questions of their patients to get them that information.

Admittedly, the tools available for determining breast cancer risk are not perfect. There’s plenty of debate about the clinical usefulness of applying the Gail model to an individual woman, especially if she is African American. But that’s the calculator that everyone uses, and it’s the one that most studies use to determine risk. Other calculators commonly used by genetic counselors are far more complicated.

Without first making such risk assessment a standard practice in primary care, we’re never going to get to the point where a woman deems it acceptable to take a medication – and endure all of its related side effects and potential associated adverse events – for primary breast cancer prevention.

Even among women who already have a personal history of breast cancer, the associated side effects from taking tamoxifen or aromatase inhibitors are not infrequently deemed too bothersome to continue taking the medication for secondary prevention.

We know from the STAR trial that in postmenopausal women who are at increased risk for the disease, tamoxifen and raloxifene cut the risk of invasive breast cancer by 50%. Exemestane cut that risk in a similar population by about 65%.

But is that added risk reduction enough?

In absolute terms, the annual incidence of invasive breast cancer was 0.55% among women who took placebo versus 0.19% among those who took exemestane; 94 women would need to undergo treatment to prevent 1 case of breast cancer at 3 years. We know from just 3 years, that patients taking exemestane were more likely to develop hot flashes and arthritis. Whether that will dampen enthusiasm for this medication in larger populations of women treated in community settings and not part of a clinical trial – which may be composed of a somewhat self-selected population – remains to be seen.

Finally, let’s acknowledge that the real tipping point in breast cancer chemoprevention would be some drug or other agent that is simple to take and safe to use with very few side effects and risks. Vitamin D, for example, might be such an agent, but the evidence is not sufficient to make a recommendation that it be used to prevent cancer in women at high risk at this time.

Another example is low-dose aspirin, which is widely accepted for the primary prevention of cardiovascular events and is considered safe for this purpose by many medical professionals and accepted by patients at risk, notwithstanding that it has some uncommon but significant side effects.

Strategies for the primary prevention of breast cancer may well have to get to that level of acceptance before they are going to be widely used by women at high risk of developing breast cancer. Only then will we be able to make real inroads into helping women reduce their risk of this all too common cancer.

Dr. Lichtenfeld is deputy chief medical officer for the American Cancer Society. He serves on the editorial advisory board for Internal Medicine News. He reports having no conflicts of interest.