On June 4, 2011, research was presented at the American Society of Clinical Oncology conference regarding the use of the drug exemestane (Aromasin), an aromatase inhibitor, for use in healthy postmenopausal women to reduce the risk of invasive breast cancer.
The authors conclude that exemestane reduces the risk of breast cancer for postmenopausal women over the 3 years of follow up in the study. In the study side effects such as hot flashes, fatigue sweating, insomnia and arthralgia were more common in women on exemestane but didn’t affect overall self reporting on quality of life. The study was led by Canada’s NCIC Clinical Trials Group and financed in part by the pharmaceutical giant Pfizer, which manufactures Aromasin.
Read on for BCAction’s opinion on this new study and “pills for prevention” in general.
Need robust definition of “High Risk”
When exploring prophylactic treatment for breast cancer in healthy women, the bar needs to be especially high. By failing to adopt a rigorous definition of “high risk” women, this study opens the door to exposing thousands and thousands of healthy women who will never get breast cancer to the side effects of a powerful drug, on the basis of nothing more than age.
Specifically, we take issue with this study’s categorization as “high risk” any women who is age 60 years or older. This definition of “high risk” opens the door to recommending treatment for all women age 60 and older with this aromatase inhibitor. We are concerned with the lack of rigor around the identified risk factors that qualified postmenopausal women for the study.
Looking at the trend of developing so-called breast cancer prevention pills, we note the tendency to expand approved treatment drugs into broader and broader markets. Most of the so-called breast cancer prevention pill types were initially used as treatments for advanced breast cancer, then to treat women with early breast cancer, and finally considered to lower risk in women without symptoms. Currently the official line is to market these drugs to women with a high risk of developing breast cancer — a bit less than a 2 percent chance over five years. We are concerned with this trend, which Eric Schneider, a medical and public health professor at Harvard, has called “prevention creep”.
We are concerned that healthy women, the majority of whom will never get breast cancer, are being recommended for prophylactic treatment with an aromotase inhibitor which has been demonstrated to have significant side effects.
Because breast cancer is a relatively low occurrence in women, including those at high risk, differences in incidence portrayed using “relative risk” tend to appear much larger than absolute risk differences. The study reports that “at a median follow up of three years, the group receiving exemestane had a 65% reduction in invasive breast cancers.” What this does not clearly show is that in a group of 4560 women, there is a possible benefit to 21 women. Another way of saying this is that in order to prevent one case of breast cancer, 94 women would have to be treated for three years.
While every woman (or man) diagnosed with breast cancer is one too many, in a situation where we are exploring systematic treatment to reduce the risk of breast cancer, we must look at the absolute numbers to understand the real picture.
Looking at this study, we see that 4517 women were exposed to the treatment who would not have otherwise developed breast cancer. That is, looking at the 11 women who developed breast cancer in the exemestane group, the 32 women who developed breast cancer in the placebo group, and factoring in the possible 21 women who did not get breast cancer in the exemestane group, we still find that no more than 64 women out of 4560 in the study would have developed breast cancer, resulting in more than 4500 women who were unnecessarily treated.
Need longer follow-up
Like other studies of breast cancer “prevention,” this study does not provide evidence over a long enough period of time to adequately assess the risks and benefits of this “preventative” use of exemestane. Most breast cancer develops over a period of a decade or longer. Even among this “high risk” group of women, there were a total of 43 breast cancers over the three year study period out of a total group of 4560 women. When looking at lifetime risk of breast cancer, three years is too short a time frame to adequately derive information about the persistence of the protective benefit. Does the medication actually prevent cancer or delay its development? We have no way to determine overall survival in the study groups.
Furthermore, even if we were to allow a breast cancer benefit in the short term, the clinical benefit for healthy women is compromised because the extent of harmful long-term side effects is unknown, as is the long-term survival benefit. We need additional study to assess rarely occurring adverse outcomes and long-term safety or to assess the possibility that risks continue to develop after cessation of treatment.
Three years is not enough follow up to adequately understand the risks and benefits of this prophylactic use of exemestane. In order to make informed decisions about medical treatments, we need sound data to consider risks and benefits together.
Understanding the risks of side effects
The use of prophylactic aromatase inhibitors has prompted concern because they cause serious side effects, many of which may not be fully understood in the short time frame of the study. Reported side effects include increased risk of osteoporosis and bone fractures, joint and muscle pain, high cholesterol, and cognitive problems. While the study reports that these serious side effects were equal in the exemestane and control groups, we believe more study is warranted given the seriousness of the side effects of other AIs.
Breast Cancer Action, while clearly understanding the large numbers of women at risk for developing breast cancer, does not advocate using drugs to treat risk. At Breast Cancer Action we are committed to ending the current breast cancer epidemic. In addition to better treatment options and overall health equity for people living with breast cancer we must identify and eliminate the root causes of this epidemic that lead to so many of us being affected, including environmental triggers of the disease.
There is a growing body of evidence linking environmental exposures to breast cancers. Yet the majority of national resources devoted to breast cancer prevention have been on the development of drugs to lower the incidence of breast cancer—which is risk-reduction rather than actual prevention. This is a huge moneymaker for any company and we believe it is the wrong path to take. We believe these resources would be better spent on primary prevention including finding the disease’s environmental triggers.
At Breast Cancer Action, we believe there are significant problems created by current efforts to bring new medical products to market to reduce breast cancer incidence in healthy women. The focus on pills for prevention of disease diverts resources from finding and eradicating environmental causes of, as well as effective treatments for, breast cancer. We do not support a pills-based approach to breast cancer prevention.