A paper presented today at the annual meeting of the American Association for Cancer Research (AACR) in Washington DC (and being published simultaneously in the journal Cancer Prevention Research) highlights an issue that has been “out there” for quite some time, namely the use of medications to prevent breast cancer and why more women and their doctors don’t take advantage of what we know works.
Although we have known for several years that we can reduce the risk of breast cancer by lifestyle changes (think overweight and obesity in postmenopausal women as well as decreasing alcohol intake) as well as the use of preventive medicines for women at higher than average risk of the disease, there has been little “uptake” of this approach by patients and their health professionals. The net result is that most women still don’t know their own risk of breast cancer, and even fewer seem to be doing much about it.
The current study, which is a longer term follow-up of a study reported in 2006, confirms that two medicines—tamoxifen and raloxifene—are both effective in preventing breast cancer, although one may be somewhat more effective than the other. And while both have side effects, one is clearly less “toxic” than the other. But this “balance” may not be enough to move women to take these medicines in an effort to decrease their chance of getting breast cancer.
A brief recap of the research reported today would probably be helpful.
The trial reported at AACR is called the STAR trial, and has been conducted by a very highly regarded and effective clinical research organization called the National Surgical Adjuvant Breast and Bowel Project, or NSABP for short, which is based in Pittsburgh, Pennsylvania. This group of researchers has worked for several decades to improve the care offered women with breast cancer, and they have had a remarkable influence on much of the progress we have seen in the treatment of this disease.
The STAR trial (STAR is short for “Study of Tamoxifen and Raloxifene”) was started many years ago to determine whether these two drugs were truly effective in reducing the risk of breast cancer, based on previous suggestions in other research that such was the case.
Tamoxifen has been around for many years and widely used since the mid-1970s as a treatment for advanced breast cancer and subsequently as an effective treatment to prevent the return of breast cancer in many women whose cancers were hormone sensitive. Raloxifene is a widely used medicine—similar in type to tamoxifen—whose main use had been in the prevention of osteoporosis.
In the STAR trial, almost 20,000 postmenopausal women were treated with either tamoxifen or raloxifene for a planned 5 years to see if these drugs could reduce the risk of breast cancer. The participants were carefully followed not only to see whether they developed invasive or non-invasive (commonly called “DCIS”) breast cancer, but also whether the side effects differed significantly between the two medicines.
In order to participate in the trial, women had to be postmenopausal, at least 35 years old, and have a 5 year breast cancer risk as determined by the Gail model (which is a readily available online method to determine one’s breast cancer risk). That risk had to be at least 1.66, meaning that the women had to have at least a 1.66% chance of developing breast cancer over the next five years.
In the initial reports on the STAR trial in 2006, both drugs were effective in reducing invasive breast cancer about 50%. However, tamoxifen was more effective than raloxifene in reducing the risk of non-invasive breast cancer. Unfortunately, tamoxifen had been known to increase the risk of uterine cancer and thromboembolic events (blood clots in the veins that can break off and go to other parts of the body, such as the lungs). Raloxifene had many fewer of these problems than did tamoxifen.
Because of lingering questions about the initial results of the STAR trial, the researchers decided to take another look at the women involved in the trial. This time, the follow-up extended for a median of 81 months compared to the 47 months at the prior report (median means half the women were on the trial for less than the period of time in question, and half were on longer).
It turns out that although the breast cancer risk “cutoff” was 1.66% for the trial, the women who participated actually had an average breast cancer risk of 4.03%, which means that they had about a 4% chance of developing breast cancer over the next five years if nothing was done.
In the current report, the researchers found that although both drugs were effective in reducing the risk of developing invasive breast cancer, women who took raloxifene had a slightly greater risk of developing invasive breast cancer than those who took tamoxifen (24% higher risk). For non-invasive breast cancer, the women on raloxifene again had a higher risk of being diagnosed with this disease, but for this indication—although the percentage increase was 22%--it wasn’t clear from the study that the numbers were actually meaningfully different.
When it came to side effects, however, the women on raloxifene had a 45% less chance of developing uterine cancer and a 25% less chance of developing a thromboembolic event.
Death rates over the time of the study were actually the same for both groups of women, and didn’t differ whether they took tamoxifen or raloxifene.
As noted by the researchers in the abstract they presented at the AACR meeting today, “Our longer term (81 months) results show that raloxifene retained 76% of the effectiveness of tamoxifen in preventing invasive disease and grew closer to tamoxifen in preventing noninvasive disease, while remaining far less toxic.”
Their conclusion?
“With deep public-health implications, these results help clarify that both raloxifene and tamoxifen are good preventive choices for higher-risk postmenopausal women, depending largely on a woman’s personalizing risk factors. The results should encourage widespread acceptance of raloxifene and greater acceptance of tamoxifen for breast-cancer prevention among postmenopausal women at an elevated risk, ultimately reducing the burden of breast cancer on the public health.”
So those are the conclusions and the recommendations of the researchers who understand breast cancer prevention as well as anyone in the country.
But there is another side to this discussion that bears attention and discussion, and that is the overwhelming avoidance by patients and their health professionals in recommending and using these drugs to prevent breast cancer. And that is a question that has many experts scratching their heads: If millions of women could benefit from reducing their risk of breast cancer by using these medications, why aren’t they doing it?
With this question in mind, over the past several weeks as I have given lectures around the country on the prevention and early detection of cancer, I have been asking my audiences to share with me how many women know their breast cancer risk and how many women have learned their risk as a result of a recommendation or discussion with their health care professional?
These audiences have ranged from about 150 to several hundred, and many of the attendees are women. In some of the audiences, they are women who may be physicians or other health professionals of various types, but are at least involved in health care delivery and theoretically are very educated consumers.
The bottom line: very few hands go up to the first question, and almost none go up in response to the second.
The take home message? Women and their health professionals aren’t exactly knocking the door down to find out if they are at risk of developing breast cancer, let alone considering their options for preventive treatment if their risk is elevated.
I think it is appropriate to point out that there are different levels of risk of a woman getting breast cancer.
The typical woman has a 1 in 8 chance of getting breast cancer. Some women have genetic changes that put them at very, very high risk of getting breast cancer sometime during their lives. Other women have a slightly increased risk, such as those who participated in this study. But the reality is what the reality is: most women don’t have significantly identifiable risk factors for breast cancer, and many women haven’t taken the time to find out what their real risk of getting breast cancer.
Then there is the question of what we in medicine call the “benefit/risk ratio.”
Yes, these medicines can reduce risk of getting breast cancer by about 50%, plus/minus based on the results reported today. So that means if you are a woman with a 1.66% of getting breast cancer over the next five years, you can reduce that risk by half to about 0.83%. For some women, that is an acceptable risk/benefit ratio. For others they may want a higher level of benefit (and perhaps less risk of medication side effects) to consider taking one of these medicines. For example, I can imagine that if a woman had a 10 or 15% risk of getting breast cancer over the next five years, she might be more inclined to take a pill once a day for five years to reduce her risk by half, and consider the potential side effects reasonable under the circumstances compared to a woman with, say, a 1.66% risk.
Ultimately, these are all individual decisions. But before we get to the treatment, we have to understand the circumstances. And until we make breast cancer risk assessment part of routine preventive health care, we aren’t going to get where we need to be.
So the discussions will go on. The studies show that we can offer an effective treatment to reduce the risk of breast cancer, but it comes at a price which is both economic (the cost of the medicines and the medical care required when taking these medicines) as well as “risk” based, which might mean getting uterine cancer or a serious blood clot if one decides to take these medicines.
Some women may view these as reasonable things to do, and others may not. But those decisions can’t be made until we take the very first step, and that is asking the basic question: what is my risk of getting breast cancer?
Until we recommend getting a breast cancer risk assessment routinely as part of our routine preventive medical care (which probably won’t happen until women start asking that question of their health care professionals), we are not going to be as successful as we could in our more global efforts to reduce the incidence and deaths from this too common disease.
So as is too frequently the case with many well done medical research studies, the impact and opportunity offered by this research rests not so much with the quality and size of the study but with the willingness of medical professionals and their patients to start asking the appropriate questions, having the appropriate discussions, and making the appropriate decisions based on high-quality, effective information such as provided by this study.
Until we change that dynamic by becoming more informed and engaged medical consumers and take charge of our health, we are destined to continue to do things the same old way with much the same old (expensive) results. And that is not the best way to improve the quality of our health care and the quality of our lives.
Maybe understanding your risk of getting breast cancer is one place to start.
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