National Center for Health Research: April 19, 2017
Thank you for the opportunity to express our views on the draft research plan for Breast Cancer: Medications for Risk Reductions. The National Center for Health Research is a nonprofit research center staffed by scientists, medical professionals, and health experts who analyze and review research on a range of health issues.
In their previous recommendation, USPSTF found that treatment with tamoxifen or raloxifene was beneficial for a subpopulation of women at increased risk. However, these treatments only slightly reduced the occurrence of invasive breast cancer in these women and came with serious risks.
We appreciate and support the USPSTF’s efforts to review and update recommendations based on evolving research. The current draft research plan should identify relevant research for the review and subsequent recommendations. We want to emphasize some points that we consider particularly pertinent.
When considering the harms and benefits of medications to reduce the risk for invasive breast cancer, it would be beneficial to also compare the effect size to other options, such as lifestyle changes. Behaviors such as maintaining a healthy diet, exercising, abstaining from smoking, and low levels of alcohol consumption have been shown to be protective against several types of cancer, including breast cancer. In other words, the risk of developing breast cancer may be reduced by changes in lifestyle that have many other advantages and no risks. That context is important for women as they consider drug therapy that may help prevent breast cancer but that also increases the risk of other types of cancer as well as very unpleasant side effects.
We greatly support the inclusion of key question 4 to look at the difference between population subgroups for outcome measures. Studies that target understudied populations and/ or that include subgroup analyses for racially and socioeconomically diverse populations will enable the reviewers to understand the prevalence of breast cancer risk across demographic groups but also enable them to evaluate the effectiveness and risks of drug therapy for these subpopulations. This will enable the USPSTF to determine if recommendations should be different for some demographic groups.
We also support the inclusion of quality of life as an outcome measurement, as this is an important dimension in assessing the harms and benefits of using drug therapy to reduce breast cancer risk. Quality of life outcomes are important for the decision to undergo treatment and to continue after adverse effects become apparent. Considering how drug therapies affect quality of life will provide doctors and patients with important information for making an informed decision about prophylactic medication.
It is important that the review evaluate the long-term health outcomes in terms of benefit and harms extending beyond when treatment stops. Several studies evaluated for the previous USPSTF review suggested that reduced breast cancer risk continued for at least 3 to 5 years and the risks of some harms returned to baseline after cessation of treatment. However, it was unclear how long the benefit might continue or to what extent any or all risks diminished.
These studies showed only a small benefit of treatment (5 to 9 fewer invasive cancers per 1000 people treated). This was not very different from the increased risk for harm (4 to 7 more thromboembolic events, 4 to 5 more cases of endometrial cancer, and up to 15 more cases of cataracts per 1000 people treated). If these numbers change over longer time frames, then it could shift the risk/benefit ratio. This is especially important because, as the previous recommendation noted, women are already cautious of treatment due to the small benefit and potentially serious harms. It is also important to determine which women will most likely benefit from treatment, to increase cases of reduced risk and limit the chance of harms.
Most important, the studies used for the previous USPSTF review were not sufficiently long-term to determine if there was an effect on mortality. Given the similar statistics for benefits and serious harms noted above, the impact on mortality could be a deciding factor for many women considering these drugs.
In conclusion, we support the USPSTF’s efforts to re-evaluate recommendations as the scientific evidence expands and improves. The proposed draft review should facilitate this process and includes questions and outcomes that we agree are important. In addition, we strongly urge the USPSTF to consider how the apparently modest benefits of medications compare to specific lifestyle changes for reducing breast cancer risk.
The Cancer Prevention and Treatment Fund is the major program of the National Center for Health Research. For questions or more information, please contact Stephanie Fox-Rawlings at firstname.lastname@example.org.
USPSTF Final Recommendation Statement: Breast Cancer: Medications for Risk Reduction. U.S. Preventive Services Task Force. December 2016. http://bit.ly/2oPF1nQ
USPSTF Draft Research Plan: Breast Cancer: Medications for Risk Reduction. U.S. Preventive Services Task Force. April 2017. http://bit.ly/2paSkjJ