Update on Breast Cancer Prevention

Breast cancer is the most common malignancy diagnosed in American women today. Given the frequency of the diagnosis, approaches that reduce breast cancer incidence also have the potential to provide a major impact on morbidity of the disease and its treatment, cost to the individual and to society, and overall cancer mortality. In their paper, Rastogi and Vogel present a concise and comprehensive review of the four prospective randomized clinical trials of tamoxifen(Drug information on tamoxifen) for chemoprevention of breast cancer, as well as ongoing and future studies examining hormonal alternatives to tamoxifen. Different Perspectives
As oncologists, we add the preventive benefits to the "plus" column when we review the risks and benefits of tamoxifen for women who have been diagnosed with hormone receptor- positive invasive breast cancer or ductal carcinoma in situ. In these instances, prevention is not usually the major indication for considering tamoxifen. However, for other practitioners such as geneticists, gynecologists, internists, family practitioners, primary care physicians, and breast surgeons, the tamoxifen discussion may focus exclusively on prevention as an indication for treatment. In this situation, identification of patients most likely to benefit and least likely to experience significant toxicity is key. This review helps more clearly define these patients. Four Major Trials
The authors present a detailed summary of the patient populations from the four tamoxifen prevention trials. Perhaps most importantly, they define the differences in study participants that may account for the conflicting data from these trials and identify particular subgroups within each trial whose results differ from the study group as a whole. While subgroup analysis can be fraught with error, it is a rational approach to clarifying differences in outcomes between these studies and for generating hypotheses that will aid in the design of future studies. In the United States, the findings of the National Surgical Adjuvant Breast and Bowel Project (NSABP) P1 trial have been widely embraced, in part because, of these four trials, the P1 patient population most clearly represents patients seen in our current clinical practices. For example, most physicians would not recommend tamoxifen to women currently taking hormone replacement therapy (HRT)- a practice that was allowed in the Italian, Royal Marsden, and International Breast Cancer Intervention Study (IBIS-I) trials. Understanding the similarities and differences between these trials will help health-care providers define and individualize a given patient's probability of benefiting from tamoxifen and the individual potential for tamoxifen-related side effects. Shifting Sands
How might the information presented in this review alter hormonal chemoprevention practices? We currently stand on shifting sands regarding the use of postmenopausal HRT. The Women's Health Initiative study published last year showed that overall health risks, including breast cancer, exceeded benefits from the use of combined estrogen plus progestin among healthy postmenopausal US women.[1] With this information, it is expected that many women will discontinue the use of HRT and may seek out ways to decrease their breast cancer risk. In the IBIS-I study, women who met other high-risk criteria and who had used HRT before initiating tamoxifen therapy had a statistically significant 57% reduction in their risk of breast cancer. This would suggest that prior use of HRT in conjunction with other high-risk criteria might define a group at increased risk who may derive a greater benefit from tamoxifen. Within the general population, women perceive their risk of breast cancer to be lower than that of other women. However, women with a history of benign breast disease and those with a female relative with breast cancer consistently overestimate their personal breast cancer risk.[2] Therefore, these women may also overestimate their potential to benefit from tamoxifen. An understanding of the relative and absolute benefits from tamoxifen, such as the summary data presented in the first table of the Rastogi/ Vogel article, is critical to an informed patient decision. Table 1 above lists patient characteristics that indicate her potential for benefit from tamoxifen chemoprevention. Conclusions
Before we decide to put tamoxifen in the drinking water, we need to recognize that, to date, there has been no survival advantage for any defined patient population taking tamoxifen for breast cancer prevention. One of the key issues regarding the trials reviewed in this paper is whether the early observed benefits of tamoxifen will be maintained over time. If the curves continue to separate as the trials mature, we may begin to see greater clinical benefits including a survival advantage. Alternatively, tamoxifen may simply delay the diagnosis of breast cancer. Although this is a worthwhile clinical benefit on its own, patients and physicians should not automatically associate a decrease in breast cancer incidence with improved survival. Meanwhile, as we await mature follow-up from completed studies and the completion of ongoing studies, concise reviews such as this one will help patients and practitioners make informed individual decisions about hormonal chemoprevention.