Update on Breast Cancer Prevention

The "Update on Breast CancerPrevention" by Rastogi andVogel provides a comprehensiveand balanced review of the currentstatus of breast cancer chemoprevention.Several areas that the authorsaddress warrant further attention.Available Data
The authors appropriately suggestthat tamoxifen has established "proofof principle" for breast cancer chemoprevention,whereas raloxifene (Evista)remains investigational despite theintriguing results of the Multiple Outcomesof Raloxifene Evaluation(MORE) trial.[1] Conclusions regardingtamoxifen use in breast cancerrisk reduction are based on four randomizedtrials with breast cancer asthe primary study end point in whicha cumulative total of over 750 breastcancer cases developed.[2,3] Currentviews concerning raloxifene's impacton breast cancer are based on a secondaryanalysis of a single study, inwhich a total of 61 invasive breastcancers developed.[1]In addition, there is substantial evidencefrom randomized trials regardingtamoxifen's effectiveness inreducing contralateral breast cancer;nearly a 50% reduction in contralateralbreast cancers involving over 800cases has been seen.[4] Since raloxifeneis relatively inactive against establishedbreast cancer, there is noevidence for raloxifene's effectivenessagainst contralateral breast cancer. Inthis regard, the results of the comparativeStudy of Tamoxifen and Raloxifene(STAR) are highly anticipated.Despite evidence of efficacy, useof tamoxifen in the clinic for primarybreast cancer prevention is extremelylimited, largely due to concerns regardingendometrial cancer and vascularevents (pulmonary embolus andstroke). This may well reflect an overlyconservative view of the risk/benefitratio for tamoxifen use in thissetting. Recently, Freedman and colleagues,[5] using data from a nationalhealth interview survey, applied therisk/benefit index developed by Gailand colleagues[6] to determine thenumber of women who could benefitfrom tamoxifen chemoprevention inthe United States. Of the approximately65 million women aged 35 to 79years, they estimated that over 10 millioncould potentially benefit fromtamoxifen chemoprevention.Risk Assessment Tools
It has been suggested that the developmentof new risk assessmenttools and decision aids that incorporatemortality estimates could facilitatea clearer understanding of risk/benefit issues and lead to wider tamoxifenuse.[7] As one example, Col andcolleagues[8] used a Markov modelingapproach to address the impact oftamoxifen on survival among womenat varying levels of risk for breast andendometrial cancer and hip fracture.In their model, a 50-year-old womanwithout a uterus taking tamoxifen for5 years would increase her life expectancyby 1 to 4 months, even if shewas only at average breast cancer risk.These estimates incorporate the residualcarryover impact of tamoxifenon breast cancer risk seen for yearseven after its discontinuation.[9] Furtherrefinement continues to makesuch modeling approaches "clinicusable."Broader Perspectiveon Prevention
Finally, although the focus ofRastogi and Vogel's update was onchemoprevention, the title uses themore general term "prevention,"which would include consideration oflifestyle interventions for breast cancerrisk reduction. Most oncologistsare familiar with the ongoing STARchemoprevention trial comparingtamoxifen to raloxifene, but fewer maybe familiar with the status of ongoinglifestyle intervention trials targetingbreast cancer.For example, one component of arandomized dietary modification trialis exploring dietary fat intake reductionin more than 48,000 postmenopausalwomen in the Women's HealthInitiative, with breast cancer as a primarystudy end point.[10] In addition,accrual has been completed fortwo randomized secondary prevention(adjuvant) trials evaluating dietarychange including fat intake reduction,with over 5,000 breast cancer patientsparticipating.[11-13] All three trialshave successfully completed accrual,have reported successful maintenanceof adherence, and are designed to reportclinical outcomes in about 2 years.As data emerge from these ongoingchemoprevention and lifestyle interventiontrials, the remaining issuewill be the extent to which clinicaloncologists choose to incorporatebreast cancer risk reduction activitiesinto their practice.

Disclosures:

The author(s) have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

References:

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