Several issues raised in the article by Cianfrocca and Wolff and the accompanying reviews in the January issue of ONCOLOGY (21:63-80, 2007) deserve further comment. First, all authors address American resource-rich patient populations only. According to data from Parkin et al, nearly two-thirds of all new cases of breast cancer globally (a total of 1 million cases) occur among poor women. Half of these (500,000 cases) are in premenopausal women with hormone-receptor-positive tumors.[1] We need to broaden our horizons to consider these much larger populations whenever we discuss breast cancer therapies.

Second, some discussion of emerging thinking about disease growth models seems appropriate. The authors mostly describe but do not evaluate currently available results. Breast cancer stem cell hypotheses, for example, warrant comments in light of population statistics, combined clinical trial data, and MA.17 trial results, all of which show significant rates of "late" recurrence despite 5 years of adjuvant hormonal therapies.[2-4] Uncertainties about the optimal duration of hormonal therapies must be considered in light of these data.

It is troubling to acknowledge that for prostate cancer (also apparently with limited data), there is considerably greater unwillingness to stop lutenizing hormone-releasing hormone (LHRH) agonist therapy even with the progression of disease considered "hormone-refractory." In the discussions about the superiority of adjuvant aromatase inhibitors over tamoxifen(Drug information on tamoxifen), I miss thoughts about why this makes biologic sense.

Third, the limited references to emerging data showing differences in the frequency of side effects and in rates of efficacy with tamoxifen therapy according to host genotype (for critical metabolizing enzymes) or use of selective serotonin-reuptake inhibitor (SSRI) drugs, suggest discomfort with the way we have promoted SSRI use, and limited sensitivity to how big these issues may be in some populations.[5,6]

Finally, I understand the uncertainty about "optimal" hormonal therapies being addressed by the Suppression of Ovarian Function Trial (SOFT), Tamoxifen and Exemestane(Drug information on exemestane) Trial (TEXT), and Premenopausal Endocrine-Responsive Chemotherapy Trial (PERCHE), but I find the enthusiasm for these trials disturbing. Results will be a long time in coming, and the differences among therapies tested are likely to be small. We need to be proposing and testing bolder hypotheses and strategies. One such approach follows from our observation that the timing of surgical oophorectomy may have a significant impact on long-term outcomes.[7]

Richard R. Love, MD
Professor of Medicine
Hematology/Oncology
Professor of Public Health
Epidemiology/Biometrics
Director of International Oncology
Comprehensive Cancer Center
The Ohio State University
Columbus, Ohio

References

1. Parkin DM, Pisani P, Bray F, et al: Estimates of the worldwide mortality from 25 cancers in 1990. Int J Cancer 83:18-29, 1999.