Reply to A. Sánchez-Muñoz et al
Authors: Filippo Montemurro, Lucia Del Mastro, Massimo Aglietta
Journal: Journal of Clinical Oncology (2009)

We thank Dr Sa `nchez-Mun ˜oz and colleagues for their interest in our letter 1 on aromatase inhibitors (AIs) in the adjuvant treatment of postmenopausal women with hormone receptor-positive breast cancer.Most of their concerns about AIs in this clinical setting were also expressed by Seruga and Tannock in their Comments and Controversies article, 2 which was the subject of our previous submission.4][5][6][7][8] Furthermore, AIs are accompanied by an increase in the rate of osteoporosis and osteoporotic fracture, myalgias and arthralgias, which is likely to impact negatively on patient tolerance and compliance with treatment.Based on these and other concerns, Dr Sa `nchez-Mun ˜oz and colleagues propose that both tamoxifen and AIs, either alone or administered sequentially, are valuable therapeutic options in postmenopausal women with hormone receptor-positive early breast cancer.Treatment choices in the clinical practice should rely on factors other than differences in efficacy, where efficacy is the ability to prolong survival.Interestingly, patient preferences after adequate information on the options available are not explicitly considered among the factors influencing treatment selection.Compared with tamoxifen, AIs have been associated with consistent reductions in the rate of breast cancer-related events.Moreover, as presented in Table 1 of Dr Sa `nchez-Mun ˜oz et al's letter, trends toward an improvement in overall survival favoring AIs are emerging.Should we omit this information when, in the clinical practice, we are advising a postmenopausal woman about the most appropriate endocrine treatment for her hormone receptor-positive disease?A recently presented meta-analysis showed an absolute 5-year gain in recurrence-free survival favoring AIs over tamoxifen of approximately 3% regardless of the strategy used ("upfront" or "early switch"). 9Focusing on 9,015 patients enrolled in "early switch" trials, a 6-year gain in breast cancer-specific survival of 1.6% was observed in patients assigned to AIs. 9 These data do confirm the superiority of AIs over tamoxifen, although we believe that the ongoing debate around the clinical relevance of these small improvements is fully justified.In contrast, we have also to consider that more than half of relapses and deaths in patients with hormone receptor-positive breast cancer occur beyond 5 years from surgery. 10,11As presented in Table 1 of Dr Sa `nchez-Mun ˜oz et al's letter, follow-up of these trial ranges between 28 and 100 months, which could be considered a fragment of the natural history of this type of disease.Due to the "carryover effect" of endocrine therapy, recently confirmed in the Arimidex, Tamoxifen Alone, or in Combination trial for anastrozole with respect to recurrence-free survival, 3 one should cautiously abstain from excluding that improvements or trends toward better outcomes will increase in magnitude or become significant with additional follow-up.Regarding toxicity, we insist on the fact that two most fearsome complications related to tamoxifen, thromboembolic events,