Reply to Impact of radiation and hormonal therapy on the locoregional recurrence of elderly breast cancer: Are these necessary after breast___conserving surgery?

Abstract

We thank Corso et al for sharing their findings in response to our report on locoregional recurrence (LRR) among older, lowrisk breastconservation patients. Although we reported that radiotherapy (RT) and hormonal therapy (HT) each confer similar locoregional control, Corso et al conducted an analysis revealing that an absence of RT yields significantly higher LRR in both univariable (hazard ratio [HR], 4.59; 95% CI, 2.329.09) and multivariable analyses (HR, 4.91; 95% CI, 2.429.99), whereas an absence of HT does not influence LRR (HR, 0.63; 95% CI, 0.152.71). Although numerically dissimilar, both studies support consideration of adjuvant RT monotherapy as an option for those who may otherwise forego adjuvant HT. There are a number of potential causes for the divergence in our findings, population heterogeneity being chief among them, as noted by Corso et al. For example, we both found that LRR was highest among those receiving neither HT nor RT, although that rate was 11% in our study and 5.4% in theirs. The discrepancy in benefits from HT may similarly be due to our classification of HT because we investigated adherence to HT rather than HT intent to treat. Because HT trials are fraught with 50% to 60% rates of noncompliance, 5 including such patients could abrogate the effect estimate of HT on LRR. The RT classes in our studies also differed to some extent: our RT monotherapy group included 118 patients (13.3% of the cohort), whereas theirs included only 26 patients (2.4% of the entire cohort). This revealed differences in RT practice between the 2 populations. Similarly, we included those receiving accelerated partial breast irradiation (9.8% of our RT group) rather than only those who received whole breast irradiation, although this latter point is unlikely to have influenced associations with LRR. Although not a focus of our study design, partial breast irradiation is being evaluated prospectively in older women with earlystage breast cancer in the EUROPA study, a phase 3 trial comparing partial breast irradiation alone and HT alone after breastconserving surgery. A distinguishing feature of our model was the inclusion of the Suemoto Index to account for comorbidity status, which in many ways incorporates physicians’ impressions of anticipated benefits from HT or RT. In agreement with our study and others, it is probable that fitter patients receive more aggressive therapy (in this case HT and RT), whereas those with comorbidities forgo various components of treatment. If those who forgo HT die of illness before the putative longer term benefits of HT might manifest, there would not appear to be a comparative improvement in LRR for those who receive HT. The goal of adjuvant therapy after breastconserving surgery is to improve disease control and survival outcomes. To that end, there is a large body of literature demonstrating the benefit of adjuvant RT and HT in ER+ patients. Yet, as is true with any intervention, these therapies come at a cost, and for older women, it is essential that we prioritize consideration of comorbidities, remaining life years, and quality of life when we are developing a personalized treatment plan. Cancer and Leukemia Group B (CALGB) trial 9343 has highlighted that although RT does indeed reduce LRR in conjunction with HT for patients older than 70 years, those receiving tamoxifen without RT also exhibit excellent LRR without a decrement in survival. PRIME II yielded similar findings for those older than 65 years. Yet, contemporary trials of RT monotherapy (omitting HT) are lacking. This paradigm is particularly relevant for older patients with potential contraindications or poor tolerance of HT or for those who may prefer a brief course of RT to several years of systemic therapy, particularly in an era of shortened RT fractionation schemes, conformal plans, and excellent tolerability. This discussion supports several ongoing efforts to prospectively inform adjuvant treatment selection among lowrisk breast cancer patients. As the efficacy and toxicity profiles of our therapies improve, we must ensure that our decisionmaking paradigms evolve accordingly. Indeed, as more sophisticated methods of prognostication and prediction are incorporated into risk/benefit determinations, patients will be increasingly empowered to act on personalized risk preferences.