Reply to H.L. McArthur et al
Authors: Ines Vaz-Luis, Nancy U. Lin
Journal: Journal of Clinical Oncology (2014)

We would like to thank McArthur et al 1 for their comments.We do not disagree that adjuvant chemotherapy with trastuzumab has a role in the treatment of some patients with T1abN0 human epidermal growth factor receptor 2 (HER2) -positive breast cancers.Our analyses were undertaken to better define the absolute risks of recurrence which could be used to estimate benefits of chemotherapy and trastuzumab and allow more informed decision-making on the part of patients and physicians.Our comments to the specific issues raised in their letter are as follows.First, with respect to lost follow-up/follow-up time, we acknowledge in our article that over the study period, 19% of patients were deemed lost to follow-up.Recognizing the potential impact of this on our results, we performed a sensitivity analysis comparing the characteristics of patients who were deemed lost to follow-up versus the others; with the exception of age and year of diagnosis, no other significant differences in clinicopathologic characteristics were found between groups, and therefore we believe that our results are still informative.In addition, we also recognize that a 5.5 year of median follow-up time does not capture all the recurrences expected in this patient population (especially among patients with hormone receptor-positive tumors), however it is unlikely that chemotherapy or trastuzumab will have a major impact on outcomes after 5 years and therefore we believe our estimates still can assist chemotherapy/trastuzumab decision making. 2 Second, with respect to variation in chemotherapy use over time, we acknowledge that our experience, like all other similar reports, is a nonrandomized experience and therefore potentially subject to selection bias.As expected, clinicopathologic characteristics differed between treated and nontreated groups.Given the changes in practice over the past decade one potential method to reduce selection bias would be to compare outcomes before and after the widespread use of trastuzumab, however, although we had data on more than 500 patients with T1ab HER2-positive tumors (257 patients not treated with chemotherapy or trastuzumab), we were not able to conduct a sensitivity analysis by year, because the differences in follow-up time (longer in patients in earlier years) would tend to bias toward more recurrences in the untreated group.Still, our experience represents the largest collected experience in untreated HER2-positive disease and we were able to stratify our analyses by size, tumor size and treatment and if anything the bias referred would favor the estimates among the treated group. 2 Third, with respect to outcome estimates for treated and nontreated patients, the McArthur et al 3 study represents the experience of 45 patients with T1abN0 HER2-positive breast cancer who did not receive trastuzumab.However, in contrast to our study nearly half of those patients received chemotherapy.Consistent with our results, within this experience, the outcomes reported were highly favorable even for patients not treated with anti-HER2 therapy (3-year distant recurrence-free survival of 97% [95% CI, 92% to 100%]).Ultimately we agree with the authors conclusion that the 'decision to prescribe adjuvant therapy should be individualized based on careful consideration of the risks and benefits as detailed in current recommendations from the National Comprehensive Cancer Network. 3 However, we believe our results also suggest both caution to avoid overtreatment and also highlight the critical need to develop less toxic regimens in the setting of small predicted absolute benefits.