Our work published in the February 2021 issue of JNCCN showed that in patients with HER2-positive early breast cancer, obesity at baseline is a poor prognostic factor and that weight loss during treatment and follow-up negatively impact on clinical outcomes.1 Therefore, dietary counseling should be part of survivorship care programs.
Puklin et al rightfully raise concerns regarding the clinical implication of our surprising finding that weight loss ≥5% at 2 years after randomization is associated with poorer breast cancer outcomes. The presented results of the prognostic impact of baseline body mass index (BMI) and weight change in patients with HER2-positive early breast cancer was unplanned and exploratory. In this regard, any conclusion should be viewed only as hypothesis-generating. We agree that not knowing whether weight loss was intentional versus unintentional is an additional limitation in interpreting these findings. However, we hope that our analysis and this intriguing finding will raise interest for future studies to collect this type of information to allow a better understanding of the relationship between BMI and outcomes in patients with breast cancer. As acknowledged in our discussion, obesity has been associated with increased mortality and impacts negatively on health outcomes2,3 and our findings further support the current recommendations for dietary counseling in breast cancer survivorship programs.
Additionally, Iyengar and Ligibel provide a valuable hypothesis explaining the relationship between weight loss and poor outcomes in our ALTTO analysis. Indeed, the association between weight loss and worse outcomes was primarily significant in premenopausal patients or hormone receptor– positive tumors and was restricted to the lapatinib-alone arm in ALTTO, which was prematurely stopped due to futility analysis. We agree that the adverse effects associated with lapatinib, which include diarrhea, may impact on treatment completion, which then may lead to worse breast cancer outcomes. However, this association was not seen in the trastuzumab followed by lapatinib arm or in the trastuzumab and lapatinib combination arm. A possible confounder variable within an exploratory unplanned analysis may also be an explanation. Weight loss interventions for breast cancer survivors conducted within clinical trials such as the ongoing phase III Breast cancer WEight Loss study (BWEL) will provide more solid evidence in this regard by minimizing the potential effect of confounding factors.
Martel S, Lambertini M, Agbor-Tarh D, et al. Body mass index and weight change in patients with HER2-positive early breast cancer: exploratory analysis of the ALTTO BIG 2-06 trial. J Natl Compr Canc Netw 2021;19:181–189.
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, Martel S , Lambertini M , Agbor-Tarh D Body mass index and weight change in patients with HER2-positive early breast cancer: exploratory analysis of the ALTTO BIG 2-06 trial. J Natl Compr Canc Netw 2021; 19: 181– 189. 10.6004/jnccn.2020.7606 33401235
Berrington de Gonzalez A, Hartge P, Cerhan JR, et al. Body-mass index and mortality among 1.46 million white adults. N Engl J Med 2010;363:2211–2219.
National Task Force on the Prevention and Treatment of Obesity. Overweight, obesity, and health risk. Arch Intern Med 2000;160:898–904.