Weight loss leads to worse outcomes in women with HER2+ early-stage breast cancer


A team of international researchers partnered with the National Cancer Institute and Mayo Clinic to conduct a research opportunity that led to unexpected findings.

More than 40% of U.S. adults aged 20 or over are obese, according to results from the latest National Health and Nutrition Examination Survey.1 The rate is even higher among cancer survivors.2 A meta-analysis in 2014 concluded that each 5kg/m2 increment in body mass index (BMI) after breast cancer diagnosis resulted in worse patient outcomes.3

However, many studies that have analyzed the specific relationship between obesity and prognosis in human epidermal growth factor receptor 2-positive (HER2+) early-stage breast cancer have proved inconclusive.

A team of international researchers partnered with the National Cancer Institute and Mayo Clinic to investigate, which ultimately led them to unexpected findings.

Published last month in the Journal of the National Comprehensive Cancer Network, the study concluded that weight loss of 5% or greater over 2 years negatively impacted clinical outcomes. Weight gain during that same time did not affect survival rates.4

The finding that weight loss, not weight gain, was associated with worse outcomes surprised lead researcher Samuel Martel, MD, Universitè de Sherbrooke, Quebec, Canada. "We hope our findings highlight the importance of incorporating consecutive and prolonged data collection on weight in oncology trials and gaining greater understanding of the metabolic processes after cancer diagnosis that may impact outcomes,” he said in a recent press release.5

The World Health Organization's BMI categories

Underweight as <18.5 kg/m2

Normal weight as 18.5 to <25 kg/m2

Overweight as greater than or equal to 25 to <30 kg/m2

Obese as greater than or equal to 30 kg/m2

The data were derived from ALTTO BIG 2-06, a phase III trial in women with HER2+ early-stage breast cancer, which included initial BMI data of 8,381 patients with HER2+ early-stage breast cancer who were being treated with chemotherapy plus trastuzumab and/or lapatinib.

Initial obesity was associated with worse distant disease-free survival (adjusted hazard ratio [aHR], 1.25; 95% CI, 1.04–1.50) and OS (aHR, 1.27; 95% CI, 1.01–1.60).

Weight loss of 5% or more after 2 years was associated with significantly poorer disease-free survival, (aHR, 1.34; 95% CI, 1.05–1.71); distant disease-free survival, (aHR, 1.46; 95% CI, 1.07–1.98); and overall survival (aHR, 1.83; 95% CI, 1.18–2.84).

Anti-HER2 treatment type did not influence outcomes, but hormone receptor and menopausal status did. No impact weight change after 2 years was observed among postmenopausal women. In premenopausal patients, however, weight loss was associated with worse disease-free survival (aHR, 1.57; 95% CI, 1.11–2.22); worse distant disease-free survival (aHR, 1.97; 95% CI, 1.29–3.02); and worse overall survival (aHR, 2.97; 95% CI, 1.55–5.68). Also in premenopausal patients, weight gain was associated with worse distant disease-free survival (aHR, 1.51; 95% CI, 1.06–2.14).

The report concluded with a recommendation to include dietary counseling as part of survivorship care programs.


  1. Hales CM, Carroll MD, Fryar CD, Ogden CL. Prevalence of obesity and severe obesity among adults: United States, 2017–2018. NCHS Data Brief, no 360. Hyattsville, MD: National Center for Health Statistics. 2020
  2. Courneya KS, Katzmarzyk PT, Bacon E. Physical activity and obesity in Canadian cancer survivors: population-based estimates from the 2005 Canadian Community Health Survey. Cancer 2008;112:2475–2482.
  3. MY3 Chan DSM, Vieira AR, Aune D, et al. Body mass index and survival in women with breast cancer-systematic literature review and meta-analysis of 82 follow-up studies. Ann Oncol 2014;25:1901–1914
  4. 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 [published online ahead of print, 2021 Jan 5]. J Natl Compr Canc Netw. 2021;1-9. doi:10.6004/jnccn.2020.7606
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