Does Weight Gain After Breast Cancer Affect Outcome?

Women who gain a more substantial amount of weight after being diagnosed with breast cancer face an increased risk of dying from the disease, according to findings from a new study.

However, that higher mortality risk only appears to apply to women who are overweight or at a healthy weight before diagnosis, not to those who are obese prediagnosis, explained lead study author Sixten Harborg, MD, PhD, with Aarhus University, Aarhus, Denmark, who presented the findings at European Society for Medical Oncology (ESMO) Breast Cancer 2025.

Obesity at breast cancer diagnosis is associated with dismal prognosis, but the effect of postdiagnosis weight change remains underinvestigated and “the evidence is inconclusive,” Harborg told attendees.

The researchers set out to identify weight gain thresholds associated with breast cancer mortality using the prospective Nurses’ Health Study. Harborg and colleagues focused on a subpopulation of 6803 women with nonmetastatic breast cancer and calculated the relative weight change from prediagnosis and postdiagnosis weight records as percentage of weight change from the last reported prediagnosis weight to the first postdiagnosis weight. Weight change was classified as stable weight (−2% to +2%), moderate weight loss (−2% to −5%), major weight loss (< −5%), moderate weight gain (+2% to +5%), and major weight gain (> +5%).

Overall, 1179 women died of breast cancer during a median follow-up of 8.5 years. Compared with women with stable weight after diagnosis, women with major weight gain had an increased risk for breast-cancer mortality (adjusted hazard ratio [aHR], 1.26). The increased risk associated with major weight gain after diagnosis was observed in women with healthy weight or overweight before diagnosis (aHR, 1.32 and 1.37, respectively) but not in those with obesity before diagnosis (aHR, 1.01).

There was also a trend towards increased breast cancer mortality in women with major weight loss, although this was not statistically significant (aHR, 1.14; 95% CI, 0.96-1.34), and moderate weight gain or loss was not associated with increased mortality risk.

Those who are overweight or a healthy weight at diagnosis seem to be most affected by weight gain post-diagnosis, Harborg concluded.

Invited discussant for the study, Hope Rugo, MD, with University of California San Francisco Comprehensive Cancer Center, said the effect of weight gain on breast cancer mortality is “fascinating.”

That the risk was seen only in women at a healthy weight or overweight at diagnosis is “presumably because those who are obese at the start already have a higher risk of mortality from breast cancer,” said Rugo.

Rugo noted that in a recent meta-analysis of 64 studies looking at weight change in relation to breast cancer prognosis, higher postdiagnosis body mass index (BMI) was associated with an increased all-cause mortality, breast cancer–specific mortality, and second primary breast cancer.

So, what can be done? 

“The BWEL trial stands out as a trial that may help us understand what the benefit of weight loss [is],” Rugo told attendees.

That trial enrolled more than 3100 overweight or obese women (BMI ≥ 27) with stages II-III breast cancer diagnosed within the past 14 months who had completed treatment.

The study team showed that a telephone-based weight loss intervention led to clinically meaningful weight loss and sustained weight loss over 12 months, which was associated with improved metabolic markers and insulin resistance.

Rugo also noted that in the Prospective Studies of Diet and Cancer study, compared with stable weight, sustained weight loss, even modest amounts, was associated with a lower risk of developing breast cancer for women aged 50 years or older.

“We still don’t know what weight loss does,” she concluded. But “we know that prevention of weight gain is better, and we will look to the BWEL study over time, as well as exercise intervention studies that are ongoing for more insights.”

The study had no commercial funding. Harborg had no relevant conflicts of interest. Rugo disclosed relationships with NAPO, Blueprint, Daichi, Chugai, and Eisai.