Excess Weight May Speed Breast Cancer Relapse

Heavier women may be at higher risk of recurrence of the most common type of breast cancer after treatment, and less likely to survive the disease, researchers found.

Based on an analysis of three adjuvant trials, obesity predicted 24% poorer disease-free survival (DFS) chances and 37% lower odds for overall survival in hormone receptor-positive disease treated with standard chemohormonal therapy, Joseph A. Sparano, MD, of Montefiore Medical Center in New York City, and colleagues reported online in Cancer.

The higher a woman’s body mass index (BMI) at diagnosis, the poorer the outcomes in both recurrence and survival in the hormone receptor-positive, human epidermal growth receptor 2 (HER2)-negative subset of breast cancers that account for two-thirds of cases.

Extra pounds didn’t appear to be a factor in HER2-positive or triple-negative disease in the three adjuvant clinical trials examined.

“What remains uncertain, however, is whether dietary and lifestyle interventions resulting in weight loss after a breast cancer diagnosis could substantially reduce the risk of recurrence, and also perhaps provide secondary benefits in reducing cardiovascular morbidity and mortality,” Sparano’s group cautioned.

One prior study, the Women’s Intervention Nutrition Study (WINS) trial, had shown that weight loss of 6 pounds on average with a low-fat diet reduced recurrence risk by a significant 24%, which Sparano’s group noted is comparable to the impact of adjuvant chemotherapy.

The benefits in that trial, though, were greatest in the hormone receptor-negative group.

Dietary intervention without weight loss didn’t trim recurrence risk in the Women’s Healthy Eating and Living (WHEL) trial.

To assess the impact of obesity independent of other factors, Sparano’s group examined outcomes of 4,770 women with stage I to III cancers by BMI in three National Cancer Institute-sponsored trials, which were primarily designed to look at chemotherapy or endocrine therapy regimens.

Confounding was minimized in that all three excluded women with significant comorbidities, administered standardized care, and finished before the approval of trastuzumab (Herceptin) was approved as adjuvant therapy for HER2-positive disease.

Across the entire population in one trial regardless of hormone status, the 37% of women who were obese were at 17% higher risk of recurrence or death from breast cancer than other women (P=0.0077) and 23% higher overall mortality risk (P=0.0025).

The effect was more pronounced in the hormone receptor-positive, HER2-negative subset.

In that subset, obese women had 40% higher risk of a poor outcome for DFS (P=0.0007) and 69% higher risk of death from any cause compared with women in the normal range for BMI.

Higher BMI (>30 kg/m2) as a continuous variable was linked to both worse DFS (P=0.00063) and poorer overall survival ( P=0.00067) in hormone receptor-positive, HER2-positive women, “indicating that excessive weight may also be a surrogate for other factors contributing to recurrence not only in obese but also in overweight patients,” the authors stated.

Results were similar in the other two trials in a multivariate analysis adjusted for age, race, menopausal status, tumor size, number of positive axillary lymph nodes, and type of surgery.

A link between weight and cancer recurrence is biologically plausible, the researchers noted, pointing to elevated insulin growth factors.

“Further evaluation of dietary and lifestyle modification is warranted,” the researchers concluded.