Effect of Obesity on Breast Cancer Outcomes Varies by Subtype

Among women with nonmetastatic breast cancer, obesity was associated with poorer outcomes only among those with luminal A cancers based on PAM50 gene expression analysis, according to a new study.

Among women with nonmetastatic breast cancer, obesity was associated with poorer outcomes only in those with luminal A cancers based on PAM50 (prediction analysis of microarray 50), according to a new study.

“Although prediagnosis obesity is an established risk factor for postmenopausal breast cancer, studies of obesity and breast cancer survival have produced heterogeneous results,” wrote study authors led by Elizabeth M. Cespedes Feliciano, ScD, ScM, of Kaiser Permanente Northern California in Oakland. Those conflicting results could be due to methodological issues, but the authors also noted that tumor heterogeneity could play a role.

To test this possibility, they conducted a study of 1,559 women diagnosed with stage I–III breast cancer from 1996 to 2013 who had PAM50 assay results available. The assay defines four distinct subtypes: luminal A (562 patients), luminal B (345 patients), basal-like (310 patients), and HER2-overexpressing (342 patients). They correlated these subtypes with body mass index (BMI) to determine connections with outcome; the results were published in Cancer.

Over a median follow-up of 9 years, there were 378 recurrences and 544 deaths, including 312 deaths from breast cancer. When all the breast cancer subtypes were examined together, there was no association between BMI and recurrence or breast cancer death. The hazard ratio (HR) per 5-kg/m2 increase was 1.05 (95% CI, 0.95–1.15) for breast cancer death, and 1.03 (95% CI, 0.92–1.13) for cancer recurrence.

When divided by subtype, BMI did correlate with outcome in some women. Among those with luminal A cancer, each 5-kg/m2 increase in BMI had an HR for breast cancer death of 1.31 (95% CI, 1.11–1.54), and 1.24 for recurrence (95% CI, 1.00–1.54). Among women with a BMI of 35 kg/m2 or higher, the HR for breast cancer death was 2.24 (95% CI, 1.22–4.11). Recurrence risk was also elevated, though this did not reach statistical significance, with an HR of 2.17 (95% CI, 0.92–5.11).

The authors noted that the lack of association between obesity and more aggressive cancer subtypes raises questions of whether lifestyle interventions would be as effective in those patients. “An alternative approach would be to tailor lifestyle interventions for those patients most likely to derive benefit,” they wrote. A previous study found that luminal A cancers were preferentially responsive to exercise. “These results provide additional support for the idea that the impact of obesity and obesity-related behaviors on breast cancer outcomes could differ according to the molecular features of the tumor.”