Higher body mass index (BMI) is an established risk factor associated with poor prognosis in HER-2 positive early breast cancer. However, recent studies have indicated that high BMI may be associated with improved outcomes in some advanced cancers, termed the ‘obesity paradox’. However, the relationship has been minimally explored in HER-2 positive advanced breast cancer (ABC). The aim of the study was to assess the association between BMI and survival outcomes in patients with HER-2 positive ABC enrolled within the phase III CLEOPATRA, MARIANNE, EMILIA, and THERESA clinical trials.
The study was a pooled post-hoc analysis of individual-participant data (IPD). BMI was categorized according to the World Health Organization definition. Cox proportional hazards analysis was used to assess the association between pre-treatment BMI and survival outcomes. Analyses were stratified by study and treatment and adjusted for age, race, plasma albumin concentration levels, ER and PR status, performance status, presence of visceral disease and brain metastases and presence of cardiovascular disease and diabetes.
IPD was available from 3207 patients with HER-2 positive ABC of which 100 (3%) were classified as underweight, 1508 (43%) normal-weight, 997 (31%) overweight and 715 (22%) obese at trial initiation. Adjusted analysis indicated that overweight (HR [95%CI] = 0.85 [0.76-0.96]) and obese (0.82 [0.72-0.95]) individuals had improved overall survival compared to normal-weight individuals (P=0.014). Similar findings were identified with progression-free survival (overweight = 0.91 [0.83-1.01]; obese = 0.87 [0.77-0.98]; P=0.034).
Within high-quality large IPD, high BMI was associated with improved survival outcomes. The association was independent of cardiovascular disease, diabetes, albumin levels, and other known prognostic factors. Prospective studies are required to appreciate the basis of the ‘obesity paradox’ as chronic inflammation secondary to obesity and higher levels of leptin are few of the pro-tumorigenic effects seen in patients with increased BMI.