Discussion
obesity, DFS, death, obese, HR+ BC, overweight, fractures, HR+, cardiovascular or metabolic diseases, overweight or obese postmenopausal
OBESITY, OBESE, SECOND PRIMARY CANCER, OSTEOPENIA OR OSTEOPOROSIS, ADVERSE EVENTS, EVENTS
In this study, we evaluated the prognostic and predictive effect of BMI in 1781 postmenopausal women with nonmetastatic HR+ BC from the phase III DATA study. We confirmed the results from previous studies, showing a negative association between obesity and DFS in the overall study population. Interestingly, however, subgroup analyses demonstrated that the negative association between obesity and DFS was statistically significant in patients aged younger than 60 years, but not in patients aged 60 years or older. The effect modification by age is of potential interest.We observed that obesity was associated with a decrease in DFS and OS in younger postmenopausal HR+ BC patients only. However, while obesity was also associated with an increase in OCM in younger patients only, it seemed to increase the risk of BCSM irrespective of age. These findings indicate that different mechanisms might apply to the association between obesity and OCM and the association between obesity and BCSM. Primarily, the increased risk of OCM in younger obese patients may be the result of developing cardiovascular or metabolic diseases at a younger age (In our study, we did not observe a reduced efficacy of extended anastrozole therapy in overweight or obese postmenopausal women with HR+ BC. In the analysis of aOS, however, we did observe a potential difference in treatment effects between BMI classes. In fact, 6 versus 3 years of anastrozole was associated with a non–statistically significantly increased risk of death in normal weight patients (HR = 1.48; 95% CI = 0.98 to 2.23), whereas it was associated with a non–statistically significantly decreased risk of death in overweight patients (HR = 0.72; 95% CI = 0.51 to 1.02). Obviously, as the number of patients and events per subgroup was low, this difference in treatment effects could simply be a chance finding. Alternatively, one might speculate that normal weight patients receiving extended aromatase inhibition are at an increased risk of developing endocrine resistance, as an increased risk of BCSM was also observed. We did not, however, observe a decrease in the DFS of normal weight patients receiving extended aromatase inhibition, although this might also be the result of a decrease in the incidence of second primary cancers in the extended therapy group. In addition, one might speculate that normal weight patients receiving 6 years of anastrozole experience an increased risk of death due to adverse events, ie, cardiovascular events or bone fractures. In a previous report of the DATA study, it was shown that the incidence of cardiovascular events and bone fractures during the first 6 years after randomization did not differ between patients receiving 6 versus 3 years of anastrozole, but the incidence of osteopenia or osteoporosis was higher in the extended therapy group (The major strength of our study is the use of data from patients who participated in a randomized controlled trial, in which endpoints were well defined and consistently measured during follow-up. Another strength of our study is the long-term follow-up period of more than 13 years after randomization. Our study also has some limitations. Patients may experience changes in body weight after BC diagnosis (In this study among 1781 postmenopausal women with HR+ BC, we have shown that obese patients experienced an increased risk of BCSM irrespective of age. These findings highlight the need for maintaining a healthy BMI in all patients with HR+ BC. In addition, we did not observe a reduced efficacy of extended anastrozole therapy in overweight and obese patients. Therefore, we conclude that (extended) aromatase inhibitor therapy can also be considered in overweight and obese patients with HR+ BC.