Aromatase inhibitors are often the adjuvant endocrine therapy of choice for postmenopausal women with hormone receptor-positive (HR+) breast cancer. However, this therapy may be less effective for patients with breast cancer and obesity. High body mass index (BMI) is a known risk factor for developing postmenopausal breast cancer and can increase the likelihood HR+ tumors. High BMI is also associated with poorer prognoses for women with breast cancer.
Obesity can alter drug metabolism and distribution, affecting response to cancer treatments such as endocrine therapy, including aromatase inhibitors. Aromatase is highly expressed in adipose tissue, where it triggers the transformation of androgens into estrogen. Preclinical studies have shown an incomplete suppression of estrogen levels using aromatase inhibitors in HR+ breast cancer when exposed to excess adipose tissue. In a recent investigation published in JAMA Network Open, investigators examined the associations of BMI with breast cancer recurrence in a large, national Danish cohort (N = 13,230). This population-based cohort study confirmed that obesity is a risk factor for recurrence and mortality among postmenopausal women with early-stage, HR+ breast cancer treated with aromatase inhibitors. Higher BMI was associated with higher rates of comorbidities, higher histologic grade, increased likelihood of lymph node involvement, and larger tumors at diagnosis compared with patients with a healthy weight. These women were also more likely to undergo breast-conserving surgery and be treated with adjuvant chemotherapy and/or radiotherapy.
This study highlights the need for consideration of BMI for optimization of care in patients with breast cancer and obesity. Patients with obesity treated with aromatase inhibitors may derive less benefit from their therapy than those with lower BMI. The authors encouraged further investigation into whether postmenopausal women with obesity and early-stage HR+ breast cancer should receive endocrine therapies other than the currently recommended aromatase inhibitors for better outcomes. Additional studies of the association of BMI with breast cancer recurrence will help support the development of more personalized treatment strategies. Specifically, a study using individual patient data for a meta-analysis of previous clinical trials would be helpful to assess whether aromatase inhibitors are inferior to tamoxifen in these patients.
This study showed that women with HR+ breast cancer and obesity do not achieve the same benefit from aromatase inhibitors as women with a healthy weight. Clinicians should consider BMI when securing optimal treatment for postmenopausal patients with HR+ breast cancer. The authors suggest that independent of estrogen, inflammation, insulin, and dyslipidemia may influence breast cancer prognosis among women with obesity, and they recommend additional strategies such as physical activity and diet interventions to help improve outcomes for these patients.