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Obesity is a risk factor for cancer recurrence in resected hormone-sensitive breast cancer patients undergoing adjuvant chemotherapy with aromatase inhibitors, according to a recent study.

Aromatase inhibitors (AIs) are extensively used for treating hormone-sensitive breast cancer (BC). In post-menopause, estrogen is mainly formed in the adipose tissue via aromatase-mediated androgen conversion, which might impair the efficacy of AIs in obese patients. 

A study in Current Oncology assessed the body mass index (BMI) cut-off with a significant impact on BC recurrence risk after radical resection and under adjuvant AI therapy.

Study Population

The study comprised 319 BC (stage I–IIA) patients treated with radical breast-conserving therapy and radiotherapy, followed by adjuvant endocrine therapy, chemotherapy, or both. Estrogen or progesterone receptor expression was positive in 254 patients. The proportion of postmenopausal patients was 69.9%. Overweight/obesity was observed in 50.2% of the patients. The “non-breast” control group comprised 116 post-resection colorectal cancer female patients, 44% of whom were obese/overweight. The median follow-up period was 71.6 months.

Impact of BMI on Post-Resection BC Recurrence With AI Therapy

The maximally selected rank statistics analysis was performed on 172 BC patients receiving adjuvant AI therapy to identify the BMI cut-off. A BMI value of >29 was associated with the poorest prognosis in terms of disease-free survival (DFS). The curve-fitting analysis demonstrated that for a BMI cut-off >29, DFS increasingly deteriorated, with an increasing recurrence risk for higher BMI values.

Obesity Significantly Reduced Two-Year Disease-Free Survival and Increased Recurrence Risk

Kaplan–Meier curve analysis for the impact of BMI on 2-year DFS revealed that the identified BMI cut-off was specific only for postmenopausal BC patients under adjuvant AI therapy. In this cohort, a BMI of ≥29 caused a three-fold increased recurrence risk compared to a BMI <29, with a 2-year DFS of 94% vs. 77%, respectively. If the follow-up was protracted at 10 years, only 66% of patients with a BMI ≥29 were disease-free.

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In BC patients treated with tamoxifen or not given endocrine therapy due to triple-negative BC, no significant difference was observed in the 2-year DFS between patients with a BMI greater than 29 and those with a BMI less than 29. Similarly, no significant difference was observed in the 2-year DFS between patients with a BMI greater than 29 and those with a BMI less than 29 in the “non-breast” control group.

Prognosis in Obese Patients With Specific Biochemical and Histopathological Parameters

To hypothesize the reasons for the detrimental effect of obesity on the efficacy of adjuvant AI, biochemical and histopathological parameters of BC patients were analyzed. Seven baseline parameters showed statistically significant differences between patients with BMI >29 and <29: fibrinogen, vitamin D, glucose, urea, creatinine, total cholesterol, and cell proliferation index Ki67 expression.

Source

Riondino, S., Formica, V., Valenzi, E., Morelli, C., Flaminio, V., Portarena, I., Torino, F., & Roselli, M. (2023). Obesity and Breast Cancer: Interaction or Interference with the Response to Therapy? Current Oncology, 30(1), 1220–1231. https://doi.org/10.3390/curroncol30010094