Obesity and outcome of post-menopausal women receiving adjuvant letrozole for breast cancer

Abstract

IntroductionAromatase enzyme activity is predominant in adipose tissue. This has led to speculation that aromatase activity is elevated in obese women and subsequently decreased the clinical activity of adjuvant aromatase inhibitors (AIs) in women with estrogen receptor positive (ER+) breast cancer (BC). We investigated the effect of obesity on the outcome of this population.Patients and methodsRecords of 320 consecutive post-menopausal (PM) women with ER+ BC starting single agent adjuvant letrozole between years 2005 and 2014 were retrospectively reviewed. Tumour and patients characteristic including body mass index (BMI) on the day of starting letrozole were extracted. Endpoints of main interest were: (1) Frequency of obesity; (2) relapse-free survival (RFS) in nonobese (G1; BMI < 30) and obese (G2; BMI ≥ 30) patients.ResultsObesity (BMI: 30–34.99) and morbid obesity (BMI ≥ 35) were present in 105/320 (32.8%) and 115/320 (35.9%) women, respectively. Median follow-up of patients was 49 months; RFS at 5 years (G1: 69% versus G2: 78%) and at 8 years (G1: 69% versus G2: 71%). Median RFS is not reached in both groups (Log rank; P = 0.097). There was no correlation between BMI and RFS (correlation coefficient r = 0.075; P = 0.174).ConclusionIn this cohort, more than two-thirds of PM women starting adjuvant AIs are obese. Obesity did not adversely affect the outcome of women on adjuvant letrozole.

Lifestyle Intervention on Body Weight and Physical Activity in Patients with Breast Cancer Can Reduce the Risk of Death in Obese Women: The EMILI Study

“…In fact, obesity represents the most frequent condition in postmenopausal status, where AI are mostly used. However, as reported by a recent study that investigated the BC prognosis in obese women treated with AI [37], no worse outcome was seen compared to normal patients, not supporting the speculation that an elevated aromatase activity decreases the clinical efficacy of AIs in these women [38][39][40][41][42]. Our BC specific survival curves did not show a difference between overweight and normal patients, suggesting that other causes of death could impact on the worst prognosis in this group of women.…”

Estrogens and breast cancer: Mechanisms involved in obesity-related development, growth and progression

“…Coscia et al showed a reduction in plasma estrone and estradiol following anastrozol treatment, but no significant changes in steroid concentration in association with BMI [198]. Two recent studies showed no significant relationship between high BMI and the efficacy of two different aromatase inhibitors [199,200]. In a cohort where more than two thirds of postmenopausal women receiving adjuvant letrozole therapy were obese, there was no association for worse outcome in the obese women compared with lean women receiving the same treatment [200].…”

“…Two recent studies showed no significant relationship between high BMI and the efficacy of two different aromatase inhibitors [199,200]. In a cohort where more than two thirds of postmenopausal women receiving adjuvant letrozole therapy were obese, there was no association for worse outcome in the obese women compared with lean women receiving the same treatment [200]. Zewenghiel et al found no statistically significant difference between the three BMI categories (normal weight, overweight and obesity) and time to progression during fulvestrant treatment in their 173 patient cohort [199].…”

Metformin as an adjuvant therapy to an aromatase inhibitor in overweight and obese postmenopausal women with breast cancer: A pilot study

“…Activity of aromatase enzyme is predominant in adipose tissue and this leads to the assumption that, aromatase activity could be elevated in obese females. In this context, the clinical activity of aromatase inhibitors in those females may be declined [21]. Metformin is a "star" drug used for type 2 diabetes mellitus whereas growing evidence demonstrated that, it may be a promising chemotherapeutic agent [22].…”