Effect of Body Mass Index on Recurrences in Tamoxifen and Anastrozole Treated Women: An Exploratory Analysis From the ATAC Trial

2010 ◽  
Vol 28 (21) ◽  
pp. 3411-3415 ◽  
Author(s):  
Ivana Sestak ◽  
Wolfgang Distler ◽  
John F. Forbes ◽  
Mitch Dowsett ◽  
Anthony Howell ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Mass Index ◽  
Postmenopausal Women ◽  
Body Mass ◽  
Aromatase Inhibitors ◽  
Hormone Receptor ◽  
Early Stage ◽  
Double Blind ◽  
Overweight Women ◽  
Hormone Receptor Positive

Purpose Third-generation aromatase inhibitors have been widely used in postmenopausal women for the adjuvant treatment of hormone receptor–positive breast cancer. As aromatase inhibitors work by inhibiting the conversion of androgens to estrogens in adipose tissue, we hypothesized that anastrozole may be more effective in women with a high body mass index (BMI). Patients and Methods The Arimidex, Tamoxifen Alone or in Combination (ATAC) study was a double-blind randomized clinical trial in which postmenopausal women with early-stage breast cancer were randomly assigned to receive oral daily anastrozole (1 mg) alone, tamoxifen (20 mg) alone, or the combination in a double-blind fashion. Analyses were based on the 100-month median follow-up for women with hormone receptor–positive breast cancers (estrogen [ER] and/or progesterone [PgR] positive). Here, we investigate the impact of BMI on recurrence and the relative benefit of anastrozole versus tamoxifen according to baseline BMI. Results Overall, women with a high BMI (BMI > 35 kg/m2) at baseline had more recurrences than those women with a low BMI (BMI < 23 kg/m2; adjusted hazard ratio [HR], 1.39; 95% CI, 1.06 to 1.82; Pheterogeneity = .03) and significantly more distant recurrences (adjusted HR, 1.46; 95% CI, 1.07 to 1.61; Pheterogeneity = .01). Overall, the relative benefit of anastrozole versus tamoxifen was nonsignificantly better in thin women compared to overweight women. Conclusion These results confirm the poorer prognosis of obese women with early-stage breast cancer. Recurrence rates were lower for anastrozole than tamoxifen for all BMI quintiles. Our results suggest that the relative efficacy of anastrozole compared to tamoxifen is greater in thin postmenopausal women and higher doses or more complete inhibitors might be more effective in overweight women, but this requires independent confirmation.

Prognostic significance of body mass index in breast cancer patients with hormone receptor-positive tumours after curative surgery

2013 ◽  
Vol 36 (6) ◽  
pp. 297 ◽  
Author(s):  
Peng Xing ◽  
Ji-Guang Li ◽  
Feng Jin ◽  
Ting-Ting Zhao ◽  
Qun Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Mass Index ◽  
Body Mass ◽  
Hormone Receptor ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Axillary Lymph ◽  
Nodal Stage ◽  
Hormone Receptor Positive ◽  
High Bmi

Purpose: Obesity has been recognized as a significant risk factor for postmenopausal breast cancer. The aim of this study is to investigate the prognostic significance of body mass index (BMI) in hormone receptor-positive, operable breast cancer. Methods: In this retrospective cohort study, 1,192 consecutive patients with curative resection of primary breast cancer were enrolled. Patients were assigned to two groups according to BMI: normal or underweight (BMI < 23.0 kg/m2) and overweight or obese (BMI ≥23.0 kg/m2). Associations among BMI and clinicopathological characteristics and prognosis of patients were assessed. Results: A high BMI was significantly (P < 0.01) correlated with age, nodal stage, ALNR, ER positivity, PR positivity and menopausal status at diagnosis. Univariate analysis revealed that BMI, pathologic T stage, nodal stage, axillary lymph node ratio (ALNR) and adjuvant radiotherapy history were significantly (P < 0.05) associated with disease-free survival and overall survival, irrespective of tumour hormone receptor status. Multivariate analysis revealed BMI as an independent prognostic factor in all cases and in hormone receptor-positive cases. Conclusion: A high BMI (≥23.0 kg/m^2) is independently associated with poor prognosis in hormone receptor-positive breast cancer.

scholarly journals Fulvestrant in advanced breast cancer: evidence to date and place in therapy

2017 ◽  
Vol 9 (7) ◽  
pp. 465-479 ◽  
Author(s):  
Katalin Boér
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Postmenopausal Women ◽  
Endocrine Therapy ◽  
Aromatase Inhibitors ◽  
Hormone Receptor ◽  
Single Agent ◽  
Advanced Breast ◽  
Hormone Receptor Positive ◽  
Metastatic Setting

Breast cancer is a classical hormone-dependent tumour; therefore, endocrine therapy is the mainstay of treatment for hormone receptor-positive, human epidermal growth factor 2-negative advanced breast cancer. Until recently, classical endocrine agents such as tamoxifen, steroidal and nonsteroidal aromatase inhibitors and fulvestrant have been widely used in postmenopausal patients to treat locally advanced or metastatic disease. However, for patients with this subtype of breast cancer, the landscape of endocrine therapy is rapidly changing. Therapies targeting oestrogen modulation have evolved in recent years following the introduction of targeted agents, mTOR and CDK 4/6 inhibitors that are administered in combination with hormone therapy. As a result, options for endocrine therapy have expanded in recent years, and a variety of single-agent or combinations of targeted drugs and endocrine therapies are accepted. Fulvestrant is a selective oestrogen receptor downregulator (SERD) which was introduced to clinical practice in 2002, initially with the indication to treat postmenopausal women with hormone-receptor-positive advanced breast cancer as second-line therapy postdisease progression after aromatase inhibitors or tamoxifen. Additionally, fulvestrant has also been shown to be active in patients previously untreated with endocrine therapy, either both in the neoadjuvant and the metastatic setting, alone or in combination with other targeted therapies. Currently, the standard dose is 500 mg, which is administered with a loading dose. Fulvestrant received a new FDA indication in December 2016, in combination with palbociclib, both in pre/peri/postmenopausal women with breast cancer progressing after endocrine therapy. This manuscript aims to give an overview of new efficacy data and the current role of fulvestrant in the systemic therapy of hormone-receptor-positive advanced breast cancer, in the context of other available therapeutic modalities.

Interaction between body mass index and bone turnover during aromatase inhibition: Evidence from the letrozole (L), exemestane (E), and anastrozole (A) pharmacodynamics (LEAP) trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 560-560 ◽  
Author(s):  
E. McCloskey ◽  
R. Hannon ◽  
G. Lakner ◽  
G. Clack ◽  
A. Miyamoto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Mass Index ◽  
Bone Resorption ◽  
Bone Turnover ◽  
Postmenopausal Women ◽  
Body Mass ◽  
Early Breast Cancer ◽  
Aromatase Inhibitors ◽  
Baseline Bmi ◽  
High Bmi

560 Background: High body mass index (BMI) protects against postmenopausal osteoporotic fracture, mediated in part by higher endogenous levels of oestradiol. Third-generation aromatase inhibitors (AIs) show superior efficacy and tolerability than tamoxifen in the adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer. We examined the interactions between BMI and bone turnover during treatment with 3 aromatase inhibitors in the LEAP trial, an open, randomized, pharmacodynamic study in postmenopausal women. Methods: Healthy volunteers from the UK and Hungary with normal bone density and BMI between 18 and 34 kg/m2 were randomized to receive A (1 mg/day), L (2.5 mg/day), or E (25 mg/day) orally, once daily for 24 weeks. Effects on bone resorption (log transformed serum C-telopeptide crosslinks, CTX) and bone formation (bone alkaline phosphatase and propeptide of type I procollagen, PINP) were compared. Changes in biochemical markers of bone resorption and formation during treatment were all statistically inter- correlated (p<0.01) with no notable differences between the 3 agents studied, so that the groups were pooled for analysis. Spearman correlation coefficients and the p-values were computed. Results: A total of 90 participants were evaluable at baseline and at 24 weeks (29 A, 29 L, 32 E). As expected, baseline BMI correlated with pre-treatment circulating endogenous oestradiol (r=0.28, p=0.007) and both BMI and oestradiol negatively correlated with baseline serum CTX (r=-0.32, p=0.0025 and r=-0.35, p=0.0007 respectively) and PINP (r=-0.30, p=0.004 and r=-0.26, p=0.016 respectively). Baseline BMI and oestradiol were significantly correlated with the increase in serum CTX (r=0.26, p=0.015 and r=0.23, p=0.032 respectively) and BMI also correlated significantly with the increase in serum PINP (r=0.23, p=0.030). Conclusions: Steroidal and non-steroidal AIs increase bone turnover with the greatest increase in women with high BMI and higher oestradiol levels at baseline. As increased bone turnover is an independent risk factor for fracture, a high BMI may not confer a reduced fracture risk in the setting of AI use in early breast cancer. No significant financial relationships to disclose.

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