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

Šestak, Ivana; Distler, W.; Forbes, John F.; Dowsett, Mitch; Howell, Anthony; Cuzick, Jack

doi:10.1200/jco.2009.27.2021

Cited by 286 publications

(267 citation statements)

References 26 publications

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“…In the ATAC study women with BMI of >35 kg/m 2 were more likely to relapse than those with a BMI of <23 kg/m 2 and had significantly more distant recurrences [28]. Similar results were recorded in the German BRENDA-cohort [29].…”

Section: Aromatasesupporting

confidence: 68%

Perioperative Progesterone for Obese Women with Breast Cancer May Improve Survival

Fentiman

2016

Womens Health (Lond Engl)

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Section: Aromatasesupporting

confidence: 68%

Perioperative Progesterone for Obese Women with Breast Cancer May Improve Survival

Fentiman

2016

Womens Health (Lond Engl)

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“…In the three trials, an aromatase inhibitor was associated with improved outcomes compared with that of tamoxifen at all BMI values. Notably, BMI did not significantly interact with letrozole (vs. tamoxifen) in the BIG 1-98 trial (25), whereas the ATAC investigators concluded that the relative benefit of anastrozole (vs. tamoxifen) may be more pronounced in women of a lower weight (24). These findings do not support the notion that BMI can predict the benefit of aromatase inhibitors (vs. tamoxifen) as adjuvant therapies in postmenopausal patients with breast cancer (27).…”

Section: Discussionmentioning

confidence: 92%

Prognostic impact of progesterone receptor status combined with body mass index in breast cancer patients treated with adjuvant aromatase inhibitor

et al. 2015

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Abstract.Aromatase inhibitors have played a central role in endocrine therapy for the treatment of estrogen receptor (ER)-positive breast cancer in postmenopausal patients. However, prognostic factors for recurrence following such treatment have not been identified. The current study aimed to validate the prognostic value of endocrine-related progesterone receptor (PgR) status combined with body mass index (BMI). Among 659 consecutive patients with primary breast cancer who underwent curative surgery between 2002 and 2012, 184 postmenopausal patients with ER-positive (ER+) and human epidermal growth factor receptor type 2-negative (HER2-) breast cancer who were treated with adjuvant aromatase inhibitor therapy were assessed. The patients were assigned to groups based on BMI, according to the WHO cut-off value: ≥25 kg/m 2 (high, H) or <25 kg/m 2 (low, L). Positive nodal status, negative PgR status, BMI-H and a high Ki-67 labeling index (≥20%) were found to be significantly associated with a short recurrence-free interval (RFI) upon univariate analysis (P=0.048, 0.007, 0.027, and 0.012, respectively). The patients were further grouped based on their combined PgR/BMI status. The RFI was significantly shorter in the PgR-and/or BMI-H group compared with that of the PgR+/BMI-L group (P=0.012). Multivariate analysis revealed PgR-tumors and/or BMI-H and positive nodal status to be independent prognostic factors (P=0.012 and 0.020, respectively). The present findings indicate that PgR/BMI status may serve as a practical tool in the management of ER+ and HER2-breast cancer in patients treated with adjuvant aromatase inhibitors. IntroductionAromatase inhibitors have been widely administered as adjuvant treatment for hormone receptor-positive breast cancer in postmenopausal women. The results of recent clinical trials have demonstrated that third-generation aromatase inhibitors, including anastrozole, letrozole and exemestane, are more effective than tamoxifen in treating early stage or metastatic breast cancer in postmenopausal women (1). Thus, aromatase inhibitors are now considered to be the gold standard of endocrine therapy for such patients in adjuvant and metastatic settings (2,3). Characterization of the risk of recurrence for patients who receive aromatase inhibitors is important for selecting appropriate treatment. However, factors that can predict the outcomes of aromatase inhibitor treatment remain unknown.A number of studies have investigated tumor biomarkers that indicated differential benefit from aromatase inhibitors versus tamoxifen in patients with early breast cancer (4-6). Such biomarkers included the conventional factors, estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor type 2 (HER2) and Ki-67, and did not identify patients who derived a differential relative benefit from aromatase inhibitors over tamoxifen. Expression of the PgR gene is thought to largely depend on an intact ER signaling pathway, and the expression of PgR is associated with endocrine responsiv...

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“…This theory has been supported by the results of clinical studies with anastrazole and letrozole showing a reduction in the efficacy of these aromatase inhibitors with increasing BMI (8,9). Plasma estradiol and estrone sulfate levels in obese patients remain significantly elevated in comparison to nonobese patients following letrozole treatment (10), indicating that this reduced response rate may be related to suboptimal inhibition of obesity-associated aromatase activity.…”

Section: Introductionmentioning

confidence: 88%

NSAID Use Reduces Breast Cancer Recurrence in Overweight and Obese Women: Role of Prostaglandin–Aromatase Interactions

et al. 2014

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Obesity is associated with a worse breast cancer prognosis and elevated levels of inflammation, including greater cyclooxygenase-2 (COX-2) expression and activity in adipose-infiltrating macrophages. The product of this enzyme, the proinflammatory eicosanoid prostaglandin E2 (PGE2), stimulates adipose tissue aromatase expression and subsequent estrogen production, which could promote breast cancer progression. This study demonstrates that daily use of a nonsteroidal anti-inflammatory drug (NSAID), which inhibits COX-2 activity, is associated with reduced estrogen receptor a (ERa)-positive breast cancer recurrence in obese and overweight women. Retrospective review of data from ERa-positive patients with an average body mass index of >30 revealed that NSAID users had a 52% lower recurrence rate and a 28-month delay in time to recurrence. To examine the mechanisms that may be mediating this effect, we conducted in vitro studies that utilized sera from obese and normal-weight patients with breast cancer. Exposure to sera from obese patients stimulated greater macrophage COX-2 expression and PGE2 production. This was correlated with enhanced preadipocyte aromatase expression following incubation in conditioned media (CM) collected from the obese-patient, sera-exposed macrophages, an effect neutralized by COX-2 inhibition with celecoxib. In addition, CM from macrophage/preadipocyte cocultures exposed to sera from obese patients stimulated greater breast cancer cell ERa activity, proliferation, and migration compared with sera from normal-weight patients, and these differences were eliminated or reduced by the addition of an aromatase inhibitor during CM generation. Prospective studies designed to examine the clinical benefit of NSAID use in obese patients with breast cancer are warranted. Cancer Res; 74(16); 4446-57. Ó2014 AACR.

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

Cited by 286 publications

References 26 publications

Perioperative Progesterone for Obese Women with Breast Cancer May Improve Survival

Perioperative Progesterone for Obese Women with Breast Cancer May Improve Survival

Prognostic impact of progesterone receptor status combined with body mass index in breast cancer patients treated with adjuvant aromatase inhibitor

NSAID Use Reduces Breast Cancer Recurrence in Overweight and Obese Women: Role of Prostaglandin–Aromatase Interactions

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