Dataset Information

The prognostic and predictive effect of body mass index in hormone receptor-positive breast cancer.

ABSTRACT:

Background

Obesity has been associated with an adverse prognosis and reduced efficacy of endocrine therapy in patients with hormone receptor-positive (HR+) breast cancer (BC). This study determines the prognostic and predictive effect of body mass index (BMI) on the disease-free survival (DFS) of postmenopausal HR+ BC patients.

Methods

Patients were identified from the DATA study (NCT00301457), a randomized controlled trial evaluating the efficacy of 6 vs 3 years of anastrozole after 2 to 3 years of adjuvant tamoxifen in postmenopausal women with HR+ BC. Patients were classified as normal weight (BMI: 18.5-24.9 kg/m2), overweight (25.0-29.9 kg/m2), or obese (≥30.0 kg/m2). The primary endpoint was DFS, evaluated from randomization (prognostic analyses) or 3 years after randomization onwards (predictive analyses; aDFS) using multivariable Cox regression analyses. P-values were 2-sided.

Results

This study included 678 normal weight, 712 overweight, and 391 obese patients. After a median follow-up of 13.1 years, overweight and obesity were identified as negative prognostic factors for DFS (hazard ratio (HR) = 1.16; 95% confidence interval (CI) = 0.97 to 1.38 and HR = 1.26; 95% CI = 1.03 to 1.54, respectively). The adverse prognostic effect of BMI was observed in women aged younger than 60 years, but not in women aged 60 years or older (P-interaction = .009). The effect of extended anastrozole on aDFS was similar in normal weight (HR = 1.00; 95% CI = 0.74 to 1.35), overweight (HR = 0.74; 95% CI = 0.56 to 0.98), and obese patients (HR = 0.97; 95% CI = 0.69 to 1.36) (P-interaction = .24).

Conclusion

In this study among 1781 HR+ BC patients, overweight and obesity were adverse prognostic factors for DFS. BMI did not impact the efficacy of extended anastrozole.

SUBMITTER: Lammers SWM

PROVIDER: S-EPMC10697786 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Publications

The prognostic and predictive effect of body mass index in hormone receptor-positive breast cancer.

Lammers Senna W M SWM Geurts Sandra M E SME van Hellemond Irene E G IEG Swinkels Astrid C P ACP Smorenburg Carolien H CH van der Sangen Maurice J C MJC Kroep Judith R JR de Graaf Hiltje H Honkoop Aafke H AH Erdkamp Frans L G FLG de Roos Wilfred K WK Linn Sabine C SC Imholz Alexander L T ALT Smidt Marjolein L ML Vriens Ingeborg J H IJH Tjan-Heijnen Vivianne C G VCG

JNCI cancer spectrum 20231001 6

<h4>Background</h4>Obesity has been associated with an adverse prognosis and reduced efficacy of endocrine therapy in patients with hormone receptor-positive (HR+) breast cancer (BC). This study determines the prognostic and predictive effect of body mass index (BMI) on the disease-free survival (DFS) of postmenopausal HR+ BC patients.<h4>Methods</h4>Patients were identified from the DATA study (NCT00301457), a randomized controlled trial evaluating the efficacy of 6 vs 3 years of anastrozole af ...[more]

PMID: 37991939

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Project description:BackgroundHigh body mass index (BMI) has been associated with worse clinical outcomes in patients with early-stage breast cancer (BC), and its negative effects could be mediated by hyperglycemia/diabetes. However, the prognostic impact of high BMI in early-stage HER2-positive (HER2+) BC patients remains controversial.MethodsWe conducted a retrospective study to investigate the impact of baseline BMI or glycemia on relapse-free survival (RFS) and overall survival (OS) in patients with surgically resected, stage I-III HER2+ BC treated with standard-of-care, trastuzumab-containing adjuvant biochemotherapy. The optimal BMI and glycemia cut-off values for RFS were identified through maximally selected rank statistics. Cox regression models were used to assess the impact of BMI, glycemia and other relevant variables on clinical outcomes.ResultsAmong 505 patients included in the study, a BMI cut-off of 27.77 kg/m2 was identified as the best threshold to discriminate between patients with low BMI (n = 390; 77.2%) or high BMI (n = 115; 22.8%). At multivariable analysis, higher BMI was associated with significantly worse RFS [hazard ratio 2.26; 95% confidence interval (CI): 1.08-4.74, p = 0.031] and worse OS (hazard ratio 2.25, 95% CI 1.03-4.94, p = 0.043) in the whole patient population. The negative impact of high BMI was only observed in patients with hormone receptor (HR)-negative/HER2+ BC (hazard ratio 2.29; 95% CI: 1.01-5.20; p = 0.047), but not in patients with HR-positive (HR+)/HER2+ BC (hazard ratio 1.36; 95% CI: 0.61-3.07, p = 0.452). By contrast, hyperglycemia (⩾109 mg/dl) at baseline was associated with a trend toward significantly worse RFS at multivariable analysis only in patients with HR+/HER2+ BC (hazard ratio 2.52; 95% CI: 0.89-7.1; p = 0.080).ConclusionsHigh BMI is associated with worse clinical outcomes in early-stage HR-/HER2+ BC patients treated with trastuzumab-containing adjuvant biochemotherapy, while baseline hyperglycemia could be a predictor of worse RFS in HR+/HER2+ BC patients. Prospective studies are needed to investigate if modifying patient BMI/glycemia during treatment can improve clinical outcomes.

Project description:The prognostic importance of tumor-specific nuclear insulin receptor (InsR) expression in breast cancer is unclear, while membrane and cytoplasmic localization of InsR is better characterized. The insulin signaling network is influenced by obesity and may interact with the estrogen receptor α (ERα) signaling. The purpose was to investigate the interplay between nuclear InsR, ER, body mass index (BMI), and prognosis. Tumor-specific expression of nuclear InsR was evaluated by immunohistochemistry in tissue microarrays from 900 patients with primary invasive breast cancer without preoperative treatment, included in a population-based cohort in Sweden (2002-2012) in relation to prognosis. Patients were followed for up to 11 years during which 107 recurrences were observed. Nuclear InsR+ expression was present in 214 patients (23.8%) and increased with longer time between surgery and staining (P < 0.001). There were significant effect modifications by ER status and BMI in relation to clinical outcomes. Nuclear InsR+ conferred higher recurrence-risk in patients with ER+ tumors, but lower risk in patients with ER- tumors (Pinteraction = 0.003). Normal-weight patients with nuclear InsR+ tumors had higher recurrence-risk, while overweight or obese patients had half the recurrence-risk compared to patients with nuclear InsR- tumors (Pinteraction = 0.007). Normal-weight patients with a nuclear InsR-/ER+ tumor had the lowest risk for recurrence compared to all other nuclear InsR/ER combinations [HRadj 0.50, 95% confidence interval (CI): 0.25-0.97], while overweight or obese patients with nuclear InsR-/ER- tumors had the worst prognosis (HRadj 7.75, 95% CI: 2.04-29.48). Nuclear InsR was more prognostic than ER among chemotherapy-treated patients. In summary, nuclear InsR may have prognostic impact among normal-weight patients with ER+ tumors and in overweight or obese patients with ER- tumors. Normal-weight patients with nuclear InsR-/ER+ tumors may benefit from less treatment than normal-weight patients with other nuclear InsR/ER combinations. Overweight or obese patients with nuclear InsR-/ER- tumors may benefit from more tailored treatment or weight management.

Dataset Information

The prognostic and predictive effect of body mass index in hormone receptor-positive breast cancer.

Background

Methods

Results

Conclusion

Publications

The prognostic and predictive effect of body mass index in hormone receptor-positive breast cancer.

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