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. 2022 Oct 4;31(10):1944-1951.
doi: 10.1158/1055-9965.EPI-22-0013.

Obesity and Breast Cancer Metastasis across Genomic Subtypes

Linnea T Olsson  1 , Andrea Walens  2 , Alina M Hamilton  3 , Halei C Benefield  1 , Jodie M Fleming  2   4 , Lisa A Carey  2 , Stephen D Hursting  5 , Kevin P Williams #  6 , Melissa A Troester #  1   2   3
Affiliations

Obesity and Breast Cancer Metastasis across Genomic Subtypes

Linnea T Olsson et al. Cancer Epidemiol Biomarkers Prev. .

Abstract

Background: Obese women have higher risk of aggressive breast tumors and distant metastasis. However, obesity has rarely been assessed in association with metastasis in diverse populations.

Methods: In the Carolina Breast Cancer Study Phase 3 (2008-2013), waist-to-hip ratio (WHR), body mass index (BMI), and molecular subtype [PAM50 risk-of-recurrence (ROR) score] were assessed. Obesity measures were evaluated in association with metastasis within five years of diagnosis, overall and stratified by race and ROR score. Absolute risk of metastasis and risk differences between strata were calculated using the Kaplan-Meier estimator, adjusted for age, grade, stage, race, and ER status. Relative frequency of metastatic site and multiplicity were estimated in association with obesity using generalized linear models.

Results: High-WHR was associated with higher risk of metastasis (5-year risk difference, RD, 4.3%; 95% confidence interval, 2.2-6.5). It was also associated with multiple metastases and metastases at all sites except brain. The 5-year risk of metastasis differed by race (11.2% and 6.9% in Black and non-Black, respectively) and ROR score (19.5% vs. 6.6% in high vs. low-to-intermediate ROR-PT). Non-Black women and those with low-to-intermediate ROR scores had similar risk in high- and low-WHR strata. However, among Black women and those with high ROR, risk of metastasis was elevated among high-WHR (RDBlack/non-Black = 4.6%, RDHigh/Low-Int = 3.1%). Patterns of metastasis were similar by BMI.

Conclusions: WHR is associated with metastatic risk, particularly among Black women and those with high-risk tumors.

Impact: Understanding how risk factors for metastasis interact may help in tailoring care plans and surveillance among patients with breast cancer.

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Conflict of interest statement

Conflicts of interest:

The University of North Carolina, Chapel Hill has a license of intellectual property interest in GeneCentric Diagnostics and BioClassifier, LLC, which may be used in this study. The University of North Carolina, Chapel Hill may benefit from this interest that is/are related to this research. The terms of this arrangement have been reviewed and approved by the University of North Carolina, Chapel Hill Conflict of Interest Program in accordance with its conflict-of-interest policies.

Figures

Figure 1.
Figure 1.. 5-year risk of metastasis by waist-to-hip ratio-defined obesity status.
Women who were categorized as obese based on their waist-to-hip ratio experienced significantly shorter time-to-event and higher 5-year risk of metastasis than women with low WHR. The 5-year risk of metastasis among women with high WHR was approximately 4.3 percentage points higher than among women with low WHR [RD (95% CI): 0.043 (0.022, 0.065)].
Figure 2.
Figure 2.. 5-year risk of metastasis by waist-to-hip ratio obesity status, stratified by race.
Both overall and stratified by WHR categories, Black women experienced substantially higher rates of metastasis than non-Black women. The association between WHR and 5-year risk of metastasis was evident among both Black and non-Black women, but had a slightly higher magnitude among Black women. [RD (95% CI) among Black women: 0.046 (0.013, 0.080); RD (95% CI) among non-Black women: 0.028 (0.001, 0.055)]
Figure 3.
Figure 3.. 5-year risk of metastasis by waist-to-hip ratio obesity status, stratified by molecular intrinsic risk score.
Among women with available gene expression data (n=1,321), women with high WHR with tumors categorized as having a high molecular risk of recurrence were far more likely to experience a metastasis within 5 years than women with low WHR with high-risk tumors [RD (95% CI): 0.131 (0.043, 0.219)]. There was little evidence for a risk difference between WHR categories among women with low or intermediate-risk tumors [RD (95% CI): 0.015 (−0.015, 0.044)].
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