Abstract

Abstract INTRODUCTION: Triple Negative Breast Cancer (TNBC) is a subtype of breast cancer associated with poor clinical outcome. Patients diagnosed with TNBC may experience many treatment-associated changes, including weight gain, reduced physical activity levels, and worsening metabolic profiles. We sought to identify the association between baseline metabolic syndrome (MetS) components with survival outcomes in WHI participants diagnosed with TNBC. METHODS: The WHI comprises 161,308 post-menopausal women aged 50-79 who were enrolled from 1993-1998 and were at low risk of 3-year mortality at study screening. After excluding women with a history of cancer and those randomized to the dietary modification treatment arm, we identified 615 participants diagnosed with non-metastatic TNBC while on study. MetS status at baseline was assessed at study entry (prior to subsequent breast cancer diagnosis) using the following risk factors: 1) high waist circumference (≥88 cm), 2) high blood pressure (>135 mg Hg systolic and/or > 85 diastolic, or anti-hypertension medication use), 3) history of high cholesterol, and 4) history of diabetes. Groups were stratified into: 1) no MetS components (none), 2) 1-2 MetS components, and 3) 3-4 MetS components. All breast cancers were verified by medical record review. Survival status was augmented by serial National Death Index queries. Outcomes of interest included breast cancer specific survival, as well as all-cause survival after breast cancer, with survival time calculated from date of TNBC diagnosis to date of death or off-study. Baseline demographic, clinicopathologic, and treatment differences were assessed across MetS groups using chi-squared analyses. Kaplan-Meier curves were plotted across MetS groups and survival rates were compared using the log-rank statistic. RESULTS: Of 615 participants diagnosed with TNBC, the distribution of MetS was as follows: 29% had no MetS components (n=178), 53% had 1-2 components (n=323), and 7% had 3-4 components (n=43). The median time from enrollment to TNBC diagnosis was 8.6 years (median), with those in the highest MetS group having a significantly shorter time to diagnosis than those without any MetS (7.0 years vs. 9.8 years, respectively, p<0.001). In addition, those in the highest MetS group were more often black (28% 3-4 vs. 4% none, p<0.001), had incomes <$50,000/year (83% 3-4 vs. 49% none, p<0.001), and had lower rates of menopausal hormone therapy use at baseline (p=0.02). There were no differences in tumor characteristics or treatment modalities across baseline MetS groups. After 8.3 years (median) follow-up since TNBC, breast cancer survival rates at 10 years were lower in participants with 3-4 MetS (63%) compared to those with 1-2 (79%) or none (84%) (p=0.09). All-cause survival rates at 10 years after breast cancer diagnosis were also lower in participants with 3-4 MetS (45%) compared to those with 1-2 (65%) or none (71%) (p=0.008). CONCLUSION: Although TNBC is associated with poor clinical outcome, differences in all-cause mortality in women with TNBC remain significantly influenced by MetS. TNBC patients with 3-4 MetS components have 10-year all-cause survival rates over 35% lower than TNBC survivors with no MetS components. This finding highlights the importance of women’s overall health status and medical condition, even after the diagnosis of an aggressive breast cancer. Table 1. Breast cancer and all-cause survival rates by MetS group.MetSNBreast Cancer Survival (%)All-Cause Survival (%)3-year5-year10-yearp-value3-year5-year10-yearp-value01789087840.098782710.0081-23238983798777653-443877363836445 Citation Format: Yuan Yuan, Rebecca Nelson, Kathy Pan, Jessica Yan, Susan E Yost, Rami Nassir, Rowan Chlebowski. Metabolic syndrome impacts survival in postmenopausal women with triple negative breast cancer: Results from the women’s health initiative [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-07-03.

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