Metabolic syndrome and outcomes following early-stage breast cancer

Abstract

The prevalence of risk factors contributing to metabolic syndrome (MetS) is increasing, and numerous components of MetS are associated with increased primary breast cancer (BC) risk. However, less is known about the relationship of MetS to BC outcomes. The aim of this study was to evaluate whether MetS, characterized by increased weight, hypertension, low HDL-cholesterol, high triglycerides, and diabetes or impaired glucose tolerance, is associated with risk of second breast cancer events (SBCE) and BC-specific mortality. Retrospective cohort study of women diagnosed with incident early-stage (I-II) BC between 1990 and 2008, enrolled in an integrated health plan. Outcomes of interest were SBCE, defined as recurrence or second primary BC, and BC-specific mortality. We used multivariable Cox proportional hazards models to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for time-varying exposure to MetS components while accounting for potential confounders and competing risks. Among 4,216 women in the cohort, 26% had ≥3 MetS components and 13% developed SBCE during median follow-up of 6.3 years. Compared to women with no MetS components, presence of MetS (≥3 components) was associated with increased risk of SBCE (HR = 1.50, 95% CI 1.08-2.07) and BC-specific mortality (HR = 1.65, 95% CI 1.02-2.69). Of the individual components, only increased weight was associated with increased risk of SBCE (HR = 1.26, 95% CI 1.06-1.49). MetS is associated with modestly increased risk of SBCE and BC-specific mortality. Given the growing population of BC survivors, further research in larger and more diverse populations is warranted.

Figure 1

Patient flow diagram showing Group Health Cooperative (GH) selection of women with stage I or II breast cancer diagnosed between 1990 and 2008 to the Commonly Used Medications and Breast Cancer Outcomes (COMBO) study cohort

Figure 2. Adjusted hazard ratios and 95% confidence intervals for the relation between number of metabolic syndrome components with risk of SBCE, breast cancer-specific mortality and overall mortality

Note: Reference group for all estimates is 0 MetS components. Hazard ratios are adjusted for age (18–39, 40–49, 50–59, 60–69, 70–79, 80+ years), incident breast cancer diagnosis year, AJCC stage (I, IIA, IIB), hormone receptor status (ER−/PR−, ER+/PR−, ER−/PR+, ER+/PR+), primary treatment for the initial breast cancer (mastectomy +/− radiation, BCS + radiation, BCS), chemotherapy (yes/no), endocrine therapy (yes/no, time-varying), race (White, African American, American Indian/Alaska Native, Asian/Pacific Islander, unknown), smoking status (current, past, never), menopausal status (pre- or perimenopausal, postmenopausal), receipt of surveillance mammography (yes/no in prior 12 months, time-varying) as categorical variables; accounting for competing risks in multivariate-adjusted models. Tables of risk estimates with number of events and person-years in Online Resource 3 and 4.

Figure 3. Adjusted hazard ratios and 95% confidence intervals for the relation between individual metabolic syndrome components and risk of SBCE, breast cancer-specific mortality and overall mortality

Note: Hazard ratios are adjusted for age (18–39, 40–49, 50–59, 60–69, 70–79, 80+ years), incident breast cancer diagnosis year, AJCC stage (I, IIA, IIB), hormone receptor status (ER−/PR−, ER+/PR−, ER−/PR+, ER+/PR+), primary treatment for the initial breast cancer (mastectomy +/− radiation, BCS + radiation, BCS), chemotherapy (yes/no), endocrine therapy (yes/no, time-varying), race (White, African American, American Indian/Alaska Native, Asian/Pacific Islander, unknown), smoking status (current, past, never), menopausal status (pre- or perimenopausal, postmenopausal), receipt of surveillance mammography (yes/no in prior 12 months, time-varying) as categorical variables; accounting for competing risks in multivariate-adjusted models. Tables of risk estimates with number of events and person-years in Online Resource 3 and 4.

Figure 3. Adjusted hazard ratios and 95% confidence intervals for the relation between individual metabolic syndrome components and risk of SBCE, breast cancer-specific mortality and overall mortality

Note: Hazard ratios are adjusted for age (18–39, 40–49, 50–59, 60–69, 70–79, 80+ years), incident breast cancer diagnosis year, AJCC stage (I, IIA, IIB), hormone receptor status (ER−/PR−, ER+/PR−, ER−/PR+, ER+/PR+), primary treatment for the initial breast cancer (mastectomy +/− radiation, BCS + radiation, BCS), chemotherapy (yes/no), endocrine therapy (yes/no, time-varying), race (White, African American, American Indian/Alaska Native, Asian/Pacific Islander, unknown), smoking status (current, past, never), menopausal status (pre- or perimenopausal, postmenopausal), receipt of surveillance mammography (yes/no in prior 12 months, time-varying) as categorical variables; accounting for competing risks in multivariate-adjusted models. Tables of risk estimates with number of events and person-years in Online Resource 3 and 4.

Figure 3. Adjusted hazard ratios and 95% confidence intervals for the relation between individual metabolic syndrome components and risk of SBCE, breast cancer-specific mortality and overall mortality

Note: Hazard ratios are adjusted for age (18–39, 40–49, 50–59, 60–69, 70–79, 80+ years), incident breast cancer diagnosis year, AJCC stage (I, IIA, IIB), hormone receptor status (ER−/PR−, ER+/PR−, ER−/PR+, ER+/PR+), primary treatment for the initial breast cancer (mastectomy +/− radiation, BCS + radiation, BCS), chemotherapy (yes/no), endocrine therapy (yes/no, time-varying), race (White, African American, American Indian/Alaska Native, Asian/Pacific Islander, unknown), smoking status (current, past, never), menopausal status (pre- or perimenopausal, postmenopausal), receipt of surveillance mammography (yes/no in prior 12 months, time-varying) as categorical variables; accounting for competing risks in multivariate-adjusted models. Tables of risk estimates with number of events and person-years in Online Resource 3 and 4.

Figure 3. Adjusted hazard ratios and 95% confidence intervals for the relation between individual metabolic syndrome components and risk of SBCE, breast cancer-specific mortality and overall mortality

Note: Hazard ratios are adjusted for age (18–39, 40–49, 50–59, 60–69, 70–79, 80+ years), incident breast cancer diagnosis year, AJCC stage (I, IIA, IIB), hormone receptor status (ER−/PR−, ER+/PR−, ER−/PR+, ER+/PR+), primary treatment for the initial breast cancer (mastectomy +/− radiation, BCS + radiation, BCS), chemotherapy (yes/no), endocrine therapy (yes/no, time-varying), race (White, African American, American Indian/Alaska Native, Asian/Pacific Islander, unknown), smoking status (current, past, never), menopausal status (pre- or perimenopausal, postmenopausal), receipt of surveillance mammography (yes/no in prior 12 months, time-varying) as categorical variables; accounting for competing risks in multivariate-adjusted models. Tables of risk estimates with number of events and person-years in Online Resource 3 and 4.