Kathleen E. Malone

Background: Cardiovascular disease is a leading cause of death for long-term breast cancer survivors. We evaluated whether a polygenic risk score for coronary artery disease (CAD-PRS) was associated with the risk of incident CAD for survivors of unilateral or contralateral breast cancer. Methods: The study included 1307 women with breast cancer first diagnosed at younger than 55 years of age who participated in the Women’s Environmental Cancer and Radiation Epidemiology Follow-up Study. The CAD-PRS was based on a PRS developed and validated in a separate population. We modeled the association between incident CAD and the CAD-PRS, adjusting for age, CAD risk factors, first (and second) breast cancer treatment, study recruitment phase, and genetic population stratification. We also explored whether the risk of CAD depended on interactions between the CAD-PRS and cardiotoxic cancer treatment. Results: There were 66 incident CAD diagnoses reported at a median of 16 years after breast cancer diagnosis. Participants with CAD-PRS at or above the median had a 2.48-times increased risk of CAD (95% confidence interval [CI] = 1.44 to 4.29) relative to participants with CAD-PRS below the median. Anthracycline-based chemotherapy was associated with increased CAD risk (hazard ratio [HR] = 2.04, 95% CI = 1.04 to 3.98), and the association was not modified by the CAD-PRS. The association between incident CAD and left-sided radiation therapy (RT) was increased for those with CAD-PRS at or above the median (HR = 2.90, 95% CI = 1.26 to 6.68) but not for those with CAD-PRS below the median (HR = 0.96, 95% CI = 0.32 to 2.88). There was evidence of super-additive interaction between the CAD-PRS and left-sided RT (relative excess risk due to interaction = 2.06, 95% CI = 0.05 to 4.06). Conclusion: A genome-wide CAD-PRS was associated with nonfatal CAD risk for long-term breast cancer survivors, providing potential utility for personalized cardiovascular care, particularly after RT.

Supplementary Table 1 presents the distribution of patient characteristics among those with and without extended follow-up for recurrence.

Background:We evaluated the association between metabolic syndrome (MetS; obesity plus two metabolic risk factors) and breast cancer outcomes according to molecular subtype.Methods:This population-based prospective cohort consisted of 3,267 women ages 20 to 69 years diagnosed with a first primary invasive breast cancer from 2004 to 2015 in the Seattle–Puget Sound region. Breast cancer was categorized into three subtypes based on estrogen receptor (ER), progesterone receptor, and HER2 expression: luminal (ER+), triple-negative (ER−/progesterone receptor negative/HER2−), and HER2-overexpressing (H2E; ER−/HER2+) subtypes. We used time-varying Cox models to assess the association of prevalent and incident MetS with risks of recurrence, breast cancer–specific mortality (BCSM), and all-cause mortality (ACM).Results:MetS was associated with a greater risk of recurrence [HR, 3.24; 95% confidence interval (CI), 1.13–9.33] and BCSM (HR, 5.34; 95% CI, 2.32–12.31) only for the H2E subtype and greater risks of ACM for luminal (HR, 1.92; 95% CI, 1.37–2.68), H2E (HR, 5.09; 95% CI, 2.51–10.32), and all cases combined (HR, 1.90; 95% CI, 1.42–2.53). We also observed heterogeneity in recurrence and mortality outcomes across specific components of MetS and molecular subtypes.Conclusions:MetS is associated with ACM among women with breast cancer and with BCSM among women with the H2E subtype.Impact:These results highlight the importance of managing comorbidities to decrease the risk for adverse outcomes among breast cancer survivors.

Supplementary Table 2 presents results for breast cancer recurrence associated with metabolic syndrome and its components by molecular subtype of breast cancer and stratified by age at diagnosis.

Supplementary Table 5 presents results for breast cancer specific and all-cause mortality associated with metabolic syndrome and its components by molecular subtype of breast cancer and stratified by stage at diagnosis.

Supplementary Table 4 presents results for breast cancer recurrence associated with metabolic syndrome and its components by molecular subtype of breast cancer and stratified by stage at diagnosis.

Flow diagram describing collection of comorbidity diagnoses and treatments with respect to breast cancer diagnosis.

Supplementary Table 3 presents results for breast cancer specific and all-cause mortality associated with metabolic syndrome and its components by molecular subtype of breast cancer and stratified by age at diagnosis.

Background: We evaluated the association between metabolic syndrome (MetS; obesity plus two metabolic risk factors) and breast cancer outcomes according to molecular subtype. Methods: This population-based prospective cohort consisted of 3,267 women ages 20 to 69 years diagnosed with a first primary invasive breast cancer from 2004 to 2015 in the Seattle–Puget Sound region. Breast cancer was categorized into three subtypes based on estrogen receptor (ER), progesterone receptor, and HER2 expression: luminal (ER+), triple-negative (ER−/progesterone receptor negative/HER2−), and HER2-overexpressing (H2E; ER−/HER2+) subtypes. We used time-varying Cox models to assess the association of prevalent and incident MetS with risks of recurrence, breast cancer–specific mortality (BCSM), and all-cause mortality (ACM). Results: MetS was associated with a greater risk of recurrence [HR, 3.24; 95% confidence interval (CI), 1.13–9.33] and BCSM (HR, 5.34; 95% CI, 2.32–12.31) only for the H2E subtype and greater risks of ACM for luminal (HR, 1.92; 95% CI, 1.37–2.68), H2E (HR, 5.09; 95% CI, 2.51–10.32), and all cases combined (HR, 1.90; 95% CI, 1.42–2.53). We also observed heterogeneity in recurrence and mortality outcomes across specific components of MetS and molecular subtypes. Conclusions: MetS is associated with ACM among women with breast cancer and with BCSM among women with the H2E subtype. Impact: These results highlight the importance of managing comorbidities to decrease the risk for adverse outcomes among breast cancer survivors.

Background: Preclinical evidence suggests improved breast cancer survival associated with statin use, but findings from observational studies are conflicting and remain inconclusive. The objective of this study was to assess the association between statin use after cancer diagnosis and cancer outcomes among breast cancer patients.Methods: In this retrospective cohort study, 38,858 women aged ≥66 years who were diagnosed with localized and regional stage breast cancer from 2008 through 2017 were identified from the linked Surveillance, Epidemiology, and End Results Medicare database. Statin use was ascertained from Medicare Part D pharmacy claims data. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between post‐diagnosis statin use and risks of breast cancer recurrence and breast cancer–specific mortality.Results: Over a median follow‐up of 2.9 years for recurrence and 3.7 years for mortality, 1446 women experienced a recurrence, and 2215 died from breast cancer. The mean duration of post‐diagnosis statin use was 2.2 years. Statin use post‐diagnosis was not associated with recurrence risk (HR, 1.05; 95% CI, 0.91–1.21), but was associated with a reduced risk of cancer‐specific mortality (HR, 0.85; 95% CI, 0.75–0.96). The reduction was more pronounced in women with hormone receptor–positive/human epidermal growth factor receptor 2–negative breast cancer (HR, 0.71; 95% CI, 0.57–0.88).Conclusions: These findings suggest that post‐diagnosis statin use is associated with improved cancer‐specific survival in women with breast cancer and should be confirmed in randomized trials of statin therapy in breast cancer patients.