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  • Cheng, Richard  (4)
  • Laurent, Cecile A.  (4)
  • Shen, Hanjie  (4)
  • 1
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 4_Supplement ( 2022-02-15), p. PD5-03-PD5-03
    Abstract: Purpose: Endocrine therapy is associated with cardiovascular disease among breast cancer (BC) survivors, with observed opposing effects between aromatase inhibitors (AIs) and tamoxifen. AIs deplete endogenous estrogen levels, while tamoxifen has mixed estrogenic and antiestrogenic activity. Yet, observational studies comparing AI vs. tamoxifen use may be confounded by indication and few have tested their associations with cardiometabolic risk factors. Therefore, we examined the association of AI or tamoxifen use on the incidence of newly diagnosed hypertension, diabetes, and dyslipidemia in a cohort of BC survivors within Kaiser Permanente Northern California (KPNC). Methods: The Pathways Heart Study is an ongoing cohort study within KPNC examining incident CVD outcomes and risk factors in 14,942 women with history of BC. Eligibility was: 1) stage I-IV invasive BC diagnosis between Nov 2005 and Mar 2013; 2) & ge;21 years; and 3) active KPNC membership & ge;12 months at diagnosis. KPNC records were used to collect demographic, socioeconomic, and health characteristics. Endocrine therapy was collected from outpatient pharmacy data. Incident hypertension, diabetes, and dyslipidemia were identified from ICD-9/10 codes, laboratory results, and/or medication use. Hazard ratios (HR) and 95% confidence intervals (CI) from Cox proportional models were used to determine whether AI and tamoxifen use were associated with incident hypertension, diabetes, and dyslipidemia compared to BC survivors not receiving either of these therapies. For each cardiometabolic risk factor, models adjusted for demographic, socioeconomic, and health characteristics and excluded women with the cardiometabolic risk factor at baseline. Results: Among 14,942 women with a history of BC, mean age at baseline was 61.2±12.8 years and mean follow-up time was 7.0±3.5 years (range 1-13.4). The frequency of use was: AI, n=6,070 (40.6%); tamoxifen, n=1,755 (11.8%); and neither, n=7,117 (47.6%). Regression models showed AI use was associated with increased risk of incident hypertension (HR: 1.1, 95% CI: 1.00-1.21) and increased risk of incident dyslipidemia (HR: 1.18, 95% CI: 1.07-1.3) relative to BC survivors who did not use endocrine therapy. (Table). In contrast, tamoxifen use was associated with decreased risk of dyslipidemia (HR: 0.8, 95% CI: 0.68-0.94) relative to BC survivors who did not use endocrine therapy. Neither AI nor tamoxifen use was associated with risk of incident diabetes. Conclusion: Compared to BC survivors who did not use endocrine therapy, women treated with AIs had a higher risk of incident hypertension and dyslipidemia, while women treated with tamoxifen had a lower risk of dyslipidemia. AIs reduce endogenous estrogen levels, which can alter lipid profiles, although prior studies have been inconsistent, possibly due to differences in steroidal and non-steroidal AIs. More work is needed to understand the implications of these associations on long-term cardiovascular health and how to best manage cardiometabolic risk factors in BC survivors with a history of endocrine therapy use. Table. Adjusted1 hazard ratios (95% confidence intervals) of incident cardiometabolic risk factors among women with a history of breast cancer, by endocrine therapy useNo Endocrine Therapy(n=7,117)Endocrine TherapyAromatase inhibitor(n=6,070)Tamoxifen(n=1,755)Incident HypertensionRef1.10 (1.00, 1.21)0.98 (0.85, 1.14)Incident DiabetesRef0.99 (0.87, 1.13)0.98 (0.80, 1.20)Incident DyslipidemiaRef1.18 (1.07, 1.30)0.80 (0.68, 0.94)1Adjusted for age, race/ethnicity, baseline body mass index, AJCC stage, menopausal status, smoking status, education level, income, chemotherapy, radiation therapy, and prevalent cardiovascular disease. Citation Format: Heather Greenlee, Eileen Rillamas-Sun, Carlos Iribarren, Richard Cheng, Romain Neugebauer, Jamal S. Rana, Mai Nguyen-Huynh, Zaixing Shi, Cecile A. Laurent, Valerie S. Lee, Janise M. Roh, Hanjie Shen, Dawn L. Hershman, Lawrence H. Kushi, Marilyn L. Kwan. Development of cardiometabolic risk factors following endocrine therapy: The pathways heart study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD5-03.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 15 ( 2022-05-20), p. 1647-1658
    Abstract: To examine cardiovascular disease (CVD) and mortality risk in women with breast cancer (BC) by cancer therapy received relative to women without BC. METHODS The study population comprised Kaiser Permanente Northern California members. Cases with invasive BC diagnosed from 2005 to 2013 were matched 1:5 to controls without BC on birth year and race/ethnicity. Cancer treatment, CVD outcomes, and covariate data were from electronic health records. Multivariable Cox proportional hazards models estimated hazard ratios (HRs) and 95% CIs of CVD incidence and mortality by receipt of chemotherapy treatment combinations, radiation therapy, and endocrine therapy. RESULTS A total of 13,642 women with BC were matched to 68,202 controls without BC. Over a 7-year average follow-up (range 〈 1-14 years), women who received anthracyclines and/or trastuzumab had high risk of heart failure/cardiomyopathy relative to controls, with the highest risk seen in women who received both anthracyclines and trastuzumab (HR, 3.68; 95% CI, 1.79 to 7.59). High risk of heart failure and/or cardiomyopathy was also observed in women with BC with a history of radiation therapy (HR, 1.38; 95% CI, 1.13 to 1.69) and aromatase inhibitor use (HR, 1.31; 95% CI, 1.07 to 1.60), relative to their controls. Elevated risks for stroke, arrhythmia, cardiac arrest, venous thromboembolic disease, CVD-related death, and death from any cause were also observed in women with BC on the basis of cancer treatment received. CONCLUSION Women with BC had increased incidence of CVD events, CVD-related mortality, and all-cause mortality compared with women without BC, and risks varied according to the history of cancer treatment received. Studies are needed to determine how women who received BC treatment should be cared for to improve cardiovascular outcomes.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 3
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 82, No. 4_Supplement ( 2022-02-15), p. PD5-01-PD5-01
    Abstract: Purpose: Studies on long-term cardiovascular disease (CVD) risk in breast cancer (BC) survivors are limited. We examined CVD risk associated with exposure to specific BC therapies and explored whether body mass index (BMI) or prevalent CVD risk factors at BC diagnosis modified these associations. Methods: The Pathways Heart Study is a prospective cohort study examining incident CVD outcomes and risk factors in women with BC at Kaiser Permanente Northern California (KPNC). Eligible women were diagnosed with stage I-IV invasive BC from 2005-2013, & ge;21 years old, and KPNC members & ge;12 months at diagnosis. KPNC records provided demographic and BC therapy characteristics. Incident CVD outcomes [ischemic heart disease, heart failure/cardiomyopathy (HF/CM), stroke] were assessed from ICD9/10 codes. Multivariable Cox models estimated hazard ratios (HR) and 95% confidence intervals (CI) of each CVD outcome by cancer therapy received compared to not receiving that therapy, excluding those with prevalent CVD. Separate regression models included interaction terms for cancer therapy by overweight, obesity, diabetes, dyslipidemia, and hypertension to test whether the CVD outcome risk varied by presence of these factors at diagnosis. Results: Among 4,181 BC survivors with mean age of 59.6±12.0 years and mean follow-up of 7.9±3.5 years (range: 0.04-13.3), cancer therapies were not associated with incident CVD. However, CVD risks varied by BMI and prevalence of CVD risk factors at BC diagnosis. Normal weight (NW) women who received anthracyclines had higher risk of ischemic heart disease and HF/CM relative to NW women not receiving these therapies; interaction terms indicated HF/CM risk was statistically different than risks for obese women (Table). NW women who received cyclophosphamide or left-sided radiation had higher risk of HF/CM and stroke relative to NW women not receiving these therapies; these risks were statistically different from obese (for cyclophosphamide) or overweight (for radiation) women. Relative to women not receiving these therapies, higher HRs for HF/CM were observed among non-diabetic women who received cyclophosphamide (2.03, CI: 1.22-3.37), non-dyslipidemic women who received anthracyclines (3.65, CI: 1.69-7.87), and non-hypertensive women who received either anthracyclines (4.04, CI: 1.81-9.03) or cyclophosphamide (2.66, CI: 1.23-5.74) (P for interaction range: 0.04 to 0.06). Conclusion: Certain chemotherapy drugs may increase the risk of CVD in NW BC survivors; overweight and obese BC survivors may experience less risk than NW women. While chemotherapy also appears to increase HF/CM risk for women without diabetes, dyslipidemia, and hypertension, these conditions are more prevalent among overweight/obese women. Analysis within these subgroups is needed and forthcoming. Table. Adjusted HRs (95% CI) of CVD outcomes among breast cancer survivors receiving select cancer therapies* stratified by BMI status at diagnosisBMI Ischemic heart diseaseHeart failure/CardiomyopathyStrokeAnthracycline, n=1283Normal4.22 (1.59, 11.2)5.27 (2.54, 10.9)1.89 (0.79, 4.53)Overweight1.66 (0.73, 3.77)2.17 (1.15, 4.11)0.40 (0.16, 0.99)Obese1.26 (0.56, 2.85)1.1 (0.54, 2.27)a0.33 (0.13, 0.83)aCyclophosphamide, n=1705Normal1.63 (0.61, 4.31)3.28 (1.59, 6.75)2.21 (1.01, 4.84)Overweight1.59 (0.75, 3.39)1.63 (0.9, 2.97)0.73 (0.34, 1.58)Obese0.85 (0.39, 1.86)0.75 (0.38, 1.47)a0.31 (0.13, 0.71)aLeft-Side Radiation, n=1331Normal1.44 (0.56, 3.69)2.04 (1.0, 4.18)2.38 (1.28, 4.42)Overweight1.47 (0.68, 3.16)0.68 (0.34, 1.34)b0.72 (0.37, 1.4)bObese1.32 (0.73, 2.38)1.30 (0.79, 2.16)1.05 (0.61, 1.82)*Cancer therapies with non-significant findings (i.e., Trastuzumab, taxanes, aromatase inhibitors, Tamoxifen, and any-side radiation) are not shown.ap≤0.05 normal weight v. obese; bp≤0.05 normal weight v. overweight Citation Format: Heather Greenlee, Eileen Rillamas-Sun, Carlos Iribarren, Richard Cheng, Romain Neugebauer, Jamal S. Rana, Mai Nguyen-Huynh, Zaixing Shi, Cecile A. Laurent, Valerie S. Lee, Janise M. Roh, Hanjie Shen, Dawn L. Hershman, Lawrence H. Kushi, Marilyn L. Kwan. Cardiovascular disease risk of breast cancer therapies: The pathways heart study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD5-01.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 4
    In: Breast Cancer Research and Treatment, Springer Science and Business Media LLC, Vol. 201, No. 1 ( 2023-08), p. 117-126
    Type of Medium: Online Resource
    ISSN: 0167-6806 , 1573-7217
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2004077-5
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