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  • 1
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2014
    In:  Nature Genetics Vol. 46, No. 1 ( 2014-1), p. 45-50
    In: Nature Genetics, Springer Science and Business Media LLC, Vol. 46, No. 1 ( 2014-1), p. 45-50
    Type of Medium: Online Resource
    ISSN: 1061-4036 , 1546-1718
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2014
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    SSG: 12
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  • 2
    In: Biomedicine & Pharmacotherapy, Elsevier BV, Vol. 141 ( 2021-09), p. 111814-
    Type of Medium: Online Resource
    ISSN: 0753-3322
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
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  • 3
    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
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 4
    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
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
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  • 5
    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
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  • 6
    In: Annals of the Rheumatic Diseases, BMJ, Vol. 77, No. 3 ( 2018-03), p. 417-417
    Abstract: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of considerable genetic predisposition. Genome-wide association studies have identified tens of common variants for SLE. However, the majority of them reside in non-coding sequences. The contributions of coding variants have not yet been systematically evaluated. Methods We performed a large-scale exome-wide study in 5004 SLE cases and 8179 healthy controls in a Han Chinese population using a custom exome array, and then genotyped 32 variants with suggestive evidence in an independent cohort of 13 246 samples. We further explored the regulatory effect of one novel non-coding single nucleotide polymorphism (SNP) in ex vivo experiments. Results We discovered four novel SLE gene regions ( LCT , TPCN2 , AHNAK2 and TNFRSF13B ) encompassing three novel missense variants (XP_016859577.1:p.Asn1639Ser, XP_016859577.1:p.Val219Phe and XP_005267356.1:p.Thr4664Ala) and two non-coding variants (rs10750836 and rs4792801) with genome-wide significance (p meta 〈 5.00×10 −8 ). These variants are enriched in several chromatin states of primary B cells. The novel intergenic variant rs10750836 exhibited an expression quantitative trait locus effect on the TPCN2 gene in immune cells. Clones containing this novel SNP exhibited gene promoter activity for TPCN2 (P=1.38×10 −3 ) whose expression level was reduced significantly in patients with SLE (P 〈 2.53×10 −2 ) and was suggested to be further modulated by rs10750836 in CD19+ B cells (P=7.57×10 −5 ) in ex vivo experiments. Conclusions This study identified three novel coding variants and four new susceptibility gene regions for SLE. The results provide insights into the biological mechanism of SLE.
    Type of Medium: Online Resource
    ISSN: 0003-4967 , 1468-2060
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    Language: English
    Publisher: BMJ
    Publication Date: 2018
    detail.hit.zdb_id: 1481557-6
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 15 ( 2022-05-20), p. 1635-1646
    Abstract: The incidence of cardiometabolic risk factors in breast cancer (BC) survivors has not been well described. Thus, we compared risk of hypertension, diabetes, and dyslipidemia in women with and without BC. METHODS Women with invasive BC diagnosed from 2005 to 2013 at Kaiser Permanente Northern California (KPNC) were identified and matched 1:5 to noncancer controls on birth year, race, and ethnicity. Cumulative incidence rates of hypertension, diabetes, and dyslipidemia were estimated with competing risk of overall death. Subdistribution hazard ratios (sHRs) were estimated by Fine and Gray regression, adjusted for cardiovascular disease–related risk factors, and stratified by treatment and body mass index (BMI). RESULTS A total of 14,942 BC cases and 74,702 matched controls were identified with mean age 61.2 years and 65% non-Hispanic White. Compared with controls, BC cases had higher cumulative incidence rates of hypertension (10.9% v 8.9%) and diabetes (2.1% v 1.7%) after 2 years, with higher diabetes incidence persisting after 10 years (9.3% v 8.8%). In multivariable models, cases had higher risk of diabetes (sHR, 1.16; 95% CI, 1.07 to 1.26) versus controls. Cases treated with chemotherapy (sHR, 1.23; 95% CI, 1.11 to 1.38), left-sided radiation (sHR, 1.29; 95% CI, 1.13 to 1.48), or endocrine therapy (sHR, 1.23; 95% CI, 1.12 to 1.34) continued to have higher diabetes risk. Hypertension risk was higher for cases receiving left-sided radiation (sHR, 1.11; 95% CI, 1.02 to 1.21) or endocrine therapy (sHR, 1.10; 95% CI, 1.03 to 1.16). Normal-weight (BMI 〈 24.9 kg/m 2 ) cases had higher risks overall and within treatment subgroups versus controls. CONCLUSION BC survivors at KPNC experienced elevated risks of diabetes and hypertension compared with women without BC depending on treatments received and BMI. Future studies should examine strategies for cardiometabolic risk factor prevention in BC survivors.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 12017-12017
    Abstract: 12017 Background: Women with a history of breast cancer (BC) are at increased long-term risk of dying from cardiovascular disease (CVD). However, the onset of CVD risk factors in women with BC has not been well-described. We compared risk of incident CVD risk factors in women with and without BC enrolled in the Kaiser Permanente Northern California (KPNC) integrated health system. Methods: Data were extracted from KPNC electronic health records. All invasive BC cases diagnosed between 2005-2013 were identified and matched 1:5 with controls on birth year, race/ethnicity and KPNC membership at the date of BC diagnosis. Cox regression models assessed the hazard of incident hypertension (based on diagnosis codes and filled prescriptions), dyslipidemia (based on diagnosis codes, filled prescriptions, and lab values), and diabetes (KPNC Diabetes Registry). Models were adjusted for baseline BMI, menopausal status, smoking status, neighborhood median household income, education, prevalent CVD conditions, and other baseline CVD risk factors. Subgroups of women who received chemotherapy, radiation therapy, and endocrine therapy were compared with controls. Results: A total of 14,942 women with a new diagnosis of invasive BC were identified and matched to 74,702 controls. On average, women were 62.0 years, 28.3 kg/m 2 BMI, 64.9% non-Hispanic white. Overall, cases were more likely to develop hypertension (HR: 1.18, 95% CI: 1.13, 1.24) and diabetes (HR: 1.23, 95% CI: 1.16, 1.31). Across the board, receipt of any of the three therapies (chemotherapy, radiation therapy and endocrine therapy) was associated with increased risk of hypertension and diabetes, compared to controls. Risk-factor specific hazard ratios for receipt of chemotherapy were (HR 1.18, 95% CI: 1.10, 1.27) and (HR 1.38, 95% CI: 1.26, 1.51), for hypertension and diabetes, respectively. For receipt of radiation therapy, risk-factor specific hazard ratios were (HR: 1.17, 95% CI: 1.09, 1.26) and (HR: 1.15, 95% CI: 1.04, 1.27), for hypertension and diabetes, respectively. Risk-factor specific hazard ratios for receipt of endocrine therapy were (HR: 1.22, 95% CI: 1.14, 1.30) and (HR: 1.16, 95% CI: 1.06, 1.27), for hypertension and diabetes, respectively. Conclusions: The risk of developing hypertension and diabetes is increased in women with BC who received chemotherapy, radiation therapy, and/or endocrine therapy. Future studies should examine the roles of CVD risk factor diagnosis and management on cardiometabolic risk in women with a BC history.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 9
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. 12016-12016
    Abstract: 12016 Background: Breast cancer (BC) survivors are at increased risk of cardiovascular disease (CVD) following diagnosis, as compared to women without BC. To provide a population-based estimate of CVD risk in BC survivors, we compared risk of CVD events in women with and without BC history enrolled in the Kaiser Permanente Northern California (KPNC) integrated health system. Methods: Data were extracted from KPNC electronic health records. All invasive BC cases diagnosed between 2005-2013 were identified and matched 1:5 with non-BC controls on birth year, race/ethnicity and KPNC membership at date of BC diagnosis. Cox regression models were used to assess differences in the hazard of four major CVD events (ischemic heart disease (IHD), heart failure (HF), cardiomyopathy, and stroke). Models were adjusted for factors known to influence risk of breast cancer or CVD.Other CVD events included arrhythmia, cardiac arrest, carotid disease, myocarditis/pericarditis, transient ischemic attack, valvular disease, and venous thromboembolism (VTE). We additionally examined subgroups of cases who received chemotherapy, radiation, and endocrine therapy, and their controls. Results: A total of 14,942 women with a new diagnosis of invasive BC were identified and matched to 74,702 women without BC history. On average, women were 62.0 years, 28.3 kg/m 2 BMI, 64.9% non-Hispanic white. Among all cases and controls, there were no significant differences in hazard of developing IHD, cardiomyopathy, and stroke; there was a borderline difference in HF (HR: 1.08, 95% CI: 0.99, 1.19). Cases were more likely to have a cardiac arrest (HR: 1.39, 95% CI: 1.09, 1.78) and develop VTE (HR: 1.97, 95% CI: 1.74, 2.23). Women treated with chemotherapy were more likely than controls to develop HF (HR: 1.44, 95% CI: 1.21, 1.72), cardiomyopathy (HR: 2.01, 95% CI: 1.02, 3.98), and VTE (HR: 3.15, 95% CI: 2.62, 3.79). Women who received radiation therapy were more likely to develop carotid disease (HR: 5.49, 95% CI: 1.22, 24.66) and VTE (HR: 1.65, 95% CI: 1.35, 2.03) than controls. Women who received endocrine therapy were more likely to experience a cardiac arrest (HR: 1.49, 95% CI: 1.07, 2.09) and develop VTE (HR: 1.70, 95% CI: 1.42, 2.03) than controls. Conclusions: Women with BC were at increased risk of heart failure, cardiomyopathy, cardiac arrest, VTE and carotid disease. These risks varied by cancer treatment, with higher risk in those who received chemotherapy. Future studies should explore the effects of chemotherapy class and radiation dose exposure on diverse CVD endpoints in BC survivors.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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