Estrogen Alone and Health Outcomes in Black Women by African Ancestry

Transcription

1 Estrogen Alone and Health Outcomes in Black Women by African Ancestry Wendy E. Barrington, PhD, MPH Rowan T. Chlebowski, Aaron K. Aragaki, JoAnn E. Manson, Gloria Sarto, Mary J. O Sullivan, Jane A. Cauley, Lihong Qi, Robert L. Wallace, Ross L. Prentice

2 Disparities in Breast Cancer Breast Cancer among African-American women: Lower incidence of breast cancer Higher breast cancer mortality Elevated risk of breast cancer mortality may be due to differences in: Genetic characteristics Environmental exposures (e.g. SES, access to healthcare, lifestyle behaviors) Known breast cancer risk factors may differentially affect African-American women

3 WHI Hormone Therapy (HT) Program Design Postmenopausal women with prior hysterectomy N= 10,739 CEE (Conjugated equine estrogen) mg/d Placebo Postmenopausal women with no prior hysterectomy N= 16,608 CEE mg/d + medroxyprogesterone acetate (MPA) 2.5 mg/d Placebo Eligibility Age No prior breast cancer Informed consent Time Intervention: 7.1 years Cumulative follow-up: 13.2 years Rossouw, Anderson, Prentice, et al. JAMA 2002;288: Anderson, Limacher, Assaf, et al and the WHI Steering Committee. JAMA 2004;291:

4 Hormone Therapy and Breast Cancer Incidence Estrogen Plus Progestin 1 Increased risk during intervention period (HR: 1.24; 95% CI: ) Risk decreased, but remained elevated during early postintervention period Similar findings in the OS 2 Estrogen Alone 1 Decreased risk during intervention period (HR: 0.79; 95% CI: 0.61, 1.02) Risk decreased further during early post-intervention period (HR: 0.55; 95% CI: 0.34, 0.89) Recommendation for use of HT in black and obese women 3 1 Manson et al. JAMA 2013;310(13): Chlebowski et al. JNCI 2013;105(8): Hou et al. JNCI 2013;105(18):

5 Hormone Therapy and Other Clinical Outcomes Estrogen Alone* *Overall Cumulative Findings Chlebowski, Rohan, Manson, et al JAMA Oncol (Published online April 16, 2015)

6 Why Examine Racial Differences? Black women are at greater risk for: obesity, diabetes, stroke, and deaths due to heart disease compared to white women 1-5. Despite widespread use, menopausal hormone therapy influence on health outcomes among black women has received extremely limited attention. Among studies of CHD and HT conducted between , only 173 of 148,437 (0.1%) study participants were black 6. 1 Ma et al Am J Epidemiol 2013;178: Jha et al Circulation 2006;108: Chlebowski et al J Natl Cancer Inst 2005;97:939 4 Carey et al JAMA 2006;295: Igbal et al JAMA 2015;13:725 6 Nicholson et al Menopause 1999;6:147

7 Trial Monitoring Coronary heart disease (primary benefit endpoint) Invasive breast cancer (primary harm endpoint) Trial monitoring also included a Global Index defined as time to first event of: coronary heart disease breast cancer stroke pulmonary emboli colorectal cancer hip fracture death from all other causes

8 Outcome Assessment Clinical outcomes were assessed at 6 month intervals through March 31, 2005 and yearly self-report. All clinical outcomes in the Global Index were verified by medical record review by continuous blinded to randomization with final adjudication at the WHI Clinical Coordinating Center. Verification of strokes additionally included adjudication by centrally trained neurologist reviews.

9 Statistical Analyses Analyses incorporated time-to-event methods based on intention-to-treat principle with Hazard Ratios (HRs) and 95% CIs estimated using Cox regression methods. HRs were also estimated in case-only analyses using logistic regression of treatment assignment, stratified by 3 ordinal groups of African admixture. Analyses were stratified by race/ethnicity, age, and WHI DM randomization.

10 African Ancestry In women self-reported as black, African admixture was determined using validated genetic ancestry information from 656,852 markers (available in 66% [n=106] of 1616 black women) The African admixture contribution (0-100%) was estimated using Frappe software 1 Black women were subdivided by median ancestry ( 80% African ancestry and < 80% African ancestry) White women assumed to have lowest % African ancestry Only 1.2% of women in WHI had >2% African ancestry 1 Tang et al Genet Epidemiology 2005;28:289

11 Baseline Characteristics by Race/Ethnicity and Randomization Characteristic Active, % (n=4,009) White Placebo, % (n=4,075) Active, % (n=781) Black Placebo, % (n=835) Age at screening, y, mean (SD) 64.3 (7.2) 64.3 (7.3) 61.7 (7.0) 61.5 (7.1) Menopausal Hormone Therapy Never used Past user Current user Baseline vasomotor symptoms, % None Mild Moderate/severe

12 Baseline Characteristics by Race/Ethnicity and Randomization Characteristics Active, % (n=4,009) Body mass index, kg/m 2, median (IQR) 29.0 (25.3, 33.3) Whites Placebo, % (n=4,075) 28.7 (25.4, 32.9) Active, % (n=781) 31.2 (27.4, 35.9) Blacks Placebo, % (n=835) 30.9 (27.5, 35.8) Systolic BP, mm Hg, mean (SD) (17.3) (17.5) (17.5) (17.6) Diastolic BP, mm Hg, mean (SD) 76.0 (9.0) 75.9 (9.2) 79.3 (9.4) 79.2 (9.4) Smoking, % Never Past Current yr breast-cancer risk score* < to > *Estimated from Gail model

13 Baseline Characteristics by Race/Ethnicity and Randomization White Black Characteristic Active, % (n=4,009) Placebo, % (n=4,075) Active, % (n=781) Placebo, % (n=835) Medical treatment, % For diabetes For hypertension or BP 140/ For cholesterol Statin use Aspirin use ( 80mg/d)

14 Estrogen Alone and Clinical Outcomes by Race/Ethnicity White Black *p-value corresponds to a test of the interaction between randomization arm and race

15 Estrogen Alone Influence on Clinical Outcomes in Black Women by Randomization Group

16 Estrogen Alone and Global Index by Race/Ethnicity White Black

17 Estrogen Alone and Stroke Risk in Black Women Estrogen alone did not increase stroke risk in black women (32 vs. 29 cases, HR 1.18; 95% CI: ) The result requires cautious interpretation since: Increased stroke risk evidenced in white women (376 vs. 311 cases, HR % CI ) 1 with no interaction by race/ethnicity seen. 2 1 Manson, Chlebowski et al JAMA 2013;310(13): Hendrix, Wassertheil-Smollen, et al Circulation 2006;313(20):

18 Baseline Characteristics by Percentage African Ancestry Characteristic 80% African (n=531), % < 80% African (n=530), % Age at screening, years, mean (SD) 61.0 (6.8) 62.4 (7.2) Menopausal hormone therapy use status Never used Past user Current user Baseline vasomotor symptoms, % None Mild Moderate/severe Body mass index, kg/m 2, median (IQR) 31.5 (27.9, 36.8) 30.7 (26.9, 35.1) Other characteristics were closely comparable

19 Estrogen Alone and Clinical Outcomes by % African Ancestry

20 Conclusions Among black postmenopausal women with prior hysterectomy, estrogen alone significantly reduced breast cancer incidence No apparent adverse influence on CHD, stroke, or mortality. Greater reduction in breast cancer incidence with estrogen alone in black women with 80% African ancestry Possible genetic basis for the finding Protective association between estrogen alone and Global Index in black women years old warrant further study Findings provide reassurance for black women who are close to menopause and considering estrogen alone for climacteric symptom management

21 Thank you for your attention!

22 Estrogen Alone and Breast Cancer Incidence Over Time Intervention HR (95% CI) = 0.79 (0.61, 1.02) Postintervention HR (95% CI) = 0.79 (0.65, 0.97) Chlebowski, Rohan, Manson, et al JAMA Oncol (Published online April 16, 2015)

23 Estrogen Alone Effect on Invasive Breast Cancer Incidence by African Ancestry in Case-Only Analysis African Ancestry HR 95% CI Interaction p All 0.47 ( ) 0.04 < 80% 0.62 ( ) 80% 0.32 ( ) Results suggest possible estrogen alone effect modification on breast cancer risk by African ancestry.