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Breast Cancer in the Women’s Health Initiative Trial of Estrogen Plus Progestin

Breast Cancer in the Women’s Health Initiative Trial of Estrogen Plus Progestin. For the WHI Investigators Rowan T Chlebowski, MD., Ph.D. Menopausal Hormone Therapy and Breast Cancer (Background).

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Breast Cancer in the Women’s Health Initiative Trial of Estrogen Plus Progestin

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  1. Breast Cancer in the Women’s Health Initiative Trial of Estrogen Plus Progestin For the WHI Investigators Rowan T Chlebowski, MD., Ph.D.

  2. Menopausal Hormone Therapy and Breast Cancer (Background) Preponderance of observational studies suggest long duration estrogen plus progestin increases breast cancers which have: - Low stage and favorable prognosis - Receptor positive preponderance - More lobular histology Holli J Clin Oncol 1998; 16: 3115 Gapstur JAMA 1999; 281: 2021 Delgado Maturitas 2001; 38: 147 Lower Breast Cancer Res Treat 1999; 58: 205 Chen, JAMA 287: 734, 2002 Coldity Am JEpid 147 (5): 645, 1998

  3. Descriptive Characteristics in WHI Participants Age Age at menarche Relatives with breast ca (n) Ethnicity Term pregnancies (n) Benign breast disease Education Age at first birth Prior estrogen (E) alone use Gail Risk Children breastfed (n) Prior E + progestin (P) use BMI Oral Contraceptive use NSAID use Alcohol Use % Energy from fat Physical Activity None of these characteristics differed significantly between treatment groups

  4. Descriptive Characteristics By Treatment Group “Current” users required three month washout

  5. WHI Estrogen+Progestin TrialBreast Safety • Baseline mammogram and clinical breast exams required for eligibility • Annual mammograms and clinical breast exams required when on study • Study medications withheld if safety procedures not performed

  6. Breast Cancers by Category and Treatment Group 1 Hazard ratios (HR) from unweighted Cox proportional hazards regression models 2 P values from weighted Cox proportional hazards regression models

  7. Invasive Breast Cancer By Group Hazard ratios (HR) from unweighted Cox proportional hazards regressions models Z Statistics and p values from weighted Cox proportional hazards regression models

  8. Sensitivity Analysis of Adherent Participants Invasive Breast Cancers by Group Participants were censored 6 months after becoming non-adherent (taking < 80% study meds or taking non-protocol hormones) Hazard ratios (HR) from unweighted Cox proportional hazards regressions models Z Statistics and p values form weighted Cox proportional hazards regression models

  9. Breast Cancers (Annualized Percentage) by Age P-value tests interactions of E+P and age

  10. Breast Cancer (Annualized Percentage) by BMI P-value tests for interaction of E+P with BMI

  11. Breast Cancers (Annualized Percentage) by Prior Menopausal Hormone Therapy (MHT) Use More breast cancers on E+P in both groups Non-significant trend, no interaction Ever users at somewhat lower risk Cumulative exposure versus selection bias 1 P value tests for interaction with E+P and prior MHT

  12. Breast Cancer Incidence by Prior MHT Use and Randomization Assignment

  13. Breast Cancer Characteristics by Group 1 P value tests association with treatment groups Similar histology and grade on E+P and placebo

  14. 1 The first P value tests association with treatment groups 2 P-value for “missing” rows test the association of % missing with treatment group Both receptor positive and negative breast cancers greater on E+P

  15. Breast Cancer Characteristics by Group 1 mean (SD) for tumor with known tumor size 2 P-values from weighted Cox proportional hazards models More advanced stage on E+P

  16. Year 1 Mammogram Findings by Group 1 p < .0001 comparing E+P versus placebo Increased abnormal mammograms after 1 year on E+P

  17. SummaryMammogram Findings by Group and Time 1 % of women due for visit with mammogram in study period who had mammogram 2 % of women with any category of abnormal mammogram 3 p < 0.0001 E+P versus placebo

  18. Abnormal Mammograms: Associated with Short Duration E+P Use 4 % absolute increase in abnormal mammograms after one year on E+P 10% absolute increase in abnormal mammograms after about 5 years on E+P

  19. Recent Results from the UK Million Women Study National Health Service Breast Cancer Screening Program Inform Interpretation of WHI Results

  20. Million Women Study • NHSBSP in the UK invites women 50-69 for mammography screening q 3 years by letters • A questionnaire regarding HT use was added to the screening invitation letter • HT use data was linked to NHS central registries for breast cancer and death outcomes • 1,084,110 women flagged • 9,364 incident invasive breast cancers seen Lancet 2003; 362: 419-27.

  21. Relative Risk of Fatal Breast Cancer by HT Use at Baseline in the Million Women Study Based on 517 deaths after 4.1 years * P = 0.05 for current versus never Lancet 2003; 362; 419-27. HT associated with increased breast cancer mortality in “short term” users

  22. Relative Risk of Breast Cancer in the Million Women Study By E+P Duration E+P associated with increased breast cancers in < 1 year

  23. Relative Risk of Breast Cancer in the Million Women Study By Hormone Type

  24. Conclusions Combined E+P use increases breast Ca, diagnosed at more advanced stage and increases abnormal mammograms These results suggest: Use of E+P may stimulate breast cancer growth and hinder breast cancer diagnosis

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