Hormone therapy (HT) Epidemiological aspects jvind Lidegaard - PowerPoint PPT Presentation

Hormone therapy (HT) Epidemiological aspects Øjvind Lidegaard Professor, DMSc Gynaecological Clinic 4232 Rigshospitalet Copenhagen University www.lidegaard.dk/slides

Hormone therapy; an update • Hormone use • HT - breast cancer • HT - endometrial cancer • HT - ovarian cancer • HT - colo-rectal cancer • HT - heart and circulation • HT - death • Conclusion

HT sale DK 2002. DDD/1,000 per day 250 www.dachre.dk Local Mirena 200 Comb cont Comb cycl Progestagen 150 Oestrogen 100 50 0 15-39 40-44 45-49 50-54 55-59 60-64 65-69 70+ Danish Sex Hormone Register Study (DaHORS).

HT sale DK 2004. DDD/1,000 per day 250 www.dachre.dk Local Mirena 200 Comb cont Comb cycl Progestagen 150 Oestrogen 100 50 0 15-39 40-44 45-49 50-54 55-59 60-64 65-69 70+ Danish Sex Hormone Register Study (DaHORS).

Hormone therapy; an update • Hormone use • HT - breast cancer • HT - endometrial cancer • HT - ovarian cancer • HT - colo-rectal cancer • HT - heart and circulation • HT - death • Conclusion

HT and cancer Axes of significance: • Duration of therapy • Regimen (ET, EPT, tibolone) • Long cycle, cyclic, cont. combined • Route: Oral, dermal, vaginal, IUD • Estrogen dose • Progestagen type • Progestagen dose

Breast cancer incidence rate by age Incidence per 100,000 400 352 368 350 Total: 4,000 per year 342 326 338 324 Lifetime risk: 10% 300 271 250 244 200 189 150 127 100 50 50 20% 80% 22 3 2 0 0 0 5 9 4 9 4 9 4 9 4 9 4 9 4 9 4 + 1 1 2 2 3 3 4 4 5 5 6 6 7 7 8 5 < - - - - - - - - - - - - - - 8 5 0 5 0 5 0 5 0 5 0 5 0 5 0 1 2 2 3 3 4 4 5 5 6 6 7 7 8 Health statistics, National Board of Health, DK 2003

BC incidence rate in Norway 2005 Incidence per 100,000 400 332 323 350 305 272 270 300 252 226 250 212 179 200 150 96 100 55 21 50 6 1 0 0 0 5 9 4 9 4 9 4 9 4 9 4 9 4 9 4 + 1 1 2 2 3 3 4 4 5 5 6 6 7 7 8 5 < - - - - - - - - - - - - - - 8 5 0 5 0 5 0 5 0 5 0 5 0 5 0 1 2 2 3 3 4 4 5 5 6 6 7 7 8 Cancer Registry, Norway

BC incidence rate in DK 1945-2000 Incidence per 100,000 age standardised 120 119 110 112 100 105 98 90 92 86 80 78 70 72 66 60 63 62 61 50 45 50 55 60 65 70 75 80 85 90 95 20 Li/07 Oksbjerg S. Ugeskr Læger 1997; 159: 7134-40.

Body mass index and risk of breast cancer 1,6 Cases: 6548 Confounder control: Controls: 9057 parity, menarche, family histpry of BC, age at 1,4 1,41 first full-term pregn, alcohol consumption, education 1,2 1,21 1,14 1,09 1,04 1,02 1 1 1 0,93 0,87 0,8 13-20.2 20.2-21.7 21.8-23.4 23.5-26.5 26.6-54 Trentham-Dietz. Am J Epidemiol 1997; 145: 1011-9 .

Physical activity and breast cancer Cohort study of 25,624 women. Follow up: 13.7 years Relative risk (95% CI) 1,1 1 1 1 0,93 0,9 0,84 0,8 0,74 0,7 0,63 0,6 Work 0,5 0,48 Leisure 0,4 0,3 Adjusted for age, BMI, residence, number of births 0,2 Little Moderate Regular Heavy Thune I, N Engl J Med 1997; 336: 1269-75

Fruit and vegetables: influence on pre-menopausal BC Confounder control: Risk of premenopausal BC (95% 1,1 Age at first birth, menarche, education, 1 family BC, BMI, and 0,9 total caloric intake 0,8 CL) 0,7 0,6 Cases: 297 0,5 Controls: 311 0,4 0,3 g/day <16 16-19 20-24 >24 Freundenheim. J Natl Canc Inst 1996; 88: 340-8.

Alcohol intake and risk of breast cancer 1,5 Risk of BC (95% CL) 1,4 1,3 13%/drink 7.1%/drink 1,2 1,1 drinks per day 1 0 1 2 3 4 Longnecker. Canc Causes and Control 1994; 5: 73-82 Beral V et al. Lancet 2002; 87: 234-45

Family disposition and BC 4 3,9 Risk of BC (95% CL) 3,5 3 2,9 2,5 2 1,8 1,5 1 1 0 1 2 3+ Collaborative group, Lancet 2001; 358: 1389-99

Age at first birth and risk of BC 1,8 Risk of BC 1,7 (95% CL) 1,6 Case-control study Norway 1,5 373 cases 1,150 controls 1,4 1,2 1,1 1 1 <20 20-24 25-29 30+ Vatten LJ. Br J Cancer 2002, 86: 89-91

Age at first birth DK 1965-2006 30 30 Childless at 49 years 1995: 7.9% 29 Childless at 49 years 2000: 12.1% 28,1 Childless at 49 years 2005: 12.7% 27,5 28 26,4 27 25,5 26 24,6 25 24 23,7 Increase: 1 year/5 years 24 22,7 23 22 1965 1970 1975 1980 1985 1990 1995 2000 2006 Online statistics: www.dst.dk

Age at first birth DK and No 30 30 29 28,1 27,5 27,5 28 26,9 26,4 27 26 25,5 26 25 24,6 24,4 25 24 23,7 23,6 Increase: 1 year/5 years 24 22,8 22,7 22,5 23 22 1965 1970 1975 1980 1985 1990 1995 2000 2006 Online statistics: www.dst.dk and www.fhi.no

Breast cancer and birth weight 3,5 Nurses Health Study Cohort study 3 582 nurses with BC 5358 women 1,569 without Sweden 2,4 2 1,8 1,6 1,6 1,24 1,2 1 1 1 1 1 0,9 0,75 0 <2½ 2½-3 3-3½ 3½-4 >4 <3 3-3½ 3½-4 >4 Lancet 1996; 348: 542-6. BMJ 2003; 326: 248-53 .

Breastfeeding, parity and breast cancer Relative risk (95% CI) 1 1 0,94 0,97 0,9 0,93 0,86 0,84 Never breastfeed 0,8 0,83 0,73 0,7 0,73 Ever breastfeed Number of births 0,64 0,6 1 2 3 4 >4 Collaborative group. Lancet 2002; 360: 187-95.

Can we explain the increase? Yes: • Increase in age at first birth 21 → 29 years • Higher birth weight • Less physical activity • Fewer children per woman • Increase in daily alcohol consumption • Dramatic increase in BMI These factors fully explain the increase Lidegaard & Kroman. Eur Clinics Obstet Gynaecol 2005; 1: 24-8

Breast cancer: Risk factors Family breast cancer (RR 2) Night work (RR 1-1.5) HT Age at first birth Breast cancer 30 vs 20: (RR 1.5) Fibers (RR 0.5) Alcohol (RR 1.10/drink) Physical activity (RR 0.5) Adiposity (RR 1.4)

HT and breast cancer (BC) Metaanalysis from 1996 • Current HT increases the risk of breast cancer by 10-30% (5-15 years) • The risk was 16% higher for comb. HT. • The risk increased with duration of use • The risk faded out after cessation • Women with BC and previous HT have a better survival than BC patients without previous HT => no increased risk of death Metaanalysis: 52,705 cases, 108,411 controls. Lancet 1997

HT and BC: Randomised studies Risk after 5.2 and 6.8 years MPA+EE 2,5 WHI study: Cohort: 8,506 EE+MPA, 8,102 placebo. 2 Follow up: 5.2 yrs. Endpoints: 166 exposed, 1,5 124 non-exposed 1,27 1,26 HERS: 5,100 women with AMI 1 randomised for EE+ MPA 2,5mg. Follow up 6.8 years. 0,5 Endpoints: 49 exposed, 39 non-exposed women with BC 0 WHI HERS Rossouw et al. JAMA 2002; 288: 321-33. Hulley et al. JAMA 2002; 288: 58-66

WHI results EPT ET 50-59 • Coronary heart disease 1.3 0.9 0.6 • Stroke 1.4 1.4 1.1 • Venous thromboembolism 2.1* 1.3 1.2 • Breast cancer 1.3 0.8 0.7 • Endometrial cancer 0.8 hysterect. • Colorectal cancer 0.6 1.1 0.6 • Hip fracture 0.7 0.6 NA • Vertebral fracture 0.7 0.6 NA • All cause mortality 1.0 1.0 0.7 Rossouw et al. JAMA 2002; 288: 321-33.

Million women study Design: • A prospective cohort study Cohort: • Women invited with invitation to breast cancer screening. 75% accepted screening, 71% of screened (53% of all) accepted participation in the study. • Age: 50-64 years at baseline • Recruitment: May 1996 – March 2001 Follow up • Incidence: Dec 2000 or 2001; 2.6 years • Mortality: December 2002; 4.1 years Lancet 2003; 362: 419-27

Risk in women currently on HT 1,8 1,7 1,66 1,6 1,5 1,4 1,3 1,2 1,1 1,04 1,01 1,01 1 1 0,9 0,9 0,8 0,7 Never use Current All past Last use Last use Last use use use <5 yrs 5-9 yrs 10+ Lancet 2003; 362: 419-27

Risk on different regimens 2,1 2 1,9 1,7 1,5 1,45 1,3 1,3 1,22 1,1 1 0,9 Never Est only Est + Prog Tibolone Death

Oestrogen only therapy 2 1,8 1,6 1,4 1,32 1,3 1,25 1,24 1,2 1,19 1 1 0,8 Never Oest only Estrad Estrad Oral Dermal <1mg >1mg

Oestrogen-progestagen therapy Influence from different progestagens <5 years 2,6 2,4 2,4 2,2 2,2 2,1 2,1 2 1,8 1,8 1,6 1,6 1,5 1,4 >5 years 1 MPA NETA Levo Seq. Cont. MPA NETA Levo Seq. Cont.

Danish sex Hormone Register Study DaHoRS (1.8 mio women study) Hormone therapy and breast cancer Øjvind Lidegaard Ellen Løkkegaard Lisbeth Møller Carsten Agger Anne Helms Andreasen

DaHoRS: Principal study design • A National cohort of women • 15-69 years old per January 1, 1995 • Followed from January 1995 through 2002 • Exposures and outcomes from national registers • Assessing the influence of OC and HT on the risk of cardiovascular diseases and cancer • Details on www.dachre.dk Danish Sex Hormone Register Study (DaHoRS): www.dachre.dk

Hormone therapy and breast cancer • Cohort: Included women 50-69: 785,397 • Exposed women (current+prev): 234,955 • Control women (never users): 550,442 • Women currently on HT with BC: 3,010 2.5 • Women previously on HT w BC: 1,957 1.7 • Women never on HT with BC: 7,864 1.4 • Included with BC: 12,831 Danish Sex Hormone Register Study (DaHoRS): www. dachre.dk