1 / 44

Breast cancer in the menopause

Breast cancer in the menopause. Anne Gompel, Geneviève Plu-Bureau and Jean-Michel Foidart. Descriptive epidemiology. Breast c ancer. 1 , 151,298 million newly diagnosed cases annually in the world ASR* = 37.4/100,000/year 410,712 death s from breast cancer

ericsmith
Download Presentation

Breast cancer in the menopause

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Breast cancerin the menopause Anne Gompel, Geneviève Plu-Bureau and Jean-Michel Foidart

  2. Descriptive epidemiology

  3. Breast cancer • 1,151,298 million newly diagnosed cases annually in the world • ASR* = 37.4/100,000/year • 410,712 deaths from breast cancer • ASR* = 13.2/100,000/year • 20–30% ofall cancers in women *ASR = age-standardized rate or age-adjusted http://www-dep.iarc.fr/

  4. < 19.5 < 25.9 < 34.2 < 52.2 < 101.1 BreastAge-standardized incidence rate per 100,000 Globocan 2002, IARC

  5. Globally, breast cancer is the most prevalent cancer in women ASR (incidence): 37.7 ASR (deaths): 13.2 New cancer cases (all ages), females 5,060,657 1151289 (22.7%) 493243 (9.7%) 472687 (9.3%) 386891 (7.6%) 330518 (6.5%) 204499 (4.0%) 198783 (3.9%) 184043 (3.6%) 146723 (2.9%) 1491972 (29.5%) http://www-dep.iarc.fr/ Globocan 2002, IARC

  6. Breast cancer incidence inFrance, Denmark and USA 500 400 300 200 100 0 Breast cancer diagnosis USA (Connecticut) Denmark France New cases/100,000/year 20 30 40 50 60 70 80 90 100 Age (years)

  7. Risk factors:individual evaluation

  8. Risk factors, RR ≥ 4 High risk Low risk Age Old age (linear) Young age Place of birth Northern Europe Asia, Africa North America 2 first-degree relatives, Yes Nomother and sister Hyperplasia with atypia Yes No

  9. Risk factors, RR 2–4 High risk Low risk Mother or sister Yes No Benign breast disease Yes Nowithout atypia Breast density > 75% Yes No Thoracic radiotherapy Yes No

  10. Risk factors, RR 1–2 High risk Low risk Socioeconomic status High Low Oophorectomy < 40 years No Yes Nulliparity Yes No Age at first full-term pregnancy (years) ≥ 30 < 30 Age at menarche (years) ≤ 11 ≥ 15 Age at menopause (years) ≥ 55 < 45 Personal history of endometrial Yes Noor ovarian cancer Obesity: postmenopausal breast cancer Obese Lean Obesity: premenopausal breast cancer Lean Obese Breast feeding (premenopausal cancer) > 12 months Exercise > 2 hours/week

  11. Debated risk factors, RR 1–2 High risk Low risk Alcohol intake High Low Smoking Yes No Fatty food Yes No

  12. Oxford meta-analysis Randomized controlled trials Hormone therapyand breast cancer risk • HERS • WHI estrogen–progestin • WHI estrogen-only

  13. Oxford meta-analysis (1997): 50,000 cases and 100,000 controls 2 0 Increased risk in current users Combined HT RR 1.53 (SE: 0.33) ≥ 5 years Estrogen HT RR 1.34 (SE: 0.09) No risk after 5 years since last use Relative risk (SE) < 1 1–4 5–9 10–14 > 14 Duration of use (years) CGHFBC. Lancet 1997

  14. Randomized trials: description WHI WHICharacteristic HERS II E + P E n 1380/1383 8506/8102 5310/5429 Mean age (years) 67 63 64 Time since 19 15 > 10menopause (years) Previous HT 24% 26% 48%

  15. Randomized, controlled trials: results HERS II WHI E + P E + P E Follow-up (years) 6.8 6.2 7.1 RR of BC (ITT) 1.27 1.26 0.80 95% CI 0.8–1.9 1.0–1.6 0.62–1.04 RR of BC (adherent) 1.49 0.67 95% CI 1.13–1.96 0.47–0.97 Hulley JAMA 1998; Chlebowski JAMA 2002, JAMA 2003; Stefanick, JAMA 2006

  16. HT and breast cancer risk: WHI effectsof previous treatment and duration 10 1 0.1 No previous treatment: no increase at 6 years 12,297 never users No prior use HR: 1.02 (0.77–1.36) 4311 prior users Prior use HR: 1.96 (1.17–3.27) Relative risk 1 2 3 4 5 6+ Duration (years) p = 0.02 JAMA, 2003; Maturitas, 2006

  17. Discussion of the RRfrom ET and CEPT in the WHI • Differences in clinical characteristics, different population • Body mass index • Different percentage of drop-out in the two arms/trials: similar patients? • Differences in clinical characteristics between CEE and placebo groups: • Less bilateral oophorectomy: 39.5% vs. 42% • More first-degree relatives with breast cancer: 12.9% vs. 11.9% • Less biopsy for benign breast disease 19.3% vs. 21.7%

  18. Other studies Estrogen alone (ET)vs. combined estrogen + progestin (CEPT)

  19. Meta-analysis Oxford 1996 Meta-analysis, UK 1.34 (SE 0.09) 1.5 (SE 0.33) Magnusson 1999 Case–control, Sweden 1.9 (1.5–2.6) 1.6 (1.4–1.9) Persson 1999 Cohort, Sweden 1.1 (0.6–1.6) 1.9 (1.3–2.8) Schairer 2000 Cohort, USA 1.1 (1.0–1.3) 1.3 (1.0–1.6) Ross 2000 Case–control, USA 11 (1.0–1.2) 1.2 (1.1–1.5) Porch 2002 Cohort, USA 1.0 (0.7–1.4) 1.4 (1.1–1.8) Chen 2002 Case–control nested, USA 1.2 (0.9–1.6) 1.5 (1.0–2.1) Weiss 2002 Case–control, USA 0.8 (0.7–1.1) 1.2 (0.9–1.5) Olsson 2003 Cohort, Sweden 0.7 (0.4–1.3) 1.2 (0.7–2.0) Li 2003 Case–control, USA 1.0 (0.8–1.3) 1.7 (1.3–2.2) Million Study 2003 Cohort, UK 1.3 (1.2–1.4) 2.0 (1.9–2.1) Bakken 2004 Cohort, Norway 1.8 (1.1–2.9) 2.5 (1.9–3.2) Stahlberg 2004 Cohort, Denmark 1.96 (1.16–3.35) 2.70 (1.96–3.73) Fournier 2005 Cohort, France 1.10 (0.8–1.6)* 1.3 (1.1–1.5) *increased by ≥ 6 years Ewertz 2005 Cohort, Denmark 1.35 (1.01–1.80)1.05 (0.62–1.79) Chen 2006 Cohort USA (ER+) 1.48 (1.05–2.07)* * ≥ 15 years MWS 2006 Cohort, UK 1.3 (1.2–1.4) 2.14 (2.04–2.24) Dinger 2006 Case–control, Germany 0.8 (0.7–1.0) 1.2 (1.0–1.3) Lyytinen 2006 Cohort, Finland 0.93 (0.80–1.04) < 5 years1.44 (1.29–1.59) ≥ 5 years Type of study, country ET CEPT

  20. Million Women Study • 1,084,110 UK women, 50–64 years old • Recruited from mammography screening • Initial questionnaire on treatment, re-evaluation after 2.8 years only in a subset of 12,221 patients • Ever users: RR: 1.43 (1.36–1.50) • Current users: RR: 1.66 (1.58–1.75) • Past-users: RR: 1.01 (0.94–1.09) • ET users: RR: 1.30 (1.21–1.40) • CEPT users: RR: 2.00 (1.88–2.12) Beral, et al. Lancet 2003

  21. Conclusions • Weak increased risk of breast cancer with CEPT after 6 years of use • No increase with ET in RCT • But the risk factors were different between the E and E + P WHI trials • Role of estrogens in breast cancer is demonstrated: • from Beatson (1887) to the STAR study • Raloxifene decreases the RR of ER+ breast cancers by an antiestrogen effect

  22. Conclusions • Increased risk with duration of HT • At least 5 years (may be more) with CEPT • Increased risk after longer time of exposure with ET

  23. HT may promote pre-existing tumors but does not induce new breast cancer • In all recent studies, former HT users have no increased risk • Breast cancer risk related to HT decreases rapidly after cessation of treatment • HT increases the incidence of preinvasive (in situ) lesions in the Million Women Study in current users

  24. The so-called ‘promoting effect of HT’ could also be related to An increase in breast densitydelaying the diagnosis

  25. Continuous vs. sequential HT

  26. Conclusions • No significant difference for case–control studies • Trend for increased risk with continuous treatment in cohort studies • In cohort studies, treatment recorded at entry • Role of the regimen? • 4/5 case–control studies are USA • 5/6 cohort studies are European

  27. Histopathological typeof breast cancer during HT Lobular carcinoma

  28. Prognosis of breast cancerin HT-treated women • Most studies, except the WHI study, show a better prognosis of breast cancer in HT-treated women (size, n, grade), and an improved survival

  29. Fatality rateafter 5 years of HT vs. no HT (2,347 deaths/12,836 breast cancers) Treatment Hazard ratio E, cyclic, combined HT 0.4 Long cyclic HT 0.3 Continuous combined HT 0.7 Tibolone 0.5 All 0.5 Lidegaard, DaHoRS (Danish Sex Hormone Register Study), Istanbul, EMAS 2006

  30. Breast cancer riskand the type of progestins

  31. Type of HT Northern Europe • Predominant E2 + NETA (78% Norway) USA • Predominant CEE + MPA France • Predominant E2 + natural progesterone (25%)

  32. Specificities of progestogens Natural Agonist Antiestrogenic activity Antiandrogenic activity Progesterone CPA DRSP progesterone Progestogens Estrogenic activity NETA LNG Androgenic activity LNG NETA MPA MPA MGA Pregnanes CMA = Chlormadinone acetate MGA = Megestrol acetate CPA = Cyproterone acetate MPA = Medroxyprogesterone acetate Norsteroids NETA = Norethisterone LNG = Levonorgestrel DRSP = Drospirenone Glucocorticoid activity Progesterone DRSP Antialdosteronic activity

  33. Million Women Study in the UK No difference between • Norsteroids (norgestrel/norethisterone acetate) • Pregnane (MPA) • Dydrogesterone • E2 oral or transdermal

  34. E3N, French cohort (Fournier, et al. Int J Cancer 2005; Breast Cancer Res Treat 2007)

  35. E3N: Results • 2354 invasive breast cancers • 80,377 postmenopausal women, 8.1-year follow-up • 70% of women had used HT, mean duration of 7.0 years (SD 5.2) • Estradiol and progesterone • RR = 1.00 (0.83–1.22), n = 129 • No increase with E2 + dydrogesterone • RR = 1.16 (0.94–1.43), n = 108 • Estradiol and synthetic progestin • RR = 1.69 (1.50–1.91), n = 527 • Estrogens alone • RR = 1.29 (1.02–1.65), n = 76 • 80% of users have a body mass index < 25

  36. E2 + P does not increasethe risk at 6 years • Is it related to the regimen: transdermal E2 + P? • Is it related to a subset of patients? • Is it related to the specific clinical attitudeamong physicians who prescribe this regimen?

  37. Conclusions • No study can conclude with a level I degree of evidence about the relative risk associated with the use of different progestins • Different estrogens carry a comparable moderate dose-dependent increased risk (one study)?

  38. Role of previousoral contraceptives Three case–control studies • Brinton 1998 (increase if oral contraceptives > 10 years and HT > 3 years) • Ursin 2002 (increase in the risk) • Norman 2003 (no increase in the risk) Unsettled issue

  39. Density • Spontaneous increased density: RR increased 3–6 times • Density during HT • Edema • Stroma (androgens?) • No increase in proliferation • Breasts with increased density : RR increased by a low sensitivity • Increase the frequency of mammograms in US

  40. And the non-hormonal factors • Body mass index • Exercise • Fat

  41. Body mass index: the risk with HTis (more) apparent in lean women • Schairer et al., 2000:BMI > 24.4 kg/m2no additional risk • Rosenberg et al., 2006: BMI > 26 kg/m2 no additional risk • MWS, 2006: inverse relationship between the risk and BMI withET and CEPT • E3N cohort, 2005: 80% of users have a BMI < 25 kg/m2

  42. Tibolone • MWS:RR = 1.45 (1.25–1.68) • Stahlberg et al.: RR = 4.27 (1.74–10.51) 5 cases • Ewertz et al.: RR = 1.51 (1.25–1.82)1 case ? Prescription bias

  43. Conclusions • Moderate increase in the risk with> 5–10 years of HT (may be in subsets of patients) • No persistent effect after cessation of use: promoter effect • Confirm the indications for HT and relative risks/benefits • Consider individual risk factors

  44. Conclusions • Promote preventive life-style strategies: food, exercise, stop smoking • Evaluate breast tolerance • Increase the frequency of screening in breasts with high mammographic density

More Related