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POSTMENOPOZAL HORMON TEDAVİSİ VE KANSER Prof. Dr. Mithat Erenus Marmara Üniversitesi Tıp Fakültesi Kadın Hastalıkları Anabilim Dalı.

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1 POSTMENOPOZAL HORMON TEDAVİSİ VE KANSER Prof. Dr. Mithat Erenus Marmara Üniversitesi Tıp Fakültesi Kadın Hastalıkları Anabilim Dalı

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3 Endometrial Cancer  41,200 new cases of cancer of the uterine corpus expected in 2006 –Most of these are of the endometrium (95%) which is the most common reproductive organ cancer in the US –Accounts for 6% of all cancers in women in the US  Roughly 7350 deaths from endometrial cancer expected in 2006 –Represents 3% of cancer deaths in US women  Major risk factor is high cumulative exposure to estrogen, e.g., estrogen therapy without adequate progestin, obesity American Cancer Society. Cancer Facts and Figures Available at:

4 IN 1975 ZİEHL AND SMİTH İN TWO CASE CONTROL STUDİES REPORTED AN ASSOCİATON BETWEEN ERT AND AN İNCREASED RİSK OF ENDOMETRİAL CARCİNOMA

5 RR95%CI# of studies CEE dose > Duration (yrs) < > Regimen Cycic Continuous Relative Risk from Meta-Analysis: Postmenopausal Estrogen therapy and Endometrial Cancer

6 No Increased Risk of Endometrial Cancer With E+P Regimens *Type of HT last used, self-reported at recruitment. Million Women Study Collaborators. Lancet. 2005;365: HT Use* Mean Yrs of Use Cases per population Relative Risk (95% CI) Never--763/395, (referent) E+P, daily5.073/69, ( ) E+P, cyclic5.1242/145, ( ) E only4.633/14, ( ) Tibolone5.286/28, ( )

7 WHI Results: Hazard Ratio for Endometrial Cancer with E+P Incidence rate of endometrial cancer for the total study population was 62 cases per 100,000 person-years. Anderson GL, et al. JAMA. 2003;290: Hazard Ratio E+P % nominal CI 95% adjusted CI Placebo

8 HT and Risk of Endometrial Cancer: Summary  Unopposed estrogen increases endometrial cancer risk in postmenopausal women with an intact uterus  Estrogen in combination with a progestin has not been associated with increased endometrial cancer risk and some observational studies have noted a potential protective effect. –Progestin use must be for >10 days per month  WHI did not find a significant reduction in endometrial cancer risk in E+P group –Observational studies have shown trends in endometrial cancer incidence in women taking E+P, implying variable effects upon endometrial cancer risk. –Possibly related to BMI; progestin provides greatest protection in obese women; on average, subjects in E+P trial were overweight but not obese

9 Colorectal Cancer  A woman’s lifetime risk of developing colorectal cancer is 5.5% –3rd most common cancer and 3rd most common cause of cancer death in US women  2006 estimates: 74,746 new cases and 27,300 deaths from colorectal cancer in US women –91% of new cases and 94% of colorectal cancer deaths occur after age 50 years  10-year survival for colorectal cancer is 57% American Cancer Society. Cancer Facts and Figures Available at: Accessed 6/5/06.

10 WHI E+P Trial: Risk of Colorectal Cancer HR = % nCI = 0.38– % aCI = 0.33–0.94 Placebo E+P Kaplan-Meier Estimate Chlebowski RT, et al. N Engl J Med. 2004;350:

11 WHI E-Alone Trial: Risk of Colorectal Cancer HR = % nCI = 0.75– % aCI = 0.63–1.86 Kaplan-Meier Estimate Women’s Health Initiative Steering Committee. JAMA. 2004;291: Placebo E Alone

12 WHI E+P Trial: What Do the Results Mean for Absolute Risk of Colorectal Cancer?  A 50-year-old woman in the US has an approximate 0.5% chance of developing colorectal cancer by age 60 years 1 –This translates to an absolute risk of 5.0 cases per 1000 women  HR for colorectal cancer = 0.56 after 5.6 years of E+P use in the WHI (a 44% reduction in risk) 2 –This translates into an absolute risk of 2.8 cases per 1000 E+P users HR = hazard ratio. 1 Available at: Accessed 6/5/ Chlebowski RT, et al. N Engl J Med. 2004;350:

13 Reduced Risk of Death From Colorectal Cancer in Ever-Users of HT Calle et al, 1995 Sturgeon et al, 1995 Persson et al, 1996 Meta-analysis: Nanda et al, 1999 Relative Risk (95% CI)

14 HT and Colorectal Cancer Risk: Summary  WHI E+P Trial –Colorectal cancer reduced with E+P vs placebo –Results consistent with earlier studies showing protective effect –Greater proportion of advanced cancers in E+P users requires further study –No difference in mortality, E+P vs placebo  WHI E-Alone Trial –No significant difference in colorectal cancer rates in E-alone vs placebo

15 Ovarian Cancer  20,180 new cases expected in the US in 2006 Accounts for 3% of all cancers in women –2nd most common gynecologic cancer  15,310 deaths from ovarian cancer expected in 2006 –Causes more deaths than cervical and uterine cancer combined; ranks 5 th in cancer deaths among women.  Risk increases with age; peaks in late 70s –~2/3 of diagnosed women are over age 50  Mutations of BRCA genes increase a woman’s lifetime risk to 26% (BRCA1) and 10% (BRCA2)  Use of oral contraceptives reduces risk –primarily related to pre-menopausal use American Cancer Society. Cancer Facts and Figures Available at: Accessed 6/5/06. Nelson HD, et al. Ann Intern Med. 2005;143: La Veccia C. Eur J Cancer Prev. 2006;15:117-24

16 WHI E+P Trial: Effect of HT on Risk of Invasive Ovarian Cancer Incidence rate of invasive ovarian cancer for the total study population was 34 cases per 100,000 person-years. Anderson GL, et al. JAMA. 2003;290: Hazard Ratio % nCI 95% aCI E+P Placebo

17 Meta-Analyses Evaluating HT Use and Risk of Ovarian Cancer Relative Risk (95% CI) Garg et al, 1998 Coughlin et al, 2000 Garg PP, et al. Obstet Gynecol. 1998;92: Coughlin SS, et al. J Clin Epidemiol. 2000;53:

18 HT Does Not Increase the Risk of Ovarian Cancer in BRCA1 and BRCA2 Mutation Carriers Group Adjusted Odds Ratio P value Never Users1.00 [95% CI ( referent )] Ever Users0.93 [95% CI ( )] 0.79 BRCA1 Ever1.13 [95% CI ( )] 0.67 BRCA2 Ever1.08 [95% CI ( )] 0.87 Kotsopoulos J et al. Gynecol Oncol. 2006;100:83-8

19 HT and Ovarian Cancer Risk: Summary  Research findings are inconsistent for post- menopausal use. –If increased risk exists, it is small and difficult to demonstrate from study to study  Possible weak association with long-term (>10 years) use of unopposed E, but data are inconclusive  Overall, data are not sufficient for clinical recommendations 1 1 U.S. Preventive Services Task Force. Ann Intern Med May 17;142(10):

20 Breast Cancer  Among women in the US, breast cancer is the most common diagnosed non-skin cancer and the 2 nd leading cause of cancer-related deaths ,920 40,970  National Cancer Institute 2006 estimates: 212,920 new cases of breast cancer and 40,970 deaths  A woman’s risk of developing breast cancer in her life time is currently estimated to be 1 in 7.56 (1 in 8) irrespective of HT use National Cancer Institute:

21 Meme Kanseri Risk Faktörleri (RR>4) Yaş BRCA1 ve BRCA2 mutasyonları Postmenopozal dens (yoğun) meme

22 Risk of Breast Cancer Changes With a Woman’s Age American Cancer Society, Surveillance Research, Breast Cancer Facts and Figures 2001–2002. Available at: http//www.cancer.org/downloads/STT/BrCaFF2001.pdf. Age (years) Probability of Developing Breast Cancer Within 10 Years % (1 in 2044) % (1 in 249) % (1 in 67) % (1 in 36) % (1 in 29) % (1 in 24)

23 Meme Kanseri Risk Faktörleri RR:2.1-4  ↑ postmenopozal kemik yoğunluğu,  meme biyopsisinde atipik hiperplazi  Birinci derece akrabada meme kanseri öyküsü

24 Meme Kanseri Risk Faktörleri RR:  ilk gebelik>30  menarş <12 yaşından,  menopoz yaşı > 55,  nulliparite,  hiç emzirmemiş olmak,  postmenopozal obezite  göğüs bölgesine yüksek doz radyasyon,  günlük alkol alımı  önceden tanı almış endometrium, over veya kolon kanseri

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26 Absolute Risk of Breast Cancer in the General Population  Each 50-year-old woman has approximately a 2.8% chance of developing breast cancer by age 60 years  This translates to an absolute risk of 2.8 per 100 women All Women Aged 50 Years in the General Population— Risk for Breast Cancer by Age 60 Years In 100 women, 2.8 are at risk American Cancer Society, Surveillance Research, Breast Cancer Facts and Figures 2001–2002. Available at: http//www.cancer.org/downloads/STT/BrCaFF2001.pdf.

27 Absolute Risk of Breast Cancer After 5 Years of HT  WHI results indicate an HR for breast cancer of 1.24 after 5 years of HT use (a 24% increase in risk) 1  This translates into an absolute risk of 3.5 per 100 users Risk of Breast Cancer by Age 60 Years After 5 Years of HT Use (Assuming a 24% Increase in Risk) 1 Chlebowski RT, et al. JAMA. 2003;289: of 100 women who are HT users are at risk (<1 additional woman over baseline risk)

28 Review of Observational Studies Published From *Percents do not total 100% because 1 study did not report confidence intervals; NS = not significant. Bush TL, et al. Obstet Gynecol. 2001;98: E Alone (n = 45)*E+P (n = 20)

29 0,50,51,01,02,02,0 Yaşamın Bir Döneminde HRT Kullanılmış Olması ve Meme Kanseri Riski Rölatif Risk (%95 GA) Armstrong ve ark, 1988 Dupont ve ark, 1991* Steinberg ve ark, 1991 Sillero-Arenas ve ark, 1992 Colditz ve ark, 1993 Grady ve ark, 1992 *0,425 ya da daha az konjüge estrojen almış olan kadınlar. Meta Analizler

30 Ortaklaşa Grup Analiz Tekrarı  Meme kanseri olan kadın  Meme kanseri olmayan kadın  51 çalışma, 21 ülke  Ana analizin temel aldığı veriler: –Menopoz çağında olduğu bilinen postmenopozal kadın; (%33) HRT kullanıcısı – vaka / kontrol Collaborative Group on Hormonal Factors in Breast Cancer. Lancet. 1997;350:

31 HRT ile Meme Kanseri Riski *P < 0,01. Collaborative Group on Hormonal Factors in Breast Cancer. Lancet. 1997;350: Herhangi bir zamanda kullanmış Halen Kullanmakta Halen Kullanan >5 yıl Geçmişte kullanmış RR 1.14*1.21* HRT Kullanımı

32 Ortaklaşa Analizin Tekrarı: Klinik Sonuçlar *Her kullanım yılı ile riskte meydana gelen %2,3 artışı temel almaktadır. Collaborative Group on Hormonal Factors in Breast Cancer. Lancet. 1997;350: yıl 10 yıl 15 yıl Tahmin Edilen Fazla Meme Kanseri Sayısı/1000 Kadın* 2612 HRT Süresi Etkilenen Kullanıcıların Oranı 0,20,20,60,61,21,20,20,20,60,61,21,2

33  Over 27,000 postmenopausal women were randomized between 1993 and 1998  Age at baseline ranged from 50 yrs–79 yrs –Mean age, ~63 yrs  Primary outcomes –CHD (nonfatal MI, CHD death) –Invasive breast cancer  Approximately 8 yrs of follow-up planned CHD = coronary heart disease; MI = myocardial infarction. Writing Group for the Women’s Health Initiative Investigators. JAMA. 2002;288: Women's Health Initiative Steering Committee. JAMA. 2004;291: Women’s Health Initiative (WHI) Clinical Trials of HT

34 WHI E and E+P: Baseline Characteristics *Values are means (SD). † Overall incidence of prior cardiovascular disease = 7.7%. CABG = coronary artery bypass graft; PTCA = percutaneous transluminal coronary angioplasty. 1 Women's Health Initiative Steering Committee. JAMA. 2004;291: Writing Group for the Women’s Health Initiative Investigators. JAMA. 2002;288: Characteristic E alone 1 n = 5310 E+P 2 n = 8506 Age at screening, years*63.6 (7.3)63.2 (7.1) Prior hormone use, % Body mass index, kg/m 2 *30.1 (6.1)28.5 (5.8) Never smokers, % Diabetes, % Hypertension, % Statin use at baseline, % History of MI, % † History of CABG/PTCA, % † Family history of breast cancer, %

35 Risk of Invasive Breast Cancer in the WHI HT Trials HR = hazard ratio; nCI = nominal confidence interval; aCI = adjusted confidence interval. 1 Chlebowski RT, et al. JAMA. 2003;289: Women's Health Initiative Steering Committee. JAMA. 2004;291: Hazard Ratio Placebo E+P 1 E alone 2 HR % nCI 95% aCI

36 WHI E+P Trial: No Effect of E+P on Risk of In Situ Breast Cancer Cumulative Proportion Time (years) Chlebowski RT, et al. JAMA. 2003;289: Placebo CEE + MPA HR = % CI = 0.77–1.82

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38 WHI E+P Trial: Risk of Invasive Breast Cancer in Women With and Without Prior HT Use Hazard Ratio (95% CI) Prior HT Use None <5 Years  5 Years Overall % of WHI Population Chlebowski RT, et al. JAMA. 2003;289:

39 Breast Cancer Risk Among E+P Users in Randomized Controlled Trials Chlebowski RT, et al. JAMA. 2003;289: Hulley S, et al. JAMA. 2002;288: WHI HERS HERS II Relative Hazard (95% CI)

40 Million Women Study  Investigators recruited 1,084,110 women in the UK, aged years, between 1996 and 2001  Questionnaire about lifestyle, SES, medical history, and HT use sent in conjunction with invitation from NHSBSP for screening mammography  Mean age, 56 years; 9364 cases of invasive breast cancer and 637 breast cancer deaths identified during follow-up  Analysis of HT and breast cancer risk restricted to postmenopausal women (n = 828,923)  50% were ever-users of HT; 33% were current users; mean duration of use was 5.8 years SES = socioeconomic status; NHSBSP = National Health Service Breast Screening Programme. Million Women Study Collaborators. Lancet. 2003;362:

41 Incident Invasive Breast Cancer in Relation to Recency and Type of HT Used FCI = floated CI. *Relative to never-users, stratified by age, time since menopause, parity and age at first birth, family history of breast cancer, body mass index, region, and deprivation index. Million Women Study Collaborators. Lancet. 2003;362: HT Use at Baseline Relative Risk (95% FCI)* All never-users1.00 (0.96–1.04) All past users1.01 (0.95–1.08) Current users E-only1.30 (1.22–1.38) E+P2.00 (1.91–2.09) Tibolone1.45 (1.25–1.67) Other/unknown types1.44 (1.17–1.76)

42 Incident Invasive Breast Cancer in Relation to Recency and Type of HT Used FCI = floated CI. *Relative to never-users, stratified by age, time since menopause, parity and age at first birth, family history of breast cancer, BMI, region, and deprivation index. Million Women Study Collaborators. Lancet. 2003;362: Total Duration of HT Use by Type of HT Used at Baseline Relative Risk (95% FCI)* Never-users of HT –1.04 Past users of HT <1 year0.94 (0.84–1.05) 1–4 years1.01 (0.92–1.12) 5–9 years1.14 (1.00–1.30) ≥10 years1.05 (0.84–1.30) Current users of E alone <1 year0.81 (0.55–1.20) 1–4 years1.25 (1.10–1.41) 5–9 years1.32 (1.20–1.46) ≥10 years1.37 (1.22–1.54) Current users of E+P <1 year1.45 (1.19–1.78) 1–4 years1.74 (1.60–1.89) 5–9 years2.17 (2.03–2.33) ≥10 years2.31 (2.08–2.56)

43 Incident Invasive Breast Cancer in Current Users of E-only Preparations Dotted line represents overall relative risk for current users of estrogen-only preparations compared with never-users at baseline. *Relative to never-users, stratified by age, time since menopause, parity and age at first birth, family history of breast cancer, BMI, region, and deprivation index. Million Women Study Collaborators. Lancet. 2003;362: E-only Formulation Relative Risk (95% CI)* All E-only formulations1.30 (1.21–1.40) By constituent and dose All equine estrogen1.29 (1.16–1.43) ≤0.625 mg1.25 (1.11–1.41) >0.625 mg1.36 (1.14–1.61) All 17  -estradiol 1.24 (1.12–1.37) ≤1 mg1.25 (1.12–1.40) >1 mg1.19 (0.89–1.58) By formulation Oral1.32 (1.21–1.45) Transdermal1.24 (1.11–1.39) Implanted1.65 (1.26–2.16)

44 Incident Invasive Breast Cancer in Current Users of E+P Preparations Dotted line represents overall relative risk for current users of estrogen-progestin preparations compared with never-users at baseline. *Relative to never-users, stratified by age, time since menopause, parity and age at first birth, family history of breast cancer, BMI, region, and deprivation index. Million Women Study Collaborators. Lancet. 2003;362: Duration of Use, <5 Years E+P Formulation Relative Risk (95% CI)* All E+P formulations1.70 (1.56–1.86) By progestin constituent Medroxyprogesterone acetate1.60 (1.33–1.93) Norethisterone1.53 (1.35–1.75) Norgestrel/levonorgestrel1.97 (1.74–2.33) By type of regimen Sequential1.77 (1.59–1.97) Continuous1.57 (1.37–1.79)

45 Breast Cancer Mortality Rates in the Million Women Study Million Women Study Collaborators. Lancet. 2003;362: HT Use at Baseline Breast Cancer Deaths/Breast Cancer Cases Mortality Rate (%) Never-users238/ Current users191/ Past users88/ Total breast cancer deaths517/

46 E+P (n = 199) Placebo (n = 150)P-Value Tumor size, mean ± SD (cm)1.7 ± ± Positive lymph nodes, % Morphology, grade, % Well differentiated Moderately differentiated Poorly differentiated/anaplastic ER status, % Positive PR status, % Positive Deaths attributed to breast cancer, n (%)4 (2.0)4 (2.7)— ER = estrogen receptor; PR = progesterone receptor. Chlebowski RT, et al. JAMA. 2003;289: WHI E+P Trial: Characteristics of Invasive Breast Cancers

47 ERT/HRT Kullananlarda Meme Kanseri Nedeniyle Mortalite Sonuçları Tutarlılık Göstermektedir Mortaliteye İlişkin Rölatif Risk (%95 GA) Hunt ve ark, 1990 Henderson ve ark, 1991 Willis ve ark, 1996 Grodstein ve ark, 1997 Kullanmakta olan Geçmişte kullanmış olan Sellers ve ark, 1997 Rodriguez ve ark, 2001 Kullanmakta olan Geçmişte kullanmış olan

48 MEME KANSERİ-PROBLEM Östrojene maruz kalmak meme kanseri için risk faktörü müdür? Östrojenler yeni meme kanserine neden olur mu? Progesteron eklenmesi meme kanseri riskini etkiler mi? HT ile gözlenen meme tümörleri daha az agresif mi?

49 Hormonal risk factors for breast cancer Risk factorHigh risk groupLow risk groupRR Age at menarche< 12 years> 14 years1.5 Age at menopause >55 years< 45 years2.0 Oophorectomy-< 35 years3.0 Serum E 2 HighLow3.0 BMI> 30<232.0 Bone densityHighLow3.0 Breast densityHighLow6.0 Modified after Clemons and Goss (2001)

50 Hormone dependent carcinogenesis DNA Tumor initiation E2E2 mutagens direct DNA damage Normal cellCancer cell A

51 Hormone dependent carcinogenesis DNA Tumor initiation E2E2 mitosis Accumulation of replication damage Normal cell Cancer cell B

52 Hormone dependent carcinogenesis DNA* Tumor growth acceleration E2E2 mitosis proliferation Occult tumor Clinical tumor DNA* C

53 MEME KANSERİ GENETİK MUTASYON Biyolojik kanıtlar meme kanserinin,çok sayıda genetik mutasyonlar sonucunda meme hücresinin internal sinyal sistemindeki bozulma sonucu oluştuğunu göstermektedir. Wren BG Menopause , 2007

54 Meme kanseri Mutasyon Meme hücre mutasyonları, büyük oranda hızlı kök hücre bölünmesinin yaşandığı adölesan meme gelişimi döneminde gözlenmektedir. Wren BG Menopause , 2007

55 Meme kanseri Mutasyon Eğer aberran mutasyonlar adölesan meme oluşumu sırasında görülmezse daha ileri yıllarda meme kanseri görülme olasılığı çok nadirdir. Wren BG Menopause , 2007

56 MEME KANSERİ HORMONLAR Endojen veya exojen hormonlar malignant mutasyonları indüklemezler.EPT kök hücre replikasyonunu arttırır. Önceden genetik yapı değişikliklerinin olduğu meme hücrelerinde, hormonlar mitozu arttırabilir.Böylece spontan mutasyonları arttırarak kanser riski oluşturabilir. Wren BG Menopause , 2007

57 MEME KANSERİ HORMONLAR Adölesan meme oluşumu sırasında genetik olarak değişime uğramış kök hücre kolonileri oluşmamışsa,daha sonradan uzun süre sex hormonlarına maruz kalmak meme kanseri riskini arttırmayacaktır. Wren BG Menopause , 2007

58 MEME KANSERİ HORMONLAR Eğer aberran hücre kolonileri adelosan dönemde oluşmuşsa,histolojik olarak benign hipertrofiden,atipik hipertrofi,carcinoma insitu, mikroinvazyon,invazif kanser ve metastas dönüşümü,genetik mutasyondaki artışa bağlı görülebilecektir. Wren BG Menopause , 2007

59 BİR KARŞIT GÖRÜŞ ÖSTROJEN PROGESTERON TEDAVİSİ ÖNCEDEN VAR OLAN MEME TÜMÖRÜNÜN ERKEN TANISI VE DAHA İYİ FARKLILAŞMASINI SAĞLAYARAK BELKİ DE OLUMLU BİR SONUÇ YARATMAKTADIR LEON SPEROFF Menopause 394,2008

60 MEME KANSERİ PR-A PR-A + Meme hücrelerinde agresif büyüme gözlenir.progesterone yokluğunda PR-A isoformları dominanttır.PR-A fazlalığı ile meme kanseri ilişkilidir.ER+ tümörler PR-A isoformlarından zengindir.EPT ER+ tümörlerde PR-B nin olumlu etkilerini promote etmesi mümkündür. LEON SPEROFF Menopause 394,2008

61 VAR OLAN TÜMÖRLERDE HORMONAL ETKİ GÖZLEMLERİ EPİDEMİYOLOJİK ÇALIŞMALARDA HORMON TEDAVİSİ SONRASINDA HEMEN RİSK ARTIŞI EP İLE İLİŞKİLİ KANSER ER+ DÜŞÜK GRADE DÜŞÜK EVREDE TÜMÖRLER MEME KANSERİ PREVALANSINDAKİ YENİ DÜŞME POSTMENOPOZAL EPT KULLANIMINDAKİ DÜŞME İLE EŞ ZAMANLI. LEON SPEROFF Menopause 394,2008

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63 PROGESTİNİN VAR OLAN TÜMÖRLERE OLUMLU ETKİSİNİN KANITLARI EPT tedavisini takiben ER+ tümörlerin görülmesi. Sürekli tedavide daha sık E ile up regüle genler EPT ile down regüle olur. EPT ile aktive olan genler DNA tamirinde hücre siklus regulasyonunda kullanılır. Progestinler meme dokusu PRA reseptörlerni azaltır.PRA/PRB oranını değiştirerek daha iyi farklılaşmayı sağlar. Meme kanseri mortalitesinde EPT kullanımı ile azalma rapor edilmiştir.

64 BİR KARŞIT GÖRÜŞ Postmenopozal hormon tedavisi yeni meme tümörlerinin gelişimi ni indüklemek yerine var olan tümörlere hormonal cevabı yansıtır. EPT daha iyi farklılaşma ve erken tanıya sebep olarak belkide olumlu bir sonuç yaratmaktadır. LEON SPEROFF Menopause 394,2008

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67 HT & Breast Cancer Breast cancer risk increases with EPT use beyond 3-5 y Increased absolute risk of EPT in WHI viewed as “rare” (4-6 additional cases/ 10,000 women/y of EPT for ≥ 5 y) Unclear whether EPT risk differs between continuous and sequential progestogen use WHI ET trial showed no increased risk after 7.1 y (6 fewer cases/10,000 women/y of ET use; not statistically significant) ET for <5 y has little impact on breast cancer risk Copyright 2008 NAMS position statement. Menopause (cont’d)

68 HT & Breast Cancer (cont’d) EPT and, to a lesser extent, ET, increase breast cell proliferation, breast pain, and mammographic density EPT may impede diagnostic interpretation of mammograms Whether to use HT when history of breast cancer is unresolved (limited epidemiologic evidence mixed; no completed long-term RCTs) Copyright 2008 NAMS position statement. Menopause 2008.

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70 Selim Meme Kanseri Hikayesi Olan Kadınlarda HRT Kullanımı ve Meme Kanseri PH’si ya da KFA’sı olmayan HRT kullanıcıları (referent) Rölatif Risk (%95 GA) 0,50,51,01,05,05,02,02,0 PH = proliferatif hastalık. KFA = kompleks fibroadenom. Dupont WD ve ark. Cancer. 1999;85: HRT kullanıcıları Kullanmayanlar Tüm PH’ler HRT kullanıcıları Kullanmayanlar Atipisiz PH HRT kullanıcıları Kullanmayanlar Atipik hiperplazi

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73 MEME CA VE HT KLİNİK UYGULAMA Postmenopozal kadınlarda HT başlanması veya tedaviye devam kararı verilmesi sırasında, kadınların kombine HT nin meme kanserini arttırmada küçük ama gerçek bir riski olduğunu bilmesi gerekmektedir.ET ile bu risk daha azdır (beklide hiç yoktur)Bu riskin meme kanserini arttıran diğer risk faktörleri ile karşılaştırılması yararlı olur.

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76 BPO = Bilateral prophylactic oophorectomy Rebbeck TR, et al. J Clin Oncol. 2005;23(31): HRT in Women with BRCA1 & 2 After Prophylactic BPO RR BPO, no HRT0.38 (0.09–1.59) BPO, any HRT0.37 (0.14–0.96) BPO, E (0.12–1.61) BPO, E+P0.43 (0.07–2.68)

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80 Body Mass Index Affects Relationship Between HT and Endometrial Cancer BMI = body mass index (kg/m 2 ). Million Women Study Collaborators. Lancet. 2005;365: Incidence of endometrial cancer per 1000 women over 5 years Normal weight (BMI <25 kg/m 2 ) Continuous combined Cyclic combined Tibolone Never HRT Overweight (BMI 25–29) Obese (BMI ≥30)

81 WHI E+P Trial: Mammography Results % Abnormal* EPlaceboE+PPlacebo Year † ‡ Overall † ‡ In the US, 11% of screening mammograms have abnormal findings *Abnormal mammograms included those that were associated with recommendations for short-term follow-up, showed a suspicious abnormality, or were highly suggestive of malignancy † P <.001 vs E; ‡ P <.001 vs E+P. Chlebowski RT, et al. JAMA. 2003;289: Stefanick ML, et al. JAMA. 2006;295:

82 HRT’den Kaynaklanan Atfedilebilir Meme Kanseri Riski 50 yaşında, 10 yıl takip edilmiş, HRT almamış 50 yaşında, 10 yıl takip edilmiş, HRT almış Kanser Gelişmeme İhtimali %97,5 %96,8 Santen RJ, Petroni GR. J Clin Endocrinol Metab. 1999;84:

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"POSTMENOPOZAL HORMON TEDAVİSİ VE KANSER Prof. Dr. Mithat Erenus Marmara Üniversitesi Tıp Fakültesi Kadın Hastalıkları Anabilim Dalı." indir ppt

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