Hormone replacement therapy and breast cancer in postmenopausal

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Hormone replacement therapy and breast cancer in postmenopausal

  1. 1. Seminário da Licenciatura em Ciências BiomédicasDiana Catarina Santos nº23271
  2. 2. Ovulation does• Degeneration of not occur women’s last oocytes • There is no corpus luteaum• There is no follicular • FSH has a drastic development development increase <[progesterone] < [estrogens] Diana Catarina Santos nº23271 07-07-2011 2
  3. 3. Hot flashes;Palpitations; Anxiety;Night sweats. Insomnia; Urogenital Mood change; infections; Cardiovascular Vagina dryness; disease (CVD); Poor memory. Loss of libido Osteoporosis; Alzheimer Diana Catarina Santos nº23271 07-07-2011 3
  4. 4. • Unopposed estrogen therapy - women with uterus – continuousET proliferation of endometrium – hyperplasia – endometrial cancer • ET (eg: CEE) must only be used by hysterectomized women • Combined hormone therapy uses a progestin plus estrogens toCHT oppose them effects (eg: CEE+MPA) • Can postmenopausal women trust in HRT? What are the risks? • To answer the questions there were performed several randomized clinical trials (RCTs) and observational studies Diana Catarina Santos nº23271 07-07-2011 4
  5. 5. Expectations Results • Climacteric symptoms relief• Climacteric symptoms relief • Osteoporosis prevention• Osteoporosis prevention • Increase of stroke risk and CVD• CVD prevention • Increase of breast cancer risk Diana Catarina Santos nº23271 07-07-2011 5
  6. 6. CHT ET RegimentDuration of use selection (e.g.: progestin type) Diana Catarina Santos nº23271 07-07-2011 6
  7. 7. Breast cancer risk for users of CHT (CEE+MPA) is higher than for placebo group RCTs Women’s Health Initiative (WHI) –> HR=1,26 Heart and Estrogen/Progestin Replacement Study (HERSII) - > HR=1,30Breast cancer risk in users of CHT is higher than in never users Observational Million Women Study (MWS) Studies Collaborative Group Study –Reanalyzes of 51 studiesShah Nirav, et al -> estimated the risk of 1,39 fold increase for observational studies Diana Catarina Santos nº23271 07-07-2011 7
  8. 8. Breast cancer risk for users of CHT (CEE+MPA) is increased in time against placebo group RCTs 1 year – 8 more cases per 10 000 against placebo group 5,2 years – there are expected 46 more cases per 10 000 than in placebo groupBreast cancer risk for users also appeared to depend on time Observational MWS -> RR=1,63 (<5 years) and 2,21 (>5 years) Studies Diana Catarina Santos nº23271 07-07-2011 8
  9. 9.  Observational data: • Studies show that women using CHT sequentially (<15 days/mo) present lower risk against continuous users; • Others found an increased risk of 30% against non users for both strategies of use; After 5 years of discontinuing the hormonal therapy use, past and current users have the same relative risk. Diana Catarina Santos nº23271 07-07-2011 9
  10. 10. Breast cancer risk for users of ET (e.g.: CEE alone) presented no raise in the risk of breast cancer compared with placebo RCTs WHI –>HR=0,77 (23% decrease) Most of studies show a higher breast cancer risk in users compared with never users Observational MWS -> RR=1,30 Studies Collaborative Group Study -> RR=1,34 E3N cohort study-> RR=1,29Shah Nirav, et al -> estimated the risk of 1,16 fold increase as a review of observational studies Diana Catarina Santos nº23271 07-07-2011 10
  11. 11.  Most observational studies found that: • Breast cancer increases with the course of time for current users; • Breast cancer has a higher risk for past users; • After discontinuation of ET, breast cancer risk decreases; • Breast cancer risk increase for ET is smaller than the risk that these studies presented for CHT, according with time. Other observational studies presented similar results to WHI studies. Diana Catarina Santos nº23271 07-07-2011 11
  12. 12. Invasive lobular carcinoma (ILC) is more difficult to detect by mammography but have better prognosis than invasive ductal carcinoma (IDC) [Christopher I., et al]CHT• CHT are associated with 2.0 – 3.9 fold increased risk of ILC, but generally not with IDC.ET• Both ILC and IDC risks remain unaltered, even after prolonged use of 25 years. Diana Catarina Santos nº23271 07-07-2011 12
  13. 13.  Female primates – Macaca fascicularis • Breast epithelial proliferation increases – CEE+MPA high breast cancer risk • Breast epithelial proliferation increases – CEE alone high breast cancer risk • Breast epithelial proliferation is not altered Tibolone with this therapy • Significant increase for both ductal and E2+MPA lobular epithelial proliferation • Breast epithelial proliferation (ductal and E2+P4 lobular) remains unaltered Diana Catarina Santos nº23271 07-07-2011 13
  14. 14. CHTleads ET Abnormal Mammograms are to: mammograms not compromised Diagnostic delay 6,9% raise in breast cancer 2,9% raise in density breast cancer Worse tumors and density increased mortality Diana Catarina Santos nº23271 07-07-2011 14
  15. 15.  NHS (Nurses Health Study) and the majority of observational studies showed a decrease in the risk of death for HRT users compared with never users; These results are expected because: • Women taking HRT are more under medical supervision; • Breast cancer can be detected and treated earlier. Although observational studies have a lot of limitations: • They combined CHT and ET results; • Selection criteria is varied; • Difference in women’s age (WHI comprised older women) Diana Catarina Santos nº23271 07-07-2011 15
  16. 16.  Women taking CEE+MPA (CHT) have a high breast cancer risk, compared with women taking other HRT or compared with non-users; The risk is more apparent with continuous CHT and for ILC; Although the differences between RCTs and observational studies ET is associated with less risk than CHT is; Replacing MPA for other progestin may provide more safety for users; Mortality is still a controversial.HRT is associated with a small but significant increase in breast cancer risk Diana Catarina Santos nº23271 07-07-2011 16
  17. 17. Benefits RisksQuality of life Breast cancer increaseOsteoporosis prevention Stroke / CVD CVD Diagnostic prevention delay/Mortality Diana Catarina Santos nº23271 07-07-2011 17
  18. 18. Diana Catarina Santos nº23271 07-07-2011 18

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