Breast cancer in Young women: Fer3lity preserva3on

Transcription

1 Breast cancer in Young women: Fer3lity preserva3on Nikos F. Vlahos MD. PhD. FACOG Associate Professor of Gynecology and Obstetrics University of Athens School of Medicine Johns Hopkins Hospital School of Medicine 1

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3 EsGmated New Cancer Cases for Leading Cancer Sites 3

4 EsGmated New Cancer Cases for Leading Cancer Sites 4

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6 Breast cancer age distribugon. 6

7 Women with genegc risk for breast cancer Approximately 20%-25% of breast cancer pagents have a posigve family history 5%-10% of breast cancer cases demonstrate an autosomal dominant inheritance. LifeGme breast cancer risk ranges from 65% to 81% for BRCA1 mutagon carriers and 45% to 85% for BRCA2 carriers. Moderate risk genes including homozygous ataxia-telangiectasia (ATM) mutagons, somagc mutagons in tumor suppressor gene CHEK2, and BRCA1 and BRCA2 modifier genes BRIP1 and PALB2 confer a 20%-40% lifegme risk of breast cancer. 7

8 Five-year RelaGve Survival Rates*(%) for Selected Cancers among Individuals Aged 15 and Older in Select Countries 8

9 Ovarian reserve: Απόθεμα ωαρίων 9

10 Impact of age on ferglity 10

11 Breast cancer treatment IniGal diagnosis Surgery Chemotherapy RadiaGon therapy 11

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15 Chemotherapy and ReproducGve FuncGon High risk of prolonged amenorrhea in women Cyclophosphamide Ifosphamide Melphalan Busulfan Nitrogen mustard Procarbazine Chlorambucil Intermediate risk CisplaGn with low cumulagve dose CarboplaGn with low cumulagve dose Adriamycin Low risk Bleomycin AcGnomycin D VincrisGne Methotrexate Rodriguez-Wallberg and Oktay, J Ped Hematol Oncol, 2010, 15

16 RadiaGon and ReproducGve FuncGon High risk of amenorrhea in women Pelvic or whole abdominal radiagon dose 6 Gy in adult women Pelvic or whole abdominal radiagon dose 10 Gy in post-pubertal girls Pelvic radiagon or whole abdominal dose 15 Gy in pre-pubertal girls Intermediate risk TesGcular radiagon dose 1-6 Gy from scarered pelvic or abdominal radiagon Pelvic or whole abdominal radiagon dose 5-10 Gy in post-pubertal girls Pelvic or whole abdominal radiagon dose Gy in pre-pubertal girls Craniospinal radiotherapy dose 25 Gy Rodriguez-Wallberg and Oktay, J Ped Hematol Oncol, 2010, 16

17 FerGlity preservagon in pagents with cancer. OpGons for management FerGlity preserving surgery ProtecGon from radiagon therapy ProtecGon from chemotherapy TransposiGon of the ovaries Shield during treatment GnRH analogs Oral ContracepGves 17

18 FerGlity preservagon in pagents with breast cancer. OpGons for management ChemoprotecGon FerGlity preservagon Assisted reproducgve technologies 18

19 Chemoprophylaxis from radiagon or chemotherapy Human ReproducGon Update, Vol.14, No.6 pp ,

20 Human ReproducGon Update, Vol.14, No.6 pp ,

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22 FerGlity preservagon in pagents with cancer. OpGons for management ChemoprotecGon FerGlity preservagon Assisted reproducgve technologies 22

23 FerGlity preservagon in pagents with cancer. OpGons for management Assisted reproducgve technologies Ovarian sgmulagon prior to chemo Ovarian cryopreservagon Oocyte donagon Oocyte or embryo freezing 23

24 Embryo/Oocyte cryopreservagon for cancer pagents Embryo and or oocyte cryopreservagon represent the most efficacious method for ferglity preservagon in women with breast cancer But Requires ovarian sgmulagon to harvest oocytes, which may delay chemotherapy Associated with high E2 levels Sperm is also required!!!!! 24

25 Problem #1 Offering ferglity preservagon opgons to a breast cancer pagent may delay chemotherapy 25

26 Ovarian sgmulagon protocol (GnRH antagonists) Day 9 of Cycle Day of hcg (Day 13) Egg collection ( Day 15) GnRH Antagonist Ovarian stimulation with gonadotropins menses Day 3 of cycle Duration of stimulation: days

27 Time from diagnosis to egg harvesgng Oocyte harvesgng Diagnosis of Cancer Ovarian sgmulagon Day 1 Day 28 Day15 28 to 45 days 27

28 Time from diagnosis to chemotherapy 28

29 Time from diagnosis to chemotherapy Results Mean TTC was 12.0 weeks overall and increased over the study period. The largest effects were associated with therapeugc factors, immediate post-mastectomy reconstrucgon (2.7 weeks; P <.001), re-excision (2.1 weeks; P <.001), and use of the 21-gene RTPCR assay (2.2 weeks; P <.001). 29

30 Problem #2 Ovarian sgmulagon may increase estradiol levels 30

31 FerGl Steril 2012;98:

32 FerGl Steril 2012;98:

33 FerGl Steril 2012;98:

34 CryopreservaGon of embryos and oocytes 34

35 Oocyte CryopreservaGon 35

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37 Evidence indicates that oocyte vitrifica3on and warming should no longer be considered experimental. This document replaces the document last published in 2008 Gtled, Ovarian Tissue and Oocyte CryopreservaGon, FerGl Steril 2008;90:S FerGl Steril 2013;99:

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42 FerGlizaGon, in-vitro embryo development, and pregnancy rates using vitrified nondonor and donor oocytes are similar to those achieved with fresh oocytes; success rates with slow-freezing are lower compared with vitrifica3on. As a result of significantly improved clinical outcomes reported for vitrified oocytes, oocyte cryopreserva3on now represents the most applicable op3on for single reproducgve-age women in need of ferglity preservagon. Curr Opin Obstet Gynecol June 42

43 FerGlity preservagon for cancer pagents 43

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46 Access to InformaGon American FerGlity AssociaGon: hrp:// American Society of Clinical Oncology: hrp:// guidelines/ferglity American Society of ReproducGve Medicine: hrp:// FerGle Hope: hrp:// InternaGonal Council on InferGlity InformaGon DisseminaGon: hrp:// OncoferGlity ConsorGum: hrp:// RESOLVE: the NaGonal InferGlity AssociaGon: hrp:// 46

47 Ελληνική Εταιρία Διατήρησης Αναπαραγωγής hrp:// 47

48 Thank you 48

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51 Gametogenesis 51

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53 Gynecological cancer/ferglity preserving surgery FerGlity-sparing intervengons in female pagents. Rodriguez-Macias Wallberg et al, J Pediatric Blood & Cancer, 2009, 53

54 Gynecological cancer/ferglity preserving surgery FerGlity-sparing intervengons in female pagents. Rodriguez-Macias Wallberg et al, J Pediatric Blood & Cancer, 2009, 54

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57 Ovarian cryopreservagon for subsequent re-implantagon CryopreservaGon of ovarian Gssue is the only opgon available for prepubertal girls and for women who cannot delay the start of chemotherapy The most common reasons given for not discussing ferglity preservagon opgons in a pediatric cancer populagon include not at significant risk in 29% of cases, too young in 27%, techniques unproven in 22%, no faciliges in 10%, and no funding in 8% (6, 10, 13). Donnez. TransplantaGon of ovarian Gssue. FerGl Steril

58 Ovarian cryopreservagon for subsequent re-implantagon Donnez. TransplantaGon of ovarian Gssue. FerGl Steril

59 The amount of ovarian cortex to remove is influenced mainly by the esgmated risk of ovarian failure related to the planned treatment and exisgng ovarian volume. For cases with pelvic irradiagon, TBI, and high doses of alkylagng agents, oophorectomy should be performed. It should also be performed in very young girls owing to the small size of the ovaries 59

60 Pregnancy a er ovarian transplantagon 60

61 Ovarian cryopreservagon for subsequent re-implantagon There is concern regarding the potengal for reseeding tumor cells following ovarian transplantagon procedures in cancers that can involve the ovary, such as leukemia Therefore, transplantagon of ovarian Gssue is not recommended in pagents with a history of leukemia S Joshi et al. FerGlity preservagon in HCT recipients Bone Marrow TransplantaGon (2014),

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63 Ovarian sgmulagon for oocyte retrieval 63