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Il tumore mammario nelle giovani donne Lucia Del Mastro SS Sviluppo Terapie Innovative 12 maggio 2012 IRCCS Azienda Ospedaliera Universitaria San Martino.

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Presentation on theme: "Il tumore mammario nelle giovani donne Lucia Del Mastro SS Sviluppo Terapie Innovative 12 maggio 2012 IRCCS Azienda Ospedaliera Universitaria San Martino."— Presentation transcript:

1 Il tumore mammario nelle giovani donne Lucia Del Mastro SS Sviluppo Terapie Innovative 12 maggio 2012 IRCCS Azienda Ospedaliera Universitaria San Martino – IST Istituto Nazionale per la Ricerca sul Cancro

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4 4.5% in donne 20-39 anni = 6.400

5 Breast cancer - Incidence in Italy 2010 – Breast cancer incidence age 20-84: 37947 Rate: 165/100.000 – Breast cancer incidence age 20-39: 1788 (4%) Rate: 25/100.000 http://www.tumori.net/it/banca_dati

6 Baseline risk assessment – Prognostic factors Age T size N Histologic grade HER2 ER (?) Expected benefit of therapy – Predictive factors ER -> endocrine therapy HER2 -> Trastuzumab Chemotherapy benefit: no reliable predictive factors Adjuvant therapy decision making

7 Age less than 35 years: a cut-off for defining young age-onset breast cancer Han et al; Breast Cancer Res Treat (2010)

8 Aggressive Clinico-Pathologic Features of Breast Cancer in Young Women Women < 35 yrs of age, have higher % of ER and PR negative breast tumors and LVI (p < 0.001) compared to those aged 35 – 50 years Differences in T size, nodal and Her2 status have been less clear across studies Adami et al. NEJM 1986. El Saghir et al. BMC 2006. Holli et al. Eur J Cancer 1997. Colleoni et al. Ann Oncol 2002. Anders et al. JCO 2008. Albain et al. JNCI 1994.

9 Kroman et al, BMJ 2000 Factors influencing the effect of age on prognosis

10 Adj chemotherapy and outcome according to age (1) Aebi et al Lancet 2000

11 Adj chemotherapy and outcome according to age (2) Goldhirsch et al. J Natl Cancer Inst Monogr 2001 RELATIVE RISK OF RELAPSE AND 5-YEAR DISEASE-FREE SURVIVAL IN ER-POSITIVE AND ER-NEGATIVE DISEASE

12 Breast cancer in young women: specific clinical issues Risk of hereditary breast cancer Optimal endocrine treatment Fertility/pregnancy issues

13 Hereditary breast cancer Estimate the likelihood that BRCA1-2 mutation is present BRCA1 (cr.17)/BRCA2 (cr.13) – High penetrance: 45-84% lifetime risk of BC. Increased risk of contralateral BC (up to 60%). 11-62% lifetime risk of ovarian cancer BRCA1 – More likely triple negative – BRCA1 mutation: 11-28% of patients with triple negative BC – Triple negative BC at age <= 40 y: BRCA1 mutation in 11-47% Management of patients with BRCA1/2 mutations – Consider bilteral risk reduction mastectomy – Consider bilateral risk reduction salpingo-oophorectomy after completion of childbearing

14 Breast cancer in young women: specific clinical issues Risk of hereditary breast cancer Optimal endocrine treatment Fertility/pregnancy issues

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20 Breast cancer in young women: specific clinical issues Risk of hereditary breast cancer Optimal endocrine treatment Fertility/pregnancy issues

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26 Petrek, J. A. et al. J Clin Oncol; 24:1045-1051 2006 Fig 2. Bleeding after chemotherapy by patient age Early menopause by age - < 35 y: 10% - 35-40 y: 50% - >40 y: 85%

27 Acute ovarian failure underestimates agespecific reproductive impairment for young women undergoing chemotherapy for cancer Cancer pages n/a-n/a, 17 AUG 2011 DOI: 10.1002/cncr.26403 http://onlinelibrary.wiley.com/doi/10.1002/cncr.26403/full#fig1 http://onlinelibrary.wiley.com/doi/10.1002/cncr.26403/full#fig1

28 Ovarian function/fertility preservation options in breast cancer patients InterventionDefinitionFertility preservationPreservation of ovarian function Embryo cryopreservation Harvesting eggs,IVF, embryo criopreservation + ? Small case series no Oocyte cryopreservation Harvesting and freezing of unfertilized eggs ? Small case series, case reports; 2% live birth per thawed oocyte no Ovarian cryopreservation and transplantation Freezing of ovarian tissueand reimplantation ? Only 2 live birth reported ? Limited life span of ovarian tissue Ovarian suppression with GnRH analogs or antagonists GnRH given before and during CT to protect ovaries ? Normal pregnancies reported (3-8%) yes Modified from Lee; JCO 2006

29 Gonadotropin releasing hormone (GnRH) analogs or antagonists Role in preventing chemotherapy- induced menopause in breast cancer patients

30 Copyright ©2007 AlphaMed Press Blumenfeld, Z. Oncologist 2007;12:1044-1054 Figure 1. A suggested pathophysiologic mechanism of chemotherapy-induced gonadotoxicity 2. Decrease in utero Ovarian perfusion 3. Activation of GnRH Receptors-> decreased Apoptosis 4. Protection of undiffe- rentiated germ line Stem Cells

31 Risk of CT-induced menopause w/o LH-Rha protection STUDYCT+LHRHaCT aloneHR95% CL PROMISE GIM-611\13931\1210.250,12 – 0,52 GBG 37 ZORO9\3013\300.560,19 – 1,62 MUNSTER3\262\211.240,19 – 8,19 BADAWY4\3926\390.060,02 – 0,19 SVERRISDOTTIR41\5138\430.540,17 – 1,72 DEMEESTERE9\457\391.140,38 – 3,42 BEHRINGER1\103\90.220,02 – 2,67 TOTAL78\340120\3020.460,3 - 0,72 LHRHa betterLHRHa worse

32 Long-term outcomes CT alone N=133 CT + Triptorelin N=148 Pregnancies13 Cancer recurrences1314 Deaths38

33 Meta-analisi di 7 studi sulle stimolazioni per crioconservazione di ovociti e/o embrioni: Totale cicli di stimolazione 226 5 studi su 7 hanno riportato i dati dello scongelamento Totale cicli di scongelamento 20 (sia embrioni che ovociti) Gravidanze 13

34 What women want From March 2010 to march 2012 – 28 patients <= 40 yrs treated at IST-Genoa were offered strategies for fertility/ovarian function preservation – Oocyte cryopreservation 3/28 accepted : 11.0% – GnRHa temporary ovarian suppression 25/28 accepted : 89.0%

35 Ca mammario: gravidanza e fertilità. Protocollo interaziendale per la gestione clinica e per la ricerca applicata IST S.S. Senologia Chirurgica S.C. Oncologia Medica A S.C. Diagnostica per immagini IRCCS Giannina Gaslini Dipartimento Ostetrico Neonatale Ospedale S. Martino Centro di Fisiopatologia della Riproduzione umana dellUO di Clinica Ostetricia e Ginecologia. by L. Del Mastro and G. Canavese http://clinicaltrials.istge.it/ist/prefer


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