il tumore mammario nelle giovani donne lucia del mastro ss sviluppo terapie innovative 12 maggio...
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Il tumore mammario nelle giovani donne
Lucia Del MastroSS Sviluppo Terapie Innovative
12 maggio 2012
IRCCS Azienda Ospedaliera Universitaria San Martino – IST Istituto Nazionale per la Ricerca sul Cancro
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4.5% in donne 20-39 anni = 6.400
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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
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• 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
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Age less than 35 years:a cut-off for defining young age-onset
breast cancer
Han et al; Breast Cancer Res Treat (2010)
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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.
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Kroman et al, BMJ 2000
Factors influencing the effect of age on prognosis
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Adj chemotherapy and outcome according to age (1)
Aebi et al Lancet 2000
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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
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Breast cancer in young women: specific clinical issues
• Risk of hereditary breast cancer• Optimal endocrine treatment• Fertility/pregnancy issues
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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
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Breast cancer in young women: specific clinical issues
• Risk of hereditary breast cancer• Optimal endocrine treatment• Fertility/pregnancy issues
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Breast cancer in young women: specific clinical issues
• Risk of hereditary breast cancer• Optimal endocrine treatment• Fertility/pregnancy issues
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Copyright © American Society of Clinical Oncology
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%
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Acute ovarian failure underestimates age specific reproductive impairment for young women ‐undergoing chemotherapy for cancer
Cancerpages n/a-n/a, 17 AUG 2011 DOI: 10.1002/cncr.26403http://onlinelibrary.wiley.com/doi/10.1002/cncr.26403/full#fig1
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Ovarian function/fertility preservation options in breast cancer patients
Intervention Definition Fertility preservation
Preservation 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
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Gonadotropin releasing hormone (GnRH) analogs or antagonists
Role in preventing chemotherapy-induced
menopause in breast cancer patients
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Copyright ©2007 AlphaMed Press
Blumenfeld, Z. Oncologist 2007;12:1044-1054
Figure 1. A suggested pathophysiologic mechanism of chemotherapy-induced gonadotoxicity
2. Decrease in uteroOvarian perfusion
3. Activation of GnRHReceptors-> decreasedApoptosis
4. Protection of undiffe-rentiated germ line Stem Cells
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Risk of CT-induced menopause w/o LH-Rha protection
STUDY CT+LHRHa CT alone HR 95% CL
PROMISE GIM-6 11\139 31\121 0.25 0,12 – 0,52
GBG 37 ZORO 9\30 13\30 0.56 0,19 – 1,62
MUNSTER 3\26 2\21 1.24 0,19 – 8,19
BADAWY 4\39 26\39 0.06 0,02 – 0,19
SVERRISDOTTIR 41\51 38\43 0.54 0,17 – 1,72
DEMEESTERE 9\45 7\39 1.14 0,38 – 3,42
BEHRINGER 1\10 3\9 0.22 0,02 – 2,67
TOTAL 78\340 120\302 0.46 0,3 - 0,72
LHRHa better LHRHa worse
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Long-term outcomesCT alone
N=133
CT + Triptorelin
N=148
Pregnancies 1 3
Cancer recurrences 13 14
Deaths 3 8
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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
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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%
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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 dell’UO di Clinica Ostetricia e Ginecologia.
by L. Del Mastro and G. Canavesehttp://clinicaltrials.istge.it/ist/prefer