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
4.5% in donne 20-39 anni = 6.400
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
• 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
Age less than 35 years:a cut-off for defining young age-onset
breast cancer
Han et al; Breast Cancer Res Treat (2010)
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.
Kroman et al, BMJ 2000
Factors influencing the effect of age on prognosis
Adj chemotherapy and outcome according to age (1)
Aebi et al Lancet 2000
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
Breast cancer in young women: specific clinical issues
• Risk of hereditary breast cancer• Optimal endocrine treatment• Fertility/pregnancy issues
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
Breast cancer in young women: specific clinical issues
• Risk of hereditary breast cancer• Optimal endocrine treatment• Fertility/pregnancy issues
Breast cancer in young women: specific clinical issues
• Risk of hereditary breast cancer• Optimal endocrine treatment• Fertility/pregnancy issues
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%
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
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
Gonadotropin releasing hormone (GnRH) analogs or antagonists
Role in preventing chemotherapy-induced
menopause in breast cancer patients
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
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
Long-term outcomesCT alone
N=133
CT + Triptorelin
N=148
Pregnancies 1 3
Cancer recurrences 13 14
Deaths 3 8
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
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%
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