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
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
Adjuvant therapy decision making
• 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
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.
Factors influencing the effect of age on
prognosis
Kroman et al, BMJ 2000
Adj chemotherapy and outcome according to age
(1)
Aebi et al Lancet 2000
Adj chemotherapy and outcome according to age
(2)
RELATIVE RISK OF RELAPSE AND 5-YEAR DISEASE-FREE SURVIVAL IN ER-POSITIVE
AND ER-NEGATIVE DISEASE
Goldhirsch et al. J Natl Cancer Inst Monogr 2001
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
Fig 2. Bleeding after chemotherapy by patient age
Early menopause by age
- < 35 y: 10%
- 35-40 y: 50%
- >40 y: 85%
Petrek, J. A. et al. J Clin Oncol; 24:1045-1051 2006
Copyright © American Society of Clinical Oncology
Acute ovarian failure underestimates age‐specific 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
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 chemotherapyinduced menopause in breast
cancer patients
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 undifferentiated germ line
Stem Cells
Blumenfeld, Z. Oncologist 2007;12:1044-1054
Copyright ©2007 AlphaMed Press
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 outcomes
CT 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
ovociti)
Gravidanze 13
20 (sia embrioni che
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

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Dipartimento Ostetrico
Neonatale
Ospedale S. Martino
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Centro di Fisiopatologia della
Riproduzione umana dell’UO di
Clinica Ostetricia e Ginecologia.
http://clinicaltrials.istge.it/ist/prefer
by L. Del Mastro and G. Canavese