Download Introduction - Belgian Breast Meeting 2015

Breast cancer during
pregnancy and pregnancy
after treatment
Belgian Breast Meeting
13-10-2006
Frederic Amant
Gynaecologic Oncology
Multidisciplinary Breast Center
Katholieke Universiteit Leuven
‘To begin my life with the beginning of my
life, I record that I was born’
Ch. Dickens in :
The personal history of David Copperfield, 1850
Negative influence on human
development
Infections
Teratogens
Alcohol
Cocaine
Tobacco
Nutritional deficiency
Cytotoxic treatment????
Breast cancer during pregnancy
Surgery
Radiotherapy
Chemotherapy
Farmacology
Short term neonatal outcome
Long term pediatric outcome
Prospective data
Pregnancy after breast cancer
Study center Perinatal Epidemiology (SPE)
Distribution of maternal age in Flanders
Percentage
50
40
30
20
10
0
<20
20-24
25-29
30-34
Maternal age
35-39
>=40
1988
1994
1997
2002
2004
Pathology
It appears that the histopathologic and
immunohistochemical findings of the tumors of
pregnant women with BC are similar to those of
non-pregnant young women with BC.
It is more likely that age at diagnosis rather than
the pregnancy determines the biologic features
of the tumor.
Breast cancer during pregnancy
Surgery
Radiotherapy
Chemotherapy
Farmacology
Short term neonatal outcome
Long term pediatric outcome
Prospective data
Pregnancy after treatment
Breast cancer surgery during
pregnancy



Risk of abortion is highest before 12 weeks
Majority underwent mastectomy due to fear for
radiotherapy
Breast conserving surgery with axillary LN dissection



Especially third trimester
Chemotherapy before radiation
Sentinel node: Tc


Gentilini et al., Ann Oncol 2004;15:1348-51
Keleher et al., Breast J 2004;10:492-5
Breast cancer during pregnancy
Surgery
Radiotherapy
Chemotherapy
Farmacology
Short term neonatal outcome
Long term pediatric outcome
Prospective data
Pregnancy after treatment
Radiotherapy, Kal, Lancet Oncol 2005
Breastca, supradiaphragmatic Hodgkin’ disease,
Brain tumors, head– and necktumors
Distance
Shielding with lead protection
< 0.01 Gy exposure
Slight increase leukemia, tumors during childhood
0.003-0.004 (nl 0.002-0.003)
0.2 Gy: effect dependent pregnancy duration
Multidisciplinary approach
Breast cancer during pregnancy
Surgery
Radiotherapy
Chemotherapy
Farmacology
Short term neonatal outcome
Long term pediatric outcome
Prospective data
Pregnancy after treatment
Anthracyclins
Doxorubicin (Adriblastina°)
Epirubicin (Peccatori et al., Lancet Oncol 2004;5:398)







Slightly more lipophylic
Faster influx
Less intracellular retention
Shorter elimination half life
Better therapeutic index
Less systemic and cardial toxic effects
No fetal complications (n=14)
Idarubicin


More lipophylic
Higher affinity for DNA
Pharmacokinetics during pregnancy:
preliminary data
Doxorubicin
100
VK 15+19
VK 23+27
VDBP 31+35
VDBP pp
10
Time (h)
52
50
48
46
44
42
40
38
36
34
32
30
28
26
24
22
20
18
16
14
12
10
8
6
4
2
1
0
Concentratie (ng/ml)
1000
Taxanes during pregnancy
Author
Chemotherapy
Start chemo
(w)
Delivery (w)
Status child
(age, mts)
De Santis,
2000
Docetaxel, 3 x
24
32
Nl (20)
Sood, 2001
Paclitaxelcisplatin, 3x
30
37
Nl (30)
Mendez, 2003
Paclitaxelcarboplatin, 6x
16
35
Nl (15)
Gadducci,
2003
Epirubicin x4,
paclitaxel x3
14
36
Nl (36)
Potluri, 2006
Doxo-cyclo x4,
docetaxel x4
14
Nl
Doxodocetaxel x6
14
Nl
FEC x4,
docetaxel x4
13
NL (birth)
Nieto, 2006
Trastuzumab during pregnancy
Dosage
Gestational
age
Complication
Outcome
child
Watson et al.,
2005
580mg, 3
weekly
Untill 20w
anhydramnion
Nl
Fanale et al.,
2005
weekly
27w
none
Nl
Waterston et
al., 2006
1 cycle, 523
mg
First
trimester
none
Nl
Breast cancer during pregnancy
Surgery
Radiotherapy
Chemotherapy
Farmacology
Short term neonatal outcome
Long term pediatric outcome
Prospective data
Pregnancy after treatment
Chemotherapy during 2nd and 3rd trimester:
IUGR, premature birth, IUD, neonatal death
Pizzuto et al., Cancer Treat Rep 1980;64:679
Mulvihill et al., Cancer 1987;60:1143
Zemlickis et al., Arch Intern Med 1992;152:573
Zemlickis et al., Am J Obstet Gynecol 1992;166:781
Partridge & Garber, Sem Oncol 2000;27:712
Hansen et al., Am J Obstet Gynecol 2001;97:809
Peres et al., Braz J Med Biol Res 2001;34:1551
Ali et al., Leuk Res 2003;27:381
Follow up in high-risk obstetrical unit to determine
optimal moment of delivery
Chemotherapy during pregnancy:
1966-2004
Cardonick & Iacobucci, Lancet Oncol 2004;5:283
N = 376, mostly after organogenesis
 19 (5%) foeti and 1% neonati died



16 in hematological malignancies
2/3 received idarubicine for breastca
28 (7%) IUGR, 18 (5%) premature birth
 15 (4%) neonatal transient myelosuppression
 9/11 malformations occurred after 1st trimester
exposure

Avoidance of prematurity
Zhao et al., Int J Gynecol Cancer 2006;16:8-15
Series of 22 cases of ovarian cancer during
pregnancy
14 deliveries
1 neonatal death
C/S at 31 weeks
 Died of respiratory distress syndrome

Fetal maturity
100
90
80
mortality
70
60
hyaline membrane
dysplasia
bronchopulmonar
dysplasia
intraventricular
hemorrhage
50
40
30
20
10
0
24-25
26-27
28-29
30-31
32-33
34-35
18 year experience from 5 London
teaching hospitals
Ring et al., J Clin Oncol 2005;18:4192-7



28 women (24 curative, 4 palliative)
Chemotherapy: AC or EC (n=16) or CMF (n=12)
1/28: 1e trim → miscarriage
median
range
GA, D/, w
17
4-33
GA, surgery, w
16
5-29
GA, chemo,w
20
15-33
GA, delivery, w
37
30-40
Weight < P10
0
Transfer neonato
5
Last chemo-delivery: > 3w interval
Maternal neutropenia and thrombocytopenia
Metabolisation in placenta (fœtus) versus inefficient
neonatal liver and kidney function (neonate)
Neonatal myelosuppression
o
o
o
o
o
o
Okun et al., Med Ped Oncol 1979;7:315
Pizzuto et al., Cancer Treat Rep 1980;64:679
Reynoso et al., JCO 1987;5:1098
Raffles et al., Br J Obstet Gynaecol 1989;96:1099
Avilés et al., Am J Hematol 1991;36:243
Garcia et al., J Perinatol 1999;19:230
Breast cancer during pregnancy
Surgery
Radiotherapy
Chemotherapy
Farmacology
Short term neonatal outcome
Long term pediatric outcome
Prospective data
Pregnancy after treatment
Long term outcomes: retrospective data
Avilés and Neri, Clinical Lymphoma 2001;2:173-7
Update on Aviles et al., Am J Hemat 1991;36:243-8
84 children
Hematological malignancies (29 malignant lymphoma,
26 Hodgkin, 29 acute leukemia)
38 received chemotherapy during 1st trimester
19 y follow up (range, 6-29 years)
Normal fysical, neurological, psychological,
hematological and immunological function
MD Anderson data
Hahn et al., Cancer 2006



N = 57 (32 adj CT, 25 NACT), FAC
Survey: mail or telephone
Children age (n=40): 2-157 mts
Outcome
N (%)
Reported incidence
general population
Down syndrome
1 (2.5)
1:700 (30-34y)
Clubfoot
1 (2.5)
1:1000
Cong bilat ureteral reflux
1 (2.5)
3-4% some uro problem
“normal development”
39 (97)
Requires special attention
in school
2/18 (11)
Breast cancer during pregnancy
Surgery
Radiotherapy
Chemotherapy
Farmacology
Short term neonatal outcome
Long term pediatric outcome
Prospective data
Pregnancy after treatment
Methods
Retrospective search of cases
Prospective


o
o
Standardised clinical neurologic assessment
Echocardiografy with dopplers
Results: maternal data (last FU, 9-2006)
Diagnosis
N
RT
Surgery
Chemotherapy
Orofaryngeal ca,
1
2 x cisplatin (25mg/m²) + fluoroblastin (100mg/m²)
(30, 32)
Spinocellular
cervixca,
1
6 x cisplatin (75mg/m²)
(17, 19, 20, 23, 24, 27)
Breastca
5
4
3 x doxorubicin (60mg/m²) + cyclophosphamide(600mg/m²)
(23.4, 25.4, 28.4)
3 x doxorubicin (60mg/m²) + cyclophosphamide(600mg/m²)
(26, 29, 32)
6 x cyclophosphamide (600mg/m²) + epirubicin (100mg/m²)
+ 5-FU (500mg/m² ) (21, 24, 27, 30, 33, 36)
6 x cyclophosphamide (500mg/m²) + epirubicin(100mg/m²)
+ 5-FU (500mg/m²) (20, 23, 26, 29, 32, 35)
3x
3 x doxorubicin + cyclophosphamide
ALL
1
HOVON 37 cycle 1 and 2 (21, 26)
AML
2
2 x idarubicine (12mg/m²) + cytarabine (100mg/m²)
(15, 20)
retinoinic acid started at 31w
3 x idarubicine (12mg/m²) + cytarabine (100mg/m²)
(15, 21, 26)
Glioblastoma
1
Hodgkin
3
1
1
Temodal ( 18-21, 26, 30, 34)
3 x ABVD
2 x ABVD (29, 33)
4 x ABVD (15, 19, 23, 27)
Results: neonatal and pediatric follow-up
(last FU, 9-2006)
N
GA birth (w)
Birth weight
(gr)
Neonatal complications
FU
(Mts)
Outcome child
1
34.5
2840 (p 79)
Prematurity
2.5
Asymmetric tonick nek reflex and delayed
visual fixation
1
32
1715 (p 23)
Prematurity
HMD I: ncpap
Pneumomediastinum
↑ creatinin
16
Normal development
Complication
s
1
Sepsis
(26)
P-PROM
(28)
28.3
720 (p 0.5)
Prematurity
Pancytopenia
2 d HFO
-> cpap till d 31
21
Minor delay expressive language development
1 (twin)
P-PROM
(32.4)
33
1630 (p 5)
Prematurity
HFO
39
Autistic disorder, mental and motoric
retardation (< unilateral polymicrogyria)
1 (twin)
P-PROM
(32.4)
33
1390 (p 0.8)
Prematurity
39
Normal development
10
1 x Sepsis
(29)
34-39 (36.3)
2743 (21403370)
4 x Prematurity
26 (166)
Normal development
Standard echocardiographic data
Patients
Controls
P value
LVEDD/BSA (mm)
54.2 ± 10.7
53.2 ± 8.1
0.82
LVESD/BSA (mm)
34.7 ± 6.8
34.8 ± 6.1
0.98
ILWTD/BSA (mm)
9.1 ± 2.7
10.0 ± 3.2
0.48
FS (%)
35.7 ± 3.4
33.7 ±3 .4
0.21
LVMI (gr/m2)
57.3 ± 9.3
65.2 ± 12.9
0.14
101.4 ±19.7
97.2 ± 11.8
0.58
2.2 ± 0.6
2.2 ± 0.5
0.81
105.8 ± 22.3
119.1 ± 17.6
0.16
IVRT (msec)
47.4 ± 8.2
51.1 ± 8.2
0.35
PuVe systole (cm/sec)
54.8 ± 6.3
51.2 ± 4.0
0.17
PuVe diastole (cm/sec)
61.3 ± 6.9
64.2 ±8.3
0.46
Septal annular motion (mm)
10.2 ± 2.1
11.2 ± 1.1
0.42
Lateral annular motion (mm)
13.4 ± 1.5
13.0 ± 1.3
0.98
RV annular motion (mm)
15.8 ± 2.5
17.0 ± 1.8
0.14
Mitral E (cm/sec)
E/A ratio
Decceleration E (msec)
Van Calsteren et al., J Clin Oncol 2006;24(12):e16-7
Breast cancer during pregnancy
Surgery
Radiotherapy
Chemotherapy
Farmacology
Short term neonatal outcome
Long term pediatric outcome
Prospective data
Pregnancy after treatment
Pregnancy after treatment
No difference in survival
‘Two year cancer diagnosis anniversary’
Higher rate of miscarriages
Individual’s response to therapy
Receptor positive:
Tamoxifen contraindicated (ambiguous genitalia,
Goldenhar syndrome)
After completion hormonal treatment
Breast cancer during pregnancy and
pregnancy after treatment : conclusions
Radiotherapy is possible
Chemotherapy
Short term (neonatal) safety evidence
Long term outcome: retrospective data suggest
safety
Prospective trials needed
 Larger
numbers
 Longer follow up
 Thorough assessment
Morbidity related to –induced- prematurity
¡¡¡ Thank you!!!