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Pregnancy after Breast Cancer
Prof. Dr. Sibylle Loibl
Chair, German Breast Group
Centre for Haematology and Oncology, Bethanien, Frankfurt
Goehte University Frankfurt
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Topics
Risk of Recurrence
Treatment induces failure of ovarian function
How to measure ovarian failure
Amenorrhea as prognostic factor
Prognosis in women with pregnancy after breast cancer
GnRH to protect ovarian function
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Age at TNBC diagnosis by gBRCA mutation status
Couch FJ, et al. J Clin Oncol 2015;33:304-11
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POSH study OS in young patients with gBRCA
Copson E Lancet Oncol 2018
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OS in TNBC with gBRCA – POSH study
Copson E Lancet Oncol 2018
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n = 325r2 = 0.81
Age (in months from conception to birth; in years from birth to menopause)
Ovarian reserve
Wallace WHB, Kelsey TW. PLoS ONE 2010;5:e8772
NG
F p
op
ula
tio
n
(lo
g 10
scal
e)
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Amenorrhoea rate and influence of age and chemotherpay
Petrek JA, et al. J Clin Oncol 2006;24:1045-51
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>40 years
≤40 years
Ganz P, et al. J Clin Oncol 2011;29:1110-6
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-- without alkylating substances-- with alkylating substances
15–24 years25–34 years
35–44 years ≥45 years
Time to menopause after treatment for Hodgkin's lymphoma by age at start of treatment
van der Kaaij MA, et al. J Clin Oncol 2012;30:291-9
Age 15-24 Age 25-34
Age 35-44 Age 45+
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Chemotherapy induced ovarian insufficiency
Furlantetto J et al. Loibl S SABCS 2 2017JCO 35.15_suppl.10068017; Cancer Res 78(4 Suppl):Abstract No PD7-09 and ASCO 2017 ; J ClinOncol JCO 35.15_suppl.10068
TIMEPOINT EOT 6 M 12 M 18 M 2 M
CIOF % 85.7 62.2 54.0 43.5 38.3
CT REGIMEN dtEC-dtD PMCb iddEnPC PM P nP-EC P-EC Cz
CIOF % 95.6 95.2 94.6 93.1 89.7 82.9 81.3 29.0
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gBRCA1 vs gBRCA2
Proportion of patients with induced amenorrhoea by age at diagnosis*
*All patients received chemotherapy
Valentini A, et al. J Clin Oncol 2013;31:3914-9
Mutation carriers vs noncarriers
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Baseline AMH and age as predictors of amenorrhoea
Anderson RA, et al. Eur J Cancer 2013;49:3404-11
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12-month landmark analysis of OS and DFS, according to amenorrhoea status
Swain SM, et al. N Engl J Med 2010;363:2268-70
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4-years DFS by pre-vs post-menopausal hormone levels at EOT
• OS appeared qualitatively similar to DFS, but not significant due to less mature data
• In patients with HR-positive BC, OS almost reached statistical significance with an advantage for those patients with postmenopausal hormone levels at EOT
Overall
HR-positiveAge <30 years
84.4%
65.0%
87.8%
62.6%
92.8%
69.5%
Furlantetto J et al. Loibl S SABCS 2 2017JCO 35.15_suppl.10068017; Cancer Res 78(4 Suppl):Abstract No PD7-09 and ASCO 2017 ; J ClinOncol JCO 35.15_suppl.10068
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DFS between the pregnant group and matched nonpregnant group
Azim HA Jr, et al. J Clin Oncol 2013;31:73-9
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DFS depending on pregnancy outcome and interval from primary diagnosis to pregnancy
Azim HA Jr, et al. J Clin Oncol 2013;31:73-9
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Schedule for planning pregnancy while still on ET
C Sibylle Loibl
18-36 months
ResumeEndocrineTherapy
Pregnancy andlactation
EndocrineTherapy
contraception
Sto
pp
En
do
crin
eh
tera
py
18-36 months2-3 months Up to two years Re
-Sta
rt e
nd
ocr
ine
ther
apy
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Breast cancer-specific survival for subjects with and without a pregnancy: from date of breast cancer
The impact of pregnancy on breast cancer survival in women who carry a BRCA1 or BRCA2 mutation
Survival of gBRCA carriers
Valentini A, et al. Breast Cancer Res Treat 2013;142:177-85
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Lambertini M, et al. Ann Oncol 2015;26:2408-19
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PROMISE-GIM62,3 POEMS/SWOG S02304 Moffitt-led trial5 GBG-37 ZORO6 Anglo Celtic Group
OPTION7
Definition of POI No resumption of
menstrual activity and
postmenopausal levels
of FSH and E2
Amenorrhoea for the
prior 6 months and
postmenopausal levels
of FSH
No maintenance of
menses and no
resumption of menses
No re-appearance of two
consecutive menstrual
periods within 21 to 35
days
Amenorrhoea with
elevated FSH
Timing of POI after
chemotherapy
12 months 24 months 24 months 6 months Between 12 and 24
months
Sample size 281 257 48 60 227
ER status for eligibility ER-positive and ER-
negative
ER-negative only ER-positive and ER-
negative
ER-negative only ER-positive and ER-
negative
Upper age limit for
eligibility
≤ 45 years ≤ 49 years ≤ 44 years ≤ 45 years None
Type of GnRHa Triptorelin Goserelin Triptorelin Goserelin Goserelin
Study characteristics1
1. Lambertini M, et al. Presented at SABCS 2017 (Abstract GS4-01); . Del Mastro L, et al. JAMA 2011;306:269-76; 3. Lambertini M, et al. JAMA 2015;314:2632-40; 4. Moore HCF, et al. N Engl J Med 2015;372:923-32; 5. Munster P, et al. J Clin Oncol 2012;30:533-8; 6. Gerber B et al, J Clin Oncol 2011;29:2334-41; 7. Leonard RCF, et al. Ann Oncol 2017;28:1811-6
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OR* 0.38 (95% CI 0.26-0.57)
p<0.001
0%
10%
20%
30%
40%
50%
14.1%
GnRHa group
n=363
Control group
n=359
30.9%
Overall (I≤=0%,p=0.73) 51/363 111/359
GBG-37 ZORO
OPTION
Study
UCSF-led trial
POEMS/SWOG S0230
PROMISE-GIM6
6/28
GnRHa
21/95
Events/pts
3/26
5/66
16/148
13/29
Control
41/107
Events/pts
2/21
15/69
40/133
0.37 (0.25, 0.57)
0.54 (0.14, 2.07)
0.41 (0.20, 0.81)
OR (95% CI)
1.17 (0.14, 9.55)
0.33 (0.10, 1.14)
0.29 (0.15, 0.57)
0.37 (0.25, 0.57)
0.54 (0.14, 2.07)
0.41 (0.20, 0.81)
OR (95% CI)
1.17 (0.14, 9.55)
0.33 (0.10, 1.14)
0.29 (0.15, 0.57)
1.0982 1 10.2
GnRHa better Control better
Premature ovarian insufficiency rate
*OR adjusted for age, estrogen receptor status, type and duration of chemotherapy administered
Lambertini M, et al. Presented at SABCS 2017 (Abstract GS4-01) and JC Lin Oncol 2019
Meta-analysis approach
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OR* 0.92 (95% CI 0.66-1.28); p=0.623
0%
10%
20%
30%
40%
50%
36.8% 40.4%
0%
10%
20%
30%
40%
50%
18.2% 30.0%
OR* 0.51 (95% CI 0.31-0.85); p=0.009
One-year amenorrhoea Two-year amenorrhoea
GnRHa group
n=214
Control group
n=210
Amenorrhoea rates
GnRHa group
n=386
Control group
n=374
*OR adjusted for age, estrogen receptor status, type and duration of chemotherapy administeredLambertini M, et al. Presented at SABCS 2017 (Abstract GS4-01)
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GnRHa group: 37/359 (10.3%)
vs.
Control croup: 20/367 (5.5%)
IRR 1.83 (95% CI 1.06-3.15)
p=0.030 Meta-analysis approach
GnRHa
group
(n = 37)
No. (%)
Control
group
(n = 20)
No. (%)
Age distribution, years
≤ 40
≥ 41
37 (100)
0 (0.0)
20 (100)
0 (0.0)
Estrogen receptor
status
Positive
Negative
6 (16.2)
31 (83.8)
2 (10.0)
18 (90.0)
Overall (I≤=0%,p=0.85) 37/359 20/367
POEMS/SWOG S0230
PROMISE-GIM6
Study
OPTION
22/105
8/148
GnRHa
Events/pts
7/106
12/113
3/133
Control
Events/pts
5/121
1.82 (1.05, 3.14)
1.77 (0.87, 3.57)
2.52 (0.67, 9.50)
IRR (95% CI)
1.54 (0.49, 4.85)
1.82 (1.05, 3.14)
1.77 (0.87, 3.57)
2.52 (0.67, 9.50)
IRR (95% CI)
1.54 (0.49, 4.85)
1.105 1 9.5
Control better GnRHa better
Post-treatment pregnancy rate
Lambertini M, et al. Presented at SABCS 2017 (Abstract GS4-01) and J Clin Oncol 2019
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Summary
Pregnancy after Breast Cancer should not be discouraged
Individual counselling of the women including risk of recurrence
Young women have higher risk of recurrence especially when having an HR+/HER2- tumour
Young women with TNBC are very likely gBRCA carriers
gBRCA carriers have a better prognosis
Chemotherapy induces amenorrhoea
GnRH may be used to prevent chemotherapy-induced amenorrhea
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Greetings from Frankfurt