Treatment of breast cancer during pregnancy: an observational study.
BACKGROUND
Little is known about the treatment of breast cancer during pregnancy. We aimed to determine whether treatment for breast cancer during pregnancy is safe for both mother and child.


METHODS
We recruited patients from seven European countries with a primary diagnosis of breast cancer during pregnancy; data were collected retrospectively if the patient was diagnosed before April, 2003 (when the registry began), or prospectively thereafter, irrespective of the outcome of pregnancy and the type and timing of treatment. The primary endpoint was fetal health for up to 4 weeks after delivery. The registry is ongoing. The study is registered with ClinicalTrials.gov, number NCT00196833.


RESULTS
From April, 2003, to December, 2011, 447 patients were registered, 413 of whom had early breast cancer. Median age was 33 years (range 22-51). At the time of diagnosis, median gestational age was 24 weeks (range 5-40). 197 (48%) of 413 women received chemotherapy during pregnancy with a median of four cycles (range one to eight). 178 received an anthracycline, 15 received cyclophosphamide, methotrexate, and fluorouracil, and 14 received a taxane. Birthweight was affected by chemotherapy exposure after adjustment for gestational age (p=0·018), but not by number of chemotherapy cycles (p=0·71). No statistical difference between the two groups was observed for premature deliveries before the 37th week of gestation. 40 (10%) of 386 infants had side-effects, malformations, or new-born complications; these events were more common in infants born before the 37th week of gestation than they were in infants born in the 37th week or later (31 [16%] of 191 infants vs nine [5%] of 195 infants; p=0·0002). In infants for whom maternal treatment was known, adverse events were more common in those who received chemotherapy in utero compared with those who were not exposed (31 [15%] of 203 vs seven [4%] of 170 infants; p=0·00045). Two infants died; both were exposed to chemotherapy and delivered prematurely, but both deaths were thought not to be related to treatment. Median disease-free survival for women with early breast cancer was 70·6 months (95% CI 62·1-105·5) in women starting chemotherapy during pregnancy and 94·4 months (lower 95% CI 64·4; upper 95% CI not yet reached) in women starting chemotherapy after delivery (unadjusted hazard ratio 1·13 [95% CI 0·76-1·69]; p=0·539).


CONCLUSIONS
Although our data show that infants exposed to chemotherapy in utero had a lower birthweight at gestational age than did those who were unexposed, and had more complications, these differences were not clinically significant and, since none of the infants was exposed to chemotherapy in the first trimester, were most likely related to premature delivery. Delay of cancer treatment did not significantly affect disease-free survival for mothers with early breast cancer. Because preterm birth was strongly associated with adverse events, a full-term delivery seems to be of paramount importance.


BACKGROUND
BANSS Foundation, Biedenkopf, Germany and the Belgian Cancer Plan, Ministry of Health, Belgium.
German Breast Group, Neu-Isenburg, Germany. sibylle.loibl@germanbreastgroup.de
Sibylle
S
Loibl
Sileny N
SN
Han
Gunter
G
von Minckwitz
Marijke
M
Bontenbal
Alistair
A
Ring
Jerzy
J
Giermek
Tanja
T
Fehm
Kristel
K
Van Calsteren
Sabine C
SC
Linn
Bettina
B
Schlehe
Mina Mhallem
MM
Gziri
Pieter J
PJ
Westenend
Volkmar
V
Müller
Liesbeth
L
Heyns
Brigitte
B
Rack
Ben
B
Van Calster
Nadia
N
Harbeck
Miriam
M
Lenhard
Michael J
MJ
Halaska
Manfred
M
Kaufmann
Valentina
V
Nekljudova
Frederic
F
Amant
D000014:Abnormalities, Drug-Induced / Q000453:epidemiology*; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001034:Apgar Score; D001724:Birth Weight / Q000187:drug effects*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D044584:Carcinoma, Ductal / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology / Q000556:secondary; D018275:Carcinoma, Lobular / Q000175:diagnosis / Q000188:drug therapy / Q000473:pathology / Q000556:secondary / Q000601:surgery; D015331:Cohort Studies; D036861:Delivery, Obstetric / Q000706:statistics & numerical data; D018572:Disease-Free Survival; D005060:Europe; D005260:Female; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000139:chemically induced* / Q000453:epidemiology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D009926:Organ Preservation; D011247:Pregnancy; D011252:Pregnancy Complications, Neoplastic / Q000188:drug therapy; D011256:Pregnancy Outcome / Q000453:epidemiology*; D012042:Registries; D012189:Retrospective Studies; D055815:Young Adult