TY - JOUR
T1 - The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations
AU - Terry, Mary Beth
AU - Liao, Yuyan
AU - Kast, Karin
AU - Antoniou, Antonis C
AU - McDonald, Jasmine A
AU - Mooij, Thea M
AU - Engel, Christoph
AU - Nogues, Catherine
AU - Buecher, Bruno
AU - Mari, Véronique
AU - Moretta-Serra, Jessica
AU - Gladieff, Laurence
AU - Luporsi, Elisabeth
AU - Barrowdale, Daniel
AU - Frost, Debra
AU - Henderson, Alex
AU - Brewer, Carole
AU - Evans, D Gareth
AU - Eccles, Diana
AU - Cook, Jackie
AU - Ong, Kai-Ren
AU - Izatt, Louise
AU - Ahmed, Munaza
AU - Morrison, Patrick J
AU - Dommering, Charlotte J
AU - Oosterwijk, Jan C
AU - Ausems, Margreet G E M
AU - Kriege, Mieke
AU - Buys, Saundra S
AU - Andrulis, Irene L
AU - John, Esther M
AU - Daly, Mary
AU - Friedlander, Michael
AU - McLachlan, Sue Anne
AU - Osorio, Ana
AU - Caldes, Trinidad
AU - Jakubowska, Anna
AU - Simard, Jacques
AU - Singer, Christian F
AU - Tan, Yen
AU - Olah, Edith
AU - Navratilova, Marie
AU - Foretova, Lenka
AU - Gerdes, Anne-Marie
AU - Roos-Blom, Marie-José
AU - Arver, Brita
AU - Olsson, Håkan
AU - Schmutzler, Rita K
AU - Hopper, John L
AU - van Leeuwen, Flora E
AU - EMBRACE, GENEPSO, BCFR, HEBON, kConFab and IBCCS
PY - 2018/12
Y1 - 2018/12
N2 - Background: Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC risk in the immediate years following an FTP. No large prospective studies, however, have examined whether the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers.Methods: Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events are associated with BC risk for mutation carriers using a retrospective cohort (5707 BRCA1 and 3525 BRCA2 mutation carriers) and a prospective cohort (2276 BRCA1 and 1610 BRCA2 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort.Results: For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (combined hazard ratio [HRc] = 0.99, 95% confidence interval [CI] = 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc = 0.79, 95% CI = 0.69 to 0.91; HRc = 0.70, 95% CI = 0.59 to 0.82; HRc = 0.50, 95% CI = 0.40 to 0.63, for 2, 3, and ≥4 FTPs, respectively, Ptrend < .0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort Ptrend = .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] = 1.69, 95% CI = 1.09 to 2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc = 1.33, 95% CI = 1.05 to 1.69), and there was no apparent decrease in risk associated with multiparity except for having at least 4 FTPs vs. 1 FTP (HRc = 0.72, 95% CI = 0.54 to 0.98).Conclusions: These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers.
AB - Background: Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC risk in the immediate years following an FTP. No large prospective studies, however, have examined whether the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers.Methods: Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events are associated with BC risk for mutation carriers using a retrospective cohort (5707 BRCA1 and 3525 BRCA2 mutation carriers) and a prospective cohort (2276 BRCA1 and 1610 BRCA2 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort.Results: For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (combined hazard ratio [HRc] = 0.99, 95% confidence interval [CI] = 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc = 0.79, 95% CI = 0.69 to 0.91; HRc = 0.70, 95% CI = 0.59 to 0.82; HRc = 0.50, 95% CI = 0.40 to 0.63, for 2, 3, and ≥4 FTPs, respectively, Ptrend < .0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort Ptrend = .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] = 1.69, 95% CI = 1.09 to 2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc = 1.33, 95% CI = 1.05 to 1.69), and there was no apparent decrease in risk associated with multiparity except for having at least 4 FTPs vs. 1 FTP (HRc = 0.72, 95% CI = 0.54 to 0.98).Conclusions: These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers.
U2 - 10.1093/jncics/pky078
DO - 10.1093/jncics/pky078
M3 - Journal article
C2 - 30873510
SN - 2515-5091
VL - 2
SP - pky078
JO - JNCI cancer spectrum.
JF - JNCI cancer spectrum.
IS - 4
ER -