The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations

Mary Beth Terry; Yuyan Liao; Karin Kast; Antonis C. Antoniou; Jasmine A. McDonald; Thea M. Mooij; Christoph Engel; Catherine Nogues; Bruno Buecher; Veronique Mari; Jessica Moretta-Serra; Laurence Gladieff; Elisabeth Luporsi; Daniel Barrowdale; Debra Frost; Alex Henderson; Carole Brewer; D. Gareth Evans; Diana Eccles; Jackie Cook; Kai-ren Ong; Louise Izatt; Munaza Ahmed; Patrick J. Morrison; Charlotte J. Dommering; Jan C. Oosterwijk; Margreet G. E. M. Ausems; Mieke Kriege; Saundra S. Buys; Irene L. Andrulis; Esther M. John; Mary Daly; Michael Friedlander; Sue Anne McLachlan; Ana Osorio; Trinidad Caldes; Anna Jakubowska; Jacques Simard; Christian F. Singer; Yen Tan; Edith Olah; Marie Navratilova; Lenka Foretova; Anne-Marie Gerdes; Marie-Jose Roos-Blom; Brita Arver; Hakan Olsson; Nadine Andrieu; EMBRACE; GENEPSO; Breast Cancer Family Registry (BCFR); HEBON; Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab); IBCCS; E. B. Gomez-Garcia; M. J. Blok

doi:10.1093/jncics/pky078

The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations

Mary Beth Terry, Yuyan Liao, Karin Kast, Antonis C. Antoniou, Jasmine A. McDonald, Thea M. Mooij, Christoph Engel, Catherine Nogues, Bruno Buecher, Veronique Mari, Jessica Moretta-Serra, Laurence Gladieff, Elisabeth Luporsi, Daniel Barrowdale, Debra Frost, Alex Henderson, Carole Brewer, D. Gareth Evans, Diana Eccles, Jackie CookKai-ren Ong, Louise Izatt, Munaza Ahmed, Patrick J. Morrison, Charlotte J. Dommering, Jan C. Oosterwijk, Margreet G. E. M. Ausems, Mieke Kriege, Saundra S. Buys, Irene L. Andrulis, Esther M. John, Mary Daly, Michael Friedlander, Sue Anne McLachlan, Ana Osorio, Trinidad Caldes, Anna Jakubowska, Jacques Simard, Christian F. Singer, Yen Tan, Edith Olah, Marie Navratilova, Lenka Foretova, Anne-Marie Gerdes, Marie-Jose Roos-Blom, Brita Arver, Hakan Olsson, Nadine Andrieu^*, EMBRACE, GENEPSO, Breast Cancer Family Registry (BCFR), HEBON, Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab), IBCCS, E. B. Gomez-Garcia, M. J. Blok

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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, P-trend <.0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort P-trend = .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.

Original language	English
Article number	078
Number of pages	14
Journal	JNCI Cancer Spectrum
Volume	2
Issue number	4
DOIs	https://doi.org/10.1093/jncics/pky078
Publication status	Published - Oct 2018

Keywords

REPRODUCTIVE FACTORS
COLLABORATIVE REANALYSIS
INDUCED-ABORTION
CARRIERS
SUSCEPTIBILITY
KCONFAB
OVARIAN
PARITY
COHORT
BIRTH

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Terry, M. B., Liao, Y., Kast, K., Antoniou, A. C., McDonald, J. A., Mooij, T. M., Engel, C., Nogues, C., Buecher, B., Mari, V., Moretta-Serra, J., Gladieff, L., Luporsi, E., Barrowdale, D., Frost, D., Henderson, A., Brewer, C., Evans, D. G., Eccles, D., ... Blok, M. J. (2018). The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations. JNCI Cancer Spectrum, 2(4), Article 078. https://doi.org/10.1093/jncics/pky078

@article{0627d01629f54a68872206e6b64ca808,

title = "The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations",

abstract = "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, P-trend <.0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort P-trend = .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.",

keywords = "REPRODUCTIVE FACTORS, COLLABORATIVE REANALYSIS, INDUCED-ABORTION, CARRIERS, SUSCEPTIBILITY, KCONFAB, OVARIAN, PARITY, COHORT, BIRTH",

author = "Terry, {Mary Beth} and Yuyan Liao and Karin Kast and Antoniou, {Antonis C.} and McDonald, {Jasmine A.} and Mooij, {Thea M.} and Christoph Engel and Catherine Nogues and Bruno Buecher and Veronique Mari and Jessica Moretta-Serra and Laurence Gladieff and Elisabeth Luporsi and Daniel Barrowdale and Debra Frost and Alex Henderson and Carole Brewer and Evans, {D. Gareth} and Diana Eccles and Jackie Cook and Kai-ren Ong and Louise Izatt and Munaza Ahmed and Morrison, {Patrick J.} and Dommering, {Charlotte J.} and Oosterwijk, {Jan C.} and Ausems, {Margreet G. E. M.} and Mieke Kriege and Buys, {Saundra S.} and Andrulis, {Irene L.} and John, {Esther M.} and Mary Daly and Michael Friedlander and McLachlan, {Sue Anne} and Ana Osorio and Trinidad Caldes and Anna Jakubowska and Jacques Simard and Singer, {Christian F.} and Yen Tan and Edith Olah and Marie Navratilova and Lenka Foretova and Anne-Marie Gerdes and Marie-Jose Roos-Blom and Brita Arver and Hakan Olsson and Nadine Andrieu and EMBRACE and GENEPSO and {Breast Cancer Family Registry (BCFR)} and HEBON and {Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab)} and IBCCS and Gomez-Garcia, {E. B.} and Blok, {M. J.}",

year = "2018",

month = oct,

doi = "10.1093/jncics/pky078",

language = "English",

volume = "2",

journal = "JNCI Cancer Spectrum",

issn = "2515-5091",

publisher = "Oxford University Press",

number = "4",

}

Terry, MB, Liao, Y, Kast, K, Antoniou, AC, McDonald, JA, Mooij, TM, Engel, C, Nogues, C, Buecher, B, Mari, V, Moretta-Serra, J, Gladieff, L, Luporsi, E, Barrowdale, D, Frost, D, Henderson, A, Brewer, C, Evans, DG, Eccles, D, Cook, J, Ong, K, Izatt, L, Ahmed, M, Morrison, PJ, Dommering, CJ, Oosterwijk, JC, Ausems, MGEM, Kriege, M, Buys, SS, Andrulis, IL, John, EM, Daly, M, Friedlander, M, McLachlan, SA, Osorio, A, Caldes, T, Jakubowska, A, Simard, J, Singer, CF, Tan, Y, Olah, E, Navratilova, M, Foretova, L, Gerdes, A-M, Roos-Blom, M-J, Arver, B, Olsson, H, Andrieu, N, EMBRACE, GENEPSO, Breast Cancer Family Registry (BCFR), HEBON, Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab), IBCCS, Gomez-Garcia, EB & Blok, MJ 2018, 'The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations', JNCI Cancer Spectrum, vol. 2, no. 4, 078. https://doi.org/10.1093/jncics/pky078

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, Veronique

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-Jose

AU - Arver, Brita

AU - Olsson, Hakan

AU - Andrieu, Nadine

AU - EMBRACE

AU - GENEPSO

AU - Breast Cancer Family Registry (BCFR)

AU - HEBON

AU - Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab)

AU - IBCCS

AU - Gomez-Garcia, E. B.

AU - Blok, M. J.

PY - 2018/10

Y1 - 2018/10

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, P-trend <.0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort P-trend = .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, P-trend <.0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort P-trend = .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.

KW - REPRODUCTIVE FACTORS

KW - COLLABORATIVE REANALYSIS

KW - INDUCED-ABORTION

KW - CARRIERS

KW - SUSCEPTIBILITY

KW - KCONFAB

KW - OVARIAN

KW - PARITY

KW - COHORT

KW - BIRTH

U2 - 10.1093/jncics/pky078

DO - 10.1093/jncics/pky078

M3 - Article

C2 - 30873510

SN - 2515-5091

VL - 2

JO - JNCI Cancer Spectrum

JF - JNCI Cancer Spectrum

IS - 4

M1 - 078

ER -