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; Véronique 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-josé Roos-blom; Brita Arver; Håkan Olsson; Rita K Schmutzler; John L Hopper; Flora E Van Leeuwen; David Goldgar; Roger L Milne; Douglas F Easton; Matti A Rookus; Nadine Andrieu

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, Véronique 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-josé Roos-blom, Brita Arver, Håkan Olsson, Rita K Schmutzler, John L Hopper, Flora E Van Leeuwen, David Goldgar, Roger L Milne, Douglas F Easton, Matti A Rookus, Nadine Andrieu

Research output: Contribution to journal › Article › 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, 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.

Original language	English
Journal	JNCI Cancer spectrum
Volume	2
Issue number	4
Early online date	8 Mar 2019
DOIs	https://doi.org/10.1093/jncics/pky078
Publication status	Published - 2019

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https://academic.oup.com/jncics/article/doi/10.1093/jncics/pky078/5370381

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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., ... Andrieu, N. (2019). The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations. JNCI Cancer spectrum, 2(4). https://doi.org/10.1093/jncics/pky078

@article{739f402822a84e00a8fb9b248e118cc4,

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, 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.",

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 V{\'e}ronique 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-jos{\'e} Roos-blom and Brita Arver and H{\aa}kan Olsson and Schmutzler, {Rita K} and Hopper, {John L} and {Van Leeuwen}, {Flora E} and David Goldgar and Milne, {Roger L} and Easton, {Douglas F} and Rookus, {Matti A} and Nadine Andrieu",

year = "2019",

doi = "10.1093/jncics/pky078",

language = "English",

volume = "2",

journal = "JNCI Cancer spectrum",

issn = "1475-4029",

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, Roos-blom, M, Arver, B, Olsson, H, Schmutzler, RK, Hopper, JL, Van Leeuwen, FE, Goldgar, D, Milne, RL, Easton, DF, Rookus, MA & Andrieu, N 2019, '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. 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, 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 - Goldgar, David

AU - Milne, Roger L

AU - Easton, Douglas F

AU - Rookus, Matti A

AU - Andrieu, Nadine

PY - 2019

Y1 - 2019

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 - Article

SN - 1475-4029

VL - 2

JO - JNCI Cancer spectrum

JF - JNCI Cancer spectrum

IS - 4

ER -

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

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