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 |
|---|---|
| Article number | pky078 |
| Journal | JNCI cancer spectrum |
| Volume | 2 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 1 Oct 2018 |
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In: JNCI cancer spectrum, Vol. 2, No. 4, pky078, 01.10.2018.
Research output: Contribution to journal › Article › Academic › peer-review
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.
N1 - Funding Information: The German Consortium of Hereditary Breast and Ovarian Cancer (GC-HBOC) is supported by the German Cancer Aid (grant number 110837, Rita K. Schmutzler). Funding Information: This work was supported by grants to kConFab and the kConFab Follow-Up Study from Cancer Australia (809195); the Australian National Breast Cancer Foundation (IF 17); the National Health and Medical Research Council (454508, 288704, 145684); the US National Institute of Health (1RO1CA159868); the Queensland Cancer Fund; the Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia; and the Cancer Foundation of Western Australia. Funding Information: The Spanish National Cancer Centre (CNIO) was partially supported by the Spanish Ministry of Economy and Competitiveness (MINECO) SAF2014-57680-R, the Spanish Research Network on Rare diseases (CIBERER). CNIO was also partially supported by FISPI16/00440. Funding Information: MODSQUAD Czech Republic, Brno was supported by MH CZ—DRO (MMCI, 00209805) and by MEYS—NPS I - LO1413 to LF, MN. Funding Information: INHERIT was supported by the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer program (grant number CRN-87521) and the Ministry of Economic Development, Innovation and Export Trade (grant number PSR-SIIRI-701). The PERSPECTIVE project was supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research (GPH-129344), the Ministère de l’Économie, de la Science et de l’ Innovation du Québec through Genome Québec, and the Quebec Breast Cancer Foundation. Funding Information: The DKFZ study was supported by the Dresden and German Cancer Research Center (DKFZ). Funding Information: This work was supported by Cancer Research UK grants C1287/A17523, C1287/23382, C1287/A16563, C12292/A20861, and C12292/A11174. The Breast Cancer Family Registry (BCFR) was supported by the US National Institute of Health (grant number RO1CA159868). The Australian BCFR was supported in Australia by the National Health and Medical Research Council, the New South Wales Cancer Council, the Victorian Health Promotion Foundation, the Victorian Breast Cancer Research Consortium, Cancer Australia, and the National Breast Cancer Foundation. The six sites of the Breast Cancer Family Registry (BCFR) were supported by grant UM1 CA164920 from the US National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the BCFR, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government or the BCFR. The Spanish National Cancer Centre (CNIO) was partially supported by the Spanish Ministry of Economy and Competitiveness (MINECO) SAF2014-57680-R, the Spanish Research Network on Rare diseases (CIBERER). CNIO was also partially supported by FISPI16/00440. INHERIT was supported by the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer program (grant number CRN-87521) and the Ministry of Economic Development, Innovation and Export Trade (grant number PSR-SIIRI-701). The PERSPECTIVE project was supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research (GPH-129344), the Minist?re de l??conomie, de la Science et de l? Innovation du Qu?bec through Genome Qu?bec, and the Quebec Breast Cancer Foundation. Jacques Simard is Chairholder of the Canada Research Chair in Oncogenetics. The DKFZ study was supported by the Dresden and German Cancer Research Center (DKFZ). The Epidemiological Study of Familial Breast Cancer (EMBRACE) is supported by Cancer Research UK grants C1287/A23382 and C1287/A16563. D. Gareth Evans is supported by a National Institute for Health Research (NIHR) grant to the Biomedical Research Centre, Manchester. The investigators at the Institute of Cancer Research and the Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at the Institute of Cancer Research and the Royal Marsden NHS Foundation Trust. Ros Eeles and Elizabeth Bancroft are supported by Cancer Research UK grant C5047/A8385. Ros Eeles is also supported by NIHR support to the Biomedical Research Centre at the Institute of Cancer Research and the Royal Marsden NHS Foundation Trust. Antonis C. Antoniou is funded by Cancer Research UK grants C12292/A20861 and C12292/A11174. MT is funded by the European Union Seventh Framework Program (2007? 013)/European Research Council (310018). The German Consortium of Hereditary Breast and Ovarian Cancer (GC-HBOC) is supported by the German Cancer Aid (grant number 110837, Rita K. Schmutzler). The national French cohort, GENEPSO, had been supported by a grant from the Fondation de France and the Ligue Nationale Contre le Cancer and is being supported by a grant from INCa as part of the European program ERA-NET on Translational Cancer Research (TRANSCAN-JTC2012, n?2014-008). Hospital Clinico San Carlos (HCSC) was supported by CIBERONC 161200301 from ISCIII (Spain), partially supported by European Regional Development FEDER funds. The HEBON study is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756; the Netherlands Organisation of Scientific Research grant NWO 91109024; the Pink Ribbon grants 110005 and 2014-187.WO76; the BBMRI grant NWO 184.021.007/CP46; and the Transcan grant JTC 2012 Cancer 12-054. The International Hereditary Cancer Center (IHCC) was supported by grant PBZ_KBN_122/P05/2004 and ERA-NET TRANSAN JTC 2012 Cancer 12-054 (ERA-NET-TRANSCAN/07/2014). This work was supported by grants to kConFab and the kConFab Follow-Up Study from Cancer Australia (809195); the Australian National Breast Cancer Foundation (IF 17); the National Health and Medical Research Council (454508, 288704, 145684); the US National Institute of Health (1RO1CA159868); the Queensland Cancer Fund; the Cancer Councils of New South Wales, Victoria, Tasmania, and South Australia; and the Cancer Foundation of Western Australia. MODSQUAD Czech Republic, Brno was supported by MH CZ?DRO (MMCI, 00209805) and by MEYS?NPS I - LO1413 to LF, MN. The Hungarian Breast and Ovarian Cancer Study was supported by Hungarian Research grants KTIA-OTKA CK-80745 and NKFI OTKA K-112228 and the Norwegian EEA Financial Mechanism HU0115/NA/2008-3/?P-9. Lund-BRCA collaborators are supported by the Swedish Cancer Society, Lund Hospital Funds, and European Research Council Advanced grant ERC-2011-294576. Stockholm-BRCA collaborators are supported by the Swedish Cancer Society. Funding Information: The Hungarian Breast and Ovarian Cancer Study was supported by Hungarian Research grants KTIA-OTKA CK-80745 and NKFI OTKA K-112228 and the Norwegian EEA Financial Mechanism HU0115/NA/2008-3/OP-9.€ Funding Information: The Breast Cancer Family Registry (BCFR) was supported by the US National Institute of Health (grant number RO1CA159868). The Australian BCFR was supported in Australia by the National Health and Medical Research Council, the New South Wales Cancer Council, the Victorian Health Promotion Foundation, the Victorian Breast Cancer Research Consortium, Cancer Australia, and the National Breast Cancer Foundation. The six sites of the Breast Cancer Family Registry (BCFR) were supported by grant UM1 CA164920 from the US National Cancer Institute. The content of this manuscript does not necessarily reflect the views or policies of the National Cancer Institute or any of the collaborating centers in the BCFR, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government or the BCFR. Funding Information: D. Gareth Evans is supported by a National Institute for Health Research (NIHR) grant to the Biomedical Research Centre, Manchester. The investigators at the Institute of Cancer Research and the Royal Marsden NHS Foundation Trust are supported by an NIHR grant to the Biomedical Research Centre at the Institute of Cancer Research and the Royal Marsden NHS Foundation Trust. Ros Eeles and Elizabeth Bancroft are supported by Cancer Research UK grant C5047/A8385. Ros Eeles is also supported by NIHR support to the Biomedical Research Centre at the Institute of Cancer Research and the Royal Marsden NHS Foundation Trust. Antonis C. Antoniou is funded by Cancer Research UK grants C12292/A20861 and C12292/ A11174. MT is funded by the European Union Seventh Framework Program (2007– 013)/European Research Council (310018). Funding Information: Lund-BRCA collaborators are supported by the Swedish Cancer Society, Lund Hospital Funds, and European Research Council Advanced grant ERC-2011-294576. Stockholm-BRCA collaborators are supported by the Swedish Cancer Society. Funding Information: The Epidemiological Study of Familial Breast Cancer (EMBRACE) is supported by Cancer Research UK grants C1287/A23382 and C1287/A16563. Funding Information: Hospital Clinico San Carlos (HCSC) was supported by CIBERONC 161200301 from ISCIII (Spain), partially supported by European Regional Development FEDER funds. Funding Information: This work was supported by Cancer Research UK grants C1287/A17523, C1287/23382, C1287/A16563, C12292/A20861, and C12292/A11174. Funding Information: The national French cohort, GENEPSO, had been supported by a grant from the Fondation de France and the Ligue Nationale Contre le Cancer and is being supported by a grant from INCa as part of the European program ERA-NET on Translational Cancer Research (TRANSCAN-JTC2012, n°2014-008). Funding Information: The International Hereditary Cancer Center (IHCC) was supported by grant PBZ_KBN_122/P05/2004 and ERA-NET TRANSAN JTC 2012 Cancer 12-054 (ERA-NET-TRANSCAN/07/ 2014). Funding Information: The HEBON study is supported by the Dutch Cancer Society grants NKI1998-1854, NKI2004-3088, NKI2007-3756; the Netherlands Organisation of Scientific Research grant NWO 91109024; the Pink Ribbon grants 110005 and 2014-187.WO76; the BBMRI grant NWO 184.021.007/CP46; and the Transcan grant JTC 2012 Cancer 12-054. Publisher Copyright: © The Author(s) 2018.
PY - 2018/10/1
Y1 - 2018/10/1
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.
UR - http://www.scopus.com/inward/record.url?scp=85072583152&partnerID=8YFLogxK
U2 - 10.1093/JNCICS/PKY078
DO - 10.1093/JNCICS/PKY078
M3 - Article
C2 - 30873510
AN - SCOPUS:85072583152
SN - 2515-5091
VL - 2
JO - JNCI cancer spectrum
JF - JNCI cancer spectrum
IS - 4
M1 - pky078
ER -