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dc.contributor.authorNilsson, Martin P
dc.contributor.authorHartman, Linda
dc.contributor.authorIdvall, Ingrid
dc.contributor.authorKristoffersson, Ulf
dc.contributor.authorJohannsson, Oskar T
dc.contributor.authorLoman, Niklas
dc.date.accessioned2014-11-05T16:35:52Z
dc.date.available2014-11-05T16:35:52Z
dc.date.issued2014-02
dc.date.submitted2014
dc.identifier.citationBreast Cancer Res. Treat. 2014, 144 (1):133-42en
dc.identifier.issn1573-7217
dc.identifier.pmid24477976
dc.identifier.doi10.1007/s10549-014-2842-9
dc.identifier.urihttp://hdl.handle.net/2336/333739
dc.descriptionTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.en
dc.description.abstractAll women in the South Sweden Health Care Region with breast cancer diagnosed aged less than 41 during the period between 1990 and 1995 were contacted in 1996 and offered germline mutation analysis of the BRCA1 and BRCA2 genes. Mutation carriers (n = 20) were compared with noncarriers (n = 201) for overall survival (OS) and risk of contralateral breast cancer (CBC). Mutation carriers were younger at diagnosis and more likely to have ER-negative, PgR-negative and grade III tumors. Median follow-up was 19 years. The 5-, 10-, 15-, and 20-year OS were 60, 45, 39, and 39 % for mutation carriers and 82, 70, 59, and 53 % for noncarriers, respectively (5-year log-rank P = 0.013; 10-year P = 0.008; 15-year P = 0.020; and 20-year P = 0.046). In univariable analysis, there was a trend for an inferior OS for mutation carriers (HR 1.8; 95 % CI 1.0-3.3). When stratified for use of (neo)adjuvant chemotherapy, an inferior OS was significant only for the subgroup of patients who did not receive chemotherapy (HR 3.0; 95 % CI 1.2-7.7). In multivarible analysis, BRCA1/2 mutation status was a significant predictor of OS when adjusting for tumor stage, age, and use of chemotherapy, but not when ER status was also included in the model. The 15-year cumulative risk of CBC was 53 % for mutation carriers and 10 % for noncarriers (HR 5.9; 95 % CI 1.9-18.6); among the noncarriers the risks were 5, 22, and 30 % for patients without close relatives having breast cancer, with second-degree relatives having breast cancer, and with firstdegree relatives with breast cancer, respectively. In conclusion, the poor prognosis of young BRCA1/2 mutation carriers with breast cancer is mainly explained by the prevalent occurrence of negative prognostic factors rather than mutation status per se, and can to at least some extent be abrogated by the use of chemotherapy.
dc.description.sponsorshipSkane County Counsil's Research and Development Foundation The Swedish Breast Cancer Association (BRO) BioCAREen
dc.language.isoenen
dc.publisherSpringeren
dc.relation.urlhttp://dx.doi.org/10.1007/s10549-014-2842-9en
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3924030/en
dc.rightsopenAccessen
dc.subjectBrjóstakrabbameinen
dc.subjectArfgengien
dc.subject.meshAdulten
dc.subject.meshAge of Onseten
dc.subject.meshBRCA1 Proteinen
dc.subject.meshBRCA2 Proteinen
dc.subject.meshBreast Neoplasmsen
dc.subject.meshCohort Studiesen
dc.subject.meshDNA Mutational Analysisen
dc.subject.meshFollow-Up Studiesen
dc.subject.meshGerm-Line Mutationen
dc.subject.meshHumansen
dc.subject.meshKaplan-Meier Estimateen
dc.subject.meshMaleen
dc.subject.meshNeoplasms, Second Primaryen
dc.subject.meshPrognosisen
dc.subject.meshProportional Hazards Modelsen
dc.titleLong-term prognosis of early-onset breast cancer in a population-based cohort with a known BRCA1/2 mutation status.en
dc.typeArticleen
dc.contributor.departmentDepartment of Oncology, Skåne University Hospital, Clinical Sciences, Lund University, S-221 85, Lund, Sweden, martin.nilsson@med.lu.se.en
dc.identifier.journalBreast cancer research and treatmenten
dc.rights.accessOpen Accessen
refterms.dateFOA2018-09-12T13:55:00Z
html.description.abstractAll women in the South Sweden Health Care Region with breast cancer diagnosed aged less than 41 during the period between 1990 and 1995 were contacted in 1996 and offered germline mutation analysis of the BRCA1 and BRCA2 genes. Mutation carriers (n = 20) were compared with noncarriers (n = 201) for overall survival (OS) and risk of contralateral breast cancer (CBC). Mutation carriers were younger at diagnosis and more likely to have ER-negative, PgR-negative and grade III tumors. Median follow-up was 19 years. The 5-, 10-, 15-, and 20-year OS were 60, 45, 39, and 39 % for mutation carriers and 82, 70, 59, and 53 % for noncarriers, respectively (5-year log-rank P = 0.013; 10-year P = 0.008; 15-year P = 0.020; and 20-year P = 0.046). In univariable analysis, there was a trend for an inferior OS for mutation carriers (HR 1.8; 95 % CI 1.0-3.3). When stratified for use of (neo)adjuvant chemotherapy, an inferior OS was significant only for the subgroup of patients who did not receive chemotherapy (HR 3.0; 95 % CI 1.2-7.7). In multivarible analysis, BRCA1/2 mutation status was a significant predictor of OS when adjusting for tumor stage, age, and use of chemotherapy, but not when ER status was also included in the model. The 15-year cumulative risk of CBC was 53 % for mutation carriers and 10 % for noncarriers (HR 5.9; 95 % CI 1.9-18.6); among the noncarriers the risks were 5, 22, and 30 % for patients without close relatives having breast cancer, with second-degree relatives having breast cancer, and with firstdegree relatives with breast cancer, respectively. In conclusion, the poor prognosis of young BRCA1/2 mutation carriers with breast cancer is mainly explained by the prevalent occurrence of negative prognostic factors rather than mutation status per se, and can to at least some extent be abrogated by the use of chemotherapy.


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