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Long-term prognosis of early-onset breast cancer in a population-based cohort with a known BRCA1/2 mutation status.

Nilsson, Martin LU ; Werner Hartman, Linda LU ; Idvall, Ingrid LU ; Kristoffersson, Ulf LU ; Johannsson, Oskar T and Loman, Niklas LU (2014) In Breast Cancer Research and Treatment 144(1). p.133-142
Abstract
All 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... (More)
All 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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Breast Cancer Research and Treatment
volume
144
issue
1
pages
133 - 142
publisher
Springer
external identifiers
  • pmid:24477976
  • wos:000331649300013
  • scopus:84894676157
ISSN
1573-7217
DOI
10.1007/s10549-014-2842-9
language
English
LU publication?
yes
id
e767f982-ae09-41ad-8fb2-58f2a5300fbc (old id 4286553)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24477976?dopt=Abstract
date added to LUP
2014-02-07 11:02:57
date last changed
2017-10-01 03:22:35
@article{e767f982-ae09-41ad-8fb2-58f2a5300fbc,
  abstract     = {All 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.},
  author       = {Nilsson, Martin and Werner Hartman, Linda and Idvall, Ingrid and Kristoffersson, Ulf and Johannsson, Oskar T and Loman, Niklas},
  issn         = {1573-7217},
  language     = {eng},
  number       = {1},
  pages        = {133--142},
  publisher    = {Springer},
  series       = {Breast Cancer Research and Treatment},
  title        = {Long-term prognosis of early-onset breast cancer in a population-based cohort with a known BRCA1/2 mutation status.},
  url          = {http://dx.doi.org/10.1007/s10549-014-2842-9},
  volume       = {144},
  year         = {2014},
}