Incidence and outcome of BRCA mutations in unselected patients with triple receptor-negative breast cancer

Ana M. Gonzalez-Angulo, Kirsten M. Timms, Shuying Liu, Huiqin Chen, Jennifer K. Litton, Jennifer Potter, Jerry S. Lanchbury, Katherine Stemke-Hale, Bryan T. Hennessy, Banu K. Arun, Gabriel N. Hortobagyi, Kim Anh Do, Gordon Mills, Funda Meric-Bernstam

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Abstract

Purpose: To investigate the incidence of germline and somatic BRCA1/2 mutations in unselected patients with triple-negative breast cancer (TNBC) and determine the prognostic significance of carrying a mutation. Methods: DNA was obtained from 77 TNBC and normal tissues. BRCA1/2 exons/flanking regions were sequenced from tumor and patients classified as mutant or wild type (WT). Sequencing was repeated from normal tissue to identify germline and somatic mutations. Patient characteristics were compared with chisquare. Survival was estimated by Kaplan-Meier method and compared with log-rank. Cox proportional hazards models were fit to determine the independent association of mutation status with outcome. Results: Median age was 51 years (27-83 years). Fifteen patients (19.5%) had BRCA mutations: 12 (15.6%) in BRCA1 (one somatic), and 3 (3.9%) in BRCA2. Patients with BRCA mutations tended to be younger than WT, (P = 0.005). Grade, histology, and stage were not associated with mutation status. At a median follow-up of 43 months (7-214 months), there were 33 (42.9%) recurrences and 35 (45.5%) deaths. Five-year recurrence-free survival estimates were 51.7% for WT versus 86.2% for patients with mutations, (P = 0.031); and 5-year overall survival estimates were 52.8% for WT versus 73.3% for patients with mutations (P = 0.225). After adjustment, patients with BRCA mutations had a significantly better RFS (HR: 0.19, 95% CI: 0.045-0.79, P = 0.016) compared with WT. Conclusions: In this unselected cohort of TNBC, we found a 19.5% incidence of BRCA mutations. Genetic testing should be discussed with patients with TNBC. Patients with TNBC with BRCA mutations had a significantly lower risk of relapse.

Original languageEnglish (US)
Pages (from-to)1082-1089
Number of pages8
JournalClinical Cancer Research
Volume17
Issue number5
DOIs
StatePublished - Mar 1 2011
Externally publishedYes

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Triple Negative Breast Neoplasms
Mutation
Incidence
Recurrence
Survival
Germ-Line Mutation
Genetic Testing
Proportional Hazards Models
Exons
Histology

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Gonzalez-Angulo, A. M., Timms, K. M., Liu, S., Chen, H., Litton, J. K., Potter, J., ... Meric-Bernstam, F. (2011). Incidence and outcome of BRCA mutations in unselected patients with triple receptor-negative breast cancer. Clinical Cancer Research, 17(5), 1082-1089. https://doi.org/10.1158/1078-0432.CCR-10-2560

Incidence and outcome of BRCA mutations in unselected patients with triple receptor-negative breast cancer. / Gonzalez-Angulo, Ana M.; Timms, Kirsten M.; Liu, Shuying; Chen, Huiqin; Litton, Jennifer K.; Potter, Jennifer; Lanchbury, Jerry S.; Stemke-Hale, Katherine; Hennessy, Bryan T.; Arun, Banu K.; Hortobagyi, Gabriel N.; Do, Kim Anh; Mills, Gordon; Meric-Bernstam, Funda.

In: Clinical Cancer Research, Vol. 17, No. 5, 01.03.2011, p. 1082-1089.

Research output: Contribution to journalArticle

Gonzalez-Angulo, AM, Timms, KM, Liu, S, Chen, H, Litton, JK, Potter, J, Lanchbury, JS, Stemke-Hale, K, Hennessy, BT, Arun, BK, Hortobagyi, GN, Do, KA, Mills, G & Meric-Bernstam, F 2011, 'Incidence and outcome of BRCA mutations in unselected patients with triple receptor-negative breast cancer', Clinical Cancer Research, vol. 17, no. 5, pp. 1082-1089. https://doi.org/10.1158/1078-0432.CCR-10-2560
Gonzalez-Angulo, Ana M. ; Timms, Kirsten M. ; Liu, Shuying ; Chen, Huiqin ; Litton, Jennifer K. ; Potter, Jennifer ; Lanchbury, Jerry S. ; Stemke-Hale, Katherine ; Hennessy, Bryan T. ; Arun, Banu K. ; Hortobagyi, Gabriel N. ; Do, Kim Anh ; Mills, Gordon ; Meric-Bernstam, Funda. / Incidence and outcome of BRCA mutations in unselected patients with triple receptor-negative breast cancer. In: Clinical Cancer Research. 2011 ; Vol. 17, No. 5. pp. 1082-1089.
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abstract = "Purpose: To investigate the incidence of germline and somatic BRCA1/2 mutations in unselected patients with triple-negative breast cancer (TNBC) and determine the prognostic significance of carrying a mutation. Methods: DNA was obtained from 77 TNBC and normal tissues. BRCA1/2 exons/flanking regions were sequenced from tumor and patients classified as mutant or wild type (WT). Sequencing was repeated from normal tissue to identify germline and somatic mutations. Patient characteristics were compared with chisquare. Survival was estimated by Kaplan-Meier method and compared with log-rank. Cox proportional hazards models were fit to determine the independent association of mutation status with outcome. Results: Median age was 51 years (27-83 years). Fifteen patients (19.5{\%}) had BRCA mutations: 12 (15.6{\%}) in BRCA1 (one somatic), and 3 (3.9{\%}) in BRCA2. Patients with BRCA mutations tended to be younger than WT, (P = 0.005). Grade, histology, and stage were not associated with mutation status. At a median follow-up of 43 months (7-214 months), there were 33 (42.9{\%}) recurrences and 35 (45.5{\%}) deaths. Five-year recurrence-free survival estimates were 51.7{\%} for WT versus 86.2{\%} for patients with mutations, (P = 0.031); and 5-year overall survival estimates were 52.8{\%} for WT versus 73.3{\%} for patients with mutations (P = 0.225). After adjustment, patients with BRCA mutations had a significantly better RFS (HR: 0.19, 95{\%} CI: 0.045-0.79, P = 0.016) compared with WT. Conclusions: In this unselected cohort of TNBC, we found a 19.5{\%} incidence of BRCA mutations. Genetic testing should be discussed with patients with TNBC. Patients with TNBC with BRCA mutations had a significantly lower risk of relapse.",
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T1 - Incidence and outcome of BRCA mutations in unselected patients with triple receptor-negative breast cancer

AU - Gonzalez-Angulo, Ana M.

AU - Timms, Kirsten M.

AU - Liu, Shuying

AU - Chen, Huiqin

AU - Litton, Jennifer K.

AU - Potter, Jennifer

AU - Lanchbury, Jerry S.

AU - Stemke-Hale, Katherine

AU - Hennessy, Bryan T.

AU - Arun, Banu K.

AU - Hortobagyi, Gabriel N.

AU - Do, Kim Anh

AU - Mills, Gordon

AU - Meric-Bernstam, Funda

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N2 - Purpose: To investigate the incidence of germline and somatic BRCA1/2 mutations in unselected patients with triple-negative breast cancer (TNBC) and determine the prognostic significance of carrying a mutation. Methods: DNA was obtained from 77 TNBC and normal tissues. BRCA1/2 exons/flanking regions were sequenced from tumor and patients classified as mutant or wild type (WT). Sequencing was repeated from normal tissue to identify germline and somatic mutations. Patient characteristics were compared with chisquare. Survival was estimated by Kaplan-Meier method and compared with log-rank. Cox proportional hazards models were fit to determine the independent association of mutation status with outcome. Results: Median age was 51 years (27-83 years). Fifteen patients (19.5%) had BRCA mutations: 12 (15.6%) in BRCA1 (one somatic), and 3 (3.9%) in BRCA2. Patients with BRCA mutations tended to be younger than WT, (P = 0.005). Grade, histology, and stage were not associated with mutation status. At a median follow-up of 43 months (7-214 months), there were 33 (42.9%) recurrences and 35 (45.5%) deaths. Five-year recurrence-free survival estimates were 51.7% for WT versus 86.2% for patients with mutations, (P = 0.031); and 5-year overall survival estimates were 52.8% for WT versus 73.3% for patients with mutations (P = 0.225). After adjustment, patients with BRCA mutations had a significantly better RFS (HR: 0.19, 95% CI: 0.045-0.79, P = 0.016) compared with WT. Conclusions: In this unselected cohort of TNBC, we found a 19.5% incidence of BRCA mutations. Genetic testing should be discussed with patients with TNBC. Patients with TNBC with BRCA mutations had a significantly lower risk of relapse.

AB - Purpose: To investigate the incidence of germline and somatic BRCA1/2 mutations in unselected patients with triple-negative breast cancer (TNBC) and determine the prognostic significance of carrying a mutation. Methods: DNA was obtained from 77 TNBC and normal tissues. BRCA1/2 exons/flanking regions were sequenced from tumor and patients classified as mutant or wild type (WT). Sequencing was repeated from normal tissue to identify germline and somatic mutations. Patient characteristics were compared with chisquare. Survival was estimated by Kaplan-Meier method and compared with log-rank. Cox proportional hazards models were fit to determine the independent association of mutation status with outcome. Results: Median age was 51 years (27-83 years). Fifteen patients (19.5%) had BRCA mutations: 12 (15.6%) in BRCA1 (one somatic), and 3 (3.9%) in BRCA2. Patients with BRCA mutations tended to be younger than WT, (P = 0.005). Grade, histology, and stage were not associated with mutation status. At a median follow-up of 43 months (7-214 months), there were 33 (42.9%) recurrences and 35 (45.5%) deaths. Five-year recurrence-free survival estimates were 51.7% for WT versus 86.2% for patients with mutations, (P = 0.031); and 5-year overall survival estimates were 52.8% for WT versus 73.3% for patients with mutations (P = 0.225). After adjustment, patients with BRCA mutations had a significantly better RFS (HR: 0.19, 95% CI: 0.045-0.79, P = 0.016) compared with WT. Conclusions: In this unselected cohort of TNBC, we found a 19.5% incidence of BRCA mutations. Genetic testing should be discussed with patients with TNBC. Patients with TNBC with BRCA mutations had a significantly lower risk of relapse.

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