title: Predictive Factors for BRCA1 and BRCA2 Genetic Testing in an Asian Clinic-Based Population.
abstract: OBJECTIVE
  The National Comprehensive Cancer Network (NCCN) has proposed guidelines for the genetic testing of the BRCA1 and BRCA2 genes, based on studies in western populations. This current study assessed potential predictive factors for BRCA mutation probability, in an Asian population.
  
  
  METHODS
  A total of 359 breast cancer patients, who presented with either a family history (FH) of breast and/or ovarian cancer or early onset breast cancer, were accrued at the National Cancer Center Singapore (NCCS). The relationships between clinico-pathological features and mutational status were calculated using the Chi-squared test and binary logistic regression analysis.
  
  
  RESULTS
  Of 359 patients, 45 (12.5%) had deleterious or damaging missense mutations in BRCA1 and/or BRCA2. BRCA1 mutations were more likely to be found in ER-negative than ER-positive breast cancer patients (P=0.01). Moreover, ER-negative patients with BRCA mutations were diagnosed at an earlier age (40 vs. 48 years, P=0.008). Similarly, triple-negative breast cancer (TNBC) patients were more likely to have BRCA1 mutations (P=0.001) and that these patients were diagnosed at a relatively younger age than non-TNBC patients (38 vs. 46 years, P=0.028). Our analysis has confirmed that ER-negative status, TNBC status and a FH of hereditary breast and ovarian cancer (HBOC) are strong factors predicting the likelihood of having BRCA mutations.
  
  
  CONCLUSIONS
  Our study provides evidence that TNBC or ER-negative patients may benefit from BRCA genetic testing, particularly younger patients (<40 years) or those with a strong FH of HBOC, in Asian patients.
authors.affiliation: Division of Medical Sciences, Humphrey Oei Institute of Cancer Research, National Cancer Centre, Singapore, Singapore.
authors.forename: Edward S Y
authors.initials: ES
authors.lastname: Wong
authors.affiliation: Division of Medical Sciences, Humphrey Oei Institute of Cancer Research, National Cancer Centre, Singapore, Singapore.
authors.forename: Sandhya
authors.initials: S
authors.lastname: Shekar
authors.affiliation: Division of Medical Sciences, Humphrey Oei Institute of Cancer Research, National Cancer Centre, Singapore, Singapore.
authors.forename: Claire H T
authors.initials: CH
authors.lastname: Chan
authors.affiliation: Institute of Molecular and Cell Biology, Singapore, Singapore.
authors.forename: Lewis Z
authors.initials: LZ
authors.lastname: Hong
authors.affiliation: Institute of Molecular and Cell Biology, Singapore, Singapore.
authors.forename: Suk-Yean
authors.initials: SY
authors.lastname: Poon
authors.affiliation: Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Toomas
authors.initials: T
authors.lastname: Silla
authors.affiliation: Human Genetics, Genome Institute of Singapore, Singapore, Singapore.
authors.forename: Clarabelle
authors.initials: C
authors.lastname: Lin
authors.affiliation: Human Genetics, Genome Institute of Singapore, Singapore, Singapore.
authors.forename: Vikrant
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Human Genetics, Genome Institute of Singapore, Singapore, Singapore.
authors.forename: Sonia
authors.initials: S
authors.lastname: Davila
authors.affiliation: Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Mathijs
authors.initials: M
authors.lastname: Voorhoeve
authors.affiliation: Department of Pathology, Singapore General Hospital, Singapore, Singapore.
authors.forename: Aye Aye
authors.initials: AA
authors.lastname: Thike
authors.affiliation: Department of Surgical Oncology, National Cancer Centre, Singapore, Singapore.
authors.forename: Gay Hui
authors.initials: GH
authors.lastname: Ho
authors.affiliation: Division of Medical Oncology, National Cancer Centre, Singapore, Singapore.
authors.forename: Yoon Sim
authors.initials: YS
authors.lastname: Yap
authors.affiliation: Department of Pathology, Singapore General Hospital, Singapore, Singapore.
authors.forename: Puay Hoon
authors.initials: PH
authors.lastname: Tan
authors.affiliation: Division of Medical Oncology, National Cancer Centre, Singapore, Singapore.
authors.forename: Min-Han
authors.initials: MH
authors.lastname: Tan
authors.affiliation: Division of Medical Oncology, National Cancer Centre, Singapore, Singapore; OncoCare Cancer Centre, Mount Elizabeth Novena Specialist Centre, Singapore, Singapore.
authors.forename: Peter
authors.initials: P
authors.lastname: Ang
authors.affiliation: Division of Medical Sciences, Humphrey Oei Institute of Cancer Research, National Cancer Centre, Singapore, Singapore; Department of Physiology, Yong Yoo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Office of Clinical and Academic Faculty Affairs, Duke-NUS Graduate Medical School, Singapore, Singapore.
authors.forename: Ann S G
authors.initials: AS
authors.lastname: Lee
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D044466:Asian People / Q000235:genetics*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D016009:Chi-Square Distribution; D004252:DNA Mutational Analysis / Q000379:methods / Q000706:statistics & numerical data; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D005820:Genetic Testing / Q000379:methods* / Q000706:statistics & numerical data; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D020125:Mutation, Missense; D011237:Predictive Value of Tests; D011960:Receptors, Estrogen / Q000378:metabolism; D012307:Risk Factors; D012846:Singapore; D064726:Triple Negative Breast Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: D011960:Receptors, Estrogen