Mutation detection rates associated with specific selection criteria for BRCA1/2 testing in 1854 high-risk families: A monocentric Italian study

Jacopo Azzollini, Giulietta Scuvera, Eleonora Bruno, Patrizia Pasanisi, Daniela Zaffaroni, M. Calvello, Barbara Pasini, Carla Barbara Ripamonti, Mara Colombo, Valeria Pensotti, Paolo Radice, Bernard Gilles Peissel, Siranoush Manoukian

Research output: Contribution to journalArticle

Abstract

Background: BRCA mutation screening is frequently offered on the basis of the fulfillment of empirical selection criteria, thought to be indicative of a genetic predisposition to breast/ovarian cancer (BrCa/OvCa). This study aimed to evaluate, in a large cohort of BrCa/OvCa families, the mutation detection rate (DR) associated with specific clinical features and the relative performance of the employed selection criteria. Methods: BRCA gene analysis was performed on 1854 family probands. The Fisher exact test was used to compare the DRs associated with different clinical features. In a subset of families fulfilling only mutually exclusive criteria, odds ratios and 95% CI were estimated to test the relative effectiveness of each criterion. Results: The overall DR was 29.3%. Among BrCa-only families, the DRs were significantly higher in the presence of early-onset compared with late-onset cases, and of bilateral compared with unilateral cases. In families with bilateral cases, ages at diagnosis of both the first and second tumour were significantly lower in mutation carriers. In families fulfilling mutually exclusive criteria, OvCa was the best predictor of BRCA mutations, with DRs (range: 31.8%-80.0%) significantly higher compared with the other criteria. Conversely, isolated early-onset BrCa and three or more late-onset BrCa displayed significantly lower predictive values (7.9% and 7.2%, respectively). Conclusions: The observed estimates, albeit confirming a DR above 10% for most of the considered criteria, highlighted some relevant differences among them. Such differences should be taken into account in the identification of patients who might benefit from genetic counselling and subsequent testing.

Original languageEnglish
JournalEuropean Journal of Internal Medicine
DOIs
Publication statusAccepted/In press - Feb 4 2016

Fingerprint

Mutation Rate
Patient Selection
Mutation
Genetic Counseling
Genetic Predisposition to Disease
Ovarian Neoplasms
Odds Ratio
Breast Neoplasms
Genes
Neoplasms

Keywords

  • BRCA1 gene
  • BRCA2 gene
  • Genetic testing
  • Hereditary breast and ovarian cancer syndrome
  • Selection criteria

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Mutation detection rates associated with specific selection criteria for BRCA1/2 testing in 1854 high-risk families : A monocentric Italian study. / Azzollini, Jacopo; Scuvera, Giulietta; Bruno, Eleonora; Pasanisi, Patrizia; Zaffaroni, Daniela; Calvello, M.; Pasini, Barbara; Ripamonti, Carla Barbara; Colombo, Mara; Pensotti, Valeria; Radice, Paolo; Peissel, Bernard Gilles; Manoukian, Siranoush.

In: European Journal of Internal Medicine, 04.02.2016.

Research output: Contribution to journalArticle

@article{0bbae2050e0e4cd6852a20f15d6b4bb3,
title = "Mutation detection rates associated with specific selection criteria for BRCA1/2 testing in 1854 high-risk families: A monocentric Italian study",
abstract = "Background: BRCA mutation screening is frequently offered on the basis of the fulfillment of empirical selection criteria, thought to be indicative of a genetic predisposition to breast/ovarian cancer (BrCa/OvCa). This study aimed to evaluate, in a large cohort of BrCa/OvCa families, the mutation detection rate (DR) associated with specific clinical features and the relative performance of the employed selection criteria. Methods: BRCA gene analysis was performed on 1854 family probands. The Fisher exact test was used to compare the DRs associated with different clinical features. In a subset of families fulfilling only mutually exclusive criteria, odds ratios and 95{\%} CI were estimated to test the relative effectiveness of each criterion. Results: The overall DR was 29.3{\%}. Among BrCa-only families, the DRs were significantly higher in the presence of early-onset compared with late-onset cases, and of bilateral compared with unilateral cases. In families with bilateral cases, ages at diagnosis of both the first and second tumour were significantly lower in mutation carriers. In families fulfilling mutually exclusive criteria, OvCa was the best predictor of BRCA mutations, with DRs (range: 31.8{\%}-80.0{\%}) significantly higher compared with the other criteria. Conversely, isolated early-onset BrCa and three or more late-onset BrCa displayed significantly lower predictive values (7.9{\%} and 7.2{\%}, respectively). Conclusions: The observed estimates, albeit confirming a DR above 10{\%} for most of the considered criteria, highlighted some relevant differences among them. Such differences should be taken into account in the identification of patients who might benefit from genetic counselling and subsequent testing.",
keywords = "BRCA1 gene, BRCA2 gene, Genetic testing, Hereditary breast and ovarian cancer syndrome, Selection criteria",
author = "Jacopo Azzollini and Giulietta Scuvera and Eleonora Bruno and Patrizia Pasanisi and Daniela Zaffaroni and M. Calvello and Barbara Pasini and Ripamonti, {Carla Barbara} and Mara Colombo and Valeria Pensotti and Paolo Radice and Peissel, {Bernard Gilles} and Siranoush Manoukian",
year = "2016",
month = "2",
day = "4",
doi = "10.1016/j.ejim.2016.03.010",
language = "English",
journal = "European Journal of Internal Medicine",
issn = "0953-6205",
publisher = "Elsevier B.V.",

}

TY - JOUR

T1 - Mutation detection rates associated with specific selection criteria for BRCA1/2 testing in 1854 high-risk families

T2 - A monocentric Italian study

AU - Azzollini, Jacopo

AU - Scuvera, Giulietta

AU - Bruno, Eleonora

AU - Pasanisi, Patrizia

AU - Zaffaroni, Daniela

AU - Calvello, M.

AU - Pasini, Barbara

AU - Ripamonti, Carla Barbara

AU - Colombo, Mara

AU - Pensotti, Valeria

AU - Radice, Paolo

AU - Peissel, Bernard Gilles

AU - Manoukian, Siranoush

PY - 2016/2/4

Y1 - 2016/2/4

N2 - Background: BRCA mutation screening is frequently offered on the basis of the fulfillment of empirical selection criteria, thought to be indicative of a genetic predisposition to breast/ovarian cancer (BrCa/OvCa). This study aimed to evaluate, in a large cohort of BrCa/OvCa families, the mutation detection rate (DR) associated with specific clinical features and the relative performance of the employed selection criteria. Methods: BRCA gene analysis was performed on 1854 family probands. The Fisher exact test was used to compare the DRs associated with different clinical features. In a subset of families fulfilling only mutually exclusive criteria, odds ratios and 95% CI were estimated to test the relative effectiveness of each criterion. Results: The overall DR was 29.3%. Among BrCa-only families, the DRs were significantly higher in the presence of early-onset compared with late-onset cases, and of bilateral compared with unilateral cases. In families with bilateral cases, ages at diagnosis of both the first and second tumour were significantly lower in mutation carriers. In families fulfilling mutually exclusive criteria, OvCa was the best predictor of BRCA mutations, with DRs (range: 31.8%-80.0%) significantly higher compared with the other criteria. Conversely, isolated early-onset BrCa and three or more late-onset BrCa displayed significantly lower predictive values (7.9% and 7.2%, respectively). Conclusions: The observed estimates, albeit confirming a DR above 10% for most of the considered criteria, highlighted some relevant differences among them. Such differences should be taken into account in the identification of patients who might benefit from genetic counselling and subsequent testing.

AB - Background: BRCA mutation screening is frequently offered on the basis of the fulfillment of empirical selection criteria, thought to be indicative of a genetic predisposition to breast/ovarian cancer (BrCa/OvCa). This study aimed to evaluate, in a large cohort of BrCa/OvCa families, the mutation detection rate (DR) associated with specific clinical features and the relative performance of the employed selection criteria. Methods: BRCA gene analysis was performed on 1854 family probands. The Fisher exact test was used to compare the DRs associated with different clinical features. In a subset of families fulfilling only mutually exclusive criteria, odds ratios and 95% CI were estimated to test the relative effectiveness of each criterion. Results: The overall DR was 29.3%. Among BrCa-only families, the DRs were significantly higher in the presence of early-onset compared with late-onset cases, and of bilateral compared with unilateral cases. In families with bilateral cases, ages at diagnosis of both the first and second tumour were significantly lower in mutation carriers. In families fulfilling mutually exclusive criteria, OvCa was the best predictor of BRCA mutations, with DRs (range: 31.8%-80.0%) significantly higher compared with the other criteria. Conversely, isolated early-onset BrCa and three or more late-onset BrCa displayed significantly lower predictive values (7.9% and 7.2%, respectively). Conclusions: The observed estimates, albeit confirming a DR above 10% for most of the considered criteria, highlighted some relevant differences among them. Such differences should be taken into account in the identification of patients who might benefit from genetic counselling and subsequent testing.

KW - BRCA1 gene

KW - BRCA2 gene

KW - Genetic testing

KW - Hereditary breast and ovarian cancer syndrome

KW - Selection criteria

UR - http://www.scopus.com/inward/record.url?scp=84962433273&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84962433273&partnerID=8YFLogxK

U2 - 10.1016/j.ejim.2016.03.010

DO - 10.1016/j.ejim.2016.03.010

M3 - Article

JO - European Journal of Internal Medicine

JF - European Journal of Internal Medicine

SN - 0953-6205

ER -