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Limited family structure and triple-negative breast cancer (TNBC) subtype as predictors of BRCA mutations in a genetic counseling cohort of early-onset sporadic breast cancers

  • Epidemiology
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Abstract

Early-onset diagnosis is an eligibility criterion for BRCA1 and BRCA2 (BRCA) testing in sporadic breast cancer patients. Limited family structure has been proposed as a predictor of BRCA mutation status in this group of patients. An overwhelming amount of data supports a strong association between BRCA1 mutations and triple-negative breast cancer (TNBC). Here, we analyze the feasibility of using limited family structure and TNBC as predictors of BRCA mutation status in early-onset breast cancer patients attending genetic counseling units. We have conducted the study in a cohort of sporadic early-onset (≤35 years) breast cancer patients (N = 341) previously selected for BRCA genetic testing in Academic Hereditary Cancer Clinics from Spain. A retrospective review of medical records available at the time of risk assessment allowed us classifying patients according to family structure and TNBC. In addition, BRCAPRO score was calculated for all patients. Association between categorical variables was investigated using the Fisher’s exact test. Binary Logistic Regression Analysis was used for multivariate analysis. Limited family structure (OR 3.61, p = 0.013) and TNBC (OR 3.14, p = 0.013) were independent predictors of BRCA mutation status. Mutation prevalence in the subgroup of patients with at least one positive predictor was 14 %, whereas it dropped to 3 % in non-TNBCs with adequate family history (OR 5.31, 95 % CI 1.38–23.89, p = 0.006). BRCAPRO correctly discerned between limited and adequate family structures. Limited family structure and TNBC are feasible predictors of BRCA mutation status in sporadic early-onset (≤35 years) breast cancer patients attending genetic counseling units. The low prevalence of mutations observed in non-TNBCs with adequate family structure suggests that this subgroup of patients might be excluded from genetic testing.

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Acknowledgments

This work was supported by research Grants (PI12/00539) to M. de la Hoya, Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Science and Innovation & Eurpean Regional Development Fund (ERDF) “A way to make Europe”, research grants (RD06/0020/1051 and RD12/0036/008) from Red Temática de Investigación Cooperativa en Cáncer (RTICC) to E. Diaz-Rubio, Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Science and Innovation & Eurpean Regional Development Fund (ERDF) “A way to make Europe”, research Grant (10PXIB 9101297PR), Xunta de Galicia, and research grant FMM Foundation to A. Vega.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standards

The study complies with current Spanish laws.

Author information

Author notes

  1. Jon Zugazagoitia

    Present address: Department of Medical Oncology, Instituto de Investigación i+12, Hospital 12 de Octubre, Madrid, Spain

Authors and Affiliations

  1. Genetic Counseling Unit, Department of Clinical Oncology, Hospital Clínico San Carlos, Madrid, Spain

    Jon Zugazagoitia, Pedro Pérez-Segura, Arancha Manzano & Eduardo Díaz-Rubio

  2. Department of Medicine, Medical School, Universidad Complutense, Madrid, Spain

    Pedro Pérez-Segura & Eduardo Díaz-Rubio

  3. Molecular Oncology Laboratory, Instituto de Investigación Sanitaria San Carlos (IdISSC), Hospital Clínico San Carlos, Martín Lagos s/n, 28040, Madrid, Spain

    Pedro Pérez-Segura, Pilar Garre, Atocha Romero, Trinidad Caldés, Eduardo Díaz-Rubio & Miguel de la Hoya

  4. Genetic Counseling Unit, Hereditary Cancer Program, Instituto Catalán de Oncología (ICO), Barcelona, Spain

    Ignacio Blanco & Alex Teulé

  5. Genomic Medicine Group, “Fundación Pública Galega de Medicina Xenómica-SERGAS”, CIBERER, IDIS, Santiago de Compostela, Spain

    Ana Vega & Laura Fachal

  6. Genetic Counseling Unit, Department of Medical Oncology, Hospital Universitario La Paz, Madrid, Spain

    Ana Custodio & Beatriz Martínez

  7. IBMCC, IBSAL and Molecular Medicine Unit, Department of Medicine, Universidad de Salamanca-CSIC-SACYL, Salamanca, Spain

    Rogelio González-Sarmiento & Juan Jesús Cruz-Hernández

  8. Genetic Counseling Unit, Department of Medical Oncology, Hospital Clínico de Valencia, Valencia, Spain

    Isabel Chirivella & Vicente Garcés

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  1. Jon Zugazagoitia
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Correspondence to Miguel de la Hoya.

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Zugazagoitia, J., Pérez-Segura, P., Manzano, A. et al. Limited family structure and triple-negative breast cancer (TNBC) subtype as predictors of BRCA mutations in a genetic counseling cohort of early-onset sporadic breast cancers. Breast Cancer Res Treat 148, 415–421 (2014). https://doi.org/10.1007/s10549-014-3167-4

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