title: Triple-negative breast cancer frequency and type ofBRCAmutation: Clues from Sardinia.
abstract: Germline mutations inBRCA1orBRCA2genes have been demonstrated to increase the risk of developing breast cancer. Among the prognostic factors currently used in clinical practice, the disease stage and the receptor status play a crucial role in the management of breast carcinoma. Triple-negative breast cancer (TNBC) has been classified as a disease subgroup that is negative for oestrogen, progesterone and HER2 receptor expression, and presents a poor prognosis. The present study investigated the correlation betweenBRCA1/2mutations and TNBC status in a large series (n=726) of breast cancer patients from Sardinia. TheBRCAmutation screening was performed on genomic DNA from peripheral blood samples by denaturing high-performance liquid chromatography analysis and automated DNA sequencing. Overall, 21/726 (2.9%) patients carried a germline mutation inBRCA1orBRCA2. The TNBC phenotype was significantly associated with theBRCA1mutations (P<0.001), whereas no association was found with theBRCA2mutations (P=0.837). With respect to patient origin within Sardinia, a significant inverse distribution of mutations was found;BRCA1andBRCA2mutations represented 86 and 93% of the mutated cases in Southern and Middle-Northern Sardinia, respectively (P<0.001). Patients from the geographical area withBRCA1mutation prevalence presented a TNBC incidence much higher than that observed in cases from the area withBRCA2mutation prevalence (12 vs. 4%, respectively; P=0.037). These findings further confirmed that the occurrence of TNBC is significantly associated with theBRCA1mutation carrier status and that a different 'genetic background' may have a phenotypic impact in the onset of breast cancer.
authors.affiliation: Institute of Biomolecular Chemistry (ICB), National Research Council (CNR), Sassari, Sassari, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Palomba
authors.affiliation: Service of Epidemiology, Local Health Unit 1 (ASL1), Sassari, Sassari, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Budroni
authors.affiliation: Unit of Medical Oncology, Local Health Unit 1 (ASL1), Sassari, Sassari, Italy.
authors.forename: Nina
authors.initials: N
authors.lastname: Olmeo
authors.affiliation: Department of Medical Oncology, Hospital-University Health Unit (AOU), Cagliari, Cagliari, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Atzori
authors.affiliation: Department of Medical Oncology, Hospital-University Health Unit (AOU), Cagliari, Cagliari, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Ionta
authors.affiliation: Institute of Biomolecular Chemistry (ICB), National Research Council (CNR), Sassari, Sassari, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Pisano
authors.affiliation: Institute of Pathology, University of Sassari, Sassari, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Tanda
authors.affiliation: Service of Pathology, Hospital-University Health Unit (AOU), Sassari, Sassari, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cossu
authors.affiliation: Institute of Biomolecular Chemistry (ICB), National Research Council (CNR), Sassari, Sassari, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palmieri
keywords: BRCA1 and BRCA2 genes; mutation analysis; triple-negative breast cancer