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      BRCA1 mutation in breast cancer patients: Analysis of prognostic factors and survival

      1 , 2 , 3
      Oncology Letters
      Spandidos Publications

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          Abstract

          <p class="first" id="d2837786e144">The presence of BRCA1 mutations is associated with an increased risk of breast and ovarian cancer. The present study compared clinicopathological characteristics and overall survival (OS) of hereditary and sporadic breast cancer. Using data collected from a previous study conducted between 2007–2016 at the Maria Skłodowska Curie Cancer Center and Institute of Oncology (Gliwice, Poland), the prognostic factors and survival in 60 breast cancer mutation carriers were analyzed. A control group was selected from the breast cancer patients without BRCA mutations (n=386). BRCA mutation carriers had significantly worse survival when compared with non-carriers (P=0.017). The 10-year OS rate was 78.0% for all analyzed groups: 65.9% for BRCA mutation carriers and 81.1% for non-carriers. In the univariate analyses, BRCA mutation carriers had a significantly higher risk of mortality in comparison to non-carriers [hazard ratio (HR)=1.87; 95% confidence interval (CI) 1.08–3.25]. Increased tumor size (HR=3.64), lymph node metastases (HR=2.45) and higher histological grade (HR=2.84) were significant factors for worse OS. Positive estrogen receptor status was associated with a better OS (HR=0.49, P=0.022). Age ≤40 years (HR=0.48, P=0.081) was an insignificantly favorable factor. The 10-year survival rate was significantly decreased in patients with BRCA1 mutation. Therefore, negative factors for OS in mutation carriers included lymph nodes metastases, negative steroid receptor status and increased tumor size. </p>

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          Clinical outcomes of breast cancer in carriers of BRCA1 and BRCA2 mutations.

          Some features of breast cancer in women with a BRCA1 mutation suggest that hereditary breast cancer has a poor outcome. We conducted a national population-based study of Israeli women to determine the influence, if any, of a BRCA1 or a BRCA2 mutation on the prognosis in breast cancer. We obtained data on all incident cases of invasive breast cancer that were diagnosed from January 1, 1987, to December 31, 1988, and recorded in the Israel National Cancer Registry. We requested a paraffin-embedded tumor block or an unstained slide and the corresponding pathological and clinical records for all such cases. DNA extracted from the tumor specimens was analyzed for the three founder mutations in BRCA1 and BRCA2. For each subject, available pathological and oncologic records were reviewed. We were able to retrieve a pathological sample from 1794 of 2514 subjects (71%). Among those women, we obtained medical records for 1545 (86%). A BRCA1 or BRCA2 mutation was identified in 10% of the women who were of Ashkenazi Jewish ancestry. The adjusted hazard ratios for death from breast cancer were not significantly different among mutation carriers and noncarriers (hazard ratio among BRCA1 carriers, 0.76; 95% confidence interval [CI], 0.45 to 1.30; P=0.31; hazard ratio among BRCA2 carriers, 1.31; 95% CI, 0.80 to 2.15; P=0.28). Among women who were treated with chemotherapy, the hazard ratio for death among BRCA1 carriers was 0.48 (95% CI, 0.19 to 1.21; P=0.12). Breast cancer-specific rates of death among Israeli women are similar for carriers of a BRCA founder mutation and noncarriers. Copyright 2007 Massachusetts Medical Society.
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            Founder mutations in the BRCA1 gene in Polish families with breast-ovarian cancer.

            We have undertaken a hospital-based study, to identify possible BRCA1 and BRCA2 founder mutations in the Polish population. The study group consisted of 66 Polish families with cancer who have at least three related females affected with breast or ovarian cancer and who had cancer diagnosed, in at least one of the three affected females, at age <50 years. A total of 26 families had both breast and ovarian cancers, 4 families had ovarian cancers only, and 36 families had breast cancers only. Genomic DNA was prepared from the peripheral blood leukocytes of at least one affected woman from each family. The entire coding region of BRCA1 and BRCA2 was screened for the presence of germline mutations, by use of SSCP followed by direct sequencing of observed variants. Mutations were found in 35 (53%) of the 66 families studied. All but one of the mutations were detected within the BRCA1 gene. BRCA1 abnormalities were identified in all four families with ovarian cancer only, in 67% of 27 families with both breast and ovarian cancer, and in 34% of 35 families with breast cancer only. The single family with a BRCA2 mutation had the breast-ovarian cancer syndrome. Seven distinct mutations were identified; five of these occurred in two or more families. In total, recurrent mutations were found in 33 (94%) of the 35 families with detected mutations. Three BRCA1 abnormalities-5382insC, C61G, and 4153delA-accounted for 51%, 20%, and 11% of the identified mutations, respectively.
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              Is Open Access

              Effect of BRCA germline mutations on breast cancer prognosis

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                Author and article information

                Journal
                Oncology Letters
                Oncol Lett
                Spandidos Publications
                1792-1074
                1792-1082
                November 28 2018
                November 28 2018
                Affiliations
                [1 ]Outpatient Clinic, Maria Skłodowska‑Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, 44‑101 Gliwice, Poland
                [2 ]Biostatistics Unit, Maria Skłodowska‑Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, 44‑101 Gliwice, Poland
                [3 ]Center for Translational Research and Molecular Biology of Cancer, Maria Skłodowska‑Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch, 44‑101 Gliwice, Poland
                Article
                10.3892/ol.2018.9770
                6341769
                30675265
                c55b4890-779c-46c8-b1e8-a233f4522de9
                © 2018
                History

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