Associations of pathogenic mutations responsible for breast cancer risk with histology and immunohistochemistry in Romanian population

Abstract Introduction: Breast cancer is the most common cancer in women worldwide, and Romania makes no exception from this trend. Genetic screening for Hereditary Breast and Ovarian Cancer began to be used on a larger scale after the introduction of Next Generation Sequencing. The aim of this study was to assess the association of deleterious mutations responsible for breast cancer with histopathological and immunohistochemical prognostic factors and to identify some genetic variants in the BRCA1 and BRCA2 genes. Method: 80 patients with breast cancer and negative genetic test or pathogenic variants on BRCA1/2, TP53, PALB2, CHEK2, ATM genes were included. All the cases had a prior histological diagnosis and complete immunohistochemical features. The genetic testing was conducted through a multigene panel. Results: 65% of patients had a deleterious mutation on BRCA genes. In 97.5% of cases the histology was invasive ductal carcinoma. Significant differences were identified between BRCA1 group and negative mutation group regarding estrogen receptor (ER) (p=0.0051), progesterone receptor (PR) (p=0.0004) and Ki67 (p=0.001). Seven breast cancer patients had BRCA1 c.3607C>T variant, which was statistically significantly associated with triple- negative breast cancer (p <0.0001). Of the 7 cases diagnosed with BRCA 2 mutations we identified the c.8755-1G>A variant in 3 cases and the c.9371A>T variant in 3 cases. Discussion and conclusion: Our study confirmed the association of BRCA1 mutations with negative ER, PR or triple negative breast cancer (TNBC). Description of BRCA1 c.3607C>T mutation for the first time in Romanian population and its association with TNBC will need further investigation.

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Screening of BRCA1 and BRCA2 germline mutations in unselected triple‐negative breast cancer patients: A series from north of Morocco

Precision Medical Sciences ◽

10.1002/prm2.12009 ◽

2020 ◽

Vol 9 (1) ◽

pp. 43-48

Author(s):

Mohammed Mansouri ◽

Touria Derkaoui ◽

Joaira Bakkach ◽

Ali Loudiyi ◽

Naima Ghailani Nourouti ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Germline Mutations ◽

Breast Cancer Patients ◽

Brca1 And Brca2

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Study of the Genetic Variants in BRCA1/2 and Non-BRCA Genes in a Population-Based Cohort of 2155 Breast/Ovary Cancer Patients, Including 443 Triple-Negative Breast Cancer Patients, in Argentina

Cancers ◽

10.3390/cancers13112711 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2711

Author(s):

Angela R. Solano ◽

Pablo G. Mele ◽

Fernanda S. Jalil ◽

Natalia C. Liria ◽

Ernesto J. Podesta ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Population Based ◽

Breast Cancer Patients ◽

Ovary Cancer ◽

Brca Gene ◽

Pathogenic Variants ◽

Brca Genes

Gene/s sequencing in hereditary breast/ovary cancer (HBOC) in routine diagnosis is challenged by the analysis of panels. We aim to report a retrospective analysis of BRCA1/2 and non-BRCA gene sequencing in patients with breast/ovary cancer (BOC), including triple-negative breast cancer (TNBC), in our population. In total 2155 BOC patients (1900 analyzed in BRCA1/2 and 255 by multigenic panels) gave 372 (17.2.6%) and 107 (24.1%) likely pathogenic/pathogenic variants (LPVs/PVs), including BRCA and non-BRCA genes, for the total and TNBC patients, respectively. When BOC was present in the same proband, a 51.3% rate was found for LPVs/PVs in BRCA1/2. Most of the LPVs/PVs in the panels were in BRCA1/2; non-BRCA gene LPVs/PVs were in CDH1, CHEK2, CDKN2A, MUTYH, NBN, RAD51D, and TP53. TNBC is associated with BRCA1/2 at a higher rate than the rest of the breast cancer types. The more prevalent PVs in BRCA1/2 genes (mostly in BRCA1) do not rule out the importance to panels of genes, although they are certainly far from shedding light on the gap of the 85% predicted linkage association of BOC with BRCA1/2 and are still not elucidated.

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Analysis of pathogenic variants in BRCA1 and BRCA2 genes using next-generation sequencing in women with triple negative breast cancer from South India

Molecular Biology Reports ◽

10.1007/s11033-022-07129-2 ◽

2022 ◽

Author(s):

Taruna Rajagopal ◽

Arun Seshachalam ◽

Arunachalam Jothi ◽

Krishna Kumar Rathnam ◽

Srikanth Talluri ◽

...

Keyword(s):

Breast Cancer ◽

Next Generation Sequencing ◽

Triple Negative Breast Cancer ◽

South India ◽

Triple Negative ◽

Next Generation ◽

Brca1 And Brca2 ◽

Pathogenic Variants ◽

Brca1 And Brca2 Genes ◽

Generation Sequencing

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Prevalence of BRCA1/2 pathogenic variants in triple negative breast cancer patients stratified according to age at diagnosis.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e13677 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e13677-e13677

Author(s):

Ana Blatnik ◽

Marta Banjac ◽

Ksenija Strojnik ◽

Simona Hotujec ◽

Vida Stegel ◽

...

Keyword(s):

Breast Cancer ◽

Genetic Testing ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Age At Diagnosis ◽

Breast Cancer Patients ◽

Detection Rates ◽

Mutational Spectrum ◽

Pathogenic Variants ◽

Brca1 Brca2

e13677 Background: Triple negative breast cancer (TNBC) is strongly associated with germline BRCA1 pathogenic/likely pathogenic variants (PV/LPVs), with up to 28% TNBC patients being BRCA1 PV/LPV carriers. More recently, PALB2 variants have also been shown to be associated with TNBC. Genetic testing in Slovenian hereditary breast and ovarian cancer (HBOC) patients yields consistently high BRCA1/2 detection rates. Four BRCA1 PVs are particularly common, suggesting possible founder effects. Our aim was to analyze the results of panel based genetic testing in Slovenian TNBC patients, with an emphasis on BRCA1/BRCA2 mutational spectrum and detection rates depending on age at diagnosis. Methods: We evaluated the results of genetic testing, performed using a multi-gene panel in 1000 consecutive breast cancer cases. Only 210 patients with TNBC were included in further analysis. We analyzed the mutational spectrum and BRCA1/2 detection rates in TNBC patients stratified according to age at diagnosis. Results: In 80/210 (38.1%) TNBC patients PV/LPVs in BRCA1/2 were identified. Of these, the majority (74/80) were BRCA1-positive. The following variants: c.181T > G, c.5266dupC, c.1687C > T, and c.844_850dupTCATTAC were identified in 64.4% of BRCA1 carriers. BRCA1/2 detection rate decreased with age at diagnosis but was still 18.2% after age 60 (for BRCA1/2 detection rates stratified according to age at diagnosis see table). In 12/210 (5.7%) TNBC patients PV/LPVs in three other genes were identified (3.3% PALB2, 1.4% CHEK2, and 1% ATM). Conclusions: Prevalence of PVs in BRCA1 appears very high in Slovenian TNBC patients and warrants further population-based allele frequency studies with implications for future population screening. High rates of BRCA1/BRCA2 PVs in patients older than 60 years at diagnosis justify testing all TNBC patients, especially in view of treatment options which now include PARP inhibitors. PALB2 was the second most commonly mutated gene in our patients. [Table: see text]

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A Case of Triple-Negative Breast Cancer with Germline Pathogenic Variants in Both BRCA1 and BRCA2

Case Reports in Oncology ◽

10.1159/000520148 ◽

2021 ◽

pp. 1645-1651

Author(s):

Miyuki Kitahara ◽

Yasuo Hozumi ◽

Mitsuki Machinaga ◽

Yuka Hayashi

Keyword(s):

Breast Cancer ◽

Genetic Testing ◽

Family History ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Ductal Carcinoma ◽

Outer Part ◽

Left Breast ◽

Cancer Syndrome ◽

Pathogenic Variants

We report a rare case of hereditary breast and ovarian cancer syndrome (HBOC) with pathogenic variants in both BRCA1 and BRCA2. The patient was a 78-year-old woman who visited the hospital after noticing a lump in her left breast 6 months before, which gradually increased in size. According to her family history, her maternal aunt developed breast cancer in her 40s. On palpation, a 4-cm large mass was palpated in the upper outer part of the left breast. A needle biopsy revealed invasive ductal carcinoma of the breast, which was negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor type 2. The patient was diagnosed with cT2N0M0 stage IIA, and primary systemic treatment was planned. The patient developed drug-induced interstitial pneumonia after receiving paclitaxel. Although she recovered spontaneously, she did not wish to receive further chemotherapy, and thus surgery was performed. Four months after the surgery, the patient became aware of dyspnea. After a thorough examination, she was diagnosed with postoperative cancer recurrence of the left breast with multiple liver metastases, cancerous peritonitis, multiple bone metastases, and multiple lymph node metastases. Genetic testing was performed, and pathogenic variants were found in both BRAC1 and BRCA2. However, her condition worsened, and she died 8 months after the surgery. BRCA pathogenic variants had more advanced breast cancer on initial diagnosis and worse cancer-related outcomes. It is desirable to consider the optimal approach to the treatment of breast cancer in pathogenic variants. In elderly patients with triple-negative breast cancer, HBOC may be suspected, based on biomarkers and family history. It is important to provide information on genetic counseling, genetic testing, and effective treatment plans proactively.

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Analysis of Pathogenic Variants in BRCA1 and BRCA2 Genes using Next-Generation Sequencing in Women with Triple Negative Breast Cancer from South India

10.21203/rs.3.rs-813826/v1 ◽

2021 ◽

Author(s):

Taruna Rajagopal ◽

Arun Seshachalam ◽

Arunachalam Jothi ◽

Krishna Kumar Rathnam ◽

Srikanth Talluri ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Brca Mutation ◽

Mutation Screening ◽

Preventive Therapy ◽

Brca1 And Brca2 ◽

Indian Women ◽

Pathogenic Variants ◽

South Indian

Abstract The frequency of triple-negative breast cancer (TNBC) incidence varies among different populations, suggesting the involvement of genetic component towards TNBC development. Previous studies have reported that BRCA1/2 germline mutations confer a lifetime risk of developing TNBC. However, there is hardly any information regarding the common pathogenic variants (PVs) in BRCA1/2 genes that contribute to TNBC in the Indian population. Hence, we screened for PVs in BRCA1/2 and their association with clinico-pathological features in TNBC patients. Among the 59 TNBC genomic DNA samples sequenced, 8 BRCA mutations were detected in 59 TNBC patients (13.6%). Almost 50% pre-menopausal TNBC patients had a BRCA mutation. Of the 8 BRCA mutations, we observed BRCA1 mutations in 6 TNBC patients, and BRCA2 mutations in 2 TNBC patients. Among the 6 BRCA1 mutations, three were c.68_69delAG (185delAG) mutation. Remarkably, all the TNBC patients with BRCA mutations exhibited higher-grade tumors (grade 2 or 3). However, among the BRCA mutation carriers, only one patient with a BRCA2 mutation (p.Glu1879Lys) developed metastasis in the observed cohort. Our data advocates that South Indian women with higher grade TNBC tumors and without hereditary breast and ovarian cancer should be considered for BRCA mutation screening, thereby enabling enhanced decision-making and preventive therapy.

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Assessing Clinicopathological Features and Prognosis of Triple-Negative Breast Cancer Patients: A Single-Center Study in Turkey

Archives of Breast Cancer ◽

10.32768/abc.202184297-304 ◽

2021 ◽

pp. 297-304

Author(s):

Saliha Karagöz Eren ◽

Alaettin Arslan ◽

Ebru Akay ◽

Nail Özhan ◽

Yunus Dönder

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Ductal Carcinoma ◽

Disease Free Survival ◽

Breast Cancer Patients ◽

Free Survival ◽

The Mean ◽

Disease Free

Background: Triple-negative breast cancer (TNBC) is defined as tumors without estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. This cancer is associated with higher rates of recurrence risk when compared to other subtypes of breast cancers. In this study, we aimed to explore the basic clinicopathological characteristics, prognosis, and recurrence patterns of TNBC patients. Methods: In the current study, forty-five TNBC female patients operated on for breast cancer in the General Surgery Clinic of Kayseri City Training and Research Hospital between 2016 and 2021 were included and retrospectively evaluated. Results: The percentage of TNBC was 12% of the 502 breast cancer patients who could access all three pieces of receptor information. The mean age of the patients was 58.9±15.2 years (27-90), and the mean BMI was 30.4±5.17 (21.5-40.6). It was observed that the most common histological subtype was invasive ductal carcinoma, and at the time of diagnosis, 11 patients were stage 1 (24.4%), 31 patients were stage 2 (68.8%), 2 patients were stage 3 (4.4%), and 1 patient was stage 4 (2.2%). During the follow-up period, 11 patients (24,4%) developed metastasis and the most common sites were the brain and bones. The mean time from diagnosis to metastasis was 20.7±5.75 (12-29) months. The 3-year disease-free survival was 62%, and the 3-year overall survival (OS) was 70%. Conclusion: TNBCs are cancers with varying prevalence, poor prognosis, and limited treatment alternatives. The prevalence of TNBC in our center was found to be lower than the literature rates and consistent with the literature, the lymph node stage was related to poor OS and disease free survival (DFS).

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