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

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 <i>BRCA1</i> and <i>BRCA2</i>. 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 <i>BRAC1</i> and <i>BRCA2</i>. However, her condition worsened, and she died 8 months after the surgery. <i>BRCA</i> 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.

scholarly journals Assessment of genetic referrals and outcomes for women with triple negative breast cancer in regional cancer centres in Australia

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lucie G. Hallenstein ◽  
Carol Sorensen ◽  
Lorraine Hodgson ◽  
Shelly Wen ◽  
Justin Westhuyzen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Testing ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cancer Genetics ◽  
Eligibility Criteria ◽  
Pathogenic Variants ◽  
Genetics Services ◽  
Age Of Diagnosis ◽  
Over Time

Abstract Background Guidelines for referral to cancer genetics service for women diagnosed with triple negative breast cancer have changed over time. This study was conducted to assess the changing referral patterns and outcomes for women diagnosed with triple negative breast cancer across three regional cancer centres during the years 2014–2018. Methods Following ethical approval, a retrospective electronic medical record review was performed to identify those women diagnosed with triple negative breast cancer, and whether they were referred to a genetics service and if so, the outcome of that genetics assessment and/or genetic testing. Results There were 2441 women with newly diagnosed breast cancer seen at our cancer services during the years 2014–2018, of whom 237 women were diagnosed with triple negative breast cancer. Based on age of diagnosis criteria alone, 13% (31/237) of our cohort fulfilled criteria for genetic testing, with 81% (25/31) being referred to a cancer genetics service. Of this group 68% (21/31) were referred to genetics services within our regions and went on to have genetic testing with 10 pathogenic variants identified; 5x BRCA1, 4x BRCA2 and × 1 ATM:c.7271 T > G. Conclusions Referral pathways for women diagnosed with TNBC to cancer genetics services are performing well across our cancer centres. We identified a group of women who did not meet eligibility criteria for referral at their time of diagnosis, but would now be eligible, as guidelines have changed. The use of cross-discipline retrospective data reviews is a useful tool to identify patients who could benefit from being re-contacted over time for an updated cancer genetics assessment.

scholarly journals BRCA Detection Rate in an Italian Cohort of Luminal Early-Onset and Triple-Negative Breast Cancer Patients without Family History: When Biology Overcomes Genealogy

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1252 ◽  
Author(s):  
Angela Toss ◽  
Eleonora Molinaro ◽  
Marta Venturelli ◽  
Federica Domati ◽  
Luigi Marcheselli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Testing ◽  
Family History ◽  
Triple Negative Breast Cancer ◽  
Early Onset ◽  
Detection Rate ◽  
Triple Negative ◽  
Brca2 Mutation ◽  
Brca Testing ◽  
Brca Genetic Testing

NCCN Guidelines recommend BRCA genetic testing in individuals with a probability >5% of being a carrier. Nonetheless, the cost-effectiveness of testing individuals with no tumor family history is still debated, especially when BRCA testing is offered by the national health service. Our analysis evaluated the rate of BRCA pathogenic or likely-pathogenic variants in 159 triple-negative breast cancer (TNBC) patients diagnosed ≤60 years, and 109 luminal-like breast cancer (BC) patients diagnosed ≤35 without breast and/or ovarian family histories. In TNBC patients, BRCA mutation prevalence was 22.6% (21.4% BRCA1). Mutation prevalence was 64.2% ≤30 years, 31.8% in patients aged 31–40, 16.1% for those aged 41–50 and 7.9% in 51–60 s. A total of 40% of patients with estrogen receptors (ER) 1–9% were BRCA1 carriers. BRCA detection rate in early-onset BCs was 6.4% (4.6% BRCA2). Mutation prevalence was 0% between 0–25 years, 9% between 26–30 years and 6% between 31–35 years. In conclusion, BRCA testing is recommended in TNBC patients diagnosed ≤60 years, regardless of family cancer history or histotype, and by using immunohistochemical staining <10% for both ER and/PR. In luminal-like early-onset BC, a lower BRCA detection rate was observed, suggesting a role for other predisposing genes along with BRCA genetic testing.

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

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]

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

2018 ◽  
Vol 26 (2) ◽  
pp. 165-175 ◽  
Author(s):  
Iulian Gabriel Goidescu ◽  
Dan Tudor Eniu ◽  
Gabriela Valentina Caracostea ◽  
Gheorghe Cruciat ◽  
Florin Stamatian
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Ductal Carcinoma ◽  
Breast Cancer Patients ◽  
Brca1 And Brca2 ◽  
Pathogenic Variants ◽  
Romanian Population ◽  
First Time ◽  
Histology And Immunohistochemistry

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.

scholarly journals BRCA detection rate in an Italian cohort of luminal early-onset and triple-negative breast cancer patients without family history: when biology overcomes genealogy.

2020 ◽  
Author(s):  
Angela Toss ◽  
Eleonora Molinaro ◽  
Marta Venturelli ◽  
Federica Domati ◽  
Luigi Marcheselli ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Testing ◽  
Family History ◽  
Triple Negative Breast Cancer ◽  
Early Onset ◽  
Detection Rate ◽  
Triple Negative ◽  
Brca2 Mutation ◽  
Mutational Status ◽  
Brca Genetic Testing

Abstract BACKGROUND: NCCN Guidelines recommend BRCA genetic testing in individuals with a probability >5% of being a carrier. This analysis aimed to evaluate the rate of BRCA mutations in triple-negative breast cancer (TNBC) patients diagnosed ≤60 years and luminal-like breast cancer (BC) patients diagnosed ≤35 without breast and/or ovarian family history. METHODS: 159 TNBC patients diagnosed ≤60 years and 109 luminal-like BC patients diagnosed ≤35 years without family history were retrospectively identified. Mutation prevalence and clinical-pathological characteristics associated with mutational status were evaluated. RESULTS: In TNBC patients, BRCA mutation prevalence was 22.6% (21.4% BRCA1 and 1.2% BRCA2). BRCA1-related TNBC patients were younger (p <0.001). Mutation prevalence was 64.2% ≤30 years, 31.8% in patients aged 31-40, 16.1% for those aged 41-50 and 7.9% for those between 51 and 60 years of age. A total of 40% of patients with estrogen receptor (ER) 1-9% were BRCA1 carriers. BRCA detection rate in early-onset BCs was 6.4% (1.8% BRCA1 and 4.6% BRCA2). Mutation prevalence was 0% 0-25 years, 9% 26-30 years and 6% 31-35 years. BRCA2-positive luminal-like early-onset BCs were more likely associated with low progesterone receptor (PR) expression (p = 0.049). CONCLUSIONS: BRCA genetic testing is recommended in TNBC diagnosed ≤ 60 years, regardless of cancer family history, histotype and by using immunohistochemical staining <10% of nuclei for both ER and/PR as a cut-off. In luminal-like early-onset BC patients, a lower BRCA detection rate was observed, suggesting a role for other predisposing genes.

scholarly journals Influence of Germline BRCA Genotype on the Survival of Patients with Triple-Negative Breast Cancer

2021 ◽  
Vol 1 (3) ◽  
pp. 140-147
Author(s):  
Cynthia Villarreal-Garza ◽  
Ana S. Ferrigno ◽  
Alejandro Aranda-Gutierrez ◽  
Paul H. Frankel ◽  
Nora H. Ruel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Point Mutations ◽  
Treatment Resistance ◽  
Cancer Center ◽  
Breast Cancers ◽  
Entire Cohort ◽  
Pathogenic Variants ◽  
Mutational Status

The presence of BRCA pathogenic variants (PV) in triple-negative breast cancer (TNBC) is associated with a distinctive genomic profile that makes the tumor particularly susceptible to DNA-damaging treatments. However, patients with BRCA PVs can develop treatment resistance through the appearance of reversion mutations and restored BRCA expression. As copy-number variants (CNV) could be less susceptible to reversion mutations than point mutations, we hypothesize that carriers of BRCA CNVs may have improved survival after treatment compared with carriers of other BRCA PVs or BRCA wild-type. Women diagnosed with stage I–III TNBC at ≤50 years at a cancer center in Mexico City were screened for BRCA PVs using a recurrent PV assay (HISPANEL; 77% sensitivity). Recurrence-free survival (RFS) and overall survival (OS) were compared according to the mutational status. Among 180 women, 17 (9%) were carriers of BRCA1 ex9–12del CNVs and 26 (14%) of other BRCA PVs. RFS at ten years for the whole cohort was 79.2% [95% confidence interval (CI), 72.3–84.6], with no significant differences according to mutational status. 10-year OS for the entire cohort was 85.3% (95% CI, 78.7–90.0), with BRCA CNV carriers demonstrating numerically superior OS rates other PV carriers and noncarriers (100% vs. 78.6% and 84.7%; log-rank P = 0.037 and P = 0.051, respectively). This study suggests that BRCA1 ex9–12del CNV carriers with TNBC may have a better OS, and supports the hypothesis that the genotype of BRCA PVs may influence survival by limiting treatment resistance mediated by reversion mutations among CNV carriers. Significance: Large CNV BRCA carriers in a cohort of young Mexican patients with TNBC had superior OS rates than carriers of other BRCA pathogenic variants (i.e., small indels or point mutations). We hypothesize that this is due to the resistance of CNVs to reversion mutations mediating resistance to therapy. If validated, these findings have important prognostic and clinical treatment implications for BRCA-associated breast cancers.

Breast cancer associated pathogenic variants among women 61 years and older with triple negative breast cancer

2020 ◽  
Author(s):  
Yanin Chávarri-Guerra ◽  
Catherine A. Marcum ◽  
Carolyn B. Hendricks ◽  
Deborah Wilbur ◽  
Terrence Cescon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Pathogenic Variants

Pathologic characteristics of breast cancer with special emphasis on prevalence of triple-negative breast cancer from Kenya: A 4-year experience.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 35-35
Author(s):  
S. Sayed ◽  
Z. Moloo ◽  
S. Mukono ◽  
R. Wasike ◽  
R. R. Chauhan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Ductal Carcinoma ◽  
Significant Proportion ◽  
Small Sample ◽  
University Hospital ◽  
Breast Cancers ◽  
Grade 3

35 Background: Previous sub classification of breast cancer in Kenya has been fraught by small sample size, non uniform staining methodology and lack of independent review. Triple Negative Breast Cancer (TNBC) is a “special interest” cancer since it represents a significant proportion of breast cancer patients and is associated with a poorer prognosis. We aimed to determine the estrogen receptor (ER), progesterone receptor (PR) and Her2/neu receptor characteristics of breast cancers and the prevalence of TNBC diagnosed at Aga Khan University Hospital, Nairobi (AKUHN) between 2007 to date. Methods: Slides and blocks of archived invasive breast cancers diagnosed at AKUHN were identified, retrieved and reviewed by two independent pathologists. Histological type, grade and pathological stage were documented. Representative sections from available blocks were stained for ER, PR, Her2 with appropriate internal controls. Scores for ER/PR were interpreted based on the ALLRED system, Her2 /neu scoring followed CAP guidelines. The initial 111 cases were validated and confirmed at Sunnybrook Health Sciences Centre, Toronto. Results: 456 cases of invasive breast cancers were diagnosed at AKUHN during the study period. 91% of cases were invasive ductal carcinomas (NOS).The rest were special types. 37% of the tumors were grade 3 and 63% were grade 2. Blocks for 318 of 456 cases were available for receptor analysis. 54% were ER and/or PR positive, with 52% of these in women < 50 yrs. 86% of the ER and/or PR positive tumors were grade 2. Only 12% were Her2/neu positive. Of the 318 cases studied, 111 (32%) were identified as TNBC. Median age was 53 yrs. 88% were grade 3. Conclusions: Invasive ductal carcinoma (NOS) was the most common breast cancer in our study. Nearly half of our cases were ER and/or PR positive and a third were TNBC. Both occurred predominantly in women less than 50 yrs. This represents the largest validated pathologic sub classification of breast cancer from a tertiary academic hospital in Kenya. Expansion of this study to encompass all breast cancers diagnosed in Kenya is underway.

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