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.

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 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 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

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.

scholarly journals Underdiagnosis of Hereditary Breast Cancer: Are Genetic Testing Guidelines a Tool or an Obstacle?

2019 ◽  
Vol 37 (6) ◽  
pp. 453-460 ◽  
Author(s):  
Peter D. Beitsch ◽  
Pat W. Whitworth ◽  
Kevin Hughes ◽  
Rakesh Patel ◽  
Barry Rosen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Testing ◽  
Germ Line ◽  
Test Results ◽  
Eligibility Criteria ◽  
Exact Test ◽  
Nccn Guidelines ◽  
Current Testing ◽  
Panel Testing ◽  
Pathogenic Variants

Purpose An estimated 10% of breast and ovarian cancers result from hereditary causes. Current testing guidelines for germ line susceptibility genes in patients with breast carcinoma were developed to identify carriers of BRCA1/ 2 variants and have evolved in the panel-testing era. We evaluated the capability of the National Comprehensive Cancer Network (NCCN) guidelines to identify patients with breast cancer with pathogenic variants in expanded panel testing. Methods An institutional review board–approved multicenter prospective registry was initiated with 20 community and academic sites experienced in cancer genetic testing and counseling. Eligibility criteria included patients with a previously or newly diagnosed breast cancer who had not undergone either single- or multigene testing. Consecutive patients 18 to 90 years of age were consented and underwent an 80-gene panel test. Health Insurance Portability and Accountability Act–compliant electronic case report forms collected information on patient demographics, diagnoses, phenotypes, and test results. Results More than 1,000 patients were enrolled, and data records for 959 patients were analyzed; 49.95% met NCCN criteria, and 50.05% did not. Overall, 8.65% of patients had a pathogenic/likely pathogenic (P/LP) variant. Of patients who met NCCN guidelines with test results, 9.39% had a P/LP variant. Of patients who did not meet guidelines, 7.9% had a P/LP variant. The difference in positive results between these groups was not statistically significant (Fisher’s exact test P = .4241). Conclusion Our results indicate that nearly half of patients with breast cancer with a P/LP variant with clinically actionable and/or management guidelines in development are missed by current testing guidelines. We recommend that all patients with a diagnosis of breast cancer undergo expanded panel testing.

scholarly journals Pathogenic variants inBRCA1/2genes among patientswith triple-negative breast cancer: a case series

Mastology ◽  
2021 ◽  
Vol 31 ◽  
Author(s):  
Rafael Everton Assunção Ribeiro da Costa ◽  
Fergus Tomás Rocha de Oliveira ◽  
Ana Lúcia Nascimento Araújo ◽  
Sabas Carlos Vieira
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Residual Disease ◽  
Molecular Subtype ◽  
Clinical Stage ◽  
Case Series ◽  
Neoplastic Disease ◽  
Ki 67 ◽  
Pathogenic Variants

Triple-negative breast cancer (TNBC) is an uncommon molecular subtype (representing 15%–20% of breast cancers) characterized by the non-expression of estrogen receptor, progesterone receptor, and human epidermal growth receptor factor 2. More aggressive and lethal, TNBC is often associated with pathogenic variants in BRCA1/2 genes. This study aimed to describe a series of seven cases of patients with TNBC and pathogenic variants in BRCA1/2 genes. All patients were female and under 50 years of age at diagnosis. Four of them presented a family history of breast cancer and/or other neoplasms. The predominant clinical stage was IIB, and the main anatomopathological stage was pT2pN0M0. The mean tumor size in the series was 2.5 cm (1.0 to 3.2 cm). Ki-67 was > 30% in all patients. Three cases (43%) had pathological complete response, and only one presented extensive residual disease after neoadjuvant chemotherapy. Six patients showed pathogenic variants in BRCA1 (86%) and one in BRCA2+ (14%). After a mean follow-up of 38 months (19 to 68 months), five patients were alive and without neoplastic disease, and two progressed to metastasis.

Prevalence of germline BRCA pathogenic variants in a monoinstitutional cohort of patients with triple negative breast cancer

2020 ◽  
Vol 138 ◽  
pp. S79
Author(s):  
E. De Matteis ◽  
M. Ciccarese ◽  
G. Ronzino ◽  
R. Forcignanò ◽  
V.E. Chiuri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Pathogenic Variants
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