scholarly journals Prospective Evaluation of Universal BRCA Testing for Women With Triple-Negative Breast Cancer

2020 ◽  
Vol 4 (2) ◽  
Author(s):  
Trisha S Emborgo ◽  
Donika Saporito ◽  
Kimberly I Muse ◽  
Angelica M Gutierrez Barrera ◽  
Jennifer K Litton ◽  
...  
Keyword(s):  
Breast Cancer ◽  
National Comprehensive Cancer Network ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cancer Center ◽  
Brca Testing ◽  
Clinical Genetic ◽  
Large Rearrangement ◽  
Pathogenic Variants ◽  
Cancer Network

Abstract Background Limited published literature exists on women with triple-negative breast cancer (TNBC) diagnosed over the age of 60 years with breast cancer gene (BRCA) pathogenic variants. Our study determined whether the rate of BRCA pathogenic variants in a prospective cohort of TNBC patients outside the definition of current clinical genetic testing (GT) guidelines warrants a change in recommendations. Methods A prospective study of 395 women with TNBC underwent genetic counseling and 380 (96.2%) underwent clinical BRCA GT regardless of age of diagnosis beginning January 2014 to October 2015 at The University of Texas MD Anderson Cancer Center, Houston. TNBC patients older than 60 years who did not meet clinical GT guidelines had comprehensive sequencing and large rearrangement GT as part of the research protocol. Results Fifty-one of 380 (13.4%) women with TNBC who underwent clinical BRCA GT were BRCA positive. Of the 86 patients diagnosed at age over 60 years and underwent GT, only two (2.3%) were positive for BRCA. These two patients would have met clinical testing criteria due to family or ancestral history. Conclusions Our study does not support universal BRCA testing for TNBC patients diagnosed older than 60 years as their only risk factor for a BRCA pathogenic variant. Both of the positive BRCA patients older than 60 years identified would have met current National Comprehensive Cancer Network criteria for testing. Therefore, our study demonstrates that the National Comprehensive Cancer Network guidelines provide sufficient criteria for identifying BRCA pathogenic variants in women with TNBC at 60 years or younger.

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.

Are patients with triple-negative breast cancer screened for BRCA mutations according to NCCN guidelines?

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 7-7
Author(s):  
Staci Aubry ◽  
Lindsay Floch Petersen ◽  
Kelly Burgess ◽  
Ruta D. Rao ◽  
Katherine Kopkash ◽  
...  
Keyword(s):  
Breast Cancer ◽  
African American ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Brca Testing ◽  
Brca Mutations ◽  
Exact Test ◽  
Nccn Guidelines ◽  
Primary Payer ◽  
Cancer Network

7 Background: Ten to 25 percent of patients diagnosed with breast cancer have triple negative breast cancer (TNBC), defined as tumors negative for estrogen, progesterone, and Her2-neu receptors. TNBC is more aggressive than receptor positive cancer. The National Comprehensive Cancer Network (NCCN) recommends BRCA genetic testing for women less than age 60 when diagnosed with TNBC. Methods: The Commission on Cancer registry tumor database was queried for TNBC from 2006 to 2013. Patient demographics were analyzed. Data regarding pathologic details and BRCA testing was collected. Analyses using the Fisher's exact test were conducted. Results: TNBC tumors were identified in the database (n = 173). Sixty-one percent (105/173) of patients were less than 60 years of age, therefore BRCA testing was indicated. Fifteen patients were BRCA positive. Eighty-three percent (87/105) of patients underwent BRCA testing. Seventeen percent (18/105) of patients did not receive BRCA testing that should have under the current guidelines. Patients that did not undergo recommended BRCA testing were more likely to be greater than or equal to 55 years of age (p = 0.002), African-American (p = 0.001), have Medicaid listed as a primary payer (p = 0.021), and have American Joint Commission on Cancer (AJCC) stage 3 disease (p = 0.014). Conclusions: Risk factors for not completing BRCA testing include older age, African-American race, Medicaid insurance status, and stage 3 disease. Health provider awareness of this opportunity for improvement is important to decrease these health disparities. [Table: see text]

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.

321 Phase I clinical trial assessing the combination of systemic chemokine modulatory regimen targeting TLR3 with neoadjuvant chemotherapy in triple negative breast cancer

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A347-A347
Author(s):  
Shipra Gandhi ◽  
Mateusz Opyrchal ◽  
Cayla Ford ◽  
Victoria Fitzpatrick ◽  
Melissa Grimm ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Phase I ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Early Stage ◽  
Standard Dose ◽  
Surrogate Marker ◽  
Comprehensive Cancer Center ◽  
Cancer Center

BackgroundNeoadjuvant chemotherapy (NAC) with taxanes is the standard of care in triple negative breast cancer (TNBC). Intratumoral prevalence of CD8+ cytotoxic T-lymphocytes (CTLs) is associated with an improvement in relapse-free survival (RFS) and overall survival (OS), while regulatory T-cells (Treg) and myeloid derived suppressor cells (MDSC) are associated with poor survival. Higher ratio of CTL/Treg is associated with higher probability of obtaining pathological complete response (pCR), a surrogate marker for RFS. Intratumoral production of CCL5, CXCL9, CXCL10 and CXCL11 is critical for local infiltration with CTLs, while CCL22 is responsible for Treg attraction. Previous studies have shown that CXCL9 expression in the pre-treatment breast tissue is associated with a three-fold higher rate of achieving pCR. Our preclinical data show that Chemokine modulating (CKM) regimen, combining rintatolimod (TLR3 agonist), interferon (IFN)-α2b, and celecoxib (COX-2 inhibitor) increases CTL-attracting, and decreases MDSC-, Treg-favoring chemokines, increasing CTL/Treg ratio in tumor microenvironment, with preferential tumor tissue activation than adjacent healthy tissues. We hypothesize that the combination of CKM with paclitaxel will result in infiltration of TNBC with CTLs, and along with doxorubicin/cyclophosphamide (AC), result in higher pCR, translating into improved RFS and OS.MethodsIn this phase I study NCT04081389, eligibility includes age ≥18 years, confirmed resectable TNBC, radiographically measurable disease ≥1 cm, ECOG PS ≤ 2, adequate organ and marrow function. Patients with autoimmune disease, serious mood disorders, invasive carcinoma within 3 years, history of peptic ulcers or hypersensitivity to NSAIDs will be excluded. We plan to treat three patients with early stage TNBC with paclitaxel 80 mg/m2 IV weekly for 12 weeks, rintatolimod 200 mg IV, celecoxib 200 mg oral twice daily, and accelerated titration of IFN-α2b at doses 0, 5, or 10 million units (MU)/m2 [Dose Levels (DL) 1, 2 and 3 respectively] on days 1–3 (no intra-patient dose escalation) in weeks 1–3. Dose-limiting toxicity (DLT) is defined as grade 3 or higher toxicities within the first 3 weeks. Any DLT will mandate recruitment per the 3+3 model. If no DLT, three patients will be enrolled at DL 4 at 20 MU/m2 IFN- α2b. This will be followed by standard dose-dense AC, and then surgery. The primary endpoint is safety and tolerability of combination and to identify the appropriate DL of CKM and paclitaxel for extended efficacy study. The secondary endpoints include investigation of efficacy (pCR and breast MRI response), along with RFS and OS. Intratumoral biomarkers will be analyzed in an exploratory manner.ResultsN/AConclusionsN/ATrial RegistrationNCT04081389Ethics ApprovalThe study was approved by Roswell Park Comprehensive Cancer Center Institution’s Ethics Board, approval number I-73718.

scholarly journals OC-0158: Histologic heterogeneity of triple negative breast cancer: a National Cancer Center Database study

2018 ◽  
Vol 127 ◽  
pp. S80-S81
Author(s):  
M. Mills ◽  
G. Yang ◽  
D. Oliver ◽  
C. Liveringhouse ◽  
K. Ahmed ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Cancer Center ◽  
Database Study ◽  
Histologic Heterogeneity

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.

BRCA1/2 mutation prevalence among triple-negative breast cancer patients from a large commercial testing cohort.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1544-1544 ◽  
Author(s):  
Kristilyn Dillman Zonno ◽  
Rajesh R. Kaldate ◽  
Christopher Arnell ◽  
Jennifer Saam ◽  
Brian Abbott ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
African Ancestry ◽  
Parp Inhibitors ◽  
Ashkenazi Jewish ◽  
Breast Cancer Patients ◽  
Cancer Network ◽  
Testing Criteria

1544 Background: BRCA1/2 deleterious mutation identification among triple-negative breast cancer (TNBC) patients has gained importance due to cancer-risk management implications for patients and their relatives, and also has an emerging role in guiding treatment selection for therapies such as PARP inhibitors. The National Comprehensive Cancer Network (NCCN) currently recommends BRCA1/2 testing for TNBC patients diagnosed at age <60. Mutation prevalence among TNBC patients has previously been studied only in small regionalized cohorts. A recent study in unselected patients using the updated definitive criteria for TNBC reported mutation prevalence as 10.6%. Methods: Following the 2011 NCCN Hereditary Breast and Ovarian Cancer (HBOC) Testing Criteria update, serial cohorts of > 5,000 Ashkenazi Jewish and > 65,000 non-Ashkenazi Jewish breast cancer patients undergoing commercial BRCA1/2 testing were analyzed. Age at diagnosis, ethnicity, and provider-reported TN status were obtained from test requisition forms completed by ordering providers, and correlated with test results. Neither the accuracy nor definitive criteria used for TN status reported was independently verified. Results: Incidence of TNBC was reported as 9.7% among non-Ashkenazi patients and 16.5% within the subset with African ancestry. Incidence of TNBC was reported as 4.5% among Ashkenazi patients, but this is likely affected by test ordering for this population. The Table displays the BRCA1/2mutation rates classified by ethnicity and age-group. Conclusions: This study provides the most robust estimate to date of BRCA1/2 mutation prevalence among TNBC patients of all ages. The mutation rates seen among TNBC patients diagnosed after age 60 also illustrate the importance of testing such patients who may not meet the current NCCN HBOC testing criteria. [Table: see text]

Adherence to National Comprehensive Cancer Network Guidelines for BRCA testing among breast cancer patients.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. e13624-e13624 ◽  
Author(s):  
Nadine M. Tung ◽  
Priyanka J. Bobbili ◽  
Temitope O. Olufade ◽  
Maral DerSarkissian ◽  
Rachel Bhak ◽  
...  
Keyword(s):  
Breast Cancer ◽  
National Comprehensive Cancer Network ◽  
Cancer Patients ◽  
Breast Cancer Patients ◽  
Brca Testing ◽  
Cancer Network
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