scholarly journals Germline Mutations in Triple-Negative Breast Cancer

Breast Care ◽  
2017 ◽  
Vol 12 (1) ◽  
pp. 15-19 ◽  
Author(s):  
Eric Hahnen ◽  
Jan Hauke ◽  
Christoph Engel ◽  
Guido Neidhardt ◽  
Kerstin Rhiem ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Positive Family History ◽  
Therapy Response ◽  
Hereditary Disease ◽  
Biological Entity ◽  
Breast Cancer Predisposition ◽  
Mutational Status

Triple-negative breast cancer (TNBC) is associated with a poor prognosis and defines a subgroup of patients who do not benefit from endocrine or anti-HER2 therapy. Rather than being a biological entity, TNBC represents a heterogeneous disease, and further subtyping is necessary to establish targeted therapies. Germline mutational status may serve as a robust biomarker predicting therapy response, especially with respect to compounds challenging the DNA repair machinery. Patients with TNBC usually show an early onset of the disease, as well as a positive family history of breast and/or ovarian cancer in more than one third of all cases, which suggests that TNBC is closely associated with a hereditary disease cause. In unselected TNBC cases, the prevalence of pathogenic germline BRCA1/2 mutations is approximately twice as high as in breast cancer overall. Early age at diagnosis and positive family history are strong predictors for an increased BRCA1/2 mutation probability, which is up to 40% when both risk factors are considered. Apart from BRCA1/2, the rarely mutated breast cancer predisposition genes PALB2 and FANCM have been associated with TNBC. This review summarizes the role of germline mutational status in TNBC pathogenesis. Clinical trials addressing BRCA1/2 mutation carriers are discussed.

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 Epidemiological Profile and Clinicopathological Correlates of Triple Negative Breast Cancer Patients at Regional Cancer Centre

2021 ◽  
Vol 6 (4) ◽  
pp. 457-460
Author(s):  
Richa Verma ◽  
Shankar Lal Jakhar ◽  
Neeti Sharma ◽  
H. S. Kumar ◽  
Surender Beniwal
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Triple Negative Breast Cancer ◽  
Late Stage ◽  
Triple Negative ◽  
Positive Family History ◽  
Clinical Staging ◽  
High Grade ◽  
Incidence And Mortality ◽  
Epidemiological Profile

Background: Breast Cancer is the most common cancer among woman worldwide. In India breast cancer remains the leading cause of both incidence and mortality. Triple negative breast cancer is more difficult to treat as it does not respond to hormone therapy medicines or medicines that target receptor proteins (like HER 2 Neu). It is crucial for the physician to know the status of the disease as the patient can be subjected to a whole new avenue of treatment. The present study was done to assess the epidemiological profile and clinicopathological correlates of patients of triple negative breast cancer. Material and Methods: This retrospective study was carried out in Acharya Tulsi Cancer and Research Institute located in the state of Rajasthan, Bikaner, India, among Ca Breast patients presenting to Medical Oncology, Radiation Oncology and Surgical Oncology outdoor & indoor from April 2016 to March 2017. Out of the total 1017 patients of carcinoma breast 957 were included in this Study. Exclusion criteria was non availability of ER, PR, HER2 neu status reports because of various reasons like affordability. Out of the total 957 patients 249 were found to be triple negative. Statistical analysis was done using IBM SPSS version 21. Results: Mean age of the patients was 46±11.23 years. Out of total 249 patients of triple negative breast carcinoma, 91 (%) were found to have had clinical staging I and II (Early stage) and 158 (%) patients were found to have clinical staging III & IV (Late Stage). Mean size of the tumor was 3.6±1.94cm. 151 (60.6%) were pre-menopausal, 103 (41.4%) and 12 (4.8%) patients had positive family history. All of or patients diagnosed to have Ductal type of carcinoma. Lympho-vascular invasion was seen in 51 (20.5%) patients and High grade Histological Grading was seen in High Grade 169 (67.9%) patients. 172 (69.1%) undergone MRM (Modified Radical Mastectomy) and BCS was done in 74 (29.7%) patients. After comparison of triple Negative Breast Cancer with non-triple Negative Breast Cancer, lower age, later stages (III and IV), pre-menopausal status and high grade (on histology) were significantly more in negative type of Ca breast. Occurrence of early Menarche (< 13 Years) and history of OC pills used was almost equal in both the groups. Conclusion: Triple Negative Breast Cancer was found to present at an earlier age and more in pre – menopausal women. Such patients presented with a higher histological grade of tumor and late stage of presentation. There was no statistically significant association between TNBC and age of menarche, use of OC pill, previous exposure to radiotherapy and positive family history in first degree relative.

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.

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.

BRCA Mutational Status is a Promising Predictive Biomarker for Platinum- based Chemotherapy in Triple-Negative Breast Cancer

2020 ◽  
Vol 21 (10) ◽  
pp. 962-973 ◽  
Author(s):  
Amal Tazzite ◽  
Hassan Jouhadi ◽  
Abdellatif Benider ◽  
Sellama Nadifi
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Checkpoint Inhibitors ◽  
Susceptibility Gene ◽  
Predictive Biomarkers ◽  
Predictive Biomarker ◽  
Breast Cancer Susceptibility Gene ◽  
Mutational Status ◽  
Platinum Based Chemotherapy

Triple-negative breast cancer (TNBC) can be distinguished from other breast malignancies by the lack of expression of estrogen receptors (ER), progesterone receptors (PR) as well as human epidermal growth factor receptor 2 (HER2). TNBC is associated with adverse clinical outcomes and high risk of metastasis. Currently, several clinical and translational reports are focusing on developing targeted therapies for this aggressive cancer. In addition to approved targeted drugs such as poly(ADP-ribose) polymerase inhibitors (PARPi) and immune-checkpoint inhibitors, platinum-based chemotherapy is still a cornerstone therapeutic option in TNBC. However, despite the observed improved outcomes with platinum- based chemotherapy in TNBC, there is still a large proportion of patients who do not respond to this treatment, hence, the need for predictive biomarkers to stratify TNBC patients and therefore, avoiding unwanted toxicities of these agents. With the emergence of genetic testing, several recent studies suggested mutations in breast cancer susceptibility gene (BRCA) in TNBC patients as important predictors of outcomes. These mutations alter the homologous recombination repair (HRR) mechanisms leading to genomic instability. Consequently, sensitivity to platinum-based treatments in this subpopulation of TNBC patients may be explained by cell death enhanced by deoxyribonucleic acid (DNA) damage induced by these potent anticancer drugs. Through this paper, we review several recent studies on this topic to better understand the mechanisms and discuss the potential of BRCA mutational status as a predictive biomarker of platinum-based chemotherapy in TNBC.

A retrospective review of demographics and stage of triple-negative breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11553-e11553
Author(s):  
F. N. Rana
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Triple Negative Breast Cancer ◽  
Hormone Receptors ◽  
Triple Negative ◽  
Smoking Status ◽  
Linear Trend ◽  
Published Data ◽  
Breast Cancers ◽  
Demographic Risk

e11553 Background: Triple negative breast cancer (TNBC) is a recently recognized subtype of breast cancer, notable to metastasize early. It accounts for 15–20% of all breast cancers, and is more prevalent in African-American and Hispanic women, and women younger than 40 years of age. Continual decline in breast cancer deaths since 1990 has been attributed to earlier detection, better treatment including hormonal blockade in estrogen- and progesterone-receptor positive cancers, as well as the addition of Trastuzumab, a monoclonal antibody directed against the Her2/neu receptors. These hormone receptors are not found in TNBC, and therefore the traditional targets for endocrine manipulation cannot be therapeutically exploited. While lower socioeconomic status and racial predisposition to this disease have been observed, there exists a paucity of research into other demographic risk factors. We reviewed data between January 2000 to December 2005 from our tumor registry with particular attention to age, race, family history, tobacco use, and stage of presentation, comparing this subset of patients (n=39) to other records (n=303). We included only those patients in whom the status of all three receptors were recorded. Results: Comparisons were made for TNBC vs non-TNBC patients respectively as follows: mean age (59.87± yrs vs 60.09±yrs). Analysis using χ2 test (χ2=0.855) and CMH test for Linear Trend analysis (p=0.47) showed no difference in percentages in association with the 5 stages or TNBC status and no linear trend respectively. Conclusions: This data suggests that at our institution, TNBC is less prevalent (12.87%) than estimates of 15- 20% published in other studies. There was no difference in age at diagnosis (p=0.92), with black patients more likely to have TNBC (p=0.004, OR=2.75). There was no significant association between smoking status and TNBC (p=0.43). There was no significant association between a family history of cancer and TNBC (p=0.8384). When accounting for samples size, TNBC was as prevalent as non TNBC at all stages of diagnosis. These results differ from other published data and may reflect differences in statistical analysis. No significant financial relationships to disclose.

BRCA 1 and BRCA 2 mutations in Saudi breast cancer patients (single institution).

2014 ◽  
Vol 32 (26_suppl) ◽  
pp. 10-10 ◽  
Author(s):  
Omalkhair A. M. Abulkhair
Keyword(s):  
Breast Cancer ◽  
Family History ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Bilateral Breast Cancer ◽  
Cultural Practice ◽  
Reproductive Pattern ◽  
Saudi Women ◽  
Brca 1 ◽  
Brca 2

10 Background: Breast cancer is the commonest malignancy among Saudi females accounting for 25% of all female cancers with a median age at diagnosis of 47 years (1,2). In Saudi, breast cancer showed an increased incidence attributed to many factors such as different lifestyles, reproductive pattern, family history, which was reported to account for 59%, dietary or cultural practice of Saudi women (2,3,4,5). The multifunctional and highly penetrant BRCA 1 and BRCA 2 are the two major breast cancer pre-disposition genes, accounting for about 20% of breast cancer families (6,7). To our knowledge, the prevalence of BRCA 1 and BRCA 2 mutations in native Saudi population is sparse (8,9). Our aim is to describe the findings of BRCA mutation testing in native Saudi patients with breast cancer in a large Ministry of National Guard Health Affairs (NGHA) community-based teaching hospital. Methods: In this study, 75 out of 516 patients with breast cancer who were clinically and histopathologically diagnosed at NGHA from October 2010 to April 2014 were included. Selection criteria: aged ≤ 40 years bilateral breast cancer, triple-negative breast cancer, strongly first degree family history at young age and male breast cancer. Molecular alterations were performed by direct gene sequencing, multiple ligation – dependent probe amplification (MLPA) at Bioscentia human genetic testing in Germany. Results: 75 native Saudi were enrolled and test performed for them. 18 patients (24%) were found to have mutation of which 10 in BRCA One and six in BRCA 2. Two have both BRCA 1 and BRCA 2. Seven patients have the same with deleterious mutations in BRCA 1 gene. Two of them are mother and daughter and other five are unrelated. The mean age of breast cancer diagnosis in the mutation carriers was 38 years. Triple negative breast cancer (TNBC) diagnosed in six patients, bilateral breast cancer diagnosed in one, first-degree family history in eight and second degree in 10 patients and four with no family history. Conclusions: BRCA 1 and BRCA 2 mutations are an important contributor to the etiology of breast cancer in Saudi women. A mutation in BRCA 1, C 1648 > C p, Asn550His in exon 10 has been reported as disease causing (11) and it is found in our study in seven patients. Such mutation might be specific for Saudi, so further studies are highly recommended.

Family history of breast and/or ovarian cancer (FHBOC) as an independent prognostic factor in triple negative breast cancer overall survival.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12579-e12579
Author(s):  
Patricia Rioja ◽  
Rossana Ruiz ◽  
Zaida Morante ◽  
Raul Mantilla ◽  
Gabriel Antonio De la Cruz Ku ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Overall Survival ◽  
Family History ◽  
Prognostic Factor ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Independent Prognostic Factor ◽  
Inheritance Pattern ◽  
History Of

e12579 Background: Triple negative breast cancer (TNBC) seems to be associated with a hereditary disease cause based on the earlier age of onset, the high rate of TNBC cases with a positive family history of cancer, and the higher prevalence of breast cancer susceptibility genes. The impact of family history in breast and/or ovarian cancer (FHBOC) in TNBC overall survival is unclear, we conducted this study to evaluate this factor in a Peruvian cohort. Methods: Retrospectively reviewed the medical files from TNBC patients diagnosed at Instituto Nacional de Enfermedades Neoplásicas (INEN) in Lima, Peru, from 2000 to 2014. New cases with histologically confirmed TNBC defined as lack of expression of estrogen and progesterone receptors by immunohistochemistry and HER2- were included. A positive FHBOC was defined as a history of breast and/or ovarian cancer in 1st, 2nd and/or 3rd degree relatives at any age. Patients who had three affected relatives in two generations with two of them being first-degree relatives were considered as exhibiting a clinical autosomal dominant (AD) inheritance pattern. Results: 2006 patients, 99.8% were females. Mean age was 50.2 years old (19 - 95) and 54.6% were postmenopausal. According clinical staging: stage I, 7.2%; stage II, 34.2%; stage III, 51.0%; and stage IV, 6.5%. 76.5% of women underwent surgery. 13% (n=266) had a positive FHBOC. Of these, 44.0% (n=117), 35.0% (n=93), and 13.5% (n=36) had 1st, 2nd, and 3rd degree affected relatives, respectively. An AD inheritance pattern was observed in 20.7% (n=55) of patients with FHBOC. With a median follow-up of 80 months (range 0 - 249), 5y-overall survival (OS) for the whole population was 53.8%. 5 year-OS was significantly better in patients with FHBOC as compared to those without it; 64.5% vs. 52.2%, respectively (HR 0.73; 95% CI [0.60-0.88] p=0.001). FHBOC showed a positive impact on survival rates among patients with stages III and IV (5-year OS 42.3% vs. 32.7%; HR 0.79; 95% CI [0.64-0.99], p=0.041) but not in stages I and II (5-year OS 88.4% vs. 81.3%; HR 0.72; 95% CI [0.49-1.08], p=0.11). The 5y-OS for the patients with an AD inheritance pattern was 70.9%. However, pairwise multiple comparison did not find a significant difference between these patients and those with FHBOC without an AD inheritance pattern (62.8%). On multivariate analysis, FHBOC (HR: 0.80; 95% CI [0.66-0.97], p=0.023), had an independent effect on OS, adjusted for age, menopausal status, clinical stage and surgery. Conclusions: A positive FHBOC was associated with an improved survival in patients with TNBC, suggesting FHBOC as an independent prognostic factor. These results need validation and confirmation through additional retrospective cohorts and analysis in prospective clinical trials.

Sign in / Sign up

Export Citation Format

Share Document