Frequency of Triple-Negative Breast Cancer in BRCA1 Mutation Carriers: Comparison Between Common Ashkenazi Jewish and Other Mutations

2012 ◽  
Vol 30 (35) ◽  
pp. 4447-4448 ◽  
Author(s):  
Nadine Tung ◽  
Judy E. Garber ◽  
Anne Lincoln ◽  
Susan M. Domchek
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Brca1 Mutation ◽  
Ashkenazi Jewish ◽  
Mutation Carriers

scholarly journals Characteristics of Triple-Negative Breast Cancer in Patients With a BRCA1 Mutation: Results From a Population-Based Study of Young Women

2011 ◽  
Vol 29 (33) ◽  
pp. 4373-4380 ◽  
Author(s):  
Eunjung Lee ◽  
Roberta McKean-Cowdin ◽  
Huiyan Ma ◽  
Darcy V. Spicer ◽  
David Van Den Berg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Brca1 Mutation ◽  
Population Based ◽  
Age At Menarche ◽  
Ashkenazi Jewish ◽  
Jewish Women ◽  
Mutation Status ◽  
Receptor Status ◽  
Mutation Carriers

Purpose Triple-negative breast cancers (TNBCs) are tumors with low or no expression of estrogen receptor, progesterone receptor, or human epidermal growth factor receptor 2. These tumors have a poor prognosis, remain a clinical challenge, and are more common among women with BRCA1 mutations. We tested whether there are distinguishing features of TNBC after BRCA1 mutation status has been taken into account. Patients and Methods We sequenced BRCA1 and BRCA2 genes in a population-based sample of 1,469 patients with incident breast cancer age 20 to 49 years from Los Angeles County (California). Information on tumor receptor status was available for 1,167 women. Clinical, pathologic, and hormone-related lifestyle characteristics were compared across patient subgroups defined by BRCA1 mutation status and triple-negative receptor status. Results Forty-eight percent of BRCA1 mutation carriers had TNBC compared with only 12% of noncarriers. Within BRCA1 mutation carriers, as well as within noncarriers, triple-negative receptor status was associated with younger age at diagnosis and higher tumor grade. Among women without a BRCA1 mutation, we observed that women with TNBC had higher premenopausal body mass index and earlier age at first full-term pregnancy than those with non-TNBC. Age at menarche and other reproductive factors were not associated with triple-negative status regardless of BRCA1 mutation status. Within BRCA1 mutation carriers, Ashkenazi Jewish women were about five times more likely to have TNBC than non–Ashkenazi Jewish women. Conclusion Our results suggest that among BRCA1 mutation carriers, as among noncarriers, there are unique characteristics associated with the triple-negative subtype. The findings in Ashkenazi Jewish BRCA1 mutation carriers should be confirmed.

scholarly journals Clinical outcome of triple negative breast cancer in BRCA1 mutation carriers and noncarriers

Cancer ◽  
2011 ◽  
Vol 117 (14) ◽  
pp. 3093-3100 ◽  
Author(s):  
Larissa J. Lee ◽  
Brian Alexander ◽  
Stuart J. Schnitt ◽  
Amy Comander ◽  
Bridget Gallagher ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Outcome ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Brca1 Mutation ◽  
Mutation Carriers

Neo-adjuvant doxorubicin and cyclophosphamide followed by paclitaxel in triple-negative breast cancer among BRCA1 mutation carriers and non-carriers

2016 ◽  
Vol 157 (1) ◽  
pp. 157-165 ◽  
Author(s):  
Shani Paluch-Shimon ◽  
Eitan Friedman ◽  
Raanan Berger ◽  
Moshe Papa ◽  
Maya Dadiani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Brca1 Mutation ◽  
Mutation Carriers

scholarly journals Triple-negative breast cancer: BRCAness and concordance of clinical features with BRCA1-mutation carriers

2013 ◽  
Vol 108 (10) ◽  
pp. 2172-2177 ◽  
Author(s):  
E H Lips ◽  
L Mulder ◽  
A Oonk ◽  
L E van der Kolk ◽  
F B L Hogervorst ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Features ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Brca1 Mutation ◽  
Mutation Carriers

scholarly journals The Interaction of PI3K Inhibition with Homologous Recombination Repair in Triple Negative Breast Cancer Cells

2019 ◽  
Vol 22 ◽  
pp. 599-611
Author(s):  
Gamze Guney Eskiler
Keyword(s):  
Breast Cancer ◽  
Homologous Recombination ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Apoptotic Cell ◽  
Human Cancer ◽  
Brca1 Mutation ◽  
Annexin V ◽  
Pi3k Inhibition ◽  
Recombination Repair

Purpose: Aberrant activation of the phosphatidylinositol 3'-kinase (PI3K)-Akt signaling pathway is observed in many types of human cancer including triple negative breast cancer (TNBC). Additionally, dysregulation in the homologous recombination (HR)-dependent DNA-repair is associated with TNBC phenotype due to BRCA1/2 mutations or HR deficiency. Therefore, the hypothesis of this study was to evaluate the association of PI3K inhibition with HR pathway in TNBC in terms of BRCA1 mutation status. Methods: To examine the potential therapeutic effect of LY294002, an inhibitor of PI3K, on TNBC cell lines with known BRCA1 status, WST-1, annexin V, cell cycle analysis and AO/EB staining were performed. Additionally, RT-PCR and immunofluorescence analysis was used to explore the interaction between the inhibition of PI3K and HR functionality. Results: The findings showed that LY294002 could significantly inhibited the proliferation of TNBC cells. Furthermore, the suppression of PI3K resulted in HR impairment by BRCA1 and RAD51 downregulation and apoptotic cell death by the induction of DNA damage and BAX overexpression. Therefore, LY294002 was more effective in BRCA1-deficient TNBC cells. Conclusions: Consequently, targeted therapies based on the interaction of PI3K inhibition with BRCA1 mutations or HR deficiency in TNBC may be a promising strategy for the treatment of patients with TNBC.

scholarly journals BRCA1/2 Mutations and Bevacizumab in the Neoadjuvant Treatment of Breast Cancer: Response and Prognosis Results in Patients With Triple-Negative Breast Cancer From the GeparQuinto Study

2018 ◽  
Vol 36 (22) ◽  
pp. 2281-2287 ◽  
Author(s):  
Peter A. Fasching ◽  
Sibylle Loibl ◽  
Chunling Hu ◽  
Steven N. Hart ◽  
Hermela Shimelis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Strong Predictor ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Hazard Ratio ◽  
Brca1 And Brca2 ◽  
Mutation Carriers

Purpose BRCA1/2 mutations are frequent in patients with triple-negative breast cancer (TNBC). These patients are often treated with primary systemic chemotherapy. The aim of this study was to analyze the effects of BRCA1/2 mutations on pathologic complete response (pCR) and disease-free survival (DFS) in a cohort of patients with TNBC treated with anthracycline and taxane–containing chemotherapy, with or without bevacizumab. Patients and Methods Germline DNA was sequenced to identify mutations in BRCA1 and BRCA2 in 493 patients with TNBC from the GeparQuinto study. The pCR rates were compared in patients with and without mutation, as well as in patients treated with and without bevacizumab. In addition, the influence of BRCA1/2 mutation status and pCR status on DFS was evaluated relative to treatment. Results BRCA1/2 mutations were detected in 18.3% of patients with TNBC. Overall, patients with mutations had a pCR rate of 50%, compared with 31.5% in patients without a mutation (odds ratio [OR], 2.17; 95% CI, 1.37 to 3.46; P = .001). The pCR rate among patients treated with bevacizumab was 61.5% for BRCA1/2 mutation carriers and 35.6% for those without mutations (OR, 2.90; 95% CI, 1.43 to 5.89; P = .004). pCR was a strong predictor of DFS for patients without BRCA1/2 mutations (hazard ratio, 0.18; 95% CI, 0.11 to 0.31) but not for patients with BRCA1/2 mutations (hazard ratio, 0.74; 95% CI, 0.32 to 1.69). Conclusion The addition of bevacizumab may increase the pCR after standard neoadjuvant chemotherapy for patients with TNBC with BRCA1/2 mutations. In patients treated with anthracycline and taxane–based chemotherapy (with or without bevacizumab), pCR was a weaker predictor of DFS for BRCA1/2 mutation carriers than for patients without mutations.

scholarly journals Inherited Breast Cancer in Nigerian Women

2018 ◽  
Vol 36 (28) ◽  
pp. 2820-2825 ◽  
Author(s):  
Yonglan Zheng ◽  
Tom Walsh ◽  
Suleyman Gulsuner ◽  
Silvia Casadei ◽  
Ming K. Lee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Invasive Breast Cancer ◽  
Triple Negative ◽  
Brca1 Mutation ◽  
The United States ◽  
Age At Diagnosis ◽  
Cancer Genes ◽  
Loss Of Function ◽  
Nigerian Women

Purpose Among Nigerian women, breast cancer is diagnosed at later stages, is more frequently triple-negative disease, and is far more frequently fatal than in Europe or the United States. We evaluated the contribution of an inherited predisposition to breast cancer in this population. Patients and Methods Cases were 1,136 women with invasive breast cancer (mean age at diagnosis, 47.5 ± 11.5 years) ascertained in Ibadan, Nigeria. Patients were selected regardless of age at diagnosis, family history, or prior genetic testing. Controls were 997 women without cancer (mean age at interview, 47.0 ± 12.4 years) from the same communities. BROCA panel sequencing was used to identify loss-of-function mutations in known and candidate breast cancer genes. Results Of 577 patients with information on tumor stage, 86.1% (497) were diagnosed at stage III (241) or IV (256). Of 290 patients with information on tumor hormone receptor status and human epidermal growth factor receptor 2, 45.9% (133) had triple-negative breast cancer. Among all cases, 14.7% (167 of 1,136) carried a loss-of-function mutation in a breast cancer gene: 7.0% in BRCA1, 4.1% in BRCA2, 1.0% in PALB2, 0.4% in TP53, and 2.1% in any of 10 other genes. Odds ratios were 23.4 (95% CI, 7.4 to 73.9) for BRCA1 and 10.3 (95% CI, 3.7 to 28.5) for BRCA2. Risks were also significantly associated with PALB2 (11 cases, zero controls; P = .002) and TP53 (five cases, zero controls; P = .036). Compared with other patients, BRCA1 mutation carriers were younger ( P < .001) and more likely to have triple-negative breast cancer ( P = .028). Conclusion Among Nigerian women, one in eight cases of invasive breast cancer is a result of inherited mutations in BRCA1, BRCA2, PALB2, or TP53, and breast cancer risks associated with these genes are extremely high. Given limited resources, prevention and early detection services should be especially focused on these highest-risk women.

scholarly journals Clinical and Pathologic Characteristics of Patients With BRCA-Positive and BRCA-Negative Breast Cancer

2008 ◽  
Vol 26 (26) ◽  
pp. 4282-4288 ◽  
Author(s):  
Deann P. Atchley ◽  
Constance T. Albarracin ◽  
Adriana Lopez ◽  
Vicente Valero ◽  
Christopher I. Amos ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Characteristics ◽  
Triple Negative ◽  
Brca1 Mutation ◽  
Brca Mutations ◽  
Tumor Pathology ◽  
Mutation Carriers ◽  
Pathologic Features ◽  
Her 2 ◽  
Brca Negative

Purpose Mutations in the BRCA1 and BRCA2 genes confer greater risk of developing breast cancer. We determined whether tumor pathologic features and clinical features differ in patients with and without BRCA mutations. Patients and Methods Tumor pathologic features and clinical characteristics were examined in 491 women with breast cancer who underwent genetic testing for BRCA mutations between 1997 and 2006. A retrospective review of medical records was conducted to determine clinical characteristics including ethnicity, age and clinical stage at diagnosis, age at parity, number of full-term pregnancies, use of oral contraceptives and hormone replacement therapy, and BRCA mutation status. Tumor pathology was reviewed to determine histologic type, tumor grade, and estrogen receptor, progesterone receptor, and HER-2/neu status. Results Of the 491 patients with identified breast cancers, 391 patients were BRCA negative, and 86 patients were BRCA positive. Triple-negative breast cancer (ie, those with negative estrogen receptor, progesterone receptor, and HER-2/neu status) was diagnosed in 57.1% of the BRCA1-positive patients, 23.3% of the BRCA2-positive patients, and 13.8% of the BRCA-negative patients. BRCA1 mutation carriers had higher nuclear grade tumors than the other two groups (P < .001). Of the triple-negative cancer patients, BRCA2 mutation carriers were older when diagnosed than BRCA1 mutation carriers and noncarriers (P < .01). Conclusion These results suggest that tumors associated with BRCA1 mutations may be divided into two distinct groups, triple-negative and non–triple-negative groups. Future studies should seek to determine whether patients with BRCA1 mutations and triple-negative breast cancer respond to treatment better than BRCA-negative patients with similar tumor pathology.

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