The role of BRCA status on prognosis in patients with triple-negative breast cancer

Xie, Yuxin; Gou, Qinglong; Wang, Qianqian; Zhong, Xiaorong; Zheng, Hong

doi:10.18632/oncotarget.19895

Cited by 33 publications

(45 citation statements)

References 54 publications

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“…There are studies investigating the effect of BRCA mutation on the prognosis of patients. [12] However, there is limited information about how the family history of cancer affects the prognosis of breast cancer. Occurrence of the disease at a young age and the high histological grade of the tumor are common clin-ical and pathological features of TNBC.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Role of Family History in Patients with Triple Negative Breast Cancer

Altinok¹

2020

TJ Oncol

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OBJECTIVEBreast cancer is divided into four subtypes according to the receptor type. Patients with all three of the ER, PR, and c-erb2 receptors negative constitute 20% of all breast cancer cases. Cases of this group, called triple negative (TN), progress more aggressively than other subtypes. Additionally, familial transmission is more frequent in these patients. Therefore, we planned this study to investigate whether the family history was prognostic on survival in patients with TN breast cancer (TNBC). METHODSA total of 158 patients who were diagnosed with TNBC between 1996 and 2017 were retrospectively reviewed. Patients' age, family history, stage, grade, type of surgery, clinical follow-up, adjuvant, and neoadjuvant treatments of the tumor according to TNM system, and their effects on general and disease-free survival were analyzed. RESULTSThe median age was 46 years (range 24-82). The mean follow-up period was 72 months (range 10-224). A total of 64 (41%) patients had family risk for cancers (other than breast and ovarian). A total of 57 (36%) patients had breast cancer history in their family, 11 (7%) had ovarian cancer history in their family, and 4 (3%) had history of both cancers in their family. There was no significant difference between tumor characteristics and family history. In addition, there was no difference between patients with and without family history (breast and ovarian cancer) in terms of local control, disease-free, and overall survival (respectively p=0.13, p=0.11, p=0.59). The only statistically significant outcome was that diagnosis of a second primary cancer in the opposite breast for no family history group was 2% compared to 14% for those with family histories (p=0.03). CONCLUSIONThe family history of breast cancer did not affect the prognosis of the patient independently of the degree of consanguinity. These patients should be carefully monitored for the second primary of the opposite breast.

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Section: Discussionmentioning

confidence: 99%

Prognostic Role of Family History in Patients with Triple Negative Breast Cancer

Altinok¹

2020

TJ Oncol

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“…Or perhaps, target pathways that have been significantly compromised due to these new mutations introduced in the early passages of MSH2-deficient cells. [16] (C) Proportion of observed MSH2 KO cells that contain add(10)(q26).…”

Section: Discussionmentioning

confidence: 99%

“…Unlike other subtypes of breast cancer, majority of BLBC commonly does not express ER, PR, and human epidermal HER2 [13]. This histological feature is known as triple-negative breast cancer (TNBC) and BLBC makes up for 70-80% of TNBC, which contributes to the resistance of targeted therapies that other subtypes may respond to as well as having the lowest five year survival rate out of all breast cancer at 78.5% [7,14,16,17,18]. While patients who were diagnosed with other subtypes of breast cancer have access to wide range of effective therapies that target ER, PR, or HER2 pathways, BLBC patients do not effectively respond to any of these targeted therapies [9].…”

Section: Breast Cancer Subtypesmentioning

confidence: 99%

“…This is of our interest, because 30% of hereditary breast cancer patients carry an inherited BRCA1/2 mutation [21,22]. Out of that population of BRCA1/2 mutation carriers, BLBC accounts for 49% of BRCA1 mutation carriers in breast cancer patients (70% for TNBC) and 14% of BRCA2 mutation carriers (20% for TNBC) in breast cancer patients [14,16,17,18,22] (Figure 1B, C).…”

Section: Clinical Trials and Parp-1 Inhibitormentioning

confidence: 99%

“…This therapy is promising for the treatment of triple-negative breast cancer. However, BRCA1 mutation carrier only comprises of about 14% of BLBC group (20% of TNBC) and BRCA2 mutation carrier comprises of 5% of BLBC (7% of TNBC) [16,32] (Figure 1B, C). Additionally, patients'…”

Section: Clinical Trials and Parp-1 Inhibitormentioning

confidence: 99%

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Targeting MSH2-MSH6 heterodimer in treating basal-like breast cancer

Jo¹

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______________________________ Maria Spies ______________________________ Andrean Simons-Burnett ______________________________ Munir Tanas ii ACKNOWLEDGEMENTS First and foremost, I would like to thank Dr. Weizhou Zhang for his guidance and support throughout the years. I have never met anyone who is this dedicated to science and who can see clear through any noises and obstacles so effortlessly both in life and in research. He is who I aspire to be. Thank you to Dr. Meng Wu for high-throughput screening guidance and support throughout all of the hardships. Also, thank you to Dr. Kuo-Kuang Wen for lending his support and for countless interesting conversations. I would also like to thank Nicholas Borcherding for bioinformatics support and analysis throughout the years. He inspired me to get back into programming. It's really amazing what we can do with computers these days. Thanks Edward Cho for assistance for the past few months. You will carry the torch from here on out with Nick. So good luck guys. Also, to the rest of the lab members: Wei, Paige, Ryan, Gaurav, Kawther, and Ajay (my brother from another mother), thanks for all the help. Working in the lab wouldn't have been as enjoyable without you guys. I would also like to thank my thesis committee for helpful advices they have given me. Last but not least, thank you Dr. Waldschmidt for giving me this great opportunity to experience what scientists actually go through. I remember when I was first applying for graduate schools, I was genuinely curious about what it would really feel like to be knee deep in scientific research. In the end, I got more than what I bargained for and I will carry them with me for the rest of my life. iii ABSTRACT To identify novel therapeutic targets for basal-like breast cancer (BLBC) subtype, we investigated several DNA repair mechanisms associated with maintenance of high genomic instability for cell survival in cancer cells. We identified that the expressions of mismatch repair proteins, MutS protein homolog 2 and 6 (referred to as MSH2/6 hereafter), are elevated across BLBC samples compared to other breast cancer subtypes. High expression level of MSH2/6 in BLBC is associated with worse prognosis and survivability for patients. Therefore, we knocked out MSH2/6 in BLBC cell lines and performed in vivo xenograft and syngeneic mice model studies to find significant attenuation of tumor growth in MSH2 KO group. Also, MSH2/6-deficient BLBC cells have a increased rate of mutations. Additionally, we tested the efficacy of conventional chemotherapeutics and radiation treatment that would further tip the genomic instability in MSH2/6-deficient BLBC cells towards cell death, but found them to be ineffective in vivo. With our focus on improving BLBC therapeutics, we performed highthroughput screening of 1280 FDA-approved compounds to discover that calcium channel blockers preferentially destroy MSH2/6-deficient BLBC cells over MSH2/6proficient BLBC cells. This was likely due to association of significantly mutated pathways that involved...

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Prevalence of BRCA1 and BRCA2 gene mutations in Chinese patients with high‐risk breast cancer

Wang

Liu

Maimaitiaili

et al. 2019

Molec Gen & Gen Med

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Background Breast cancer is the most common cancer among women worldwide. Here, we report the prevalence of BRCA1/2 mutations in patients with high‐risk breast cancer from Inner Mongolia and Jilin, China, which was a part of a nationwide project on the detection of BRCA1/2 mutations in Chinese patients with hereditary breast cancer. Methods According to the criteria, index patients from a total of 245 independent families were initially recruited. All 49 exons of BRCA1 and BRCA2 and adjacent noncoding regions were screened for mutations based on next‐generation sequencing from collected saliva. Results We detected 17 BRCA1/2 variants in 18 of 216 (8.3%) index patients with high‐risk breast cancer. Among these, seven mutations were novel, including four BRCA1 mutations (c.123_124delCAinsAT, c.5093_5096delCTAA, c.5396‐2A>G, and c.2054delinsGAAGAGTAACAAGTAAGAAGAGTAACAAGAAG), and three BRCA2 mutations (c.304A>T, c.7552_7553insT, and c.9548_9549insA). The BRCA1/2 variants were identified in 14% (8/57) of the patients with triple‐negative breast cancer and in 6.3% (10/159) of the patients with non‐triple‐negative breast cancer. There was no significant difference between the two groups (p = 0.07). A higher frequency for BRCA1 mutations was observed in patients with triple‐negative breast cancer than in those with non‐triple‐negative breast cancer (12.3% vs. 2.5%, p = 0.004). The frequencies of the BRCA2 mutations were not significantly different between patients with triple‐negative breast cancer and those with non‐triple‐negative breast cancer (1.8% vs. 3.8%, p = 0.46). Conclusion We found that patients with triple‐negative breast cancer had a higher frequency of BRCA1 mutations than those with non‐triple‐negative breast cancer. In this study, no significant associations between the BRCA1/2 mutation status and age, family history of breast cancer, ovarian cancer, pancreatic cancer and prostate cancer, number of primary lesions, tumor size, or lymph node metastasis were observed.

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The role of BRCA status on prognosis in patients with triple-negative breast cancer

Cited by 33 publications

References 54 publications

Prognostic Role of Family History in Patients with Triple Negative Breast Cancer

Prognostic Role of Family History in Patients with Triple Negative Breast Cancer

Targeting MSH2-MSH6 heterodimer in treating basal-like breast cancer

Prevalence of BRCA1 and BRCA2 gene mutations in Chinese patients with high‐risk breast cancer

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