Metastatic Breast Cancer with BRCA Mutation Discovered By Next-Generation Sequencing Responding to Olaparib

Rizvi, Wajeeha; Truong, Phu; Truong, Quoc Van

doi:10.7759/cureus.1337

Cited by 6 publications

(6 citation statements)

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“…Breast cancers have low expression of MHC I antigens and relatively low state of immunogenicity to escape from immune recognition. 16 – 18 However, breast cancers with high TMB value were indicative of potentially more neoantigens and elicited an appropriate adaptive immune response with immunotherapy. In support of this, a retrospective study using TMB as a marker in the Phase III clinical trial of CheckMate 026 showed that TMB was superior to PD-L1 expression as a biomarker to distinguish those who would benefit from Opdivo in non-small-cell lung cancer.…”

Section: Discussionmentioning

confidence: 99%

Prediction of tumor mutation burden in breast cancer based on the expression of ER, PR, HER-2, and Ki-67

Xu¹,

Guo²,

Jing³

et al. 2018

OTT

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ObjectiveCancer immunoediting is the process of eliminating highly immunogenic tumor cells by somatic evolution and protecting the host from tumor development in the host immune system. Frequencies of somatic mutations or tumor mutation burden (TMB) were associated with immunogenicity of breast cancer. This study aimed to predict the level of TMB in patients with breast cancer by the expression of estrogen (ER), progesterone (PR), HER-2, and Ki-67, thereby anticipating the prognosis of patients and the possible response to immunotherapy.Patients and methodsIn 53 patients with breast cancer, the 453 multigenes panel based on NGS was used to determine the TMB value of breast cancer in the patient’s primary tumor tissues. The predicted TMB value was divided into 4 groups: A (0–3.33), B (3.33–5.56), C (5.56–8.89), and D (>8.89), according to the quartile method, with group A as reference level. Logistic regression was used to analyze the risk ratio of each molecule type, and the prediction model was established. Survival probabilities by covariates were assessed using Kaplan–Meier estimator survival analysis and Cox’s proportional hazards models.ResultsIn 53 patients, the TMB value measured by the NGS polygenic panel was between 0 and 14.4/Mb. TMB distribution in 53 cases of breast cancer tissue: 18 cases in A group, 22 cases in B group, 10 cases in C group, and 3 cases in D group. HER-2 expression positivity was significantly associated with TMB (HER-2 positive vs HER-2 negative, odds ratio [OR] =34.81, 95% confidence interval [CI]: 3.711–821.689, P=0.0065). Higher TMB was distributed in the patients who were Ki-67 expression positive (>14%) than those who were Ki-67 expression negative (≤14%) (OR =0.217, 95% CI: 0.054–0.806, P=0.0242). However, no significant differences of TMB were found between ER-positive group and ER-negative group (OR =3.133, 95% CI: 0.124–127.687, P=0.4954) and between PR-positive group and PR-negative group in terms of TMB (OR =1.702, 95% CI: 0.162–20.335, P=0.6492). The predicted model is TMB = −1.14×ER +0.53×PR +3.55×HER-2-1.53×Ki-67+ CONSTANT (INTERCEPT). Patients with low TMB had a better disease-free survival (DFS) than those with high TMB (83 vs 59 m, P=0.002). In a multivariate analysis, high TMB (>5.56) was an independent predictive factor for decreased DFS (adjusted hazard ratio [HR], 5.594; 95% CI: 1.694–18.473; P = 0.005).ConclusionThe preliminary results suggest that the level of TMB value in patients with breast cancer can be predicted based on the expression levels of ER, PR, HER-2, and Ki-67, which may indicate the prognostic and predictive value of immunotherapy in patients with breast cancer.

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Section: Discussionmentioning

confidence: 99%

Prediction of tumor mutation burden in breast cancer based on the expression of ER, PR, HER-2, and Ki-67

Xu¹,

Guo²,

Jing³

et al. 2018

OTT

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“… 1 According to the American Cancer Society, an estimated 252 710 new cases of invasive BC will be diagnosed and 40 610 cancer deaths will be occurred in BC in 2017. 2 The main carcinogenic factors, including genetic mutations, endocrine disorders, and decline in immune function may increase the risk of developing BC. 3 Chemotherapy is one of the current main anticancer therapies for the treatment of BC which has shown to inhibit tumor growth and prolong patient survival.…”

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confidence: 99%

Involvement of miR-451 in resistance to paclitaxel by regulating YWHAZ in breast cancer

et al. 2017

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MicroRNAs (miRNAs) have been identified as major post-transcriptional regulators of the initiation and progression of human cancers, including breast cancer. However, the detail role of miR-451 has not been fully elucidated in breast cancer. In this study, we aimed to investigate the biological role and molecular mechanisms of miR-451 in drug resistance in breast cancer cell lines and in xenograft model. We show that miR-451 is decreased in human breast cancer specimens and in paclitaxel-resistant (PR) cells. Ectopic expression of miR-451 could inhibit the cell migration and invasion, promoted apoptosis, induced cell-cycle arrest Furthermore, tyrosine3-monooxygenase/tryptophan5-monooxygenase activation protein zeta (YWHAZ) was identified as a direct target of miR-451. Remarkably, the expression of YWHAZ is inversely correlated with the level of miR-451 in human breast cancer samples. Co-treatment with miR-451 mimics and YWHAZ-siRNA significantly enhanced YWHAZ knockdown in both SKBR3/PR and MCF-7/PR cells Moreover, miR-451 markedly inhibited expression of β-catenin via YWHAZ and subsequently inhibited downstream gene cyclin D1, c-Myc expression. The results of xenograft model in vivo showed that intratumor injection of miR-451 agomir induced a tumor-suppressive effect in SKBR3/PR drug-resistant xenograft model. Taken together, our findings suggested that miR-451 might be considered as important and potential target in paclitaxel-resistant breast cancer treatment.

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“…Patients with ovarian cancer who carry BRCA1/2 mutations are very sensitive to platinum‐based chemotherapy with good prognosis (Byrski et al, ), and can benefit from treatment with poly ADP‐ribosome polymerase inhibitors (Isakoff, ; Rouleau, Patel, Hendzel, Kaufmann, & Poirier, ; Ström et al, ). Clinical studies have shown that prophylactic bilateral mammectomy or bilateral oophorectomy can reduce 50%–90% of the risk of breast and ovarian cancer in women who have family history of breast cancer and carry BRCA1/2 mutations (Domchek & Kaunitz, ; Rizvi, Truong, & Truong, ). With the advancement of precision medicine and targeted therapy, detection of BRCA1/2 mutations in blood and/or tumor tissues of patients with breast and ovarian cancer will help select targeted drugs and chemotherapy regimens and better assess prognosis (Robson et al, ).…”

Section: Discussionmentioning

confidence: 99%

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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Metastatic Breast Cancer with BRCA Mutation Discovered By Next-Generation Sequencing Responding to Olaparib

Cited by 6 publications

References 5 publications

Prediction of tumor mutation burden in breast cancer based on the expression of ER, PR, HER-2, and Ki-67

Prediction of tumor mutation burden in breast cancer based on the expression of ER, PR, HER-2, and Ki-67

Involvement of miR-451 in resistance to paclitaxel by regulating YWHAZ in breast cancer

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

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