Association of BRCA1 germline mutations in young onset triple-negative breast cancer (TNBC)

Andrés, Raquel; Pajares, Isabel; Balmañà, Judith; Llort, Gemma; Cajal, Teresa Ramón y; Chirivella, Isabel; Aguirre, Elena; Robles, Luis; Lastra, Enrique; Pérez‐Segura, Pedro; Bosch, N.; Yagüe, Carmen; Lerma, Enrique; Godino, Javier; Miramar, María Dolores; Moros, Manuel; Astier, P.; Sáez, Berta; Vidal, María; Arcusa, Àngels; Cajal, S. Ramón y; Calvo, María Teresa; Trés, A.

doi:10.1007/s12094-013-1070-9

Cited by 24 publications

(12 citation statements)

References 18 publications

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“…The percentage of patients with deleterious BRCA mutation in the KU series is consistent with other reported studies from the United States (15, 19). The Spanish series reported a slightly lower percent of patients with deleterious BRCA mutations, but this prevalence rate is also consistent with the reported rates in Spanish women with TNBC non-selected for family history(48, 49). We noted a pCR rate of 59% in BRCA mutation carriers, which is consistent with previously reported pCR rates with single agent platinum and platinum-anthracyline-taxane combination chemotherapy in BRCA mutation carriers(24, 50).…”

Section: Discussionsupporting

confidence: 86%

Efficacy of Neoadjuvant Carboplatin plus Docetaxel in Triple-Negative Breast Cancer: Combined Analysis of Two Cohorts

Sharma

López-Tarruella

García-Sáenz

et al. 2017

Clinical Cancer Research

120

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PURPOSE Recent studies demonstrate that addition of neoadjuvant (NA) carboplatin (Cb) to anthracycline/taxane chemotherapy improves pathological complete response (pCR) in triple negative breast cancer (TNBC). Effectiveness of anthracycline-free, platinum combinations in TNBC is not well known. Here we report efficacy of NA carboplatin + docetaxel (CbD) in TNBC. PATIENTS AND METHODS The study population includes 190 patients with stage I-III TNBC treated uniformly on two independent prospective cohorts. All patients were prescribed NA chemotherapy regimen of Cb (AUC 6) + D (75mg/m2) given every 21 days × 6 cycles. Pathological complete response (pCR: no evidence of invasive tumor in the breast and axilla) and Residual Cancer Burden (RCB) were evaluated. RESULTS Among 190 patients, median tumor size was 35mm, 52% Lymph Node positive and 16% had germline BRCA1/2 mutation. The overall pCR and RCB 0+1 rates were 55% and 68%, respectively. pCR in patients with BRCA associated and wild-type TNBC were 59% and 56%, respectively (p=0.83). On multivariable analysis stage III disease was the only factor associated with a lower likelihood of achieving a pCR. 21% and 7% of patients, respectively, experienced at least one grade 3 or 4 adverse event. CONCLUSION The CbD regimen was well tolerated and yielded high pCR rates in both BRCA associated and wildtype TNBC. These results are comparable to pCR achieved with addition of Cb to anthracycline-taxane chemotherapy. Our study adds to the existing data on the efficacy of platinum agents in TNBC and supports further exploration of the CbD regimen in randomized studies.

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Section: Discussionsupporting

confidence: 86%

Efficacy of Neoadjuvant Carboplatin plus Docetaxel in Triple-Negative Breast Cancer: Combined Analysis of Two Cohorts

Sharma

López-Tarruella

García-Sáenz

et al. 2017

Clinical Cancer Research

120

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“…The basal-like BC subtype commonly refers to any mammary gland that lacks expression of the progesterone receptor (PR), estrogen receptor (ER), and human epidermal growth factor receptor (HER) 2, which is widely regarded as triple-negative BC (TNBC) ( 3 – 5 ). TNBC is characterized as a mesenchymal phenotype, high proliferation, aggressive clinical behavior and young age accounts for approximately 8–15% of all BC and ( 6 , 7 ). Recently, researchers have drawn particular attention to TNBC because of its poor unfavorable clinical outcome and lower 5-year survival rate ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-182 promotes proliferation and metastasis by targeting FOXF2 in triple-negative breast cancer

Zhang

Liu

et al. 2017

Oncology Letters

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Triple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer (BC), is characterized as high proliferation, young age and poor prognosis. MicroRNA-182 (miR-182) was reported to have oncogenic potential in many cancers. We aimed to elucidate pathobiological effects of miR-182 expression by targeting forkhead-box F2 (FOXF2) in TNBC. In this study, we explored the functional role of miR-182 expression in TNBC. Quantitative real-time PCR (qRT-PCR) was applied to evaluate the expression of miR-182 in cell lines and tissues. A series of in vitro and in vivo assays were performed in the MCF-7 and MDA-MB-231 cell lines with miR-182 overexpression. Luciferase reporter assays and western blot analysis were used to identify FOXF2 as the direct and functional target of miR-182. In TNBC tissues and cell lines, we found that miR-182 was significantly upregulated. Transwell assay showed that re-expression of miR-182 increased cell migration and invasion abilities and MTT assay showed that it promoted cell growth in vitro. In vivo assay, re-expression of miR-182 significantly increase tumor volume and enhanced instant metastasis in the lungs of mice. Besides, FOXF2 was identified as a direct and functional target of miR-182. These results indicated that miR-182 plays an important role in the initiation and progression of TNBC by targeting FOXF2 and the miR-182/FOXF2 axis may present a new therapeutic strategy for TNBC in the future.

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“…Triple negative tumors represent 8–15% of all breast cancer cases and 10–15% of basal-like tumors [11]. Triple-negative and basal-like breast cancers are often associated with high proliferation, high grade, young age (<38 years), lack of BRCA1 protein expression and aggressive clinical behavior (lymph node and distant metastases occurrence) [12].…”

Section: Introductionmentioning

confidence: 99%

MicroRNAs Expression in Triple Negative vs Non Triple Negative Breast Cancer in Tunisia: Interaction with Clinical Outcome

et al. 2014

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IntroductionMicroRNAs are small, non coding regulatory molecules containing approximately 21 to 25 nucleotides. They function as controllers of expression at post transcriptional levels of most human protein-coding genes and play an essential role in cell signaling pathways. The objective of the present study is to evaluate the expression profile of the following micro-RNAs: miR-10b, miR-17, miR-21, miR-34a, miR-146a, miR-148a and miR-182, and to determine their possible interaction in triple-negative and non triple-negative primary breast cancers based on clinical outcome.Methods60 triple-negative and non triple-negative breast cancer cases, along with their corresponding normal samples were investigated in relation to the expression of the seven studied miRNAs using qPCR Syber Green.ResultsWe observed that miR-21, miR-146a and miR-182 were significantly over expressed in triple negative breast cancer. Moreover, miR-10b, miR-21 and miR-182 were significantly associated to lymph node metastases occurrence in triple negative breast carcinoma while only miR-10b was associated with grade III in non triple negative breast cancer cases. Almost all the analyzed microRNAs were strongly associated with patients’ genico-obstetric history in non triple negative breast cancer cases except for miR-34a. All the studied microRNAs were strongly correlated with the use of the contraceptive pills in non triple negative breast cancer groups. The additive effect of hormonal factors in triple negative breast cancer cases showed an association with all the studied miRs except for miR-34 and miR-146a.ConclusionThe studied microRNAs are strongly influenced by environmental factors especially with hormonal patients’ history. Moreover, miR-10b, miR-21 and miR-182 could be defined as biomarkers in breast cancer to predict both lymph node metastases and grade III occurrence.

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Association of BRCA1 germline mutations in young onset triple-negative breast cancer (TNBC)

Abstract: Patients with apparently sporadic TNBC younger than 50 years and a non-informative family history are candidates for germline genetic testing of BRCA1.

Cited by 24 publications

References 18 publications

Efficacy of Neoadjuvant Carboplatin plus Docetaxel in Triple-Negative Breast Cancer: Combined Analysis of Two Cohorts

Efficacy of Neoadjuvant Carboplatin plus Docetaxel in Triple-Negative Breast Cancer: Combined Analysis of Two Cohorts

MicroRNA-182 promotes proliferation and metastasis by targeting FOXF2 in triple-negative breast cancer

MicroRNAs Expression in Triple Negative vs Non Triple Negative Breast Cancer in Tunisia: Interaction with Clinical Outcome

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