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Prognostic role of microRNA 182 and microRNA 18a in locally advanced triple negative breast cancer.

ABSTRACT: BACKGROUND:The study assessed the epigenetic regulation and the role of microRNA (miR) expression in locally advanced triple negative breast cancers (TNBC) and comparison with the clinico-pathological variables and survival. METHODS:Fifty patients of locally advanced TNBC during the period 2011-2013 were included. Expression level of test microRNA (miR-182 and miR-18a) was determined using Taqman quantitative Real time polymerase chain reaction (qRT-PCR) from formalin fixed paraffin embedded biopsy blocks. Clinical and demographic information and survival data was retrieved from the Hospital medical records. RESULTS:An improved clinical complete response (cCR) was observed in patients with age ? 45 years (80%), premenopausal status (70%), tumor size < 6 cms (80%), nodal status N0-N1 (95%) and grade II-III tumor (80%). A statistically significant correlation was observed on comparison of cCR with menopausal status (p-value 0.020), T category (p-value 0.018) and the clinical nodal status (p-value 0.003). pCR also correlated with clinical nodal status (p-value 0.008). Epigenetically, miR-18a under expression (< 8.84) was most commonly associated with tumor size < 6 cms (76.7%), clinical nodal status N0-N1 (90%), cCR (60%) and pCR (53.3%). A similar trend was observed with miR-182. Statistical significance was observed with T category (p-values 0.003 and 0.004), clinical nodal status (p-values 0.001 and 0.001), clinical response (p-values 0.002 and 0.002) and pathological response (p-values 0.007 and 0.006) with respect to miR-18a and miR-182, respectively. Also, the menopausal status significantly correlated with the miR-182 expression (p-value 0.009). miR-182 overexpression (? 6.32) was not observed in any of the postmenopausal patients. A univariate cox proportional hazard regression model also showed statistical interactions (p-values <0.004). CONCLUSION:miR-182 and miR-18a overexpression correlates with worse clinical and pathological tumor characteristics in locally advanced TNBC and hence could be used to predict the outcomes and prognosis in these patients.

SUBMITTER: Bajaj R

PROVIDER: S-EPMC7657558 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Prognostic role of microRNA 182 and microRNA 18a in locally advanced triple negative breast cancer.

Bajaj Rajat R Tripathi Rupal R Sridhar T S TS Korlimarla Aruna A Choudhury Kumardeep Dutta KD Suryavanshi Moushumi M Mehta Anurag A Doval Dinesh Chandra DC

PloS one 20201111 11

<h4>Background</h4>The study assessed the epigenetic regulation and the role of microRNA (miR) expression in locally advanced triple negative breast cancers (TNBC) and comparison with the clinico-pathological variables and survival.<h4>Methods</h4>Fifty patients of locally advanced TNBC during the period 2011-2013 were included. Expression level of test microRNA (miR-182 and miR-18a) was determined using Taqman quantitative Real time polymerase chain reaction (qRT-PCR) from formalin fixed paraff ...[more]

PMID: 33175907

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Project description:PurposeWomen with locally advanced/high-risk triple-negative breast cancer treated with the current standard chemotherapy continue to have a poor prognosis. High-dose chemotherapy with autologous stem cell transplant as treatment for locally advanced/high-risk breast cancer remains controversial due to a lack of survival benefit seen in previous phase III trials. However, these trials evaluated a heterogeneous group of patients with different receptor subtypes. A marginal benefit was observed in certain subgroups. We report long-term outcomes of women with stage IIB or III triple-negative breast cancer treated with high-dose chemotherapy followed by autologous stem cell transplant at our institution between 1995 and 2001.MethodsThis is a retrospective analysis of stage IIB or stage III triple-negative breast cancer treated with high-dose chemotherapy followed by autologous stem cell transplant. We excluded women with hormone-positive, HER2/neu-positive/unknown, and/or metastatic disease prior to transplant as per updated AJCC 7th edition guidelines. Patients underwent surgery and either neoadjuvant or adjuvant anthracycline and taxane-based chemotherapy and then proceeded to high-dose chemotherapy and autologous stem cell transplant using carmustine 600 mg/sqm, cyclophosphamide 5.6gm/sqm, and cisplatin 165 mg/sqm (STAMP 1 regimen) for consolidation. This was followed by locoregional breast and lymph node radiation per standard of care.ResultsTwenty-nine women (2 stage IIB and 27 stage III) were evaluated. The median age at diagnosis was 43 years (IQR: 40, 51). Eleven patients had 4-9 regional lymph nodes (LN) involved and 16 had 10+ involved LNs. Four patients had T4 or inflammatory breast cancer and two had ipsilateral supraclavicular LNs involved. The median follow-up time is 16 years (95% CI: 12, 19, range <1-19 y) posttransplant. The median overall survival was 15 years (95% CI: 3, 19); the median DFS was 14 years (95% CI: 1, 19).ConclusionsThis study of locally advanced/high-risk triple-negative breast cancer treated with adjuvant high-dose chemotherapy and autologous stem cell transplant reveals high overall survival rate. With the current improvement in treatment-related mortality, re-evaluating this approach in this subset of high-risk breast cancer in prospective randomized studies may be worthwhile.

Dataset Information

Prognostic role of microRNA 182 and microRNA 18a in locally advanced triple negative breast cancer.

Publications

Prognostic role of microRNA 182 and microRNA 18a in locally advanced triple negative breast cancer.

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