A three lncRNA set: AC009975.1, POTEH-AS1 and AL390243.1 as nodal efficacy biomarker of neoadjuvant therapy for HER-2 positive breast cancer

2021 ◽  
Author(s):  
Zhao Bi ◽  
Yue Zhang ◽  
Xing-Guo Song ◽  
Peng Chen ◽  
Peng-Fei Qiu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Therapy ◽  
Disease Free Survival ◽  
Tumor Type ◽  
Breast Cancers ◽  
Clinical Factors ◽  
Her2 Breast Cancer ◽  
Potential Biomarker ◽  
Her 2 ◽  
Auc Value

Abstract Background and purpose LncRNAs have been found to play regulatory role in the chemoresistance after neoadjuvant therapy (NAT) of breast cancers. The breast pathological complete response (pCR) was different from the axillary nodal pCR (apCR) after NAT. And this difference was most significant in HER-2 positive (HER2+) subtype. The aim was to explore whether lncRNA expression in primary tumor had nodal predicting value for HER2 + breast cancer who received NAT. Methods Total RNA was extracted from 103 HER2 + breast cancer tissues before NAT, as well as from 48 pairs of cancers and para-cancers tissues which did not receive NAT. LncRNAs were selected by microarray, validated by qPCR, and analyzed combined with related clinical factors to illuminate its potential as nodal efficacy biomarkers of NAT. Results Our results demonstrated that three lncRNA set: lncRNA- AL390243.1, POTEH-AS1, and lncRNA-AC009975.1 were significantly up-regulated in non-apCR tissues, the AUC value was 0.789 (95%CI: 0.703–0.876). Combined with clinical factors and genomics, the multivariate analysis showed that the expression of lncRNA-AL390243.1 (OR 5.143; 95% CI: 1.570-16.847), tumor type (OR 0.144; 95% CI: 0.024–0.855) and nodal stage (OR 0.507; 95% CI: 0.289–0.888) were indicated as independent predictors for apCR after NAT in HER2 + patients (all p < 0.05). These three predictors were used to create a predictive nomogram. The AUC value was 0.859 (95%CI: 0.790–0.929). The calibration curve showed a satisfactory fit between predictive and actual observation based on internal validation with a bootstrap resampling frequency of 1000. Patients with higher level of lncRNA-AL390243.1 expression had a worse survival, especially in disease-free survival. The expression of lncRNA-AL390243.1 was significantly higher in nodal positive subgroup than in nodal negative subgroup (p = 0.0271). Conclusion The expression of LncRNA-AC009975.1, POTEH-AS1, and lncRNA-AL390243.1 were upregulated in non-apCR tissues and acted as a new potential biomarker for the nodal efficacy prediction of NAT.

scholarly journals A Three lncRNA Set: AC009975.1, POTEH-AS1 and AL390243.1 as Nodal Efficacy Biomarker of Neoadjuvant Therapy for HER-2 Positive Breast Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Zhao Bi ◽  
Peng-Fei Qiu ◽  
Yue Zhang ◽  
Xing-Guo Song ◽  
Peng Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Therapy ◽  
Molecular Mechanisms ◽  
Multivariate Logistic Regression Analysis ◽  
Predictive Biomarkers ◽  
Tumor Type ◽  
Primary Tumors ◽  
Her2 Breast Cancer ◽  
Auc Value ◽  
Cancer Tissues

PurposeThe study aimed to explore whether the expression of lncRNAs in primary tumors could predict nodal efficacy after neoadjuvant therapy (NAT) for HER2+ breast cancer.MethodsTotal RNA was extracted from HER2+ breast cancer tissues before NAT (n=103) and from 48 pairs of cancers and para-cancers tissues that did not receive NAT. Different lncRNAs were selected by microarray, validated by qPCR, and analyzed to illuminate their potential as nodal efficacy biomarkers after NAT.ResultsOur results demonstrated that three lncRNA sets, lncRNA-AL390243.1, POTEH-AS1, and lncRNA-AC009975.1, were up-regulated in non-apCR tissues. The AUC value was 0.789 (95%CI: 0.703-0.876). The multivariate logistic regression analysis identified the expression of lncRNA-AL390243.1 (OR 5.143; 95% CI: 1.570-16.847), tumor type (OR 0.144; 95% CI: 0.024-0.855), and nodal stage (OR 0.507; 95% CI: 0.289-0.888) as independent predictors for apCR after NAT in HER2+ patients (all p&lt;0.05). Then the three predictors were used to create a predictive nomogram. The AUC value was 0.859 (95%CI: 0.790-0.929). The calibration curve showed a satisfactory fit between predictive and actual observation based on internal validation with a bootstrap resampling frequency of 1000. Patients with higher expression of lncRNA-AL390243.1 had worse survival. LncRNA-AL390243.1 was up-regulated more in the nodal positive subgroup than in the nodal negative subgroup (p=0.0271).ConclusionThe lncRNA-AL390243.1, POTEH-AS1, and lncRNA-AC009975.1 were upregulated in non-apCR breast cancer tissues. These three lncRNAs might have the potential to be used as predictive biomarkers of nodal efficacy of HER2+ breast cancer. Further studies are required to illuminate the underlying molecular mechanisms further.

scholarly journals Association between ultrasound findings, tumor type, grade, and biological markers in patients with breast cancer

2019 ◽  
Vol 50 (1) ◽  
Author(s):  
Yasmine Mohamed Elsaeid ◽  
Dina Elmetwally ◽  
Salwa Mohamed Eteba
Keyword(s):  
Breast Cancer ◽  
Biological Markers ◽  
Tumor Grade ◽  
The State ◽  
Tumor Type ◽  
Breast Cancers ◽  
Duct Carcinoma ◽  
Ultrasound Findings ◽  
Her 2 ◽  
And Biological Markers

Abstract Background This prospective study included 65 female patients with primary breast cancer. Ultrasound was performed for all patients. Ultrasound findings were analyzed according to the ACR BI-RADS lexicon 5th edition and correlated with tumor type, grade, and biological markers (ER, PR, HER-2/neu, and Ki67). The purpose of this study is to assess the association between ultrasound findings, tumor type, grade, and the state of biological markers in patients with breast cancer. Results Irregular shape and speculated margins are more frequently associated with invasive duct carcinoma than DCIS (p value < 0.001). There were no association between the ultrasound findings (shape, margin, orientation, echopattern, and posterior features) and the tumor grade (p value 1.0, 0, 0.544, 1.0, and 1.0), respectively. Irregular shape is more frequently seen in ER and PR positive breast cancers (p value = 0.036 and 0.026, respectively). Non-circumscribed margins were frequently seen in PR positive breast cancers (p value = 0.068). No statistically significant difference between US descriptors and HER-2/neu-positive cases. Conclusion Irregularly shaped tumors with speculated margins are frequently seen in invasive duct carcinoma and also more frequently seen in ER-, PR-, and Ki67-positive cases. No relation between ultrasound descriptors and the tumor grade of invasive duct carcinoma. Also, there were no relation between ultrasound descriptors and the state of HER-2/neu.

Disease-free survival pattern in breast cancer patients in India treated in a single institution.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e12030-e12030 ◽  
Author(s):  
Basavalinga S. Ajaikumar ◽  
Kodaganur Srinivasachar Gopinath ◽  
B S Srinath ◽  
Ramesh Bilimagga S ◽  
Nalini K Rao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Advanced Breast ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Distant Failure ◽  
Her 2 ◽  
Disease Free

e12030 Background: This study elucidates data from a 5 year retrospective study evaluating survival rates and prognostic factors in breast carcinoma patients in a private cancer set up in south India. Methods: 1046 patients who were treated between years 2003 to 2008 were analyzed. Clinical data including stage, histopathology type, age, node positivity, treatment plan, chemotherapy regimen, ER/ PR and Her2 Neu status, type of surgery etc were abstracted in a database. Five year disease free survival, local failure free survival and distant failure free survival was calculated using Kaplan Meier survival curves. Log rank mantel hazel tests were used to compare two survival curves. Results: Local recurrence was seen in 4% and distant metastases in 22% of the study sample. 62% of patients presented with early breast cancer (AJCC Stage I, II and IIIA). 85.6% of early and 73.1% of locally advanced breast cancers were disease free at 5 years (p<0.001).90.6% of early and 82.4% of locally advanced breast cancers had distant failure free survival at 5 years (p=0.001). Local failure free survival was 96.1% in both early and locally advanced breast disease at 5 years.94.9% of her 2 negative and 83.5% Her 2 positive were disease free at 5 years (p=0.001). 5 years progression free survival was 91.5% for breast conservation surgery vs 84.1% for mastectomy with axillary clearance (p=0.01). 75.4% with triple negative status and 80.8% non triple negative receptor status had 5 years DFS. Conclusion: This is a first report of survival patterns of breast cancer patients treated in a single centre in India. High early stage patient numbers and high median disease free survival times could be because of improvement in screening and treatment of breast cancer in a developing country like India.

Adjuvant treatment with paclitaxel plus trastuzumab for node-negative breast cancer: real-life experience

2021 ◽  
Author(s):  
Omer Diker ◽  
Burak Yasin Aktas ◽  
Recep Ak ◽  
Bahadır Koylu ◽  
Onur Bas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Life Experience ◽  
Real Life ◽  
Disease Free Survival ◽  
Invasive Disease ◽  
Breast Cancers ◽  
Node Negative ◽  
Her2 Breast Cancer ◽  
Node Negative Breast Cancer

Background: In node-negative HER2-overexpressed breast cancers, adjuvant paclitaxel plus trastuzumab treatment is a successful de-escalation approach with excellent survival outcomes. Methods: All patients with HER2+ breast cancer treated in our centers were retrospectively reviewed. Results: We analyzed 173 patients who were treated with adjuvant paclitaxel plus trastuzumab. The mean tumor size was 2.2 cm. There were eight invasive disease events or death: four distant recurrences (2.3%), three locoregional recurrences (1.7%) and one death without documented recurrence after a 52 month follow-up. The 3-year disease-free survival and recurrence-free interval rate was 96.6%. Conclusion: This real-life experience with adjuvant paclitaxel plus trastuzumab demonstrated few distant recurrences and is compatible with the APT trial findings.

Can Radiologic Tumor Size Following Neoadjuvant Therapy Reliably Guide Tissue Resection in Breast Conserving Surgery in Patients with Invasive Breast Cancer?

2020 ◽  
Vol 86 (10) ◽  
pp. 1248-1253
Author(s):  
Sarah Walcott-Sapp ◽  
Marissa K. Srour ◽  
Minna Lee ◽  
Michael Luu ◽  
Farin Amersi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Therapy ◽  
Invasive Breast Cancer ◽  
Tumor Size ◽  
Disease Free Survival ◽  
Positive Margin ◽  
Breast Conserving Surgery ◽  
Breast Cancers ◽  
Positive Margin Rate

Optimum tissue resection volume for patients with invasive breast cancer undergoing breast conserving surgery following neoadjuvant therapy (NAT) is not known. We compared positive margin and in-breast tumor recurrence (IBTR) between 2 groups that were created based on radiologic tumor size (RTS (cm3)) at diagnosis, RTS post-NAT, and volume of tissue resected (VTL): Pre-NAT group, patients with VTL closer to RTS at diagnosis, and post-NAT group, patients with VTL closer to post-NAT RTS. 82 patients with 84 breast cancers treated with NAT between 2007 and 2017 who had pre- and post-NAT imaging were identified from a prospectively maintained database. RTS at diagnosis, RTS post-NAT, and VTL were determined. Clinical and treatment characteristics, IBTR, and disease-free survival (DFS) were compared between pre-NAT (n = 51) and post-NAT (n = 33) groups. Compared to post-NAT patients, pre-NAT patients had smaller RTS at presentation (9.2 vs. 33.5 cm3, P < .001) and post-NAT (1.2 vs. 8.2 cm3, P = .024). At median follow-up of 4 years, there were no differences between groups in pathologic tumor size, positive margin rate, adjuvant therapy, IBTR, or DFS. Resection volumes that matched RTS on post-NAT imaging were not associated with increased positive margins or IBTR. It may be appropriate to use post-NAT imaging to guide lumpectomy volume.

Comparison of the sensitivity to endocrine therapy of PR+/ER- patients and ER+/PR- patients with HER2+ breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11558-e11558
Author(s):  
X. Hao ◽  
Y. Liu ◽  
R. Hui ◽  
J. Zhang
Keyword(s):  
Breast Cancer ◽  
Survival Rate ◽  
Endocrine Therapy ◽  
Disease Free Survival ◽  
Her2 Breast Cancer ◽  
Significant Difference ◽  
Her 2 ◽  
Disease Free Survival Rate ◽  
Post Menopausal

e11558 Background: Her2 and PR expression are important indicators for prognosis of breast cancer. Aslo, it's proved that their expression could guide chemotherapy, endocrine therapy and targeted therapy in many studies. Methods: Collected 3,677 primary breast cancer cases from 2002 to 2004 in Tianjin University Cancer Hospital. All of the cases were confirmed by pathohistological method. All patients are female, aged from 15 to 92 years old, with median age 50 years old. Median follow-up time is 40 months. Her-2, PR and ER expression were detected by immunohistochemical methods. Results: 1. With Her2+ breast cancer, 168 patients are PR+/ER- and 211 patients are ER+/PR-. 2. All patients treated with anthracycline-based adjuvant chemotherapy with 6 cycles and then given endocrine therapy: Pre-menopausal patients were given TAM (10mg P.O Bid); Post-menopausal patients were given AI (letrozole 2.5m po. bid or anastrozole 1 mg P.O Qd). Median follow-up time is 45 months. With Her2+ BC, 3-year DFS(disease-free survival rate) of PR+/ER- patients is 94.53%, higher than that of PR-/ER+ ones (91.81%).With Her2- BC, 3-year DFS of PR+/ER- patients is lower than that of PR-/ER+ (p<0.05). 3. Total of 1853 cases with 5-year followed up, and 1297 cases have been given endocrine therapy. 5-year overall survival rate was 83.41%. With Her2+ BC, it's significant difference that 5-year OS of PR+/ER- patients is higher than that of PR-/ER+ ones. However, there's no difference of 5- year OS between them with Her2- BC. Conclusions: With Her2+ breast cancer, 3-year DFS of PR+/ER- patients is higher than ER+/PR- and also PR+/ER- patients may more sensitive to endocrine therapy than ER+/PR- patients. No significant financial relationships to disclose.

Significance of chromosome 17 polysomy in breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e12002-e12002
Author(s):  
Robert W. Galamaga ◽  
Rachel Mariani ◽  
Imad Almanaseer ◽  
Jacob D. Bitran
Keyword(s):  
Breast Cancer ◽  
Survival Data ◽  
Copy Number ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Chromosome 17 ◽  
Gene Copy ◽  
Breast Cancers ◽  
Her 2 ◽  
Disease Free

e12002 Background: Human epidermal growth factor receptor 2 (HER-2) overexpression occurs in up to 30% of breast cancers and has been associated with poor clinical outcomes that have improved with advances in HER-2 directed therapy. The HER-2 gene resides on the long arm of chromosome 17 and amplification is typically assessed via immunohistochemistry or fluorescence in situ hybridization (FISH); HER-2 is interpreted as amplified, non-amplified, or equivocal. The effect and clinical impact of chromosome 17 polysomy in specimens interpreted as HER-2 non-amplified has not been well-established in breast cancer patients. This subgroup may represent a unique set of patients who may benefit from HER-2 directed therapy given the increase in HER-2 gene copy number. If tumors with polysomy 17 share biologic similarities with those positive for HER-2 amplification this may significantly influence the approach to treating these patients. In a single institution study we reviewed all breast cancer cases diagnosed in 2008 which were reported as HER-2 equivocal or non-amplified via FISH and with chromosome 17 polysomy in order to extrapolate disease-free and overall survival data within this subset. Methods: HER-2 expression via FISH from patients diagnosed with breast cancer in 2008 was reviewed. In those patients with equivocal or non-amplified HER-2 expression we selected those with chromosome 17 polysomy defined as a chromosome 17 centromere copy number of > 3 per tumor cell. A total of 9 patients were identified. Results: The median age was 74 (36-88). Median tumor size was 1.6 cm (0.7-4.9) and 8 patients (88%) had both estrogen and progesterone positive tumors. Stage distribution was as follows: stage IA: 4 (44%); stage IIA: 2 (22%); stage IIB: 2 (22%) and stage IIIA: 1 (11%). The actuarial 3 year disease free survival was 67%. Conclusions: Breast cancers with equivocal or non-amplified HER-2 expression with chromosome 17 polysomy represent a unique subset of tumors with a biology that is not well-understood. Previously published studies have yielded conflicting results regarding the prognostic significance of this genotype. Our study reflects a three year survival of 67% which suggests that these patients represent an aggressive subset.

Dose-dense docetaxel, carboplatinum and trastuzumab (ddTCH) as neoadjuvant therapy for human epidermal receptor 2 (HER2) positive breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 11003-11003 ◽  
Author(s):  
H. S. Han ◽  
P. Doliny ◽  
M. Blaya ◽  
S. Gluck ◽  
J. Slingerland ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Therapy ◽  
Pathologic Complete Response ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Grade Ii ◽  
Her 2 ◽  
Dose Dense ◽  
Grade Iii ◽  
Positive Breast Cancer

11003 Background: Docetaxel, cisplatin, and trastuzumab given every 21 days in Her 2-postitive breast cancer demonstrates a pathologic complete response (pCR) rate of 23%. Decreasing the interval between doses of chemotherapy has lead to improvement in survival in the adjuvant setting. In one study dose dense chemotherapy improved response only in patients whose tumors overexpressed her-2. We conducted a phase II trial to evaluate the efficacy and safety of neoadjuvant dose-dense TCH for HER 2-positive breast cancer. Methods: Patients with T2–4 N0–3 M0 HER-2 positive (by FISH) breast cancers were eligible. Neoadjuvant therapy consisted of carboplatinum (AUC 6) Day 1,15,29,43, docetaxel (75mg/m2) Day 1,15,29, 43 and weekly trastuzumab for 10 weeks 4mg/kg Day 1 then 2mg/kg Day 8,15,22,29,36,43,50,57,64, Pegfilgastrim Day 2,16,30,44. The primary end point was the rate of pCR. Results: Twenty patients are evaluable for response. The median age was 51.5 years (range 29–73). Mean tumor size was 5.6 cm. Patients had stage IIA (30%), IIB (15%), IIIA (45%), IIIB (5%), and IIIC (5%). Estrogen receptors were positive in 36% of tumors. No grade 4 or 5 toxicity occurred. The most frequent toxicity was hand-foot syndrome (Grade I 15%, Grade II 10%, Grade III 15%). Neutropenia occurred in 5 patients (Grade II 10%, Grade III 15%) There were no episodes of febrile neutropenia or hospitalizations. Grade I cardiotoxicity was seen in 30%. The rate of pCR was 40% in the breast and 35% in both breast and axilla. 16/20 patients (80%) had pathologically negative lymph nodes. Conclusions: Changing the scheduling of TCH from every 21 days to every 14 days improves the pCR rate from 23 to 40%. The regimen was well tolerated. No significant financial relationships to disclose.

scholarly journals Bioinformatics-based analysis of TCGA to identify the prognostic biomarkers in HR-positive/HER2-negative tamoxifen-treated breast cancer

2019 ◽  
Author(s):  
Liyun Zeng ◽  
Dengjie Ouyang ◽  
Qiongyan Zou ◽  
Qitong Chen ◽  
Na Luo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Histological Grade ◽  
Cumulative Risk ◽  
Disease Free Survival ◽  
Tamoxifen Therapy ◽  
Tamoxifen Treatment ◽  
Receptor Interaction ◽  
Breast Cancers ◽  
Clinical Factors ◽  
Disease Free

Abstract Background Patients with hormone receptor-positive (HR+) breast cancer, which accounts for approximately 70% of all breast cancers, receive tamoxifen therapy to inhibit recurrence and improve overall survival. However, the cumulative risk of distant recurrence in the past 20 years is still as high as 22 to 52% after 5 years of endotherapy. TNM stage, histological grade and age are important clinical factors related to recurrence. Differential gene analysis based on matching clinical factors will be helpful for understanding the molecular mechanism of recurrence; however, there have been no reports yet.Results In our study, we identified 647 DEGs in a TCGA dataset that included 20 patients, of which 10 patients had relapsed after tamoxifen treatment and 10 did not. Ten genes were found by the CytoHubba APP in Cytoscape. After analysis of the GO terms and KEGG pathways, we found that the genes were mainly enriched in the inflammatory response and cytokine-receptor interaction, and then these results were verified in the GEPIA2 and KM-plot websites. Finally, we identified CXCL1, CXCL2 and CX3CL1 as prognostic factors, and their overexpression in HR-positive/HER2-negative breast cancer predicted a longer disease-free survival.Conclusion In conclusion, the high expression of CXCL1, CXCL2, and CX3CL1 can predict longer disease-free survival in breast cancer after tamoxifen treatment and may be a biomarker for tamoxifen therapy.

scholarly journals Cisplatin +/− rucaparib after preoperative chemotherapy in patients with triple-negative or BRCA mutated breast cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Maitri Kalra ◽  
Yan Tong ◽  
David R. Jones ◽  
Tom Walsh ◽  
Michael A. Danso ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Neoadjuvant Therapy ◽  
Triple Negative ◽  
Residual Disease ◽  
Disease Free Survival ◽  
Parp Inhibition ◽  
High Risk Population ◽  
Risk Population ◽  
The Impact

AbstractPatients with triple-negative breast cancer (TNBC) who have residual disease after neoadjuvant therapy have a high risk of recurrence. We tested the impact of DNA-damaging chemotherapy alone or with PARP inhibition in this high-risk population. Patients with TNBC or deleterious BRCA mutation (TNBC/BRCAmut) who had >2 cm of invasive disease in the breast or persistent lymph node (LN) involvement after neoadjuvant therapy were assigned 1:1 to cisplatin alone or with rucaparib. Germline mutations were identified with BROCA analysis. The primary endpoint was 2-year disease-free survival (DFS) with 80% power to detect an HR 0.5. From Feb 2010 to May 2013, 128 patients were enrolled. Median tumor size at surgery was 1.9 cm (0–11.5 cm) with 1 (0–38) involved LN; median Residual Cancer Burden (RCB) score was 2.6. Six patients had known deleterious BRCA1 or BRCA2 mutations at study entry, but BROCA identified deleterious mutations in 22% of patients with available samples. Toxicity was similar in both arms. Despite frequent dose reductions (21% of patients) and delays (43.8% of patients), 73% of patients completed planned cisplatin. Rucaparib exposure was limited with median concentration 275 (82–4694) ng/mL post-infusion on day 3. The addition of rucaparib to cisplatin did not increase 2-year DFS (54.2% cisplatin vs. 64.1% cisplatin + rucaparib; P = 0.29). In the high-risk post preoperative TNBC/BRCAmut setting, the addition of low-dose rucaparib did not improve 2-year DFS or increase the toxicity of cisplatin. Genetic testing was underutilized in this high-risk population.

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