scholarly journals ERCC1 Is a Predictor of Anthracycline Resistance and Taxane Sensitivity in Early Stage or Locally Advanced Breast Cancers

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1149 ◽  
Author(s):  
Tarek M. A. Abdel-Fatah ◽  
Reem Ali ◽  
Maaz Sadiq ◽  
Paul M. Moseley ◽  
Katia A. Mesquita ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Protein Level ◽  
Early Stage ◽  
Locally Advanced ◽  
Complete Response ◽  
Breast Cancers ◽  
Test Set ◽  
Anthracycline Resistance ◽  
Distant Relapse ◽  
Taxane Chemotherapy

Genomic instability could be a beneficial predictor for anthracycline or taxane chemotherapy. We interrogated 188 DNA repair genes in the METABRIC cohort (n = 1980) to identify genes that influence overall survival (OS). We then evaluated the clinicopathological significance of ERCC1 in early stage breast cancer (BC) (mRNA expression (n = 4640) and protein level, n = 1650 (test set), and n = 252 (validation)) and in locally advanced BC (LABC) (mRNA expression, test set (n = 2340) and validation (TOP clinical trial cohort, n = 120); and protein level (n = 120)). In the multivariate model, ERCC1 was independently associated with OS in the METABRIC cohort. In ER+ tumours, low ERCC1 transcript or protein level was associated with increased distant relapse risk (DRR). In ER−tumours, low ERCC1 transcript or protein level was linked to decreased DRR, especially in patients who received anthracycline chemotherapy. In LABC patients who received neoadjuvant anthracycline, low ERCC1 transcript was associated with higher pCR (pathological complete response) and decreased DRR. However, in patients with ER−tumours who received additional neoadjuvant taxane, high ERCC1 transcript was associated with a higher pCR and decreased DRR. High ERCC1 transcript was also linked to decreased DRR in ER+ LABC that received additional neoadjuvant taxane. ERCC1 based stratification is an attractive strategy for breast cancers.

scholarly journals O24 Predictive and prognostic roles of polymeric immunoglobuilin receptor in breast cancer

2021 ◽  
Vol 108 (Supplement_5) ◽  
Author(s):  
W Asanprakit ◽  
A M Zaitoun ◽  
D N Lobo ◽  
O Eremin ◽  
A J Bennett
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Mrna Expression ◽  
Cancer Patients ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Complete Response ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Significant Difference

Abstract Introduction Neoadjuvant chemotherapy (NAC) is used with increasing frequency as the primary treatment for breast cancer. Pathological complete response (pCR) which contributes to survival benefit is achieved in only 25–30% of patients with little benefit and significant morbidity in the remainder. Therefore, predicting the patients who are likely to achieve a pCR before commencing NAC is desirable. A pilot study using next generation RNA sequencing of 10 large and locally advanced breast cancer biopsy specimens demonstrated that the expression of polymeric immunoglobulin receptor (PIGR) was significantly increased in breast cancers with pCR. The predictive and prognostic roles of PIGR in breast cancer were expanded in the present study. Method PIGR mRNA expression was determined by RNA in situ hybridization assay in formalin-fixed paraffin-embedded (FFPE) specimens of pre-treatment breast cancer core biopsy from 46 women with breast cancer who received NAC. The expression of PIGR and its associations with pCR and overall survival was examined. Results PIGR mRNA expression was lower in breast cancer compared with normal breast tissue (median H score: 0 vs. 120, P < 0.0001). There was no statistically significant difference in the proportion of pCR in PIGR positive compared with PIGR negative tumours (22.2% vs. 32.1%, P = 0.466). Five-year overall survival of the patients with PIGR positive and negative tumours was 88.9% and 78.3%, respectively. However, overall survival was not significantly different (P = 0.406). Conclusions The expression of PIGR did not appear to be associated with pCR after NAC and did not correlate with overall survival in breast cancer patients. Take-home Message The expression of PIGR did not appear to be associated with pCR after NAC and did not correlate with overall survival in breast cancer patients.

Results of the East Carolina Breast Center phase II trial of neoadjuvant metronomic chemotherapy in triple-negative breast cancer (NCT00542191).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11550-e11550
Author(s):  
Stephen Tiley ◽  
Rachel Elizabeth Raab ◽  
Lisa Sheri Bellin ◽  
Jan H. Wong ◽  
Jackie Unger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Inflammatory Breast Cancer ◽  
Triple Negative ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Metronomic Chemotherapy ◽  
Complete Response ◽  
Weekly Paclitaxel ◽  
Breast Cancers ◽  
Grade 3

e11550 Background: Triple negative (ER negative, PR negative and HER 2 negative) breast cancers (TNBC) lack effective targeted therapy. We sought to determine the benefit of metronomic neoadjuvant chemotherapy utilizing doxorubicin with cyclophosphamide followed by paclitaxel with carboplatin in women with TNBC. Methods: Patients (pts) with TNBC>2cm were eligible (including locally advanced or inflammatory breast cancer). Pretreatment sentinel node biopsy (SLNB) was performed in patients with clinically N0 disease. Treatment consisted of weekly doxorubicin 24 mg/m2 + daily oral cyclophosphamide 60 mg/m2 x 12 weeks followed by weekly paclitaxel 80 mg/m2 + weekly carboplatin AUC 2 x 12 weeks. Granulocyte colony stimulating factor was added for ANC<= 1000. Pts received standard surgery and radiation therapy as indicated. The primary endpoint was pathologic response. Results: Between 2006 and 2011, 17 pts with infiltrating ductal TNBC were enrolled and 15 were analyzed. Age ranged from 25 to 83 (mean age 45yrs), primary tumor size ranged from 2cm to 7cm (mean 3.5cm). Three pts presented with inflammatory breast cancer, 4 had clinical N1 disease and 2 had clinical N0 disease that did not receive SLNB. Six pts underwent SLNB; 3 were pN0 and 3 were pN positive. Two pts came off study due to prolonged neutopenia. Three pts died during therapy-one of MI, one of PE and one had progressive pulmonary disease. No deaths were therapy related. Ten pts completed therapy. One experienced grade 3 (G3) thrombocytopenia, five patients had G4 neutropenia and one developed G3 neuropathy. Ten pts had a clinical complete response (cCR), four had a clinical partial response (cPR) and one progressed on therapy. The rate of pathologic complete response (pCR) was 46.6% (40% pCR, 6.6% CR with foci of DCIS). One patient had a 0.7cm focus of residual invasive carcinoma. Positive nodes were identified in 13.3%-one patient who progressed on therapy and one who experienced a cPR. Conclusions: Neoadjuvant metronomic chemotherapy with weekly doxorubicin plus daily oral cyclophosamide followed by weekly paclitaxel plus carboplatin revealed high rates of pCR with toxicities limited to marrow suppression.

scholarly journals Clinical Significance of Expression of Immunoadjuvant Molecules (LAG-3, TIM-3, OX-40) in Neoadjuvant Chemotherapy for Breast Cancer

2021 ◽  
Author(s):  
Yuka Asano ◽  
Shinichiro Kashiwagi ◽  
Sae Ishihara ◽  
Koji Takada ◽  
Wataru Goto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Cell Activity ◽  
Growth Factor Receptor ◽  
Tumor Infiltrating Lymphocytes ◽  
Complete Response ◽  
Breast Cancers ◽  
Malignant Breast ◽  
Immune Response To Cancer ◽  
Infiltrating Lymphocytes

Abstract Purpose Various immunosuppressive factors that inhibit the immune response to cancer are present in cancer cells and the cancer microenvironment. Co-inhibitory and co-stimulatory receptors are dynamically expressed on T-cells as immunoadjuvant molecules that regulate the state of T-cell activity. In this report we focus on immunoadjuvant molecules such as LAG-3, TIM-3, and OX-40, for which there have been few published reports. We investigated the expression of LAG-3, TIM-3, and OX-40 in tumor-infiltrating lymphocytes (TILs), and clinically verified the significance of that expression in relation to neoadjuvant thermotherapy (NAC). Methods A total of 177 patients with resectable early-stage breast cancer were treated with NAC. Estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), Ki67, LAG-3, TIM-3 and OX-40 status were assessed by immunohistochemistry. Results There were 47 (26.6%) patients with high LAG-3 expression, 31 (17.5%) patients had high TIM-3 expression, and 32 (18.1%) patients had high OX-40 expression. The group with low-LAG-3 expression was significantly smaller than the group with high expression in triple-negative breast cancer (TNBC) (p = 0.038) and HER2-enriched breast cancer (HER2BC) (p = 0.021), and the total number of pathological complete response (pCR) patients was greater (p < 0.001). In TNBC and HER2BC, the pCR rate was significantly higher in the low-LAG-3 expression group than in the high-LAG-3 expression group (p < 0.001) (p = 0.020). Moreover, on multivariate analysis also showed that low-LAG-3 expression status was an independent factor to predict the favorable prognosis (p = 0.014, HR = 8.124) (p = 0.048, HR = 10.400). Conclusions Our findings suggest that LAG-3 may become a biomarker in highly malignant breast cancers such as TNBC and HER2BC that can predict the therapeutic efficacy of NAC.

scholarly journals Can Tumor-Infiltrating Lymphocytes (TILs) Be a Predictive Factor for Lymph Nodes Status in Both Early Stage and Locally Advanced Breast Cancer?

2019 ◽  
Vol 8 (4) ◽  
pp. 545 ◽  
Author(s):  
Alexandra Caziuc ◽  
Diana Schlanger ◽  
Giorgiana Amarinei ◽  
George Calin Dindelegan
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Lymph Nodes ◽  
Early Stage ◽  
Locally Advanced ◽  
Lymph Node Status ◽  
Breast Cancers ◽  
Axillary Clearance ◽  
Node Status ◽  
Response To Chemotherapy

The status of axillary lymph nodes is an important prognostic factor in the outcome of breast cancer tumors. New trials changed the attitude towards axillary clearance. In the era of development of new immune therapies for breast cancer, it is important to identify a biomarker that can predict lymph node status. Tumor-infiltrating lymphocytes (TILs) are a valuable indicator of the immune microenvironment that plays the central role in new anticancer drugs. Although the correlation between TILs and response to chemotherapy was established by previous studies, our retrospective study investigated the correlation between TILs and lymph node status. We analyzed data on 172 patients. According to stage, patients were divided in two groups: patients who underwent primary surgical treatment (breast-conserving or mastectomy and sentinel lymph node (SLN) biopsy +/− axillary clearance in conformity with lymph node status) and patients who received chemotherapy prior to surgical treatment (breast-conserving or mastectomy + axillary clearance). We showed a good inverse correlation between TILs and lymph nodes status for both early stage and locally advanced breast cancers. Moreover, TILs are a predictor for positive lymph nodes in the axilla in patients undergoing axillary clearance after SLN biopsy, with no statistical difference between the intrinsic or histological subtype of breast cancers. We also obtained a significant correlation between TILs and response to chemotherapy with no significative difference according to histological subtype. Although further data have still to be gathered before meeting the criteria for clinical utility, this study demonstrates that TILs are one of the most accredited forthcoming biomarkers for breast cancer (BC) patients.

Survival of patients with locally advanced triple-negative breast cancer after neoadjuvant platinum-containing chemotherapy: Experience of a single institute.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 274-274
Author(s):  
E. A. Ibrahim
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Pathological Complete Response ◽  
Locally Advanced ◽  
Complete Response ◽  
Biological Entity ◽  
Breast Cancers

274 Background: Primary systemic chemotherapy is a standard approach to treating women with locally advanced breast cancers, with higher survival rates reported among patients who attain a pathologic complete response. Triple-negative breast cancer is a special biological entity that remains major challenge to oncologist. Around 12%-20% of breast cancers are triple negative. The current phase II study was conducted to evaluate the pathological complete response (pCR) using cis-platinum containing regimen as neoadjuvant chemotherapy in locally advanced triple negative breast cancer. Methods: Eighteen women with stage III triple negative breast cancer who were recruited between July 2007 and February 2010 at King Fahad Specialist Hospital, Dammam, Saudi Arabia. Neoadjuvant chemotherapy consisted of 4 cycles of AC or FEC 100, followed by 4 cycles consisted of docetaxel-cisplatin every 3 weeks. Primary end point was pathological complete response. Results: Median age: 49 y (24-70); premenopausal: 16; 25% were below 35 years of age; Median tumor size: 9 cm (3.5-19); Grade III: 15; Stage IIIA: 3, IIIB:14, IIIC:1; all but 2 had positive nodes at diagnosis (89%). Clinical evaluation of response by RECIST criteria pre surgery: OR: 17/18 (94%), CR: 9 (50%); PR: 8 (44%).The second sequence with D-Cis-T doubled the rate of clinical CR obtained with AC/FEC. One patient was not operated due to disease progression. Pathological assessment, revealed that 8 (47%) pts had no residual invasive carcinoma in the breast; 3 (18%) had residual occasional scattered tumor cells less than 5 mm (pT1a); 10 (59%) had negative nodes; 8 achieved CpR and 2 nCpR. Patients with residual invasive component and/or nodal involvement had high baseline Ki 67 level. After a median follow up of 24 months, cumulative overall survival at 24 months is 88.9% for whole group. Cumulative overall survival in relation to response was 100% for patients who achieved pCR while overall cumulative survival rate for patients without pCR was 83.3% without statistical significance. Conclusions: This cisplatin based neoadjuvant chemotherapy regimen was well tolerated and achieved a high rate of pCR/npCR.

scholarly journals Phase II randomized trial of capecitabine with bevacizumab and external beam radiation therapy as preoperative treatment for patients with resectable locally advanced rectal adenocarcinoma: long term results

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Ramón Salazar ◽  
◽  
Jaume Capdevila ◽  
Jose Luis Manzano ◽  
Carles Pericay ◽  
...  
Keyword(s):  
Overall Survival ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Complete Response ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Link Type ◽  
Distant Relapse

Abstract Background Preoperative chemoradiotherapy with capecitabine is considered as a standard of care for locally advanced rectal cancer. The “Tratamiento de Tumores Digestivos” group (TTD) previously reported in a randomized Ph II study that the addition of Bevacizumab to capecitabine-RT conferred no differences in the pre-defined efficacy endpoint (pathological complete response). We present the follow-up results of progression-free survival, distant relapse-free survival, and overall survival data at 3 and 5 years. Methods Patients (pts) were randomized to receive 5 weeks of radiotherapy (45 Gy/25 fractions) with concurrent Capecitabine 825 mg/m2 twice daily, 5 days per week with (arm A) or without (arm b) bevacizumab (5 mg/kg once every 2 weeks). Results In our study, the addition of bevacizumab to capecitabine and radiotherapy in the neoadjuvant setting shows no differences in pathological complete response (15.9% vs 10.9%), distant relapse-free survival (81.0 vs 80.4 and 76.2% vs 78.2% at 3 and 5 years respectively), disease-free survival (75% vs 71.7 and 68.1% vs 69.57% at 3 and 5 years respectively) nor overall survival at 5-years of follow-up (81.8% vs 86.9%). Conclusions the addition of bevacizumab to capecitabine plus radiotherapy does not confer statistically significant advantages neither in distant relapse-free survival nor in disease-free survival nor in Overall Survival in the short or long term. Trial registration EudraCT number: 2009–010192-24. Clinicaltrials.gov number: NCT01043484.

scholarly journals The Differential Contribution of the Innate Immune System to a Good Pathological Response in the Breast and Axillary Lymph Nodes Induced by Neoadjuvant Chemotherapy in Women with Large and Locally Advanced Breast Cancers

2017 ◽  
Vol 2017 ◽  
pp. 1-21 ◽  
Author(s):  
Viriya Kaewkangsadan ◽  
Chandan Verma ◽  
Jennifer M. Eremin ◽  
Gerard Cowley ◽  
Mohammad Ilyas ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Neoadjuvant Chemotherapy ◽  
Lymph Nodes ◽  
Locally Advanced ◽  
Complete Response ◽  
Advanced Breast ◽  
Axillary Lymph Nodes ◽  
Axillary Lymph ◽  
Breast Cancers ◽  
Hla Dr

The tumour microenvironment consists of malignant cells, stroma, and immune cells. The role of adaptive immunity in inducing a pathological complete response (pCR) in breast cancer with neoadjuvant chemotherapy (NAC) is well studied. The contribution of innate immunity, however, is poorly documented. Breast tumours and axillary lymph nodes (ALNs) from 33 women with large and locally advanced breast cancers (LLABCs) undergoing NAC were immunohistochemically assessed for tumour-infiltrating macrophages (TIMs: M1 and M2), neutrophils (TINs), and dendritic cells (TIDCs) using labelled antibodies and semiquantitative methods. Patients’ blood neutrophils (n=108), DCs (mDC1 and pDC), and their costimulatory molecules (n=30) were also studied. Pathological results were classified as pCR, good (GPR) or poor (PRR). In breast and metastatic ALNs, high levels of CD163+ TIMs were significantly associated with a pCR. In blood, high levels of neutrophils were significantly associated with pCR in metastatic ALNs, whilst the % of mDC1 and pDC and expression of HLA-DR, mDC1 CD40, and CD83 were significantly reduced. NAC significantly reduced tumour DCs but increased blood DCs. PPRs to NAC had significantly reduced HLA-DR, CD40, and CD86 expression. Our study demonstrated novel findings documenting the differential but important contributions of innate immunity to pCRs in patients with LLABCs undergoing NAC.

scholarly journals Neoadjuvant Chemotherapy for Breast Cancer: Past, Present, and Future

2020 ◽  
Vol 14 ◽  
pp. 117822342098037
Author(s):  
Mariko Asaoka ◽  
Shipra Gandhi ◽  
Takashi Ishikawa ◽  
Kazuaki Takabe
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Residual Disease ◽  
Early Stage ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Definitive Surgery ◽  
Individual Drug Response ◽  
The Individual

Neoadjuvant chemotherapy (NAC) had been developed as a systematic approach before definitive surgery for the treatment of locally advanced or inoperable breast cancer such as inflammatory breast cancer in the past. In addition to its impact on surgery, the neoadjuvant setting has a benefit of providing the opportunity to monitor the individual drug response. Currently, the subject of NAC has expanded to include patients with early-stage, operable breast cancer because it is revealed that the achievement of a pathologic complete response (pCR) is associated with excellent long-term outcomes, especially in patients with aggressive phenotype breast cancer. In addition, this approach provides the unique opportunity to escalate adjuvant therapy in those with residual disease after NAC. Neoadjuvant chemotherapy in breast cancer is a rapidly evolving topic with tremendous interest in ongoing clinical trials. Here, we review the improvements and further challenges in the NAC setting in translational breast cancer research.

Neoadjuvant platinum-based chemotherapy (CT) for triple-negative locally advanced breast cancer (LABC): Retrospective analysis of 125 patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 625-625 ◽  
Author(s):  
J. P. Leone ◽  
V. Guardiola ◽  
A. Venkatraman ◽  
M. D. Pegram ◽  
C. Welsh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Growth Factor Receptor ◽  
Complete Response ◽  
Invasive Disease ◽  
Breast Cancers ◽  
Platinum Based Chemotherapy

625 Background: Triple-negative breast cancer (TNBC), defined by lack of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, accounts for 15–20% of all breast cancers and is associated with poor prognosis. There is no consensus regarding optimal CT for treatment of such patients. Preclinical data suggests TNBC may be sensitive to platinums because of deficiencies in BRCA-associated DNA repair. The aim of this study was to evaluate pathologic complete response (pCR) and overall survival (OS) in patients with TNBC treated with neoadjuvant platinum-based CT. Methods: We identified 674 patients with LABC who received neoadjuvant CT between January 1999 and June 2008 at University of Miami. Of these, 125 (18.5%) had histopathologic confirmation of TNBC. All patients received neoadjuvant platinum salts + docetaxel. 76 (61%) also received neoadjuvant AC, while 42 (34%) received adjuvant AC. pCR was defined as no residual invasive disease in breast and axilla. OS was calculated according to Kaplan-Meier. Results: Demographics: median age 50 (28–86 years). 60% premenopausal. TNM stage distribution: T1 0.9%, T2 5.2%, T3 53.4%, T4 40.5%, N0 25.0%, N1 36.2%, N2 35.4%, N3 3.4%, M0 100%, inflammatory 11%, median tumor size = 9.5 cm. Follow up duration ranged from 0.3 to 8.9 years. pCR was observed in 42 of 125 patients (34%; 95% CI 26–43%). Among patients receiving neoadjuvant AC, 30 of 76 (40%; 95% CI 28–51%) had pCR, while amongst those receiving adjuvant AC, 12 of 42 (29%, 95% CI 16–45%) had pCR at the time of definitive surgery. Patients achieving pCR had significantly higher OS (5-yr rate = 73% in pCR, vs. 49% in non-pCR; p < 0.001). OS in TNBC patients receiving cisplatin/docetaxel was significantly superior to those receiving carboplatin/docetaxel (11 mortality events out of 78 patients receiving cisplatin based CT vs 24 out of 47 receiving carboplatin based CT logrank p = 0.001). Conclusions: To date, this is the largest single institution cohort of locally advanced TNBC uniformly treated with platinum+docetaxel-based CT regimens. Platinum/docetaxel-based neoadjuvant CT provided high rates of pCR and excellent OS for women with locally advanced TNBC. No significant financial relationships to disclose.

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