Prognostic Significance of GRP78 Expression Patterns in Breast Cancer Patients Receiving Adjuvant Chemotherapy

2011 ◽  
Vol 26 (3) ◽  
pp. 188-196 ◽  
Author(s):  
Mauricio Z. Baptista ◽  
Luis Otavio Sarian ◽  
José Vassallo ◽  
Glauce A. Pinto ◽  
Fernando A. Soares ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endoplasmic Reticulum ◽  
Adjuvant Chemotherapy ◽  
Cell Membrane ◽  
Cancer Patients ◽  
Expression Patterns ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Significant Difference

This study examined the associations between GRP78 expression and breast cancer recurrence and survival in patients treated with anthracyclines in the adjuvant setting. GRP78 expression was assessed in 106 stage II/III breast cancer patients. Tissue microarray was used to perform immunohistochemistry and to determine the GRP78 expression in endoplasmic reticulum and cell membrane of breast tumors. Four distinct scenarios (low and high thresholds) were developed. For high thresholds, 16% and 40% of our cases were GRP78-positive for endoplasmic reticulum and cell membrane, respectively. For low thresholds, 74% and 87% of our cases were GRP78-positive for endoplasmic reticulum and cell membrane, respectively. In the endoplasmic reticulum high-threshold scenario, GRP78 positive was found to be significantly frequent in T3 tumors (p=0.02), and inversely related to ERBB2 overexpression (p=0.03). There was a lower proportion of GRP78-positive cases among women between 50 and 65 years of age (p=0.02). In the endoplasmic reticulum low-threshold scenario, the proportion of GRP78-positive cases was significantly higher in women younger than 50 years and in those who were premenopausal (p=0.04). No statistically significant difference was found in survival probabilities among the scenarios examined. In our cohort, GRP78 overexpression was not a predictor of overall or disease-free survival of patients receiving anthracycline-based adjuvant chemotherapy.

Taxane-based adjuvant chemotherapy in node positive, early stage Turkish breast cancer patients

Open Medicine ◽  
2009 ◽  
Vol 4 (4) ◽  
pp. 454-458
Author(s):  
Ahmet Alacacioglu ◽  
Baha Zengel ◽  
Ali Denecli
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Early Stage ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Node Positive ◽  
Significant Difference ◽  
Disease Free

AbstractAdjuvant chemotherapy decreases the risk of breast cancer recurrence in patients with breast cancer. In addition, it increases the rate of survival. Therefore, various chemotherapy regimens are administered in the treatment of breast cancer. The efficacy of taxane-based adjuvant chemotherapies has been demonstrated in various trials. This trial was designed to retrospectively evaluate the efficacy of taxane-based chemotherapies in lymph node-positive, early-stage Turkish breast cancer patients. 29 patients receiving TAC regimen and 29 patients receiving AC+P regimen were evaluated. 6 courses of TAC regimen were administered every 3 weeks (docetaxel 75 mg/m2, doxorubicine 50 mg/m2, cyclophosphamide 500 mg/m2). The other patient group was administered AC+P regimen (4 courses of doxorubicin 60mg/m2, cyclophosphamide 600 mg/m2 combination every 2 weeks, followed by paclitaxel 175 mg/m2 for 4 courses every 2 weeks). The 1-year, 2-year and 3-year disease-free survival (DFS) rates were 96.3%, 81.1% and 72.8% respectively. No significant difference was detected in DFS between premenopausal and postmenopausal patients on the taxane regimen (p=0.82). There was no significant difference in DFS between estrogen or progesterone receptor positive and negative patients (p=0.46). Disease-free survival of patients receiving TAC and AC+P adjuvant chemotherapy regimen was compared. The follow-up period of patients on AC+P chemotherapy was longer than those receiving TAC (AC+P mean 38.6±12.8 months, TAC mean 17.1±5.4 months). No significant difference was observed upon evaluation of both treatment arms with respect to DFS (p=0.92). In conclusion, this trial once more demonstrated that taxane-based adjuvant chemotherapy was effective and safe in lymph node-positive, early-stage Turkish breast cancer patients.

Two months of doxorubicin-cyclophosphamide with and without interval reinduction therapy compared with 6 months of cyclophosphamide, methotrexate, and fluorouracil in positive-node breast cancer patients with tamoxifen-nonresponsive tumors: results from the National Surgical Adjuvant Breast and Bowel Project B-15.

1990 ◽  
Vol 8 (9) ◽  
pp. 1483-1496 ◽  
Author(s):  
B Fisher ◽  
A M Brown ◽  
N V Dimitrov ◽  
R Poisson ◽  
C Redmond ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Positive Node ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
National Surgical Adjuvant Breast ◽  
Significant Difference ◽  
Bowel Project ◽  
Disease Free

The National Surgical Adjuvant Breast and Bowel Project (NSABP) implemented protocol B-15 to compare 2 months of Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) and cyclophosphamide (AC) with 6 months of conventional cyclophosphamide, methotrexate, and fluorouracil (CMF) in patients with breast cancer nonresponsive to tamoxifen (TAM, T). A second aim was to determine whether AC followed in 6 months by intravenous (IV) CMF was more effective than AC without reinduction therapy. Through 3 years of follow-up, findings from 2,194 patients indicate no significant difference in disease-free survival (DFS, P = .5), distant disease-free survival (DDFS, P = .5) or survival (S, P = .8) among the three groups. Since the outcome from AC and CMF was almost identical, the issue arises concerning which regimen is more appropriate for the treatment of breast cancer patients. AC seems preferable since, following total mastectomy, AC was completed on day 63 versus day 154 for conventional CMF; patients visited health professionals three times as often for conventional CMF as for AC; women on AC received therapy on each of 4 days versus on each of 84 days for conventional CMF; and nausea-control medication was given for about 84 days to conventional CMF patients versus for about 12 days to patients on AC. The difference in the amount of alopecia between the two treatment groups was less than anticipated. While alopecia was almost universally observed following AC therapy, 71% of the CMF patients also had hair loss and, in 41%, the loss was greater than 50%. This study and NSABP B-16, which evaluates the worth of AC therapy in TAM-responsive patients, indicate the merit of 2 months of AC therapy for all positive-node breast cancer patients.

Association of polymorphic drug metabolizing enzymes (DME) with outcomes in breast cancer patients treated on the ECOG 2190/Intergroup 0121 (E2190/Int0121) study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 596-596
Author(s):  
P. P. Gor ◽  
R. J. Gray ◽  
M. Horn ◽  
T. R. Rebbeck ◽  
P. A. Gimotty ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Cox Regression ◽  
Disease Free Survival ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Breast Cancer Patients ◽  
Stem Cell Rescue

596 Background: Disparate outcomes of breast cancer patients after adjuvant chemotherapy may be influenced by variation in drug metabolism due to genetic polymorphisms in DME. Cyclophosphamide and thiotepa require activation by cytochrome P450 (CYP) and detoxification by glutathione-S-transferase, two highly polymorphic enzymes. We hypothesized that variants in CYP3A4(*1B), GSTM1 and GSTT1 would impact survival outcomes after adjuvant chemotherapy, with effects potentially modulated by chemotherapy dose. Methods: We performed a retrospective cohort study of patients enrolled on E2190/Int0121, a randomized trial of cyclophosphamide (C), doxorubicin (A), and fluorouracil (F) versus CAF + high dose chemotherapy (HDC) using cyclophosphamide and thiotepa followed by stem cell rescue; disease-free survival (DFS) and overall survival (OS) were equivalent in the clinical trial. PCR-based methods were used to genotype hematologic stem cells. Hazard ratios for genotypes were obtained using Cox regression. Results: Stem cell samples and clinical data from August 1, 1991 through August 1, 2005 were available for 347/540 of patients enrolled; 151 patients on CAF and 196 on CAF + HDC arms, respectively. Median follow-up was 9.8 years. See table . CYP3A4*1B allele carriers had significantly poorer DFS (HR 1.84) in the combined cohort and CAF arm (HR 1.87), but not in the HDC arm; OS was not significant by CYP3A4 genotype. GSTM1 null homozygotes in the combined cohort and HDC arm had significantly better DFS (HR 0.70 and 0.66, respectively) and OS (HR 0.67 and 0.57, respectively), but not in the CAF arm. GSTT1 null homozygotes had significantly worse DFS (HR 2.3) and OS (2.02) in the CAF arm, but not in the HDC arm or combined cohort. Conclusions: In the overall E2190/Int0121 cohort, polymorphisms in activating (CYP3A4*1B) and inactivating (GSTM1) DME significantly impact DFS and OS. The detrimental effect of GSTT1 in the CAF arm appears to be ameliorated by HDC. [Table: see text] No significant financial relationships to disclose.

scholarly journals Postmastectomy radiotherapy after neoadjuvant chemotherapy in cT1-2N+ breast cancer patients: a single center experience and review of current literature

2022 ◽  
Author(s):  
Meng Luo ◽  
Huihui Chen ◽  
Hao Deng ◽  
Yao Jin ◽  
Gui Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Cox Regression ◽  
Medical Center ◽  
Clinical Stage ◽  
Disease Free Survival ◽  
Her2 Overexpression ◽  
Breast Cancer Patients ◽  
Significant Difference

Abstract PurposePostmastectomy radiotherapy (PMRT) after NAC in breast cancer patients with initial clinical stage cT1−2N+, especially for those who achieved ypT1−2N0, is still controversial. This study was to evaluate the survival prognosis of cT1−2N+ patients after NAC with or without PMRT, and to discuss the selection of patients who may omit PMRT.Patients and MethodsFrom January 2005 to December 2017, 3055 female breast cancer patients underwent mastectomy in our medical center, among whom 215 patients of cT1−2N+ stage, receiving neoadjuvant chemotherapy (NAC) with or without PMRT were finally analyzed. The median follow-up duration was 72.6 months. The primary endpoint was overall survival, and the secondary endpoint was disease-free survival. Comparison was conducted between PMRT and non-PMRT subgroups.ResultsOf the 215 eligible patients, 35.8% (77/215) cT1−2N+ patients achieved ypT0−2N0 after NAC while 64.2% (138/215) of the patients remained nodal positive (ypT0−2N+). The 5-year DFS of ypT0−2N0 non-PMRT was 79.5% (95% confidence interval [CI] 63.4-95.6%). No statistically significant difference was observed between the ypT0−2N0 PMRT and non-PMRT subgroups for the 5-year DFS (78.5% vs 79.5%, p = 0.673) and OS (88.8% vs 90.8%, p = 0.721). The 5-years DFS didn’t obviously differ between the ypT0−2N0 non-PMRT subgroup and cT1−2N0 subgroup (79.5% vs 93.3%, p = 0.070). By using Cox regression model in multivariate analyses of prognosis in ypT0−2N+ PMRT subgroup, HER2 overexpression and triple-negative breast cancer were significantly poor predictors of DFS and OS, while ypN stage was significant independent predictors of OS.ConclusionAn excellent response to NAC (ypT0−2N0) indicates a sufficiently favorable prognosis, and PMRT might be omitted for cT1−2N+ breast cancer patients with ypT0−2N0 after NAC.

scholarly journals Stromal Tumor Infiltrating Lymphocytes (sTILs) as a putative prognostic marker to identify a responsive subset of TNBC in an Indian Breast Cancer Cohort.

2020 ◽  
Author(s):  
Pooja Vaid ◽  
Anirudha Puntambekar ◽  
Rituja Banale ◽  
Ruhi Reddy ◽  
Rohini Unde ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Response To Therapy ◽  
Stromal Tumor ◽  
Breast Cancer Patients ◽  
Infiltrating Lymphocytes ◽  
Disease Free

Objectives Prognostic significance of stromal tumor infiltrating lymphocytes; sTILs is evaluated to identify a responsive subset of TNBC in an Indian cohort of breast cancer patients. Methods A retrospective cohort of breast cancer patients from a single onco-surgeon breast cancer clinic treated with uniform treatment strategy across is evaluated for sTILs. FFPE tissue of primary tumor of invasive breast carcinoma are collected with ethical approvals. Tumor sections blinded for subtypes are stained with H&E and scored for sTILs by a pathologist following Immuno-Oncology TILs working groups scoring guidelines. Results Analysis of 144 primary breast tumors for sTILs scores re-enforces significantly higher infiltration in TNBC tumors than HER2+ve and ER+ve tumors. Higher sTILs scores co-relate with gradually incremental pathological response to therapy specifically in TNBC subset and with better disease-free survival outcomes. Within TNBC, older and post-menopausal patients harbor higher scores of sTILs. Conclusion Despite a small cohort of breast cancer patients, TNBC subtype reflected significantly higher scores of sTILs with better response to therapy and disease-free outcomes as compared to other breast cancer subtypes. A larger number of breast cancer patients from an Indian cohort will strengthen the findings to establish sTILs as a marker to identify a responsive subset of TNBC.

Incidence and Prognostic Significance of Complete Axillary Downstaging After Primary Chemotherapy in Breast Cancer Patients With T1 to T3 Tumors and Cytologically Proven Axillary Metastatic Lymph Nodes

2002 ◽  
Vol 20 (5) ◽  
pp. 1304-1310 ◽  
Author(s):  
Roman Rouzier ◽  
Jean-Marc Extra ◽  
Jerzy Klijanienko ◽  
Marie-Christine Falcou ◽  
Bernard Asselain ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Primary Chemotherapy ◽  
Axillary Lymph ◽  
Breast Cancer Patients ◽  
Distant Disease ◽  
Free Survival ◽  
Disease Free

PURPOSE: To determine the incidence and prognostic significance of eradication of cytologically proven axillary lymph node metastases in breast cancer patients treated with primary chemotherapy. PATIENTS AND METHODS: Between January 1985 and December 1994, 152 breast cancer patients with invasive T1 to T3 tumors and axillary metastases cytologically proven by fine-needle sampling underwent primary chemotherapy followed by lumpectomy or mastectomy, level I and II axillary lymph node dissection, and irradiation. We studied pathologic complete responses (pCRs) of axillary nodes and breast tumors, as well as predictors of distant metastases. RESULTS: Thirty-five patients (23%) had axillary pCRs, and 20 patients (13.2%) had pCRs of primary breast tumors. Scarff-Bloom-Richardson grade 3 tumors (P = .04) and a clinical response to chemotherapy ≥ 50% (P = .003) were associated with negative axillary status at dissection. An initial tumor size ≤ 3 cm (63 patients) was associated with pCR of the primary tumor (P = .02) but not with complete histologic clearance of axillary lymph nodes. The median length of follow-up was 75 months. In the univariate analysis, age greater than 40 years (P = .003), absence of residual nodal disease (P = .01), and pCR of the tumor (P = .05) were associated with better distant disease-free survival. Five-year distant disease-free survival rates were 73.5% ± 14.9% among patients with no involved nodes at the time of surgery and 48.7% ± 9.2% among patients with residual nodal disease. In the multivariate Cox regression analysis, parameters associated with poor distant disease-free survival were age ≤ 40 years (P = .002), persistence of nodal involvement (P = .03), and S-phase fraction greater than 4% (P = .02). CONCLUSION: Our results suggest that axillary status is a better prognostic factor than response of the primary tumor to primary chemotherapy.

Prognostic significance of bcl-2 expression in stage III breast cancer patients who received doxorubicin and cyclophosphamide followed by paclitaxel as adjuvant chemotherapy

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 670-670 ◽  
Author(s):  
K. Lee ◽  
B. Kim ◽  
S. Lee ◽  
W. Han ◽  
D. Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Prognostic Factor ◽  
Cancer Patients ◽  
Prognostic Significance ◽  
Stage Iii ◽  
Breast Cancer Patients ◽  
Stage Iii Breast Cancer ◽  
Erbb2 Overexpression ◽  
Er Expression

670 Background: Bcl-2 is an anti-apoptotic marker and regulated by hormonal receptor pathways in breast cancer. We performed this study to assess the prognostic significance of ER, PR, p53, c-erbB2, bcl-2, Ki-67, and EGFR as a marker for relapse in breast cancer patients who received same adjuvant therapy in a single institution. Methods: A cohort of 154 curatively resected breast cancer patients who had 4 lymph nodes or more and received doxorubicin and cyclophosphamide followed by paclitaxel (AC/T) as adjuvant chemotherapy was analyzed for clinicopathologic characteristics including disease-free survival (DFS). Patients with ER and/or PR expression received 5 years of tamoxifen following AC/T. The markers were analyzed by immunohistochemistry. Results: Median f/u duration was 25 months and 32 patients (20.8%) had recurrences. Stage (IIIa vs. IIIc) affected recurrences significantly, however, types of surgery, histology, histologic grade, presence of endolymphatic emboli, or close resection margin did not. Among the immunohistochemical markers, bcl-2 expression was the only one to be associated significantly with prolonged DFS (median 54 mo in bcl-2 (−) vs. not reached in bcl-2 (+); p=0.016). Furthermore, bcl-2 was an independent prognostic factor for DFS in multivariate analysis. Bcl-2 expression was significantly correlated with ER expression (p<0.001), and inversely correlated with c-erbB2 overexpression (p=0.027). Patients with both ER and bcl-2 expression had a longer DFS compared to the other patients (not reached vs. 54 mo, p=0.019). Patients with bcl-2 expression had a significantly longer DFS even in ER (+) subgroups (not reached vs 54 mo; p=0.011). Patients with c-erbB2 overexpression, ER (−) and bcl-2 (−) had a shorter DFS than the others (38 mo vs. not reached; p=0.029). Conclusions: In our homogenous patient cohort, bcl-2 expression was correlated with ER expression, and inversely correlated with c-erbB2 overexpression. Bcl-2 was an independent prognostic factor for DFS in curatively resected stage III breast cancer patients. No significant financial relationships to disclose.

Prognostic value of decrease on blood lymphocytes in breast cancer patients undergoing primary chemotherapy

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11537-e11537
Author(s):  
A. Vicente ◽  
E. García-Martínez ◽  
E. Gonzalez-Billalabeitia ◽  
M. Zafra ◽  
C. Castilla-Llorente ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Neoadjuvant Treatment ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Primary Chemotherapy ◽  
Tumor Control ◽  
Breast Cancer Patients ◽  
Blood Lymphocytes ◽  
Multivariant Analysis

e11537 Background: There is evidence about chemotherapy creating a better tumor control by inmune system. Neoadjuvant treatment is an excellent situation to study tumor behaviour. The aim of this study is to determine whether decreases on blood lymphocytes (BL) absolute number have a prognostic significance on women with breast cancer receiving primary chemotherapy (PC). Methods: A retrospective analysis was performed of 105 breast cancer patients who underwent PC. Doxorubicin (60mg/m2q3w) - Cyclophosphamide (600mg/m2q3w) x4c followed docetaxel (100 mg/m2q3w) x4c was PC regimen in 73,4%. We collected data on BL before the first cycle of PC (basal BL), just before second doxorubicin- cyclophosphamide (AC) cycle (BLa), and three weeks from the end of PC (BLb). The median decrease (MD) in blood lymphocytes has been calculated: MDa = BLa - basal BL; MDb = BLb - basal BL. Results: Of 105 patients with breast cancer 16,2% were clinical stage IIA, 19% IIB, 30,5% IIIA, 14,3% IIIB, 15,2% IIIC. The mean age was 50 years. The complete pathologic response (pCR) rate was 14,9% in primary tumor, and 37,9% in axillary nodes. The median follow up is 25 months (mo). Overall survival: (OS) 25,3 mo (range 4 - 89.3). Disease-free survival: (DFS) 21,8 mo (range 5 - 80.3). The median decrease on blood lymphocytes is MDa=300 106/L(2400, -1000), MDb=700 106/L(3900, -400). A decrease on BL just before second AC cycle (> MDa=300 106/L) is correlated with worse DFS, in univariant and multivariant analysis (HR =4.022; 95% CI:1.105–14.63; p 0.035 at first; HR=5.36; 95% CI:1.1–25.82; p 0.037 at former). Patients with BL decrease three weeks after finishing PC (>MDb=700 106/L) have worse DFS in univariant as multivariant analysis (HR=5.9 95% CI:1.2–27.5; p0.022 at first; HR=9.7 95% CI:1.11- 85.07; p 0.04 at former). We have not found significant differences in OS. Conclusions: A decrease on blood lymphocyte number in women with breast cancer undergoing primary chemotherapy is correlated with worse DFS. No significant financial relationships to disclose.

Prognostic significance of MAGE-A10 and NY-ESO-1 cancer-testis antigen in breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21126-e21126
Author(s):  
Tanja Badovinac Crnjevic ◽  
Jasminka Jakic Razumovic ◽  
Giulio C Spagnoli ◽  
Paula Podolski ◽  
Nera Saric ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Malignant Tumors ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Curative Surgery ◽  
Kaplan Meier ◽  
Expression Score ◽  
Cancer Testis

e21126 Background: Cancer testis antigens (CTAs) are expressed in a variety of malignant tumors. In normal adult tissues CTA expression is restricted predominantly to germs cells of the adult testis and placenta. Based on their tumor-restricted expression pattern, CTAs are regarded as valuable targets for cancer immunotherapy. The prognostic significance of CTAs in breast cancer has not been analyzed previously. Methods: To evaluate the potential prognostic significance of two member of this family, MAGE-A10 and NY-ESO-1 antigens, we examined their expression in breast cancer patients who underwent curative surgery at our hospital between 2002 and 2003. Paraffin embedded tumor sections were collected retrospectively from 165 breast cancer patients and immunohistochemical staining for MAGE-A10 and NY-ESO-1 was performed. Impact of MAGE-A10 and NY-ESO-1 expression on disease free survival (DFS) and overall survival (OS) was analyzed by the Kaplan-Meier method using 8-year follow up data. Results: MAGE-A10 expression (score ≥2+) was detected in 105/164 (64%) and NY-ESO-1 expression (score ≥2+) was observed in 14/164 (8.5%) patients. 8-year DFS for MAGE-A10 positive patients was 69% and 73% for MAGE-A10 negative (p=0.452). 8-year OS for MAGE-A10 positive patients was 80% and 90% for MAGE-A10 negative (p=0.134). For NY-ESO-1 positive patients 8-year DFS was 67% and 70% for NY-ESO-1 negative patients (p=0.837). 8-year OS for NY-ESO-1 positive patients was 83% and 84% for NY-ESO-1 negative patients. (p=0.991) Conclusions: To our knowledge this is the first study analyzing prognostic significance CTAs in breast cancer. In this retrospective study we did not show statistically significant correlation between MAGE-A10 and NY-ESO-1 expression and clinical outcome. Additional studies are warranted to determine weather this antigens might have prognostic value in breast cancer patients.

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