Effect of oral cyclophosphamide use on pathologic complete response rate in the neoadjuvant treatment of breast cancer.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 276-276
Author(s):  
M. Luque ◽  
P. Garcia-Teijido ◽  
Y. Fernandez ◽  
T. Sampedro ◽  
V. Reguero
Keyword(s):  
Breast Cancer ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Dose Intensity ◽  
Complete Response ◽  
Her2 Overexpression ◽  
Consecutive Series ◽  
Continuous Exposure

276 Background: Continuous exposure to cyclophosphamide (C) can result in selective cytotoxicity for endothelial cells, followed by antiangiogenic effects on tumor cells. In this study we analyzed the pathological complete response (pCR) rate in a cohort of patients (p) diagnosed with locally advanced breast cancer (LABC) treated with neoadjuvant chemotherapy (CT) based on anthracyclines and taxanes, depending on the route of administration of C (intravenous (IV) and oral arms). Methods: We retrospectively studied a consecutive series of p. with LABC treated with neoadjuvant CT in 2 hospitals in Asturias. The regimens used were CE100F, AC (regimens with IV C) or oral CAF (C 100mg/m2/day orally x 14 days, doxorubicin 30 mg/m2 day 1 and 8 and 5-FU 500 mg/m2 days 1 and 8 every 28 days) x 4 cycles. The anthracycline regimen was followed by weekly paclitaxel or docetaxel every 3 weeks. If HER2 overexpression, trastuzumab was given in combination with the taxane. Results: We identified 105 p., 65 of them treated with oral C and 40 with IV C (CEF 3 patients and AC 37 patients). The median age was slightly higher in the p. treated with C IV (52.2 vs. 47.7, p = 0.022), which also received a higher number of cycles (7.1 vs. 6.7, p = 0.025), although there were no significant differences in the anthracycline dose intensity (93% vs 89%, p = 0.093). There were no significant differences in tumor size, lymph node involvement, grade, estrogen receptor (ER) or HER2. The rate of pCR was significantly higher in p. receiving oral C (33.8% vs 10%, p = 0.004). Grade 3, negative estrogen receptors and HER2 were also significantly associated with a higher rate of pCR. On multivariate analysis only oral C was an independent factor associated with pCR. With a median follow up of 27.3 months (95% CI 24 to 30.6), there have been 10 recurrences (15.4%) in the continuous arm and 9 (22.5%) in the standard arm, without significant differences in disease free survival. Conclusions: Our results suggest that the pCR rate can be higher using oral C in the neoadjuvant treatment of LABC based on anthracyclines and taxanes. This hypothesis should be confirmed in a randomized and prospective study.

Phase II study of neoadjuvant treatment with docetaxel, capecitabine, and trastuzumab in HER-2-positive locally advanced or inflammatory breast cancer: TXH trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11581-e11581
Author(s):  
G. Perez Manga ◽  
P. Khosravi-Shahi ◽  
Y. Izarzugaza Peron ◽  
A. Soria Lovelle ◽  
R. Gonzalez del Val ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ductal Carcinoma ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Complete Response ◽  
Conservative Surgery ◽  
End Point ◽  
Her 2

e11581 Background: Preoperative chemotherapy(CT) with trastuzumab(H)improves pathologic complete responses(pCR) in patients(ps)with Her-2+locally advanced breast cancer(LABC). Methods: This is an unicenter phaseII trial of a new neoadjuvant CT with H(without anthracyclines)in Her-2+LABC.Primary end-point was pCR.Secondary endpoints were:clinical response rate(CRR);breast conservative surgery rate(BCSR);pathologic tumoral size(pTS);disease-free survival(DFS);overall survival(OS)and toxicity profile.Ps with histologically confirmed Her-2+LABC, PS ≤2, LVEF >50%,and adequate bone marrow, renal and hepatic function were eligible.Treatment:docetaxel(T)36 mg/m2IV d1,8 and 22;capecitabine(X)750 mg/m2/12h PO d1- 14;and H 4mg/kgIV 1ºd,followed by weekly 2mg/kg in a 4-week course repeated for up to 4cycles,followed by surgery.Ps received a maximum of 6 cycles,according to investigator criteria.Radiotherapy(RT)and hormonetherapy(Ht) were allowed after surgery.Expression of markers was determined by immunohistochemistry(IHC)before CT. Results: The trial was closed due to poor accrual on March 2008.N=16ps:median age=47years(30–68); premenopausal=69%; ductal carcinoma=94%; left side=37,5%; clinical(c)stage:IIA=6.2%,IIB=43.8%;IIIA=31.2%;IIIB=18.8%;c node+=50%; median c tumoral size= 5cm(2- 10);grade:G2=53%and G3=47%;ER+ =75%;PgR+=62.5%;RP+/RE+ =62.5%;EGFR negative =87.5%;p53+=37.5;median KI67=22.5%(2- 79%);Her2+ by IHC+++ =87.5%and IHC++/FISH+ =12.5%;RT= 50%;median dose=50Gy;Ht=75%;and all ps received adjuvant H. 1º End Point: Three ps(18.8%) had pCR in breast and nodes;4ps(25%)had pCR in primary site,and among ps with c node+ 37.5%(3ps)had pCR in nodes. 2º End-Points: 1)CRR=81.2%(complete response=25%;partial=56.2%;no response=18.8%);2)BCSR=6.2%;3)Median pTS=2cm(0–5cm);4)Safety:TXH is very well tolerated:dose delays=14%;dose reductions=7%;no p had a decreased LVEF after neoadjuvant CT.Three ps had decreased LVEF during adjuvant H(median=43%).5)Only 2 events had occurred.Survival data will be reported in the meeting. Conclusions: Neoadjuvant TXH is a new active regimen in Her- 2+LABC with a manageable toxicity profile. No significant financial relationships to disclose.

Association of NBS1 expression with improved pathologic complete response rate in HER2-overexpressing breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11534-e11534
Author(s):  
Fatma Sen ◽  
Ekrem Yavuz ◽  
Gulcin Yegen ◽  
Hasan Karanlik ◽  
Sitki Tuzlali ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Protein Expression ◽  
Response Rate ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Complete Response ◽  
Protein Loss ◽  
Paraffin Sections ◽  
Her2 Breast Cancer

e11534 Background: Our aim was to investigate potential correlation between expression levels of Nijmegen breakage syndrome1 (NBS1) protein and phosphatidylinositol-3 kinase (PI3K) and pathologic complete response (pCR) rate to neoadjuvant treatment in locally advanced HER2+ breast cancer. We also assess possible association between NBS1 and PI3K expressions. Methods: Totally 42 patients (median age 49 years), received neoadjuvant treatment due to locally advanced HER2+ breast cancer, were included. Immunohistochemical analyses were performed on paraffin sections, obtained during initial diagnosis. Paraffin sections were stained with anti-NBS1 (P95-NBS1 antibody, Y112, ab32074) and anti-PI3K (PI3-Kinase p85 alpha+gamma antibody, ab741369) antibodies to determine positivity of related proteins. Results: NBS1 protein loss was detected in 19 (%45) patients whereas p85 loss was shown in 25 (%60). There was no initial clinicopathologic variable predicting pCR. Fifteen of 30 patients, received neoadjuvant trastuzumab, had pCR, whereas only 1 of 12 patients, not received trastuzumab, achieved pCR (P = 0.012). p85 loss did not predict treatment response, however NBS1 protein expression positively correlated with increased response rate to neoadjuvant treatment (P = 0.007). Conclusions: NBS1 protein expression associates with increased pCR rate in HER2+ breast cancer. However, P85 positivity did not associate with pCR rate or NBS1 overexpression.

Phase II open clinical trial to evaluate efficacy and safety of neoadjuvant trastuzumab in HER2-positive locally advanced breast cancer (LABC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 592-592
Author(s):  
C. H. Arce-Salinas ◽  
F. U. Lara ◽  
E. Leon
Keyword(s):  
Breast Cancer ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Complete Response ◽  
Her2 Positive ◽  
Primary Systemic Therapy ◽  
Her 2 ◽  
Grade 3

592 Background: LABC in Mexico represents between 50–60% of the new diagnosed cases, and 25–30% of those cancers are HER-2/neu positive. Primary systemic therapy trastuzumab-based combination chemotherapy (ChT) has shown clinical benefit and pathologic complete response rates are obtained between 17%-67%. The aim of this study was evaluate the complete pathologic response (pR) rate with the combination of four cyles of FAC (5FU/Doxorubicin/Cyclophosphamide) followed by weekly paclitaxel (PTX) and trastuzumab. As secondary endpoint was evaluate cardiac safety. Methods: All patients with LABC HER-2 positive (IHC 3+ or FISH amplification) with stages IIb-IIIc were included, patients with palpable nodes underwent fine needle aspiration to confirm metastatic nodal disease (MND), other inclusion criteria was FEVI ≥55% determined by MUGA, hematologic, renal and hepatic function normal. We exclude inflammatory breast cancer. All patients received 4 cycles of FAC followed by weekly PTX (80 mg/m2) concomitantly with trastuzumab, 2 mg/kg, at the end of treatment surgery was performed, and pR was evaluable. Complete pR was defined as the absence of tumor cells in breast and axillary nodes. Disease free survival (DFS) was calculated with Kaplan-Meier method. Protocol was approved by local ethical committee. NCT 00533936. Results: We included 92 patients, median age was 48 (27–68) yrs. Median tumor size was 6 (5.4–6.5) cm, 84.9% had MND. Efficacy analysis was made in 71 patients; 21 patients are still under treatment. Overall clinical response was reached in 71% (complete 37% and partial 42%). Eleven patients were considered inoperable (skin affection, larger size > 5 cm or fixed to chest wall and received radiotherapy 50 Gy). Complete pR was reported in 48% of cases. Median follow-up was 17.4 (CI95% 14.9, 17.6) mo and media of DFS was 25.1 (CI95% 23.5, 26.7) mo. We found cardiac toxicity (CT) grade 3 in 1.1%, and grade 2 in 3.2%. Conclusions: Combination of PTX and trastuzumab after 4 cycles of FAC is highly active in terms of complete pR. This scheme was tolerated, with CT grade 3–4 in less than 2%. No significant financial relationships to disclose.

Randomized Parallel Study of Doxorubicin Plus Paclitaxel and Doxorubicin Plus Cyclophosphamide As Neoadjuvant Treatment of Patients With Breast Cancer

2004 ◽  
Vol 22 (24) ◽  
pp. 4958-4965 ◽  
Author(s):  
Véronique Diéras ◽  
Pierre Fumoleau ◽  
Gilles Romieu ◽  
Michèle Tubiana-Hulin ◽  
Moïse Namer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Complete Response ◽  
Conservative Surgery ◽  
Axillary Lymph Nodes ◽  
Axillary Lymph ◽  
Cancer Management

Purpose This randomized, noncomparative, parallel-group study was designed to evaluate the pathologic complete response (pCR) rate of combined doxorubicin plus paclitaxel (AP) and doxorubicin plus cyclophosphamide (AC) as neoadjuvant chemotherapy in patients with previously untreated breast cancer who were unsuitable for conservative surgery. Patients and Methods A total of 200 patients with T2-3, N0-1, M0 disease were randomly assigned in a 2:1 ratio to receive preoperative chemotherapy with either doxorubicin 60 mg/m2 plus paclitaxel 200 mg/m2 as a 3-hour infusion (AP) or doxorubicin 60 mg/m2 plus cyclophosphamide 600 mg/m2 (AC) every 3 weeks for 4 courses followed by surgery. Results A pCR (eradication of invasive carcinoma in tumor and in axillary lymph nodes) was found in 16% and 10% of patients in the AP and AC arms, respectively, by study center pathologists, and in 8% and 6% of patients, respectively, by independent pathologists. Patients with pCRs tended to have unifocal disease, tumors with negative hormonal receptor status, and less differentiation (Scarff, Bloom, and Richardson scale grade 3). Breast-conserving surgery was performed in 58% and 45% of patients in the AP and AC arms, respectively. An objective clinical response was achieved in 89% of patients in the AP arm and 70% in the AC arm. At a median follow-up of 31 months, disease-free survival (DFS) was higher in patients who reached pCR versus those without pCR (91% v 70%). Conclusion The encouraging pathologic and clinical responses of patients with breast cancer after neoadjuvant chemotherapy with doxorubicin plus paclitaxel warrant additional investigation of paclitaxel in the neoadjuvant setting of breast cancer management.

Evaluation of TOP2A and TIMP-1 as predictive markers of pathologic complete response to neoadjuvant anthracycline-based chemotherapy.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11503-e11503
Author(s):  
Joyce Maria L. Maia ◽  
Elizabeth Santana Santos ◽  
Rafael Costa Lessa ◽  
Felipe D'Almeida Costa ◽  
Stephania Bezerra ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Predictive Biomarker ◽  
Complete Response ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Her2 Breast Cancer ◽  
Pre Treatment

e11503 Background: Factors predictive of response to anthracyclines can help selecting patients who really benefit from its use. HER2 amplification, TOP2A aberrations, and changes in tissue inhibitor of metalloproteinase (TIMP-1) expression in breast carcinomas have been shown to be associated with incremental benefit from anthracycline chemotherapy. Methods: We retrospectively analyzed data on the outcome of patients undergoing neoadjuvant anthracycline-based chemotherapy. Evaluated nuclear TOP2A protein expression and cytoplasmatic TIMP-1 expression in tumor cells in breast cancer biopsies by immunohistochemistry (IHC) and reviewed the pathological responses after completion of neoadjuvant treatment. Results: From 2002 to 2012, data from 97 patients was reviewed. Sixty four patients had the paraffin blocks corresponding to the pre-treatment biopsy to analysis the TOP2A and forty nine to TIMP-1. Patients were considered positive for TOP2A if the level of expression in IHC was higher than 20% and graduated TIMP-1 as weak, moderate or strong expression. Thirty percent of the patients achieved pathologic complete response (pCR) in pos-treatment surgical specimens. There was an association between TOP2A IHC expression and tumor pathological complete response (pCR) with higher pCR in TOPO2A positive tumors (pCR 44% vs 14%; p=0.008). There was no association between TIMP-1 expression and pCR. A moderate or strong TIMP-1 expression was associated with higher disease-free survival in multivariate analysis (p=0,005). No difference in PFS and OS was observed between patients with pCR after a median follow-up of 36 months. Conclusions: The expression of TOP2A seems to be a promising predictive biomarker of pCR to antracycline-based neoadjuvant chemotherapy in HER2 breast cancer. The predictive value and form of assessment of TIMP-1 remain uncertain. These findings should be better evaluated in prospective neoadjuvant trials.

Circulating tumor cells in locally advanced breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22159-e22159
Author(s):  
J. A. García-Sáenz ◽  
M. Martín ◽  
M. Maestro ◽  
M. Vidaurreta ◽  
S. Veganzones ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Response Rates ◽  
Complete Response ◽  
Circulating Tumor Cell ◽  
Advanced Breast

e22159 Background: A prospective study was conducted to determine the value of changes in circulating tumor cell (CTC) levels prior to and after the first cycle of neoadjuvant treatment in early prediction of pathologic response in locally advanced breast cancer (LABC). Methods: Two blood samples were obtained from 72 eligible LABC patients to isolate and enumerate CTCs before neoadjuvant chemotherapy started on day 1, and on day 21, immediately before second cycle administration. Results: Sixty patients (83.3%) had ≤1 CTC in the first sample and response rates in this cohort were: pathologic complete response (PCR) in 2 patients (5%); partial response (PR) in 35 (87.5%); stable disease (SD) in 2 (5%); progressive disease (PR) in 1 (2.5%). Twelve patients (16.7%) had ≥2 CTCs in the first sample; these patients were more likely to have triple negative tumors. All 12 had fewer CTCs in the second sample. Response rates in this second cohort of 12 patients were: PCR in 4 (34%); PR, 6 (50%); SD, 1 (8%); and PD, 1 (8%). pCR rate was markedly better in this second cohort (p<0.0042; OR 14.5, 95% CI 2.3–92). Conclusions: This study suggests that the presence of CTCs prior to neoadjuvant therapy might be a predictor of response to this therapy. No significant financial relationships to disclose.

Comparison of Clinical Outcomes in Patients With Localized or Locally Advanced Urothelial Carcinoma Treated With Neoadjuvant Chemotherapy Involving Gemcitabine-Cisplatin and High Dose-Intensity MVAC

2021 ◽  
Author(s):  
Yongjune Lee ◽  
Young Seok Kim ◽  
Bumsik Hong ◽  
Yong Mee Cho ◽  
Jae-Lyun Lee
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Medical Center ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Dose Intensity ◽  
Complete Response ◽  
High Dose ◽  
Muscle Invasive ◽  
High Dose Intensity

Abstract PurposeTo compare the efficacy and safety of high dose-intensity combination of methotrexate, vinblastine, adriamycin and cisplatin (HD MVAC) with gemcitabine plus cisplatin (GC) as a neoadjuvant chemotherapy (NAC) in muscle-invasive bladder cancer (MIBC) or locally advanced upper tract urothelial cancer (UTUC). Patients and MethodsA retrospective analysis was conducted for patients with UC (cT2-4aN0-1M0) who received NAC from January 2011 and December 2017 at Asan Medical Center. Pathologic complete response (pCR), down-staging (<ypT2 and no N upstaging), disease-free survival (DFS), OS and safety were compared for each regimen. ResultsOut of a total of 277 patients, 176 patients received GC and 41 patients received HD MVAC. With the exception of age (patients receiving GC were younger; p=0.002), other baseline characteristics were well balanced between groups. pCR rates were 27.0% for GC and 22.6% for HD MVAC (p=0.62), and down-staging rate was 50.8% for GC and 58.1% for HD MVAC (p=0.47). There were no differences in OS (72.1% vs 73.1% for GC vs HD MVAC; p=0.58) and DFS (54.9% vs 63.3% for GC vs HD MVAC; p=0.21) at 3 years. HD MVAC with prophylactic G-CSF was associated with a higher incidence of febrile neutropenia (p<0.001) than GC. The NAC regimen was not an independent prognostic factor for OS. ConclusionsOncologic outcomes were not significantly different between the GC and HD MVAC when used as NAC in MIBC/UTUC.

scholarly journals The Prognostic Impact of Body Composition for Locally Advanced Breast Cancer Patients Who Received Neoadjuvant Chemotherapy

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 608
Author(s):  
Toshiaki Iwase ◽  
Aaroh Parikh ◽  
Seyedeh S. Dibaj ◽  
Yu Shen ◽  
Tushaar Vishal Shrimanker ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Composition ◽  
Adipose Tissue ◽  
Neoadjuvant Chemotherapy ◽  
Advanced Breast Cancer ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Advanced Breast

Our previous study indicated that a high amount of visceral adipose tissue was associated with poor survival outcomes in patients with early breast cancer who received neoadjuvant chemotherapy. However, inconsistency was observed in the prognostic role of body composition in breast cancer treatment outcomes. In the present study, we aimed to validate our previous research by performing a comprehensive body composition analysis in patients with a standardized clinical background. We included 198 patients with stage III breast cancer who underwent neoadjuvant chemotherapy between January 2007 and June 2015. The impact of body composition on pathologic complete response and survival outcomes was determined. Body composition measurements had no significant effect on pathologic complete response. Survival analysis showed a low ratio of total visceral adipose tissue to subcutaneous adipose tissue (V/S ratio ≤ 34) was associated with shorter overall survival. A changepoint method determined that a V/S ratio cutoff of 34 maximized the difference in overall survival. Our study indicated the prognostic effect of body composition measurements in patients with locally advanced breast cancer compared to those with early breast cancer. Further investigation will be needed to clarify the biological mechanism underlying the association of V/S ratio with prognosis in locally advanced breast cancer.

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