bluuebunny/crossref_metadata_2025_split huggingface dataset:
Remarkable complete pathologic response rate after preoperative paclitaxel, gemcitabine, and trastuzumab chemotherapy in HER2 positive stage II/III breast cancer: a phase II multicenter study.
Authors: Im S , Lee K , Lee E , Kwon Y , Noh D , Park I , Ahn J , Ahn J , Kim J , Nam B , Ro J 
Published: December 2010

Abstract
Abstract #5105
Background: Preoperative paclitaxel (P) and gemcitabine (G) combination therapy given on D1/D8 every 3 weeks (wks) for 4 cycles was well tolerated and effective in stage II/III breast cancer (BC) in our previous phase II study, with an 18% pathological complete response (pCR) rate. Adding trastuzumab (H) to the preoperative chemotherapy increases both of the clinical and pathological response rates in HER2 positive BC patients (pts). Thus far, the highest pCR rate reported in the literature was obtained with anthracycline-based regimens in combination with trastuzumab. This study evaluated whether non-anthracycline combination chemotherapy with PGH could improve the pCR rate in HER2 positive BC. Methods: HER2 positive, stage II/III BC pts with cytologically confirmed axillary lymph node (LN), ≥ 18 years of age, with adequate organ function, and good performance status were eligible. No prior therapy was allowed. Pts received H intravenously (iv) at 4 mg/kg on D1 of the first cycle with subsequent weekly doses of 2 mg/kg in combination with P 80 mg/m2 and G 1,200 mg/m2, iv, on D1/D8 every 3 wks for 6 cycles. Within 2 wks postoperatively, patients received H 6 mg/kg every 3 wks for 11 cycles with tamoxifen or an aromatase inhibitor for 5 years if indicated. All pts received postoperative radiation therapy. Initial evaluation included sonogram and MRI of the breast, MUGA scan, or echocardiogram, and PET-CT. Results: All 53 planned pts were enrolled between April 2007 and February 2008. The median age was 43 years (range, 26–61 years), the median primary tumor size by sonogram was 5.3 cm (range, 2.0 to &gt; 12 cm) with 89 % ≥ stage IIIA, 42% T3/T4, and 28% N3. Twenty four tumors (45%) were multiple and 20 tumors (38%) were ER positive. By May 2008, 47 patients completed surgery with a 74% breast conservation rate. Twenty-eight of 47 (60%; 95% CI, 45-72) patients achieved pCR in both the tumor and lymph node, with 68% (32/47; 95% CI, 54-80) pCR in the primary tumor, and 77% (36/47; 95% CI, 63-86) pCR in the axillary LN. Median metastatic focus in 21 positive LNs (n=11 pts) was 1 mm (range, &lt;1–13mm). Grade III/IV adverse events (AE) were neutropenia (53%), febrile neutropenia (4%), and transient elevation of AST/ALT (9%). After 6 cycles of PGH chemotherapy, all patients maintained above normal LVEF. Conclusions: A remarkably high pCR was obtained by non-anthracyline based PGH combination therapy for HER2 positive stage II/III breast cancer. This combination is well tolerated with mild degree of AEs.&#x2028; Supported by NCC Grant No 0610240-3. Trastuzumab, paclitaxel, and gemcitabine were supplied by Roche, CJ Cheiljedang CO., and Eli Lilly and CO., respectively.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5105.
Complete pathological response according to hormonal status, c-erbB2 and P53 in two neoadjuvant treatments in locally advanced breast cancers.
Authors: Giacchetti S , Lehmann-Che J , De Roquancourt A , Cuvier C , Turpin E , Marty M , Bertheau P , de Thé H , Espie M 
Published: December 2010

Abstract
Abstract #5107
Background: We previously showed that the p53 mutation is the major factor for response to dose-dense epirubicin-cyclophosphamide regimen (PLoS Med. 2007; Lancet 2002). Some years ago Taxanes became a standart treatment in neoadjuvant setting. We study two regimens of neoadjuvant anthracycline-based chemotherapy combined with high dose cyclophosphamide (C), or with Taxotere in locally advanced breast cancers (LABC) with respect to pathologic complete response (pCR).&#x2028; Materials and methods: Between 1990 and 2003, 219 patients (pts) with LABC and/or inflammatory breast cancers (IBC) from one institution received 6 cycles (c) of dose dense C (1.2g/m2 d1)-epirubicin (E) (75mg/m2d1) q2w (SIM regimen). From 2003 to 2008, 132 pts with LABC and/or IBC from the same institution received 4 c of E (75mg/m2 d1) C(750mg/m2 d1) q3w followed by 4c of docetaxel 100mg/m2 d1q3w (ECT regimen). Surgery was done after chemotherapy and pCR was defined as no residual invasive tumour in breast and lymph nodes.&#x2028; Results: 139/219 SIM pts (63.4 %) and 96/132 ECT (72.7 %) pts had frozen biopsies, surgery after chemotherapy, ER, c-erbB2 determination (IHC and /or RT-PCR) and p53 done by yeast functional complementation assay (FASAY) and were thus included in our study.&#x2028; &#x2028; &#x2028; &#x2028; Conclusion:The high performance of the FASAY assay allows the demonstration of p53 role in the prediction of histological response in the ECT, as previously for the SIM regimen. In p53 mutant tumors, especially in ER- and ER- c-erbB2 negative tumors, high dose cyclophosphamide combined with E seems significantly better than Taxane regimen and needs to be studied prospectively. Future trials should determine the best regimen for p53 WT tumors.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5107.
Preliminary progression free survival and SPARC tumor correlatives from a phase II neoadjuvant trial of gemcitabine, epirubicin, and nab paclitaxel.
Authors: Yardley DA , Inhorn R , Daniel B , Daniel D , Naot Y , Zubkus J , Hanson S , Trieu V , Knauer D , Desai N , Burris HA 
Published: December 2010

Abstract
Abstract #5116
Background: Neoadjuvant combinations of gemcitabine (G), anthracyclines and taxanes have demonstrated significant activity with pCR rates of 20-25% albeit with significant myelosuppression. Secreted protein acidic rich in cysteine (SPARC) is an albumin binding protein that mediates intratumoral accumulation of nab-paclitaxel (nab-P) via a SPARC-albumin specific binding activity. This study was designed to evaluate a biweekly schedule of neoadjuvant nab paclitaxel (nab-P) with gemcitabine and epirubicin (E). SPARC tumor assessments were performed in consenting patients (pts) with subsequent pathologic and survival correlatives.&#x2028; Methods: Eligibility: Clinical T1c-T4d and/or N0-3, M0 breast cancer (T1N0M0 excluded), ECOG PS 0-2, normal LVEF. ER/PR/HER2 obtained for all pts. Treatment: 6 cycles neoadjuvant G 2000 mg/m2, E 50 mg/m2, and nab-P 175 mg/m2 q14 days followed by surgery. Post operative therapy: 4 cycles G 2000 mg/m2 and nab-P 220 mg/m2 q14 days. Myeloid growth factors were mandated with all cycles. 2 antibody reagents were used to probe for SPARC expressions. For this study, level 3 immunohistochemical (IHC) SPARC staining was considered positive. Results: 123 pts have enrolled with pathologic responses available for 106. 82 pts consented to SPARC testing. Median age 51 (29-72). Median tumor size 4.5 cm. Histology: 81% ductal, 10% lobular, 9% other. 42% ER and PR negative. 55% clinical T3/T4 and 66% lymph node positive at presentation. G3/4 toxicity present in &gt;5% of pts: neutropenia 16% (febrile neutropenia 1 pt), thrombocytopenia 9% with arthralgias 11%, fatigue 10%, and infection 7%. 20 pts did not complete study treatment for the following reasons: disease progression 7, toxicity 3, pt/MD request 5, and other 5. pCR was noted in 23 pts (22%) with PRs in 76 pts (71%), and 6 SD. SPARC IHC staining was available for 76 tumors. SPARC level 3 IHC staining was noted in 65 tumors (86%); 65% were associated with a PR or pCR. Median PFS was 23 months and overall survival at 24 months is 77%. Pts who relapsed ≤16 months from diagnosis were more likely to be triple negative (p = 0.04), or ER negative (p = 0.001), or PR negative (p = 0.0006). Conclusions: Neoadjuvant dose dense GEA is active and better tolerated than other gemcitabine/anthracycline/taxane combinations. The pCR rate of 22% compares favorably with other comparable neoadjuvant regimens albeit with minimal toxicity. Pts with early relapse defined as ≤16 months from diagnosis were more likely to demonstrate a triple negative phenotype or demonstrate estrogen or progesterone receptor negativity. SPARC tumor correlatives with progression free and overall survival are on ongoing and will be presented.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5116.
Phase II study of a 3-weekly liposome-encapsulated doxorubicin/docetaxel/pegfligrastrim in combination with weekly trastuzumab as primary treatment in HER2 positive early stage breast cancer patients (II-IIIa). GEICAM 2003-03 study.
Authors: Anton A , Ruiz-Simon A , Plazaola A , Calvo L , Segui M , Santaballa A , Muñoz M , Sanchez P , De Miguel A , Cirauqui B , Arcusa A , Oltra A , Puertolas T , Guerrero A 
Published: December 2010

Abstract
Abstract #5117
Objective: To assess the safety and efficacy of Myocet (M), Docetaxel (T), Trastuzumab (H) with prophylactic Pegfilgrastrim (N) as neoadjuvant chemotherapy in operable breast cancer patients (pts). The primary efficacy end point was pathologic complete response in the breast. Methods: Eligible pts had pathologically confirmed stage II or IIIA untreated breast cancer and HER2 overexpression determined by FISH in a central laboratory. M 50 mg/m2 and T 60 mg/m2 were given on day 1 and N on day 2 every 3 weeks for 6 cycles (Cy); H (4mg/Kgr loading dose, then 2 mg/Kgr/week) was given intravenously for 17 weeks, recommended dose in a phase I study (Proc ASCO 2007,25:596s Abstr.# 11.032). After all chemotherapy was completed, clinical responses were assessed. After surgery, pathological responses were evaluated using the Miller Payne scoring scale (MPSS). Results: 59 pts have been evaluated. Median age was 47.6 years (range 24-71) and median clinical tumour size 47.5 mm (range, 10-80). 19 pts (32.2%) presented with stage IIIA disease and 40 pts (67.8%) with stage II, 36 pts (61.0%) were premenopausal; 50 pts (84.8%) had histological grade 2-3 tumours; and 29 (49.2%) were ER-PgR-negative. All the pts received M and T 6 Cy with medium relative doses intense of 98.9% and 99.1% respectively. Objective clinical response rate was 84.7% (CI: 75.5-93.9) with 31 (52.5%) complete responses and 19 (32.2%) partial responses. 42 pts (71.2%) underwent conservative surgery, 17 pts (28.8%) achieved a pathological complete response in breast (Grade 5 in MPSS), of these, 16 pts (27.1%) achieved a pathological complete response in breast and axilar (Grade 5A+Grade 5D). Main grades (G) toxicities during MTHN treatment: leucopenia G3/4 was present in 18 pts (30.5%); neutropenia G3/4 in 17 pts (28.8%); febrile neutropenia G3 in 3 pts (5.1%); diarrhea G3 was present in 3 pts (5.1%); G2 rash in 2 pts (3.4%); G3 asthenia in 5 pts (8.5%) and stomatitis G3 in 1 pt (1.7%). 8 pts (13.6%) experienced asymptomatic and reversible cardiac left ventricular function G2. Conclusions: Concomitant administration of M plus THN is highly effective and active regimen with little toxicity in pts with HER2+ and early stage breast cancer.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5117.
Phase II trial of neoadjuvant chemotherapy of sequential FEC100 followed by docetaxel, carboplatin and trastuzumab (TCH) for HER-2 over-expressing locally advanced breast cancer (LABC): a multi-centre study from British Columbia.
Authors: Chia S , Bryce C , Pansegrau G , Macpherson N , Ellard S , Jepson D , Yu C , Nuraney S , Attwell A , Hayes M , Kennecke H , Gelmon K 
Published: December 2010

Abstract
Abstract #5118
Background: The role of trastuzumab either concurrent or sequential with adjuvant chemotherapy have clearly demonstrated significant benefits in early stage HER-2 positive breast cancer. There is now an accumulation of phase II and III trials also demonstrating improved pathological complete responses (pCR) in HER-2 positive breast cancer with neoadjuvant trastuzumab concurrent with chemotherapy. The number of patients on these trials are significantly fewer, and many of these trials are a mixture of primary operable and LABC. We have completed a multi-centre phase II trial of neoadjuvant chemotherapy and trastuzumab in HER-2 positive LABC.&#x2028; Methods: Women with HER-2 positive (IHC 3+ or FISH+) stage IIB-IIIC breast cancer were enrolled. Treatment consisted of 4 cycles of FEC100 (5-FU 500 mg/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2) followed by 4 cycles of TCH (Docetaxel 75 mg/m2, carboplatin AUC 6, trastuzumab 8 mg/kg loading then 6 mg/kg q3 weekly). Trastuzumab was also continued adjuvantly for 9 months following chemotherapy and surgery. Cardiac monitoring every 3 months was mandated. A correlative translational component with baseline and interval biopsies and serum collection was also performed.&#x2028; Results: A total of 30 patients (3 stage IIB; 14 IIIA; 10 IIIB and 3 IIIC) over a 3 year time period in 4 centres were accrued. Median age was 49 years (26-77 years). 60% of tumours were ER negative. There was one clinical CHF and 2 asymptomatic falls in LVEF requiring early discontinuation of trastuzumab. There were 3 episodes (10%) of febrile neutropenia. Seven patients underwent adjuvant radiotherapy prior to surgery. The pCR rate (breast and axilla) for the entire study population was 60% (18/30). There have been 3 recurrences so far (all biopsy proven) – of which 2 were brain metastases only. Further details on toxicity and changes in LVEF will be presented.&#x2028; Conclusions: This multi-centre phase II trial clearly demonstrates significant activity (pCR 60%) for neoadjuvant anthracyclines followed by concurrent taxane, platinum and trastuzumab in a HER-2 positive LABC population. Overall the treatment regimen was well tolerated. Brain metastases however appear to be a common site of relapse in this high risk patient population and further treatment strategies directed at this site should be investigated.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5118.
Accuracy of DCE – MRI in predicting response in patients treated with taxane based neoadjuvant chemotherapy.
Authors: Garimella V , Elfadl D , Elahi MB , Mahapatra TK , McManus PL , Chaturvedi A , Upadhyay S , O'Neil P , Turnbull LW , Drew PJ 
Published: December 2010

Abstract
Abstract #5120
Background: Neoadjuvant chemotherapy for locally advanced breast cancer is an established treatment option. Several studies have shown DCE-MRI scanning to be the most accurate investigation to assess response to EC chemotherapy. Recent trials have shown that addition of Taxanes increases the overall response rate and the rate of breast conserving surgery. Taxanes act by inhibiting angiogenesis in the tumour and this could potentially affect the quality of the post treatment scan images as DCE-MR scan and cause inappropriate decisions regarding the required surgery.&#x2028; Aim: To compare the accuracy of DCE-MR scan in identifying residual disease in patients treated with FEC (Fluoro uracil, Epirubicin, Cyclophosphamide) vs EC (Epirubicin, Cyclophosphamide) followed by Taxane.&#x2028; Methods: Patients treated with primary chemotherapy who subsequently underwent breast conserving surgery were identified from a prospectively maintained database. Clinical details including chemotherapy regimes, pre and post chemotherapy MRI data, number of surgical procedures and histological parameters of the excised specimen were obtained.&#x2028; Results: A total of 121 patients treated with primary chemotherapy were identified. Of these, 76 were treated with FEC or EC based chemotherapy and 45 were treated with EC+Taxane. DCE-MRI was significantly less accurate (p&lt;0.05) when predicting the size of residual disease in the Taxane group.&#x2028; &#x2028; Conclusion: DCE MR scan is not as accurate for quantifying size of residual disease in patients treated with taxane when compared with patients treated with traditional FEC/EC based primary chemotherapy. This should be considered when planning surgery after neoadjuvant therapy.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5120.
The response to neoadjuvant chemotherapy and prognosis of triple-negative breast cancer patients.
Authors: Nakano E , Hojo T , Masumura K , Kikuyama M , Akashi S , Kinoshita T 
Published: December 2010

Abstract
Abstract #5121
Purpose: It is said that triple negative breast cancer (TNBC) has poor prognosis. However, many study shows TNBC has better response to chemotherapy. Since neoadjuvant chemotherapy plays an important role to TNBC, we compared clinical and pathological response rate and prognosis between TNBC and non-TNBC.&#x2028; Patients and methods: This analysis retrospectively collected 2563 breast cancer patients for StageI-III who underwent surgery between January 2000 and September 2004 (median: 3.9 years) at National Cancer Center, Tokyo, Japan. We defined TNBC as Estorpgen and progesterone receptor negative and HER2 score 0-2+ by immnohistological report. There were 91 TNBC patients (23.1%) out of 400 patients (15.6%) who underwent neoadjuvant chemotherapy. Clinical and pathological response rate and Four-year progression free survival were compared between TNBC and non-TNBC.&#x2028; Results: There were 91 TNBC patients (23.1%). TNBC patients compared with non-TNBC had tendency to achieve cCR (91% vs 78%; p=.058) although TNBC had higher rate for cPD (6.6% vs 1.7%; p &lt;.0001). Also TNBC tended to have higher pathological CR rate of which we classified pCR only for grade 3 cases, compared to non-TNBC (13.1% vs 7.2%; p= .042 ). Interestingly HER2 overexpression type also had higher rate for pCR. As for pPD rate, TNBC had similar rate compared to non-TNBC (5.5% v 4.3%). Four-year progression free- survival rate was higher for non-TNBC. However, TNBC had higher Four-year survival free rate only when pCR were achieved after neoadjuvant chemotherapy (99% vs 82%; p=.02).&#x2028; Conclusion: Patients with TNBC tend to have clinical and pathological response of either CR or PD. Although non-TNBC had better prognosis by four-year survival free rate, TNBC could have better prognosis if neoadjuvant chemotherapy resulted in pCR. There may be some way to predict the efficacy of neoadjuvant chemotherapy and prognosis by analyzing the shrink pattern.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5121.
A randomized phase II trial of preoperative docetaxel (D) and capecitabine (C) given sequentially or concurrently for Her2 negative breast cancers.
Authors: Harichand-Herdt S , Zelnak A , Styblo T , Rizzo M , Gabram S , Bumpers H , D'Orsi C , Carlson K , Senior-Crosby D , Sellers N , Pierce T , Hicklin D , Srinivasiah J , Schnell F , Hermann R , O'Regan R 
Published: December 2010

Abstract
Abstract #5122
Background The efficacy of D and C as single agents and in combination is well established in the treatment of metastatic breast cancer. Novel sequential and concurrent regimens of D and C were evaluated in patients with her2-negative breast cancer eligible for preoperative therapy. MethodsPatients with Stage I (&gt;1.0cm), II or III, Her2- breast cancer were randomized to two treatment arms: Arm A: sequential therapy with D 100 mg/m2 Q 3 weeks for 4 cycles, followed by C 1000mg/m2 BID on days 1-14 of a 3-week cycle, for 4 cycles; Arm B: concurrent therapy with D 50mg/m2 on day 1 and C 1000mg/m2 BID on days 1-7 of a 2-week cycle for 8 cycles. The planned total dose of D and C and number of cycles were identical on both arms. Tissue was collected at baseline, midway and post-therapy for correlative studies. Endpoints included pathologic complete response (pCR) rate, response rate, and toxicity. Results To date 38 of 80 planned patients have been accrued (4/07-6/08). Data are available for 33 patients; 16 African American (AA) (49%), 16 Caucasian (49%), and 1 Hispanic (2%). Patients were accrued from a university center (59%), county hospital (31%) and community sites (10%). Histology: Infiltrating ductal carcinoma (76%), infiltrating lobular carcinoma (15%), metaplastic tumors (6%), mucinous carcinoma (3%). Four patients had inflammatory breast cancer. 17 patients (52%) had ER+ or PR+ tumors and 16 (48%) had ER-/PR- tumors (triple negative tumors or TNT). The average tumor size at baseline was 4.0cm+/-3.0cm. In 29 patients who completed therapy, both regimens were relatively well tolerated: 9 patients (Arm A, N=3 (23%); Arm B, N=6 (38%)) had grade 3 toxicity, predominantly hand-foot syndrome, diarrhea or neuropathy. Dose reductions were required for 12 patients due to toxicity (11 required for C, 1 for D). To date, the pCR rate is 7%, observed only in AA patients with TNTs. In this subgroup the pCR rate was 18%.&#x2028; &#x2028; Discussion This study represents the first effort to accrue patients through a Georgia-based trial network, providing a unique opportunity to treat patients from a region with a large AA population. Our preliminary results suggest modest activity of D and C, with greater activity in the concurrent arm and in AA patients with TNTs. An official interim analysis is planned and updated results will be presented. Correlative studies which focus on molecular differences in responders and non-responders, particularly in the TNT group will be presented.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5122.
Dosimetric analysis of prone versus supine concomitant boost IMRT technique for whole breast radiotherapy: prone is better in reducing cardiac dose for left sided breast cancer.
Authors: Reyes V , Lymberis SC , Becker S , Racsa M , Jozsef G , DeWyngaert K , Formenti SC 
Published: December 2010

Abstract
Abstract #5129
Introduction: Prone whole breast radiotherapy is feasible and can be delivered with a hypofractionated, concomitant boost IMRT regimen (JCO, vol. 25, 16, 2007). We hypothesized that in occasional patients a supine set-up could better spare heart and lung while optimally treating the target breast. We designed NYU 05-181 protocol to test this hypothesis. Herein we performed a dosimetric analysis by comparing treatment plans in both the prone and supine position for patients with left breast cancer.&#x2028; Methods: Early stage breast cancer patients after segmental mastectomy are eligible for this IRB-approved prospective study. A supine CT simulation with images acquired every 2.5 mm is performed. The patient is then repositioned prone using a dedicated breast mattress and a second CT is obtained. The treatment volume (TV) is the whole index breast, determined according to conventional breast simulation with the patient in the supine position. Each patient is planned in both positions and is treated based on the optimal plan defined as the one that best satisfies each of the following criteria: 1) inclusion of the TV; 2) maximum heart sparing; 3) maximum lung sparing. Dosimetric analysis of the prone and supine treatment plans was performed to compare coverage of the whole breast, PTV coverage of the tumor bed, and the dose to lung and heart.&#x2028; Results: Twenty-five patients with a left breast cancer were analyzed. Five patients were treated supine, and 20 patients were treated prone because this position enabled optimal breast coverage and heart and lung sparing. However, all patients were simulated and planned in both positions. As shown in Table 1, whole breast coverage is better for the prone position although not statistically significant (p=0.38), PTV coverage was superior in the prone position (p&lt;0.001).&#x2028; &#x2028; Importantly, heart dose was not increased in the prone position (p&lt;0.001). Additionally, lung dose was markedly reduced in the prone position (p&lt;0.001).&#x2028; Conclusions: Contrary to many concerns that the prone position leads to anterior displacement of the heart within the treatment field this was only observed in 5 of the 25 patients. This dosimetric analysis demonstrates that in fact prone breast irradiation when compared to supine results in reduced exposure to both heart and lung while enabling complete coverage of the whole breast and tumor bed for the vast majority of patients. There are few left breast patients who are better positioned supine and the NYU protocol 05-181 is currently accruing to fully characterize this infrequent subset.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5129.