bluuebunny/crossref_metadata_2025_split huggingface dataset:
P3-14-01: Panitumumab in Combination with FEC 100 (5-Fluorouracile, Epirubicin, Cyclophosphamide) Followed by Docetaxel (T) in Patients with Operable, Triple Negative Breast Cancer (TNBC): Final Results of a Multicentre Neoadjuvant Pilot Phase II Study.
Authors: Nabholtz J-M , Weber B , Gligorov J , Mouret-Reynier M-A , Tredan O , Vanlemmens L , Petit T , Mayer F , Van Praagh-Doreau I , Dubray-Longeras P , Nayl B , Ferriere J-P , Jouannaud C , Devaud H , Tubiana-Mathieu N , Abrial C , Kwiatkowski F , Planchat E , Chalabi N , Penault-Llorca F , Chollet P 
Published: June 2012

Abstract
Background: Panitumumab is an antibody targeting the epidermal growth factor receptor (EGFR) to which a role has been suggested in TNBC. Consequently, we evaluated the combination of a standard chemotherapy (FEC 100 followed by T) with panitumumab as neoadjuvant therapy of oprable TNBC.
Methods: 60 patients with stage II-IIIA disease were prospectively included in this multicentre pilot study. Systemic therapy (ST) consisted of 4 cycles of FEC 100 (500/100/500 mg/m2) q.3 weeks followed by 4 cycles of T (100 mg/m2) q.3 weeks, in combination with panitumumab (9 mg/kg) for 8 cycles q.3 weeks. All patients underwent surgery at completion of ST. Complete pathologic response (pCR) was the primary endpoint (Sataloff/J Am Coll Surg 1995; Chevallier: Am J Clin Oncol 1993), with toxicity and biologic ancillary studies as secondary endpoints.
Results: Patients characteristics are as follows: mean age 47 [27-72]; T2: 74%, T3: 26%, (mean tumor size: 40 mm [20-120]); N0: 65%, N1: 28% and N2: 7%; invasive ductal carcinoma: 96%; Scarff-Bloom-Richardson Grade III: 72%, grade II: 28%. The median number of cycles was: FEC 100: 4 [2-4], T: 4 [0-4], Panitumumab: 7 [1-8]. Pathological response showed a pCR according to Sataloff's classification of 57.1% [95% IC: 40.7−73.5] and according to Chevallier's classification of 51.4% [95% IC: 34.8−68.0] with an overall clinical response rate of 60% (29% CR) [95% IC: 43.8−76.2]. Conservative surgery was performed in 79% of cases. Skin toxicity was the main side-effect: Cutaneous toxicity grade IV: 12%, grade III: 26%, grade II: 23%. No ocular complications have been reported. Neutropenia grade IV: 23.7%; febrile neutropenia: 4.2%. Infection: 0%. Hand-foot syndrome grade III: 4%. Ungueal toxicity grade IV: 2.5%, grade II: 25 .5%.
Conclusions: These results suggest that Panitumumab in combination with FEC100 followed by T appears efficacious with acceptable toxicity in the neoadjuvant therapy of operable TNBC.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-14-01.
P3-14-10: Early Predictive Value of Non-Responder to Docetaxel in Neoadjuvant Chemotherapy in Breast Cancer Using 18F- FDG-PET.
Authors: Hirakata T , Fujisawa T , Yanagita Y , Horikoshi H , Oya N , Akiyoshi T , Kinoshita T , Kuwano H 
Published: June 2012

Abstract
Background; Clinical response is determined after several cycles of chemotherapy by changes in tumor size in imaging procedures including ultrasound, MRI or CT. The aim of this prospective study was to early detect non-responder to docetaxel (DTX) in neoadjuvant chemotherapy using 18F- FDG-PET in patients with breast cancer. Method; 41 patients were eligible for this study. 37 were assessable (4 were not eligible or not evaluable) with Invasive carcinoma (T1:10%, T2: 83%). All 37 patients were treated with 4 cycles of docetaxel (75mg per square meter) followed by 4 cycles of FEC(cyclophosphamide/epirubicin/fluorouracil: 500/75/500 mg per square meter) before surgery. 18F-FDG-PET response rate was evaluated between before and after the first cycle of DTX. 18F-FDG-PET images were analyzed by standardized uptake value, SUVmax. Clinical response is determined by reduction rate in tumor size with MRI (RECIST criteria) between before the first cycle and after the fourth cycle of DTX. Pathological response evaluated by core needle biopsy after the fourth cycle of DTX.
Result; 18F-FDG-PET response rate after the first cycle of DTX showed correlation with tumor size reduction rate with MRI image after the fourth cycle of DTX (r=0.746)(P &lt;.001). 0 out of 8 patients (0%) revealed cPR with MRI changes in SUV decrease less than 18% (p &lt;.001). 8 out of 13 patients (62%) showed cPR (cCR = 0) with MRI in SUV decrease over 19 to 44% (P &lt;.001). 9 out of 16 patients (56%) were cPR, and 7 out of them (44%) showed cCR with MRI in SUV decrease over 45% (P &lt;.001).
Conclusion; Changes of 18F-FDG SUVs in tumors were statistically significantly different between responding and nonresponding (P &lt;.001). SUV decrease less than 18% after the first cycle indicated potential failure to DTX in neoadjuvant chemotherapy.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-14-10.
P3-14-18: Primary Tumor Response to Neoadjuvant Chemotherapy Is Significantly Associated with Nodal Pathological Complete Response in Breast Cancer Patients with Cytologically Proven Axillary Node Metastasis.
Authors: Hwang H , Park S , Lee JS , Kim S-I , Park B-W 
Published: June 2012

Abstract
Background: Axillary node status is the most significant factor for the prediction of outcome in breast cancer patients whether they received neoadjuvant chemotherapy or not. However, a reliable method to predict nodal response to neoadjuvant chemotherapy is not established yet. The aim of this study was to identify the predictive factors of axillary pathological complete response (pCR) after neoadjuvant chemotherapy in breast cancer patients with cytologically proven axillary lymph node metastases.
Patients and methods: A total of 123 patients with axillary metastases confirmed by ultrasound-guided fine-needle aspiration biopsy were subsequently treated with four cycles of anthracycline (60mg/m2) plus cyclophosphamide (600mg/m2) followed by doxetaxel (75-100mg/m2) between August 2008 and March 2011. After neoadjuvant chemotherapy, all patients underwent a definite breast surgery with complete axillary lymph node dissection. Clinicopathological parameters were evaluated using a chi-square test and logistic regression model in association with node pCR.
Results: The mean age at diagnosis was 47.9 years in all patients. Eighty-one (65.9%) patients were preoperative clinical T2 stage, 74 (60.2%) showed estrogen receptor (ER)-positivity, and 36 (29.3%) demonstrated HER2−positivity. A pCR of the axilla and breast was determined in 56 (46%) and 40 (31.7%) patients, respectively. Breast Pcr rate is significantly associated with age≤50 at diagnosis, ER(−),PR(−) and higher Ki-67 proliferation. Axillary pCR rate is significantly associated with age at diagnosis of 50 or less, smaller primary tumor size at diagnosis, tumor responsiveness to neoadjuvant chemotherapy, estrogen hormone receptors-negativity, higher Ki-67 proliferative index at diagnosis, and subtypes of HER2−enriched or triple negative breast cancer. When these factors entered logistic regression model, tumor response( SD+PD vs CR+PR: OR 8.603, P=0.007), Ki67((−) vs (+): OR 7.157, p=0.009), ER status((+) vs (−) : OR 4.943, P=0.036), pre-operation tumor size(&gt;2cm vs ≤2cm: OR 5.116, p=0.044), HER2 status( (−) vs (+): OR 5.029,p=0.046) remained to be significant for the prediction of axillary pCR, favorable nodal response.
Conclusion: Our study suggests that primary tumor response to neoadjuvant chemotherapy is significantly associated with favorable nodal response. The factors of tumor and nodal response were similar. There are many issues remained to be determined yet.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-14-18.
P3-14-20: Concomitant Taxane-Anthracyclin Regimen for Neoadjuvant Chemotherapy of Primary Breast Cancer: Experience from a Cohort of 223 Patients Treated in a Single Institution.
Authors: Coquan E , Guizard A-V , Heutte N , Bor C , Allouache D , Delcambre C , Switsers O , Guilloit J-M , Leiber N , Delier T , Levy C 
Published: June 2012

Abstract
Background: Neoadjuvant chemotherapy (NAC) may be an alternative to mastectomy for localized breast cancer ineligible for breast conservation. The optimal schedule (sequential versus concomitant) remains controversial. Based on encouraging results of a phase 2 study (Luporsi E. et al, ASCO 2000) a concomitant docetaxel (D) and epirubicin (E) neoadjuvant combination is applied in neoadjuvant setting in our institution since 2001 for HER2−negative patients (pts). The results of this combination are presented, with a particular focus on pathological complete response (pCR) and conservation rate.
Methods: Between 2001 and 2010, 223 pts received NAC for a T2-T3 breast cancer initially ineligible for conservative surgery, but with hope of breast conservation in case of downstaging by pre-operative medical treatment. Six cycles of D (75mg/m2) and E (75mg/m2) were administered every 3 weeks before surgery, with prophylactic support of G-CSF in order to reduce the risk of febrile neutropenia and to maintain the dose-intensity of the NAC. All patients eligible for breast conservation after NAC underwent lumpectomy, the others were treated by mastectomy. In all cases, an axillary dissection was performed. After lumpectomy all patients received radiation therapy, after mastectomy RT was limited to high risk of loco-regional relapse. Patients with positive hormonal receptors (HR+) received hormonal therapy. Results were analyzed in term of breast conservation rate (BCR), pathologic response rate (pCR defined as no residual invasive tumour in breast and axilla, according to Sataloff's classification) and safety.
Results: Mean age of patients was 49,6 years (range: 26–71). Median clinical tumor size was 40mm (range 20–110). Histological subtypes were:78,0 % ductal, 15,3 lobular, 1,8 % ductal/lobular and 4,9 % other types. SBR grading was: grade I: 14,3 %, grade II: 46,2 %, grade III: 33,2 % and 6,3 % unspecified. 77,3 % were HR+, 19,7 % of tumours were triple negative (HER2 unknown for 38 cases). A breast conservation was achievable for 73,5% of patients, the pCR rate was 20,6%. At a median follow up of 48 months, 31 pts relapsed: 9 pts (4%) experienced a local relapse, 5 regional and 28 distant recurrences occured. Additional data about safety and survival will be provided for the meeting.
Conclusions: For HER2−negative tumours, 6 cycles of a concomitant taxane-anthracyclin pre-operative combination allowed a 20,6% pCR rate, slightly lower than obtained with 8 cycles of a sequential regimen in several published trials. However breast conservation rate was similar with a low risk of local recurrence. According to these results, concomitant cytotoxic combination is an acceptable option for neoadjuvant treatment of breast cancer.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-14-20.
P3-14-21: Neoadjuvant Therapy Response, Subtype and BRCA Status in an Underserved Population.
Authors: Tripathy D , Ahmed S , Bahl P , Wang Y , Ji L , Ricker C , Weng Grumley J , Liu SV , Sener SF , Klipfel N , Kaur C 
Published: June 2012

Abstract
Background
Preoperative (neoadjuvant) chemotherapy is typically used for larger operable breast cancer cases, and the degree of pathological response correlates with long term outcome. Therapeutic response also depends on biological and molecular subtype and is increasingly studied in the research setting to identify prognostic biomarkers and potential therapeutic targets. Little is known about the interactions of neoadjuvant response with biomarker subtypes and genetic predisposition in underserved and minority populations.
Methods: IRB approval was obtained to capture demographic, clinicopathological and genetic testing data on patients diagnosed with invasive breast cancer and treated with preoperative chemotherapy and definitive surgery between 2005 and 2010 at Los Angeles County Medical Center, which serves a primarily Hispanic and indigent population. Treatment followed NCCN guidelines with the exception that not all patients with HER2+ disease received trastuzumab. Genetic counseling and testing has been available at this center since 2007. Pathological complete response (pCR) was defined as no residual invasive disease in breast or nodes. Chi-square or Fisher's Exact test was used to examine associations between pCR and clinical factors, and logistic regression analyses were applied to assess each variable's contribution to pCR.
Results: Among 104 patients, of whom 79% were Hispanic, the overall pCR rate was 27%. Significantly higher pCR rates were seen in age ≥50, clinical N0, HER2+, triple negative, and lumpectomy cases. No differences in pCR rate was seen in Hispanics vs. others, Grade III vs. I and II or in the 9 BRCA mutations carriers among 45 tested compared to no mutation or those not tested. Of the 43 patients with HER2+ disease, the pCR rate was higher in the 32 patients who received trastuzumab (pCR 50.0 vs. 27.3%). Subset pCR rates and odds ratios (OR) of achieving pCR are shown below:

Conclusions: In this underserved cohort, with 43% undergoing genetic testing, significantly higher pCR rates were seen in HER2+ and triple negative and lumpectomy cases, with a trend seen in older patients and smaller tumors. There was an unexpected trend of lower pCR rate seen in BRCA mutation carriers (pCR OR 0.33), albeit with small numbers. No differences were seen in Hispanic cases compared to other ethnicities. Further tissue analyses are planned to examine established and novel markers and to define exploratory markers that could be used for decision-making and target discovery in larger datasets within this population.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-14-21.
P3-14-23: Response to Neoadjuvant Chemotherapy and Survival in Japanese Patients with Triple-Negative Breast Cancer.
Authors: Ohtani S , Kochi M , Ito M , Takada S , Matsuura H , Higaki K 
Published: June 2012

Abstract
Background
Triple-negative breast cancer (TNBC) is defined by the lack of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2)expression. In this study, we compared response to neoadjuvant chemotherapy and survival between Japanese patients with TNBC and non-TNBC.
Patients and Methods
Analysis of a prospectively collected clinical database was performed. We analyzed 335 Japanese patients who received neoadjuvant chemotherapy at Hiroshima City Hospital for stage I-III breast cancer from 2002–2010. Clinical and pathological parameters, pathological complete response (pCR) rates, survival measurements, and organ specific relapse rates were compared between with TNBC and non-TNBC.
Results: 21.1% had TNBC. Patients with TNBC compared with non-TNBC had not significantly higher pCR rate (28% v 19%; p=0.09), similar disease progression-free survival (DFS) rate (p=0.59), but decreased overall survival (OS) rate (p=0.02). TNBC was associated with increased risk for visceral metastasis (p&lt;0.0001) and shorter postrecurrence survival (p=0.017). If pCR was achieved, patients with TNBC and non-TNBC had similar survival. In contrast, patients with residual disease (RD) had worse OS if they had TNBC compared with non-TNBC (p=0.01). Conclusion: TNBC patients with pCR after neoadjuvant chemotherapy have excellent survival. However, TNBC patients with RD have significantly worse survival, compared with non-TNBC patients with RD. Japanese patients with TNBC have also similar results with those in other ethnic group reported before.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-14-23.
P3-14-26: The Effect of Biologic Subtype in Patients Treated with Neoadjuvant Chemotherapy: A UAB Experience.
Authors: Keene KS , De Los Santos JF , Meredith R , Hinton B , Li Y , Krontiras H , Bland K , Carpenter JT , Forero A 
Published: June 2012

Abstract
Purpose: Previous studies have suggested that the pre treatment clinical stage drives loco-regional recurrence (LRR), distant metastasis (DM) and survival in patients treated with neoadjuvant chemotherapy. This retrospective analysis was performed to look at the effect of biologic subtype on patient outcomes.
Methods: Between 1999 and 2005, 115 patients treated with neoadjuvant chemotherapy, surgery, and +/−radiation therapy at UAB were identified. Patient, tumor, and treatment characteristics were recorded. Pathologic complete response was defined as resolution of both invasive disease and DCIS in both the primary and nodal disease. Survival was measured using the Kaplan Meier statistics. Univariate and multivariate analyses of covariates associated with LRR, DM, progression-free (PFS) and overall survival (OS) were performed. Results: The mean age was 49 years, with a mean follow-up of 5.8 years. Subtype distribution was as follows: 52 luminal A, 17 luminal B, 36 triple negative, 9 Her2+ and one patient with an unknown biologic subtype. Distribution of clinical stage was as follows: 40 IIA, 34 IIB, 26 IIIA, 10 IIIB, and 5 IIIC. Tumors were down-staged following neoadjuvant therapy as follows: 18: pCR, 6: residual DCIS, 17: I, 38: IIA, 11: IIB, 13: IIIA, 5: IIIB, and 7: IIIC. Pre-treatment clinical stage did not significantly influence LRR, DM or progression free and overall survival; however, final pathologic T, N and group stage were associated with both progression free, p=0.003, 0.011, 0.005 and overall survival, p=0.02, 0.037, and 0.009. Complete resolution of tumor by mammographic or MR imaging to neoadjuvant chemotherapy, was associated with an increased overall survival, p=0.0025. Univariate analysis did not show a significant effect of biologic subtype, age, grade, use of radiation therapy or anti-hormonal therapy.
Discussion: In this retrospective series, response to chemotherapy and the final pathologic stage, representing the volume of residual disease, were important predictors of survival. Further study to determine factors predictive of chemotherapy response is needed.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-14-26.
P3-16-06: Phase II Trial of TS-1 in Combination with Oxaliplatin (SOX) in Patients with Metastatic Breast Cancer (MBC) Previously Treated with Anthracycline and Taxane Chemotherapy [TORCH] [Korean Cancer Study Group (KCSG) BR07-03].
Authors: Im S-A , Oh D-Y , Lee KS , Ahn J-H , Shon J , Ahn JS , Kim JH , Han SW , Lee MH , Lee KE , Lee K , Kim HJ , Keam B , Kim S-Y , Kim SB , Im YH , Ro J , Park H-S 
Published: June 2012

Abstract
Background
Oxaliplatin, a platinum analogue, is an active drug in advanced anthracycline and taxane-pretreated breast cancer patients as a single agent and with 5-fluorouracil (5-FU) combination. TS-1 was developed by the scientific theory of both potentiating antitumor activity of 5-FU and reducing gastrointestinal toxicity. This trial was performed to evaluate the efficacy and safety of TS-1 in combination with oxaliplatin in metastatic breast cancer (MBC) patients previously treated with anthracycline and taxane chemotherapy.
Methods: Between October 2007 and October 2009, MBC patients were enrolled in this prospective multicenter trial. Eligible criteria included age ≥18 years, at least one measurable lesion, prior treatment with anthracycline and taxane chemotherapy, and ECOG Performance Status 0–2. TS-1 40 mg/m2 b.i.d. on days 1–14 with oxaliplatin 130 mg/m2 on day 1 were administered every 3 weeks till disease progression. Primary end-point was response rate, and secondary end-points were time-to-progression (TTP), overall survival (OS), duration of response (DOR) and toxicities. Response was evaluated every 6 weeks according to the RECIST criteria v. 1.0 and toxicity was assessed with NCICTCAE v.3.0.(ClinicalTrials.gov identifier NCT00527930).
Results: A total of 87 patients were enrolled. Median age was 48 years (range 30–71 years). Nineteen patients (21.8%) had de novo stage IV and 68 patients (78.2%) had recurrent disease. Thirty-five patients (40.2%) received two-lines of prior chemotherapy in palliative setting. Forty-eight patients (55.2%) had ≥ 3 disease sites. Fifty-four patients (62.1%) were hormone receptor positive, and 25 patients (28.7%) were triple negative. Five patients received prior anti-HER2 therapy. A total of 525 cycles were administered (median 6 cycles, range: 1 ∼ 22+ cycle). In per-protocol analysis, overall response rate was 38.5% (95% CI: 27.7−49.3) (CR 0%, PR 38.5%) and disease control rate (CR, PR, and SD) was 67.9% (95% CI: 57.5−78.3). Median TTP, OS, and DOR were 6.0 months (95% CI: 5.1−6.9 months), 19.4 months (95% CI: not estimated), 6.6 months (95% CI: 3.7−9.6 months), respectively. RR was not different by triple negativity (39.1% in TNBC vs. 38.2% in non-TNBC, P=0.361). TTP was not different according to the number of prior chemotherapy regimens. Reported grade 3 or 4 toxicities (per cycle) were neutropenia (10.3%), thrombocytopenia (5.5%), diarrhea (1.9%), vomiting (1.9%), and stomatitis (0.2%). There was no treatment-related death.
Conclusions: SOX is an effective regimen in anthracycline and taxane pretreated MBC patients with manageable toxicities.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-16-06.
P3-18-03: In Vitro Potency of mTOR Kinase (TOR1/TOR2) Inhibitor, INK128 in ER+ and HER2 Overexpressing Breast Cancer Cells.
Authors: De P , Sun Y , Dey N , Leyland-Jones B 
Published: June 2012

Abstract
Background
Persistent activation of the PI3K-AKT-mTOR1/2 signaling pathway drives aberrant cell growth and proliferation in a variety of tumor types including breast tumors. Recent works have demonstrated a strong association between mutational activation of PIK3CA or loss of function of PTEN and resistance to therapies targeted against the ER or HER2 pathway.
Purpose: Since PI3K-AKT-mTOR is one of the major signaling pathways responsible for the progression of breast cancer, as well as appears to be upregulated during development of the resistance to the endocrine and trastuzumab treatment, suppression of this pathway by administration of INK128 (mTOR1/2 kinase inhibitor) may therefore be efficacious in ER+ and HER2+ breast cancer models.
Experimental Design: To examine this possibility, INK128 was treated in ER+ (MCF7, BT483, T47D and MDA-MB-415), trastuzumab-sensitive HER2+ (BT474), trastuzumab-resistant (BT474HR), and PIK3CA mutated/HER2+ breast cancer cells (HCC1954 and UACC893). We have tested the effects of INK128 on the, (a) cell survival/proliferation, (b) integrin-directed cell migration, and small GTP-ase activation, (c) downstream signaling pathways for proliferation and apoptosis, and (d) 3D ON-TOP-colony formation.
Results: Treatment of ER+ and HER2+ cell lines with INK128 in vitro showed that 1) cell lines were sensitive to single agent INK128 with 50% inhibitory concentration ranging from 15 nM-10 μM in ER+ cell lines and 20 nM −50 nM in HER2+ cell lines, 2) 70–80% anti-proliferative activities were observed on 3D-ON TOP colony formation assay in both ER+ and HER2+ cells, 3) INK128 dose- and time-dependently blocked downstream effectors of mTOR1/2 pathway i.e. p-AKT (at Ser473), p-P70S6K, p-S6 ribosomal protein, p-4EBP1(interestingly, potent inhibition was also observed in cell line resistant to trastuzumab), 4) INK128 also blocked AKT phosphorylation at Thr308 (although in lesser extent than at Ser473), 5) rapalog-mediated AKT activation was blocked when cells were treated with INK128, 6) in ER+ cell lines INK128 more efficiently blocked p-4EBP1 than rapalog, 7) HER3 expression was significantly upregulated following treatment of trastuzumab-resistant cells (BT474HR) with INK128, and 8) integrin-dependent cell migration was significantly abrogated with INK128 in association with inhibition of RAC1-GTP.
Conclusion: Our preclinical in vitro data demonstrate that concurrent inhibition of mTOR1and mTOR2 is likely to be a more effective in both ER+ and HER2+ breast cancer cells than the inhibition of mTOR1 alone. We are currently studying the effect of INK128 on downstream apoptotic signals in ER+ and HER2+ cell lines, the results of which will be presented in the meeting.
INK128 was generously supplied by Inkellikine, San Diego, CA.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-18-03.