bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular marker correlates of clinical outcome in a phase II study of gefitinib or placebo in combination with anastrozole in postmenopausal women with hormone receptor-positive metastatic breast cancer.
Authors: Valero V , Bacus S , Mangalik A , Rabinowitz I , Arena F , Kroener J , Curcio E , Watkins C , Magill P , Cristofanilli M 
Published: December 2010

Abstract
Abstract #3131
Background: Preclinical data suggest that crosstalk between growth factor receptor pathways and estrogen receptor (ER) is involved in the development of endocrine resistance. Therefore, inhibition of epidermal growth factor receptor (EGFR) is a potential target in this setting. This phase II randomized, double-blind, multicenter study evaluated the efficacy and tolerability of gefitinib (Iressa) or placebo in combination with anastrozole (Arimidex) in postmenopausal women with newly diagnosed hormone receptor-positive (HR+) metastatic breast cancer (MBC).&#x2028; Methods: Patients were randomized (1:1) to anastrozole 1 mg/day and either gefitinib 250 mg/day or placebo. The primary objective was progression-free survival (PFS); and secondary objectives included clinical benefit rate (CBR; defined as objective response plus stable disease ≥24 weeks), objective response rate (ORR) by RECIST, overall survival, safety and correlative biological markers. Biomarkers in tumor tissue (ErbB family receptors including EGFR, or other downstream related effectors and other markers of proliferation and apoptosis) by immunohistochemistry were assessed to explore potential correlations with outcome. Enrollment closed early due to slow recruitment and formal statistical testing was not performed.&#x2028; Results: 94 women were randomized to gefitinib plus anastrozole, and 43 to placebo plus anastrozole, 50 from 30 centers in 4 countries. PFS was significantly longer for gefitinib plus anastrozole over placebo plus anastrozole (HR [gefitinib:placebo] 0.55, 95% CI 0.32-0.94; median PFS 14.5 vs 8.2 months). A numerical advantage in CBR was seen for gefitinib plus anastrozole over placebo plus anastrozole (49% [21/43; 95% CI 35-65] vs 34% [17/50; 95% CI 21-49]). ORR was 2% (1/43) with gefitinib plus anastrozole and 12% (6/50) with placebo plus anastrozole. Too few patients died before data cut-off to allow conclusions on overall survival to be drawn. Safety and tolerability profiles showed no unexpected findings. Correlative biological markers data will be available later in the year after which the abstract will be updated and resubmitted.&#x2028; Discussion: This clinical trial demonstrated that EGFR inhibition and estrogen deprivation with gefitinib in combination with anastrozole was associated with a marked advantage in PFS and CBR vs placebo plus anastrozole in ER+ MBC. These data suggest that EGFR inhibition in combination with anastrozole warrants further investigation.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3131.
Decrease in serum extracellular domain of HER2 at 4 and 8 weeks is associated with prolonged progression-free survival on lapatinib monotherapy.
Authors: Lipton A , Leitzel K , Ali S , Carney W , Platek G , O'Rourke L , Martin A , Maltzman J 
Published: December 2010

Abstract
Abstract #3140
Background: The extracellular domain of the HER2 oncoprotein (ECD HER2) is shed into the serum and can be detected by ELISA. This study investigated whether baseline serum ECD HER2 level is associated with prolonged progression-free survival (PFS) on lapatinib monotherapy. Additionally, we analyzed whether change in serum ECD HER2 at week 4 and 8 after start of lapatinib therapy is associated with prolonged PFS.&#x2028; Methods: Study EGF20009 investigated lapatinib monotherapy in 138 HER2-positive patients with metastatic breast cancer who had not previously received chemotherapy or trastuzumab. Serum was collected at baseline and every 4 weeks after initiation of oral lapatinib (1,500 mg daily or 500 mg twice daily). Disease assessment was performed at week 8, 12 and every 12 weeks thereafter. Disease status was assessed by an independent radiology committee, and response was measured using RECIST. Serum ECD HER2 was measured using the ELISA from Siemens HealthCare DX/Oncogene Science. A serum ECD HER2 decrease or increase ≥ 20% from baseline was defined as a significant change.&#x2028; Results: Baseline ECD HER2 was not associated with PFS; however, a ≥ 20% decrease from baseline serum ECD HER2 was associated with prolonged PFS, and a ≥ 20% increase from baseline was associated with shorter PFS. Patients who experienced a ≥ 20% decrease from baseline serum ECD HER2 at week 4 had a median PFS of 199 days (95% confidence interval [CI] = 145, 253) compared with 135 days (95% CI = 104, 171) for patients who did not (p = 0.016). Similarly, patients who experienced a ≥ 20% increase from baseline serum ECD HER2 at week 4 had a median PFS of 113 days (95% CI = 59, 135) compared with 199 days (95% CI = 142, 253) for patients who did not (p &lt; 0.001). Similar associations were observed for the week-8 changes in serum ECD HER2 levels.&#x2028; Conclusions: Baseline ECD HER2 was not associated with PFS, whereas a ≥ 20% decrease from baseline serum ECD HER2 at week 4 and 8 was associated with prolonged PFS on lapatinib monotherapy. Single-agent lapatinib could be considered for the subset of patients whose ECD HER2 declines in the first 8 weeks of therapy, whereas a combination of chemotherapy with anti-HER2 therapy may be more appropriate for the patients whose ECD increases by ≥ 20%. Identification of a subgroup of patients who may be able to avoid cytotoxic chemotherapy in the MBC setting is an attractive prospect in our quest to find suitable therapies for appropriate patients.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3140.
Lapatinib (L) with weekly paclitaxel (P) as first-line therapy for patients (pts) with HER2+ metastatic breast cancer (MBC).
Authors: Jagiello-Gruszfeld A , Tjulandin Sergei S , Dobrovolskaya N , Manikhas A , Pienkowski T , Knott A , DeSilvio M , Oliva C 
Published: December 2010

Abstract
Abstract #3145
L, an oral tyrosine kinase inhibitor of EGFR/HER2, is active as monotherapy and in combination with chemotherapy for HER2+ MBC. In a planned subgroup analysis of a Ph III trial, EGF30001, L (1500mg QD) + P (175mg/m2 q3w), significantly improved overall response rate (ORR) and progression free survival (PFS) compared with P alone as initial therapy for HER2+ MBC. Here we report final results of a phase II, single-arm multicenter trial, EGF105764, assessing activity of L with weekly P in first line MBC.&#x2028; Methods: Safety and efficacy of L (1500 mg QD)+P (80 mg/m2/wk x 3q wk) was evaluated in 57 pts with newly diagnosed, HER2 FISH+, Stage IV MBC. Primary endpoint was ORR.&#x2028; Results and Discussion: All pts had ECOG PS ≤1, no pt received previous trastuzumab but 61% received prior adjuvant/neo-adjuvant chemo- or anti-hormonal therapy. Median time from prior chemotherapy was 63 weeks. No patient had suspected baseline CNS disease. At time of data cut-off, 41 (72%) pts progressed or withdrawn. The median duration of L treatment was 45 (range 2-87) wks, and 26 (range 0 to 80) wks for P. The investigator-assessed ORR was 77% (44/57), with 3 CR and 41 PR, (95% CI: 64.2, 87.3) with a median duration of response (DoR) of 42.3 wks (95% CI: 37.7, 64.1). The independently confirmed ORR was 51% (29/57), with 0 CR and 29 PR, (95% CI: 37.3, 64.4) with a median DoR of 39.7 wk (95% CI: 26.9, 50.0). CNS relapse was reported in 4/41 pts (10%). Most common AEs were diarrhoea (56%, ≥gr3: 5%), neutropenia (44%, ≥gr3: 26%), rash (40%, ≥gr3: 3%), fatigue (25%, ≥gr3: 0%), and neurological (25%, ≥gr3: 0%). Four pts had 1 dose reduction of L (2 due to diarrhoea) and 19 pts had ≥1 dose delay (6 due to diarrhoea). Dose reductions for P occurred in 7 pts; 45 pts had ≥1 dose delay (63% due to toxicity). There were no protocol defined LVEF decreases.&#x2028; In the 86pt subset with HER2+ tumors in EGF30001, the investigator reported ORR was 63% in the L+q3w P and 38% for P+placebo. The safety profile of L+P used qw or q3w is comparable: diarrhoea all grades (56% vs 58%), rash all grades (40% vs 43%), and neurological events all grades (25% vs 26%). Neutropenia (all grades) was more common in the qw schedule of P (44% vs 26%), but the incidence of ≥gr3 was comparable (26% vs 21%, for qw vs 3qw respectively).&#x2028; Conclusions: L + weekly P as first-line therapy for HER2+ MBC was well tolerated and produced a high, investigator assessed ORR of 77%. These data suggest that the combination of L and P (at any schedule) may be an option for newly diagnosed patients with HER2+ MBC.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3145.
Phase II study of liposomal doxorubicin (Myocet®), docetaxel and trastuzumab combination as first line treatment of patients with her-2/neu positive locally advanced or metastatic breast cancer.
Authors: Amadori D , Gasparini G , Ardizzoni A , Comella G , Saracchini S , Barone C , Bordonaro R , Djazouli K , Barbato A 
Published: December 2010

Abstract
Abstract #3149
Objective: the aims of the study are to assess activity and safety of liposomal doxorubicin (Myocet®) in combination with Docetaxel and Trastuzumab as first-line treatment of patients with HER-2/neu positive MBC.&#x2028; Methods: forty-six (46) non treated patients with metastatic HER2-overexpressing BC were planned to receive Myocet 50 mg/m2 (d1) and Docetaxel 30 mg/m2 (d2 and d9) plus Trastuzumab (d2, 4 mg/kg followed by 2 mg/kg weekly) for at least 6 cycles (up to a maximum of 8 unless occurrence of unacceptable toxicity or PD). Cycles were repeated every 21 days. Objective response was assessed according to WHO criteria every 3 cycles. To evaluate the tolerability WHO grading toxicity events were assessed at each cycle. Cardiotoxicity was defined as signs and/or symptoms of CHF and/or a decrease in LVEF below normal limit (&lt; 50%) or a decline ≥ 15% from baseline value. To evaluate LVEF an echocardiography was done at baseline and at cycles 3, 6 and 8.&#x2028; Results: we reported preliminary results of 46 patients enrolled. 41 patients completed at least 3 cycles and at first response evaluation Complete Response was seen in 2 pts (CR=4,9%), Partial Response in 22 pts (PR=53,7%), Stable Disease in 15 pts (SD=36,6%) and Progression Disease in 2 pts (PD=4,9%). The Overall Response Rate (ORR) was 58,6%.&#x2028; 36 pts completed the planned chemotherapy (6 cycles): Complete Response was seen in 4 pts (CR=11,1%), Partial Response in 15 pts (PR=41,7%), Stable Disease in 9 (SD=25,0%) and Progression Disease in 8 pts (PD=22,2%). The Overall Response Rate (ORR) was 52,8%. 12 pts were entered in the follow up and for this subgroup median TTP was 13 months.&#x2028; All 46 enrolled patients were included in the safety analysis. Most frequent toxicity events occurred during the study were: granulocytopenia Grade 4 in 16 pts (30.4%), leukocytopenia Grade 3 in 15 pts (32.6%), increase of transaminase levels Grade 1 in 14 pts (30.4%), alopecia Grade 4 in 16 pts (34.8%) and nausea Grade 2 in 13 pts (28.3%). In 2 patients LVEF dropped &lt; 50% and other 2 pts registered a decrease of LVEF &gt;15% with respect to baseline value. In the whole population LVEF mean value changed from 62.6 ± 4.9 at baseline to 61.0 ± 5.5 at cycle 3, to 62.9 ± 6.4 (cycle 6) and to 60.0 ± 8.1 (cycle 8).&#x2028; Conclusion: these preliminary results suggest that the combination of non-pegylated liposomal doxorubicin, docetaxel and trastuzumab has shown a promising activity in first line MBC. The combination is safe with no significant change in LVEF values from baseline to the end of therapy.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3149.
Phase II trial of neoadjuvant 5-fluorouracil, epirubicin and cyclophosphamide (FEC100) followed by weekly paclitaxel and trastuzumab (PH) for HER2 positive breast cancer (Kinki Multidisciplinary Breast Oncology Group; KMBOG-0402).
Authors: Masuda N , Nakayama T , Matsunami N , Kashiwaba M , Kamigaki S , Yamamura J , Anami S , Takeda M , Yasumura Y , Taguchi T 
Published: December 2010

Abstract
Abstract #3160
Background: Achievement of pathological complete response (pCR) by primary systemic chemotherapy (PST) correlates with improved disease-free survival in operable breast cancer patients. Based on data of the higher pCR rate with concomitant chemotherapy and trastuzumab (H) presented by the randomized prospective trial (Buzdar AU, et al: JCO 23:3676-85; 2005), we performed a multi-center, prospective phase II study to assess the addition of H to primary systemic chemotherapy in HER2+ pts in Japan.&#x2028; Methods: Generally, the concomitant combination therapy with anthracycline-containing regimens and H is not recommended because of the increasing rate of cardiac toxicity. This study was designed to evaluate the efficacy and safety of PST for the operable breast cancer with HER2+ phenotype. PST is the sequential chemotherapy with 4 cycles of FEC100 followed by 12 times in combination with weekly paclitaxel (P) 80mg/m2 and H 2mg/kg (PH x 12).. The inclusion criteria is pts with histopathologically confirmed invasive breast carcinoma, T1-3N+M0/T2-3N0M0, HER2 positive by FISH or immunohistochemistry (IHC) 3+, PS=0-1, adequate hematologic, renal, hepatic and cardiac function and a written informed consent. The study was designed to detect a pCR rate of &gt;43% in at least 42 pts. The evaluation of pathological response was carried out on all the surgical specimens sliced every 5 mm interval.&#x2028; Results: From Dec 2004 to Dec 2007, 43 pts were enrolled. Pre-reviewed data is now available for all pts: median age 56 [26-75 years]; 15 (35%) pre-menopausal; median clinical tumor size 40 mm [15-80]; 14 (33%) were ER-positive phenotype. All pts had a normal cardiac function before entry and after FEC→PH. No episodes of serious adverse events were reported. Febrile neutropenia was observed on 5 pts (12%). Grade 2 or 3 neuropathy was limited to 4 pts (9%). Other grade 3 non-hematological toxicities were not observed. Two pts requested to stop the treatment with P after 6 times of infusion because of neuropathy, edema and hyperpigmentation on the face, however, they had completed 12 times of H infusion. After PST, breast conservative surgery was done in 38 patients (88%) and mastectomy in 5 (12%). The overall pCR rate was 60% (26/43), and 6 of 26 pts had only component of DICS.&#x2028; Conclusions: In HER2+ pts, PST with FEC100x4 followed by PHx12 was active and promising, achieving high pathological complete response without significant toxicity.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3160.
Diagnosis of mass forming lesions in combination with real-time tissue elastography.
Authors: Nishiyama Y , Kawagoe A , Sakaguchi U , Nishiyama R 
Published: December 2010

Abstract
Abstract #4013
[Purpose]&#x2028; Although “hardness” is a characteristic of invasive carcinomas, it was not given much importance until now because of its poor quantitative nature and reproducibility. However, due to the development of real-time tissue elastography (EG), the objective measurement of “hardness” is now possible. Moreover, we examined whether mammography (MMG) + B-mode ultrasound (US) in combination with EG improves diagnosability.&#x2028; [Subjects and methods]&#x2028; One hundred and seventy-seven patients with mass-image-forming lesions (135 benign, 42 malignant) whose tissues were diagnosed by core and mammotome biopsies from Oct 2007 to May 2008 were included in the study. Instruments used were Hitachi EUB-8500 and HV-900. The hardness is scored on a scale 1 to 5. Score 1: Distortion appears in the image of the entire low echo tumors, Score 2: Image of most of tumors are distorted but no distortion is seen in certain areas, Score 3: Distortion appears only in the peripheral areas, Score 4: No distortion appears in the entire tumors, and Score 5: No distortion appears even in the peripheral areas. The cases over score 4 are assumed to be malignant. US of category 4 or more, and MMG of category 3 or more were evaluated as malignant.&#x2028; [Results]&#x2028; In 57 patients with lesions of less than 1.1 cm (50 benign, 7 malignant), US + MMG showed sensitivity and specificity of 71.4% and 88.0%, respectively, whereas US + MMG + EG showed sensitivity and specificity of 100% and 80.8%. Moreover, when EG was combined with conventional methods, sensitivity increased from 71.4% to 100%. On the other hand, in 120 patients with lesions of 1.1 cm or more (85 benign, 35 malignant), US + MMG showed sensitivity and specificity of 100% and 55.3%, respectively, whereas US + MMG + EG showed sensitivity and specificity of 100% and 61.2%. There were no significant differences in sensitivity and specificity between the 2 methods, and no additional advantages were observed when EG was used.&#x2028; [Conclusions]&#x2028; Thus, in this study sensitivity could be increased by EG for tumors with a diameter of less than 1.1 cm. Therefore, it was suggested that biopsy may be omissible for low EG scores.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4013.
Evaluation of response to neoadjuvant chemotherapy in primary breast cancer using PET.
Authors: Choi J , Kim K , Kim W , Lee S , Lim H , Cho E , Han B , Kim Y , Ahn J , Im Y , Lee J , Nam S , Yang J 
Published: December 2010

Abstract
Abstract #4019
Purpose&#x2028; To estimate the usefulness of PET scan to assess the response of neoadjuvant chemotherapy, PET scan results were compared with conventional imaging modalities(US and MRI).&#x2028; Patients and Methods&#x2028; Fourty-one patients undergoing neoadjuvant chemotherapy between December 2004 and March 2008 were included. PET scan was performed before and after chemotherapy. Pathologic results were classified into two groups; pathological complete response(pCR) and non-pCR. Clinical responses were assessed with the results of imaging modalities such as post-chemotherapy size or pSUV(postTx), size difference between treatment(delta) and reduction rate(RR) of size or pSUV, and they are compared with postoperative pathologic results.&#x2028; Results&#x2028; 7 out of 41 patients (17.1%) had pCR. The results of US shows that postTx size (1.7±1.5cm) of pCR was not dfferent from those of non-pCR (3.6±3.0cm), and the delta (3.1±1.9cm) and RR (67.7±29.1%) of pCR were higher than those of non-pCR (1.3±1.3cm, 31.0±25.4%), respectively. As a result of MRI, postTx size, delta, RR of pCR was differ from those of non-pCR (1.0±1.7cm vs 2.8±1.7cm p&lt;0.05; 4.5±1.0cm vs 2.3±1.8cm, p&lt;0.05; 88.0±20.8% vs 44.6±24.7%, p&lt;0.01). In PET scan, only postTx pSUV of pCR was differ from that of non-pCR (1.4±1.3 vs 5.3±8.3cm, p&lt;0.05). As a result of receiver operating characteristic curve analyses for the prediction of pathological response of breast cancer, area under curve values (95% confidence interval) of US, MRI, PET for delta were 0.83(0.69∼0.98), 0.91(0.80∼1.01), 0.62(0.38∼0.86), and those of RR were 0.80(0.60∼0.99), 0.90(0.77∼1.02), 0.72(0.47∼0.96), respectively&#x2028; Conclusions&#x2028; We suggest that MRI is useful method to evaluate the response of neoadjuvant chemotherapy. Although PET scan shows less effective for evaluating the response of chemotherapy than MRI, PET scan with the ability to detect the distant metastatic lesions may be helpful to decide the proper management plans for advanced breast cancer.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4019.
Insulin-like growth factor binding protein-1 (IGFBP-1) targets both the insulin-like growth factor (IGF) and integrin pathways for the inhibition of breast cancer cell motility.
Authors: Ibrahim YH , Hartel J , La Parra K , Yee D 
Published: December 2010

Abstract
Abstract #402
The insulin-like growth factor (IGF) system is a relevant therapeutic target for the treatment of breast cancer. Besides receptor targeted therapies, inhibition of ligand-receptor interactions by IGF-sequestering agents such as IGF binding proteins has also proven efficacious. We have used IGF binding protein (IGFBP-1) to neutralize IGF action. This binding protein both binds IGF-I and binds integrins through a RGD sequence and blocks IGF-I induced proliferation and motility. To examine the functional motifs in IGFBP-1, we studied breast cancer cells and examined IGF-induced signaling and biology after exposure to native recombinant human IGFBP-1 (rhIGFBP-1), reduced rhIGFBP-1, and an RGD mutant (Trp-Gly-Asp, WGD) rhIGFBP-1. Native and WGD IGFBP-1 retained IGF-I binding affinity, whereas reduced IGFBP-1 lost ligand binding as confirmed by western ligand blot. Chronic (&gt;3 hour) 80nM rhIGFBP-1 treatment abrogated paxillin phosphorylation and initiated MAPK activation in an IGF-independent manner, and inhibited basal motility and adhesion to fibronectin. While 80nM native rhIGFBP-1 abolished IGF-induced IRS, PKB/Akt and ERK phosphorylation, 80nM reduced rhIGFBP-1 only inhibited IGF-induced PKB/Akt phosphorylation. rhIGFBP-1 inhibited IGF-induced motility, adhesion to fibronectin and anchorage independent growth at IC50 40-80nM. In contrast, efficacy of reduced IGFBP-1 ranged between 80-160nM. Both the IGF-binding and the integrin-binding mechanisms of action of IGFBP-1 were inhibitory to IGF-induced integrin functions. In contrast, IGF-neutralization (but not integrin effects) was required for the inhibition of biology of breast cancer cells in monolayer. Therefore, this study demonstrates that IGFBP-1 has two distinct functional motifs that contribute to the inhibition of breast cancer basal and IGF-induced functions, and that the integrin and IGF-binding motifs of IGFBP-1 cooperatively inhibit IGF-action.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 402.
Accuracy of breast MRI in predicting tumor extent.
Authors: Yao K , Rachel D , Bova D , Hulvat M , Rychlik K 
Published: December 2010

Abstract
Abstract #4022
Introduction: The use of breast MRI to delineate tumor extent prior to surgical resection is becoming more commonplace. How well breast MRI predicts tumor size and extent compared to standard breast imaging is still under investigation.&#x2028; Objective: To determine which imaging modality; mammogram (MGM), ultrasound (U/S), or MRI most accurately predicted tumor size and number of tumor foci.&#x2028; Methods: This was a retrospective review of a prospectively collected database of all breast MRIs performed prior to surgical resection for invasive and noninvasive breast cancer. MGM, U/S, and MRI reports were reviewed and correlated with pathologic tumor size and number of foci.&#x2028; Results: A total of 89 patients with breast cancer underwent bilateral breast MRI prior to surgical resection. Sixty (67%) of the tumors were ductal carcinomas, 21 (24%) were lobular carcinomas, 7 (7%) ductal carcinoma in situ and 2 (2%) were mixed ductal and lobular. The mean tumor size was 1.5cm (0.1-6.0cm) and 32 (38%) were node positive. Fifty three (60%) of the patients underwent lumpectomy and 36 (40%) underwent mastectomy. Of the three imaging modalities, MGM, U/S, and MRI; MRI predicted tumor size significantly more accurately then MGM or U/S (correlation coefficient 0.59 vs 0.78 vs 0.81 respectively). MRI also predicted the number of foci significantly more accurately then MGM or U/S (correlation coefficient 0.48 vs. 0.44 vs. 0.26 respectively). MRI overestimated tumor size by at least 1cm in 12 (14%) patients and the number of tumor foci in 11(16%) patients.&#x2028; &#x2028; Thirteen (15%) of the patients benefitted from MRI while 14 (16%) did not.&#x2028; Conclusions: MRI predicted tumor size and number of foci more accurately then MGM or U/S. Despite these findings, MRI overestimated tumor size and number of tumor foci in a greater percentage of patients then MGM or U/S. More studies are needed to determine the true value of MRI for preoperative surgical planning.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4022.