bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activity and safety of sunitinib in combination with trastuzumab for the treatment of metastatic breast cancer: initial results from a phase II study.
Authors: Bachelot T , Lluch A , Gutierrez M , Martin MM , Kozloff MF , Prady C , Tassell V , Kern K , Huang X , Verma S , Blay J 
Published: December 2010

Abstract
Abstract #4115
Background: Sunitinib (SU) is an oral, multitargeted tyrosine kinase inhibitor of VEGFRs, PDGFRs, KIT, RET, FLT3, and CSF-1R, with proven single-agent activity in pts with advanced BC. Trastuzumab (T) is indicated as both monotherapy for second-line treatment and in combination with taxane-based therapies for first-line treatment of metastatic BC. This study investigates the activity and safety/tolerability of SU administered in combination with T in pts with advanced, HER2+ BC.&#x2028; Materials and methods: Eligible pts have unresectable, locally recurrent or metastatic HER2+ BC. Pts received SU at a starting dose of 37.5 mg/d po continuous daily dosing (CDD). T was administered iv wkly (loading 4 mg/kg then wkly 2 mg/kg) or q3w (loading 8 mg/kg then 6 mg/kg q3w). Due to changes in standard of care, the trial was amended from a randomized, placebo controlled design, to a single-arm study, and eligibility criteria were changed to allow inclusion of pts who had previously received CT in the first-line setting. Previous treatment with T (± lapatinib) was also permitted. The planned sample size is 53 pts and the primary endpoint is ORR.&#x2028; Results: In this ongoing trial, a total of 49 pts have been enrolled to date (6 pts under the original protocol and 43 under the amendment). All 43 pts enrolled under the amendment were evaluable for safety/tolerability, and antitumor activity, measured by RECIST. As of May 2008, 25 pts continue on study and 18 have discontinued, 4 due to AEs. Pts started a total of 167 cycles of treatment with a median of 4 cycles/pt (range: 1–8). The planned dose of SU (37.5 mg/d) was maintained in 31/43 pts (72%). It was reduced to 25 mg/d in 12/43 pts (28%). One pt achieved a CR and 10 a PR. SD occurred in 20 pts and PD in 6 pts. This translated into an ORR of 26% (95% CI, 13.5–41.2) and a clinical benefit rate of 35% (95% CI, 21.0–50.9). Median PFS was 25.3 wks (95% CI, 19.3–32.0). The most common treatment-related AEs were diarrhea (55.8%), asthenia (48.8%) and hypertension (37.2%) of which most were G1 or 2. The most frequent G3 AEs were neutropenia (14%) and asthenia (11.6%). There were 2 treatment-related G4 events: thrombocytopenia (2.3%) and LVEF decline (2.3%). There was 1 treatment-related G5 AE (cardiogenic shock).&#x2028; Conclusions: SU 37.5 mg/d on a CDD schedule in combination with T (wkly or q3w) appears to have a manageable safety profile and antitumor activity in pts previously treated for advanced HER2+ BC.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4115.
Primary analysis of study MO19391, an open-label safety study of bevacizumab (B) plus taxane-based therapy as 1st-line treatment of patients (pts) with locally recurrent (LR) or metastatic breast cancer (mBC).
Authors: Smith IE , Biganzoli L , Cortés-Funes H , Stroyakovskiy D , Franke FA , Chlistalla A , Pierga J , Thomssen C , Pritchard K 
Published: December 2010

Abstract
Abstract #4118
Background: The addition of B (15mg/kg q3w) to 1st-line taxane therapy significantly improved PFS in pts with LR or mBC in 2 phase III studies, E2100 and AVADO. MO19391 investigated B plus 1st-line taxane-based chemotherapy (CTx) in LR or mBC to obtain safety and efficacy data in a community-based population.&#x2028; Methods: This open-label, multicentre study has completed enrolment of 2,000 pts with LR or mBC and an ECOG PS of 0–2. Exclusion criteria included prior CTx for LR or mBC and evidence of CNS metastases. The primary endpoint was safety; secondary endpoints included TTP and OS. B was administered at 10mg/kg q2w or 15mg/kg q3w plus the physician's choice of taxane regimen (or investigator's SOC, excluding anthracyclines). Treatment with B continued until disease progression or unacceptable toxicity. As well as AEs, attention was paid to AEs of special interest (hypertension, proteinuria, wound-healing complications, thromboembolic events, CNS bleeding, other haemorrhages, GI perforation, fistulae, RPLS and CHF). The safety population included all pts who received at least one dose of B.&#x2028; Results: As of March 2008, the safety population consisted of 1,553 pts from 35 countries. The median number of cycles received was 6 for both B (range 1–28) and CTx (range 1–28). Pts received: single-agent taxane 66.2%, taxane combination 13.5%, other single agent 8.5%, other combination 3.3%. Frequently reported AEs are shown below. Grade 3/4 AEs of special interest were reported in 6.3% of pts, most commonly hypertension 2.2%, proteinuria 0.7%, pulmonary embolism 0.5%, epistaxis 0.4%. AEs leading to death during the study phase were reported in 27 pts (1.7%)*.&#x2028; &#x2028; Conclusions: MO19391 is the largest study population of pts with LR or mBC receiving B plus CTx. Toxicity was low and preliminary results are consistent with previous B safety studies. Final analysis of the primary endpoint and secondary efficacy analyses will be presented.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4118.
Tolerability of sunitinib in combination with docetaxel and trastuzumab as first-line therapy for HER2+ advanced breast cancer.
Authors: Cardoso F , Canon J , Amadori D , Dirix L , Villa E , Aldrighetti D , Machiels J , Verkh L , Huang X , Giorgetti C 
Published: December 2010

Abstract
Abstract #4120
Background: Trastuzumab (T) combined with docetaxel (D) is approved for the first-line treatment of HER2+ advanced BC (ABC). Sunitinib (SU) is an oral, multitargeted tyrosine kinase inhibitor of VEGFRs, PDGFRs, KIT, RET, and FLT3 with single-agent activity in pts with previously treated ABC. The tolerability and preliminary antitumor activity of SU combined with D and T was investigated in this exploratory study as a first-line regimen for ABC.&#x2028; Materials and methods: A target of 25 female pts (≥18 yrs, ECOG PS 0 or 1) with unresectable, locally recurrent or metastatic HER2+ BC are being enrolled. Starting doses for the 3 treatments are listed in the table below. The primary objective is safety. Secondary endpoints are PK and preliminary tumor activity according to RECIST. After discontinuation of D, responsive pts (PR or SD) can continue SU and T until PD.&#x2028; &#x2028; Results: As of May 2008, 18 pts were enrolled; 11 pts continue on study therapy and 7 have discontinued (5 due to PD; 1 due to pt decision; 1 due to G3 fatigue). Of the 18 pts enrolled, 16 are evaluable for safety and 11 for activity. Pts completed 75/96/98 cycles of D/SU/T, respectively, with a median of 5 cycles/pt for each drug (range: 1-13/1-12/1-13). The planned dose of SU (37.5 mg/d) was reduced to 25 mg/d in 6/16 pts due to G4 neutropenia (1); G3 febrile neutropenia (1); G3 fatigue (1); G2 hyperbilirubinemia (1); G2 hypertension (1); and G2 diarrhea (1). D was reduced in 4 pts due to febrile neutropenia (2) and G4 neutropenia (2). T was given q3w in 12 pts and wkly in 4 pts. T dosing was delayed by ≥4 days in 6 pts, 4 due to D dose delay and 2 due to AEs when D was already discontinued (G2 neutropenia and G3 fatigue). Overall, the most frequent AEs were fatigue (68.8%) and neutropenia (43.8%), consistent with the most common toxicities of D. No GI perforation or bleeding were reported. The most frequently reported severe AEs were neutropenia (1 G3 and 6 G4) and febrile neutropenia (5 G3). G-CSF was administered to 8 pts. Of the 11 pts evaluable for antitumor activity, 1 showed a confirmed CR, 7 a confirmed PR, 2 had PD and 1 was not evaluable.&#x2028; Conclusions: The combination of SU 37.5 mg/d (Schedule 2/1) with D 75 mg/m2 q3w and T wkly/3-wkly, given as first-line treatment to HER2+ pts with ABC, shows manageable toxicities. The use of G-CSF appears beneficial. Preliminary antitumor activity is encouraging. Enrollment is ongoing.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4120.
Carcinoma of breast in males in Turkey: a Turkish oncology group study.
Authors: Bolukbasi Y , Kucucuk S , Aydin A , Yetmen O , Haydaroglu A 
Published: December 2010

Abstract
Abstract #4132
Purpose: Compared to breast carcinoma in women breast carcinoma in males is frequent and information in males is limited. The aim of this multicentric study is to evaluate the treatment results of male patients with breast cancer treated in cancer centers in Turkey.&#x2028; Methods: Between 1973-2006, 167 male breast cancer patients who were treated, analyzed retrospectively respect to clinical presentation, treatment, survival and prognostic factors. Median age was 61 (range: 32-90), 51.5% were found in right breast. Majority of the tumors were occured in the central(36.5%) and upper outer quadrant (32.9%). Except one patient, all of them underwent mastectomy. Stage distrubution was as follows; Stage I 9%, Stage II 34.7 %, stage III 44.9%, stage IV 4.8% and 11 patients (6.6%) can not be staged due to Tx or Nx status. The most common histologic type was invasive ductal carcinoma (89.8%). Contralateral breast cancer developed in 3 patients. Of the patients 81.4% (136) received adjuvan radiotherapy for the whole breast and also to the periferial lymphatics for patients carrying high risk factors. Median total dose was 50 Gy with a daily fraction dose of 2 Gy. Five patients were treated with radiotherapy due to recurrences, 3 patients were treated for metastases and one patient was treated for curative intent. Radiation therapy was not given to 22 patients. Adjuvant chemotherapy and hormonal therapy were used in 83 and 70 patients, respectively.&#x2028; Results: During a median follow-up duration of 66 months (range: 1-237 months) . Isolated local-regional recurrence and distant metastases were observed in 13.2% and 34.1% of cases, respectively. Five-years overall survival, disease free survival and local control were, 66.1%, 63.4%, 89%, respectively. The prognostic factors influencing overall survival were presence of positive axillary lymp node (p=0.000), T stage (p=0.000), lymph node ratio (&gt;50%) (p=0.001), AJCC stage (p=0.000), skin invasion (p=0.00), nipple invasion (p=0.027) and blood vessel invasion (0.006) in the univariate analysis. In the multivarian analysis, the only prognostic factor which has impact on overall survival was AJCC stage (p=0.023). No prognostic factor was found to be significant for disease free survival and local control.&#x2028; Conclusion: In the present study positive axillary lymp node, T stage, Lymph node ratio (&gt;50%), AJCC stage (p=0.000), skin invasion, nipple invasion and blood vessel invasion were the significant prognostic factors for overall survival. In absence of prospective randomised trials, retrospective review data from multi-centre approaches are necessary and this can provide useful guidelines for understanding the biology of breast cancer in males.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4132.
Is there any benefit in routine wound drainage following mastectomy and axillary clearance?.
Authors: Shokuhi S , McArdle K , Rai S , Brown H , Vishwanath L 
Published: December 2010

Abstract
Abstract #4153
Introduction: Seromas are the most frequent complication of breast cancer surgery and are often considered a "necessary evil". Despite limited evidence, suction drains are routinely used to reduce their risk. Drains are an important factor contributing to increased hospital stay as patients are usually reluctant to be discharged before their removal. The aim of this study was to compare the seroma rate post mastectomy and axillary clearance with and without insertion of suction drains.&#x2028; Methods: All patients undergoing mastectomy and axillary clearance treated under the care of three consultant breast surgeons were studied. Data was collected prospectively and analysed retrospectively. Outcome measures included incidence and volume of postoperative seroma, number of aspirations, length of stay and complication rate. Mann-Whitney U test and difference between proportions was used for statistical analysis.&#x2028; Results: Between December 2006 and March 2008 a total of 74 women, median age 63 (range 44-88) underwent 78 mastectomy and axillary clearance (4 bilateral). Patients were divided into three groups. Group 1 no drain, Group 2 one drain, Group 3 two drains.&#x2028; &#x2028; There was no significant difference between the 3 groups in rate of seroma formation. Total volume of seroma and out patient aspirations were significantly higher in group 1 compared with group 3 (P=0.008 and P=0.03 respectively) however there was no significant difference between group 2 and 3. There was no significant difference in complication rates in the three groups. There was a significant reduction in hospital stay in groups 1 and 2 compared to group 3 (P=0.014).&#x2028; Conclusion: Drains did not prevent seroma formation, and were associated with a longer postoperative stay. There was no benefit in insertion of a second drain in reducing seroma volume and number of aspirations required. Second drain leads to a significantly longer hospital stay. The routine use of suction drains post mastectomy may not be warranted. Insertion of two drains is not justified.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4153.
Cyclin B as a prognostic factor in low-risk node negative breast cancer.
Authors: Koliadi A , Nilsson C , Ahlin C , Fjällskog M 
Published: December 2010

Abstract
Abstract #4161
Background: The cell cycle regulation is a well-controlled mechanism in normal non-transformed cells. Cyclins are important proteins for this regulation. Cyclin B1 plays an essential role as a mitotic cyclin in the entry of mitosis from G2 phase. Previous studies have suggested that cyclin B1 over-expression could be a poor prognostic factor in breast cancer. We wanted to examine cyclin B1 as a prognostic factor in a group of patients with low-risk node negative breast cancer.&#x2028; Material and Methods: We compared women that died from their breast cancer (n=17) with women free from relapse &gt; 8 years after initial diagnosis (n=24). All women had stage I, low-risk breast cancer. The groups were matched regarding tumour size, receptor status, adjuvant chemotherapy and tumor differentiation. Tumor samples were analyzed regarding cyclin B1 expression using immunohistochemistry with commercial antibodies and optical microscopy.&#x2028; Results: The mean percentage of cyclin B1 was significantly higher (p=0,00008) in women that died from their breast cancer (13%) compared with women free from relapse (5%). Mortality was significantly higher (p=0,001) in patients with high cyclin B (85%) than with low cyclin B (21%) using 9% as cut-off value.&#x2028; Conclusion: In our study, we found that low-risk node negative patients with high expression of cyclin B1 had a significantly worse outcome than patients with low expression of cyclin B1. We suggest that cyclin B1 could be a potent prognostic factor in this low-risk patient group. However, further studies are needed to confirm our findings.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4161.
Bone scintigraphy (BS) may no longer be relevant in the era of integrated PET/CT for women undergoing evaluation for suspected metastatic breast cancer (MBC).
Authors: McArthur HL , Lynch C , Morris P , Larson S , Grabski K , Howard J , Patil S , Hudis CA , Dickler MN 
Published: December 2010

Abstract
Abstract #5007
Background: &#x2028; The accurate detection of osseous metastases frequently has significant prognostic and therapeutic implications at metastatic breast cancer (MBC) diagnosis. However, the ideal paradigm for accurate detection of osseous metastases has not yet been determined. In this retrospective, single-institution study, we compare the diagnostic performance of integrated positron emission tomography/computed tomography (PET/CT) versus bone scintigraphy (BS) for women undergoing extent-of-disease (EOD) evaluation for suspected MBC.&#x2028; Methods:&#x2028; Women undergoing EOD evaluation for suspected MBC with integrated PET/CT and bone scintigraphy (BS) between January 1, 2005 and Dec 31, 2007 were identified through institutional databases. Patients with PET/CT and BS imaging completed within 30-days of each other were included. Women with a prior history of MBC or an active second malignancy were excluded. Electronic medical record (EMR) reports were reviewed and classified as positive, negative or equivocal for detecting osseous metastases. All EMR reports deemed potentially equivocal were reviewed by 2 investigators and consensus reached regarding the final classification. Bone biopsy data, where available, was also recorded.&#x2028; Results:&#x2028; The median age of the 62 eligible women was 54y (33-90y). Overall, PET/CT and BS demonstrated a high degree of concordance. Of the 41 concordant studies, 13 (21%) and 28 (45%) were reported as positive and negative for osseous metastases, respectively. No studies were classified as equivocal by both modalities. Ten positive PET/CT studies were negative by BS, but no PET/CT-negative studies were positive by BS. Of the 10 patients with PET/CT-positive, BS-negative studies, 4 had subsequent bone biopsies, all of which confirmed osseous metastases.&#x2028; &#x2028; Conclusions:&#x2028; This study supports the diagnostic performance of integrated PET/CT in detecting osseous metastases when EOD evaluation for suspected MBC is considered. Whether PET/CT may supplant BS entirely in this setting has not yet been determined.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5007.
A novel breast tissue feature strongly associated with risk of breast cancer.
Authors: McKian KP , Reynolds CA , Anderson S , Vierkant RA , Visscher DW , Frost MH , Pankratz VS , Nassar A , Hartmann LC 
Published: December 2010

Abstract
Abstract #5008
Background: Accurate, individualized risk prediction for breast cancer is lacking. Tissue-based features, such as the terminal duct lobular unit (TDLU), may help to stratify women into different risk levels as breast lobules are the anatomic sites of origin of breast cancer. As women age, these lobular structures should regress, which results in reduced breast cancer risk. Regression, however, does not occur in all women.&#x2028; Materials and Methods: We have quantified the extent of lobule regression on a benign breast biopsy in 85 breast cancer cases and 142 age-matched controls from the Mayo Benign Breast Disease Cohort, by determining number of acini/lobule and lobular area. We also calculated Gail model 5-year predicted risks for these women.&#x2028; Results: There is a step-wise increase in breast cancer risk with increasing numbers of acini/lobule (p=0.0004). Adjusting for Gail model score, parity, histology, and family history did not attenuate this association.&#x2028; &#x2028; Lobular area was similarly associated with risk. The Gail model estimates were associated with risk of breast cancer (p=0.03). We examined the individual accuracy of these measures using the concordance (c) statistic. The Gail model c-statistic was 0.60 (95% CI; 0.50-0.70); the acinar count c-statistic was 0.65 (95% CI; 0.54-0.75). Combining acinar count and lobular area, the c-statistic was 0.68 (95% GI; 0.58-0.78). Adding the Gail model to these did not improve the c-statistic.&#x2028; &#x2028; Discussion: Novel, tissue-based features that reflect the status of a woman's normal breast lobules are strongly associated with breast cancer risk. These features appear to provide more accurate risk assessment than the currently used Gail model.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5008.
A prospective evaluation of the utility of clinical breast examination.
Authors: Goodson III WH , Hunt Jr. TK , Plotnik J , Moore II DH 
Published: December 2010

Abstract
Abstract #5012
Emphasis on mammography, and to a lesser extent MRI, for breast cancer screening, is temporally associated with decreased practice of clinical breast examination (CBE). To assess the role of CBE in current practice, we prospectively evaluated CBE in a community, primary care practice. Because CBE is a low yield procedure, we embedded in this study a test of whether an attention focusing intervention would increase the so-called “call rate” for screening CBE. METHODS: With IRB approval, over an 18 month period, we prospectively asked clinicians in a community, primary care practice to record findings from screening CBE for 1522 routine visits. Clinicians were randomized to use one of two forms: 1. a short form that collected brief historical information about the patient and asked the clinician to mark any areas of abnormality on a graphic of the breasts; or 2. a long form that, in addition to the information on the short form, asked the clinician to record several descriptors of the patient's breasts in general. For historical controls, we retrospectively abstracted the same information as in the short form from charts of 300 women seen for routine care in year before the study. To assess the success in finding cancer, we compared the cancer identification rate to the cancers expected on the basis of age adjusted SEER data. RESULTS: There were no statistically significant differences between the two prospective groups in terms of age, presence of a mass prior to CBE according to the patient, or abnormal mammogram before the examination. The call rate for CBE was the same in both study groups for all CBE, CBE when the patient did not think a mass was present, and for CBE when the patient did not think a mass was present and there was not an abnormal mammogram. The call rate for the prospective study patients (8.3%) was, however, significantly higher than the call rate in the preceding year (4.7%; p=0.032) suggesting that the collection of data on separate forms had a Hawthorne Effect in which the conditions of data collection functions as an independent variable. SEER data predicted 3.7 cancers in the 1822 women. We found 4. CONCLUSIONS: Because a simple form as an intervention to focus attention on CBE successfully improved the call rate of CBE and because we found the number of cancers SEER data would anticipate, we question enthusiasm for training in special techniques for CBE and legislative efforts to require separate CPT codes for CBE. We conclude that focusing attention is as successful as special CBE choreography, so that in lieu of training in special techniques, quality efforts should encourage implementation of simple ways to focus clinician attention during CBE.
Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5012.