bluuebunny/crossref_metadata_2025_split huggingface dataset:
P5-14-16: Molecular Classification in Primary Breast Cancer and Corresponding Lymph Node Metastasis Show Impaired Prognostic Profile in the Metastatic Node.
Authors: Falck A-K , Ferno M , Bendahl P-O , Rydén L 
Published: June 2012

Abstract
Introduction The heterogeneity of breast cancer disease has emphasized the need to optimize prediction of outcome by molecular classification of the primary tumor. Clinical management of primary breast cancer is based on biomarkers measured in the primary tumor, whereas biomarker analysis in metastatic lymph nodes is not used for clinical decision making. Recently, microarray-based expression profiling and subsequent immunohistochemical studies have identified biologically distinct subtypes using a combination of biomarkers. The present study aimed to classify primary breast cancer tumors and corresponding lymph node metastases by multiple biomarkers into Luminal A, Luminal B, HER2 type and Triple negative phenotype and compare outcome.
Material and method The study is based on a cohort of patients where biomarker expression (hormone receptor status (ER, PR), human epidermal growth factor receptor 2 (HER2) and Ki67) in primary breast cancer and ipsilateral lymph node metastasis recently were reexamined and individually related to prognosis. In the present study, 85 patients of the original cohort were possible to classify into the four subtypes: Luminal A (ER+, PR+/− and Ki67 ≤ 20%), Luminal B (ER+, PR+/−, HER2+/− and Ki67 &gt; 20%), HER2− type (ER-, HER2+) and Triple negative (ER-, PR-, HER2−). The classifications of primary tumors and corresponding lymph node metastases were compared using the McNemar-Bowker test of symmetry and the molecular subgroups were related to clinical outcome in terms of 5-years distant disease-free survival (DDFS) by Cox analysis with luminal A as the reference group.

In 7 cases (16%) the biomarker classification was discordant between the primary tumor and the lymph node metastasis. All of the discordant cases shifted to a subtype with a worse prognosis according to the lymph node metastasis (p=0.06, Mc Nemar-Bowker test of symmetry). When comparing Luminal A to non-Luminal A in the primary tumor and the lymph node, the deviation from symmetry was significant, p=0.02. DDFS was worse in all subtypes compared to the prognosis for Luminal A using Cox analysis in both primary tumors and lymph node metastasis.
Conclusion Our data shows discordance in classification according to a multiple molecular phenotype between primary tumors and lymph node metastasis in breast cancer patients. The discordant cases were shifted from Luminal A to a subtype where survival analysis showed an impaired prognosis compared to this subgroup. The finding that the molecular phenotype is shifted from a “good” prognostic signature in the primary tumor to a “bad” prognostic signature in the metastatic node can be of clinical importance for the choice of adjuvant systemic therapy in primary breast cancer with lymph node positive disease.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-14-16.
P5-14-20: Neoadjuvant Chemotherapy (NCT) in 466 Patients for Operable Breast Cancer: The Prognostic Value of SBR Grade Variation.
Authors: Abrial C , Mouret-Reynier M-A , Wang-Lopez Q , Durando X , Thivat E , Raoelfils I , Gimbergues P , Van Praagh-Doreau I , Nabholtz J-M , Chollet P , Penault-Llorca F 
Published: June 2012

Abstract
Purpose of the study: In a new database harbouring the patients of several prospective phase II neoadjuvant trials (fec 50–100, net, tncf, taxotere/tncf, taxotere alone), the predictive value of tumour factors (SBR grade, RH, Her2, Ki-67 and cycline D1) was studied in 466 women with stage II-III operable breast cancer treated between 1991 and 2006.
Patients and methods: Median age of the patients was 48 years [27-76]. Median diameter of the invasive tumour was 40 mm [10-130]. 382 (82%) patients had a canalar, 57 (12.2%) a lobular, 14 (3%) a mixed or invasive carcinoma, 3 (0.6%) neoplasic cells only and 10 (2.2%) another carcinoma. Before chemotherapy, 33% were grade III SBR. The median number of NCT courses was 6 [1-8] followed by a surgery for 98%, a radiotherapy for 93%, an adjuvant chemotherapy (20%) and/or a hormonotherapy (56%).
Results: Overall response rate was 73% (18% complete). The complete pathological response (pCR) rate was 17.2% according to Chevallier's classification. On 455 patients operated, 324 (71%) had a conservative surgery. On 390 patients with an axillary dissection, 195 (50%) had involved nodes (median number: 2 [1-20]). After a median follow-up of 135 months, DFS and actuarial survival at 120 months were 61.9% and 73%, respectively.
After chemotherapy, we found a significant variation for SBR grade ***: there was five fold more patients for whom we observed a down grading of the SBR grade (grade 2/3 to grade 1) than up grading (grade 1 to grade 2/3), p=6.1.10−6. For patients in objective response, we observed a significant decrease of SBR grade (p=1.7.10−3).
Moreover, the variation of SBR grade was also pronostic. Indeed, the disesase-free survival for patients who presented a SBR down grading after chemotherapy was significantly better (p=0.031) compared to patients for whom SBR grade remained stable or was in up grading. There was a tendancy for overall survival (p=0.15).
Conclusion: Down grading of SBR grade appears linked to response and so may constitute a parameter of better prognostic. At the opposite, up grading of SBR grade is an adverse prognostic factor. To conclude, it is interesting to emphasize that SBR grade variations can be assessed when patients are not in pCR, ie plays a complementary role.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-14-20.
P5-14-27: Prognostic Factors of Node-Negative, High Risk and 1–3 Positive Lymph Nodes Breast Cancer by Intrinsic Subtype in Patients with Adjuvant Chemotherapy.
Authors: Kojima Y , Hashimoto K , Harano K , Shimizu C , Yunokawa M , Yonemori K , Tamura K , Katsumata N , Ando M , Kinoshita T , Fujiwara Y 
Published: June 2012

Abstract
Purpose: St. Gallen 2007 categorized high risk, node-negative breast cancer (HNBC) and 1–3 lymph nodes positive BC (LNBC) without HER2 overexpression as intermediate risk. We hypothesized that triple negative BC (TNBC) and hormone-receptor positive without HER2 overexpression (H-BC) in intermediate risk have different prognostic factor in patients with adjuvant chemotherapy (AdC).
Methods: We examined disease-free survival (PFS) and overall survival (OS) of TNBC and H-BC with regard to potential prognostic factors. All the patients included in this study were categorized intermediate risk by St.Gallen 2007 and received AdC.
Results: A total of 470 patients were identified; H-BC (n=360) and TNBC (n=110). Age (&lt;35) was significantly associated with DFS in TNBC while it was not in H-BC (p=0.0.1 and p=0.63, respectively). Tumor size (&gt;2cm) and tumor grade related to DFS in H-BC but not in TNBC. Tumor grade was not associated with DFS in both H-BC and TNBC (p=0.64 and p=0.91, respectively). Lymph node metastasis was a significant factor of DFS only for H-BC (p=0.009 and p=0.19). Conclusions: In TNBC, age was only a significant factor associated with DFS while in H-BC, lymph node status and tumor size rather age related to DFS.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-14-27.
P5-18-06: Taxanes and Cyclophosphamide Are Equally Effective in Breast Cancer: A Meta-Analysis of Ten Phase III Trials in Early and Advanced Disease.
Authors: Vriens BE , Lobbezoo DJ , Voogd AC , Veeck J , Tjan-Heijnen VC 
Published: June 2012

Abstract
Background Overall taxanes did not improve survival in metastatic breast cancer trials (n=10 trials), whereas they do so in (neo-)adjuvant breast cancer trials (n=28 trials). We also noticed that in a substantial number of ‘negative’ metastatic trials, taxane-regimens were used without cyclophosphamide. To further explore this, we compared the outcome of studies in early and advanced breast cancer with a similar design, that is all studies substituting taxanes for cyclophosphamide.
Methods We identified 10 phase III taxane-based chemotherapy trials in early and advanced disease, in which taxanes were used instead of cyclophosphamide. They all compared a regimen of an anthracycline combined with a taxane versus an anthracycline combined with cyclophosphamide, i.e., AT versus AC. A pooled analysis was performed using the Review Manager software (RevMan 5) provided by the Cochrane Collaboration.
Results In total, 5 studies in advanced disease, 2 studies in neoadjuvant, and 3 studies in adjuvant disease setting were included and analyzed for their primary endpoint. In metastatic breast cancer studies, the hazard ratio of overall survival was 1.03 (95% CI 0.92 to 1.15) for taxanes as compared to cyclophosphamide. Also, studies on early breast cancer with a similar design showed no improvement for taxanes, resulting in an odds ratio for pCR of 0.91 (95% CI 0.57 to 1.43) in the neo-adjuvant setting and a hazard ratio for 5-year disease-free survival of 0.96 (95% CI 0.84 to 1.09) in the adjuvant setting.
Conclusion Re-assessment of studies of drugs both assessed in metastatic and early breast cancer provides a new tool for improved understanding. This meta-analysis shows that cyclophosphamide in breast cancer patients is equally effective as taxanes, and thus should be considered of pivotal importance in the treatment of metastatic and early breast cancer. Full appreciation of its relevance will prevent replacement of cyclophosphamide in future trials or in daily practice. Funding: Netherlands Organization for Health Research and Development (ZonMw 80–82500-98-10901)
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-18-06.
P5-19-01: Final Results of a Three-Arm Randomised Phase II Study of Oral Vinorelbine Plus Capecitabine Versus Oral Vinorelbine and Capecitabine in Sequence Versus Docetaxel Plus Capecitabine in Patients with Metastatic Breast Cancer Previously Treated with Anthracyclines.
Authors: Campone M , Dobrovolskaya N , Tjulandin S , Chen S-C , Fourie S , Mefti F , Konstantinova M , Lefresne F , Meheust N , Jassem J 
Published: June 2012

Abstract
Purpose: Owing to the increasing number of patients treated with anthracycline-based adjuvant chemotherapy, there is a need for new effective and tolerable non-anthracycline based regimens in metastatic breast cancer.
Patients and methods: Patients with HER2−negative metastatic breast cancer previously treated with anthracyclines in (neo) adjuvant setting were randomised to fully oral 3-weekly cycles of the combination of oral vinorelbine with capecitabine (V+C), to the same drugs alternating every 3 cycles (V ⇔ C), or to the combination of docetaxel and capecitabine (D+C). V was given at 80 mg/m2 (after the first cycle at 60 mg/m2) on days 1 and 8 in the V+C arm and weekly in the V ⇔ C arm, C at 1,000 mg/m2 bid from days 1 to 14, and D on day 1 at 75 mg/m2. The primary endpoint was disease control rate (CR+PR+NC ≥ 3 months).
Results: A total of 139 patients were randomly assigned to V+C (44 patients), V ⇔ C (47 patients) and D+C (48 patients). After an independent review, the disease control rate in the intent-to-treat population in the V+C, V ⇔ and D+C arms [95% CI] was 70.5% [54.8−83.2], 37.0% [23.2−52.5] and 70.8% [55.9−83.1]. The response rate was 31.8% [18.6−47.6], 8.7% [2.4−20.8] and 35.4% [22.2−50.5], respectively. The median duration of progression-free survival in the V+C, V ⇔ C and D+C arms [95% CI] was 7.2 months [5.3−8.9], 3.4 months [2.6−5.6] and 8.9 months [7.2−12.0]; the median overall survival [95% CI] was 22.2 [18.8; 29.9], 19.4 [12.5; 35.4] and 24.2 [14.2; 38.5] months, respectively. Lower efficacy observed in the sequential arm could be due to higher prevalence of patients with visceral disease in this arm (91.3% in comparison to 65.9% in V+C and 64.6% in D+C arm). Combinations of V+C or D+C showed similar efficacy and a different toxicity profile; V+C induced less neutropenia, infection, hand-foot syndrome, fatigue/asthenia and alopecia, whereas D+C- less gastrointestinal toxicity.
Conclusions: V+C combination constitutes a valuable fully oral alternative option to D+C in patients with metastatic breast cancer previously treated with anthracyclines in (neo)adjuvant setting, while offering the advantages of an all-oral treatment.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-19-01.
P5-19-08: Pooled Analysis of Individual Patient Data from Capecitabine Monotherapy Clinical Trials in Anthracycline-/Taxane-Pretreated Locally Advanced or Metastatic Breast Cancer (LA/MBC).
Authors: Blum JL , Barrios CH , Feldman N , Verma S , McKenna E , Lee S , Scotto N , Gralow J 
Published: June 2012

Abstract
Background
Capecitabine (C) has shown efficacy as monotherapy in anthracycline (A)-/taxane (T)-pretreated LA/MBC in phase II/III trials. Since its approval, the treatment landscape in MBC has evolved, and C has served as the combination partner and/or active comparator in trials of novel agents in pretreated MBC. This pooled analysis of clinical trial data, spanning a 12-yr period, assessed the efficacy and safety of C across treatment lines and the impact of disease characteristics on clinical outcomes with C.
Methods: Individual patient (pt) data were pooled from 7 clinical trials conducted by Roche/GNE from Feb 1996-Jun 2008 where C monotherapy was the test/control regimen for pts with LA/MBC with/without prior A/T therapy. Analyses were performed on an ITT basis. Univariate and multivariate regression analyses assessed the impact of pt/disease characteristics and prior therapy on outcomes.
Results: Data from 805 pts enrolled to intermittent C monotherapy were analyzed: 268 in the 1st-line metastatic setting; 537 in the ≥2nd-line metastatic setting (table).

Median age: 55 yrs (range 23–90). Most pts were Caucasian (81%) with ECOG PS of 0 (55%). Baseline demographics were balanced across treatment lines. Data on A/T treatment history were available for 719 pts; 557 pts received prior A/T therapy, 176 were A-refractory, 234 T-refractory and 154 A- and T-refractory. Pooled overall response rate (ORR) was 21.0% (1.7% complete; 19.3% partial). ORR was 25.0% and 19.0% for pts treated in the 1st- and ≥2nd-line settings (OR 0.70, 95% CI: 0.5−1.0; p=0.0486). Median PFS was 126.9 days (95% CI: 119–132) in the pooled analysis, and significantly longer in pts receiving 1st- vs ≥2nd-line C: 150.0 vs 112.0 days (HR 1.45, 95% CI: 1.23−1.71; p&lt;0.0001). Pooled median OS was 482.1 days (95% CI: 438–516). Significantly longer median OS was seen in pts receiving 1st- vs ≥2nd-line C: 666.0 vs 396.0 days (HR 1.98, 95% CI: 1.62−2.41; p&lt;0.0001). 62 pts (8%) withdrew due to C-related AEs, which were severe in 4% of pts and life threatening in 2%. AEs of special interest occurred in 489 pts (63%); these were severe in 24% of pts and life threatening in 2%. Gastrointestinal disorders were most frequent (417 pts [53%]), and were severe or life threatening in 13% and 1% of pts.
Conclusions: This pooled analysis of pt data (n=805) revealed significantly longer ORR/survival in pts receiving 1st- vs ≥2nd-line C for A-/T-pretreated MBC. Univariate and multivariate analyses are ongoing; results will be presented. Safety data were in-line with findings from phase III trials of C in MBC.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-19-08.
P5-19-13: A Randomized Phase II Trial of First-Line Metastatic Breast Cancer (MBC) Patients: Sub-Set Analysis of Albumin-Bound Paclitaxel (ab-pac) Given Weekly at 150 mg/m2.
Authors: Gradishar WJ , Krasnojon D , Cheporov S , Makhson AN , Manikhas GM , Clawson A , Bhar P 
Published: June 2012

Abstract
Background
We previously reported the results of a phase II study evaluating the efficacy and safety of 3 different dosing regimens of ab-pac and docetaxel for the first-line treatment of MBC (Gradishar et al. J ClinOncol. 2009;27:3611). Here we report outcomes for a subset of patients (pts) during treatment with ab-pac at 150 mg/m2 weekly for the first 3 weeks of a 4-week schedule (qw 3/4).
Methods: Patients (N = 300) with previously untreated MBC were randomized to 1 of 4 treatment arms: arm A, ab-pac at 300 mg/m2 q3w; arm B, ab-pac at 100 mg/m2 qw 3/4; arm C, ab-pac at 150 mg/m2 qw 3/4; arm D, docetaxel at 100 mg/m2 q3w. A step-down statistical approach was used for pairwise comparisons of treatment groups. The trial was powered for antitumor activity and safety.
Results: Treatment arm C produced the longest overall survival (OS) (33.8 months) with an 11.6-month longer median OS vs arm B (22.2 months, HR 0.575; P = .008) and a 7.2-month longer median OS vs arm D (26.6 months, HR 0.688; P not statistically significant). Median OS in arm A was 27.7 months. These OS data were consistent with previously published overall response rates (ORR) and progression-free survival (PFS). Forty-seven percent of pts in arm C required dose reduction due to toxicity, including 27% due to neutropenia (np), 15% due to sensory neuropathy (SN), 3% due to allergy/immunology, 1% due to febrile np, and 1% due to ulceration of the skin. The median OS for the subset of pts requiring DRs in arm C was comparable to pts not dose reduced: 35.2 and 31.8, respectively. Pts who were dose reduced in arm C received a median of 2 additional cycles of treatment compared with those without DRs: 10 (range 2 — 27) vs 8 (range 1 — 27). Investigator assessed ORR and PFS were numerically higher in pts dose reduced vs those not reduced. Baseline characteristics were similar between pts requiring DRs vs not.

qw 3/4, first 3 out of 4 weeks; CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group performance status. aInvestigator assessed. bAll grade 3, no grade 4.
Conclusion: Pts in the ab-pac 150 mg/m2qw 3/4 arm who were dose reduced achieved a similar OS compared to patients who were not dose reduced. No clear trends in baseline characteristics emerged to predict the requirement for dose reduction in the 150 mg/m2 ab-pac arm. The ab-pac 150 mg/m2 qw 3/4 dosing regimen provided a survival advantage in this phase II trial in first-line MBC and dose reductions could be used to manage toxicities and prolong treatment duration without compromising efficacy.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-19-13.
P5-21-01: A Renewable Tissue Resource of Phenotypically Stable Human Breast Cancer Xenografts for Preclinical Studies.
Authors: Zhang X , Dobrolecki LE , Lai Q , Landis MD , Wong H , Tsimelzon A , Claerhout S , Contreras A , Gutierrez C , Huang J , Wu M-F , Pavlick AC , Froehlich AM , Hilsenbeck SG , Mills GB , Wiechmann L , Petrovic I , Rimawi MF , Schiff R , Chang JC , Lewis MT 
Published: June 2012

Abstract
Introduction Translational breast cancer research is hampered severely by difficulties in obtaining and studying primary human breast tissue, and by the lack of in vivo preclinical models that accurately reflect patient tumor biology. These limitations are due, in part, to the fact that traditional immunocompromised mouse models are not generally permissive for growth. We sought to circumvent some of these limitations by transplanting and growing human mammary tumors in the mammary fat pad of SCID/Beige immunocompromised mice in the absence of exogenous human fibroblasts.
Aims and Methods To establish a set of stable human breast cancer xenografts for preclinical studies. Human breast cancer biopsies were received, minced into small fragments and then transplanted directly into “cleared” fat pads of recipient SCID/Beige immunocompromised mice. Transplanted fat pads were checked weekly. After initial tumor was palpated and harvested, tumor fragments were transplanted into new SCID/Beige hosts for subsequent transplant generations. Serial immunohistochemical evaluations were performed to confirm human origin and biomarker status. Analytical flow cytometry for evaluating expression of proposed “cancer stem cell” markers, and gene and protein expression analysis were carried out on all stable lines.
Results and Conclusions Xenograft lines were established directly from breast cancer patient samples, without intervening culture in vitro, using the epithelium-free mammary fat pad as the transplantation site. Of the conditions tested, xenograft take rate was highest in the presence of a low-dose estradiol pellet without exogenous human fibroblasts. Thirty six stably transplantable xenograft lines representing 27 patients were established, using pre-treatment, mid-treatment, and/or post-treatment samples. Most patients yielding xenografts were “triple-negative” (ER-PR-HER2−) (n=21), we were able to establish lines from three ER-PR-HER2+ patients, one ER+PR+HER2−, one ER+PR-HER2−and one “triple-positive” (ER+PR+HER2+) patients. Serially passaged xenografts show phenotypic consistency with the tumor of origin at the histopathology level, and remarkable stability across multiple transplant generations at both the genomic, transcriptomic, and proteomic levels. Of 27 lines evaluated fully, thirteen xenografts showed metastasis to the mouse lung. These models thus serve as a renewable, quality-controlled tissue resource, and should prove useful for preclinical evaluation of experimental therapeutics.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-21-01.
P5-21-04: Patient Attitudes towards Undergoing Additional Breast Biopsy for Research Purposes.
Authors: Naim FM , Ballinger R , McLauchlan R , Hadjiminas DJ , Hogben K , Palmieri C , Cleator SJ 
Published: June 2012

Abstract
Background
Acquisition of additional breast tissue for research has become integral to breast oncology research but no data exists regarding patient attitudes to additional, non-diagnostic biopsies. Baseline research biopsies may be obtained as part of the diagnostic process as extra passage(s) of the needle through a ‘generic consent’ process, or as an additional biopsy event after carcinoma diagnosis has been confirmed and eligibility for a specific study has been established. This study sought to explore patient perspectives to such biopsies.
Patients and Methods
Patients attending breast clinics were recruited to complete a questionnaire prior to their consultation (and any interaction with researchers or clinicians seeking consent for research biopsies) which examined willingness to undergo an extra fine needle aspirate (FNA) and/or core needle biopsy (CNB) for research either at time of the diagnostic biopsy (B1) or after diagnosis (B2). Descriptions of FNA and CNB procedures were supplied to those with no prior experience. Patient perspectives towards donating surplus tissue left over from a diagnostic procedure and/or surgery for storage for future research was also explored.
Results: 100 patients were recruited, 42% with a prior history of breast carcinoma, 23% with family history of breast carcinoma and 65%/ 42% with previous experience of CNB/FNA respectively for either benign or malignant disease. Willingness to undergo additional biopsy was greater for the B1 than the B2 time point, but equivalent for CNB and FNA (willingness CNB B1 50% vs B2 26%, willingness FNA B1 50% vs B2 29%). A statistically significant increase in willingness to undergo CNB and FNA at B1 and/or B2 was seen in association with prior diagnosis of breast cancer, family history of breast cancer, previous visit to breast clinic and prior experience of breast biopsy. Reasons for willingness or unwillingness were recorded. 83% of patients expressed a willingness to allow surplus tissue to be stored in a biobank for future research.
Conclusions: When asked by questionnaire prior to clinic consultation, additional research biopsy was much more acceptable if undertaken at time of initial diagnostic biopsy rather than at a later time point. Acceptability was equivalent for CNB and FNA. Previous experience of biopsy, previous attendance to breast clinic, a prior history of breast cancer or family history of breast cancer increased acceptability suggesting that willingness is increased with knowledge of the biopsy procedure.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-21-04.