bluuebunny/crossref_metadata_2025 huggingface dataset:
Retrospective Analysis of Pathologic Criteria in 446 Patients with pT1a and pT1b Breast Cancer: A Study from Two French Anti-Cancer Centers.
Authors: Dalenc F. , Comet B. , Lacroix-Triki M. , Charytanski H. , Chauvet M. , Ceugnart L. , Belkacemi Y.
Published: December 2010

Background: To assess the risk of recurrence and survival after locoregional and systemic treatment regarding biological features among women with a 1cm-maximal size of breast cancer.Material and Methods: Individual clinicopathological data were collected from 446 patients, treated in the Oscar Lambret and Claudius Regaud centers between 2003 and 2006. 5 patients had bilateral breast cancer. Median age was 59y (range: 26-92). None of the patient had node involvement, but patients could have isolated cells. Surgery consisted of lumpectomy, quadrantectomy or total mastectomy in 95%, 1%, 4% of the patients respectively. Sentinelle node biopsy and axillary dissection were performed in 87% and 13% of the patients, respectively. Estrogen receptor (ER, n=447) and Progesterone receptor (PR, n=448) were determined from tumor tissue microarrays using immunohistochemistry (IHC). Cut-off used for ER and PR positivity was 10% of stained cells. Radiation therapy was delivered to 432 breasts (96%; 45-50Gy) and a boost to 296 (69%; 6-16Gy). Nodal RT was delivered in 29% of the patients. Systemic therapy consisted of hormonotherapy in 380 (85%) including aromatase inhibitors in 38%. Chemotherapy was administered in 18 patients. Only two patients received 1 year of trastuzumab.Results:Pathological tumor size was ranged between 1.0 and 10.0 mm (median: 8.0 mm). The majority of tumors (n= 383 or 85%) were ductal infiltrant carcinoma and 42 (9%) were lobular infiltrant. 189 tumors (48%) contained a ductal carcinoma in situ component. 11/381 (3%) presented lymphovascular invasion. The majority were grade III (n=194 or 45%). Only 53 tumors (12%) were ER negative and 129 (28.8%) were PR negative. Nineteen (5.2%) tumors and 4 (0.9%) patients presented tumors with Her 2 overexpression or gene amplification, respectively.After a median survival of 26 months, 8 patients presented locoregional or distant recurrence. Local, locoregional, and distant metatstases were observed in 3, 2 and 4 patients. Among these 8 patients ¾ were aged more than 50y, all of them had tumors > 5mm and grade II or III. 6 out of the 9 patients were HR+. Presences of lymphovascular invasion and Her2+ status were not correlated to recurrence.ConclusionMammographic screening increased the rate of small tumors diagnosed and reduces mortality in breast cancer. It is not known if this reduction is more pronounced in certain groups of patients. In the new era of tumor biology new markers that could predict the sensitivity of tumours to local and systemic therapy have to be determined in further studies for more tailored treatments in small tumors. Further pathologic analyses are ongoing and will be presented.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6026.
Benefit of the Sequential Administration of Docetaxel after Standard FEC Regimen for Node-Positive Breast Cancer: Long-Term Follow-Up Results of the FNCLCC-PACS 01 Trial.
Authors: Coudert B. , Campone M. , Spielmann M. , Symann M. , Eichler F. , Serin D. , Delozier T. , Romieu G. , Canon J. , Orfeuvre H. , Piot G. , Petit T. , Chollet P. , Jerusalem G. , Audhuy B. , Veyret C. , Beauduin M. , Eymard J. , Martin A. , Roché H.
Published: December 2010

Objective: To evaluate the long-term impact on disease-free survival (DFS) and on overall survival (OS) of the sequential administration of docetaxel (D) following FEC100 among patients (pts) with node positive, operable breast cancer.Patients and Methods: Pts with localized, resectable, non pre-treated, unilateral breast cancer were randomly assigned to receive either Arm A: 6 cycles of FEC100 (5FU/epirubicin/cyclophosphamide 500/100/500 mg/m² day 1, every 3 weeks), or Arm B: 3 cycles of FEC100 followed by 3 cycles of docetaxel (D) 100 mg/m² (day 1, every 3 weeks). First chemotherapy cycle was to be started no more than 42 days after surgery. Radiotherapy was mandatory after conservative surgery and hormone therapy was given for 5 years if tumors were positive for at least one hormone receptor. Main inclusion criteria were: age < 65 years, at least one positive node, no metastasis and normal cardiac, hematologic and renal functions. The main end-point of this prospective, non blinded, randomized, multicentre phase III trial was the 5-year DFS. These results have been already published (Roché et. al. J Clin Oncol. 2006 24(36):5664-71). Since this first analysis, survival data have been updated.Results: Between June 1997 and March 2000, 1999 pts were recruited. Main pts characteristics were well balanced between the 2 arms: median age 50 years, conservative surgery 57%, grade III 39%, both HR negative 21%, both HR positive 60%, 1-3 involved nodes 62%. Treatment was completed for 95% and 93.4% of pts in arms A and B, respectively.As of 15 April 2009, with a median long term follow-up of 92.8 months, 639 pts have experienced at least one event: 124 loco regional relapses, 421 metastasis, 68 contra lateral breast cancer, and 26 deaths as first event. A total number of 71 second cancers and 383 deaths have been registered.8-year DFS rates were 65.8% with FEC and 70.2% with FEC-D. Cox regression analysis adjusted for age and number of positive nodes showed a 15% reduction in the relative risk of relapse with FEC-D (HR = 0.846 [95%CI 0.724 – 0.988], p=0.03).8-year OS rates were 78% with FEC and 83.2% with FEC-D. Cox regression analysis adjusted for age and number of positive nodes showed a 25% reduction in the relative risk of death with FEC-D (HR = 0.754 [95%CI 0.616 – 0.922], p=0.006).Conclusion: Initial report of 5-year benefit in DFS and OS with sequential administration of FEC followed by D are fully confirmed at 8 years.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 603.
Tumour Aromatase Expression, a Prognostic for Local Control in Young Breast Cancer Patients after Breast-Conserving Treatment?
Authors: Bollet M. , Savignoni A. , De Koning L. , Tran Perennou C. , Barbaroux C. , Degeorges A. , Sigal-Zafrani B. , Almouzni G. , Cottu P. , Salmon R. , Servant N. , Fourquet A. , de Cremoux P.
Published: December 2010

Introduction: To determine whether the levels of expression of 17 candidate genes were associated with locoregional control after breast conserving treatments of early-stage breast cancers in young, premenopausal women.Methods: Gene expression was measured using RT-PCR in the breast tumors of a series of 53 young (≤40 years), premenopausal patients. All treatments consisted in primary breast conserving surgery followed by whole-breast radiotherapy (+/- regional lymph nodes) with or without systemic treatments (chemotherapy +/- hormone-therapy). The median follow-up was 10 years.Results: The 10-year locoregional recurrence rate was 70% (95% CI 57%-87%). In univariate analysis, no clinical/pathological prognostic factors were found to be significantly associated with a decreased loco-regional control. Expression of three genes was found to be significantly associated with an increased loco-regional recurrence rate: low estrogen receptor beta, low aromatase, high GATA3. Two others were associated with only a trend (p<0.10): low HER1 and SKP2. In multivariate analysis only the absence of aromatase was significantly associated with an increased loco-regional recurrence rate (p=0.003, Relative Risk=0.49 95% CI [0.29-0.82]).Conclusions: Recent data give credit to the fact that breast cancer in young women is a distinct biological entity driven by special oncogenic pathways. Our results highlight the role of estrogen signalling pathways (mainly CYP19/aromatase, GATA3 and ERβ) in the risk of locoregional recurrence of breast cancer in young women. Confirmation in larger prospective studies are needed.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6035.
Identification of an Adverse Biologic Profile in Cyclophosphamide/Metotrexate/5-Fluorouracil Treated Early Stage Breast Cancer Patients by Immunohistochemical Analysis of PI3K/p-Akt Pathway Alterations.
Authors: Mottolese M. , Novelli F. , Di Benedetto A. , Melucci E. , Sperduti I. , Perracchio L. , Buglioni S. , Vici P. , Nisticò C. , Pinnarò P. , Fabi A. , Bria E.
Published: December 2010

Background: Akt activation through PI3K, leads to the phosphorylation of p27 protein thus avoiding nuclear entry and inducing mislocation to the cytoplasm of the protein with consequent inhibition of p27 cell cycle inhibitory function. The prognostic role of PI3K/Akt pathway alterations correlating phenotypic profiles with bio-pathologic variables of known clinical importance have been investigated in a retrospective series of early stage breast cancer patients (BC pts) treated with cyclophosphamide/metotrexate/5-fluorouracil based chemotherapy (CMF).Materials and methods: p-Akt, PI3K and p27 expression were evaluated by immunohistochemistry in a series of stage I/II BC pts who underwent conservative surgery and were candidates to receive CMF adjuvant therapy plus radiotherapy. Multiple Correspondence Analysis (MCA) was used to identify sub-groups of pts with different prognosis, while uni- and multivariate Cox regression analyses were applied to determine the impact of parameters identified by MCA on 10-yrs Disease Free Survival (DFS), together with clinico-pathological features. Receiver Operative Curve (ROC) analysis was adopted for optimal cut-off values.Results: In a series of 133 pts, with a median follow-up of 107 months (range 40 to 141), those pts characterized by high Ki67 index, p53+, p-Akt+, PI3K+ and HER2+ (Adverse Biologic Factors, ABF) were associated with tumor relapse at the MCA analysis. ROC analysis dicotomized between pts with a Favourable Biological Profile (FBP, <3 ABF) and Unfavorable Biologic Profile (UBP ≥ 3 ABF). UBP pts showed a significantly shorter 10- yrs DFS than FBP pts at Kaplan-Meier analysis (67.0% vs 91.3%, p=0.0006). According to the multivariate analysis, the biologic profile was the only significant prognostic indicator for longer DFS (p=0.002). Significant factors at uni- and multivariate analysis are shown in the table.Significant factors at uni- and multivariate analysisFactorsUnivariate (HR, 95% CI)p-valueMultivariate (HR, 95% CI)p-valueGrading3.32 (1.31-8.43)0.012--PgR2.37 (1.03-5.48)0.043--UBP4.24 (1.73-10.40)0.0024.24 (1.73-10.40)0.002 Discussion: These data suggest that the activation of Akt may contribute together with high Ki67 index, p53+, p-Akt+, PI3K+ and HER2+ in predicting recurrence in early stage BC pts homogeneously treated with CMF based therapy.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6036.
Validation of an Array CGH Test for HER2 Status Using Tumor-Targeted DNA Extraction from Formalin Fixed Tissue: Comparison with Fresh Frozen Tissue Results.
Authors: Gunn S. , Gorre M. , Mohammed M. , McCaskill C. , Hibbard M. , Barry T. , Yeh I.
Published: December 2010

Background: Recent clinical validation of a commercially available array CGH test (HerScan™) for determination of HER2 status in 97 cases of newly diagnosed breast cancer showed high accuracy and 97% concordance with fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) results meeting the CAP/ASCO validation requirements for HER2 testing. However, the validation study was performed using fresh frozen tissue, a requirement which precludes the clinical use of array CGH in the majority of breast cancer workups. In this study, 55 additional cases with known HER2 status by IHC and FISH were analyzed by array CGH using a tumor-targeted DNA extraction method designed to achieve optimal results from formalin fixed paraffin embedded (FFPE) tissue.Methods: Tumor tissue from 55 cases of invasive ductal, invasive lobular, and one mucinous carcinoma was visualized and marked on H&E stained sections cut from the FFPE block, with targeted areas captured by slide scraping or 4mm punch. Following proteinase K digestion, DNA was extracted from known HER2 positive (n=25), HER2 negative (n=25), and HER2 equivocal (n=5) samples. Verification of high molecular weight DNA was accomplished by agarose gel electropheresis followed by analysis of the tumor genomes using the HerScan test, a 1524 clone whole genome BAC microarray including 64 probes targeting the HER2/TOP2A amplicons on chromosome 17q.Results: Concordance equivalent to fresh frozen tissue results (>95%) was found between HER2 status obtained by IHC/FISH and array CGH on FFPE tissue. Five cases with equivocal results by IHC/FISH were resolved by array CGH and found to have unamplified partial chromosome 17 polysomy (n=4) and normal HER2 status (n=1). In addition, chromosome 17 status, overall genomic stability, and the presence of co-amplified genes including EGFR, MYC, MDM2, CCND1, and PDGFRalpha were clearly revealed by microarray evaluation in all cases.Conclusions: Array CGH analysis of DNA extracted from FFPE tissue provides a robust and accurate alternative for the clinical determination of HER2 status in newly diagnosed breast cancer. In addition, the complete genomic evaluation of core biopsy specimens afforded by array CGH allows clinicians to deliver personalized cancer care through incorporation of prognostic markers and potential therapeutic targets into treatment planning and prediction of disease outcome.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6038.
Impact of OncoType DXTM Recurrence Score and Tumor Size on Making Chemotherapy Decisions in Breast Cancer Patients.
Authors: Goodwin M. , Hughes J. , Diego M. , Frazier T.
Published: December 2010

Background: Oncotype DXTM is a 21 gene assay that calculates recurrence score(RS) and recurrence risk(RR) over 10 years. Despite the contention that this genomic assay is more accurate than tumor size(TS) and age in predicting outcome, these factors continue to have major impact in decision-making regarding chemotherapy(CT). We analyzed the impact of TS, RS, and age on the decision to give CT.Methods: An IRB-approved chart review of 105 lymph node(LN) negative patients with ER+ T1 and T2 tumors was performed, reviewing age, RS, TS, CT history, Her-2 status, and pathology. RS was low(0-17), intermediate(18-30), or high(>30). TS was divided into T1a(0.1-0.5 cm), T1b(0.51–1.0 cm), T1c(1.1–2.0 cm), and T2(2.1-5.0 cm).Results: Mean patient age was 60.9 years(range 35-82 years). Average(AVG) RS was 20.9; AVG RR at 10 years, 13.6%. Mean TS was 1.5 cm(median 1.3 cm). Overall, 29 patients(27.6%) received CT; 76(72.4%) did not. AVG TS for CT patients was 1.8cm, AVG RS was 29.5, and AVG age was 56.4(range 35-75). Non-CT patients' AVG TS was 1.4cm; AVG RS, 17.7; AVG age, 62.6(range 44-86). 9 patients(8.5%) had T1a tumors with an AVG RS of 19.1, and no patient received CT. 25(23.8%) had T1b tumors with an AVG RS of 21.0, and 5(20.0%) received CT. 51(48.6%) had T1c tumors with an AVG RS of 20.4, and 15(29.4%) received CT. 20(19.0%) had T2 tumors with an AVG RS of 23.1; 9(45.0%) received CT. 41 patients(39.0%) had low RS: 4(9.8%) received CT; 37(90.2%) did not. AVG TS and RS were 1.6cm and 15.0 respectively for CT patients, and 1.5cm and 11.6 for no CT patients. 49 patients(46.7%) had intermediate RS: 13(26.5%) received CT; 36(73.5%) did not. AVG TS and RS were 1.9cm and 22.7 for CT patients; 1.3cm and 22.2 for no CT patients. 15 patients(14.3%) had high RS: 12(80.0%) received CT; 3(20.0%) did not. AVG TS and RS were 1.7cm and 44.7 for CT patients; 1.3cm and 39.3 for no CT patients. 10 patients were Her-2+, 5 with high, 4 with intermediate, and 1 with low RS. 7 had CT. 5 of the 15(33.3%) high RS patients were Her-2+. AVG RS for the Her-2+ patients was 36.2, and AVG TS was 1.9cm. AVG RS was 19.3 for the non-Her-2+ patients. 16 patients were <50 years old. AVG TS was 1.5cm and AVG RS was 24.2. 8 received CT and 8 did not. 89 patients were ≥50. AVG TS was 1.5cm and AVG RS was 20.3. 21(23.6%) received CT and 68 did not. Discussion: AVG RS was 20.9 for all T stages. Overall, 27.6% of patients received CT. Of the 64 with RS>18, only 25(39.1%) received CT; 4(9.8%) of low RS patients still received CT. Patients with larger tumors and younger age were more likely to receive CT. Neither RS, TS, nor age alone seemed to influence the final decision. Multiple factors are still considered by oncologists when making CT decisions, and conversely, patients may not accept CT despite high RS.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6039.
The Influence of Oestrogen Receptor (ER) Status on the Pattern of Recurrence in Early Breast Cancer.
Authors: Mansell J. , Angerson W. , Wilson C. , Doughty J.
Published: December 2010

IntroductionThere is an early peak in recurrence in women with early breast cancer (EBC). This may be related to underlying tumour biology or secondary to a reaction to surgery. We aim to determine if ER expression influences the pattern of recurrence.MethodsData from 3 centres in Glasgow of consecutive women with EBC diagnosed between 1995 and 2001 were examined. Recurrence was defined as invasive disease at any site. Patients were grouped as high ER (≥70% expression), low ER (<70% expression) and ER negative. Kaplan Meier and Time dependent Cox survival analysis was performed.Results2779 women were included with a median follow up of 5.5yrs. 1915 (68.9%) had high ER, 310 (11.2%) had low ER and 554 (19.9%) were ER negative. At 5yrs the cumulative recurrence rates were 10.4% (9.0-11.8) vs. 19.2% (14.7-23.7) vs. 30.5% (26.6-34.4) respectively. Time dependent multivariate analysis showed that low ER and ER negative were significantly stronger predictors of recurrence within 2.5yrs from diagnosis than at later intervals (p = 0.024 and p <0.001 respectively). The hazard ratios for recurrence within 2.5 yrs for low ER and ER negative groups were 2.23 (95% CI 1.41-3.54, p=0.001) and 3.68 (2.60-5.21, p <0.001). Beyond 2.5yrs the respective hazard ratios were 1.12 (0.77-1.64, p=0.558) and 1.40 (1.03-1.90, p=0.031)ConclusionsWomen with Low ER expressing and ER negative tumours are initially at a significantly increased risk of recurrence compared with women with high ER expressing tumours suggesting that underlying tumour biology contributes to the initial peak in recurrence.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6042.
Breast Density, Ki67 and Larger Extensions of Breast Cancer.
Authors: Mameri C. , Mameri C. , Mameri C. , Sobral L. , Chambo D. , Totola H. , Mameri Filho J.
Published: December 2010

Background: Studying breast cancer, our data has demonstrated higher occurrence of large extensions and/or multiple synchronic malignant lesions in dense breasts. Following this investigation, we decided to correlate breast density with Ki67 on tumor specimens and disease extent on MRI. Methods: From August 2005 to April 2009, 193 consecutive patients diagnosed with breast cancer were evaluated about number and size of breast malignant lesions, about fibroglandular (FG) density on Mammography and about proliferation marker on immunohistochemistry of tumor cells. Fibroglandular density was classified using criteria: <50%; >50%. All patients had evaluation of hormonal receptors (estrogen and progesterone), HER2/neu and Ki67 on immunohistochemistry of tumor blocks. They were also submitted to bilateral breast MRI in 1.5 T Excite/GE equipment, 5 sequences FSPGR (90 seconds each, 1 preinjection, 4 postinjection of gadolinium 0.16 mM/kg, 3.5/0 thickness) to evaluate size of primary lesion and presence of additional malignant foci. Additional findings were submitted to pathological examination (core or excisional biopsy). Results: Among 193 patients, 66 (34%) presented FG density <50% and 127 (66%) had FG density >50%. Eighty one patients (42%) presented large single tumor (35 cases) and/or multiple synchronic malignant lesions (46 cases), which 16/81 (19%) had FG density <50% and 65/81 (81%) had FB density >50%. In 112/193 patients (58%) with small single tumor on MRI, 66 (59%) had density >50%. Expression of Ki67 was 30% positive or higher in 17/66 patients (25,7%) with FG density <50% and in 70/127 patients (55%) with FB density >50%. Correlation between high expression of Ki67 (30% or higher) and extent was significant for patients with large single tumor (17/35=48,5%), but not for patients with multiple synchronic lesions (11/46=24%). Expression of Ki67 was 30% positive or higher associated with HER2 overexpression (3+) or with triple negative tumors in 95% of both conditions (multiple synchronic or larger single tumors). Conclusions: This study demonstrated that dense breasts are associated with larger extensions of breast cancer and suggests that FB density can be correlated to higher expressions of Ki67 on immunohistochemistry, especially in single tumors.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6043.
Consistency of Effect of Docetaxel-Containing Adjuvant Chemotherapy in Patients with Early Stage Breast Cancer Independent of Nodal Status: Meta-Analysis of 12 Randomized Clinical Trials.
Authors: Laporte S. , Jones S. , Chapelle C. , Jacquin J. , Martín M.
Published: December 2010

BackgroundUp to now taxanes have been extensively evaluated in the treatment of node-positive early-stage breast cancers (ESBC). Recently, more data have become available in patients with node-negative as well as node-positive ESBC treated with docetaxel-based regimens. We conducted a meta-analysis of randomized ESBC trials in order to evaluate the efficacy of adjuvant docetaxel-based regimens in terms of disease-free survival (DFS), overall survival (OS), and whether treatment effects are maintained across different nodal status subpopulations.MethodsStudies including at least 100 patients and presented or published before December 31, 2008 were retrieved by searching the MEDLINE, CANCERLIT, and Cochrane Library databases and the proceedings of major conferences. Outcomes recorded were DFS and OS. We extracted hazard ratios (HR) and 95% CIs for DFS and OS from each trial and obtained pooled estimates using an inverse-variance model in a random effect model. In trials including both node-positive and node-negative breast cancers, and with nodal status as a clear stratification factor at randomization, HR were extracted for each subpopulation separately. A HR less than 1 indicated that docetaxel was superior to the no-taxane regimen.ResultsTwelve randomized phase III studies were included in the meta-analysis (20 698 patients). Three subsets of trials/strata were used: node-positive (10 trials or strata, 14 787 patients), node-negative (4 trials/strata, 4 274 patients), or combination of both (2 trials, 1 637 patients). Overall, the pooled HR estimate [95% CI] for DFS was 0.81 [0.74;0.89] (P<0.001) in favor of docetaxel-based chemotherapy. The results are the same for node-positive (HR=0.84 [0.77;0.91]) and node-negative breast cancer (HR=0.84 [0.72;0.99]). The overall estimated HR for OS was 0.81 [0.72;0.91] (P<0.001). Results by nodal status subpopulations are awaited.ConclusionThis meta-analysis of 12 recent randomized phase III trials shows that adjuvant docetaxel-based chemotherapy compared to regimens without taxanes is associated with an improvement in DFS and OS independent of nodal status. Other analyses will also be presented.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 605.
New HER2 Assay Using Trastuzumab for the Selection of Trastuzumab Responding Breast Cancer: The Positivity Is Significantly Associated with Pathologic Complete Response after Preoperative Chemotherapy.
Authors: Kim S. , Baek N. , Kwon B. , Kwon Y. , Ro J. , Park I. , Lee E.
Published: December 2010

Background:The evaluation of HER2 status is required for trastuzumab therapy in breast cancer. Although there are a few methods for an evaluation of HER2 status, theoretically the better method would be to check trastuzumab uptake itself in the tumor after trastuzumab administration. Therefore, we developed a different HER2 test (QHerceptest) using trastuzumab to improve an accuracy in the selection of patient for trastuzumab therapy.Patients and Methods:31 patients with HER2 positive (IHC 3+: 19 and IHC 2+ with FISH positive: 12) early breast cancer who were enrolled in a phase II preoperative paclitaxel, gemcitabin and trastuzumab (PGH) combination chemotherapy trial were evaluated. The pre-chemotherapy tumor specimens were obtained from the breast mass (n=24) or metastatic lymph nodes (n=7). After completing 6 cycles of PGH therapy, all patients underwent breast conserving surgery or mastectomy. We applied trastuzumab and Quantum dot conjugated goat anti-human IgG (QD-IgG, 655nm, Invitrogen) in the process of immunuhistochemistry for HER2 using formalin-fixed paraffin embedded specimen. After antigen retrieval, trastuzuamb was applied followed by QD-IgG. The result of QHerceptest was scored as negative, weak positive, moderate positive, or strong positive, and its relative uptake (RU) were quantified by imaging analysis program (Q-IHC, http://www.bio-miblab.org).Results:The uptake of trastuzumab by QHerceptest was heterogenous, varying between 1.3% to 193.7%. Twenty one of 31 (67.7%) patients achieved pathologic complete response (pCR): 11 of 12 patients (91.7%) with QHerceptest strong positive tumors, 6 of 9 patients (66.7%) with QHerceptest moderate positive tumors, and 4 of 7 patients (57.1%) with QHerceptest weak positive tumors, and none of 3 patients (9.4%) with QHerceptest negative tumors (p=0.0203). Besides, RU was significantly different between non-pCR and pCR groups (43.9±38.3, 80.8±47.1, p=0.0396)Conclusion:We developed a new HER2 assay using trastuzumab and applied to clinical specimen. This assay showed heterogenous trastuzumab uptake in this patient population. Although the data need to be verified by further study, the assay could possibly eliminate patients among HER2 positive breast cancer who will not get benefit by trastuzumab .This study was supported by NCC Grant No 0710292-2 and NCC Grant No 0610240.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6050.
HER2+ Tumors with Lack Steroid Receptors Showed a Shorter DFS but Similar OS Compared to HER2+ Tumors That Also Express ER and/or PR.
Authors: Gómez H. , Vigil C. , Cruz W. , Velarde R. , Abugattas J. , Suazo J. , Vidaurre T. , Neciosup S. , Vallejos C.
Published: December 2010

Background: HER2 expression is widely measured on tumor tissue from breast cancer patients since it gives prognostic and predictive information. Data suggest that breast cancer growth is regulated by the coordinated action of the estrogen receptor (ER) and receptor tyrosine kinase signaling pathways. The aim of this retrospective analysis was to evaluate the additional prognostic value of the ER/PR status for the subset of patients with HER2-positive tumors.Methods: From 2000-2002, 203 breast tumors were tested for HER2 and steroid receptors levels. HER2-positivity was defined as ≥2 copies of the HER2 gene by FISH or 3+ by IHC. A cut-off point of 10 % was used as positivity for ER and/or progesterone receptor (PR) levels.Results: Among the 203 patients, 103 had HER2+/ER-/PR- tumors and 100 had HER2+/ER+ and/or PR+ tumors. Patients' characteristics were comparable between the two groups as far as age, menopausal status, pTNM (stage I-II-III) status and type of initial therapy. All patients had surgery followed by standard chemotherapy and radiotherapy and hormonal therapy if the tumor was ER+ or PR+. No patients received adjuvant treatment with trastuzumab. The median follow-up for the entire cohort was 73 months (range 12-110). Comparisons of disease-free survival (DFS), overall survival (OS) as well as site of first recurrence were made between the two groups. The 5-year DFS was statistically different between the two groups: 69.9% for HER2+/ER-/PR- patients and 81.0% for the HER2+/ER+ and/or PR+ (p=0.037). The 5-year OS was not different between the two groups with 82.5% for HER2+/ER-/PR- patients and 86.0% for the HER2/ER+ and/or PR+ (p=0.402).Conclusions: Patients with HER2+/ER-/PR- breast cancers treated with surgery and standard adjuvant chemotherapy exhibit a statistically worse DFS compared to patients with HER2+/ER+ and/or PR+ tumors. However, overall survival was similar in both groups; additional factors should be evaluated to explain this finding.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6052.
VARS2 V552V Variant as a Prognostic Marker in Patients with Early Breast Cancer.
Authors: Chae Y. , Park H. , Jeong J. , Yang J. , Lee M. , Park J. , Kim S.
Published: December 2010

Purpose: The present study analyzed the polymorphisms of DNA repair genes and their impact on survival of patients with early breast cancer.Patients and methods: A total of 240 patients with surgically resected early invasive ductal breast cancer were enrolled in the present study, where patients who underwent neoadjuvant treatment were excluded. The genomic DNA was extracted from paraffin-embedded tumor-free tissue or blood, and thirteen single nucleotide polymorphisms of 12 DNA repair genes were determined using the Sequenom Mass array system.Results: Among the target SNPs, VARS2 rs2074511 and POLE rs5744857 were found to correlate with relapse-free survival (RFS) after curative surgery in the log-rank test. There was no difference in the clinical and tumor characteristics according to the genotypes of these two coding variants except for the higher incidence of positive ER in patients with the GG genotype of POLE rs5744857 (p = 0.025). Multivariate analysis showed that the GG genotype of VARS2 V552V (rs2301717) was marginally associated with a better RFS than the combined AA and AG genotype (HR = 0.298; 95% CI = 0.089-0.995; p = 0.049). However, there was no significant association with overall survival.Conclusion: VARS2 V552V may be considered as a prognostic factor of survival in patients with early breast cancer.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6055.
Single Nucleotide Polymorphism (SNP) in RASSF1 and Clinical Outcomes of Breast Cancer Patients Treated with Neoadjuvant Docetaxel/Doxorubicin Chemotherapy.
Authors: Keam B. , Kim H. , Im S. , Im S. , Han S. , Han S. , Oh D. , Oh D. , Kim J. , Kim J. , Lee S. , Lee S. , Chie E. , Chie E. , Han W. , Han W. , Kim D. , Kim D. , Cho N. , Moon W. , Kim T. , Kim T. , Park I. , Noh D. , Noh D. , Heo D. , Heo D. , Ha S. , Ha S. , Bang Y. , Bang Y.
Published: December 2010

PurposeThe tumor suppressor gene RASSF1 (Ras association domain family member 1) regulates cell cycle, progression, apoptosis, and microtubule stability, and is inactivated by promoter hypermethylation in breast cancer. We analyzed the SNPs in RASSF1 and their predictive and prognostic value in stage II or III breast cancer patients who received neoadjuvant docetaxel/doxorubicin chemotherapyMethodsA total of 139 stage II or III breast cancer patients who received neoadjuvant docetaxel/doxorubicin chemotherapy were enrolled in this study. The patients received three cycles of neoadjuvant chemotherapy followed by curative surgery, and received additional three cycles of docetaxel/doxorubicin chemotherapy as an adjuvant. Germline DNA from peripheral blood mononuclear cells was extracted. The genotypes were performed using Illumina GoldenGate® Assay. We analyzed 3 SNPs in RASSF1 genes: rs3213621 T>C in 3'UTR, rs2073499 G>A in intron, and rs2073498 C>A in exon 3 Ala133Ser.ResultsThe overall radiologic response rate (RR) for neoadjuvant chemotherapy was 79.8% and 10 patients (7.2%) achieved a pathologic complete remission (pCR). None of the SNPs were correlated with radiologic RR or pCR rate. SNP in intron of RASSF1 (rs2073499) was associated with relapse free survival (RFS). RFS was longer in GA/AA genotype than GG genotype (Hazard ratio [HR]=0.374, p=0.034) After adjusting age and hormone status, prognostic value of RASSF1 SNP remained significant (HR=0.393, p=0.050). Other two SNPs were not significantly associated with RFS.ConclusionsThe GA/AA genotype in SNP of RASSF1 (rs2073499) is associated with significantly longer RFS than the GG genotype. Further research is warranted to identify the biologic characteristics of RASSF1.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6061.
The Developing Nature of Menstrual and Reproductive Factors Associated with Breast Cancer Risk among Women in an Urban Region of China.
Authors: Gao J. , Zhang B. , Lian R. , Yue R. , Liang X. , Wang G.
Published: December 2010

Introduction: The incidence rate of female breast cancer has increased rapidly over the past 20 years in China. It has become the leading cause of newly diagnosed cancer and a major cause of mortality among women in some large Chinese cities with higher socio-economic status. This was partly explained by the change of lifestyle and reproductive risk factors. However, little data exists on the extent to which the menstrual and reproductive factors with breast cancer risk have changed in other less developed Chinese cities.Method: One cross sectional study was conducted in urban region of Taiyuan of China from September 2008 to March 2009. One thousand and five hundreds healthy women were invited to complete a self-administered questionnaire. Participants' characteristics, including age, education, occupation, weight, height, age at menarche, age at first birth, parity, duration of breastfeeding, and age at menopause were collected and analyzed. Study subjects were divided into six groups: younger than or equal to 20, 21 to 30, 31 to 40, 41 to 50, 51 to 60 and older than 60 years old.Results: One thousand four hundreds and twenty eight women returned the questionnaire. The response rate was 95.2%. Median age of women in this study was 39 years old (range: 16 – 86 years old). There was a 4.8cm difference in the mean height between women born in 1990s and 1940s. The average age at menarche dropped from 16 years for women aged above 60 to 14.3 years for those younger than 20 years old. The average birth rate markedly decreased from 4.4 births per woman in the 1960s to 1.1 births per woman in the 1990s. The mean age at first birth increased 5.6 years through the period from the 1940s to 1980s. The breastfeeding time significantly reduced from 20.3 months to 3.6 months over 40 years.Conclusion: This study indicates that there has been significant change in the menstrual and reproductive factors associated with breast cancer risk in the last 40 years. These changes will certainly influence the incidence rate of breast cancer in the local city. Therefore, measures are needed to enhance the awareness of breast cancer and its early-detection methods among the urban region women in China.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6068.
Prospective Study of Vitamin D Levels in Sydney Patients with a New Diagnosis of Breast Cancer.
Authors: Harris C. , Lynch J. , Thomas D.
Published: December 2010

Background: Vitamin D deficiency has been associated with malignancy in many reported studies. More recently an association has emerged between low levels of vitamin D and poorer outcome in breast cancer. Australian recommendations for vitamin D are defined as deficient if 25-OH vitamin D levels are ≤ 50nmol/L and severely deficient if ≤12.5nmol/L. We hypothesise that lower levels of vitamin D are associated with a more advanced disease at diagnosis.Methods: We conducted a prospective study in patients with a new diagnosis of breast cancer who presented to our area health service from January 1st 2008 to October 1st 2008. Patients were also included if their diagnosis occurred in the preceding 6 months and were referred onto the multidisciplinary breast care team for treatment in this time period. 25-OH vitamin D levels were measured for each patient during staging and details collected about each patients breast cancer characteristics. Patients completed a questionnaire assessing comorbidities, medications, diet and lifestyle effects which were likely to influence vitamin D levels. We used stage, disease requiring chemotherapy, and the need for mastectomy as surrogate endpoints for assessing disease extent.Results: 166 patients were recruited with a median age of 58 (range 21-100). The median vitamin D level was 48 (range of <10 to 170). 53% (n=88) patient were deficient (25-OH vitamin D ≤ 50nmol/L), 2% (n=3) patients were severely deficient (25-OH vitamin D ≤ 12.5nmol/L) and only 14% had sufficient levels (25-OH vitamin D >75nmol/L). The majority of patients reported the recommended sun exposure during weekdays (77%) and on weekends (86%). Most were had fair or medium skin tones (83%) and less than 10% wore sunscreen daily. Only 22% of patients had a potential identifiable cause for vitamin D deficiency. Vitamin D levels did not correlate directly with stage of disease (RR 1.03, 95% CI 0.86-1.23 p=0.85), however other surrogates for more advanced disease including the need for more aggressive treatment either with chemotherapy (RR 1.30, 95% CI 1.05-1.61 p=0.02) or mastectomy (RR 1.67 95% CI 1.03-2.7 p=0.04) were associated with low levels of vitamin D.Conclusions: Vitamin D deficiency is very prevalent in our population of patients diagnosed with breast cancer, despite perceived adequate sun exposure and lack of obvious cause. Lower levels of vitamin D did not directly correlate with more advanced stage of the disease at diagnosis; however patients with low levels of vitamin D were more likely to need chemotherapy or require mastectomy, which may suggest a more aggressive disease. The cause of breast cancer remains multifactorial and vitamin D deficiency is only one part of this complex disease.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6071.
An Intervention for Moving Long Overdue Women To Get a Mammogram.
Authors: Costanza M. , Luckmann R. , White M. , Rosal M. , LaPelle N. , Cranos C.
Published: December 2010

Background: While there is substantial evidence that mammography screening decreases breast cancer mortality, as many 15 million American women are overdue for a biennial mammogram. This pilot study addressed the usefulness of a computer-assisted telephone counseling program in motivating reluctant or resistant women to get a mammogram.Methods: 127 women, aged 45-79, enrolled in primary care practices and without a documented mammogram for >=27 months were identified, approved by providers and eligible for study. All women had adequate health insurance and all had received a screening recommendation from their provider. The intervention included a mailed educational booklet followed by tailored counseling call, motivational interviewing and facilitated short-interval test scheduling. Using a computer-assisted telephone counseling program, the counselor identified the subject's stage of readiness to get a mammogram, reviewed the booklet in detail, clarified any misinformation and discussed specific barriers. At the conclusion of counseling, the counselor used motivational interviewing techniques to reconcile subjects' stated values with their stage of readiness. Outcome measures included stage change and completed mammograms within 12 months of the call as documented in the claims data.Results: Of the 127 eligible women, 45 (35%) agreed to counseling. 11% of these women had never had a mammogram, 7% had not had one in 48-59 months; 62% had not had one in>=60 months. At the start of the call, 11% had decided not to get mammograms, 16% were undecided about whether to get one, 44% were planning to get one but had no specific appointment and 4% had a mammogram appointment. Of these 45 women, 73% moved 1 or more stages closer to getting a mammogram. Of 13 women initially not planning to get a mammogram, 3 scheduled a mammogram and 3 stated an intention to get one. 75 % of women who scheduled a mammogram with the counselor went on to complete the test. 58% of the 45 counseled women actually got a mammogram. Of the 82 eligible women who refused to be in the study or did not respond to the telephone calls, only 21% got a mammogram. (57.8% vs. 21.3%, p<.001)Conclusions: It is possible to reach mammogram-reluctant women and to move them to complete a mammogram. Many of the counseled women were not against having mammograms but had no definite plans to get one. Women who schedule a mammogram are likely to keep the appointment. Given the low rate of mammography in those refusing to participate or not answering our calls, we suspect this group held a large number of mammogram-resistant women.For these women, additional interventions, such a monetary enhancement might prove useful. A prospective controlled trial to evaluate this intervention is currently underway. Supportedby NIH R21-100286

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6076.
First Results from the “Patient's Anastrozole Compliance to Therapy Programme” (PACT) Evaluating the Impact of a Standardized Information Service on Compliance in Postmenopausal Women with Early Breast Cancer (EBC) Receiving Adjuvant Endocrine Therapy.
Authors: Harbeck N. , Hackisch C. , Blettner M. , Lück H. , Hadji P. , Landthaler R. , Martin R. , Schmitt D. , Schulte H. , Rexrodt von Fircks A. , Haidinger R. , Jäger D. , Zaun S. , Kreienberg R.
Published: December 2010

Background: In adjuvant treatment of hormone-responsive breast cancer, existing data document that 23% and 50% of patients were non-compliant after the first and fourth year of tamoxifen (TAM) therapy, respectively. Here, we present the PACT-study that aims to increase awareness, motivation and adherence to oral hormonal therapy, namely the aromatase inhibitor anastrozole, in routine clinical practice by simple interventions such as written standardized mailings and reminder services.Materials and Methods: In this two arm, parallel group trial with a primary duration of 12 months and 60 months follow-up, women with hormone receptor positive EBC receiving anastrozole once daily were randomized to either routine clinical care alone or to receiving additional standardized information for the first 12 months of adjuvant therapy. Primary endpoint is compliance rate in the standard versus intervention arm after 12 months, where compliance is defined by an 80% intake of the total medication. Secondary endpoints include persistence on therapy, reasons for non-compliance, influence of baseline characteristics, and of compliance on clinical outcome parameters.Compliance was evaluated by self report using standardized, detailed questionnaires at baseline and after each year of treatment. In addition, the prescription data for each patient from hospital records and physician recall was collected. Finally, quality of life and patient satisfaction were assessed using standardized questionnaires.Results: From July 2006 until November 2008, 4.924 women were enrolled with a median patient age of 64 years. Besides demographic data and patient characteristics results of patient's self reporting data will be shown for the first time at this meeting.Conclusion: PACT is the largest prospective investigation on compliance regarding an aromatase inhibitor as adjuvant therapy so far. The programme's goals are to clarify what aspects influence patients' adherence to prescribed medication and how motivation for regular intake can be accomplished. Furthermore, PACT seeks to prove if a simple intervention such as a standardized information and reminder services throughout the first year of treatment may improve compliance and thus eventually influence treatment outcomes.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6079.
Clinical Benefit Rate and Time to Response in RIBBON-1, a Randomized, Double-Blind, Phase III Trial of Chemotherapy with or without Bevacizumab (B) for the First-Line Treatment of HER2-Negative Locally Recurrent or Metastatic Breast Cancer (MBC).
Authors: Robert N. , Dieras V. , Glaspy J. , Brufsky A. , Bondarenko I. , Lipatov O. , Perez E. , Yardley D. , Phan S. , Bhattacharya S. , O'Shaughnessy J.
Published: December 2010

BackgroundRIBBON-1, a Phase III, multicenter, randomized, placebo-controlled trial in patients with previously untreated MBC was designed to evaluate the efficacy and safety of adding bevacizumab (B) to chemotherapy regimens including capecitabine (Cape; n=615); a taxane (T; n=307), or an anthracycline (Anth; n=315) compared with chemotherapy alone. Pre-specified analyses of progression-free survival PFS) in the Cape and pooled T/Anth cohorts, the primary endpoints of the study were increased upon addition of B. In the Cape cohort, median PFS increased from 5.7 to 8.6 mo (HR=0.69, p-value=0.0002) and in the T/Anth cohort, it increased from 8.0 to 9.2 mo (HR=0.64; p-value<0.0001).MethodsRECIST was used to determine objective response rate (ORR). Patients without a post-baseline tumor assessment were considered non-responders. The primary analysis for the ORR and the duration of response was performed using only patients with measurable disease at baseline. ORR was formally compared between the two treatment arms using the Mantel-Haenszel Chi-squared test, using the randomization stratification factors. Fisher's exact test was also performed. Clinical benefit rate (CBR) was defined as the proportion of patients with a complete or partial response or with stable disease at Week 24. Exploratory analyses of CBR and time to response are provided here. Summary statistics of time to response at Week 9 will be presented as will the final analysis of the secondary endpoint of overall survival.ResultsAnalyses of ORR and CBR are provided in the following table. CapeTaxaneAnth PL (n=206)B (n=409)PL (n=104)B (n=203)PL (n=103)B (n=212)Patients with measurable disease, n (%)161 (78.2)325 (61.1)85 (81.7)161 (79.3)92 (89.3)184 (86.8)ORR, %23.635.435.350.340.252.2CR, n (%)1 (0.6)7 (2.2)3 (3.5)4 (2.5)2 (2.2)3 (1.6)PR, n (%)37 (23.0)108 (33.2)27 (31.8)77 (47.8)35 (38.0)93 (50.5)Difference between arms, %11.815.012.0p-value, unstratified0.00940.030.073Duration of ORMedian, mo7.29.28.68.46.08.1HR (95% CI)0.61 (0.39–0.96)0.75 (0.45–1.27)0.53 (0.34–0.83)Log-rank p-value0.03260.2840.0047Clinical benefit rate*, %47.164.365.471.969.980.7p-value, unstratified<0.00010.240.04CR+PR at Week 9, %20.229.438.354.544.451.1B=bevacizumab, cape=capecitabine, CI=confidence interval, HR=hazard ratio, OR=objective response, PL=placebo, T/Anth=taxane/anthracycline.*For randomized patients.ConclusionsIn patients with HER2-negative MBC, the addition of bevacizumab to capecitabine, taxane or anthracycline chemotherapy induces more responses and those responses occur more rapidly. For capecitabine and anthracycline the addition of bevacizumab leads to objective responses that last longer.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6084.