bluuebunny/crossref_metadata_2025_split huggingface dataset:
P5-14-13: Favorable Prognosis in Patients with T1a,b Node-Negative Triple Negative Breast Cancers Treated with Multimodality Therapy.
Authors: Ho AY , Gupta G , Perez CA , King TA , Patil SM , Rogers KH , Brogi E , Morrow M , Hudis C , Traina T , McCormick B , Powell SN , Robson ME 
Published: June 2012

Abstract
Purpose: To evaluate the clinical characteristics, natural history and outcomes in patients with ≤1cm, node-negative triple negative breast cancer (TNBC).
Materials and Methods: After excluding patients who received neoadjuvant therapy, 1,022 TNBC patients who received definitive breast surgery from 1999 to 2006 were identified from an institutional database. Among these, 194 patients had node-negative tumors ≤1cm and comprise the study population. Clinical data was abstracted and survival outcomes were analyzed.
Results: Median follow-up time was 71 months (range 2–143). Median age at diagnosis was 55.5 years (range 27–84). T stage was T1mic in 16 (8.2%), T1a in 49 (25.3%), T1b in 129 (66.5%). The majority of tumors were poorly differentiated (N= 142, 73%), lacked lymphovascular invasion (N= 170, 87.6%) and were screening-detected (69%, N=134). Breast-conserving surgery (BCS) was employed in 129 (66.5%) and mastectomy in 65 (33.5%) patients. 113 (58%) patients received adjuvant chemotherapy and 123 (63%) received whole breast radiation. Patients who received chemotherapy tended to have more adverse clinical and disease features (younger age,T1b, poor tumor grade; all p&lt;0.05). For the entire group, 5 year local recurrence-free survival was 96% and distant metastasis-free survival was 95%, with no difference in distant relapse rates between T1mic/T1a vs. T1b patients (94.5% vs 95.5%, p=0.81 )or by receipt of chemotherapy (95.9% vs 94.5%, p=0.63).
Conclusion: Excellent 5-year locoregional and distant control rates were achievable in patients with TNBC tumors ≤ 1.0 cm, 58% of whom received chemotherapy. These results identify a group of TNBC patients with favorable outcomes following early detection and multimodality treatment.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-14-13.
P5-14-18: Today's Estrogen Receptor Positive/Her-2-neu Receptor Negative Breast Cancer Patients Do Significantly Better Than Yesterday's Estrogen Receptor Positive Breast Cancer Patients.
Authors: Madsen EV , Elias SG , Gobardhan PD , van Oort PM , van der Ent FW , Nieweg OE , Valdés Olmos RA , Smidt M , van Dalen T 
Published: June 2012

Abstract
Background: Her-2-neu receptor (Her2) positive and triple negative breast cancer patients have a poor prognosis. The majority of cancers are characterized as estrogen receptor (ER)+/Her2- and these patients may now have a better prognosis compared to before the introduction of the Her-2-neu receptor.
Material and methods: Since 1997 3424 patients were treated for cT1-2N0 breast cancer in three hospitals. Determination of Her2-neu status was introduced between 1999 and 2004. Trastuzumab treatment has been given routinely since 2005. Survival was evaluated for the different groups; ER+/Her2-, ER+/Her2+, ER+/Her2 unknown (status not determined).
Results: 2284 patients had ER+/Her2- tumors, 259 had ER+/Her2+ tumors and 262 had ER+/Her2 unknown tumors. Systemic treatment was given to 48.4%, 71.0% and 43.9% respectively. Estimated 5-and 10-year overall survival was 92.0% and 82.2% for ER+/Her2-, 91.6% and 70.8% ER+/Her2+ and 83.4% and 72.2% for ER+/Her2 unknown (p &lt; 0.001). The outcome differences between ER+/Her-2- and ER+/Her-2 unknown tumors remained following adjustment for tumor malignancy grade, nodal status and adjuvant systemic treatment (OR 0.8: CI 0.72 — 0.88; p&lt;0.001). For patients with ER+/Her2+ tumors 5 year overall survival was comparable with ER+/Her2- tumors but 10 year overall survival was comparable with ER+/Her2 unknown tumors.
Discussion: Patients with ER+/Her2- tumors have a significantly better outcome than patients who were classified as ER+ before the assessment of Her-2-neu over-expression. Current prognostic models do not take this effect into account.
The branching off of the survival curve for patients with ER+/Her2+ tumors can be explained by the standard use of trastuzumab during the last five years.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-14-18.
P5-20-08: Multicenter Results of Scalp Cooling To Prevent Chemotherapy-Induced Alopecia in 1500 Breast Cancer Patients.
Authors: van den Hurk C , Peerbooms M , Komen M , Nortier H , Breed W 
Published: June 2012

Abstract
Background Chemotherapy-induced alopecia (CIA) is a frequent occurring side effect of cancer treatment that has high psychological impact on many patients and their relatives. CIA may be prevented by scalp cooling.
Methods Breast cancer patients who received scalp cooling could participate in this registration study from 2006 and onwards. Nurses and patients completed questionnaires. Scalp cooling was performed using the Paxman PSC1 or PSC2 system and was considered satisfying when patients did not wear a wig or head cover. Logistic regression analyses will be used to examine determinants of the scalp cooling result, including age, type/length/thickness/chemical manipulation (dyeing, waving, colouring) of hair, type/dose of chemotherapy, cytostatic infusion time, post-infusion cooling time, dampening hair or use of conditioner before scalp cooling and previous treatment with chemotherapy.
Results The use of scalp cooling increased from 4 hospitals in 2005 to 60 out of 100 Dutch hospitals in 2011. The registration comprised about 1500 scalp cooled breast cancer patients of whom 79% were treated in the adjuvant setting. Overall, patients’ satisfaction with the result of scalp cooling was 50%, but varied for different chemotherapy schemes and dosages from 8% in docetaxel 75 mg/m2, doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2 (TAC) to 81% in paclitaxel 70–90 mg/m2. The results of the regression analyses will be presented at the conference.
Discussion Scalp cooling is effective in most commonly used chemotherapy regimens for breast cancer patients. Therefore, scalp cooling should be offered more often. Efficacy depends on the type and dose of chemotherapy. Other factors influencing the result have never been studied in multivariate analyses before. Scalp cooling is ineffective in patients treated with a combination of a taxane and an anthracyclin. The frequent use of scalp cooling in the adjuvant setting indicates minimal fear for an increased incidence of scalp skin metastases after scalp cooling in breast cancer patients. Multicenter registration of results improves information for medical professionals and patients and will lead to more frequent use of scalp cooling and improvement of the method.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-20-08.
P5-23-01: The Impact of Primary Tumor Resection on the Survival of Patients with Stage IV Breast Cancer According to Molecular Subtype.
Authors: Ahn SK , Moon H-G , Kim JS , You JM , Shin HC , Han W , Noh D-Y 
Published: June 2012

Abstract
Purpose: The main treatment for stage IV breast cancer is currently systemic therapy. Surgical resection of the primary tumor is usually done for treating the tumor-related complications. Recent studies have suggested that surgery may improve the long-term survival of stage IV breast cancer patients. We evaluated the impact of the primary surgical resection site on the survival of stage IV breast cancer patients according to molecular subtype using nationwide Korean breast cancer registry data.
Methods: We analyzed the records of the stage IV breast cancer patients from Korean Central Cancer Registry (KCCR) between 1999 and 2008. We used clinical assays to distinguish luminal A (HR+/HER2−, n=290), luminal B (HR+/HER2+, n=154), Basal-like (HR-/HER2−, n=107) and HER2 (HR-/HER2+, n=145). The clinical and tumor characteristics, the type of treatments and the overall survival were compared between the surgically versus nonsurgically treated patients according to molecular subtype.
Results: Of the 1091 identified patients, 719 (65.9%) received surgical excision of their primary tumor and 372 (34.1%) did not. The mean survival was 86 months versus 43 months for the surgically treated patients vs. the patients without surgery, respectively (p&lt;0.001). On a multivariate analysis with using the Cox model and after adjusting for tumor size, visceral metastases, the number of metastatic sites and bone only metastases, surgery was an independent factor for improved survival in patients with luminal A type (Hazard Ratio, 0.505; 95% Confidence Interval, 0.265−0.962, p=0.038) but not in those with luminal B (p=0.192), basal-like (p=0.128) and HER2 subtype (p=0.114).
Conclusion: Surgical resection of the primary tumor in stage IV breast cancer patients was independently associated with improved survival only in luminal A subtype.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-23-01.
PD01-07: AR Overexpression and Aromatase Inhibitor Resistance in Breast Cancer.
Authors: Rechoum Y , Iacopetta D , Barone I , Ando’ S , Morales SF , Weigel NL , Fuqua SAW 
Published: June 2012

Abstract
Background: Aromatase inhibitors (AIs) have emerged as the therapy of choice for the treatment of estrogen receptor alpha (ERα)-positive breast cancer. However, many patients develop resistance to AI treatment. Although the involvement of the ERα in AI resistance is well established, the role of the androgen receptor (AR) is not known. It has been estimated that about 60%-70% of ERα-positive breast cancer co-express the AR, and that AR agonists can either inhibit or stimulate breast cancer cell proliferation. Thus it is important to determine if there are biomarkers predicting AR's effects in breast tumors. We have previously shown a role for AR-overexpression in tamoxifen resistance in ERα-positive MCF-7 breast cancer cells; here we hypothesized that AR overexpression might similarly be involved in resistance to the AI anastrazole (Anas).
Materials and Methods: Stable transfection of MCF-7 cells was performed to generate cell lines that express the aromatase gene (MCF-7 BK Arom) and then co-transfected with an AR expression vector (MCF-7 AR Arom). Aromatase and AR expression levels were evaluated by western blot analysis, and the enzyme activity was evaluated using aromatase activity assays. Proliferation was tested using anchorage independent soft agar assays and MTT in the presence of the androgen substrate androstenedione (AD), or AD plus Anas. ERα and AR transcriptional activities were tested with ERE-luciferase reporter assays. Localization of ERα and AR within the cells was visualized using immunofluorescence microscopy.
Results: ERα-positive MCF-7 cells were stably transfected with either aromatase, or aromatase plus AR. MCF-7 aromatase clones overexpressing AR were resistant to the growth inhibitory effects of Anas when stimulated with the androgen AD. Resistance was not mediated through changes in aromatase expression or activity. The growth of several of the AR Arom-overexpressing cells was stimulated with treatment of Anas alone, suggesting that Anas was acting as an agonist. As expected, AD treatment stimulated ERα transcriptional activity, but Anas was unable to block AD-stimulated activity in AR Arom-overexpressing cells using ERE-Luciferase reporter assay. Anas was able to enhance AR and ERα colocalization in AR-overxpressing cells. Resistance was not associated with activation of known mechanisms of resistance, such as HER2, IGF-1R, or MAPK. However AR-overexpressing cells had higher constitutive phosphorylation of Akt. Accordingly, resistance to Anas was blocked using an Akt1/2 inhibitor.
Conclusion: Using a model of ERα-positive breast cancer cells expressing exogenous aromatase and AR, we have demonstrated that AR overexpression confers resistance to the AI Anas. These results suggest that in patients recurring on hormonal therapy whose tumors express elevated levels of AR, targeted therapy to Akt might restore hormone sensitivity.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD01-07.
PD01-08: Heterogeneity of Lapatinib Responses in HCC1954 HER2−Overexpressing Breast Cancer Cells Revealed by Single-Cell Automated Microscopy.
Authors: Hardeman KN , Tyson D , Quaranta V 
Published: June 2012

Abstract
In breast cancer, 20–30% of patients present with HER2 overexpression, making them potential candidates for targeted HER2 therapies such as lapatinib. Lapatinib is a dual, intracellular tyrosine kinase inhibitor of HER2 & EGFR and is standard care for metastatic breast cancer. Drug resistance to this type of therapy is a major cause of death in cancer patients. Intra-tumor heterogeneity with respect to drug response can be a driving force for relapse and/or drug resistance. In current drug response end-point assays (IC50), information on heterogeneity is lost because cell differences are averaged out over the whole population. To produce a more realistic appreciation of drug response variability within a tumor, our lab has developed an extension of high content automated microscopy, called Extended Time Resolved Automated Microscopy (ETRAM). ETRAM entails the visual tracking of single cells with fine temporal & spatial resolution, allowing for the calculation of proliferation, death, and quiescence rates from image stacks and movies. HER2+ breast cancer HCC1954 cells were fluorescently labeled w/a nuclear tag (H2BmRFP) and treated w/lapatinib in a dose-dependent manner, from 2000 nM to 0 nM (DMSO control). Using the ETRAM method we followed nearly 1000 single cells/treatment condition over 72 hours, acquiring images every 10–12 minutes. Unexpectedly, we discovered that small but significant subpopulations of HCC1954 cells are unaffected by high lapatinib concentrations (2000 nM) and continue to divide. Furthermore, a substantial subpopulation responds to high lapatinib by entering quiescence, not apoptosis. Since HCC1954 cells have a previously reported lapatinib IC50 of 300 nM, our data demonstrate a need to further investigate these subpopulations of cells in order to determine their contribution to the IC50. Image stacks are being further analyzed to extract cellular metrics of division, quiescence and death rates in the presence of lapatinib. We are also investigating single cells by immunofluorescence of signaling molecules in the HER2 pathway, along with downstream targets such as PI3K, mTOR/AKT, SHC, and RAF1, to assess molecular differences regarding dividing and quiescent subpopulations in lapatinib, versus lapatinib-sensitive cells that apoptose. Our ETRAM-based single cell analyses may stimulate a re-interpretation of lapatinib responses in HER2−overexpressing breast cancer, and hopefully point to improved strategies of lapatinib treatment.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD01-08.
PD02-08: Validation over Time of a Nomogram Predicting the Sentinel Node Positivity in Early Breast Carcinoma According to the Molecular Subtypes Classification.
Authors: Ngô C , De Rycke Y , Mouttet D , Reyal F , Fourchotte V , Hugonnet F , Falcou M-C , Bidard F-C , Vincent-Salomon A , Fourquet A , Sigal-Zafrani B , Alran S 
Published: June 2012

Abstract
Background: The molecular subtypes of breast cancer have different axillary status. A new nomogram including the interaction covariate between estrogen receptor (ER) and HER2 status has been recently published (Reyal et al. PLOSone, may 2011) and allows to identify before surgery the patients with a high risk of positive sentinel lymph node (SLN). The purpose of our study was to validate this model on an independent population.
Patients and methods: We studied 755 consecutive patients treated for operable breast cancer with sentinel node biopsies in 2009, from the Institut Curie breast cancer prospective database. Baseline characteristics were compared between our population and the population used to build the model, using Chi-square test for categorical variables and Kruskal-Wallis test for continuous variables. The multivariate model, including age, tumor size, lymphovascular invasion and interaction covariate between ER and HER2 status, was used to calculate the theoretical risk of positive sentinel lymph node (SLN) for all patients. The performance of the model on our population was then evaluated in terms of discrimination (area under the curve AUC) and of calibration (Hosmer-Lemeshow HL test).
Results: Characteristics of our population were significantly different from the training population for the following variables: tumor size (median 12mm [1-60] versus 13mm [1-100] p=0.005), lymphovascular invasion (18.6% versus 23.7% p=0.006), positive ER (91.4% versus 87% p=0.002) and age as followed: 56.7% of patients ≤ 60 versus 63.1%, 17.5% of patients between 60 and 65 versus 14.1% and 25.8% of patients above 65 versus 22.8% p=0.01. The nomogram showed similar results in our population than in the training population in terms of discrimination (AUC= 0.72 [0.68−0.76] versus 0.73 [0.7−0.75] and calibration (HL p= 0.4 versus p=0.35).
Conclusions: Despite significant differences between the two populations concerning variables which are part of the nomogram, the model was validated in our population. Our study shows that this nomogram is efficient and robust over time to predict the likelihood of positive SLN according to molecular subtypes defined by surrogate markers ER and HER2 determined by immunohistochemistry in clinical practice.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD02-08.
PD05-04: Quantitative Measurement of Antigen Degradation in NCCTG N9831 Tissue Microarrays.
Authors: Cheng H , Rimm DL , Reinholz MM , Lingle WL , Ballman KV , Dueck AC , Chen B , McCullough AE , Jenkins RB , Perez EA 
Published: June 2012

Abstract
Background: Unstained recuts from formalin-fixed paraffin-embedded tissues are commonly collected for cooperative group studies. There is concern among pathologists that improper storage conditions can lead to antigen degradation. In an effort to quantify this effect, we compared the expression of HER1 and HER2 on two sets of identical cohort tissue microarrays (TMAs) from the N9831 HER2+ adjuvant phase III trial (NCT00005970; www.clinicaltrials.gov); one freshly cut set (cut April 18, 2011) and a second set stored at 4 degrees for over two years (cut between Nov, 2007 and Jan, 2008).
Methods: The two sets of TMA slides containing 1580 tumor samples from the N9831 cohort were treated identically using the AQUA method of quantitative immunofluorescence. HER1 was tested with D38B1 (rabbit monoclonal, Cell Signaling Technology, Inc.) and HER2 with CB11 (mouse monoclonal, Biocare, Inc.) on tumors from 695 patients (712 specimens) in the fresh TMAs and 779 patients (800 specimens) in the old TMAs in up to three-fold redundancy per specimen.
Results: Frequency distributions of the expression of HER2 revealed bimodality in the fresh TMAs compared to an attenuated distribution of the old cases. The average score of the entire cohort was significantly lower in old TMAs compared to fresh cuts (paired t-test, p&lt;0.0001). Linear regression of the average HER2 scores from new TMAs versus the average scores from old TMAs showed a slope term of 0.52, which is statistically significantly different from the hypothetical value of 1 (p&lt;0.0001). Regressions between any two fresh slides showed slopes close to 1.0. Similar results were seen for HER1, but fewer positive cases made the changes less dramatic.
Conclusions: The storage condition of tissue slides is a critical pre-analytical variable that can dramatically lower the score of HER1 and HER2, artificially. Thus, studies done on inadequately stored slides, either whole sections or TMAs, must be interpreted with caution. Tissue collection and analysis of biomarkers for cooperative group studies should not include unstained recuts, but rather, entire blocks or large cores from tissue blocks.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD05-04.
S1-3: Long-Term Survival Outcomes among Postmenopausal Women with Hormone Receptor-Positive Early Breast Cancer Receiving Adjuvant Letrozole and Zoledronic Acid: 5-Year Follow-Up of ZO-FAST.
Authors: de Boer R , Bundred N , Eidtmann H , Neven P , von Minckwitz G , Martin N , Modi A , Coleman R 
Published: June 2012

Abstract
Introduction: Recent clinical trials suggest potential anticancer activity for bisphosphonates combined with adjuvant endocrine therapy in patients with hormone receptor-positive (HR+) early breast cancer (EBC). Data from the interim analysis of AZURE suggest that the benefits of adding zoledronic acid (ZOL) may be greatest in patients with low estrogen levels (Coleman RE, et al. SABCS 2010). In ZO-FAST, we have previously demonstrated that adding ZOL to adjuvant therapy significantly improved bone mineral density (BMD) and prolonged disease-free survival (DFS) vs delayed ZOL (de Boer R, et al. SABCS 2010). We report here the effect of time since menopause at breast cancer diagnosis (ie, baseline menopausal status) on DFS benefits with ZOL.
Methods: Postmenopausal women with HR+ EBC receiving letrozole (LET; 2.5 mg qd x 5 yr) with a BMD T-score ≥-2 (N=1065) were randomized to ZOL (4 mg q6mo): immediate (IMZOL) or delayed (DZOL; initiated for postbaseline T-score &lt;-2 or nontraumatic/asymptomatic fracture). Patients were followed for disease recurrence and overall survival (OS) for 5 years. Patients were eligible for the study if they had established menopause at the time of diagnosis, or if they became menopausal because of chemotherapy or ovarian suppression (ie, recently postmenopausal). The effect of baseline menopausal status on DFS was examined in Cox regression analyses.
Results: At 60 months’ follow-up in the overall population (N=1065), IMZOL significantly reduced the risk of a DFS event by 34% vs DZOL (hazard ratio [HR]=0.66; 95% confidence interval [CI], 0.44−0.97; P=.034). In exploratory analyses of women who were postmenopausal for &gt;5 years or &gt;60 years old at study entry (n=670), IMZOL improved DFS (HR=0.63; 95% CI, 0.39−1.01; P=.052) and significantly prolonged OS (HR=0.50; 95% CI, 0.27−0.92; P=.022) vs DZOL. Additional subgroup analyses including patterns of breast cancer recurrence will be presented. During 5 years of treatment, osteonecrosis of the jaw (ONJ) was reported in 4/669 patients (0.6%) who received ZOL, and there was no increase in renal adverse events (AEs) in the ZOL-treated patients. Overall, AEs were consistent with the known safety profiles of both study drugs.
Conclusions: Long-term follow-up in ZO-FAST confirms the overall survival benefits of adding ZOL (4 mg q6mo) to adjuvant LET therapy for EBC. However, subset analyses suggest that women with established postmenopausal status may benefit from ZOL therapy more than others. These results are consistent with observations in the AZURE trial, and support potentially greater ZOL benefits in a low-estrogen environment. Additional studies are needed to fully define the patient populations most likely to benefit from adjuvant ZOL in this setting.
Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr S1-3.