bluuebunny/crossref_metadata_2025_split huggingface dataset:
BOLERO-2: Health-related quality-of-life (HRQoL) in metastatic breast cancer patients treated with everolimus and exemestane versus exemestane.
Authors: Rugo Hope S. , Beck J. Thaddeus , Baselga José , Noguchi Shinzaburo , Gnant Michael , Lebrun Fabienne , Neven Patrick , Nunzi Martina , Komorowski Anna , Chouinard Edmond , Young Robyn R. , Anderson Ian , Bennett Lee , Ricci Jean-Francois , Hortobagyi Gabriel N. , Sahmoud Tarek , Burris Howard A. 
Published: February 2017

125 Background: BOLERO-2, a phase III study, randomized 724 patients with hormone-receptor–positive metastatic breast cancer, who had recurrence or progression on/after prior nonsteroidal aromatase inhibitor therapy, to everolimus (EVE) + exemestane (EXE) or EXE + placebo. A preplanned 12-mo median time interim analysis demonstrated that EVE + EXE significantly improved progression-free survival (PFS) vs EXE + placebo, but EVE + EXE resulted in a higher rate of grade 3-4 toxicity. Per-protocol patients reported HRQoL data are limited; here we report on additional post hoc analyses of these outcomes. Methods: Using the EORTC QLQ-C30 questionnaire, HRQoL was assessed at baseline and every 6 weeks thereafter until progression. QLQ-C30 consists of 30 items combined into 15 subscales, including a Global Health Status (GHS), where higher scores (range, 0-100) indicate better HRQoL. Analysis included a protocol-specified time to definitive deterioration (TTD) analysis at a 5% decrease in QoL relative to baseline, with no subsequent increase above this threshold. We report additional sensitivity analyses using 10-point minimally important difference (MID) decreases in QLQ-C30 score relative to baseline. Treatment arms were compared using a stratified log-rank test and a Cox proportional hazards model adjusted for trial stratum (visceral metastases and previous hormone sensitivity), age, sex, race, baseline score, ECOG performance status, prognostic risk factors, and treatment history. Results: Baseline QLQ-C30 GHS scores were not statistically significantly different across treatment groups (64.7 vs 65.3; difference –0.7 [95% CI, –4.3-3.0]). Median TTD in HRQoL was 7.0 mo (95% CI, 5.6-8.3) for EVE + EXE vs 5.6 (95% CI, 4.2-7.0) for EXE (p = .0792). Adjusted HR (0.80) approached significance (95% CI, 0.63-1.02). At the 10-point MID, median TTD for EVE + EXE was 9.7 mo (95% CI, 8.3-11.2) vs 8.4 mo (95% CI, 6.3-12.5) for EXE. Adjusted HR was 0.90 (95% CI, 0.69-1.18). Conclusions: These additional analyses from the BOLERO-2 study demonstrate that in addition to significantly improving PFS, EVE + EXE does not compromise HRQoL.
Maximizing metastatic breast cancer therapy selection: Physician practice patterns and competence assessment.
Authors: Stacy Tina Boyd , Haas Maureen E. , Heintz Alison A. 
Published: February 2017

127 Background: Due to the volume and pace of scientific advances within oncology, peer discussion and professional reflection regarding appropriate therapeutic decision making is necessary to provide the highest quality patient care. Increasing awareness in the breast cancer community of similarities and differences amongst practice management strategies helps to identify and benchmark individual practice patterns against one’s professional peers, ultimately leading to increased competence in therapy selection. Methods: During 2011 and 2012, educational outcomes assessments were gathered during 85 independent continuing medical education (CME) activities held within community practices and institutions across the USA. Participants were asked a series of case-based questions via an audience response system to assess baseline knowledge, competence, and identify practice patterns. Assessments were repeated post a 1-hour CME certified activity, with an additional 6-week electronic follow-up. Results: To date, over 330 physicians have participated in the program. Number of years in practice ranged from < 10 to > 30. The number of breast cancer patients seen per month ranged from ≤ 10 to > 40. Provider competency and preferences in applying guideline based therapy was assessed. Results of participant preferences including single-agent, combination, first-line, and second-line therapy preferences as well as toxicity management for select patient case scenarios in advanced breast cancer will be presented. Self-rated competence for the physician audience improved by approximately 50% as a result of participation. Conclusions: The results highlight the diversity of clinical opinion in selecting therapy for advanced breast cancer and need for continued dialogue and scientific advancement. Education and peer discussion of how to optimize translation of new scientific information into patient care contributes to maximizing physician competence in therapy selection for metastatic breast cancer.
A review of clinical endpoints and use of quality-of-life outcomes in phase III metastatic breast cancer clinical trials.
Authors: Tatla Raman , Landaverde Denis , Victor Charles , Miles David , Verma Sunil 
Published: February 2017

129 Background: The management of metastatic breast cancer (MBC) is often considered to be palliative, with most interventions intended to relieve disease symptoms, minimize treatment effects and prolong patient survival. The impact of disease and treatment on a patient's funcitonal abilities has led to an emphasis of incorporating quality of life (QoL) measures into clinical trials. The main objective of this study is to evaluate phase III clinical trials in MBC, and assess the inclusion of QOL as an endpoint, in addition to conventional efficacy endpoints. Methods: A structured PubMed search was conducted to identify phase III clinical trials published between Jan. 1990 and Aug. 2011, evaluating systemic treatment in MBC patients. Data pertaining to treatment regimens, study endpoints and clinical findings were collected, with a particular focus on progression-based (PB), overall survival (OS), and QoL endpoints. Results: Of 520 publications identified, 122 phase III MBC clinical trials met the inclusion criteria. Of these studies, 98.4% and 95.9% included PB and OS respectively, as clinical endpoints, while QoL was assessed in only 46 (37.7%) studies. While the inclusion of QoL was not associated with the significance of PB results, there was an association between the inclusion of QoL and OS results, with 59% of significant OS studies and 32% of non-significant OS studies including QoL as a clinical endpoint (p=0.016). When stratified by treatment arm, it was found that studies favouring standard therapy were more likely to include QoL (75%, p=0.045), compared to those favouring the intervention (56%), and those without significant differences (32%). Conclusions: Although the importance of QoL is often emphasized in MBC management and treatment decisions, only one-third of identified phase III clinical trials included an assessment of QoL. About half of these trials showed no statistically significant differences in the QoL endpoint; of not, instruments of varying validity were utilized. There needs to be a greater emphasis on the evaluation of QoL, with the use of standard and validated QoL tools in MBC clinical trials, especially as we increasingly focus on progression-based endpoints.
Long-term survivor (LTS) characteristics in HER2+ metastatic breast cancer (MBC).
Authors: Yardley Denise Aysel , Tripathy Debu , Brufsky Adam M. , Rugo Hope S. , Kaufman Peter Andrew , Mayer Musa , Feng Shibao , Abidoye Oyewale O. , Ulcickas Yood Marianne 
Published: February 2017

133 Background: Data characterizing LTS with HER2+ MBC are limited. The objective of this analysis is to describe LTS in terms of demographics, disease characteristics, and treatment history. Methods: registHER is an observational cohort of patients (pts) (N=1,001) with HER2+ MBC diagnosed w/in 6 mos of enrollment and followed until death, disenrollment, or 6/09 (median follow-up 27 mos). LTS were defined as pts who survived ≥36 mos from metastatic diagnosis (dx) (n=404). Baseline characteristics were examined. Multivariate analyses assessed factors associated with overall survival (OS) in all registHER pts. Results: Median progression-free survival in LTS was 17.9 mos (95% confidence interval (CI) 15.5-20.2). Similar to all registHER pts, median age at enrollment for LTS was 52 y (range 22,82), the majority were white (85.4%), and initial dx in over half of pts was stage I-III, MBC >12 mos (57.4%). LTS, however, were more likely to have estrogen receptor (ER)+ or progesterone receptor (PR)+ disease (61.6% and 52.9%, respectively) and a lower rate of underlying cardiovascular disease (CVD) (12.4% and 17.2%, respectively). First-line taxane and first-line trastuzumab use was higher in LTS pts. Physician-assessed first-line complete response was 40% in LTS and 22.8% in all registHER pts. Factors associated with OS in all registHER pts are shown in the table. Conclusions: This descriptive study examines factors commonly associated with long-term survival in pts with HER2+ MBC. LTS were primarily white, with ER+ or PR+ disease, and low rates of underlying CVD. Further study is needed to quantify the contribution of these factors to prolonging survival. [Table: see text]
Multiplex layered immunohistochemistry to predict response of HER2-positive breast cancer patients to trastuzumab therapy.
Authors: Park Soon Sik , Gillespie John Williams , James Bill , Lebowitz Michael 
Published: February 2017

136 Background: Since only 40% of HER2-positive breast cancer patients respond to trastuzumab therapy, there is a great clinical need for a test that will better predict which patients would be responders to trastuzumab therapy. Since no single biomarker will likely improve identification of responders, this study will determine the efficacy of multiple biomarkers to predict response of patients to trastuzumab therapy. Our company has developed a protein analysis platform, layered immunohistochemistry (L-IHC), for the analysis of multiple protein biomarkers from a single FFPE tissue section while retaining the histologic orientation. L-IHC is being used to develop a companion diagnostic test in which multiple protein biomarkers are analyzed in HER2-positive breast cancer specimens to predict which patients will respond to trastuzumab therapy. Methods: In this ongoing clinical exploratory study, analysis of pretreatment archival HER2-positive FFPE breast cancer tissue sections from patients whose subsequent therapy included trastuzumab and whose response to therapy (responders and non-responders) is known was performed using L-IHC. Tissue sections were probed using a panel of 14 biomarkers along the HER2 and mTOR pathways were analyzed. In a blinded fashion to the response data, the intensity of specific biomarker signals corresponding to cancer regions on an H&E was visually scored (0,1,2,3, & 4+). The pattern of biomarker expression was correlated with the responder status of the patient. Results: A total of 24 responders and 9 non-responders were analyzed. The sum of four of the 14 biomarkers including p-mTOR, p-4EBP1, pERK, and HIF1-alpha discriminated the responders and non-responders. Using 7 as a cutoff, this test correctly identified 21/24 responders and 7/9 non-responders for a sensitivity of 87%, specificity of 78%, and an accuracy of 82%. Conclusions: Results of this study strongly suggests that analysis of p-mTOR, p-4EBP1, pERK, and HIF1-alpha using L-IHC improves twofold the prediction of patient response to trastuzumab compared to Her2 alone.
Correlation of quantitative p95HER2, HER2, and HER3 protein expression with pathologic complete response (pCR) in HER2-positive breast cancer patients (pts) treated with neoadjuvant chemotherapy and trastuzumab.
Authors: Villasboas Jose Caetano , Hurley Judith , Weidler Jodi Marie , Paquet Agnes , Fernandez Carmen Gomez , Cioffi Lavina Maureen , Sperinde Jeff , Chenna Ahmed , Haddad Mojgan , Lie Yolanda , Winslow John William , Huang Weidong , Petropoulos Christos J. , Pegram Mark D. 
Published: February 2017

137 Background: Elevated p95HER2 [HER2-M611-CTF (carboxy-terminal-fragment) also known as p95] expression has been correlated with poor outcomes in HER2+ pts with metastatic breast cancer treated with trastuzumab (T); however, limited data is available on the correlation between p95 and pCR to T in the neoadjuvant (NEO) setting, where p95 was measured by immunohistochemistry. The current study aims to determine whether quantitative p95, HER3 and HER2 expression correlated with pCR in pts treated with T + chemotherapy in the NEO setting. Methods: pCR data and quantitative HER2 (H2T), p95, and HER3 (H3T) results by HERmark/VeraTag assays were available in 45 patient cases with pre-therapy, formalin-fixed, paraffin-embedded breast tumors. pCR was defined as the absence of invasive disease in the breast. Quantitative biomarker data were correlated with pCR according to previously published or presented biomarker cutoffs. Results: The overall pCR rate was 46.7% (ER+: 14.3% vs. ER-: 75%; p<0.0001) and was significantly associated with higher H2T levels (p=0.02) and lower H3T levels (p=0.04). In ER- subjects (N=24), no difference in H2T levels was observed between pCR vs non-pCR groups (median H2T=111.5 vs 150.5, respectively; p=0.721). However, within the ER+ group (N=21), H2T levels were significantly higher in the pCR group vs non-pCR group (median H2T=254 vs 37.3; p=0.024). Using multivariate logistic regression, increasing log(H2T) (p = 0.012), ER-negativity (p = 0.027) and low p95 (p = 0.074) were found to correlate or trend with pCR. Conclusions: pCR was significantly associated with high H2T, particularly in ER+ HER2+ breast cancer pts who received NEO therapy with T + chemotherapy. Lower H3T was also associated with pCR. A trend towards pCR was seen in tumors with low p95. These data suggest that quantitative H2T, H3T and p95 may provide additional information on response to T-based regimens in breast cancer stratified by ER status. Additional investigation into the relationship between quantitative H2T, p95 and H3T expression and T response in the NEO setting in larger cohorts is warranted.
Reduced re-excisions while conserving tissue volume resected in DCIS patients.
Authors: Freedman Beth Cutler , Boolbol Susan K. , Cocilovo Costanza , Tafra Lorraine 
Published: February 2017

144 Background: The ability to obtain negative margins with a single surgical procedure remains a challenge, particularly in patients with ductal carcinoma in situ (DCIS). Many techniques have been reported to lower the positive margin rate, at a cost of additional tissue resected. A novel device (MarginProbe, Dune Medical Devices, Inc.) is intended to provide surgeons with real time, intraoperative detection of cancerous tissues at the margins of excised specimens. An analysis was performed to determine the impact on tissue volume of the previously reported improvement in candidates for re-excision associated with device use for patients with a DCIS component. Methods: 596 patients undergoing breast conservation using wire localization were randomized in a prospective, international, multicenter (n=21) study. Randomization occurred in the operating room, following standard of care lumpectomy, including palpation and any indicated additional resections. Positive readings required additional resections of the cavity; device was used on main lumpectomy specimen only. Pathologists were blinded to study arm. Tissue volume of all specimens and resections was recorded. Since reducing candidates for re-excision requires removing additional tissue associated with cancer, we looked at total tissue volume removed across all surgeries, to assess the final impact to the patient. Results: Total tissue volumes removed during all surgeries (lumpectomy and re-excisions) for patients with DCIS alone was similar between the study group and control group, while the decrease in candidates for re-excision was significant (13% vs. 37%, p=0.004). For patients with DCIS and invasive carcinoma, the total volume excised was also similar, and the decrease in re-excision candidates was significant (13% vs. 33%, p<0.001). Conclusions: Unlike other techniques for reducing re-excisions, device use does not require an increase in tissue volume to achieve a significant reduction in the number of candidates for re-excision. [Table: see text]
Clinical efficacy of 2-day versus 5-day accelerated partial breast irradiation delivered via balloon-based brachytherapy: Results of a matched pair analysis.
Authors: Chen Peter Y. , Shah Chirag , Wilkinson John Ben , Wallace Michelle , Ye Hong , Fowler Ashley , Dekhne Nayana , Benitez Pamela , Martinez Alvaro A. , Vicini Frank 
Published: February 2017

148 Background: This analysis compares the efficacy of a 2-day vs. 5-day accelerated partial breast irradiation (APBI) schedule in treatment of early-stage breast cancer. Methods: Patients were treated between 6/2000 and 1/2011 with balloon-based brachytherapy using a 2-day (700 cGy x 4 BID) or a 5-day (340 cGy x 10 BID) fractionation. The CTV was a 1cm expansion from the balloon surface with a single-lumen device used in all cases. To compare efficacy between the two treatment groups, a matched-pair analysis was performed using a 1:2 ratio which paired 38 two-day with 76 five-day patients. Match criteria included minimal follow-up (FU) > 1.0 yr, clinical stage, age (+/- 3 yrs), and ER status. Clinical outcomes analyzed include local-regional recurrence [LR, RR] distant metastases (DM), disease-free, cause-specific and overall survival [DFS, CSS, and OS]. Results: No significant differences were noted for age (p=0.838), clinical stage (p=1.000), ER (p=1.000), tumor size (p=0.236), margin status (p=0.556), nodal stage (p=0.381), PR (p=0.749), use of chemotherapy (p=0.927) or endocrine therapy (p=0.129). Per the ASTRO Consensus Guidelines, no differences were noted in the clinical groups between the 2-and 5-day treatments with the majority categorized as suitable or cautionary (2-day: 92% vs. 5-day: 87% p=0.436). With a mean FU of 4.7 yrs (4.9 yrs for 2-day vs. 4.5 yrs for 5-day, p=0.279), no differences were seen in the 5-year actuarial rates of LR (0.0% vs. 2.6%, p=0.359), DFS (94.4% vs. 96.1%, p=0.618), CSS (100% vs. 94.9 %, p=0.207), or OS (97.3% vs. 92.5%, p=0.811) between the 2-and 5-day groups, respectively. There was no RR in either group. DM rates were similar for both (5.6% vs. 1.3 %, p=0.456). Conclusions: With near 5-year FU for the 2-day schedule, APBI with the 2-day regimen yielded outcomes equivalent to the 5-day schema. Reduced on-treatment days by such hypofractionation offers flexibility in clinical and patient scheduling. Further FU and more patients will be needed to substantiate equivalence of hypofractionated APBI. An HIC-approved protocol randomizing patients between the 2 vs. 5-day treatments is currently open for accrual at our institution.
The elderly breast cancer patient: Association of age, tumor size, and grade with sentinel lymph node status.
Authors: O'Malley Meaghan Working , Griffith Kent A. , Sabel Michael S. , Newman Lisa A. , Breslin Tara M. , Chang Alfred E. , Cimmino Vincent M. , Kleer Celina G. , Diehl Kathleen M. 
Published: February 2017

15 Background: Nodal evaluation of the elderly breast cancer patient remains controversial, and some have suggested that selected older women with breast cancer may not require sentinel lymph node biopsy (SLNB). Methods: An IRB-approved database was queried for patients undergoing SLNB for invasive breast cancer from 2000-2006. We compared 8 cohorts: age <40 years, 40-44, 45-49, 50-54, 55-59, 60-64, 65-69, and >70 years. Logistic regression and chi-square test were used. Results: Procedure success rate was above 95% for all groups in a total sample size of 1268 patients. Patients >70 years had lower grade tumors than patients <40 years (Grade 1: 25% vs. 7%; Grade 2: 53% vs. 47%; Grade 3: 17% vs. 40%, p<0.0001) and higher ER expression (ER+: 83% vs. 59%, p<0.0005). Patients <40 years also had a higher proportion of multifocal disease (21% vs. 9%, p<0.002), lymphovascular invasion (20% vs. 10%, p<0.007), and number of positive sentinel lymph nodes (PSLN) removed (mean: 3.7 vs. 2.7, p<0.028). Upon multivariate analysis, the odds of a PSLN decrease 9% for every 5-year increase in age (OR 0.91, p<0.003), but increase significantly with certain tumor characteristics (ER+ vs. ER-: OR 1.7, p=0.002), larger size (0.5 cm increase: OR 1.26, p<0.0001), and higher grade (Grades 2-3: OR 1.99, p<0.0007). The predicted probability of a PSLN for patients age 35, 55, and 70 years is 27%, 22%, and 16%, assuming each had a ER+, low grade, 2 cm tumor. Conclusions: Older breast cancer patients have more favorable pathology, and the chance of a PSLN decreases as age increases. However, the odds of a PSLN are significantly higher in patients with certain tumor characteristics, which are known prior to definitive surgery. Given recent reports that older patients are less likely to receive standard treatment for breast cancer and prognosis may worsen as a result, tumor size and characteristics rather than age should dictate the decision to perform SLNB, and we should continue appropriate, aggressive staging of the older breast cancer patient.
Effect of IL-8 on integrin αvβ3 expression and cell motility via PI3K, Akt, and NF-κB-dependent pathway in human breast cells.
Authors: Shao Nan , Wang Shenming , Zhang Yunjian , Lin Ying 
Published: February 2017

158 Background: αvβ3 integrin-overexpression in tumor associated vasculature is a marker of poor prognosis in breast cancer. A positive correlation between αvβ3 integrin and overexpression of Interleukin-8 (IL-8), a multifunctional cytokine associated with breast cancer aggressiveness was recently demonstrated. Here, we addressed the effects of IL-8 in migration and integrin expression in breast cancer cells. Methods: The IL-8 overexpressing breast cancer cells MDA-MB-231 and HS 578t were treated with IL-8 siRNA and evaluated for cells motility and alterations in the expression of αvβ3. Western Blotting to identify the status of PI3K, Akt and NF-κB. Results: In this study, we found that αvβ3 expression was decreased by IL-8 siRNA, especially the expression of β3. Treatment with αvβ3-blocking antibody LM609 and β3 siRNA significantly reduced invasion in the IL-8 overexpressing cells MDA-MB-231 and HS 578t. The phosphorylation of PI3K, Akt and NF-κB was abrogated after IL-8 siRNA treatment. The IL-8 siRNA can also decrease the binding of β3 promoter and the NF-κB-P65. Conclusions: These results indicate that IL-8 enhances the motility of highly invasive breast cancer cells by regulating αvβ3 expression partially through PI3K/Akt/ NF-κB signal transduction pathway.