bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of variables that may impact chemotherapy (CT) administration after determination of Oncotype DX (ODX) recurrence score (RS).
Authors: Bowen Kristina E. , Gilmore James W. , Szabo Stephen , Haislip Sally , Hassell Robert , Cooper Joseph , Richardson Steve , Fitzgerald Meghan , Feinberg Bruce A. 
Published: March 2020

571 Background: Cardinal Health Specialty Solutions (CHSS) partners with payers to manage clinical care pathways in oncology and rheumatology. Observations from one such pathway with CareFirst BlueCross Blue Shield revealed lower than expected use of CT in patients (pts) with estrogen receptor-positive early-stage breast cancer (ESBC) at high-risk for recurrence by ODX RS. To better understand physician behavior, CHSS examined patterns of care in a large private practice oncology group with a robust EMR, Georgia Cancer Specialists (GCS). Pt characteristics and physician-prescribing patterns were analyzed to determine variables that most impacted the physician’s decision to treat high-risk pts with CT. Methods: Using the GCS EMR from 2009 to 2011, we retrospectively identified pts with ESBC (stage I-II, node-negative, estrogen receptor-positive, HER2-negative) who underwent ODX testing. We determined the number of pts with a RS value in the low- (RS <18), intermediate- (RS 18-30), and high-risk (RS ≥31) groups along with the number of pts who subsequently received CT in each category. The use of CT in high-risk pts was analyzed by pt age, tumor size, tumor grade, and physician prescribing patterns. Results: Of the 1908 pts identified with ESBC, 788 were eligible for ODX testing and 288 (37%) underwent testing. Fifty percent of pts were in the low-, 34% in intermediate-, and 16% in the high-risk groups. Six percent of low-, 41% of intermediate-, and 83% of high-risk pts received CT. In high-risk pts analyzed by age, CT was used in 100% of pts ≤ 45 years (y), 86% in pts 46-55 y, 86% in pts 56-65 y, and 25% in pts >66 y. CT use in high-risk pts was 82% and 86% in pts with tumor sizes <2 cm and 2-5 cm, respectively; and, 100%, 60%, and 91% in pts with grade 1, 2, or 3 tumors, respectively. Of the 41 physicians who were evaluated, 10 (24%) used ODX <15% of the time, 13 (32%) used ODX 15-40%, 10 used (24%) used ODX 41-60%, and 8 (20%) used ODX > 60% of the time. There were no significant differences in patterns of CT use. Conclusions: The less than expected use of CT in high-risk patients appears to be related to physician preference and pt age. Tumor size and grade did not appear to influence choice of therapy.
Complementary role of Ki67 index and 70-gene signature (MammaPrint) high-risk patients in the St Gallen risk group with uncertain chemotherapy suggestion.
Authors: Pronzato Paolo , Mustacchi Giorgio , Generali Daniele Giulio , Bottini Alberto 
Published: March 2020

579 Background: St Gallen (SG) Consensus Panel on adjuvant treatment recommends the use of proliferation markers and multigene assays when choosing the appropriate treatment in addition to traditional parameters. Ki67 predictive/prognostic value is widely accepted; we tested its role in increasing the accuracy of risk prediction among Mammaprint (MP) /High(HR) or /Low Risk (LR) breast cancer patients with a SG risk uncertain for chemotherapy selection. Methods: MP was determined (courtesy of Agendia, Amsterdam) in 3 Italian Hospitals on 305 consecutive samples of breast cancer patients. We focused on SG “Intermediate Risk” Group (HER2 neg, no VI and: ER>10<50%, or G2 or Ki67 >15<30% or N1a or T>2<5cm), where the indication for adjuvant CHT still remains uncertain. In MP/HR cases, a “low” Ki67 value (<15%) was used to eliminate CHT suggestion and viceversa an “intermediate” Ki67 value (>15<30%) in MP/LR cases. Results: Overall, 72/305 pts (26.6%) were in SG intermediate risk group with a median age of 64 years (26-98). Ki67 was non available in 4.1% of cases, MP rejected in 16.6%, HR was detected in 39 (54.2%), whereas LR in 21 (29.2%). Ki67 resulted low in 23 MP/HR cases (59%), intermediate in 6 MP/LR cases (28.5%) and in 3 out 12 MP/Rejected cases (25%). The overall concordance between MP and Ki67 was 28/57 (49.1%), MP rejected excluded. Overall MP suggested 39/60 CHT (65%), Ki67 29/69 (42%). Conclusions: The risk of relapse is a continous variable and MP evaluates it in a dichotomy (low vs high) wich could decrease the accuracy of the test. In the selected SG Group, the average risk of 5 yr relapse is around 20% (EBCTCG, Lancet 2011) and MP HR cases in our experience account for 55%. A low Ki67 value could help avoid more than 20% of cytotoxic treatments suggested by MP. In the same way, according to an ER value <50% (2 cases), an intermediate Ki67 value could suggest a more aggressive treatment in a further 13% of cases MP LR (6/21) or Rejected (3/12). MP probably overestimates the risk in 20% of cases and underestimates it in further 20%. Ki67 could be usefull for a more personalized treatment in patients where the indication for adjuvant chemotherapy added to endocrine treatment is uncertain.
Immunocytochemistry staining for ER and PR in circulating tumor cells as compared to primary tumor or metastatic biopsy.
Authors: Bischoff Farideh Z. , Pircher Tony J , Pham Tam , Wong Karina , Villarin Eligie , Kalinsky Kevin , Mayer Julie Ann 
Published: March 2020

584 Background: Hormone receptor (estrogen receptor [ER] and progesterone receptor [PR]) status in all breast cancer patients is recommended for selection of treatment options. However, the analytical sensitivity of immunohistochemistry (IHC) in detecting low levels of ER/PR is often poor and is likely due to methodological variation. Because biopsy is not often feasible in all patients with recurrent and/or metastatic breast disease, circulating tumor cells (CTCs) offer an attractive alternative source of tumor tissue for determining ER/PR status and can be monitored more readily to enable a more effective course of treatment. Methods: Twenty mL of peripheral blood was collected prospectively from 15 patients diagnosed with late stage metastatic/recurrent breast cancer. CTCs were isolated using the microfluidic OncoCEE platform. A cocktail of antibodies was utilized for CTC capture and detection with an expanded anti-cytokeratin (CK) cocktail mixture and anti-CD45. ER/PR protein expression was assessed by immunocytochemistry (ICC) on the cells captured within the microchannels and compared to IHC performed on the primary tumor or metastatic biopsy. Results: CK+/CD45-/DAPI+ cells were located and assessed for ER/PR ICC. Among the 15 cases, a high concordance (13/15; 87%) in ER/PR status between IHC and ICC results was observed. Two cases were found to be discordant where one was positive by IHC and negative on the CTCs, and the other was negative by IHC and positive on the CTCs. However, both cases that were discordant had low numbers of detected CTCs. Conclusions: There is significant heterogeneity between ER/PR protein expression in CTCs and primary tumor/metastatic biopsy, and this status may change over time due to therapy. ER/PR ICC on CTCs from peripheral blood using the OncoCEE platform is shown to be feasible with high concordance (87%) in ER/PR status between primary tumor/metastatic biopsy (by IHC) and CTCs (by ICC). The significance of heterogeneity at the ER/PR protein level in CTCs ascertaining to the prognosis and predictive response to anti-estrogen therapy needs further evaluation in larger prospective clinical trials.
Multiple chemotherapy (CT) lines in metastatic breast cancer (MBC): Which survival benefit for women with hormone receptor (HR)-positive disease?
Authors: Palumbo Raffaella , Bernardo Antonio , Riccardi Alberto , Sottotetti Federico , Teragni Cristina , Bernardo Giovanni 
Published: March 2020

589 Background: Although the development of modern systemic therapies has clearly improved outcome of patients with MBC, the true impact of further CT on overall survival (OS) and QoL of these women is still debated. The aim of this study was to determine which benefit could be brought by successive CT lines in patients with HR-positive disease, aiming to identify factors affecting outcome and survival. Methods: This retrospective analysis included 980 women treated with CT for MBC at our Institution over a eight year period (July 2000-July 2008). With OS data updated in March 2010, the median follow-up was 146 months (range 48-198), OS and time to treatment failure (TTF) were calculated according to the Kaplan-Meyer method for each CT line. Cox proportional hazards model was used to identify factors that could influence TTF and OS. Results: Median OS evaluated from day 1 of each CT line decreased with the line number from 34.8 months for first line to 8.2 months for 7 or more lines). Median TTF ranged from 9.2 months to 7.8 and 6.4 months for the first, second and third line, respectively, with no significant decrease observed beyond the third line (median 5.2 months, range 4.8-6.2). No statistically significant difference was found between HR-positive and HR-negative patients in terms of OS and TTF by each CT line. In univariate analysis factors positively linked to a longer duration of TTF for each CT line were positive hormonal receptor status, more than 3 hormonotherapy lines, absence of liver metastasis, adjuvant CT exposure, response to CT for the metastatic disease; in the multivariate analysis the duration of TTF for each CT line was the only one factor with significant impact on survival benefit for subsequent treatments, in both HR-positive and negative populations (p<0.001). Conclusions: Our results support the benefit of multiple lines of CT in a significant subset of women treated for MBC, since each CT line may contribute to a longer OS. Of interest, such a benefit was also observed for patients with HR-positive disease, although the number of hormonotherpy lines received did not significantly influence the outcome.
ESR1 gene amplification and protein expression in 946 patients with resected breast cancer: A Hellenic Cooperative Oncology Group (HeCOG) translational research study.
Authors: Pentheroudakis George E. , Batistatou Anna , Dafni Urania , Bobos Mattheos , Tsolaki Eleftheria , Kotoula Vassiliki , Kampletsas Eleftherios , Lazaridis George , Papadimitriou Christos A. , Gogas Helen , Kalogeras Konstantine T. , Pavlidis Nicholas , Fountzilas George 
Published: March 2020

592 Background: Discrepant data have been reported on the incidence of ESR1 gene amplification in breast cancer, its correlation to clinicopathologic characteristics and its impact on prognosis. Methods: Formalin-fixed paraffin-embedded (FFPE) tumor tissue samples from 946 patients participating in two adjuvant chemotherapy phase III trials (HE10/97 and HE10/00) were centrally assessed in tissue microarrays by immunohistochemistry (IHC) for estrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER2). FISH was also performed for HER2, TOP2A and ESR1 using commercially available dual (for ESR1) and triple (for HER2 and TOP2A) hybridization probes. Results: The majority of patients had >T2 (69%), node-positive, ER-positive (>1% stained cells, 73%) tumors managed with resection, chemotherapy and hormonotherapy (76%). Only 38 tumors (4.0%) had ESR1 gene amplification (ESR1/CEN6 ratio >2) and 514 (54.3%) ESR1 gene gain (1<ratio<2). The number of ESR1 gene copies was 3-4 in 251 (26.5%) and 5-10 in 42 (4.4%) of cases. HER2 and TOP2A gene amplification was seen in 234 (25.3%) and 101 (10.9%) of tumors, respectively. We studied the immunohistochemical expression of ER protein by evaluating the percentage of stained cells, the Allred score (0-2, 26.8%; 3-6, 62.5%; 7-8, 10.7% of tumors) and the semiquantitative H-Score (50-100, 13.8%; 101-200, 36.8%; 201-300, 15% of tumors). ESR1 gene amplification was significantly associated with taxane therapy, age >50, postmenopausal status, grade III-IV, absence of HER2 amplification and ER protein expression (p<0.05). At a median follow-up of 92 months, univariate Cox regression analysis showed that ER protein expression, but not ESR1 gene status, was a predictor of favorable outcome. In multivariate analysis, tumor size >5 cm, >4 involved nodes and negative/low ER protein expression by Allred score were independent adverse prognostic factors. Conclusions: Our data showed a rather low incidence of ESR1 gene amplification and failed to confirm its prognostic/predictive utility. ESR1 mRNA expression data will be presented at the meeting.
Quality of life assessment in CLEOPATRA, a phase III study combining pertuzumab with trastuzumab and docetaxel in metastatic breast cancer.
Authors: Cortes Javier , Baselga José , Im Young-Hyuck , Ross Graham , Clark Emma , Knott Adam , Swain Sandra M. 
Published: March 2020

598^ Background: CLEOPATRA compared the efficacy and safety of the HER2 dimerization inhibitor pertuzumab (P) plus trastuzumab (T) and docetaxel (D) with placebo (Pla)+T+D in HER2-positive 1st-line MBC. Pts in both arms received a median of 8 cycles of D; Pla/P+T was continued until progressive disease (PD). The safety profile in both arms was similar with a substantial decrease in adverse events (AEs) once chemotherapy finished. The independently assessed progression-free survival was significantly improved with P+T+D compared with Pla+T+D; objective response and duration of response were also improved with P+T+D (Baselga NEJM 2012). Here we report health-related quality of life (HRQoL) data from CLEOPATRA. Methods: Time to deterioration of HRQoL was evaluated using the FACT-B questionnaire and defined as decrease from baseline (BL) of ≥5 points in the TOI-PFB subscale score. Female pts completed questionnaires every 3rd cycle of therapy within 3 days before each tumor assessment until independently determined PD. An exploratory analysis investigated time to deterioration in breast cancer symptoms and functions. Results: 56.7% (Pla+T+D) and 59.5% (P+T+D) of pts experienced deterioration of HRQoL during the study based on TOI-PFB. The median time to deterioration was 18.3 vs 18.4 wks (~6 cycles) (HR 0.97; P = .7161). At Cycle 6, the mean reduction in TOI-PFB score from BL was –3.5 (Pla+T+D) vs –3.0 (P+T+D). At subsequent cycles, when most pts had discontinued D, mean reductions were smaller, suggesting that after an early decline patients’ scores improved slightly. Overall, mean changes were small in both arms. Compliance with completion of the FACT-B questionnaire was ≥75% beyond the 1st year in both arms. An exploratory analysis suggested that time to deterioration in BCS score, which measures symptoms and issues relevant in breast cancer, was delayed with P+T+D (18.3 vs 26.7 wks; HR 0.77; P = .0061). Conclusions: Combining P with T+D appears to have no detrimental effect on HRQoL. Results suggest that P+T+D is associated with a substantial delay in the time to deterioration in BCS score as would be expected given the improved efficacy and the low incidence of AEs once D is discontinued.
Trastuzumab-related cardiotoxicity among older breast cancer patients.
Authors: Chavez-Mac Gregor Mariana , Zhang Ning , Buchholz Thomas A. , Zhang Yufeng , Niu Jiangong , Elting Linda S. , Hortobagyi Gabriel N. , Giordano Sharon Hermes 
Published: March 2020

600 Background: The use of trastuzumab in the adjuvant setting is associated with reduction in mortality and recurrence. Although trastuzumab is extremely well tolerated, its use is associated with congestive heart failure (CHF). The incidence of this complication in the general population remains largely unknown, especially in older patients. In this study we evaluated the rates and risk factors associated with trastuzumab-related CHF in a large cohort of older breast cancer patients. Methods: Breast cancer patients ≥ 66 years with full Medicare coverage, diagnosed with stage I-III breast cancer between 2005-2007, and treated with chemotherapy were identified in the Surveillance, Epidemiology and End Results-Medicare (SEER-Medicare) database. Chemotherapy and trastuzumab use, comorbidities and CHF were identified using ICD-9 and HCPCS codes. Analyses included descriptive statistics, Cox proportional hazard model using trastuzumab as a time-dependent variable and logistic regression. Results: A total of 3,983 patients were included, 847 (21.7%) of them received trastuzumab, median age of the entire cohort was 71 years old. Among trastuzumab users the rate of CHF was 28.6% compared to 18.1% in non-trastuzumab users (p<.0001). After adjusting for demographic and clinical characteristics, comorbidities, and type of chemotherapy used, trastuzumab users were more likely to develop CHF than non-trastuzumab users (HR 1.74; 95% CI 1.47-2.06). Among trastuzumab users, older age did not further increase the risk, however history of coronary artery disease (OR 2.23; 95%CI 1.56-3.19), heart valve disease (OR 1.41; 95%CI 1.41-2.88) and emphysema -as a proxy for smoking- (OR 2.03; 95% CI 1.13-3.63) significantly increased the risk of CHF. There was a trend for increased risk of CHF associated with anthracycline use (OR 1.36; 95% CI 0.93-2.00). Conclusions: In this large cohort of older breast cancer patients, the risk of CHF among trastuzumab users was 1.74 times higher than non-trastuzumab users, which is higher than what has been reported in younger clinical trial participants. Among older breast cancer patients treated with trastuzumab, cardiac comorbidities and emphysema may identify high risk patients.
Improving the quality of breast cancer surgical treatment decisions.
Authors: Katz Steven J. , Griggs Jennifer J. , Janz Nancy K. , Hawley Sarah T. 
Published: March 2020

6024 Background: Ensuring breast cancer treatment decisions are high quality (i.e., informed and preference-concordant) is a key component of patient centered care. Methods: A web-based decision tool, including an interactive preference clarification exercise, was developed over a one-year period with input from health communication experts, clinicians, and women with breast cancer. Newly diagnosed early stage breast cancer patients from two cancer centers were recruited and randomized to view the tool before or after completing a survey. Mean scores for key outcome measures, including surgical treatment knowledge (4 true/false questions), decision satisfaction (12 questions each with a 5-point Likert scale from strongly agree to strongly disagree), and preference-concordant decisions, were compared between the groups using t-tests. Concordance between preferences and surgical choices was evaluated using the chi-square test. Results: 110 subjects were recruited and 105 completed the study. Their mean age was 57 years, 60% had a college degree or more, and 81% were white. Those viewing the website first had higher scores on several decision outcomes than those taking the survey first (Table). Knowledge scores were also higher among those viewing the website before the survey (3.0 vs. 2.61, p=.23). The risk of recurrence was the most important treatment attribute, followed by retaining the natural breast, in both groups. Concordance between treatment choice and computer generated treatment was 65% for website first and 61% for survey first groups. Conclusions: A tool focused on improving knowledge and preference-concordant decisions produced positive results on breast cancer surgical treatment decision making. Further work should assess the impact of the tool in larger and more diverse populations. [Table: see text]
Does unblinding of treatment assignment impact participant perceptions in clinical trials?
Authors: Partridge Ann H. , Sepucha Karen , O'Neill Anne M. , Miller Kathy , Motley Christine , Swaby Ramona F. , Schneider Bryan P. , Dang Chau T. , Northfelt Donald W. , Sledge George W. ,   Eastern Cooperative Oncology Group
Published: March 2020

6025 Background: Blinding patients to treatment regimen is an important component of high quality randomized clinical trials although concern exists about how receipt of a placebo will impact participants’ views. In ECOG5103, patients were randomized to receive adjuvant chemotherapy for breast cancer with either placebo (arm A) or bevacizumab (arms B and C) and treatment assignment was unblinded by 24 weeks. We sought to determine if unblinding was associated with differential changes in participants’ views. Methods: The Decision-Making/Quality of Life component (DM-QOL) included all patients enrolling on E5103 between 1/5- 6/8/10. Women were surveyed pretreatment and after unblinding. Wilcoxon rank sum testing was used to examine differences. Results: 572 patients on DM-QOL started protocol therapy; 118 on arm A, 454 on arm B/C; the two groups (arm A vs. B/C) were well balanced. 516 patients participated in pretreatment, 514 in unblinding survey. Pretreatment, 32% reported >moderate chance of recurrence in 5 years, 27% >moderate chance of serious problem from treatment, 99% feeling at least somewhat informed, 98% at least somewhat confident in study participation, most “extremely” confident. Overall, median response scores did not change over time, with no statistically significant differences between the groups in changes in perceptions of: recurrence risk (p=0.45); chances of a serious problem (p=0.12), feeling informed (p=0.99). However, they differed in confidence about study participation (p=0.04): after unblinding, a higher % of placebo-treated patients had increased confidence (38% vs. 25%), and a higher % of bevacizumab-treated patients had decreased confidence (29% vs. 22%), although 44% across all arms had no change. Conclusions: In a placebo-controlled, double-blinded RCT, unblinding did not significantly affect most participants’ views, regardless of receipt of placebo or experimental drug. However, confidence in study participation may have been affected by knowledge of receipt of bevacizumab; publicity surrounding this experimental therapy may have affected results.