bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of Oncotype DX testing and subsequent patterns of care in patients (pts) with early-stage breast cancer (ESBC).
Authors: Fitzgerald Meghan , Hassell Robert , Haislip Sally , Gilmore James W. , Richardson Steve , Cooper Joseph , Szabo Stephen , Feinberg Bruce A. 
Published: March 2020

569 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 BlueShield revealed that pts with estrogen receptor-positive ESBC who underwent Oncotype DX testing and were found to have high-risk Recurrence Scores (RS) received less chemotherapy than expected. To better understand physician behavior as it relates to Oncotype DX testing, CHSS examined patterns of Oncotype DX use in a large private practice oncology group with a robust electronic medical record (EMR), Georgia Cancer Specialists (GCS). We aimed to determine the RS risk distribution among pts who received Oncotype DX testing and assess the patterns of care that followed. Methods: Using GCS EMR data from 2009 to 2011, the number of pts who were eligible to undergo Oncotype DX testing was compared to the number of pts who underwent testing. Pts were considered eligible for testing if they had node-negative, estrogen receptor-positive, HER2-negative ESBC. 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 chemotherapy in each category. Results: Of the 1908 patients identified with ESBC, 788 were eligible for Oncotype DX 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 chemotherapy. Seventeen percent of pts in the high-risk group did not receive chemotherapy. Conclusions: The use of chemotherapy in the low- and intermediate-risk groups was as expected based on adjuvant chemotherapy guidelines; however, an under utilization of chemotherapy was found in high-risk pts. There also appears to be a noteworthy underuse of Oncotype DX testing in eligible pts. Further data analysis is needed to understand the low use of Oncotype DX testing in eligible pts and to explain the lower than expected use of chemotherapy in high-risk pts.
Estrogen receptor (ER) signaling in normal, BRCA (B) 1 and B2 mutation associated, and ER-positive breast cancer (BC) mammary cells.
Authors: Lim Elgene , He Housheng Hansen , Chi David , Garber Judy Ellen , Richardson Andrea , Brown Myles 
Published: March 2020

576 Background: ER is expressed in ≈70% of sporadic BC and activates genes driving cell proliferation and tumorigenesis. B1 and B2 mutation associated BC have predominant triple negative and ER+ phenotypes respectively, yet hormonal manipulation with oophorectomy reduces BC risk in both B1 and B2 carriers. We have previously performed genome-wide analysis of ER binding sites in MCF-7 BC cells, and identified distinct mechanisms of ER signaling. Here, we seek to elucidate differences in ER signaling between non-malignant (normal, B1 and B2) and ER+ BC mammary cells. Methods: Breast tissue were obtained from patients undergoing reduction mammoplasties (normal), prophylactic mastectomies (B1 and B2 carriers) and surgical excision of ER+ BC. After dissociation into a single-cell suspension, ER+ EpCAM+CD49f- mature luminal (ML) and EpCAM+CD49f+ luminal progenitor (LP) subpopulations were obtained by flow cytometry. Following estrogen stimulation, RNA was extracted for gene microarray analysis. ER chromatin immunoprecipitation and DNA sequencing (ChIP-seq) was performed and DNA libraries prepared and sequenced. Results: Triplicates ofnormal, prophylactic B1 and B2, and ER+ BC tissues were analyzed.Gene ontology analysis indicates different gene expression signatures between non-malignant tissue and MCF-7 BC cells following estrogen stimulation. Genes that promotes cell cycling and proliferation were downregulated in non-malignant tissue, but were upregulated in BC cells (P < 10-5). Hierarchical clustering of the gene microarray by mutation status revealed distinct LP gene signatures in normal, B1 and B2 breast tissue, whilst the ML signatures were largely indistinguishable between the three tissue types. Conclusions: There are contrasting differences in ER signaling between normal mammary and BC cells, with estrogen having anti-proliferative effects in normal luminal cells compared to pro-proliferative effects in BC. Our data suggest that alterations in ER signaling play a major role in breast tumorigenesis. Differences in the LP population between B1 and B2 breast tissue may account for their distinct BC phenotypes.
Molecular subtyping using MammaPrint and BluePrint as an outcome predictor in 180 U.S. breast cancer (BC) patients.
Authors: Stork-Sloots Lisette , Yao Katharine , Turk Mary , Kaul Karen , Weaver JoEllen , De Snoo Femke , Cristofanilli Massimo 
Published: March 2020

577 Background: Combined use of MammaPrint and a molecular subtyping profile (BluePrint) identifies disease subgroups with marked differences in long-term outcome and response to neo-adjuvant therapy (Glück SABCS2011). The aim of this study was to evaluate the prognostic value of Molecular Subtyping using MammaPrint and BluePrint in women with early stage BC treated at US Institutions following National Comprehensive Cancer Network (NCCN) standard guidelines. Methods: Frozen tumor samples from 180 BC patients (TI-III, N0-Ib) median age 57 years at diagnosis (range 28-89) were suitable for hybridization on full genome array. MammaPrint and BluePrint Molecular Subtypes were determined and survival for Luminal A (MammaPrint Low Risk), Luminal B (MammaPrint High Risk), HER2-type and Basal-type patients was assessed. Patients were treated either with breast conserving therapy or mastectomy with axillary lymph node dissection between 1992 and 2005. The median follow-up is 12.7 years. 71% was ER positive and 20% Her2 positive by IHC/FISH. 58% received adjuvant endocrine therapy (ET) (excluding 13 patients unknown treatment), 64% received adjuvant chemotherapy (CT) (excluding 12 patients unknown treatment) and 33% received both. Results: 61 (34%) Patients with MammaPrint Low Risk/Luminal-type (Luminal A) showed 5-year DFS of 97% (34% received CT and 69% ET) and 50 (28%) patients with MammaPrint High Risk/Luminal-type (Luminal B) had a 5-year DFS of 98% (60% received CT and 68% ET). Patients with BluePrint Basal-type tumors (46 (26%)) had a 5-year DFS of 80% (78% received CT); HER2-type (23 (13%)) had a 5-year DFS of 78% (87% received CT without HER-2 targeted therapy). Conclusions: In this retrospective study evaluating 180 US patients with early BC treated according to standard guidelines we showed how combining BluePrint with MammaPrint can detect molecularly defined subgroups of patients who are at high risk of recurrence (HER2 and Basal-type). Furthermore, we confirmed that molecularly defined Luminal type disease is associated with excellent disease-free survival. MammaPrint and BluePrint molecular and prognostic stratification should be prospectively evaluated for therapeutic selection.
Impact of hormone receptor (HR) status on clinicopathological features, patterns of recurrence, and clinical outcomes among patients (pts) with human epidermal growth factor receptor-2 positive (HER2) breast cancer (BC) in the National Comprehensive Cancer Network (NCCN).
Authors: Luis Ines Maria Vaz Duarte , Ottesen Rebecca A , Hughes Melissa E , Marcom P. Kelly , Moy Beverly , Rugo Hope S. , Theriault Richard L. , Wilson John , Niland Joyce C. , Weeks Jane C. , Lin Nancy U. 
Published: March 2020

599 Background: According to gene expression profiling, HER2+ BC is heterogeneous and appears to diverge by HR status. Methods: We evaluated 3394 pts who presented to NCCN centers with stage I-III HER2+ BC between 2000-07. Pts were classified as HR+ (ER+ and/or PR+) and HR- (ER- and PR-). Chi-square, univariate logistic regression, log-rank test, and Cox hazard proportional regression were used for analysis. Results: Median follow-up was 51 months. 59% of patients had HR+ and 41% HR- disease respectively. Pts with HR- BC were more likely to be postmenopausal and to present with higher stage and high grade disease (p<0.001). Most pts received adjuvant or neoadjuvant therapy; 44% received adjuvant trastuzumab. Recurrences were recorded for 458 pts. HR- patients were more likely to recur first in the central nervous system (CNS) (OR: 1.8, 95% CI: 1.1, 2.9; p= 0.03) and less likely to recur in bone (OR: 0.5, 95% CI: 0.3, 0.8; p<0.01). No differences in risk of lung or liver recurrence were observed. Combining first and subsequent sites of recurrence, the difference in CNS involvement was lost (p=0.107) but HR- were more likely to experience lung involvement (OR: 1.5, 95% CI: 1.0, 2.2; p= 0.05). After adjusting for age, year of diagnosis (y), race, stage, and grade, HR- had worse survival after initial BC diagnosis than HR+ pts (Hazard Ratio of death [HRd] 1.4, 95% CI: 1.14, 1.7; p<0.01). However, the risk of death was not proportional over time with HR- having significantly increased hazard in the first five years: HRd 0-2 y 1.9 [1.3, 2.9]; p< 0.01; HRd 2-5y 1.5, [1.2, 2.0]; p<0.01; HRd 5+ y, 0.8, [ 0.6, 1.2], p=0.29. Conclusions: Clinicopathological features, sites of recurrence, and risk of death over time for HER2+ BC differed by HR status. This suggests that HR status in HER2+ BC is clinically relevant. These differences should be further explored from a mechanistic and therapeutic standpoint.
Cancer patient acceptance, understanding, and willingness to pay for pharmacogenetic testing (PGT).
Authors: Hon Henrique , Qiu Xin , Tobros Kimberly , Wong Chung-Kwun Amy , De Souza Bradley , McFarlane Graham , Masroor Sohaib , Azad Abul Kalam , Hasani Ekta , Rozanec Natalie , Leighl Natasha B. , Alibhai Shabbir M.H. , Xu Wei , Issa Amalia M. , Liu Geoffrey , Cuffe Sinead 
Published: March 2020

6005 Background: PGT offers the potential to improve cancer therapy through the use of specialized tests that can predict the level of efficacy and/or toxicity of specific treatments in an individual. However, there is currently little knowledge concerning cancer patient attitudes towards such testing in the clinical setting. Methods: We interviewed a broad cross-section of 278 cancer patients (20% lung, 19% breast, 20% colorectal, 40% other) using hypothetical time, efficacy, toxicity and willingness-to-pay trade-off PGT scenarios. Results: 153 potentially curable patients and 125 incurable patients received a separate series of trade-off scenarios. For curative patients, 70% accepted chemo that had a 5% absolute improvement in cure rate and <5% of severe toxicity. Of these, 99% wanted PGT where the test identifies a subset of patients benefiting from chemo; the same individuals were willing to pay a median $2,000 (range: $0-25,000) for PGT and would accept a median wait time for PGT results of 21 days (0-90). Patient preferences were insensitive to variation of fractions of individuals carrying the genetics associated with lack of benefit. In the incurable scenario, 90% of patients accepted palliative chemo with an 80% response rate and a severe side effect rate of 5%. Of these, 98% wanted PGT, where there test identifies individuals at highest risk of severe toxicity; the same individuals were willing to pay a median $1,000 ($0-15,000) for PGT, and would accept PGT turnaround times of 14 days (1-90). Patient preferences were insensitive to variation of fractions of individuals carrying the genetics associated with severe toxicity. The majority of patients (76% adjuvant; 87% metastatic) wanted to be involved in decision making regarding PGT; however, one in five patients (20% adjuvant; 22% metastatic) admitted that they lacked a basic understanding of what PGT means and its clinical implications. Conclusions: Among cancer patients willing to undergo chemo, almost all wanted PGT and were willing to pay for it, waiting several weeks for results. While patients had a strong desire to be involved in decision making for PGT, a considerable proportion lacked the necessary knowledge to make informed choices.
A comparison of primary care providers’ and oncologists’ preferences for different models of cancer survivorship care.
Authors: Cheung Winson Y. , Noone Anne Michelle , Aziz Noreen , Rowland Julia Howe , Potosky Arnold L. , Ayanian John , Virgo Katherine S. , Ganz Patricia A. , Stefanek Michael Edward , Earle Craig 
Published: March 2020

6006 Background: There is increasing interest in developing more efficient and effective strategies for coordinating and delivering cancer and non-cancer related follow-up care to survivors. The objectives of this nationwide survey were to describe and compare US physician preferences for different cancer survivorship care models. Methods: The Survey of Physician Attitudes Regarding the Care of Cancer Survivors (SPARCCS) was mailed to PCPs and oncologists in order to evaluate their views regarding physician responsibilities, knowledge levels about survivorship, and cancer follow-up testing. Using weighted univariate and multivariate models, we analyzed PCPs’ and oncologists’ preferences for different cancer survivorship care models (PCP/shared vs. oncologist vs. non-physician provider) and examined how physician attitudes towards and self-efficacy with their own skills during breast and colorectal cancer follow-up affected these preferences. Results: Of 3,434 physicians surveyed, 2,202 (64%) responded of whom 2,026 (59%) provided eligible outcomes for this study: 938 (46%) PCPs and 1,088 (54%) oncologists. In unadjusted analyses, most PCPs (51%) supported a PCP/shared care system whereas the majority of specialists (59%) strongly endorsed an oncologist-based model (p<0.001). A number of PCPs and oncologists (23% for both) preferred to involve non-physician providers. A significant proportion of cancer specialists (87%) did not feel that PCPs can take on the primary role for cancer follow-up. Many PCPs believed that they have the skills to perform breast and colorectal cancer follow-up (57%), detect recurrent cancers (74%), and offer psychosocial support (50%), but only a minority (32%) were willing to assume exclusive responsibility. In adjusted analyses, PCPs already involved with cancer surveillance (43%) were more likely to prefer a PCP/shared care system than an oncologist-based survivorship care model (OR 2.08, 95%CI 1.34-3.23, p<0.001). Conclusions: PCPs and oncologists have different preferences for models of cancer survivorship care. Prior involvement with cancer follow-up was one of the strongest predictors of PCPs' willingness to assume this responsibility.
Insurance status and cancer disparities in adolescents and young adults age 15 to 39: National Cancer Data Base, 1998-2003.
Authors: Robbins Anthony , Lerro Catherine C. , Barr Ronald 
Published: March 2020

6011 Background: Since the mid-1970s there has been little progress in improving cancer survival for adolescents and young adults (AYAs, defined by the National Cancer Institute as individuals 15 to 39 years of age), in contrast to the substantial improvements for children and older adults. The association between insurance status and cancer disparities (stage at diagnosis, survival, and treatment) in AYA patients has not been examined in a national sample. Methods: The National Cancer Data Base, a national hospital-based cancer registry, was used to examine insurance status and cancer disparities in 177,359 AYA cancer patients. Cases were diagnosed during 1998−2003 and followed for vital status through 2008. We examined the association between insurance status and stage at diagnosis, stage-specific survival, and receipt of the most frequently used stage-specific treatments for common AYA sites (thyroid, female breast, non-Hodgkin lymphoma, and acute myeloid leukemia). Results: Insurance status was strongly related to cancer disparities in AYA patients. For example, compared to patients with private insurance, uninsured patients were 1.71 times more likely to be diagnosed at stage IV (95% confidence interval [CI], 1.63−1.79), had higher risk of death within every stage [stage I, hazard ratio (HR) (95% CI), 2.43 (2.13−2.76); stage II, 1.87 (1.70−2.06); stage III, 1.55 (1.43−1.68); stage IV, 1.39 (1.31−1.48); and unstaged (leukemias, CNS tumors, etc.), 1.67 (1.58−1.76), and for the four sites listed above, were less likely to receive the most frequently used stage-specific treatments. Insurance status remained a strong independent predictor for each of these outcomes in multivariate models adjusting for patient, hospital, and tumor factors. Conclusions: In a large national sample, insurance status was a strong independent predictor of cancer disparities in AYA patients. The Affordable Care Act of 2010 should facilitate the acquisition of adequate health insurance by AYA, who are the most under- and uninsured age group in the US population, and should contribute to remediation of such disparities.
Racial differences in the impact of financial hardship on the intensity of end-of-life cancer care.
Authors: Tucker-Seeley Reginald D , Abel Gregory Alan , Prigerson Holly Gwen 
Published: March 2020

6012 Background: Research suggests that Black cancer patients have higher end-of-life (EOL) medical costs than White patients; and that Black, compared with White, families are more likely to use all or most of their savings to pay for EOL care. Although Black cancer patients receive more intense EOL care than Whites, research has yet to determine the effect of financial hardship on receipt of intensive EOL care, and whether the effect varies by the patient’s race. Methods: Coping with Cancer (CwC) is a longitudinal, multi-site cohort study of advanced cancer patients and their informal caregivers recruited from September 2002-February 2008. CwC was designed to investigate Black/White differences in EOL care. The purpose of this analysis was to determine the association between baseline financial hardship and receipt of intensive EOL care in the last week of life (CwC deceased cohort N=342), and to identify racial differences in this association. Financial hardship was defined as whether the household had to use all or most of their savings due to the family member’s illness (response =yes/no). Intensive EOL care was defined as the receipt of ventilation or resuscitation in the last week of life assessed by medical record review and patient’s caregiver. Results: Patients reporting financial hardship had higher odds of receiving intensive EOL care (OR = 2.83, CI: 1.33, 6.05). After adjusting for socio-demographic characteristics the significant association remained (OR = 2.55, CI: 1.13, 5.81). Race-stratified fully adjusted models revealed no statistically significant association between financial hardship and intensive EOL care for Whites; however, for Blacks, those reporting financial hardship had over five times higher odds of receiving intensive EOL care (OR = 5.21, CI: 1.51, 17.99) compared to those not reporting financial hardship. Conclusions: Financial hardship was associated with greater likelihood of receiving intensive EOL care. The intensity of EOL care received by White patients was insensitive to financial hardship; in contrast Black patients reporting depletion of life savings for cancer care were much more likely to die receiving intensive EOL care than their non-financially strained counterparts.
Toxicity of chemotherapy dosing using actual body weight in obese versus normal-weight patients: A systematic review and meta-analysis.
Authors: Hourdequin Kathryn Cunningham , Schpero William Lewis , Piazik Breanne Lee , McKenna Dorothy R , Larson Robin Joyce 
Published: March 2020

6013 Background: Because weight-based chemotherapy calculations can be very large in obese patients, oncologists often empirically reduce doses due to fear of excess toxicity. The resulting underdosing may negatively impact survival. We performed a systematic review and meta-analysis to determine whether, among adults receiving chemotherapy dosed by actual body weight (ABW), obese patients experience differing toxicity or survival compared to normal-weight patients. Methods: We searched MEDLINE, Cochrane Library, Web of Science, and ClinicalTrials.gov through October 2011 and reviewed reference lists. We included studies that compared outcomes of obese versus normal-weight adults receiving chemotherapy dosed according to ABW (+/- 5% variability). Studies followed subjects for at least one cycle of chemotherapy and reported at least one pre-specified outcome. Two authors independently abstracted data from eligible studies. We used random effects models to pool odds ratios (OR) for hematologic and non-hematologic toxicities. We summarized survival qualitatively. Results: Of 3,921 studies, five met inclusion criteria, for a total of 6,877 subjects. Based on three studies, Grade 3/4 hematologic toxicity occurred less often in obese patients than normal-weight patients (OR 0.68, 95% CI 0.51-0.89, I2=29%). A fourth study comparing leukocyte nadirs had variable results depending on the regimen, dosing, and patient co-morbidities. Based on two studies, Grade 3/4 non-hematologic toxicity occurred less often in obese patients than normal-weight patients (OR 0.74, 95% CI 0.63-0.87, I2=0%). A third study found rates of infection did not significantly differ. Three of four studies reported reduced overall survival in obese patients (statistical significance not reported). Conclusions: Contrary to common belief, obese patients receiving chemotherapy based on ABW appear to have lower rates of both hematologic and non-hematologic toxicities compared to normal-weight patients. These results do not support the practice of empiric dose reduction in obese patients. Further research should explore etiologies for the reduced survival in this group.