bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oncotype recurrence score (RS) and discordance in patients with secondary invasive breast events (SIBE).
Authors: Zimmerman Brittney Shulman , Cascetta Krystal Pauline , Blanter Julia , Eggert Lauren , Molot Madeline , Ru Meng , Nayak Anupma , Bleiweiss Ira , Jaffer Shabnam , Tiersten Amy 
Published: May 2019

e12016 Background: Oncotype RS is a 21-gene assay used to predict the likelihood of distant recurrence and benefit of chemotherapy in patients with node-negative, tamoxifen treated breast cancer (BC). We developed a database to determine rates of SIBE and identify cases of discordance between Oncotype RS and tumor grade (TG). Our goal was to recognize patients with discordant tumors who had SIBE, with implications for patient management. Methods: We identified 618 patients (645 samples) with early-stage, hormone positive BC treated between 2006-2018, with tumor characteristics available for analysis. Among these patients, there were 24 SIBE (n = 24) from 23 patients (3.7%). When stratified by RS using traditional cutoffs (Paik, 2004), rates of SIBE were 2.8%, 5.0% and 4.5% in low, intermediate and high-risk groups respectively. Discordance was defined as 1 or 2-step difference between RS (low, intermediate, high risk) and TG (well (WD), moderately (MD) and poorly (PD) differentiated). Prior studies demonstrated 7-19% “2-step discordance” between TG and RS (i.e. PD tumors with low-risk RS or WD tumors with high-risk RS). N(%) or median were used to describe patients’ characteristics between groups and compared by Mann-Whitney U test at the confidence level of 5%. Results: Of the 24 SIBE, 42% had low RS ( < 18), 46% had intermediate RS (18-30) 12% had high RS ( > 31). Median RS was 22 and median age at secondary event was 61 (67% post-menopausal). At time of SIBE, 54% were metastatic, 25% locally recurrent and 21% contralateral. Within this dataset, 63% were 1-step and 4% were 2-step discordant. Significantly fewer patients were treated with systemic chemotherapy in the discordant group (p < 0.01), though 94% displayed MD or PD TG. Discordant tumors tended to have lower RS (median 14 vs. 24) and be larger. There were no significant differences in menopausal status or Oncotype ER/PR score. Conclusions: Although the sample size of patients with SIBE is small, our data suggests that patients with discordant tumors of low-risk RS but higher TG may be receiving inadequate treatment (i.e. no chemotherapy). In addition to RS, other factors such as discordance, TG and size should perhaps be considered when determining treatment plans.
Role of adjuvant chemotherapy in small (≤5 mm) node-negative and hormone receptor-negative breast cancer.
Authors: Master Samip R. , Dadi Neelakanta , Shah Chintan , Burton Gary Von , Shi Runhua 
Published: May 2019

e12021 Background: There is currently lack of adequate data to support for or against the role of adjuvant chemotherapy for small( < = 5mm) hormone negative and node negative breast cancer. We did a retrospective analysis from National Cancer Database (NCDB) to assess the effect of adjuvant chemotherapy in HER2 positive/ Hormone receptor negative (HER+HR-) and triple negative breast cancer. Methods: Data was analyzed from approximately nine thousand women registered in the (NCDB) who were diagnosed with triple negative and HER+ HR-small ( < = 5mm) and node negative breast cancer between 2010 and 2014 and had follow-up to the end of 2015. The primary predictor variable was the receipt of chemotherapy, and outcome variable was overall survival. Additional variables addressed and adjusted included age, race, Charlson Comorbidity Index and grade of cancer. Results: Approximately 59% patients received adjuvant chemotherapy. The five year overall survival in women with triple negative for breast cancer who received chemotherapy was 79% , compared to 87% , for those who did not receive chemotherapy(p < 0.00001). The five year overall survival in women with Her2+HR- for breast cancer who received chemotherapy was 68% , compared to 84% , for those who did not receive chemotherapy(p < 0.00001).In multivariate analysis, after adjusting for secondary predictor variables, avoidance of adjuvant chemotherapy was associated with 59.5% reduction in risk of death. Conclusions: Our analysis suggests that there are no role for adjuvant chemo in small breast cancers that are Her+ HR- and triple negative. The receipt of adjuvant chemotherapy lead to decrease in overall survival.
Sequential versus concurrent use of chemotherapy and endocrine therapy in the adjuvant treatment of ER-positive breast cancer: A systematic review and Bayesian network meta-analysis.
Authors: Li Tianfu , Shan Zhen , Yu Liang , Kuang Xiaying , Zhang Deyuan , Lu Sihong , Zhang Qi , Shao Nan , Lin Ying 
Published: May 2019

e12040 Background: Chemotherapy followed by endocrine therapy is the standard adjuvant treatment strategy for estrogen receptor-positive breast cancer patients. However, no direct evidence so far demonstrated better efficacy of sequential use of chemotherapy and endocrine therapy over concurrent. Objective: To evaluate the efficacy between sequential and concurrent use of chemotherapy and endocrine therapy in the adjuvant treatment of ER positive breast cancer. Methods: Randomized clinical trials comparing chemotherapy and/or endocrine therapy in the adjuvant treatment of ER positive breast cancer were included. Hazard ratios (HRs) of disease-free survival (DFS) and overall survival (OS) were extracted and analyzed in Bayesian analysis. Patients were stratified by menopause status for subgroup analysis. Results: 37 trials were identified with 37225 patients enrolled in total, 37 trials with DFS results and 24 with OS. 3 comparisons were done between sequential and concurrent arms. In DFS analysis, no statistical significance was found in all 3 comparisons [CHE seq/con TAM (HR 1.01, 95%CI 0.8497 - 1.199); CHE seq/con OFS+TAM (HR 0.9119, 95%CI 0.5666 - 1.49); CHE seq/con OFS+AI (HR 1.032, 95%CI 0.6291 - 1.776)]. The same were seen in OS analysis [CHE seq/con TAM (HR 0.9512, 95%CI 0.8053 - 1.125); CHE seq/con OFS+TAM (HR 1.065, 95%CI 0.6344 - 1.789); CHE seq/con OFS+AI (HR 1.069, 95%CI 0.665 - 1.717)]. Rankings were done for preferable treatment recommendations. In DFS analyses, sequential arms ranked higher than concurrent arms [CHE seq/con OFS+AI (1 vs. 3); CHE seq/con OFS+TAM (6 vs. 7); CHE seq/con TAM (8 vs. 8)]. The same tendency was seen in OS analyses [CHE seq/con OFS+AI (1 vs. 2); CHE seq/con TAM (4 vs. 5)] except for CHE seq/con OFS+TAM (11 vs. 6-9). In subgroup ranking results, CHE seq/con OFS+AI and CHE seq/con OFS+TAM showed consistency among comparisons with concurrent arms ranked higher than sequential arms. However, CHE seq TAM ranked higher than CHE con TAM in all comparisons. Conclusions: The combination of chemotherapy and endocrine therapy in the adjuvant treatment of ER positive breast cancer demonstrated equal efficacy either used sequentially or concurrently. However, concurrent arms were recommended over sequential arms in premenopausal patients for better DFS and OS, except for the combination of chemotherapy and tamoxifen which was recommended to be used sequentially. Others: This study has been registered in PROSPERO (CRD42018104889).
The prognostic role of the androgen receptor in patients with triple-negative early breast cancers and primary surgery.
Authors: Jongen Lynn , Floris Giuseppe , Wildiers Hans , Claessens Frank , De Sutter Luna , Croes Romaric , Decloedt Jan , Laenen Annouschka , Ardui Jan , Punie Kevin , Berteloot Patrick , Vergote Ignace , Neven Patrick 
Published: May 2019

e12042 Background: The prognostic value of androgen receptor (AR) expression in triple-negative breast cancer (TNBC) is debated and might be partially masked by the use of adjuvant chemotherapy, which might benefit AR-negative TNBC more than AR-positive cases. We compared the prognostic value of AR in a case control study of consecutive women with TNBC treated or not with adjuvant chemotherapy (ACT). Methods: We retrospectively studied AR expression by immunohistochemistry in all consecutive patients with a secondary metastatic TNBC treated in UZ-Leuven between 2000 and 2009. The control group were cases of TNBC never developing secondary metastatic disease during a long follow-up period matched 1:1 for age and tumor grade. Relations between demographics and clinical pathological features and AR protein expression were studied, including stromal tumor infiltrating lymphocytes (sTILs). Secondary metastatic disease connections with AR protein expression was assessed using the Akaike information criterion; time-to metastasis (TTM) was studied using a linear model with and without ACT correcting for lymph node involvement. We explored whether results differed by AR protein expression levels (0%, 1-34%, ≥34% of tumor cells) and body-mass index (BMI) comparing normal ( < 25kg/m2) with overweight/obese patients BMI. Results: We included 139 patients (69 metastatic and 70 non-metastatic; median age 51.0 years); median follow-up for both groups was 8 years. AR protein expression level ≥ 1% was observed in 25% (n = 34) and ACT was given in 73% (n = 101). AR-positive as compared to AR-negative TNBC patients were older (p = 0.04). Results based on multivariable models including lymph node status and ACT as confounders showed that AR-negative cases have a higher metastasis risk compared to AR-positive patients (3.015 odds ratio (95% CI 1.199-7.582), p = 0.02); this difference was more significant in ACT-naive patients (10.823 odds ratio (95% CI 1.897-61.740), p = 0.007). ACT-treated patients had the best outcome if AR was low (1≤ and < 34%) followed by those with a normal weight and an AR-negative high sTIL TNBC. Conclusions: The AR is prognostic in TNBC and this is clearer in non-ACT treated patients with a TNBC. Our results might suggest that if ACT is given, only the AR-positive TNBC with low AR-expression do well.
Oncotype DX score in hormone receptor-positive/HER2-positive breast cancer: A SEER analysis.
Authors: Qasrawi Ayman , Myint Zin , Alnimer Yanal Mufeed , Romond Edward H. 
Published: May 2019

e12044 Background: The recurrence score Oncotype DX (RS) predicts the need for adjuvant chemotherapy in hormone receptor positive (HR+) early stage breast cancer (BC). However, it has not been validated for HR+/HER2+ BC cases. We aim to evaluate the results of RS in HR+/HER2+ BC by using the Surveillance, Epidemiology, and End Results Program (SEER) national database. Methods: We identified patients with non-metastatic HR+/HER2+ BC with reported RS scores from the national SEER database between 2010 and 2015. Data obtained included demographics, histologic subtypes, grading, tumor size, nodal status, HR status and overall survival (OS) outcomes. RS scores were divided into low/intermediate (≤30) and high ( > 30). Histologic subtypes were further categorized into favorable (lobular, tubular, mucinous, and cribriform) and unfavorable (infiltrating ductal, mixed ductal, and micropapillary). We used Kaplan-Meier & Cox regression to analyze the survival outcomes. Logistic regression analysis was used to analyze the correlation between variables and different RS scores. Results: A total of 1537 patients were included. Median age was 61 (25-90). Majority of the patients presented with node negative disease (85%), low/intermediate grade (71%), tumor size < 20 mm (73%), unfavorable histology (89%), and only 15% had negative progesterone receptor (PR –). High RS score ( > 30) was seen in 24% of cases. After a median follow-up of 38 m (1-72), the five-year OS was 94.5%. Chemotherapy was given to 71% and 35% of those with RS > 30 and ≤30, respectively. There was a strong correlation between age > 60 ([hazard ratio, HR] = 4.9, p < 0.0001) and RS > 30 (HR = 2.4, p = 0.004) with worse outcomes on multivariate analysis. However, there were no associations between histologic subtype, tumor size, grade, nodal status and chemotherapy with survival. Tumor size > 20 mm (OR = 1.5), unfavorable histology ([odds ratio, OR] = 3.5), PR – (OR = 4.3) and high grade tumors (OR = 4.5) were independent predictors of RS > 30 (p < 0.0001). Conclusions: Our study shows that large tumor size ( > 20 mm), higher grade, PR –, and unfavorable histology were independent risk factors for higher RS in patients with localized early stage HR+/HER2+. High RS was associated with worse outcome.
Chemotherapy-related outcomes in triple-negative breast cancer.
Authors: Wellmann Rebecca M. , Ghafouri Sanaz N. , McAndrew Nicholas Patrick , Hurvitz Sara A. 
Published: May 2019

e12049 Background: Triple-negative breast cancer (TNBC) is associated with a poor prognosis when compared to hormone receptor positive breast cancers. Anthracycline-based regimens (ABRs) are mainstays of treatment for non-metastatic TNBC. However, anthracyclines are associated with an increased risk of potentially life-threatening adverse effects. We sought to compare survival outcomes in patients with early TNBC treated with ABRs versus those treated with anthracycline-sparing regimens (ASRs). Methods: All patients treated for stage I-III TNBC who had undergone curative-intent surgery at a large academic medical center between January 2013-May 2018 were included in the study. Event-free survival (EFS) and disease-free survival (DFS) were the primary endpoints, with overall survival (OS) as a secondary endpoint and were defined as per standardized STEEP criteria. Kaplan-Meier, multivariable Cox regression, and log-rank tests were used to define key survival and treatment related differences between subjects treated with ABRs vs ASRs. Results: 137 patients met inclusion criteria with a median follow-up of 39 months. 21 patients (15%) recurred and 16 (12%) died. Patients treated with ABRs (n = 26, 19%) compared with ASRs (n = 111, 81%) had significantly shorter median EFS (38 months vs not-yet-reached, NYR, p < 0.001), DFS (37 months vs NYR, p < 0.001), and OS (50 months vs NYR, p < 0.001). Though patients in the ABR vs the ASR group were more likely to be node-positive (Odds Radio 3.46, p = 0.006), shorter survival estimates in the ABR group were observed after adjusting for nodal status. 27% of patients (7/26) had an anthracycline added after suboptimal response to an ASR. After adjusting for these patients, the survival findings were similar. 43 patients (31%) received a platinum containing ASR. In the platinum subgroup, ASRs were associated with longer EFS and DFS compared to ABRs, but this effect was not statistically significant in the node-positive group. No cardiac or secondary leukemic events were observed in either group. Conclusions: ABRs were associated with shorter EFS, DFS and OS, even after adjusting for certain high-risk clinical features. Larger studies are needed to identify the role of platinum containing ASRs in patients with early TNBC.
Does the time to initiate adjuvant chemotherapy effect outcome in patients with breast cancer? A National Cancer Database-based retrospective analysis.
Authors: Ashok Kumar Prashanth , Wang Dongliang , Sinha Shreya , Sivapiragasam Abirami 
Published: May 2019

e12054 Background: The Early Breast Cancer Trialists Collaborative Group showed that adjuvant therapy for breast cancer (BC) significantly reduces the 5-year recurrence and 15-year mortality rates. After surgery, it usually takes around 4-6 weeks to begin adjuvant chemotherapy and delay in initiating the same is believed to lead to poorer outcomes. A number of studies have sought to evaluate the role of delayed initiation of chemotherapy on survival but results have remained controversial and an optimal time has not been defined. Methods: Our aim was to determine the effect of delay in starting chemotherapy from the date of surgery on survival of patients with early BC using the National Cancer Database (NCDB) data. From the database, we selected patients aged >18 years with stage 1-3 BC who received adjuvant chemotherapy. We included all ER/PR statuses. A total of 544,005 patients were divided into 3 groups based on the time of initiating chemotherapy from the date of surgery i.e., 0-60 days, 60-90 days and >90 days and had a distribution of 38.07%, 35.90% and 26.03 % respectively. Results: Estimates from cox models showed the following adjusted Hazard Ratios(HR): 0-60 days vs >90 days (HR 0.976, CI 0.955-0.998), 60-90 days vs >90 days (HR 0.899, CI 0.879-0.920). Kaplan Meier Survival estimates revealed that the 0-60 days and the 60-90 days groups had a better 10 year survival estimate than the > 90 days group with a p<0.0001. The factors that correlate with delay in initiating adjuvant chemotherapy are African American race, poor Charlson Deyo Score, uninsured or government insurance holders, well differentiated tumors and ER/PR positive status. Conclusions: Based on our analysis from a large national database, we hypothesize that delaying adjuvant therapy for more than 90 days may have worse outcomes due to reasons like rapid growth of micro metastasis following removal of the primary tumor. Thus for stage 1-3 BC, the ideal time to start adjuvant chemotherapy from the date of surgery is before 90 days. Survival estimates from Kaplan-Meier analysis. [Table: see text]
Is it possible to predict the prognostic values of Oncotype Dx using the results of web-based mathematical prognostic value models?
Authors: Iwatani Tsuguo , Tsugawa Koichiro 
Published: May 2019

e12058 Background: The goal of the study was to determine whether the prognostic values for ER+ HER2- breast cancer can be calculated based on a test of gene expression profiles in tumors using Oncotype Dx or by entering clinicopathological factors into a web-based model. We evaluated the correlation between these results to shed light on whether the results from web-based models could serve as representative indices for Oncotype Dx. Patients: Two hundred two primary breast cancer patients whose prognostic value was evaluated using Oncotype Dx between May 2010 and October 2018 in St. Marianna University Hospital. Methods: The patients’ clinicopathological factors were extracted from their medical records. Then, the 5- and 10-year breast cancer-specific mortality rates were calculated using PREDICT (www.predict.nhs.uk/tool), while the 5–10 year distant recurrence rate was calculated using CTS5 (www.cts5-calculator.com/). The correlations with the Oncotype Dx prognostic values were evaluated by calculating the Spearman’s rank correlation coefficient, and JMP.ver13.0 (SAS Institute Inc., Cary, NC, USA) was employed for the analysis. Results: The patients’ median age was 49. There were 78 lymph node(LN)-negative patients and 124 LN-positive patients. For the disease stages, 51 patients were stage I, 99 patients were stage IIA, 41 patients were stage IIB, and 11 patients were stage III or above. All patients of the correlation between the Oncotype Dx recurrence score (RS) and the 10-year breast cancer-specific mortality rate was r = 0.1616. The correlation of LN-Negative patients of the 10-year distant recurrence rate between Oncotype Dx and CTS5 was r = 0.1768. The correlation of LN-Positive Cases of the 5-year distant recurrence rate between Oncotype Dx and CTS5 was r = 0.3374. The correlation of these cohort between the 5-year mortality rate from Oncotype Dx and PREDICT was r = 0.4298. Conclusions: There was no correlation between the Oncotype Dx RS and prognostic values calculated from web-based models, and there was also no correlation for prognostic values of lymph node-negative cases. However, there was a correlation for prognostic values of lymph node-positive cases, but the correlation was too weak to use the results from web-based models as representative indices for Oncotype Dx.
Clinical relevance of 21-gene recurrence score with lymph node involvement in HR+HER2- early breast cancer: A tumor size-match paired cohort study.
Authors: Yu Xingfei , Wang Chen , Chen Bo , Pan Xiaodan , Yang Hongjian 
Published: May 2019

e12059 Background: Axillary lymph node (LN) involvement is significantly related with high recurrent risk and influenced by tumor size, histologic grade and subtype in early breast cancer. For hormone receptor positive (HR+) and human epidermal growth factor receptor-2 negative (HER2-) breast cancer without LN involvement, 21-gene recurrence score (RS) provides an effective method evaluating the risk of recurrence and metastasis. But the correlation between RS and LN involvement is not clear currently. To investigate the effect of RS on LN involvement, we designed a retrospective cohort study based on the data of tumor size-match LN+/- HR+HER2- breast cancer. Methods: The luminal type (ER+, PR+ and HER2-) early breast cancer (cT1-2) patients with 1~3 LN+ were enrolled and were tumor size-match paired (1:3) with those LN- during the same period. We compared the 21-gene RS between the LN+ and LN- group by univariate and multivariate analyses. Results: From April 2016 to May 2018, there were 65 LN+ cases undergoing 21-gene test included and 195 LN- cases were paired. With tumor size matched, the LN+ group had significantly younger age, more positive family history, higher histologic grade and higher RS than LN- group. All those factors, excepted histologic grade, were further confirmed in multivariate analysis (Table). Conclusions: After adjusted by tumor size, RS may have a significantly independent correlation with LN involvement in HR+HER2- early breast cancer. Total HR+HER2- cases’ tumor size-match paired (1:3) clinic pathologic and RS data. Clinical trial information: NCT03638648. [Table: see text]