bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between tumor biology and occult lymph node metastases before and after primary neoadjuvant therapy (NAT) for patients with early breast cancer.
Authors: Kolberg Hans-Christian , Kolberg-Liedtke Cornelia , Krajewska Maja , Bauerfeind Ingo , Fehm Tanja N. , Fleige Barbara , Helms Gisela , Lebeau Annette , Staebler Annette , Loibl Sibylle , Untch Michael , Kuehn Thorsten 
Published: May 2019

518 Background: Scientific efforts aim at a reduction of axillary morbidity through reduced axillary intervention among patients with early breast cancer. However, it is still unclear if this approach is feasible in all subtypes based on their risk of axillary involvement. We analyzed the association of tumor biology and occult axillary involvement with data from arms A and B of the SENTINA trial (Kühn T et al., Lancet Oncol 2013). Methods: Patients were included if they presented with a clinically negative axilla before NAT (arms A and B) and stratified according to tumor biology. All patients received SLNB before NAT, in cases of negative SLNB without further axillary surgery (Arm A) and in cases of positive SLNB (Arm B) with SLNB and axillary dissection after NAT. Logistic and linear regression analyses were carried out to evaluate the association between tumor biology and axillary involvement before and after NAT. Results: Of the 1022 patients in arms A and B of the SENTINA trial 926 were evaluable for this analysis. Of these, 27.9% had triple negative (TN), 16.3% hormone receptor (HR) and HER2 positive (triple positive = TP), 47.6% HR positive and HER2 negative (luminal) and 8.2% HR negative and HER2 positive (HER2) tumors. 39.7% of the luminal, 28.9% of the HER2, 19% of the TN and 47% of the TP tumors had involved SLN before NAT. Subgroup comparisons showed a significant difference between luminal and TN (p < 0.0001), whereas the differences between luminal and TP (p = 0.115) and HER2 (p = 0.077) were not statistically significant. The 317 patients with involved SLN prior to NAT received SLNB and axillary dissection after completion of NAT. The analysis after NAT showed trends for lower rates of involved lymph nodes for the high-risk groups (TN 20% / TP 14.3% / HER2 8.7%) compared to luminal tumors (27.6%) without reaching statistical significance. Conclusions: Our analysis demonstrates that among patients enrolled in the SENTINA trial, patients with triple negative disease have the lowest risk for occult lymph node metastases at initial presentation. Our results do not justify more intense local intervention among patients with triple negative breast cancer.
Adherence to adjuvant endocrine therapy after breast cancer in Sweden 2008-2010: A nationwide survey.
Authors: Andersson Anne , Von Wachenfeldt Väppling Anna , De Jong Anna , Nyström Lennarth 
Published: May 2019

523 Background: In estrogen receptor (ER) positive early breast cancer (EBC) adjuvant endocrine therapy (AET) is crucial to reduce recurrence and mortality. Previous studies have shown that adherence to AET is lower than expected and could negatively affect outcome. Since the year of 2000, BC patients in Sweden are treated in accordance to national guidelines. Treatment is offered at a low cost for the patient. The aim of the study was to estimate the adherence to AET in Sweden by regions and age groups. Methods: Women with a first primary EBC diagnosis 2008-2010 were identified through the Swedish Cancer Registry (SCR). Individual tumour and treatment data were retrieved from the Swedish National Breast Cancer Registry (SNBCR). Patients with ER negative tumours, small tumours (≤ 10 mm) and metastatic disease was excluded from the study since there were no indication to AET. Likewise, were individuals with AET registered to be administered by a third part excluded. Dispensed treatment from pharmacies was obtained through the Swedish Prescription Registry and medication possession rate (MPR) was calculated as number of dispensed doses divided by treatment duration in days. Good adherence to treatment in a patient was set at MPR ≥ 80 %. Adherence was calculated for 3 and 5 years. Results: Twenty-one thousand sixteen (21 016) individuals with a first primary BC between 2008 and 2010 was identified through SCR of which 20 596 were registered in the SNBCR. A total of 10 176 met the inclusion criteria in the study. Adherence after 3 years was 88.0 % and after 5 years 82.5 %. Adherence differed between regions in Sweden and was positively associated with age at diagnosis between 41-74 years. Urban areas had a lower adherence than rural areas (80.7 % vs 83.6 %; p= <0.001). Conclusions: Adherence to AET in Sweden was good, although there were differences by age and urban and rural areas. Further studies are needed to identify factors affecting differences in adherence, with the purpose of initiate actions to increase adherence to AET in ER positive EBC patients.
De-escalating adjuvant trastuzumab in human epidermal growth factor receptor 2 (HER2)-positive early-stage breast cancer: A systemic review and meta-analysis.
Authors: Goldvaser Hadar , Yasmin Korzets Ceder , Shepshelovich Daniel , Yerushalmi Rinat , Sarfaty Michal , Ribnikar Domen , Thavendiranathan Paaladinesh , Amir Eitan 
Published: May 2019

524 Background: One year of adjuvant trastuzumab in combination with chemotherapy is the standard of care in early-stage HER2 positive breast cancer. Existing data on shortening trastuzumab treatment show conflicting results. Methods: A search of PubMed and conferences identified randomized trials that compared abbreviated trastuzumab therapy to one year of treatment in early-stage HER2 positive breast cancer. Hazard ratios (HRs) and 95% confidence intervals (CI) were extracted for disease free survival (DFS) and overall survival (OS). Data on the number of DFS and distant relapse events were also collected as were the number of patients at risk in each group. Subgroup analyses evaluated the effect of nodal involvement, estrogen receptor (ER) expression and the duration of abbreviated trastuzumab (9-12 weeks versus 6 months). Odds ratios (ORs) and 95% CI were computed for pre-specified cardiotoxicity events including cardiac dysfunction and congestive heart failure (CHF). Results: Analysis included 6 trials comprising 11603 patients. In most studies adjuvant chemotherapy included anthracyclines and taxanes. Shorter trastuzumab treatment was associated with worse DFS (HR = 1.14, 95% CI 1.05-1.25, p = 0.002) and OS (HR = 1.15, 95% CI 1.02-1.29. p = 0.02). The effect on DFS was not influenced by ER status (p for the subgroup difference = 0.23), nodal involvement (p = 0.44) or the different duration of trastuzumab in the experimental arm (p = 0.08). In absolute terms, after an estimated median follow-up of 71 months, shorter treatment with trastuzumab was associated with an absolute increase in DFS events of 2.3%. Shorter trastuzumab treatment was associated with lower odds of cardiac dysfunction (OR = 0.67, 95% CI 0.55-0.81, p < 0.001) and CHF (OR = 0.66, 95% CI 0.50-0.86, p = 0.003). Conclusions: Compared to one year, shorter duration of adjuvant trastuzumab is associated with significantly worse DFS and OS, despite favorable cardiotoxicity profile. One year of trastuzumab should remain the standard adjuvant treatment in early-stage HER2 positive breast cancer with appropriate cardiac monitoring.
A randomized phase III trial comparing dose-dense epirubicin and cyclophosphamide (ECdd) followed by paclitaxel (T) with paclitaxel plus carboplatin (PCdd) as adjuvant chemotherapy for early triple-negative breast cancer patients with high-recurrence risk.
Authors: Wang Jiani , Li Qing , Mu Yuxin , Zhang Tongtong , Han Ying , Wang Jiayu , Li Qiao , Luo Yang , Yuan Peng , Ma Fei , Fan Ying , Zhang Pin , Xu Binghe 
Published: May 2019

528 Background: There are no well-established adjuvant chemotherapy (AC) regimens for early triple negative breast cancer (TNBC). Our randomized phase III trial was designed to compare dose dense paclitaxel plus carboplatin (PCdd) with commonly used dose dense epirubicin and cyclophosphamide, followed by paclitaxel (ECdd-T) regimen as AC for TNBC with high recurrence risk. Methods: Between May 2011 and November 2015, TNBC patients were randomized in 1:1 ratio to receive PCdd or ECdd-T regimen as AC every two weeks for 8 cycles with administration of granulocyte stimulating factor (G-CSF) support. The primary endpoint was 3-year disease free survival (DFS).The secondary endpoints included overall survival (OS) and safety. Survival analyses were also performed for different subgroups stratified by age status (≤40 years vs >40 years), Ki 67(<50 vs ≥50), tumor size (<2cm vs ≥2cm), nodal status (N- vs N+) and treatment free survival (TFS) (<30 days vs ≥30 days). Results: In total, 132 patients with a median age of 49 years (PCdd 64 patients, ECdd-T 68 patients) were enrolled. After a median follow-up of 57.3 months, 23 events were observed (18 in ECdd-T, 5 in PCdd). Patients in the PCdd arm had significantly higher DFS rate than that in the ECdd-T arm (log-rank p = 0.0046, hazard ratio (HR) 0.305, 95% confidence interval (CI) = 0.134-0.693). The 3-year DFS rate was 93.7% with PCdd versus 77.9% with ECdd-T,respectively. Difference in 3-year OS rate was observed between the two arms (98.4% vs 92.6%), significantly higher in the PCdd arm ( p = 0.0268). Both regimens were well tolerated with manageable adverse events(AEs). Worse neutropenia (Grade 3/4: 48.5% in ECdd-T vs. 21.9% in PCdd, p=0.002) was found in ECdd-T arm. 3-year DFS rate for PCdd was superior in the following subgroups, age>40 years, clinically evaluated lymph nodes, TFS <30 days, with statistical significance ( p <0.05). Conclusions: Our data suggested that PCdd was superior to ECdd-T as AC for early TNBC in terms of improving 3-year DFS and OS. PCdd with lower hematological toxicity might be an appropriate regimen for early TNBC patients with high recurrence risk. Clinical trial information: NCT01378533.
EPHA genetics for prediction of paclitaxel-induced peripheral neuropathy sensitivity.
Authors: Marcath Lauren A , Kidwell Kelley M. , Smith Ellen M. Lavoie , Vangipuram Kiran , Gersch Christina L , Burness Monika Leigh , Griggs Jennifer J. , Van Poznak Catherine H. , Hayes Daniel F. , Henry Norah Lynn , Beutler Andreas S. , Hertz Daniel Louis 
Published: May 2019

532 Background: Chemotherapy induced peripheral neuropathy (CIPN) is a common, debilitating paclitaxel side effect that has been primarily attributed to cumulative systemic paclitaxel exposure. Paclitaxel dose-adjustment to achieve target systemic exposure decreases but does not eliminate severe CIPN, suggesting some patients are inherently CIPN-sensitive. Ephrin ( EPHA) polymorphisms have been reported to increase CIPN occurrence (Baldwin 2012, Leandro-Garcia 2013, Boora 2016) but replication has been challenging, perhaps due to the inability to isolate CIPN-sensitivity by accounting for systemic exposure differences. The study purpose was to determine if EPHA genetic variants previously associated with CIPN occurrence are associated with CIPN-sensitivity. Methods: PN was assessed at baseline and weekly using the 8-item sensory subscale (CIPN8) of the patient-reported EORTC CIPN20 in patients receiving paclitaxel 80 mg/m2 weekly x 12. EPHA4, EPHA5, EPHA6, and EPHA8 were sequenced in germline DNA. Associations with higher PN-sensitivity were tested for three genetic models (total variants, coding variants, and rs7349683) by incorporating genetics into previously published CIPN8 predictive models that included measured paclitaxel exposure. Significant associations were tested for association with higher risk of PN-related treatment disruption (i.e. dose decrease, delay, or discontinuation). Results: In the 59 included patients, carrying EPHA5 rs7349683 was associated with greater CIPN sensitivity (beta coefficient: 0.40, standard error: 0.14, p = 0.005), indicating these patients had a greater increase in CIPN8 during treatment than would be predicted based on cumulative paclitaxel exposure. Rs7349683 was not associated with increased PN-induced treatment disruption, perhaps due to the low number of events (n = 19). Conclusions: Using a novel approach that isolates CIPN-sensitivity by accounting for measured paclitaxel exposure, our results provide further evidence that EPHA5 rs7349683 may be a promising marker for CIPN. If additional validation studies confirm this association, genetic testing could enable personalized treatment strategies to prevent CIPN in patients with breast cancer.
Additional prognostic value of OncoMasTR multigene prognostic signature to clinicopathological information in patients with HR-positive, HER2-negative, lymph node-negative breast cancer from the TAILORx Tissue Bank, Ireland.
Authors: O'Connor Darran , Kelly Catherine Margaret , Crown John , Russell Niamh , Barron Stephen , Loughman Tony , Lynch Seodhna , O'Grady Anthony , Sheehan Katherine M , Fay Joanna , Saha Anurati , Dynoodt Peter , Fender Bozena , Wang Chan-Ju Angel , O'Leary Desmond , Bracken Adrian P. , Rahman Arman , Gonzalez Claudia Aura , Attar Nebras Al , Gallagher William M. 
Published: May 2019

535 Background: Multigene prognostic signatures (MGPS) can identify early stage breast cancer patients who may require less aggressive treatment. To be clinically useful, MGPSs must provide additional prognostic information to clinicopathological information routinely used by clinicians. The OncoMasTR MGPS was discovered via a novel bioinformatic transcriptional network analysis. OncoMasTR consists of genes – Master Transcription Regulators (MTRs) – that regulate previously known prognostic genes and have identified functional roles in several hallmarks of cancer including proliferation, invasion and metastasis. The OncoMasTR Molecular Score (OM) consists of just 3 MTRs. The OncoMasTR Risk Score (OncoMasTR) combines OM with lymph node status and tumour size, and categorises patients as low or high risk. The OncoMasTR Test has been analytically and clinically validated. Methods: MTR expression was measured by RT-qPCR in tissue from 404 patients enrolled in an independent translational trial (NCT02050750) that collected tissue and clinical data from patients enrolled in TAILORx in Ireland. OM, OncoMasTR and Oncotype DX Recurrence Score (RS) were compared on the additional prognostic value they provided to Ki67, Nottingham Prognostic Index (NPI) and other clinicopathological information for distant recurrence (DR) and invasive disease (ID). Results: OM (LRχ2 = 20.3, p < 0.00001, c-index = 0.84) and OncoMasTR (LRχ2 = 22.6, p < 0.00001, c-index = 0.85) were significantly prognostic, and more prognostic than RS (LRχ2 = 8.4, p = 0.004, c-index = 0.73) for DR. OM and OncoMasTR provided more additional prognostic information than RS to Ki67, NPI, tumour size, tumour grade, and age for DR. Similar results were found when OM, OncoMasTR and RS were compared on prognostic performance for ID. Conclusions: OM and OncoMasTR were significantly prognostic for DR and ID and added significant prognostic value to Ki67, NPI, and other clinicopathological information. Furthermore, OM and OncoMasTR showed superior prognostic performance to RS.
Factors associated with twenty-year (y) risks of breast cancer-specific mortality (BCSM) in the Surveillance, Epidemiology, and End Results (SEER) Registry.
Authors: Leone Jose Pablo , Vallejo Carlos Teodoro , Hassett Michael J. , Leone Julieta , Freedman Rachel A. , Tolaney Sara M. , Leone Bernardo Amadeo , Lin Nancy U. , Winer Eric P. 
Published: May 2019

540 Background: Most reports describing the risk of late relapse in breast cancer have been based on selected patients (pts) enrolled into clinical trials. The aims of this study were to report on population-based long-term risks of BCSM, and the risks of BCSM conditional on having survived 5 y. Additionally, we aimed to identify factors associated with late deaths from breast cancer. Methods: Using SEER data, we identified women with breast cancer (T1-T2, N0-N2, M0) between 1990-2005, with one primary cancer in their lifetime, and known hormone receptor (HR) status. We used Kaplan-Meier analyses to determine the effect of baseline variables on cumulative risks of BCSM, we estimated annual rate of events per 100 person-years, and performed Cox regression stratified by HR status. Results: We included 202,080 pts (median follow-up = 12.25 y). Of all breast cancer deaths, the proportion after 5 y was 65% for HR+ vs 28% for HR- (p < 0.001). The table shows risks of BCSM by HR and N status, and annual event rates. The cumulative risk of BCSM in y 5-20 ranged from 7.9% in HR-N0 to 38% in HR+N2. Among HR+ pts, adjusted risks of BCSM conditional on having survived 5 y were higher for T2 vs T1a (Hazard ratio [HzR] 3.3, p < 0.001), N2 vs N0 (HzR 3.5, p < 0.001), age at diagnosis (dx) > 64 y vs < 50 y (HzR 1.4, p < 0.001), black race vs white (HzR 1.3, p < 0.001) and grade III vs I (HzR 2.3, p < 0.001). For HR- pts, adjusted risks of BCSM conditional on having survived 5 y were higher for T2 vs T1a (HzR 2.0, p < 0.001), N2 vs N0 (HzR 2.8, p < 0.001) and age at dx > 64 y vs < 50 y (HzR 1.6, p < 0.001). Conclusions: For HR+ breast cancer, risks of BCSM remain high beyond 5 y from dx and depend on T-N status, age, race and grade. In HR- breast cancer, the risk of BCSM is highest within 5 y from dx; however, risks beyond 5 y are still considerable and depend on T-N status and age. Our results underscore the need for better adjuvant therapies in both HR+ and HR- breast cancer. [Table: see text]
A novel 95-gene signature (Curebest 95GC Breast) that predicts recurrence-risk in patients with ER-positive, HER2-negative, node-negative, early-stage primary invasive breast cancer with an intermediate Oncotype DX Recurrence Score.
Authors: Fujii Takeo , Masuda Hiroko , Cheng Yee Chung , Yang Fei , Sahin Aysegul A. , Naoi Yasuto , Matsunaga Yuki , Raghavendra Akshara Singareeka , Sinha Arup Kumar , Espinosa Fernandez Jose R. , James Anjali , Yamagishi Keisuke , Matsushima Tomoko , Tripathy Debu , Tada Sachiyo , Jackson Rubie S. , Noguchi Shinzaburo , Nakamura Seigo , Acoba Jared David , Ueno Naoto T. 
Published: May 2019

542 Background: The TAILORx trial demonstrated that adjuvant endocrine and chemoendocrine therapies had similar efficacy in patients with hormone receptor-positive, HER2-negative, node-negative breast cancer with an Oncotype DX recurrence score (RS) of 11-25. However, a predictive strategy is needed to identify patients with intermediate RS who may benefit from adjuvant chemoendocrine therapy. Curebest 95GC Breast (95GC) is a 95-gene signature that can stratify patients into two groups with high (95GC-H) and low (95GC-L) groups to predict the risk of recurrence. Our primary objective was to show that 95GC can classify patients with intermediate RS into binary recurrence risk groups. Methods: Patients with ER-positive, HER2-negative, node-negative invasive breast cancer and RS 11-30 who underwent definitive surgery and adjuvant endocrine therapy were included. RNA was derived from archived formalin-fixed, paraffin-embedded samples, and 95GC was calculated as reported previously. The Fisher exact and Brunner-Munzel tests were used to compare variables between 95GC groups. A Kaplan-Meier estimate with a log-rank test was used for recurrence-free survival (RFS) analysis. Results: The analysis included 178 patients from five institutions. The 5-year RFS rate in patients with RS 18-30 was higher in the 95GC-L group (n = 129, 96.3%) than in the 95GC-H group (n = 49, 90.9%; p = 0.002), which was consistent with results in an independent Japanese population (n = 224; p < 0.001). RFS rates significantly differed between the groups among patients with RS 11-25 as well (95GC-L, 97.4%; 95GC-H, 87.1%; p = 0.001). RFS rates did not differ between patients with RS 18-25 (94.8%) and those with RS 26-30 (93.8%; p = 0.33). Conclusions: 95GC can predict recurrence risk in patients with ER-positive, HER2-negative, node-negative invasive breast cancer and intermediate RS. Further prospective retrospective studies in the TAILORx population are warranted to confirm that 95GC can identify patients who may benefit from adjuvant chemoendocrine therapy.
Activity of durvalumab in advanced endometrial cancer (AEC) according to mismatch repair (MMR) status: The phase II PHAEDRA trial (ANZGOG1601).
Authors: Antill Yoland Catherine , Kok Peey Sei , Robledo Kristy , Barnes Elizabeth , Friedlander Michael , Baron-Hay Sally E. , Shannon Catherine M. , Coward Jermaine , Beale Philip James , Goss Geraldine , Meniawy Tarek , Yip Sonia , Smith Deborah , Spurdle Amanda B. , Parry Michelle , Andrews John , Kelly Marzena , Stockler Martin R. , Mileshkin Linda R. ,   Australia New Zealand Gynaecological Oncology Group (ANZGOG)
Published: May 2019

5501 Background: Deficient DNA mismatch repair (dMMR) occurs in approximately 15% of AEC and is associated with a high tumour mutation burden. Expression of PD-1 and PD-L1 has been reported in up to 90% of ECs, including those with proficient DNA mismatch repair (pMMR). We report here preliminary results of PHAEDRA, a single-arm phase 2 trial designed to determine the activity of single-agent durvalumab, an antibody to PD-L1, in 2 cohorts of women with AEC. Methods: Participants (pts) had pMMR AEC progressing after 1-3 lines of chemotherapy, or dMMR AEC progressing after 0-3 lines of chemotherapy, and were treated with durvalumab 1500mg IV Q4W. The primary endpoint was objective tumour response (OTR = complete response [CR] or partial response [PR] by iRECIST). Secondary endpoints included disease control at 16 weeks (DC16w = CR, PR, or stable disease at 16 weeks [SD16w]), immune-related adverse events (irAEs), PD-L1, germline mutations and MLH1 methylation. Other secondary endpoints include: OTR and DC by RECIST1.1, other AE, PFS, OS & quality of life will be reported later. Results: 71 pts with AEC were recruited from Feb 2017 to Sep 2018: 35 dMMR and 36 pMMR. Median follow-up were 8.3 vs 14.8 months in dMMR vs pMMR pts. Median age: 67 (range 36-81); ECOG PS: 0-1 in 68, and 2 in 3. Pathology: endometrioid in 94% and 58%; serous in 0% and 31%; grade: high in 42% and 83% (dMMR and pMMR respectively). Durvalumab was the 1st, 2nd and subsequent line of non-hormonal therapy in 15, 14, and 6 pts with dMMR and 0, 21, and 15 pts with pMMR. Among dMMR pts, the OTR rate was 40% (14/35, 95% CI 26-56), with 4 CR and 10 PR; 7 others had SD 16w for a DC16w rate of 60% (21/35, 95% CI 44-74). OTR rate was 40% as 1st line, 43% as 2nd line, and 33% as subsequent line treatment. Among pMMR pts, the OTR rate was 1/36 (3%, 95% CI 1-14) with 1 PR; 6 others had SD16w for a DC16w rate of 19% (7/36; 95% CI 10-35). IrAEs occurred in 14 pts: hyperthyroidism in 6, hypothyroidism in 6, pneumonitis in 1 and hepatitis in 1. Conclusions: Durvalumab monotherapy showed promising activity and safety in AEC with dMMR regardless of prior lines of chemotherapy, but there was limited evidence of activity in AEC with pMMR. Clinical trial information: ACTRN12617000106336.