bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preoperative risk assessment model for identification of lymph node metastasis in early cervical cancer.
Authors: Shim Seung-Hyuk , Kim Dae-Yeon , Lee Shin-Wha , Park Jeong-Yeol , Kim Jong-Hyeok , Kim Yong-Man , Kim Young-Tak , Nam Joo-Hyun 
Published: March 2020

5600 Background: The aim of this study was to develop a preoperative risk prediction model for lymph node metastasis in patients with early cervical cancer. Methods: The medical records of 504 patients with early cervical cancer who underwent hysterectomy and pelvic/paraaortic lymphadenectomy between 2007and 2012 in our center were retrospectively reviewed. According to the order of surgery performed, data between 2007 and 2010 were allocated to a model development cohort (n=314), and data between 2011 and 2012 were allocated to an external validation cohort (n=190). By using preoperative clinicopathologic data, magnetic resonance imaging (MRI) data, and positron emission/computed tomography (PET/CT) data, a multivariate logistic model was created. Based on this model, predictive nomogram was developed and externally validated. Results: Age, tumor size measured by MRI, and lymph node metastasis on PET/CT were found to be independent risk factors for nodal metastasis. Developed nomogram incorporating these three predictors showed good discrimination and calibration, with a bootstrap-adjusted concordance index of 0.772. Also, the validation set showed good discrimination with a bootstrap-adjusted concordance index of 0.783. Conclusions: We have developed a robust model to predict lymph node metastasis in patients with early cervical cancer. This new tool may be useful to clinicians and patients when deciding lymphadenectomy and maybe useful in designing clinical trials. [Table: see text]
Racial disparities in cervical cancer mortality over time.
Authors: Rauh-Hain Jose Alejandro , del Carmen Marcela G , Schorge John O. , Boruta David M. , Growdon Whitfield Board , Goodman Annekathryn , Clark Rachel Marie , Bradford Leslie Siriya , Clemmer Joel 
Published: March 2020

5604 Background: The aim of this study is to examine changes over time in survival for African-American (AA) and white women diagnosed with cervical cancer (CeCa). Methods: Surveillance, Epidemiology, and End Results (SEER) Program data 9 for 1983-2007 were used for this analysis. Kaplan–Meier and Cox proportional hazards survival methods were used to assess differences in survival by race at 5-year intervals. Results: The study included 23,722 women; including 19,777 whites and 3,945 AA. AAs were older (51.4 vs. 49 years; p<0.001), had a higher rate of regional (38.3% vs. 31.7; p<0.001) and distant metastasis (10.5% vs. 8.5; p<0.001). AAs received less frequently cancer-directed surgery (53.1% vs. 65.7%; p<0.001), and more frequently radiotherapy (56.9% vs. 47.3%; p<0.001). AAs had a hazard ratio (HR) of 1.40 (95% CI, 1.31-1.49) of CeCa mortality compared to whites. Adjusting for SEER registry, marital status, stage, age, surgery, radiotherapy, grade and histology, AA women had a HR of 1.15 (95% CI, 1.07-1.24) of CeCa related mortality. AAs had a higher HR of all cause mortality and CeCa related mortality for all the five-year diagnosis cohorts (Table). After adjusting for the same variables, there was a significant difference in survival in the 1988-1992 group (HR 1.26; 95% CI 1.09-1.47). Conclusions: The present data indicates significant survival differences by race for women with invasive CeCa. After adjusting for SEER registry, marital status, stage, age, surgery, radiotherapy, grade and histology, only between 1988-1992 there was a difference in survival between the groups. [Table: see text]
Relationship of tumor and stromal autophagy and endocrine responsiveness in breast cancer tissues.
Authors: Ueno Takayuki , Masuda Norikazu , Saji Shigehira , Kuroi Katsumasa , Sato Nobuaki , Takei Hiroyuki , Yamamoto Yutaka , Ohno Shinji , Yamashita Hiroko , Hisamatsu Kazufumi , Aogi Kenjiro , Iwata Hiroji , Sasano Hironobu , Toi Masakazu 
Published: March 2020

571 Background: Neoadjuvant endocrine therapy has been employed to improve surgical outcomes for endocrine responsive breast cancers in post-menopausal women. Endocrine responsiveness is estimated by the expression levels of hormone receptors although heterogeneity in the response is well recognized. To improve the clinical outcome, it is critical to understand how cancer tissues react to the endocrine treatment. Methods: Pre-treatment biopsy samples and post-treatment surgical samples were obtained from 116 patients enrolled onto the multicenter prospective study of neoadjuvant exemestane therapy, JFMC34-0601. Fifty-four paired samples were available for the study. Estrogen receptor, progesterone receptor, HER2, Ki-67 by immunohistochemistry and pathological response were centrally evaluated. Apoptosis was assessed by TUNEL (Roche Diagnostics, Mannheim) and M30 (Roche Diagnostics, Mannheim). Autophagy was assessed by anti-beclin 1 (Novus Biologicals, CO) and anti-LC3 (MBL, Nagoya). Clinical response was assessed based on the RECIST criteria. The Wilcoxon rank-sum test and chi-square test were used for the statistical analysis. Results: The expression of autophagy markers, beclin and LC3, in cancer cells showed significant increases by exemestane (beclin p=0.016; LC3 p=0.0004) whereas TUNEL did not show any change and M30 expression decreased (p=0.01). The increase of beclin expression was associated with the clinical response: responders showed an increase (p=0.039) while non-responders did not. Importantly, the treatment increased autophagy markers not only in cancer cells but in stromal cells (beclin p<0.0001; LC3 p=0.024) while it did not change TUNEL in stromal cells. Patients with stromal beclin-positive showed poor clinical response (3/12) and poor pathological response (0/12) while those with stromal beclin-negative showed good clinical response (26/39) and good pathological response (16/38) (clinical response p=0.011; pathological response p=0.0064). Conclusions: This study suggested that exemestane induced autophagy in both cancer and stromal cells. In addition, stromal autophagy correlated with clinical and pathological response to the endocrine treatment.
Low HER2-expression to predict impaired activity of endocrine therapy in patients with estrogen-receptor (ER) positive metastatic breast cancer (MBC).
Authors: Sparber Cornelia , Berghoff Anna Sophie , Rudas Margaretha , Dubsky Peter Christian , DeVries Catharina , Minichsdorfer Christoph , Sattlberger Claudia , Mader Robert M , Bago-Horvath Zsuzsanna , Fitzal Florian , Gnant Michael , Rottenfusser Andrea , Zielinski Christoph , Preusser Matthias , Steger Guenther G. , Bartsch Rupert 
Published: March 2020

573 Background: ER cross-activation by growth-factor signalling causes resistance to endocrine therapy (ET) in patients (pts) with Her2-positive MBC. Moreover, low levels of Her2-expression (Her2 1+; Her2 2+ without gene amplification), may result in reduced efficacy of ET in early breast cancer pts. In a recently published study, these tumours had a less favourable outcome as compared to tumours with a Her2-score of 0. Here, we investigated if low levels of Her2-expression could predict for shorter progression-free survival (PFS) in MBC pts on ET. Methods: PFS on first-line ET was chosen as primary endpoint and estimated with the Kaplan-Meier method. To test for differences between PFS curves, the log-rank test was used. Association of the following variables with PFS was investigated: low Her2-expression, grading, level of ER-expression, progesterone-receptor status, Ki67 (cut-off ≤20%), prior adjuvant ET, and presence of visceral metastases. For an estimated superiority of 40% in terms of PFS in favour of the Her2-negative group, a sample of 130 pts in two groups was needed in order to rule out the null-hypothesis with a 80% power and a two-sided α of 0.025. Results: A total number of 320 ER-positive MBC pts were identified from a breast cancer database; 170 pts were available for this analysis. Median PFS on first-line ET was 11 months (m) (8.56-13.44), corresponding numbers for second-line were 6 m (4.65-7.36), and third-line 4 m (1.52-6.48), respectively; median OS from diagnosis of MBC was 58 m (48.15-67.86). None of the variables investigated were significantly associated with first-line PFS. Second-line PFS, however, was significantly shorter in pts with grade 3 tumours and prior adjuvant ET; a trend towards shorter PFS was observed in high proliferating tumours. Conclusions: In this chart review, low levels of Her2 expression did not predict for shorter PFS in pts receiving ET; PFS in different treatment lines was well in line with data from clinical trials. High tumour grading and prior adjuvant ET were associated with accelerated onset of resistance, rendering those patients candidates for early combination of ET with targeted treatment approaches.
Involvement of microRNA in the regulation of progesterone receptor in breast cancer.
Authors: Shai Ayelet , Gilam Avital , Steiner Mariana , Shomron Noam 
Published: March 2020

578 Background: The progesterone receptor (PgR) is a prognostic factor in ER positive breast cancers treated by adjuvant hormonal treatment. While PgR protein is usually assessed by immunohistochemistry (IHC), RT-PCR measurement of mRNA levels is provided by Oncotype Dx and other tests. Between 20-40% of tumors are discrepant in IHC and RT-PCR PgR expression, reflecting either technical problems or biological mechanisms. MicroRNAs regulate gene expression either at the mRNA or the protein translation level. Our hypothesis is that the latter potentially explains discrepancies between IHC and RT-PCR results. Methods: ER positive tumors were divided to three groups by PgR expression according to IHC and RT-PCR: (i) positive by IHC; (ii) negative by IHC and high mRNA levels by RT-PCR; (iii) negative by IHC and low mRNA levels by RT-PCR. RNA was extracted from tumors and adjacent normal tissue and the expression of PgR and microRNAs was assessed by RT-PCR. In addition, microRNAs were transfected into MCF-7 cells. The levels of PgR mRNA and protein were analyzed. Results: The PgR gene contains potential conserved binding sites for MicroRNAs 23a, 181a, 135a and 26b. Of these, miR- 23a and miR-181a showed inverse expression relative to the PgR expression in normal and tumor tissue, as expected. MicroRNA levels were determined in tumors of all three groups. The highest expression of microRNAs 23a, 181a and 26b was seen in IHC negative tumors with low levels of mRNA. Intermediate expression was seen in IHC negative tumors with high mRNA levels, and the lowest expression was detected in IHC positive tumors. Preliminary results suggest that over expression of microRNAs 23a, 181a and 26b in MCF7 cells decreased PgR levels. Conclusions: Our results suggest that microRNAs 23a , 181a and 26b regulate the level of the progesterone receptor in breast cancer and that tumors with relatively high mRNA levels may be deficient in PgR protein due to downregulation by microRNAs. [Table: see text]
Cardiac safety and efficacy of concomitant liposomal doxorubicin, docetaxel, and trastuzumab as neoadjuvant therapy in HER2-overexpressing breast cancer: A retrospective analysis.
Authors: Brunner Christine , Jaeger Thomas , Suppan Christoph , Mueller-Holzner Elisabeth , Jasarevic Zerina , Balic Marija , Goebel Georg , Marth Christian , Stoeger Herbert , Samonigg Hellmut , Hubalek Michael , Lang Alois 
Published: March 2020

583 Background: Concurrent therapy of trastuzumab, anthracycline and taxane for the neoadjuvant treatment of breast cancer (BC) results in an improved rate of pathological complete response (pCR). However, there is considerable concern about the cardiac safety of this combination. The use of liposomal doxorubicin might be a valuable alternative with lower cardiotoxicity. We report cardiac safety and pCR-rate of a single arm, retrospective, multicenter analysis of neoadjuvant treatment for BC with liposomal doxorubicin, trastuzumab, and docetaxel. Methods: In this study 84 women with BC and HER2 overexpression were investigated in 3 oncological departments in Austria. All patients were treated with liposomal doxorubicin (50 - 60 mg/m²), docetaxel (75 mg/m²) and concurrent with trastuzumab for 6 cycles as neoadjuvant therapy. All patients were free of cardiovascular disease and had a left ventricular ejection fraction (LVEF) of ≥ 55%. Cardiac function was by LVEF and was examined at regular intervals(cycles 0-3, cycle 6, FU). Clinical response was evaluated by diagnostic breast imaging after cycles 3 and 6. All patients underwent surgery after neoadjuvant chemotherapy. The absence of any residual invasive cancer in the breast and axilla was defined as pathological complete response (pCR). Median follow up was 2.4 years. Results: Median age of the patients was 50 years. After 6 cycles of treatment the pCR rate was 46%. In this cohort a negative estrogen-and/or progesteron receptor was predictive for pCR (p<0.001). No patient progressed during treatment. None of the patients suffered symptomatic heart failure. Only one patient (1.6%) with asymptomatic LVEF of 45% was observed during follow-up. Conclusions: In this multicenter analysis we observed a considerably high rate of pCR in HER2-positive BC treated with liposomal doxorubicin, docetaxel and trastuzumab. The addition of liposomal doxorubicin instead of conventional doxorubicin or epirubicin entails a very favorable cardiotoxicity profile. This regimen is a safe treatment option in patients with HER-2 positive breast cancer.
Clinical and pathologic correlation of the activated form of the estrogen receptor (ER) in breast cancer (BC).
Authors: Bonneterre Jacques , Gilles Erard M. , Zukiwski Alexander A. , Bosq Jacques , Valent Alexander , Hutt Emilie , Fuqua Suzanne A.W. 
Published: March 2020

592 Background: About 50% of ER positive (ERpos) BC are resistant to hormone treatment. In absence of ligand, ERs are evenly distributed in nuclei in normal tissue. Upon ligand binding, ERs dimerizes and form a discrete focal subnuclear distribution pattern (FDP), which are associated with transcriptional activation of ER. This ER FDP is observed in BC. We hypothesized that in BC that the presence/absence of ER in the FDP could predict antiestrogen activity. This study describes an immunohistochemistry (IHC) method, by which a biomarker could be developed to investigate this hypothesis. Methods: 303 archived BC biopsies were obtained along with clinical and pathology data. Biopsies were analyzed for standard HES, ER, progesterone receptor (PR) and Ki67. PR positivity was determined with distinct antibodies to the A and B isoforms. The A-ER and D-ER nuclear patterns were analyzed at x1000 magnification. Results: Mean age; 58 (17 -89). Histology: ductal 85% lobular 13%, other 2%; 84% ERpos and 84% either PRApos or PRBpos, 7% ERpos and 7% PRApos or PRBpos only. All but 3 ERpos cases had received AntiEs; Adj. chemotherapy 51%, Stage: I 51%, II 43%, III 6 %. Grade: I 24%, II 51%, III 25%. Median follow up 31 months (mo). Local or distant progression (PD) was 19%. ER status was D-ER in 78% and A-ER in 22% of the biopsies and PD was associated with the D-ER pattern (p = 0.06), e.g. the hypothetically non-functional pattern D-ER was associated with a higher rate of PD (4 vs 35). With DFS defined as time to PD or death (5 year cut off), ERpos was better that ERneg (HR= 0.38, p = 0.016). For ERpos BC, A-ER was numerically better than D-ER (HR =0.3, p=0.24 two-sided). In univariate analyses, A-ER pattern was associated with higher grade (p=0.035), anisonucleosis (p=0.06), mitotic index (p=0.02), and Ki67 (=0.08). No association was found between ER pattern and age, stage or HER2 status. Conclusions: This study supports the hypothesis that AntiEs are mainly active in BC with A-ER pattern, which is targetable by AntiEs. A larger number of events are needed to reach significance in time-dependent analyses and confirmatory studies are warranted.
Independent characterization by duel staining of progesterone receptor (PR) and estrogen receptor (ER) in breast cancer (BC).
Authors: Zukiwski Alexander A. , Caillaud Jean-Michel , Bosq Jacques , Fuqua Suzanne A. W. , Lange Carol A. , O'Shaughnessy Joyce , Gilles Erard M. , Bonneterre Jacques 
Published: March 2020

596 Background: The oncology literature indicates that ER and PR are linked and in BC the presence of PR usually indicates functional ER. BCs express both ER and PR to varying degree, but little has been published on expression of ER + PR in individual cancer cells. The goal of this study is to 1. Determine the expression ER and PR at the cellular level, 2. Determine if ER and PR are expressed in the same BC cells. If ER and PR are separate, this may indicate that antiestrogens and antiprogestins may target different cells. Methods: Archived 1° BC specimens were processed using standard IHC techniques for ER/PR testing. The procedure consisted of sequential double staining on the same microtone section, where the PR was visualized through brown staining using HRP/DAB, and the ER was visualized through red staining using AP/Permanent Red. The initial testing on 13 tumor samples utilized a duel anti-PR-A/B antibody (Ab) and an ER Ab. The next 63 tumor samples utilized; 1. anti-ER and anti-PR-A Abs, 2. anti-ER and anti-PR-B Abs. A pathologist experienced with IHC, interpreted and enumerated the cells staining positive for ER only, for PR only and cells staining positive for both ER & PR. The number of cells expected to be stained for both ER & PR by chance can be calculated as the rate of total ER by the rate of total PR and compared with the observed rate (paired rank test). ER/PR positivity is defined as ≥ 5% cells positive. Results: In the first series, 11/13 tumors were ERpos, 13/13 were PRpos, 7/13 tumors had both ER & PR expressed in 5-20% (median 5%) of the same tumor cells. In the 2nd series of 63 tumors; 1. 50/53 were ERpos, 52/53 were PRApos and 44/53 had both ER & PRA expressed in <5-20% (median 5%) of the same tumor cells, 2. 44/52 were ERpos, 52/52 were PRBpos and 42/52 tumors had both ER & PRB expressed in <5-20% (median 10%) of the same tumor cells. Areas of ER or PR only predominance were frequent. A paired rank test indicates that the observed rate (median 9%) of ER/PR duel staining is less than predicted (median 18%, p <0.000). Conclusions: ER & PR were expressed in the majority of tumors examined with a minority the tumor cells expressing both ER & PR. These data support evaluating antiprogestins as a different therapeutic target from ER.
Efficacy and safety of first-line (1L) pertuzumab (P), trastuzumab (T), and docetaxel (D) in HER2-positive MBC (CLEOPATRA) in patients previously exposed to trastuzumab.
Authors: Ciruelos Gil Eva Maria , Brufsky Adam , Im Young-Hyuck , Kim Sung-Bae , Clark Emma , Knott Adam , Ross Graham , Miles David 
Published: March 2020

600 Background: CLEOPATRA is a global phase III trial of P + T + D vs placebo + T + D in HER2-positive 1L MBC. Results showed a significant improvement in PFS (Baselga NEJM 2012) and OS (Swain SABCS 2012) favoring P + T + D. CLEOPATRA started recruitment in 2008 soon after the approval of T in the adjuvant setting in 2006 and mandated a disease-free interval (DFI) of ≥12 mos from the end of adjuvant therapy to MBC diagnosis. Due to this, a low proportion of pts with prior T exposure was included. Here we present the efficacy and safety of 1L P + T + D in the subset of pts in CLEOPATRA with prior T exposure. Methods: Pts received P + T + D or placebo + T + D, had a DFI ≥12 mos, baseline left ventricular ejection fraction (LVEF) ≥50% and no LVEF decline to <50% during/after prior T therapy. Exploratory analyses of PFS and OS in pts with (neo)adjuvant therapy with or without T were conducted. Results: Of the study population, 47% had received (neo)adjuvant therapy and 11% had received (neo)adjuvant T; 82% of the prior T group came from Europe or North America. A univariate Cox regression analysis did not identify prior T therapy as a statistically significant risk factor for developing left ventricular systolic dysfunction (LVSD). However, due to the low number of LVSD events overall, this analysis has limited sensitivity. Conclusions: Data from CLEOPATRA show that pts with HER2-positive 1L MBC who have received prior T (DFI ≥12 mos) derive the same magnitude of benefit from the combination of P + T + D when compared with the whole study population or those who are T-naïve. This is in agreement with prior evidence of the activity of P + T in pts pretreated with T (Baselga JCO 2010). Efficacy and safety of P-T-based therapy is being explored in the PERUSE and PHEREXA trials, in a pt population with wider exposure to prior T and a shorter DFI, which may better represent current clinical practice. Clinical trial information: NCT00567190. [Table: see text]
E 1308: A phase II trial of induction chemotherapy (IC) followed by cetuximab with low dose versus standard dose IMRT in patients with human papilloma virus (HPV)-associated resectable squamous cell carcinoma of the oropharynx (OPSCC).
Authors: Marur Shanthi , Li Shuli , Cmelak Anthony , Gillison Maura L. , Ferris Robert L. , Bauman Julie E. , Zhao Weiqiang , Westra William H. , Chung Christine H. , Wagner Lynne I. , Trevarthen David R. , Jahagirdar Balkrishna N. , Colevas A. Dimitrios , Burtness Barbara ,   Eastern Cooperative Oncology Group
Published: March 2020

6005 Background: HPV is associated with 60-80% of OPSCC. E2399 results showed IC followed by (f/b) paclitaxel (P)/3D RT (70Gy) improved 2-yr progression-free (PFS) for HPV+ compared to HPV- OPSCC. We studied a regimen with 20% radiation dose reduction to 54Gy in HPV + OPSCC patients (pts) with a clinical complete response (CCR) to IC. Methods: Stage III/IVA,B resectable HPV+ OPSCC were included. Eligible pts received IC q3 week x 3 with P 90mg/m2 days (D) 1,8, 15, cisplatin (CDDP) 75mg/m2 D1, and cetuximab (C) 400 mg/m2 D1, cycle 1 f/b C 250 mg/m2 weekly. Primary tumor and involved nodal response to IC were determined independently. Pts recieved IMRT 54Gy/27 fxs with weekly C for CCR vs. 69.3Gy/33 fxs with weekly C if <CCR. Primary endpoint was 2-year PFS; secondary endpoints were toxicity, OS, response rate, QOL and correlative biomarkers. Results: From March 2010 to Oct 2011, 90 pts were enrolled (80 analyzable). Median age was 57 years, 95% men, 93% Caucasian, 91% PS 0, 46% never smokers, 84% not current smokers. Nodal stage: 39%-N2B, 29%-N2C, T stage: 23%-T1, 50%-T2, 16%-T3, 10%-T4. 96% received all 3 cycles of IC. Grade 3/4 toxicities included: rash (25%), neutropenia (11%). During CRT: oral mucositis (31%), dysphagia (17%), radiation dermatitis (8%). Response: Biopsy at primary site post- baseline measurements rendered 7/80 pts unevaluable (UE), 6/7 had investigator-reported CCR to IC. The centrally reviewed and investigator reported primary site CCR rate to IC was 63.8% ( 95% CI: 52.2%, 74.2%) and 71.3% (95% CI: 60.0%, 80.8%), respectively. Radiation: 73.8% (59/80 pts) received low dose IMRT/C to primary [54Gy (56), 52Gy (1), 40Gy (2)]. Best overall clinical response was 86% (CR +PR+SD) with 14% UE. Rate of post-treatment neck dissection in low dose vs other RT gp is 13.4% vs 22.2% ( p value of 0.46), respectively. Median follow up is 11.8 months. Conclusions: Overall, IC with P, CDDP and C f/b low dose RT with C was well tolerated, with all pts responding and very low grade 3/4 toxicities. Data on PFS are premature. A 2 year PFS of 85% or better will be considered worthy of further study. Clinical trial information: NCT01084083.