bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term survival of women with breast cancer with ≥10 lymph nodes at diagnosis.
Authors: Cavalcante Ludimila , Zeichner Simon B. , Suciu Gabriel P , Ruiz Ana L. , Hirzel Alicia , Trif Almos , Krill-Jackson Elisa 
Published: March 2020

e11575 Background: Axillary lymph node status is one of the most important prognostic factors in patients with breast cancer, and those with more than ten metastatic lymph nodes at diagnosis have a decreased overall survival. The purpose of this study is to better characterize the clinical course of this high-risk, poorly described patient population and determine the factors associated with long-term survival. Methods: A retrospective cohort analysis of all breast cancer patients with greater than ten metastatic lymph nodes diagnosed at Mt. Sinai Medical Center from January 1990 to December 2007 (n= 175). Descriptive frequencies, overall median survival (OMS), 5- and 10-year survival were calculated for standard prognostic factors and treatment variables. Univariate statistical analysis was performed, followed by a multivariate prognostic analysis for time-to-event data, using the Cox and extended Cox regression model. Results: The majority of patients were non-Hispanic white females between the ages of 56-70, diagnosed between 1990-1999, with tumors between 2-5 cm and 10-15 metastatic lymph nodes. Most were ER/PR positive, HER2 negative, and treated with surgery, chemotherapy, radiation and hormonal therapy. The OMS was 94 months (CI = 69-114) with 5- and 10-year survival rates of 64.3 and 41.6%, respectively. Ages between 21-45 years (OMS of 187 months, p = 0.03), tumors less than 2 cm (146 months (95% CI = 85-198), p = 0.02), ER positivity (131 months (95% CI = 94-157) vs. 39 months (95% CI = 27-59), p = 0.0003) and treatment received between 2000-2003 (98 months (95% CI = 55-133), p = 0.02) were all associated with significantly improved survival. Conclusions: Over the past decade there were significant gains in the long-term survival of breast cancer patients with greater than ten positive nodes at diagnosis, possibly due to improvements in multimodality therapy, such as the introduction of taxanes, although stage migration may be another contributing factor. Our study further showed an encouraging survival for ER positive patients and a dismal one for ER negative patients, highlighting the need for new targeted therapies directed towards ER negative tumors.
The impact of estrogen depletion by aromatase inhibitors on adiponectin serum levels in postmenopausal patients with breast cancer.
Authors: Pfeiler Georg , Konigsberg Robert , Hadji Peyman , Fitzal Florian , Tea Muy-Kheng Maria , Vogl Sonja , Berger Andreas , Exner Ruth , Seifert Michael , Singer Christian F. , Gnant Michael , Dubsky Peter Christian 
Published: March 2020

e11601 Background: Adiponectin impacts on breast cancer risk and prognosis. Obesity and insulin resistance are correlated with low adiponectin serum levels, which increase breast cancer risk and lead to a worse outcome regarding breast cancer. Additionally a cross talk between the adiponectin and estrogen signaling system has been suggested. Here we prospectively investigated the impact of estrogen depletion via aromatase inhibitors (AI) on adiponectin serum levels in postmenopausal patients with breast cancer. Methods: 68 postmenopausal ER positive patients with breast cancer, scheduled to receive anastrozole or letrozole as adjuvant endocrine treatment were prospectively included in this study. Serum was taken before (T1) and 3 months after start with aromatase inhibitors (T2). Non-fasting serum levels of adiponectin, FSH, LH, E2, glucose and insulin were analyzed immediately in the clinical routine lab and in a dedicated central lab able to measure E2 in serum at low concentrations with high sensitivity. Results: At baseline, a strong significant negative correlation between adiponectin and body mass index (BMI) as well as a positive correlation between adiponectin and FSH serum levels could be observed (r=-0.43, p=0.01 and r=0.38, p=0.03, respectively). Taking the previously proposed cut off of 15.5μg/ml, patients with low adiponectin serum levels had a significantly higher BMI and significant lower FSH serum levels. No interaction between adiponectin and estradiol serum levels could be detected. As previously shown, AI treatment significantly decreased estradiol serum levels and consequently increased FSH serum levels. However, 3 months of AI treatment did not alter adiponectin, insulin and c-peptide serum levels, respectively. Conclusions: Short term estrogen depletion via aromatase inhibitors does not impact on non-fasting adiponectin, insulin and c-peptide serum levels in postmenopausal patients with breast cancer.
Do oncology patients in an outpatient hospital receive the same care as patients in an office/clinic setting? A case study evaluating patients with non-metastatic HER2+ breast cancer (BC) receiving adjuvant trastuzumab.
Authors: Lalla Deepa , Brammer Melissa , Guérin Annie , Gauthier Geneviève , Giguere-Duval Philippe , Wu Eric Q. , Santos Eduardo 
Published: March 2020

e11603 Background: It is unknown if quality of care received by patients (pts) with BC is impacted by the location at which care is received. Using a sample of pts with HER2+ BC receiving adjuvant trastuzumab (T), we compared T treatment patterns between pts treated in office/clinic (MD) or outpatient hospital (HOSP) settings. Methods: Non-metastaticBCadult women who received ≥2 T infusions in an MD or HOSP setting from 2008-2012 were selected from the US-based Humana database. Based on the site of care where T was received, pts were classified into MD or HOSP cohorts. Pts were followed from first T infusion date to treatment discontinuation, first metastasis, or end of continuous eligibility, for a maximum of 12 months (mos). T treatment duration, discontinuation (treatment gap of ≥45 consecutive days), and the proportion of pts completing the recommended 12 mos treatment indication were compared between cohorts. Results: 730 pts were included; 67% received T in an MD setting vs. 33% in a HOSP setting. Differences between cohorts were observed in terms of healthcare insurance plan: more pts in the HOSP setting had Medicare coverage (55.5% vs. 67.1%; p=.003). Average T duration was shorter in the HOSP setting (MD cohort: 241.9 days ; HOSP cohort: 191.3 days). Among pts observed for 12 mos, a higher proportion in the MD cohort completed the 12-mo treatment (84.3% in MD vs. 75.6% in HOSP [p=.034]). After adjusting for confounding factors, the HOSP cohort was 2.4 times more likely to discontinue treatment compared to the MD cohort ( p<.001). Conclusions: Duration of adjuvant T treatment for pts with non-metastatic HER2+ BC differed based on the site at which treatment was received. This suggests that oncology pts treated in an HOSP setting, vs. MD, may be at higher risk for treatment discontinuation or to receive a shorter course of treatment than recommended. Further research should explore the impact of these differing treatment patterns on outcomes.
Fulvestrant for advanced breast cancer: A meta-analysis.
Authors: Al Mubarak Mustafa Mohammed 
Published: March 2020

e11613 Background: Fulvestrant is an endocrine agent which degrades the estrogen receptor, thereby downregulating its signaling. While fulvestrant has been consistently tested in postmenopausal women with inoperable locally advanced or metastatic breast cancer, there has been substantial heterogeneity in study populations and drug dosing. The optimal use of fulvestrant in advanced breast cancer is therefore unclear. Methods: A systematic review of electronic databases was conducted to identify randomized trials of fulvestrant versus other endocrine therapy. The hazard ratios (HR) for time to progression (TTP) and the odds ratios (OR) for serious adverse events (SAEs), discontinuation of treatment due to toxicity and commonly reported toxicities (hot flashes, venous thrombosis, gastrointestinal disturbance, arthralgia, and asthenia) were pooled in a meta-analysis. Meta-regression explored heterogeneity in study population and fulvestrant dosing. Results: Eight studies were included in the analysis. Overall, there was no difference in TTP between fulvestrant and control groups (HR:0.94, 95% CI 0.85-1.03, p=0.18). On meta-regression, fulvestrant showed reduced hazards for TTP compared to aromatase inhibitors (AI) if used in first line (p for trend <0.001), in studies where fewer patients received adjuvant endocrine therapy (p for trend <0.001) and at higher doses (p for trend <0.001). Rates of SAEs and treatment discontinuation were similar for fulvestrant and control groups, but fulvestrant monotherapy was associated with significantly less arthralgia (OR:0.73,95% CI 0.57-0.95, p=0.02). The addition of fulvestrant to AI compared with AI alone was not associated with improved TTP (HR:0.88, 0.72-1.09,P=0.25), but led to increased hot flashes (OR: 1.68,95% CI 1.30-2.16, P<0.001) and gastrointestinal disturbances (OR:1.28, , 95% CI 1.01-1.63, p=0.04). Conclusions: In unselected patients, fulvestrant monotherapy is associated with similar efficacy, but reduced arthralgia. Use of high dose fulvestrant monotherapy in first line or in patients with limited prior exposure to adjuvant endocrine therapy may delay progression compared with AI. Fulvestrant combined with AI was not associated with improved efficacy but led to increased toxicity.
Cardiotoxicity and related risk factors in long-term trastuzumab (T) administration for metastatic breast cancer (MBC): A retrospective analysis.
Authors: Pistilli Barbara , Marcellusi Andrea , Valeri Michele , Torresi Umberto , Nacciarriti Dania , Saladino Tiziana , Mariani Cinzia , Santinelli Alfredo , Ferretti Benedetta , Latini Luciano , Benedetti Giovanni 
Published: March 2020

e11616 Background: Continuing T beyond progression has become a common strategy in the treatment of human epidermal growth receptor 2- overexpressing (HER2) MBC. However, T administered for several years with concomitant chemotherapy elicits concern about cardiac safety especially in patients (pts) with risk factors. Methods: Cardiac events (CEs) and survival of HER2 MBC pts treated with T +/- chemotherapy at our institution from Dec 2003 to Jun 2012 were evaluated. CEs were graded by NCI-CTCAE v 3.0. Risk factors assessed for cardiotoxicity were: age, body mass index, antihypertensive therapy, history of cardiac disease, diabetes, hypothyroidism, smoking, prior radiotherapy on the chest wall, prior cumulative dose of anthracycline(A), interval between last A dose and first T dose, baseline LVEF, continued/interrupted T exposure, concomitant chemotherapy. Chi-square test was used to compare distribution of CEs over different times of T exposure (p≤ 0.05). Univariate and multivariate Cox regression analysis were used to assess the effect of risk predictors. Results: Sixty-two pts assessable. Median age 52 years (range, 29 to 76), median cumulative time receiving T 29.5 months (range, 3 to 99 months); 40 pts (64.5%) received T without interruption and 19 pts (30.6%) were treated for more than 36 months. CEs occurred in 11 out of all pts (17.7%): grade 1 in 3 pts (4.8%), grade 2 in 5 (8.1%) and grade 3 in 3 (4.8%). The rate of CEs showed no statistically significant difference in pts receiving T for up to 36 months and over: 7/43 (16.3%) and 4/19 (21%), respectively, (p =0.724). In univariate Cox regression analysis significant risk factors were: history of cardiac disease (HR 6,814, 95% CI: 1,384-33,542) and smoking (HR 5,228, 95% CI: 1,403-19,491). In multivariate analysis smoking was the only independent predictor (HR 5,886, 95% CI: 1,479-23,247). Median survival from MBC diagnosis was 50 months (range, 6 to 101 months). Conclusions: Despite the limited sample size, our analysis suggests that cardiotoxicity does not hamper a long-term use of T, since the rate of CEs did not increase in pts treated over 36 months. Moreover, smoking appears to be a predictive factor of T cardiotoxicity.
Phase II study of vinorelbine and capecitabine as first-line treatment for metastatic breast cancer.
Authors: El-Sadda Wael , Abdel Halim Inas Ibraheim , Abdel Aziz Mohamed 
Published: March 2020

e12004 Background: Vinorelbine (V) and capecitabine (C) are likely to have a synergisitic interaction. Vinorelbine upregulates thymidine phosphorylase; a key enzyme in the conversion of capecitabine to active 5-FU in tumor tissue. Available phase II clinical data reports response rates ranging from 48-70% in first line metastatic breast cancer (MBC) for this combination. We evaluated the efficacy and safety of vinorelbine plus capecitabine in patients with MBC relapsing after adjuvant anthracycline based treatment. Methods: Sixty patients were enrolled between Oct 2008 through Dec 2010. All patients had measurable MBC relapse after adjuvant anthracycline and/or taxanes, WHO PS < 2, adequate bone marrow, renal and hepatic functions. Patients received intravenous vinorelbine 25 mg/m2 on day 1 and 8 and oral capecitabine 1000 mg/m2 bid on days 1 to 14, cycles to be repeated every 3 weeks. Patients with PD went off the study while those with CR, PR or SD continued treatment for a maximum of 8 cycles. Results: Median age 54 years (range 35-67 years), Median WHO PS 0 (range 0-1). Previous adjuvant therapy anthracycline (100%) and hormone therapy (60%). Median disease free interval was 6 months. Main metastatic sites were lung (40%), liver (25%), bone (40%) skin (35%), and lymph nodes (35%). Twenty five percent of patients had one metastatic site, 60% had two sites, 10% had three sites and 5% had more than three sites. The total number of cycles delivered was 441 with a median number of cycles/patients of 7 (range 3-8). An objective tumor response was achieved in 36 pts (60%), complete response (CR) in 6 pts (10%), 12 pts (20%) had stable disease (SD). After a follow up period of 6-36 months, the median time to progression and median survival were 14 and 23 months, respectively. No WHO G4 toxicities were noted, 3 pts (5%) developed G3 neutropenia and one patient (1.7%) developed G3 hand and foot syndrome. G2 anemia, neutropenia and diarrhea were reported in 2 pts (3.3%), 3 pts (5%) and 6 pts (10%), respectively. Conclusions: The combination of vinorelbine and capecitabine showed significant efficacy and mild toxicity as a first-line treatment for patients with metastatic breast cancer after failure of adjuvant anthracycline based therapy.
Clinical impact of 18F-FDG–PET in breast cancer: Survival analysis and comparison of intrinsic subtypes with standardized uptake value.
Authors: Ahn Sung Gwe , Lee Hak Min , Lee Seung Ah , Jeon Tae Joo , Yoo Young Hoon , Sohn Eun Joo , Jeong Joon , Lee Hy-De 
Published: March 2020

e12005 Background: [18F] fluorodeoxyglucose positron emission tomography (18F-FDG–PET) scans are known as an important imaging study with their reflection biological activity in various malignancies. To investigate clinical impact of 18F-FDG–PET in breast cancer, we performed survival analysis with maximum standardized uptake values (SUVmax), and compared SUVmax according to breast cancer subtypes. Methods: We reviewed the medical records of 462 patients with breast cancer who underwent primary surgery between April 2004 and December 2008 at single institute. Patients were classified as 4 subtypes: luminal A, luminal B, HER2 and triple negative. The entire patients were randomly assigned as training set (n=220) and validation set (n=242). Results: High SUVmax vs. low SUVmax group was defined with cut-off points of 4 in a training set.At a median follow-up of 6.03 years, the patients with high SUVmax had a shorter disease-free survival in a validation set (p = 0.018, log-rank test). Using multivariate analysis for disease-free survival in the entire patients, high SUVmax was demonstrated as a poor prognostic factor (hazard ratio 2.34, 95% confidence interval 1.18-4.67). In the comparison among subtypes, mean of SUVmax was higher in triple negative type and HER2 type. Also, high SUVmax was significantly associated with larger tumor size, positive node, high Ki67 (≥14%), ER negative, and high histologic grade, and HER2 positive. Conclusions: In breast cancer, the patients with higher SUVmax showed a shorter disease-free survival. Higher SUVmax found in HER-2 and triple negative type suggests that 18F-FDG PET could reflect molecular signature.
Is ypT0/isn0 acceptable for Japanese population? JBCRG’s perception.
Authors: Kuroi Katsumasa , Ohno Shinji , Nakamura Seigo , Iwata Hiroji , Masuda Norikazu , Sato Nobuaki , Toi Masakazu 
Published: March 2020

e12011 Background: Pathologic complete response (pCR) is a proposed surrogate endpoint for predicting disease-free survival (DFS) or overall survival (OS). However, several definition of pCR has to be used in NAC studies, and In Japan, JBCRG conducted several study of neoadjuvant chemotherapy using QpCR(including focal residual invasive tumors as pCR) between 2002 and 2006. Methods: The regimen studied were FEC followed by Docetaxel (75 mg/m2)(FEC-DOC) (n = 186), FEC-DOC (100 mg/m2) (n = 37),DOC followed by FEC (n = 130), JBCRG-01, 02, 03, respectively. Three studies were pooled and analysed for pCR rates, DFS, OS in terms of several pCR definition and subtypes. We included patients when subtype and long-termfollow-up available for DFS and OS. We compared 5 pCR definitions: absence of invasive cancer and in situ cancer in the breast irrespective of nodal involvement (ypT0, SpCR), absence of invasive cancer and in situ cancer in the breast axillary nodes (ypT0ypN0, SpCRbn), absence of invasive cancer in the breast irrespective of nodal involvement (ypT0/is, CpCR), absence of invasive cancer in the breast axillary nodes with DCIS allowed (ypT0/isypN0, CpCRbn), and QpCR. Subtypes were classified into luminal (ER+ and/or PgR+, HER2-), luminal –HER2 (ER+ and/or PgR+, HER2+), triple-positive (TP) (ER-,PgR-, HER2-), HER2 (ER-, PgR-, HER2+) by using immunohistochemically stained specimen obtained by core needle biopsy. Results: Number of patients in each subtypes were as follows; luminal 206 (58%), luminal -HER2 34(10%), HER2 40 (11%), TN 73 (21%). pCR rate was significantly high in HER2 and TN irrespective of pCR definition (p <0.05). At median follow up 75M, pCR group showed significantly better prognosis. Cox multivariate analysis showed pCR (irrespective of pCR definition) and subtype were the significant predictors of prognosis among study, age, tumor size. Conclusions: Subtype is a useful predictive biomarker of pCR, and ypT0/isn0 is acceptable for Japanese population.
Capecitabine maintenance therapy after docetaxel/capecitabine combination chemotherapy in patients with metastatic breast cancer.
Authors: Gursoy Pinar , Surmeli Zeki Gokhan , Cakar Burcu , Arslan Cagatay , Zengel Baha , Karaca Burcak , Sezgin Canfeza , Karabulut Bulent , Sanli Ulus Ali , Uslu Ruchan 
Published: March 2020

e12018 Background: Addition of capecitabine to docetaxel improves survival outcomes compared with single agent docetaxel in metastatic breast cancer (MBC). In this study we analyzed efficacy of maintenance therapy with single agent capecitabine after six cycles of docetaxel/capecitabine chemotherapy in MBC patients. Methods: Patients with metastatic HER2 negative breast cancer were included. Six cycles of docetaxel (75mg/m2 q3wk) / capecitabine (1650mg/m2/day on days 1 to 14) followed by capecitabine (2000 mg/m2/day on days 1 to 14) were administered. Demographic features, progression free (PFS) and overall survival (OS) and response to treatment were recorded. Results: Fifty-four patients were included. Thirty-five patients (65%) were postmenopausal, and 40 (74%) were ER/PR positive. Median age was 53 (range 28 – 70). Number of metastatic sites was one in 23 patients, two in 21, three or more in 10 patients. Most common metastatic sites were bone (67%), lymph nodes (33%), lungs (30%), liver (13%); 13 patients (24%) had bone only disease. Forty-four (81.5%) patients received treatment in first-line, 10 (18.5%) received in second line setting. Median number of cycles applied (including docetaxel/capecitabine combination) was 9 (range 2 – 31, total 576). Median PFS was 9 months (10.4 for hormone receptor positive, 7.3 for negative patients) and median OS was 28 months. Objective response was assessable in 38 patients. Overall response rate (partial + complete response) was 42.6% (95% CI 29.6 – 55.6) with 1 complete response. Toxicities were evaluated in 41 patients; grade 3/4 neutropenia was observed in 10% and grade 3/4 hand-foot syndrome was observed in 24% of patients. Dose reduction was performed in capecitabine in 37%, and in docetaxel in 20% of patients. Conclusions: Maintenance with single agent capecitabine therapy after six cycles of docetaxel/capecitabine chemotherapy is an effective and tolerable treatment option for HER2 negative MBC patients.
Value of Ki-67 in prediction of response to neoadjuvant chemotherapy in breast cancer.
Authors: Kim Kwanil , Lee Kyunghee , Park Heungkyu 
Published: March 2020

e12025 Background: The expression of the human Ki-67 protein has been described as being associated with cellular proliferative activity. The objective of this study is to assess the potential value of Ki-67 for the prediction of therapeutic response after neoadjuvant chemotherapy in breast cancer. Methods: Sixty-eight patients who underwent anthracyclin based neoadjuvant chemotherapy between 2007 and 2012 were included for this study. The chemotherapy response was evaluated by comparing the pre- and post-neoadjuvant chemotherapy tumor size on radiologic imaging study with the tumor size at pathologic specimens according to RECIST (response evaluation criteria in solid tumors) version 1.1. We analyzed immunohistochemical(ER, PR, HER2, Ki-67, p53) profiles from both pre-neoadjuvant core biopsy and postoperative specimens to find their correlations with chemotherapy response. Results: Ten patients(14.7%) achieved pathologic complete response(pCR), 38 patients(55.9%) had pathologic partial response(pPR) and 20 patients(29.4%) had pathologic stable disease(pSD). The mean Ki-67 value of tumors with pCR was 61.0%, the Ki-67 value of tumors with pPR was 35.9%, and the Ki-67 value of tumors with pSD was 21.0%(p = 0.013). The analysis of Ki-67 values of the patients also showed that 25% of Ki-67 level is a reasonable cut-off value for defining higher Ki-67 level. In subgroup analysis, the higher Ki-67 level was significant factor of the response to neoadjuvant chemotherapy, especially in ER negative patients(p = 0.009) and HER2 negative patients(p = 0.009). In addition, the analaysis of response group showed that ER negative(p = 0.027), HER2 positive(p = 0.048), and higher Ki-67 level(p = 0.002) were predictive indicators of complete response. Conclusions: The higher Ki-67 level of breast cancer tissue may effectively indicate the higher response rate to chemotherapy and also the higher complete response rate. The results of our study suggest that the Ki-67 value before neoadjuvant chemotherapy is a predictive factor for the response to neoadjuvant chemotherapy. Moreover, the Ki-67 is a predictive factor of the pathologic complete response especially in patients with ER negative or HER2 positive.