bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of low-dose capecitabine in metastatic breast cancer.
Authors: Bertelsen Caitlin , Ji Lingyun , Russell Christy Ann , Spicer Darcy V. , Garcia Agustin , Sposto Richard , Tripathy Debu 
Published: March 2020

1065 Background: The FDA-approved dose of capecitabine (cape) of 1250mg/m2 twice daily (BID) is associated with treatment-limiting toxicities. Published reports suggest that lower starting doses of cape can be as effective as the approved dose in treating metastatic breast cancer (MBC). We compared the efficacy of lower than previously published doses of cape with results of registrational Phase III trials using the approved dose. Methods: We performed a retrospective analysis of patients treated at the University of Southern California hospitals who received cape as the first, second, or third line of chemotherapy for MBC to determine the progression-free survival (PFS) associated with low starting doses. The primary endpoint was PFS among patients with measurable disease, and secondary aims were to analyze the relationships between PFS and various clinical characteristics for all patients. Results: Patients (n=84) received a median cape dose of 565 mg/m2 BID, often administered as a flat dose (not adjusted for body surface area) of 1000 mg BID. Median PFS among patients with measurable disease (n=62) was 4.1 months (95% confidence interval or CI = 2.9-5.7), which was similar to the median PFS values of 4.4 months (95% CI = 4.14-5.42, n=480) (Sparano et al. JCO 2010;28:3256) and 4.2 months (95% CI = 3.81-4.50, n=377) (Thomas et al. JCO 2008;25:5210) for single-agent cape reported in the major trials with similar eligibility criteria. Among all patients, PFS was shorter in measurable disease, triple negative and HER2+ subtypes, and was similar in all lines of therapy. Only two patients (2.4%) discontinued cape due to toxicity. Conclusions: These data support the efficacy of very low doses of cape for MBC. Prospective randomized controlled trials testing lower starting doses of cape are needed to optimize the benefit/risk ratio. [Table: see text]
Cancer stem cell markers in locally advanced breast cancer.
Authors: Tiezzi Daniel G. , Sicchieri Renata D , Antonio Heriton MR , Mouro Larissa R , da Silva Joao Santana , de Andrade Jurandyr Moreira ,   Breast Disease Division - FMRP
Published: March 2020

1075 Background: the expressions of CD44/CD24, CXCR4 and ABCG2 have been reported as potential breast cancer stem-like cell (CSLC) markers. The association between the quantity of CSLCs and the response to neoadjuvant chemotherapy (NACT) remains unclear. Methods: we prospectively analyzed the expression of CD44/CD24, CXCR4 and ABCG2 in 20 patients with locally advanced or metastatic (LAMBC) invasive ductal carcinomas of the breast subjected to NACT. The mammosphere assay (Mammocult) was studied in 10 samples. Patients’ mean age was 55.6 ± 8.2 yo. According to clinical stage (CS), 5 patients were IIb, 4 - IIIa, 8 - IIIb and 3 - IV. The mean clinical tumor diameter was 6.3 ± 2.8cm. The ER, PgR and HER2 positive expression rates were 50%, 45% and 50%, respectively. Ten patients were treated with EC-T, eight were treated with EC-TH (HER2+) and two were treated with FEC75 combination as NACT. The median percentage CD44+/CD24-, CXCR4+, ABCG2+ and ESA+ cells within Lin- cells were determined by flow cytometry in fresh sampled tumors after tissue digestion. The relationship between flow cytometry analyses and clinical and pathological response to therapy was analyzed. Results: complete clinical response (cCR) and complete pathological response (pCR) was observed in 9 (45%) and 5 (25%) patients. We did not observe a significant association between pCR and ER, PgR or HER2 expression. We observed and association between the pCR with percentage of ABCG2+ cells within the tumor and with the number of mammospheres. No correlation between pCR and CD44+/CD24- cell population within the tumor was observed. The median percentage of ESA+/Lin-/ABCG2+ cells within the tumor in pCR patients was 0.6% and 3.5% in patients with no pCR (p= 0.02). The median number of sphere formation was 5/100 cells and 0.9/1000 cells in pCR and non-pCR patients, respectively (p= 0.02). Interestingly, there was a positive correlation between ABCG2 expression and the number of mammosfere formation (r= 0.66; p= 0.03). This correlation was not significant comparing to CD44+/CD24- cells or CXCR4. Conclusions: the percentage of ABCG2+ cancer cells within the tumor and the number of mammosphere formation are predictive factors for pCR in LAMBC patients subjected to NACT. ABCG2 is a potential marker for CSLCs.
BCL2 protein in prediction of relapse in triple-negative breast cancer (TNBC) treated with adjuvant anthracycline-based chemotherapy.
Authors: Bouchalova Katerina , Svoboda Marek , Kharaishvili Gvantsa , Radova Lenka , Bouchal Jan , Trojanec Radek , Koudelakova Vladimira , Hajduch Marian , Cwiertka Karel , Kolar Zdenek 
Published: March 2020

1087 Background: Preclinical data show an association of BCL2 expression and resistance to anthracyclines. The absence of BCL2 expression in prechemotherapy samples is associated with a higher probability of pathological complete response to neoadjuvant doxorubicin-based chemotherapy. The aim of our research is identification of markers predicting sensitivity to adjuvant treatment in TNBC. Here we focus on BCL2 protein as a putative predictor of sensitivity to adjuvant anthracycline-based chemotherapy. The objective was to determine whether BCL2 expression predicts relapse in TNBC patients treated with anthracycline-based regimens. Methods: The study included 187 patients with TNBC, 178 of whom were treated with adjuvant chemotherapy (164 had anthracyclines). BCL2 analysis was performed using IHC, proportion score and intensity score were counted. The data were analysed with software Statistica and R. Results: High BCL2 expression predicts poor relapse free survival (RFS) in patients treated with adjuvant anthracycline-based regimens (logrank p=.035, hazard ratio, HR 2.37, 95%CI 1.04-5.41). High BCL2 predicts trend to poor overall survival (OS) in patients treated with adjuvant anthracycline-based regimens (logrank p=0.075, HR 2.31, 95%CI 0.90-5.97). In univariate analysis of anthracycline treated patients, stage (RFS p=.0004, OS p=.0005), size (RFS p=.003, OS p=.00009) and nodal status (RFS p=0.018, OS p=.028) were associated with outcome, as well. In multivariate analysis of athracycline treated patients, BCL2, size and nodal status had an independent predictive significance for both RFS (p=.005, p=.056, p=.003) (logrank test, p=0.0004) and OS (p=.014, p=.006, p=.012) (logrank test p=0.0007). Conclusions: This study is the first to prove that high BCL2 expression predicts poor outcome in TNBC treated with adjuvant anthracycline-based chemotherapy. BCL2 expression could facilitate decision making on adjuvant treatment in TNBC patients and its assessment should be included in standard diagnostics. In patients with high BCL2 expression other types of adjuvant treatment should be considered. Grants: IGA NS10286,IGA NS10357-3 and Biomedreg CZ.1.05/2.1.00/01.0030.
Management of antiangiogenics’ renovascular safety in breast cancer subgroup and intermediate results of the MARS study.
Authors: Daniel Catherine , Janus Nicolas , Rey Jean-Baptiste , Beuzeboc Philippe , Ray-Coquard Isabelle , Gligorov Joseph , Spano Jean-Philippe , Thery Jean Christophe , Jouannaud Christelle , Goldwasser Francois , Mir Olivier , Morere Jean F. , Oudard Stephane , Azizi Michel , Dorent Richard , Deray Gilbert , Launay-Vacher Vincent 
Published: March 2020

1095 Background: Hypertension (HTN) and proteinuria (Pu) are class-side-effects of anti-VEGF drugs (AVD), related to the inhibition of the VEGF pathway. The MARS study has been conducted to assess the renovascular tolerance of AVD in the clinical setting. Methods: The MARS study is a multicentric prospective observational study of the renovascular safety of AVD in AVD-naive pts. 7 centres from 2009 to 2011. Data collected included: gender, age, serum creatinine (SCr), diabetes, HTN, hematuria (Hu) and Pu. This sub-group analysis presents the intermediate results for the 1st 155 pts with breast cancer (BC) receiving bevacizumab who completed the 1-year follow-up (f/u) (out of 337 BC pts in total). Results: Median age at inclusion: 62 years. Bone, visceral and cerebral metastasis frequencies were 74.2, 51.6 and 5.2%, respectively. Diabetes and HTN prevalences were 3.9% and 10.3%, respectively. Baseline renal assessment retrieved: Pu 14.2%, Hu 8.4%, aMDRD 98.2 ml/min/1.73m2 and 2 pts with aMDRD<60. The incidence of de novo Pu during f/u was 15% (Table). 59.1% of pts with Pu at inclusion improved. Among pts with de novo Pu, 40.0% afterwards improved/normalized. No grade 3/4 Pu has been reported and no hematuria. 12.9% developed HTN. Moreover, renal function decreased by -3.2 ml/min/1.73m2/year and 4 pts had aMDRD<60 at the end of f/u. 32.2% increased their SCr: 27.1% grade 1, 4.5% grade 2, and 0.6% grade 3. All pts with grade 2-3 returned to normal or grade 1. No thrombotic micro-angiopathy (TMA) has been reported. Conclusions: These results show that 1) TMA remains rare, 2) Pu developed in 15% of pts, with no grade 3/4, 3) less than 13% developed HTN and 4) renal function was only slightly impaired with transient elevations in SCr. Furthermore, in case of a renovascular effect, investigators followed the recommendations from the French Society of Nephrology (Halimi JM. Nephrol Ther 2008) and no treatment withdrawal for unmanageable renovascular toxicity occurred. [Table: see text]
Patterns of regional node irradiation therapy following breast-conserving surgery: Report from the National Cancer Data Base 2003-2007.
Authors: Hou Ningqi , Yao Katharine , Jaskowiak Nora T. , Hasan Yasmin , Winchester David J. , Winchester David Porter , Huo Dezheng 
Published: March 2020

1101 Background: A recent randomized trial (MA.20) showed that regional nodal irradiation (RNI) in addition to breast irradiation in high risk node negative and 1-3 node positive patients undergoing breast-conserving therapy (BCT) reduced the risk of recurrence and improved disease-free survival. We investigated the trends of RNI use in the United States and related factors for the use of RNI using the National Cancer Data Base. Methods: This study includes 292,598 stage I-III breast cancer patients without neoadjuvant therapy who underwent BCT from 2003-2007. We investigated pathological, patient, and facility factors related to RNI use, by multivariable logistic regression, with odds ratio (OR) estimations. Results: The proportion of radiotherapy use after BCT slightly declined from 78.6% in 2003 to 75.6% in 2007. The use of breast irradiation plus RNI decreased from 10.8% in 2003 to 8.3% in 2007 (p<0.0001). The number of tumor positive lymph nodes strongly determined the use of additional RNI: 4.4% patients with negative nodes, 22.8% patients with 1-3 nodes, and 39.7% patients with 4 or more nodes received breast irradiation plus RNI after undergoing BCT (p<0.0001). The proportion of patients undergoing RNI significantly decreased over the study period from 43.3% to 37.2% in the 4+ node positive group, and from 23.6% to 22.0% in the 1-3 node positive group. At comprehensive community cancer centers, 25.5% patients with 1-3 positive nodes were treated with breast irradiation plus RNI (vs. 23.2% in community cancer centers and 21.1% in academic/research cancer centers). Among node negative patients, 11.5% of those with tumor size greater than 5 cm received additional RNI, compared to 4.3% in patients with tumors less than 5cm (p<0.0001). Other significant factors related to RNI use included higher tumor grade, younger age, facility location, and facility volume. Conclusions: The use of RNI varies by number of tumor positive nodes and facility factors. Only 22.8% of patients with 1-3 positive nodes underwent RNI. Future studies are needed to determine if the use of RNI will increase after publication of the MA.20 trial especially for the 1-3 node positive group.
Breast cancer multifocality-multicentricity and survival outcomes.
Authors: Lynch Siobhan P. , Lei Xiudong , Chavez-Mac Gregor Mariana , Hsu Limin , Meric-Bernstam Funda , Buchholz Thomas A. , Zhang Hong , Hortobagyi Gabriel N. , Valero Vicente , Gonzalez-Angulo Ana M. 
Published: March 2020

1104 Background: Studies have consistently shown a correlation between multifocal (MF) and multicentric (MC) breast cancers and the rate and extent of lymph node metastases, but the literature is divided on whether there is a corresponding impact on survival outcomes. In the absence of compelling evidence to dictate otherwise, the convention according to current TNM staging guidelines has been to stage and treat MF and MC cancers according to the diameter of the largest lesions, without taking other foci of disease into consideration. We evaluated a large single institution cohort of MF and MC breast cancers to determine their frequency, clinico-pathological characteristics and effect on survival outcomes. Methods: MF and MC were defined pathologically as more than one lesion in the same quadrant and more than one lesion in separate quadrants, respectively. Patients were categorized by presence or absence of MF or MC disease. Kaplan-Meier product limit method was used to calculate relapse-free survival (RFS), breast cancer-specific survival (BCSS) and overall survival (OS). Cox proportional hazards models were fit to determine independent associations of MF/MC disease with survival outcomes. Results: Out of 3924 patients, 942 (24%) had MF (n=695) or MC (n=247) disease. MF and MC disease was associated with higher T-stages (T2 26% vs. 21.6%; T3 7.4% vs. 2.3%, P<0.001), higher nuclear grade (grade 3 44% vs. 38.2%, P<0.001), lymphovascular invasion (26.2% vs. 19.3%, P<0.001) and lymph node metastases (43.1% vs. 27.3%, P<0.001). After a median follow up of 51 months, MC but not MF breast cancers were associated with significantly worse 5-year RFS (90% vs. 95%, P=0.02) and BCSS (95% vs. 97%, P=0.01), and a trend towards worse 5-year OS (92% vs. 93%, P=0.08). After controlling for other risk factors, multifocality and multicentricity did not have an independent impact on RFS, BCSS or OS. This was true for the subset of T1N0 breast cancers as well. Conclusions: MF and MC breast cancers occurred in 24% of the cases and were associated with poor prognostic factors, but they were not independent predictors of worse survival outcomes. Our findings support the current TNM staging system of using the diameter of the largest lesion to assign T-stage.
Role of axillary ultrasound after neoadjuvant chemotherapy in women with node-positive breast cancer (T1-4, N1-2, M0) at initial diagnosis (ACOSOG Z1071).
Authors: Le-Petross Huong T. , McCall Linda Mackie , Hunt Kelly , Mittendorf Elizabeth Ann , Ahrendt Gretchen M. , Wilke Lee G , Leitch A. Marilyn , Taback Bret , Boughey Judy Caroline ,   American College of Surgeons Oncology Group
Published: March 2020

1107 Background: The role of axillary ultrasound (AUS) after neoadjuvant chemotherapy (NAC) to assess for residual nodal disease in patients presenting with node positive breast cancer remains unclear. ACOSOG Z1071 is a prospective multi-institutional trial evaluating sentinel node biopsy in patients with biopsy proven node positive breast cancer (T0-4, N1-2, M0) receiving NAC. Herein we report on the secondary objective evaluating the correlation of lymph node (LN) features on AUS with residual nodal disease. Methods: AUS images from diagnosis and after NAC were centrally reviewed for cortex size, LN size and LN morphology. Morphologic features were defined as: type I, no visible cortex, type II, < 3 mm hypoechoic cortex, type III, > 3mm hypoechoic cortex, type IV, generalized lobulated hypoechoic cortex, type V, focal hypoechoic cortical lobulation, and type VI, totally hypoechoic node with no hilum. Type I and II are considered normal. Results: Surgical and imaging data are available on 294 patients. Median age was 50 years (range 23-93 years), mean initial tumor size 3cm (0 to 15cm) and clinical stage II in 64.5% and III in 35.5%. The maximum LN diameter decreased after NAC (mean 22mm pre-NAC to 14mm post-NAC)(p<0.0001); however, there was no significant difference after NAC between the pathologically N+ (13mm, range 5-46mm) and N0 cases (12mm, range 3-32mm)(p=0.13). LN cortical thickness correlated with residual nodal disease after NAC (p-value = 0.04). Using a cutoff point of cortical thickness of 3 mm, the sensitivity was 33% (48/145) and specificity 80% (66/82). AUS morphological features after NAC was associated with false negative rate 62%, false positive rate 28%, sensitivity 38%, and specificity 72%. Conclusions: AUS after NAC is useful to assess nodal response. Cortical thickness was the best predictor of residual nodal metastasis. LN size and morphological features do not reliably exclude residual nodal metastasis in patients after NAC. [Table: see text]
Accuracy of breast MRI in predicting pathologic tumor size.
Authors: Caprio Kimberly Anne , Chagpar Anees B. , Hooley Regina , Tavassoli Fattaneh , Honarpishe Helen , Lannin Donald R. , Killelea Brigid K. , Horowitz Nina Ruth 
Published: March 2020

1109 Background: MRI use as a preoperative planning tool is increasing in women with breast cancer, yet the correlation between MRI and pathologic size of cancers is unclear. The purpose of this study was to determine the accuracy of MRI in predicting pathologic tumor size, and factors that affect this correlation. Methods: Clinicopathologic and imaging data from 84 patients diagnosed with invasive or in situ breast cancer from September 2010 to October 2011 who had preoperative MRI were reviewed. 12 patients who had neoadjuvant chemotherapy were excluded. MRI detected 147 lesions in the remaining 72 patients. Concordance between MRI and pathology size was determined using Spearman rho coefficients, and factors affecting the accuracy of MRI in predicting tumor size within +/- 0.5 cm were determined. Results: There was a modest correlation between MRI and pathology size for all MRI detected lesions (benign or malignant) with a Spearman coefficient of 0.53. Of the 147 MRI detected lesions, 45 (30.6%) had pathologic and MRI size correlating within +/- 0.5 cm; 76 (51.7%) were overestimated (>0.5cm) by MRI, and 26 (17.7%) were underestimated (>0.5cm). 101 (68.7%) of the 147 lesions were found to be malignant (either with invasive disease or DCIS). In this subgroup, 35 lesions (34.7%) had an MRI size within +/- 0.5 cm of the pathologic size; 40 (39.6%) were overestimated by MRI and 26 (25.7%) were underestimated. Patient age, tumor histology, LVI and grade did not predict concordance between pathologic and MRI size. However, small MRI lesion size more accurately correlated with pathologic tumor size. While 51.1% of tumors that had concordant MRI and pathologic findings within 0.5 cm were <1 cm on MRI, no tumor found to be > 5 cm on MRI was within +/-0.5 cm on final pathology (p=0.001). Conclusions: MRI accurately predicts pathologic tumor size only when the size of the lesion on MRI is <1 cm.
The impact of primary surgery on stage IV breast cancer.
Authors: Harris Ella , Kell Malcolm R. , Salman Reem , Stokes Maurice , Gorey Tom 
Published: March 2020

1113 Background: The role of primary surgery in metastatic breast cancer is unclear. Here in we have performed metaanalysis on available data to assess the role of surgery on oncological outcome in patients with stage IV breast cancer. Methods: A comprehensive search for published trials that examined outcome following removal of primary disease in stage IV breast cancer was performed using MEDLINE and cross referencing available data. Reviews of each study were conducted, and data were extracted. Primary outcome was overall survival related to surgical removal of primary disease. Results: We identified 15 relevant studies of which 10 were appropriate for analysis. Data was available on 28,693 patients with stage IV disease, of whom 52.8% underwent removal of the primary carcinoma. Patients undergoing primary surgery in this setting were more likely to be alive at 3 years 40% vs. 22% (OR 2.32 CI 2.08-2.6, p<0.01 (surgery vs. no surgery)). Analysis of subgroups for selection to surgery or not, favoured smaller tumours, fewer comorbidities, fewer metastases (p<0.01). There was no difference between the two groups in location of metastases, grade of tumour or receptor status. Conclusions: Patients undergoing removal of primary carcinoma in the setting of stage IV breast cancer appear to have an improved overall survival. However the available data suggest that these surgical patients probably have better prognosis stage IV disease than those patients not undergoing surgery.
Postmastectomy radiotherapy for patients with one to three positive lymph nodes: Utilization and benefit.
Authors: Huo Dezheng , Hou Ningqi , Jaskowiak Nora T. , Hasan Yasmin , Winchester David J. , Winchester David Porter , Yao Katharine 
Published: March 2020

1116 Background: The use of postmastectomy radiotherapy (PMRT) for patients with pT1-2pN1 tumors is controversial and ASCO guidelines indicate that there is insufficient evidence to make recommendation. We hypothesized that the use of PMRT in this patient group was low and has minimal impact on survival. Methods: The study includes 83,742 invasive breast cancer patients from the National Cancer Data Base who underwent mastectomy with pT1-2 and pN1 disease from 1998-2007. Neoadjuvant cases were excluded. We investigated factors related to PMRT use using cross tables and logistic regression. Survival analysis was conducted using Cox models in patients diagnosed from 1998-2002, with a median follow-up of 5.5 years. Results: The proportion of N1 patients undergoing PMRT remained stable from 1998 to 2007, at approximately 20%. PMRT use increased with larger tumor size (15.4% in T1N1 and 24.4% in T2N1), and with increasing positive lymph nodes (14.6%, 23.7%, and 35.2% for patients with one, two, or three positive nodes, respectively). Age was significantly inversely correlated with PMRT use: the proportion of patients receiving PMRT was 31.3% for age <40 years and 8.2% for 80+ years (p<0.001). Asians are more likely to receive PMRT (25.5%), compared to other races (20.3% white, 20.7% black, and 20.6% Hispanic; p<0.001). PMRT also varied considerably by facility location, the highest in the Northeast at 31.3%, and the lowest in the South at 15.8% (p<0.001). There was only minor difference in PMRT use between different types of cancer centers. Insurance status, income and education level were not associated with PMRT use. After adjusting for prognostic factors in the Cox models, PMRT use was associated with a reduced mortality (hazard ratio=0.87, 95% CI: 0.81-0.93; p<0.001). The multivariable-adjusted 5-year death rate was 16.1% in patients receiving PMRT and 18.1% in patients not receiving PMRT. For pT1N1 tumors the absolute benefit was 1.3% compared to 2.7% for pT2N1 tumors. Conclusions: PMRT use varies with facility and clinicopathologic factors, but not socioeconomic factors. The risks of radiation need to be weighed against the 2% absolute survival benefit when deciding on whether to use PMRT for pT1-2N1 patients.