bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors affecting nodal involvement in mucinous breast cancer.
Authors: Nguyen Tracy , Stash Bryce , Siwawa Portia , Misra Subhasis 
Published: February 2017

124 Background: Mucinous carcinoma of the breast is a rare type of invasive ductal breast cancer that accounts for 2-5% of all primary breast cancers. Axillary lymph node involvement for mucinous breast carcinoma is rare and correlated with a poor prognosis. However, the relation of lymph node involvement to certain factors is unknown, hence the purpose of our study. Methods: Retrospective chart review of patients diagnosed with mucinous breast carcinoma from 2004 to 2014 from the local tumor registry. Variables include age, tumor size, lymph node metastasis, diagnosis type (pure/mixed), and hormone status of patients. Chi square and T-test was performed. Results: 45 female patients were included in the study with the age range of 35 to 97 years old. 39 patients were diagnosed with mixed mucinous carcinoma and 6 had pure mucinous carcinoma. 9 patients had positive axillary lymph node involvement. 78% of patients with positive lymph node had mixed mucinous carcinoma and 22% had pure mucinous carcinoma. There is no statistical significance (p > 0.05) between lymph node involvement and diagnosis type. Tumor size ranged from 4 to 120 mm, with a mean of 28 mm. 78% of patients with positive lymph node had a tumor size smaller than 60 mm. The other two had a tumor size of 65 mm. and 120 mm. There is no statistical significance (p > 0.05) in the proportion of people who are lymph node positive to tumor size less than 60 mm. Out of the 45 patients, 42 patients expressed ER receptors, 36 expressed PR receptors, and 12 expressed HER2 receptors. 89% of positive lymph node patients express ER hormone receptors, 78% expressed PR receptors, and 56% expressed HER2 receptors. No correlation between ER/PR status and lymph node involvement (p > 0.05) was found but there was a positive correlation between HER2 receptor status and lymph node involvement (p < 0.05). Conclusions: No significant difference between diagnosis type/tumor size in relation to lymph node involvement. Although there is a trend between small tumor size to positive lymph node, it is not significant enough. There is a significant relationship between HER2 positive receptors and lymph node involvement. This is suggestive that the biological nature of the tumor has a larger influence on lymph node involvement than the physical nature.
Alterations in the cell cycle checkpoint pathway in breast cancer.
Authors: Basu Gargi Dan , White Tracey , LoBello Janine R , Kurdoglu Ahmet , Krishnan Subha , Gonzalez Laura , Royce Thomas , Kiefer Jeff , Cherni Irene , Aldrich Jessica , Izatt Tyler , Russell Megan , Nasser Sara , Carpten John D. , Craig David W. , Demeure Michael J. 
Published: February 2017

126 Background: Breast cancer is a molecularly diverse disease with molecular subtypes defined by ER, PR and HER2 status. Dysregulation of the cell cycle pathway through activation of cyclin D1 and/or inactivation of CDKN2A is a mechanism of tumor progression in breast cancer and drugs targeting CDK4/6 is undergoing investigation in this disease with promising preliminary results. We investigated several key genetic alterations in cell cycle regulatory proteins in advanced breast cancer patient samples to identify potential targets for cell cycle related treatment options. Methods: A comprehensive genomic profiling was performed on 37 breast cancer samples with the majority being metastatic. Testing included targeted exome sequencing of 562 genes in tumor and paired normal DNA. Results: Patients’ ages ranged from 27-66 years. Analysis of cell cycle regulatory genes revealed focal amplification of cyclin D1/D2 or CDKN2A loss in 9/37 (24%) of cases, of which, 45% were hormone receptor (HR) positive, HER2 negative, 33% were HR positive, HER2 positive and 22% were triple negative (TNBC) subtype. Loss of RB1 was analyzed since it negatively regulates response to CDK4/6 inhibitors. Loss of RB1 was noted in 4/37 (10.8%) of cases, all of which were TNBCs. Only a single TNBC with RB1 loss had concurrent CDK4 amplification and loss of CDKN2A. No evidence of CCNE1 amplification was found in any samples. Incidence of CDK4 and CDK6 amplification was found in samples with cyclin D1 amplification or CDKN2A loss. Our cohort included a single male TNBC patient who harbored cyclin D1 amplification as well as CDKN2A loss. Overall, amplification of cyclin D1, cyclin D2, CDK4 and CDK6 was found in 16%, 5.4%, 2.7% and 2.7% respectively. Loss of CDKN2A was noted in 5.4% of tumors profiled. Conclusions: Exome sequencing identified subsets of patients with mutated cell cycle associated genes that may benefit from CDK 4/6 inhibitors. Our data suggests loss of RB1 is more frequent in TNBC subtype which may confer resistance to CDK4/6 inhibitors. Our analysis suggests that in addition to HR positive, HER2 negative patients, a subset of HR positive, HER2 positive patients could be sensitive to CDK4/6 inhibitors due to activation of the cell cycle pathway as evidenced by mutations in key genes.
Trastuzumab-induced cardiotoxicity in Uruguayan HER2-positive breast cancer patients.
Authors: Schiavone Andrea , Diaz Mariana , Camejo Natalia , Reborido Natalia , Vazquez Horacio , Parma Gabriel , Vazquez Alvaro , Castillo Cecilia , Krygier Gabriel David , Delgado Lucia Beatriz 
Published: February 2017

143 Background: To evaluate the incidence, severity and outcome of Trastuzumab-induced cardiotoxicity in HER2 positive Uruguayan breast cancer (BC) patients. Methods: Retrospective observational analysis of HER2 positive BC patients who were treated with Trastuzumab (TTZ) from January 2007 to December 2013 at two Uruguayan centers. Cardiac monitoring included physical examination and assessment of left ventricular ejection fraction (LVEF) by echocardiography that was evaluated before TTZ administration and every 12 weeks thereafter during the duration of therapy. Cardiovascular risk factors analyzed were: obesity (BMI ≥ 30 kg/m2), hypertension, diabetes, sedentary lifestyle and high cholesterol. Results: Sixty nine female patients were found in the databases of our institutions. Median age was 48 years (range: 27-73). Stage at diagnosis was as detailed: 19 % EI, 46 % EII, 29 % EIII and 4 % EIV. Eighty nine percent of patients received adjuvant TTZ , 4 % neoadjuvant TTZ and 7 % received it as a palliative therapy. Thirty patients (43, 5%) had at least one cardiovascular risk factors: 26% hypertension, 16% obesity, 9% sedentary lifestyle, and 4% high cholesterol. Median number of TTZ cycles was 15. Cycles were administered every 3 weeks at standard dose. Nineteen patients (27%) developed cardiotoxicity, of whom 12 had a transient suspension because of a reversible fall in LVEF, 2 had a irreversible reduction in LVEF, and 5 had a symptomatic heart failure. Eighty-nine percent of our patients (62 patients) completed treatment and the rest had a definitive suspension due to a irreversible reduction in LVEF or symptomatic heart failure. Most patients that developed cardiotoxicity (15 out of 19) had cardiovascular risk factors and also most of them (16 out of 19) had received anthracyclines before TTZ. Conclusions: Cardiotoxicity incidence was similar to the incidence reported in the literature and when it was present, in most cases was transient, asymptomatic, and reversible.
Dual inhibition of DNA double strand break (DSB) repair and PI3K pathway with BEZ235 (BEZ) to sensitize refractory metastatic (met) triple negative breast cancer (TNBC) to nab paclitaxel/cisplatin (pac/cis) in a patient with an exceptional response (ExRx).
Authors: O'Shaughnessy Joyce , Espina Virginia A. , Cherni Irene , Carpten John D. , Liotta Lance A. , Craig David W. , Kiefer Jeff , Hoke Nicholas N , Levin Maren K. , Wang Kai , Ramos Corinne 
Published: February 2017

156 Background: Whether EGFR is a critical target in met TNBC is unknown. Here we report the clinical history & tumor molecular alterations in a patient with refractory metTNBC who had an ExRx to pac/cis. Methods: Following IRB-approved informed consent, targeted NGS (Foundation Medicine) and WGS (TGEN) was performed on the pt’s FFPE primary TNBC and 2 recurrent lymph nodes to characterize all classes of genomic alterations in cancer-related genes. RPPA was performed at a CLIA-certified laboratory (Theranostics Health) and George Mason Univ where immunostaining was directed against HER1/2/3 pathway and other proteins. Results: At age 58 in 2006, pt had T1c 1+ node TNBC treated with FAC/T. Between 2008 and 2011 she had 4 chemotherapy-refractory recurrences in axilla, supraclavicular (SC), internal mammary (IM) LNs treated unsuccessfully with surgery, radiation and multiple cytotoxic agents including carboplatin. In 2011, following SC LN biopsy, she was treated with BEZ, a PI3K/mTOR, ATM, ATR, DNA-PKcs inhibitor, had a 3 mo response, followed by rapidly enlarging progressive disease (PD) in IM LNs pushing sternum anteriorly. She was treated with pac/cis and had an ongoing complete response (CR) of 2.5+ yrs. NGS of 2011 SC LN (pre-BEZ) & 2012 IM LN (post-BEZ): TP53 & BRCA2 (somatic 15% mutant allele freq) mutations, FOXM1 amplification; SMARCA4 (BRG1) deletion RPPA (GMU) 2011 SC LN (Pre-BEZ): 3+ EGFR; 2+ p-EGFR, p-AKT, p-MEK1/2, p-mTOR RPPA (Theranostics) 2012 IM LN (post-BEZ): 3+ p-MEK1/2 (EGFR & p-EGFR 0) (AR-). Conclusions: Strong EGFR signaling associated with chemo-resistant metTNBC in 2011 SC LN was not present in post-BEZ rapid PD in IM LN which then had durable CR with pac/cis. BEZ inhibits DSB repair, sensitizing cancers to DNA damaging agents (Gil del Alcazar, Clin Ca Res 20:1235, 2014). Progression of p-AKT-activated TNBC following response to inhibitors of PI3K & DNA repair shows DSB repair-deficiency and MAPK activation (Juvekar, Cancer Dis 2:1048, 2012). A prospective trial of BEZ followed at PD by pac/cis in metTNBC is warranted.
Molecular profiling of triple-negative endometrial cancers (TNEC) and triple-negative breast cancers (TNBC) to reveal unique expression profiles.
Authors: Jones Nathaniel L. , Xiu Joanne , Reddy Sandeep K. , Wright Jason Dennis , Burke William M. , Tergas Ana Isabel , Hou June YiJuan 
Published: February 2017

159 Background: “Triple negative” has been used to characterize a subtype of breast cancer that lacks estrogen, progesterone, and HER2 receptor expression. They are aggressive cancers with limited treatment options. It’s unknown if similar phenotype found in other cancer types, like endometrial cancer, harbor similar molecular alterations and prognosis. We aim to compare molecular features between TNEC and TNBC. Methods: A total of 3133 endometrial cancer samples were evaluated by Caris Life Sciences (Phoenix, AZ) from Mar, 2011 to Jul, 2014 by multiplatform profiling, which included a combination of sequencing (Sanger or NGS), protein expression (IHC), and/or gene amplification (CISH or FISH). 545 TNEC and 2049 TNBC were identified based on reported pathology and compared using Fisher exact tests. Results: Compared to an incidence of 15-20% TNBC in breast cancer, 17% (545/3133) TNEC was seen in our cohort, of which 13% were endometrioid, 22% serous, 26% carcinosarcoma, 7% clear cell, and 22% other. Compared with TNBC, TNEC showed 1.9 exonic mutations per case while TNBC showed 1.2 mutations per case. As shown in the table, AR expression is lower in TNEC than TNBC. TP53 mutation was common in both but more frequent in TNBC. While BRCA1/2 mutation rates were similar, low MGMT and ERCC1 were more common in TNEC, suggesting increased aberrant DNA repair. DNA synthesis protein expression was higher in TNEC including TS, RRM1, and TOPO2A, although TNBC had higher TOPO1. PD-1 expression was more common in TNEC suggesting immune pathway involvement. PI3K/AKT/mTor, MAPK and Wnt pathways were more involved in TNEC with greater PTEN, PIK3CA, FBXW7, KRAS and CTNNB1 mutations. Conclusions: Our study reveals significantly higher overall mutation rates in TNEC than TNBC, and specifically higher activations of multiple molecular pathways including PI3K/Akt/mTor, MAPK and Wnt. Further studies are warranted to validate these findings in clinical trials.
A new model for predicting breast cancer risk in women with atypical hyperplasia.
Authors: Degnim Amy C. , Pankratz V. Shane , Winham Stacey J , Dupont William D , Vierkant Robert A. , Frank Ryan D. , Frost Marlene H. , Vachon Celine , Ghosh Karthik , Hieken Tina J. , Carter Jodi M , Haddad Tufia C. , Denison Lori , Visscher Daniel W. , Hartmann Lynn C. , Radisky Derek C 
Published: February 2017

2 Background: Women with atypical hyperplasia (AH) on breast biopsy have an aggregate increased risk of breast cancer (BC), but accurate personalized risk prediction is desirable to facilitate individual clinical management decisions. Currently used models provide poor BC risk prediction for women with AH. Our goal was to develop and validate an improved risk prediction model for women with AH. Methods: From a cohort of 13,538 women with benign breast disease from 1967-2001, pathology review confirmed 699 with AH. Clinical risk factors and histologic features of the tissue biopsy were recorded, and BC events were ascertained from study questionnaires, tumor registry, and review of medical records. Using a lasso approach, 23 variables were assessed for model inclusion. Lasso-identified features were then fit in a Cox regression model to estimate BC risk. Model discrimination was assessed with C-statistics in the model-building set and in a separate external validation set. Calibration was assessed by comparing observed to predicted breast cancer counts. Results: The model-building set comprised 699 women with 142 BC events (median follow-up 8.1 years), and the external validation set comprised 461 women with 114 BC events (median follow-up 11.4 years). The final model included three covariates: age at biopsy, age squared, and number of foci of AH. Model performance was good, with a C-statistic of 0.622 (SE = 0.027) in the model-building set and 0.594 (SE = 0.029) in the external validation set. The model is well-calibrated, with observed to expected numbers of BCs nearly equal across all post-biopsy follow-up years. Conclusions: We propose a new model for predicting BC risk in women with AH based on age at biopsy and number of foci of atypia. This model provides absolute risk estimates for women with AH, has good discriminatory ability, is well-calibrated, and validates in an external cohort.
Comparison of predictive models for local recurrence of DCIS after breast conserving surgery.
Authors: Young Rebekah L. , Desai Shiv , Kalnicki Shalom , Fox Jana Lauren 
Published: February 2017

21 Background: Efforts have been made to identify women for whom radiotherapy (RT) after breast-conserving surgery (BCS) for ductal carcinoma in-situ (DCIS) can be omitted. These include development of the Memorial Sloan-Kettering (MSK) nomogram, the Van Nuys Prognostic Index (VNPI), and the DCIS Score. We assessed correlation of the predictive qualities of these 3 approaches to determine risk of local recurrence (LR) and need for RT. Methods: We calculated VNPI score and used the MSK nomogram to determine LR risks for 48 women on whom DCIS Scores were available since January 2012. Given that the DCIS Score does not account for HT, MSK risks were calculated with and without its use. 10-year LR risks from DCIS Score reports were compared with MSK nomogram estimates using the Pearson correlation coefficient. These comparisons were done for MSK LR risks with and without HT. VNPI scores yield low, intermediate and high risk categories. To compare the 3 predictive models, each patient was assigned an RT recommendation per instrument. Two 10-year LR risk “thresholds” to recommend RT were used - 10 and 15% - to account for M.D. preference. Results: For LR risk, the MSK nomogram (excluding HT) and the DCIS Score showed weak positive correlation (R = 0.346, p < 0.02), weaker when including HT (R = 0.179, p: 0.224). VNPI Score could not be calculated on 5 patients and they were excluded in comparisons involving VNPI. DCIS Score, using 15% LR risk as the RT recommendation threshold, and VNPI RT recommendations correlated in 72.1% of cases. Lowering the threshold to10% reduced the correlation to 32.6%. Comparison of the 3 approaches’ RT recommendations with a 15% threshold showed agreement in 65.1% (28/43) of cases, and a 10% threshold reduced the agreement to 18.6% (8/43). Conclusions: Our analysis shows some correlation between the MSK nomogram and the DCIS Score, more when HT is excluded. Lowering the threshold 10-year LR risk to recommend RT from 15 to 10% reduced agreement among the 3 instruments.
Analysis of clinical characteristics in breast cancer patients with the Japanese founder mutation of BRCA1 L63X.
Authors: Yoshida Reiko , Inuzuka Mayuko , Watanabe Tomoko , Yotsumoto Junko , Kuwayama Takashi , Sawada Terumasa , Akashi-Tanaka Sadako , Nakamura Seigo 
Published: February 2017

22 Background: Hereditary breast and ovarian cancer (HBOC) is a high-penetrance inherited disease, and founder mutation has been reported in the West. However, there are yet no reports of founder mutation of HBOC on breast cancer in the Japanese population. In this study, we report the breast cancer clinical characteristics of L63X, which is one of the founder mutations in BRCA1 in the Japanese population. Methods: Data on 223 affected breast cancer patients (28 BRCA1 carriers, 19 BRCA2 carriers, and 176 non-carriers) were collected at Showa University in Tokyo from September 2010 to June 2015. In 22 independent mutations of BRCA1, the L63X mutation was detected in 9 patients. Data regarding the age of breast cancer onset, pathological features, clinical features, and family history were collected. Results: The age of onset was no significant differences between the L63X mutation and other BRCA1 mutations (39.7 vs. 38.5years). The proportion of triple negative breast cancer patients was 87.5% in the L63X mutation carriers and 89.5% in other BRCA1 mutation carriers. No patients of the L63X affected bilateral breast cancers. On the other hand, 36.7% of other BRCA1mutations affected bilateral breast cancers. There was no significant difference in pathological features (intrinsic subtype, nuclear grade and ki-67 index). The L63X carriers tended to have a family history of breast cancers. All L63X mutations were detected in the Eastern part of Japan. Conclusions: The breast cancer clinical characteristics of L63X might be considered no different from other types of BRCA1 mutations. Recently, it has been reported that breast and ovarian cancer risks varied according to the type and location of BRCA1/2 mutations. L63X mutation is located in the breast cancer cluster region in BRCA1. Further investigation is necessary for appropriate validation and accumulation of data.
Surgical decisions of newly diagnosed breast cancer patients following genetic referral.
Authors: McAlister Jennifer , Dekhne Nayana , Yadav Siddhartha , Zakalik Dana , Lowry Heather , DeLaere Angela 
Published: February 2017

40 Background: In response to many recent publications and mandates to assure referrals to genetic counseling for oncology patients, the Royal Oak (RO) Breast Care Center (BCC) at Beaumont Health System (BHS) evaluated the surgical outcomes of genetic referral(GR) in breast cancer (BC) patients. The goal of this study was to determine the impact of GR on surgical decision making and evaluate outcomes in this population. Methods: A retrospective chart review was performed, to identify patients who had a BC diagnosis and met criteria for GR from July 2012- July 2014. Age, histology, laterality of cancer, prior history of cancer, neoadjuvant chemotherapy, plastic surgery consultation, MRI, reason for MRI, additional testing, type of surgery, laterality of surgery, reconstruction, lymph node surgery, and time from diagnosis to surgery were evaluated using Chi Square analysis. Results: A total of 506 patients with a new BC diagnosis seen at the RO BCC at BHS within the inclusion dates were analyzed. There were 191 patients referred to the GP for counseling and possible genetic testing. Eighty percent of the referred patients underwent genetic testing. Twelve patients tested positive for deleterious mutations in BRCA 1 or 2. A statistically significant difference was found in the BC patients referred to the GP with respect to age, MRI usage, neoadjuvant chemotherapy, type and laterality of surgery, ALND, plastic surgery consult & reconstruction, and time from diagnosis to surgery. MRI usage in patients referred to GP was 43.5% vs. 12.7% in those not referred. Mastectomy rate in patients referred to GP was 51.3% vs. 25.5% (p<0.001) in those not referred. Bilateral mastectomy was 30.9% vs. 5.8% (p<0.001). Conclusions: We have found that patients referred to the GP have increased the use of MRI testing, which in itself has been shown to increase mastectomy rates. We also identified a trend in these patients toward bilateral mastectomy. According to our outcomes, there are multiple possible reasons for this trend, including family history, physician bias, stage at diagnosis, age and factors intrinsic to the patient. Furthermore, a multivariate analysis is needed to assess the relationship between a GR and a patient’s surgical decision.
Can adding contrast-enhanced digital mammography (CEDM) as an adjunct to diagnostic mammography/US help decrease biopsy rates in women with suspicious (BIRADS 4) breast lesions?
Authors: Patel Bhavika K , Giurescu Marina , Eversman Sarah , William Eversman , Kosiorek Heidi , Victor Pizzitola , Lorans Roxanne , Pockaj Barbara A. 
Published: February 2017

6 Background: Traditional screening mammography (MG) enables early detection of breast cancer and therefore results in decreased mortality. Mammography, however, is an imperfect tool and limited by an overall sensitivity of 75-85%. Specificity is limited as well resulting in many false-positive examinations and unnecessary follow-up examinations. The recent development of contrast-enhanced digital mammography (CEDM) has made the usage of IV contrast enhancement with mammography a possibility. CEDM is an angiographic technique that uses digital subtraction, which removes the normal mammary gland on images in order to detect breast tumors and visualize their vascularity. The literature is promising with regard to CEDM as studies have found that CEDM achieves increased sensitivity without reductions in specificity in comparison to MG, US and/or MRI. Methods: In this multi-reader study we compared the diagnostic accuracy of CEDM as an adjunct to MG/US in patients with suspicious findings (BI-RADS 4). The study population included 31 patients who were imaged with CEDM prior to their scheduled US or stereotactic-guided biopsy. We compared the relative performance of MG/US alone versus MG/US/CEDM in determining the probability of malignancy. Histology served as the gold standard. Results: See table below. Conclusions: The addition of CEDM to the workup of suspected lesions on MG and/or US preliminarily decreases the number of false-positive MG thereby with potential to reduce cost and unnecessary patient harm. [Table: see text]