bluuebunny/crossref_metadata_2025_split huggingface dataset:
Breast cancer molecular subtypes in Omani patients: Correlation with age, histology, stage distribution, and outcome—An anaylsis of 542 cases.
Authors: Mehdi I. , Abdulmasood A. a. , Al Bahrani B. J. 
Published: February 2017

219 Background: Breast cancer is the commonest malignancy and major health issue globally. There is initial evidence and high possibility of molecular differences across the ethnic and geographic groups; responsible for variation in presentation, responses to treatment, and outcome. Methods: Breast cancer data from 2006 to 2010 at National Cancer Center, The Royal Hospital Oman was retrospectively retrieved from electronic record system, and analyzed with respect to ER, PR, and HER2 status. The molecular subtypes were correlated with age, histology, and treatment out come. The results were compared with published international/regional data. Results: Total 542 cases were available for evaluation (535 male and 7 male: 459 Omani and 83 Non-Omani). Right, left, and bilateral tumors were 42.6%, 51.4%, and 6%. IDC were 79.6%. G1 were 7.7%, while other grades were equally distributed. Luminal A, B, basal-like (TNBC), and HER2 positive were 35.9%, 15.8%, 25.5%, and 22.8% respectively. Their age (cut off 50 years) was a significant factor in basal-like (63.8% vs. 36.2%) and HER2 tumors (61% vs. 39%). High-grade tumors were highest (41%) in basal tumors and lowest in Luminal A (19%). Higher stage at presentation (stage 3 and 4) was highest in HER2 tumors (59%). Mortality was recorded higher 22.4% in basal-like/TN tumors. Table shows comparison with selected published data. Conclusions: The molecular classification and subtyping have shown ethnic and geographic variation in taxonomy. These differences may have diagnostic, therapeutic, and prognostic implications. Large scale and multicenter studies may confirm these findings. They can be translated and incorporated to management strategies wherever applicable. [Table: see text]
Re-establishing pluripotency in adult cells derived from breast stromal tissue.
Authors: Lim S. M. L. , Aksoy I. , Lim K. G. C. , Karuppasamy J. , Divakar U. , Ma F. J. , Lam F. L. , Remulla S. J. N. , Stanton L. W. 
Published: February 2017

227 Background: Recent advances in pluripotent stem cell biology offer patient-specific disease models to investigate in vitro mechanisms of tumorigenesis. Induced pluripotent stem (iPS) cells were originally derived by reprogramming of human dermal fibroblasts through ectopic expression of pluripotency–associated transcription factors. A limitation to the use of dermal fibroblasts as the starting cell type for reprogramming is that it usually takes weeks to expand cells from a single biopsy, and the efficiency of the process is very low. In contrast, a large number of adipose-derived mesenchymal stromal cells (Ad-MSCs) can be easily obtained from the stroma of human breast tissue, without the time-consuming steps of cell expansion. Here we investigated the ability to induce pluripotency in committed, Ad-MSCs derived from the stroma of breast tissue. Methods: The aim of this study is to investigate the potential of using Ad-MSCs derived from surgically discarded breast stromal tissue to generate human iPS. Discarded tissue during surgical procedures was processed in vitro and Ad-MSCs were derived. These Ad-MSCs were then used to generate iPS cells by ectopic expression of “Yamanaka’s cocktail” containing OCT4, SOX2, KLF4 and c-MYC. Results: The success rate in generating iPS cells from human Ad-MSCs derived from breast stromal tissue is very high compared to the use of dermal fibroblasts. In our study, almost all human Ad-MSC cell lines can be reprogrammed into iPS cells, which share the same characteristics as skin fibroblast-derived iPS cells and human embryonic stem cells in their morphology, gene expression profile and differentiation capacities. Conclusions: We are now optimizing this approach and making it more clinically relevant by adopting an integration-free method to deliver the reprogramming factors. The successful reprogramming of breast stromal-derived Ad-MSCs into iPS cells may provide a valuable source of patient-specific iPS cells to study the mechanism of tumorigenesis in patients with breast cancer.
The influence of iPS-inducing factors NANOG and KLF4 in the prognosis of patients with breast cancer.
Authors: Nagata T. 
Published: February 2017

230 Background: iPS cell-inducing factors (Oct3/4, Sox2, Klf4, c-Myc, and Nanog) are reported that they appears not only in ES cells (embryonic stem cell), but also in normal cell or carcinoma cell, including breast carcinoma. We evaluated the expression of iPS inducing factors in the human breast cancer specimen with immunohistochemistry, and analyze the relativity of the relapse and the prognosis after the operation. Methods: 66 cases of breast cancer that were performed the surgical operation in this department were examined. Expression of c-MYC, KLF4, NANOG, OCT4, and SOX2 were determined by immunohistochemistry of tissue microarray. Results: The average of the patient’s age was 56.4 years old (36-87), and the advanced breast cancers in stage 2 or more were 44 cases (66%). About the hormone receptor and the HER2 appearance, hormone receptor-positive (HR+) types were 53 cases (80%), 6 cases (9%) were HER2-positive (HER2+) type, and 7 cases (11%) were triple-negative (TN) type. During the following period from operation, the relapse was found in 16 cases (24%), and six cases (9%) died. The average of survival time after the operation was 80.7 months (4-162). Patients with high expression group of NANOG had poor disease-free survival (p = 0.045) and overall survival (p < 0.0001) than those with low expression group. On the other hand, patients with high expression group of KLF4 had better disease-free survival (p = 0.028) than low expression group. Conclusions: High expression of NANOG was prognostic factor, but KLF4 was inversely related to prognosis in breast cancer patients. It was suggested that NANOG increased the growth and metastatic activities of breast cancer cells, while KLF4 decreased these activities.
Contralateral risk-reducing (prophylactic) mastectomy (RRM) in patients (pts) with breast cancer (BC): Experience at Mastologica Lomas Breast Center in Mexico City.
Authors: Sanchez-Forgach E. R. , Sanchez Basurto C. , Zabalaga P. 
Published: February 2017

236 Background: Contralateral RRM has increased in frequency due to patient (pt) and/or physician preference. We explore efficacy and satisfaction of procedure at our institution. Methods: A retrospective review of RRM performed from 2002 to 2010. Age, stage, BC subtype, timing of procedure, RRM pathology, reconstruction technique, complications, delay in systemic therapy, satisfaction index, and pt status were compared to pts. who did not undergo RRM. Results: 27 pts with BC had a contralateral RRM. Mean age was 34 (range 24-61). High-risk factors in 11 (40.75%) pts. Histology of BC breasts included 18 (66.66%) invasive ductal, 5 (18.52%) invasive lobular, 4 (14.81) in situ ductal carcinoma, and 1 (3.70%) tubular carcinoma. RRM was a synchronous contralateral procedure in 12 (44.44%) pts. Breast reconstruction technique for RRM: 22 (81.48%) subpectoralis implants, 2 (7.41%) tissue expanders and secondary implants, 1 (3.7%) latissimus dorsi flap with implant. RRM complications: seroma in 8 (29.63%) cases (2 required evacuation of implant), 5 (18.52%) diverse degrees of nipple-areola complex necrosis, total breast necrosis in one pt. These cases were performed earlier in the series, with a decrease in complications in the latter stages of the analysis. Pathology of RRM specimens: one (3.7%) case of ductal in situ BC in a stage IIa pt. and 4 (14.81%) atypical ductal hyperplasia. Surgical time increased a mean of 75 minutes; systemic therapy was delayed in only 2 (7.41%) pts. Recurrence presented in one pt in index breast after stage 0 BC at 13 months (7 mm invasive ductal), in reconstructed breast (3 mm invasive ductal), both treated with a total mastectomy and sentinel node biopsy. All pts are alive. Two have developed systemic metastases (brain, bone). Satisfaction results (medical and pt) were excellent or good in the RRM in 23 (85.19%), regular in 2 (7.41%), and bad in 2. Conclusions: RRM after BC is increasing in frequency, specially in young age pts. Experience at our institution has made it a safe and commonplace procedure, specially in the younger aged pts. with high risk for a contralateral BC. Longer follow-up is needed to determine efficacy.
Nomogram for predicting development of brain metastasis in patients with inflammatory breast cancer.
Authors: Raghav K. P. S. , Bekele B. N. , Valero V. , Matrana M. R. , Ibrahim N. K. 
Published: February 2017

243 Background: Inflammatory breast cancer (IBC) is associated with poor prognosis and high rates of distant metastasis. Brain metastasis is particularly important due to its morbidity and mortality. The purpose of this study was to construct a nomogram from clinicopathological factors that could predict the risk of occurrence of brain metastasis in patients with IBC. Methods: We performed a retrospective analysis of 406 patients with IBC, who were seen at the University of Texas M. D. Anderson Cancer Center between 1991 and 2009. Data was collected from IBC registry. Patients were divided in a randomized manner into a training cohort (n = 206) and a validation (n = 200) cohort. A multivariate cox proportional hazards regression analysis of selected prognostic features was performed on the training cohort. The model estimated in the training cohort was cross-validated with the validation cohort. Based on this model a nomogram was constructed to assess 5- and 10-year risk of developing brain metastasis. Results: A total of 115 (28%) patients developed brain metastasis. Univariate analysis identified menopausal status, progesterone receptor expression, number of distant metastasis, adjuvant taxane-based therapy and age at diagnosis as significant factors associated with brain metastasis (p < 0.05). Subsequent multivariate analysis showed menopausal status and number of metastasis were independently associated with development of brain metastasis (p < 0.05). Nomogram constructed using above model was evaluated for its ability to discriminate among likelihood of occurrence of brain metastasis in patients, using the validation set. The validation set showed good discrimination with the area under the receiver operating characteristic curve of 0.68. Conclusions: We have formulated a distinct predictive tool to evaluate 5 and 10-year risk for developing brain metastasis in patients with IBC. This nomogram can be potentially helpful for designing risk adapted therapeutic trials. Identifying patients at high risk for brain metastasis in IBC can help personalize therapy, surveillance, and prognostication. [Table: see text]
The effect of aerobic exercise on the metabolic risk profile of breast cancer survivors 2-6 months post chemotherapy.
Authors: Guinan E. M. , Hussey J. M. , Walsh J. M. , Kennedy M. J. , Connolly E. M. 
Published: February 2017

244 Background: Current literature suggests that weight gain during treatment for breast cancer is associated with a poorer prognosis and an increased risk of developing secondary health problems such as the metabolic syndrome (MetSyn). Physical activity (PA) can alter features of the MetSyn and improve body composition by reducing abdominal adiposity. We report metabolic results of a prospective randomized controlled trial (PEACH trial; Walsh JM, et al. [2010] BMC Cancer. 10[42]) which examines the effect of an exercise intervention on the metabolic risk profile of breast cancer survivors 2-6 months post chemotherapy. Methods: All subjects gave written informed consent and were randomized to an 8-week, twice weekly aerobic exercise intervention programme or a usual care control group consisting of routine medical advice about PA. The five clinical features of the MetSyn were measured: waist circumference (WC), resting blood pressure (BP), triglycerides, high-density lipoprotein cholesterol (HDL-C) and fasting glucose. Insulin resistance was estimated by the homeostatic model assessment (HOMA). Statistical analysis was carried out using independent sample t-tests with significance set at p < 0.05. Results: Twenty-six breast cancer survivors participated (mean (± SD) age 48.13 (8.75) years). At baseline, 50% (n = 13) of subjects were overweight and 23.1% (n = 6) were obese, with 73.1% (n = 19) centrally obese. 34.6% (n = 9) of subjects were classified with the MetSyn. There were no significant differences between groups at baseline. Intention-to-treat analysis showed no significant changes, however, analysis of those who adhered to > 70% of the supervised exercise intervention showed a significant improvement in WC when compared to the control group (p < 0.05). Conclusions: Results show that an 8-week aerobic exercise intervention significantly reduced WC but did not modify other features of the MetSyn. The decrease in WC demonstrated by this short intervention may have important implications in terms of improving survival and the metabolic risk profile of breast cancer survivors. Final follow-up assessments are ongoing and will enable change in WC over time to be evaluated further.
Nitric oxide-releasing nanoparticle combination therapy to overcome drug resistance in platinum-resistant breast cancers.
Authors: Forrest M. L. , Cai S. , Duan S. , Cohen M. S. , Yang Q. 
Published: February 2017

278 Background: The most successful cancer chemotherapy regimens usually involve the administration of multiple cytotoxic agents simultaneously. Because different chemotherapies may have different mechanisms of action; it is difficult for cancer cells to become resistant to combination therapy. Recent investigations have discovered that nitric oxide (NO) may be involved in the reversal of cisplatin (CDDP) resistance in chemotherapy. Therefore, we sought to develop a combination regimen involving a NO-releasing prodrug (NO1) and cisplatin for the treatment of breast cancer. Methods: The prodrug NO1 was synthesized to be localized in tumor cells and to release nitric oxide over 10 hours. The antiproliferative activity of NO1 was determined in human breast cancer cell line, MDA-MB-468LN. To evaluate the effectiveness of the CDDP/NO combination regimen, platinum-resistant MDA-MB-468LN cells were treated with either cisplatin alone ([CDDP]=0.01, 0.02 or 0.03 mM) or the CDDP/NO combination ([CDDP]=0.01, 0.02 or 0.03 mM; [NO1]=0.02 mM). The cell viability was determined 48 hours post-treatment using a live/dead trypan blue exclusion assay. Results: The toxicity to breast cancer cells was higher than JS-K, a systemic NO agent currently in preclinical development. (NO1: IC50=26µM; JS-K: IC50=42 µM). In addition, NO1 had a long sustained release of nitric oxide, approximately one fold longer than JS-K (NO1: t1/2=6 h; JS-K: t1/2=3 h). The combination treatments resulted in 6.6-, 6.9- and 7.5-fold increase in cell death compared to cisplatin treatment alone at cisplatin concentrations of 0.01, 0.02 and 0.03 mM, respectively. A subsequent study in a murine xenograft of head and neck cancer found NO-1 conjugated to nanoparticles increased survival a mean of 10 weeks compared to controls (p<0.0001). Conclusions: Nitric oxide prodrug NO-1 and nanoparticles of it have high anticancer activity in vivo and they can reverse platinum resistance in vitro. Ongoing studies are examining the safety and efficacy of CDDP/NO combination therapy in mouse xenografts of human breast cancer.
Evaluation of complete pathologic response and histologic toxicity using a subcutaneous delivery system with combination nanoconjugated doxorubicin and cisplatin for locally advanced breast cancer in vivo.
Authors: Cohen S. M. , Mukerji R. , Cai S. , Damjanov I. , Forrest M. L. , Cohen M. S. 
Published: February 2017

279 Background: Systemic doxorubicin (DOX) and platinum agents in breast cancer can be limited by their toxicity and have low penetration into lymphatics contributing to locoregional (LR) recurrence. Subcutaneous (s.c.) delivery of single agent nanoconjugated (HA-DOX) or cisplatin (HA-CIS) can significantly boost LR drug delivery with lower toxicity in vivo. The purpose of this study is to evaluate histologic response and toxicity of combination s.c. delivery of HA-DOX/HA-CIS as a significant improvement over IV delivery with standard drugs reduces dose levels and expands the therapeutic dosing range for these drugs. Methods: 1.5x106 MDA-MB-468LN human breast cancer cells (metastatic line) were injected into the mammary fat pad of female Nu/Nu mice. When tumors reached 6mm, mice (n=8 per group) were then treated with standard DOX/CIS IV combination therapy or s.c. injections of HA-DOX/HA-CIS at 25%,50%,75%,100%,125%, and 150% MTD for these drugs. Drugs were dosed weekly x 3 wks and tissues were collected for histology at 4 and 12wk timepoints. Results: Only the nanoconjugate groups demonstrated a complete clinical response (CR) to therapy and a complete pathologic response (CPR) histologically [CR =62.5% of mice and CPR=12.5% at 50% MTD;CR=87.5% and CPR=25% at 75%MTD; p<0.0001 vs. IV groups which had no CRs and some partial responses (12.5% at 50%MTD and 25% at 75%MTD)]. HA groups had no lymphatic or bony metastases while 1 animal (12.5%) in the IV 50% MTD group had spinal metastases (p<0.01). Mild cardiac and renal toxicity was noted in the 25% and 50% MTD IV groups respectively while no cardiac or renal toxicity was observed in the HA groups (p<0.01). Finally HA conjugation increased the therapeutic dose range of DOX and CIS up to 150% of standard formulation MTD. Conclusions: Subcutaneous nanocarrier-delivery of combination DOX/CIS demonstrated significantly improved tumor response with CPR and lower toxicity on histology compared to standard drugs. This delivery platform successfully treats LR and distant metastatic disease at lower doses and improves the dosing range of these drugs compared to standard agents.
Management of early-stage breast cancer: Are we headed in the right direction?
Authors: Zurawska U. , Baribeau D. A. , Victor C. , Giilck S. , Florescu A. , Gandhi S. , Verma S. 
Published: February 2017

284 Background: The understanding of breast cancer (BC) as a heterogeneous disease consisting of distinct subtypes based on variation in expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) has led to more personalized treatment. We postulated that with increased adoption of chemotherapy and targeted therapy for HER2 positive patients, the outcomes of ER/PR+, HER2- and of HER2+ subtypes of breast cancer would be similar. Methods: A chart review was performed of female patients >18 years old seen by a medical oncologist at an academic cancer centre in Toronto, Canada, between January 1, 2005 and December 31, 2006, for stage I-III invasive breast cancer. Clinical features, 5-year overall (OS) and relapse-free survival (RFS) of three BC subtypes were compared: ER/PR+, HER2- (hormone receptor positive, HR), HER2+ (HER2), and ER/PR-, HER2- (triple negative, TN). Results: Of 870 patient charts reviewed, 525 were analysed. There were 341 HR, 101 HER2 and 83 TN patients. TN patients were younger (p<0.001), and had higher stage (p<0.001) and higher histological grade tumors (p<0.001). The 5-year RFS and OS were: HR: 88.2% and 96.6%, HER2: 76.7% and 92%, TN: 79.8% and 83.9%. Chemotherapy was used in 41.1%, 84.2% and 83.1% of HR, HER2 and TN patients. Anthracycline plus taxane regimens were used in 48.6%, 52.9% and 68.1% of HR, HER2 and TN patients, respectively. Among HER2 patients, only 74.3% received trastuzumab. The 5-year RFS and OS for HER2 patients who received trastuzumab were 79.9% and 91.8%, and for those who did not: 69% and 91.6%. Conclusions: HR+ patients have an excellent outcome. Despite significant improvement in outcomes of HER2+ patients with early stage breast cancer, they still remain at higher risk of recurrence along with TN patients. Trastuzumab was underutilized among HER2+ patients in this cohort, which may have contributed to decreased 5 year RFS. Ongoing prospective follow up of early BC outcomes by breast cancer subtypes is important.
Capecitabine in operable triple receptor–negative breast cancer: A subgroup analysis of a randomized phase III trial.
Authors: Kelly C. M. , Green M. C. , Broglio K. , Pusztai L. , Thomas E. , Brewster A. , Valero V. , Ibrahim N. K. , Gonzalez-Angulo A. M. , Booser D. J. , Hunt K. , Hortobagyi G. N. , Buzdar A. 
Published: February 2017

292 Background: Recent data suggest that patients with operable triple negative breast cancer (TNBC) may derive greater benefit from the addition of capecitabine to anthracycline-taxane regimens. Methods: We examined pathological complete response (pCR), relapse-free survival (RFS) and overall survival (OS) in patients with TNBC randomized to paclitaxel 80mg/m2 weekly (WP) x 12 followed by fluorouracil (500mg/m2), epirubicin (100mg/m2), cyclophosphamide (500mg/m2) every 3 weeks x 4 cycles (FEC) vs. docetaxel (75mg/m2) 3 weekly and capecitabine D1-14 (1500mg/m2 daily; DX) followed by FEC. Patients were stratified by timing of chemotherapy (preoperative vs. adjuvant). Results: 149 patients with TNBC comprising 25% of all patients randomized (N=601). Median age; 49 years (IQR; 41 to 55). The number and proportion of patients by stage were; I (n=32: 21.5%), IIA (n=72: 48.3%), IIB (n=34: 22.8%), IIIA (n=9: 6.0%) and IIIC (n=2; 1.3%). Preoperative therapy was administered to 58 patients (39%) and adjuvant to 91 (61%). There were 17 events (21%) in the DX arm and 10 events (15%) in the WP arm (P=0.36) including 11 distant recurrences in the DX arm and 9 in the WP arm (P=0.99). We observed a pCR in 11 patients (37%) and 10 (36%) in the DX and WP arms respectively (P=0.94). The odds ratio for pCR for patients with TNBC given DX vs. WP was 0.98 (95% CI; 0.33 to 2.80: P=0.94). At 50-months median follow-up the RFS and OS in patients with TNBC randomized to DX or WP was 77% (66 to 86%) and 83% (73 to 92%) (P=0.41) and 78% (67 to 87%) and 87% (77 to 95%) (P=0.16) respectively. RFS and OS for WP vs. DX for non-TNBC was 93% (87 to 95%) and 92% (88 to 96%) (p=0.91) and 96% (92 to 98%) and 97% (94 to 99%) for WP and DX respectively (P=0.39). Conclusions: In this unplanned subgroup analysis there was no difference in pCR, RFS or OS in patients with operable TNBC randomized to WP or DX however, power is limited and should be considered when interpreting these data.