bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P4-09-11: Fatty Acid Synthase (FASN) expression in Triple-Negative Breast Cancer
Authors: Viñas G , Oliveras G , Perez-Bueno F , Giro A , Blancafort A , Puig-Vives M , Marcos-Gragera R , Dorca J , Brunet J , Puig T 
Published: August 2014

Abstract
Background: In approximately 15–20% of patients with breast cancer, the tumors do not express estrogen receptor (ER), progesterone receptor (PR) and do not have amplification of HER2. These tumors are called triple-negative breast cancer (TNBC) and patients with these tumors have a poor prognosis. There is no clinically validated, molecularly targeted therapy for TNBC patients and they can be treated only with chemotherapy. Thus, the identification of a novel targeted therapies for TNBC patients would be of great benefit. Fatty acid synthase (FASN) is a multi-enzyme protein that catalyzes fatty acid synthesis. Its main reaction is to synthesize palmitate from acetyl-CoA and malonyl-CoA, in the presence of NADPH, into long-chain saturated fatty acids. Expression levels of FASN are low or undetectable in normal human tissues except for the liver and the adipose tissue. In contrast, high levels of FASN expression have been detected in several human carcinomas. Several reports highlight that FASN overexpression in tumor samples correlates with progression, aggressiveness and metastatic potential of the disease. Previously, our group has shown that FASN activity inhibition induces apoptosis in several human cancer cells. The aim of our study was to evaluate the expression of tumor levels of FASN in triple-negative breast cancer patients.
Methods: FASN tumor expression was retrospectively evaluated in 30 paraffin-embedded core-biopsies of 30 patients with TNBC using the Fatty Acid Synthase polyclonal antibody (Assay design, Enzo Life Sciences, Exeter United Kingdom) and the detection kit EnVision™ (DAKO, Glostrup, Denmark). FASN expression levels were determined by immunohistochemistry (IHC) using the AutostainerPlus Link (DAKO). FASN expression was graded from 0 to 3+, meaning 0–1+ normal amounts of FASN protein compared to non-tumor breast tissue, 2+ moderate amounts and 3+ highest levels of FASN expression. In vitro, we have determined the effect of the FASN-inhibitors, EGCG and G28UCM, on cell viability (measured by the MTT assay) and apoptosis [as assessed by cleavage of poly(ADP-ribose) polymerase (PARP)] of two TNBC cell lines, MDA-MB-231 and MDA-MB-468.
Results: From 30 patients with TNBC, 66.6% (20/30) of the patients had a high expression of FASN (FASN 3+) and 33.3% (10/30) had a moderate expression of FASN (FAS 2+). None of the tumors had lack of FASN expression analysed by immunohistochemistry. In vitro, the FASN-inhibitor G28UCM induced apoptosis and showed low IC50 values of citotoxicity in both, MDA-MB-231 and MDA-MB-468 TNBC cell lines.
Conclusions: FASN is overexpressed in triple-negative breast cancer tumors. The absence of target therapies for this breast cancer subtype and its poor prognosis lead to the exploration of FASN as therapeutic target for TNBC patients.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-09-11.
Abstract P4-12-01: A nomogram based on clinical, imaging and histological data to predict the risk of upgrades to malignancy at surgery in biopsy-diagnosed premalignant lesions of the breast
Authors: Uzan C , Mazouni C , Balleyguier C , Mathieu M-C , Ferchiou M , Delaloge S 
Published: August 2014

Abstract
Background: Population-based mammography screening has resulted in the increased detection of suspicious, non-palpable lesions that require histopathological assessment. When a “pre-malignant” lesion, such as lobular carcinoma in situ (LCIS), atypical ductal or lobular hyperplasia (ADH and ALH) or flat epithelial atypia (FEA), is discovered on the primary biopsy, a surgical excision is recommended due to the risk of underestimation of the lesion. DCIS or invasive carcinoma is finally retrieved in 10–30% of the patients, meaning a large part receive unnecessary surgery. The aim of this study was to define a nomogram integrating clinical, imaging and histological data to predict for the risk of underestimation of the lesion. Intentionally, we decided to include all the premalignant lesions which implied the same management, whereas most of the previous models of the literature are focused in only one or another type of atypia.
Patients and Methods: We collected complete clinical, radiological and double-reading histological data on all patients with a diagnosis of pure atypical lesion (CLIS, ADH, ALH, FEA) on image-guided biopsy performed at the One-Stop Unjt of our breast care center from 2004 to 2011. Univariate and multivariate logistic regression analyses were used to develop a model predicting for the presence of DCIS or invasive carcinoma on the final surgical sample, and build a nomogram. This nomogram was evaluated on a training set of 205 patients treated at IGR.
Results: 205 patients were eligible for the study. Of these 205 patients, 50 cancers (24.4%) were diagnosed at definitive surgery (21 DCIS, 20 ductal and 9 lobular invasive carcinoma). Univariate analysis retrieved age (p = 0.03), number of biopsy cores (p = 0.02) and type of radiological anomalies (p = 0.02) as factors associated with cancer at surgery. The presence of microcalcifications on biopsies of limit significance was included in the multivariate analysis (p = 0.09). The final most informative nomogram included information on patient age (p = 0.03), type of radiological anomalies (p = 0.02) and number of biopsy cores (p = 0.04). The predictive accuracy of the nomogram was 0.71 and 0.68 in the training set before and after bootstrapping, respectively. The calibration of the nomogram was good. The sensitivity, specificity, positive predictive value, and negative predictive values were 68%, 73%, 45%, and 88%, respectively.
Conclusion: This nomogram could help identify a subset of patients with premalignant disease for whom surgery could be spared and who would be eligible for exclusive clinical follow-up. A validation study is currently undergoing in an external dataset.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-12-01.
Abstract P4-12-06: A mammographic density prediction model using environmental factors, endogenous hormones and growth factors in Japanese women
Authors: Yoshimoto N , Nishiyama T , Toyama T , Takahashi S , Shiraki N , Sugiura H , Endo Y , Iwasa M , Asano T , Fujii Y , Yamashita H 
Published: August 2014

Abstract
The incidence of breast cancer in Japanese women has doubled in all age groups over the past two decades, making it important to evaluate breast cancer risk factors in Japanese women. It is well known that mammographic density is positively associated with breast cancer risk in Western countries, and mammographic density is known to be affected by some environmental factors, serum hormones, and growth factors. We performed stepwise variable selection in a multiple regression model with fifteen independent variables as described below, based on the Akaike information criteria (AIC) to build a mammographic density prediction model using a dataset of 1191 women (913 women with breast cancer and 278 disease-free controls). The variables included were: environmental risk factors (body-mass index (BMI), age at menarche, pregnancy, age at first birth, breastfeeding, family history of breast cancer, age at menopause, use of hormone replacement therapy, alcohol intake and smoking), serum hormones and growth factors (estradiol, testosterone, prolactin, insulin-like growth factor 1 (IGF1) and IGF binding protein 3 (IGFBP3)) and mammographic density. The resulting prediction model is:
Mammographic density = + 0.000476 (IGF1) −0.0605 (testosterone) − 0.0508 (IGFBP3) − 0.00683 (age) − 0.0175 (BMI) + 0.00883 (age at menarche) − 0.0153 (breast feeding), (R2 = 0.336).
In this model, IGF1, testosterone, IGFBP3, age, BMI, age at menarche, and breastfeeding were considered to be important factors. IGF1 and age at menarche were positively associated with mammographic density, while on the other hand testosterone, IGFBP3, age, BMI, and breast feeding were negatively associated with mammographic density. Further studies are required to build a modified model incorporating serial measurements of serum hormones and growth factors to take into account time-dependent changes of serum hormones and growth factors, and to assess its accuracy.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-12-06.
Abstract P4-13-08: Diabetes, Related Factors and Breast Cancer Risk
Authors: Boyle P , Boniol M , Koechlin A , Bota M , Robertson C , Leroith D , Rosenstock J , Bolli GB , Autier P 
Published: August 2014

Abstract
Diabetes and breast cancer are both extremely common conditions in women and may share common risk factors. It is natural to investigate any potential common risk factors and to seek biological clarification and improve prospects for prevention.
Therefore, in order to help clarify the potential association between diabetes, related factors and breast cancer risk, a comprehensive literature review and formal meta-analysis was carried out, planned, conducted and reported following PRISMA guidelines regarding meta-analysis of observational studies. Variables studies in relation to breast cancer risk were adiposity, physical activity, glycaemic load, glycaemic index, diabetes, IGF-1, fasting glucose, fasting insulin and C-peptide, adiponectin and metformin and glargine use among patients with diabetes. For all variables except diabetes and breast cancer, only prospective studies were included in meta-analyses. Summary Relative Risks (SRR) and corresponding 95% Confidence Intervals (CI) were calculated from random effect models.
For breast cancer at all ages, the calculated risks were as follows: diabetes (SRR = 1.27 95% CI (1.16, 1.39); physical activity (SRR = 0.88, 95% CI (0.85, 0.92)); glycaemic load (SRR = 1.06, 95% CI (1.00, 1.12)); glycaemic index (SRR = 1.04, 95% CI (0.99, 1.10)); fasting glucose (SRR = 1.12, 95% CI (1.01, 1.24)); serum insulin (SRR = 1.18, 95% CI (0.75, 1.85)); c-peptide (SRR = 1.29, 95% CI (0.91, 1.82)); adiponectin (SRR = 1.16, 95% CI (0.93, 1.46)); metformin (SRR = 1.00, 95% CI (0.69, 1.46)); and glargine (SRR = 1.11, 95% CI (1.00, 1.24)). An increase of 5 units in Body Mass Index (a weight increase if 14.5 kg in a person 1.70 metres tall) was associated in post-menopausal breast cancer (SRR = 1.12, 95% CI (1.08, 1.16)) but not at pre-menopausal ages (SRR = 0.83, 95% CI (0.72, 0.95)). Serum insulin was associated with breast cancer at post-menopausal ages but not at pre-menopausal ages whereas with c-peptide there was a significant association at pre-menopausal ages but not post-menopausal. For IGF-1, Hodge's Standardised Mean Difference (HSMD) was calculated in cohort studies and there was no significant association with breast cancer at all ages (HSMD = 0.003, 95% CI (−0.059, 0.065)), at post-menopausal ages (HSMD = −0.014, 95% CI (−0.106, 0.077)) or at pre-menopausal ages (HSMD = 0.039, 95% CI (−0.038, 0.117)).
The risk of breast cancer is increased among post-menopausal women who have diabetes. Among those factors related to diabetes, key risk factors for breast cancer appear to be adiposity and lack of physical activity which are both related to the risk of developing diabetes. Action on these lifestyle factors should form the basis of a common prevention strategy. There is a need to re-evaluate potential biological mechanisms to explain the increased risk in post-menopausal women with diabetes.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-13-08.
Abstract P4-14-02: National Trends and Indications for Nipple-Sparing Mastectomy: An Analysis Using the Surveillance, Epidemiology, and End Results (SEER) Database
Authors: Agarwal S , Agarwal S , Agarwal J 
Published: August 2014

Abstract
Introduction: Nipple-sparing mastectomy (NSM) is an evolving procedure occasionally used for breast cancer treatment. However, indications for NSM are institution-specific and lack consensus in the literature. This study uses the Surveillance, Epidemiology, and End Results (SEER) database to investigate the oncologic and demographic characteristics of breast cancer patients treated with NSM in the United States from 2005–2009.
Methods: Female breast cancer patients treated from 2005–2009 with nipple-sparing/subcutaneous mastectomy (SEER code 30), defined as removal of breast tissue with preservation of nipple-areolar complex and overlying skin, were included. Variables analyzed included patient age, race, tumor stage, tumor size, lymph node status, and radiotherapy delivery.
Results: A total of 449 female breast cancer patients who underwent NSM were isolated from the SEER database. The number of patients in the SEER database who underwent NSM increased steadily each year, from 66 in 2005 to 133 in 2009. Mean age was 52 years (s.d. 12 years). Breakdown by race showed that 369 (82%) patients were White women, 42 (9%) were Black women, 36 (8%) were of Asian descent. A majority of patients (402) were documented to have ductal or lobular carcinoma. Documented tumor diameter was less than 3 cm in 63% (284) of patients. Invasive cancer was documented in 283 (63%) patients; in situ cancer was documented in 166 (37%) patients. Lymph node involvement was negative in 374 (83%) patients. Radiation therapy was delivered to 91 (20%) patients; however, 64 patients receiving radiation therapy were node-negative. Radiation was delivered to 6% (10) of patients with in situ cancer and 27% (77) of patients with invasive cancer (p &lt; 0.0001).
Conclusions: The number of NSM procedures reported in SEER for breast cancer has increased from 2005–2009. However, there is a lack of consensus in the literature as to which patients may be candidates for NSM. By utilizing a national database, we are able to aggregate and report on the national experience with therapeutic NSM, to date. Patients undergoing NSM for breast cancer were characterized predominantly by tumors less than 3 cm in diameter and with negative lymph node involvement. Patients with both invasive and in situ tumors were considered suitable candidates for NSM. A majority of patients had either ductal or lobular carcinomas. A minority of patients received radiation therapy, although there was a tendency towards providing patients with invasive tumors with radiation therapy. This national data should help guide patient selection for NSM, although future studies are needed to report on the long-term oncologic safety of this procedure.

Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-14-02.
Abstract P4-14-04: Total skin-sparing mastectomy in BRCA mutation carriers
Authors: Warren Peled A , Hwang ES , Ewing CA , Alvarado M , Esserman LJ 
Published: August 2014

Abstract
BACKGROUND: Total skin-sparing mastectomy (TSSM) with preservation of the nipple-areolar complex skin has become increasingly accepted as an oncologically safe procedure for both prophylactic and therapeutic indications. The goal of this study was to evaluate the oncologic outcomes after TSSM in BRCA mutation carriers.
METHODS: We identified 53 BRCA-positive patients who underwent bilateral TSSM for prophylactic (27 patients) or therapeutic (26 patients) indications from 2001 to 2011. Cases were age-matched (for prophylactic cases) or age- and stage-matched (for therapeutic cases) with non-BRCA-positive patients who underwent bilateral TSSM during this time period. Outcomes included tumor involvement of the resected nipple tissue, the development of new breast cancers in patients who underwent bilateral risk-reducing TSSM, and the development of any local-regional recurrence in patients who underwent therapeutic TSSM.
RESULTS: Outcomes from 212 TSSM procedures in 53 cases and 53 controls were analyzed. In patients undergoing TSSM for prophylactic indications, in situ cancer was found in 1 (1.9%) of the nipple specimens in the BRCA-positive patients vs. 2 specimens (3.7%) in the non-BRCA-positive cohort (p = 1). At a mean follow-up of 56 months, no new cancers developed in the BRCA-positive or the non-BRCA-positive cohorts. In patients undergoing TSSM for therapeutic indications, in situ or invasive cancer was found in 0 of the nipple specimens in the BRCA-positive patients vs. 2 specimens (3.9%) in the non-BRCA-positive cohort (p = 0.49). At a mean follow-up of 33 months, there were no local-regional recurrences in the BRCA-positive cohort.
CONCLUSIONS: TSSM is an oncologically safe procedure in BRCA-positive patients, as is evidenced by the low rates of tumor involvement of the nipple tissue and local-regional recurrence after therapeutic mastectomy. In BRCA-positive patients undergoing TSSM as a risk-reducing strategy, five-year follow-up demonstrates no increased risk for the development of new breast cancers; longer-term follow-up is anticipated to further confirm its safety.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-14-04.
Abstract P4-14-11: Risk reducing mastectomy for women with high personal breast cancer risk
Authors: Onyekwelu O , Shetty G , Baildam A 
Published: August 2014

Abstract
Introduction: For high-risk familial history of breast cancer, risk reducing mastectomy (RRM) is now regarded as one of the management options. The aim of this study is to analyse the outcome of women undergoing RRM from 1994 to 2010 during which surgical techniques evolved and were refined.
Methods: A cohort of women undergoing RRM was followed from this single centre. Surgical and further details about demographics, comorbidities, and follow-up were retrieved form medical records. Analysis was carried out using the IBM®-SPSS®-Statistics-19system.
Results: Of 154 women 139 had bilateral RRM and 15 had unilateral surgery after earlier contralateral breast cancer. Median age at operation was 39.4 years (22–63years). 54 (45.5%) women were BRCA1/2 gene mutation carriers. Most women had nipple sacrificing (86) skin-sparing mastectomy with immediate reconstruction. 132 (85.7%) had submuscular expander/implant reconstruction, whilst 9 had either LD flap reconstruction or TRAM flap reconstruction.
31 (20.1%) women had some complication including haematoma requiring evacuation, minor skin/nipple necrosis, but implant loss was rare (2). 52 (33.8%) women had revisional surgeries in 5 years post RRM of whom 29 had one unanticipated secondary operation. Complications were more common in the early years of the cohort.
On histology, 3 women were identified with lobular carcinoma in-situ and one was associated with 1mm of microinvasion. 4 had ductal carcinoma in-situ and 2 of them were BRCA carriers. Two (1.2%) primary breast cancers were subsequently identified during a mean follow-up period of 9.82 years (2–18 years) but this was substantially less than prediction modelling. Both were BRCA gene mutation carriers - one had nipple sparing RRM and the other did not.
Conclusions: In asymptomatic high-risk women, RRM is safe and efficacious in reducing medium term future breast cancer incidence. Surgery carries the risk of complications and cosmetic revisions can be anticipated.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-14-11.
Abstract P4-16-05: Benefit from Postoperative Radiotherapy for N1 Breast Cancer
Authors: Tsai Y-CS , Cheng H-CS , Yu B-L , Horng C-F , Chen C-M , Jian J-MJ , Chu N-M , Tsou M-H , Liu M-C , Huang AT 
Published: August 2014

Abstract
Purpose: To evaluate the outcomes for patients with Stage II breast cancer and one to three positive lymph nodes after mastectomy who were treated with observation or adjuvant radiotherapy to the chest wall (CW) and regional lymphatics; and to identify a group of patients who benefit from postmastectomy radiotherapy (PMRT).
Methods and Materials: The subjects were 716 patients diagnosed between 1990 and 2007 with Stage II breast cancer (one to three positive lymph nodes) treated with mastectomy at the Koo Foundation Sun Yat-Sen Cancer Center. 283 patients had undergone PMRT to the CW and regional lymphatics according to in-house treatment guideline or physician decision. Since 2003, we recommend PMRT for patients who had 2 or more risk factors; age less than 40 y/o, T2 disease, GrII/GrIII, prominent lymphovascular invasion (LVI), presence of extracapsular spreading (ECS), and negative Estrogen Receptor (ER(−)). Survival was analyzed by the Kaplan—Meier method. The survival free of isolated locoregional disease(LRR), metastasis free survival(MFS), disease free survival(DFS), and overall survival(OS) were analyzed according to the delivery of radiotherapy or not.

Results: The median follow-up was 80 months. LRR, MFS, DFS and OS were significantly improved by PMRT. The 5- and 10-year LRR rate without PMRT was 89.9% and 81.6%, respectively and, with PMRT was 97.7% and 97.0% respectively (p &lt;0.0001). The 5- and 10-year MFS rate without PMRT was 84.4% and 76.5%, respectively, and, with PMRT, was 90.8% and 87.2% respectively (p = 0.0153). The 5- and 10-year DFS rate without PMRT was 80.8% and 69.8%, respectively, and, with PMRT, was 89.6% and 86.1% respectively (p = 0.001). The 5- and 10-year OS rate without PMRT was 89.1% and 77.3%, respectively, and, with PMRT, was 94.6% and 86.2% respectively (p = 0.0039). 239 patients had less than 2 risk factors, their LRR, MFS and DFS did not benefit from PMRT.
Conclusion: Our data suggest that adjuvant PMRT improve LRR, MFS, DFS and OS for stage II breast cancer with one to three positive lymph nodes who had 2 or more risk factors (Age less than 40 y/o, T2, GrII/GrIII, LVI, ECS, ER(−)).
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-16-05.