bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P2-11-19: Expression of folate receptor alpha in ductal carcinoma in situ of the breast and comparison with that of invasive ductal carcinoma
Authors: Zhang Z , Wang J , Tacha D , Li P , Bremer R , Skinner K , Hicks DG , Bu H , Tang P 
Published: August 2014

Abstract
Background: We have previously shown that the expression of Folate receptor alpha (FRA) is associated with high grade ER-/PR- or triple negative (TN) invasive ductal carcinoma of the breast. The aim of the current study is to investigate the expression pattern of FRA in a cohort of ductal carcinoma in situ (DCIS), analyze its relationship with different clinicopathological features and expression of several key biomarkers, and compare these findings to our previous data on invasive ductal carcinoma (IDC).
Methods: Ninety-eight cases of DCIS of the breast diagnosed between 1997 and 2008 in our institution were identified, reviewed and 6 blocks of tissue microassays (TMA) were constructed. The association between the expression of FRA (≥10% designed as positive expression) and the clinicopathologic features, the expression of ER, PR, HER2 and Ki-67, and the clinical outcome were evaluated, and these results were compared to those from IDC (399/430 cases with informative data). Results: Among the 98 cases of DCIS in TMA, 88 cases were informative. The expression rate of FRA was 21% for DCIS, less than the 29% seen in IDC. Expression of FRA was associated with high nuclear grades (42%), though less frequently than with IDC (52%). FRA expression was also associated with ER negativity (46%), PR negativity (33%) and high Ki-67 expression (50%) in DCIS, although significantly less than in IDC (75%, 63%, and 56%, respectively for negative ER and PR, and high Ki-67). Also, only 50% of ER/PR negative, TN and basal-like DCIS expressed FRA, significantly lower than that of IDC (74%, 80% and 80%, respectively). Due to the limited cases of DCIS, we did not demonstrate a significant difference in disease-free survival between FRA positive and negative tumors (p-value = 0.1792), although we did observe that IDC with FRA expression was significantly associated with a worse disease-free survival (p-value = 0.04).
Comparison between FRA expression between DCIS and IDC FRA≥10% in DCISFRA≥10% in IDCp-value 88 cases399 cases Nuclear 342%52%0.0185ER negative46%75%0.0442PR negative33%63%0.0214HER2 3+31%37%0.7003ER-/PR-50%74%0.0973Triple Negative50%80%0.1622Basal-Like50%80%0.1739
Conclusion: Our data demonstrates that FRA expression is associated with high nuclear grade, ER/PR negative and TN DCIS, though at a significantly lower rate than was observed in IDC, suggesting a possible role for this receptor in early breast carcinogenesis. There are differences in the rates of FRA expression between DCIS and IDC, suggesting that FRA may be one of the key molecules involved in progression of DCIS to IDC.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-11-19.
Abstract P2-12-04: Evaluation of BRCA 1/2 mutation-carrier probability models, BRCAPRO and myriad II, in the Japanese population
Authors: Ito M , Yasuda Y , Furuta A , Ohuchi N 
Published: August 2014

Abstract
Background:
It is important to select high-risk group with a BRCA1/2 mutation and recommend them to provide genetic counseling and genetic testing. BRCAPRO and Myriad II are widely used for predicting BRCA mutation-carrier probability and useful for selecting eligible person of genetic testing. However, It is reported that BRCAPRO tends to underestimate the risk of BRCA1/2 mutation probability in Asian. The validation of these models are not sufficiently known in Japanese population.
Methods:
Twenty-six hundred sixty-five people visited to Ishinomaki Red Cross Hospital between 2011 and 2012.They were surveyed family history as a risk factor of inheriting breast cancer according to NCCN guideline. We calculated BRCA1/2 mutation probability by BRCAPRO and Myriad II. Those who had more than 10% mutation probability and early-onset breast cancer, triple negative breast cancer were received genetic counseling and genetic testing for applicants. We analyzed association between family history of the probands and BRCA 1/2 mutation. We also calculated sensitivity, specificity and positive predictive value(PPV) at the10% threshold in BRCAPRO and Myriad II.
Results:
Two handred forty-three(9.1%) people were selected as a risk of inheriting breast cancer, of which sixty-eight people (2.5%) were constructed family tree. The number of people who had more than 10% and 30% mutation probability by BRCAPRO was eight (0.30%) and five (0.18%).Fourteen people performed BRCA1/2 genetic testing (proband : thirteen, relative: one). Seven people carried a deleterious BRCA mutation (BRCA1: five, BRCA2: two). In the cases which had more than 30% mutation probability, all of them carried a deleterious BRCA mutation. Most of their mutation site was L63X which was most frequent in Japan.
People who had personal or family history of breast and ovarian cancer, triple negative breast cancer were significantly associated with BRCA1/2 mutation.(p = 0.035,p = 0.015,p = 0.009)
Using a 10% threshold, sensitivity, specificity, positive predictive value in BRCAPRO was 75%,83%,85% and 63%,67%,71% in Myriad II respectively. When it comes to the cases which had more than 30% mutation probability, Sensitivity, specificity, positive predictive value were all 100% in BRCAPRO.
Conclusions:
It is recommended to perform genetic testing for especially those who have personal or family history of both breast and ovarian cancer, triple negative breast cancer. 10% threshold of BRCAPRO and Myriad II is generally applicable to selecting eligible person in the Japanese population. BRCAPRO is superior to Myriad II in terms of sensitivity, specificity, PPV in our study. The cases which have more than 30% mutation probability need to have genetic testing.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-12-04.
Abstract P2-13-01: The Brazilian founder TP53 p.R337H mutation is uncommon in Portuguese women diagnosed with breast cancer
Authors: Giacomazzi J , Correia RL , Palmero EI , Gaspar JF , Almeida M , Portela C , Camey SA , Reis RM , Ashton-Prolla P 
Published: August 2014

Abstract
Since the first studies reporting the TP53 p.R337H mutation as founder mutation in Southern and Southeastern regions of Brazil, both in the general population and in patients from high risk breast cancer families with adrenocortical, choroid plexus and breast carcinomas, there has been controversy on the origin of this mutation. Preliminary analysis of the small subset of Brazilian mutation carriers that defined the founder haplotype using 29 tag SNPs revealed that the haplotype incided on a Caucasian background. The vast majority of carriers identified today reside in Brazil or, if identified in other countries, are Brazilian immigrants. To our knowledge, the only two exceptions of carriers without a recognizable link with Brazil are two European families (one Portuguese and one German) (Chompret et al., 2000; Herrmann et al. 2012). Haplotype analysis in the Portuguese family revealed the same haplotype identified in Brazilian individuals, but in the German family, a distinct haplotype was found. Knowing that a significant proportion of women with breast cancer in Southern Brazil are p.R337H carriers, we initiated TP53 genotyping in a Portuguese cohort of women with breast cancer recruited from the cities of Lisboa and Braga. Median age at diagnosis of breast cancer among the first 573 patients tested was 60 years and 100 (17.4%) patients had been diagnosed at or under the age of 45 years. Mutation screening was performed using Real-Time PCR (taqman assays), and failed to identify the mutation in the 573 patients tested. These results are in contrast with the mutation frequency observed in a study of 815 breast cancer-affected women from Southern and Southeastern Brazil, which has reached frequencies of 12.1 and 5.1% in pre- and post-menopausal women, respectively (Ashton-Prolla et al. 2012; ASCO Annual Meeting, ref 1522). We conclude that there is a significant difference in mutation frequency observed between the two cohorts (p&lt;0.001). These findings suggest that TP53 p.R337H is not a common molecular alteration in Portuguese breast cancer-affected patients.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-13-01.
Abstract P2-14-04: Effect of age at the time of diagnosis on overall and cancer-specific mortality in breast cancer: Analysis of SEER, 1990-2008
Authors: Bao J , Yu K-D , Jiang Y-Z , Di G-H 
Published: August 2014

Abstract
Background: As a critical factor, age at the time of diagnosis has a significant impact on cancer therapy and outcomes. The purpose of this study is to investigate the overall mortality (OM) and breast cancer-specific mortality (BCSM) in patients with breast cancer corresponding to age at the time of diagnosis, thus constructing an age-related pattern on breast cancer survival.
Methods: We analyzed data for 396,978 women aged 20-79 from 1990 to 2008 diagnosed with breast cancer from the population-based Surveillance, Epidemiology, and End Results (SEER) program of the U.S. national cancer institute. Clinicopathological factors and outcomes were compared using a chi-square test, the Kaplan-Meier method, and Cox proportional hazards regression model.
Results: In the multivariable analysis, a significant relationship was found between age at the time of diagnosis and OM (p&lt;0.001) as well as BCSM (p&lt;0.001). Using 70-79 years old as the reference, the hazard ratio (HR) of OM and BCSM presents a U-like shape with the bottom at the group 40-49 years old (OM: HR,0.56; P&lt;0.001; BCSM: HR,0.58; p&lt;0.001) and 50-59 years old (OM: HR,0.59; P&lt;0.001;; BCSM: HR,0.60; p&lt;0.001), increasing to both ends gradually. Analysis in subgroup according to ER and PgR status, group 20-29 years old showed no significant difference with group 70-79 years old on both OM and BCSM in all subgroups except on BCSM in ER+PR+ subgroup (HR,1.25; P = 0.002).
Conclusion: Patients at very young and very old age (20-29 years old and 70-79 years old) have the poorest outcomes while prognosis improves with age towards mean level. The very young age (20-29 years old) may be regarded as a significant hazard factor for BCSM in patients with ER+PR+ breast cancer.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-14-04.
Abstract P2-14-06: Characterization of risk factors in breast cancer young adult patients
Authors: Encinas G , Diz MDPE , Lyra EC , Katayama MLH , Pasini FS , Brentani MM , Chammas R , Góes JCGS , Folgueira MAAK 
Published: August 2014

Abstract
Background: Breast cancer diagnosis in the age group of 20-34 years represents 4% of breast cancer cases diagnosed at all ages in São Paulo state, Brazil. Risk factors in this age group of patients are little understood, especially in those not reporting familial history of breast/ovarian cancer syndrome (BOCS). Identification of predisposing factors and BRCA1/2 mutations (mut) in young Brazilian patients may contribute to characterize women with increased risk of breast cancer.
Objective: Characterize familial history and risk factors for breast cancer in young adult Brazilian patients and germline mutations in BRCA1/2 genes.
Methodology: Forty-five patients diagnosed with breast cancer at ages 18-35 years were interviewed using a comprehensive questionnaire. Genomic DNA was extracted from peripheral blood and BRCA1/2 mut were screened by Sanger sequencing of coding sequences, analyzed through Mutation Surveyor v.3.20 and searched in BIC Database, LOVD, LOVD-IARC and UMD.
Results: Mean age of patients at time of diagnosis was 33 y (24-35y); mean age of menarche was 13 y (8-19y); 32 (71.1%) patients had at least one born child, median age of first pregnancy was 22 years; 86.7% never smoked; 71.1% were no regular alcoholic drinkers; mean of body mass index was 27.14 (overweight). Most patients were diagnosed with invasive ductal carcinoma (91.1%); grades II or III (95.5%); ER/PR positive (57.8%); triple-negative (TN: 31.1%) or HER2 positive (17.8%). Among them, 22.2% reported positive familial history (NCCN criteria for BOCS). Deleterious mutation in BRCA1/2 genes was found in 17.8% of the patients (BRCA1, n = 3; BRCA2, n = 5). Among 10 and 35 patients reporting or not BOCS familial history, 3 (30%) and 5 (14.3%) respectively, had BRCA1/2mut. All BRCA1mut patients had TN tumors; BRCA2mut patients had ER/PR positive (60%), HER2 positive (20%) or TN tumors (20%). Most patients reported one or two of the following risk factors: early menarche (&lt;12y); current/previous use of oral contraceptive; no breast feeding and no parities. Among 30 patients reporting no familial history and presenting BRCA1/2 wild type, six (20%) and four (13.3%) reported three or four of these risk factors, respectively. Considering breast cancer protective factors, 17.8% of the patients breast fed &gt;16 months and 24.4% were aged &lt;20y at birth of first child. Diet habits are being analyzed.
Conclusion: In young adults with breast cancer there is a trend towards a higher rate of positive familial history among whom there is a trend towards a higher chance of BRCA1/2 mutation. A better characterization of patients reporting no familial history is urgently needed.
Financial Support: FAPESP.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-14-06.
Abstract P2-16-12: An exploratory analysis of the role of dasatinib in preventing progression of disease in bone in patients with metastatic breast cancer
Authors: Cadoo KA , Morris PG , Lake DE , D'Andrea GM , Dickler MN , Gilewski TA , Dang CT , McArthur HL , Bromberg JF , Goldfarb SB , Modi S , Robson ME , Seidman AD , Sklarin NT , Norton L , Hudis CA , Fornier MN 
Published: August 2014

Abstract
Introduction: The role of dasatinib, an oral SRC inhibitor is being explored for the treatment of metastatic breast cancer. In a phase I study, we previously established that the combination of dasatinib and weekly paclitaxel was feasible. The activity of this combination is currently being explored in an ongoing phase II trial. Since Src kinase has a major role in osteoclast function and dasatinib has established anabolic and anti-resorptive effects in bone in vitro, we hypothesized that patients receiving this combination would have good control of osseous metastases and primarily develop progression of disease in sites other than bone.
Patients and methods: Patients were included in this analysis if they participated in the phase I or II metastatic breast cancer studies and received dasatinib at or above the recommended phase II dose of 120mg with paclitaxel (80mg/m2 day 1 and 8 of each 21day cycle). Patients who discontinued therapy for reasons other than progression were excluded. Per protocol, patients were required to discontinue bisphosphonates or other bone modulating agents for the first 8 weeks of study due to the potential for hypocalcaemia. Thereafter, they were permitted to receive these agents at the discretion of their treating physician. Patients provided serum samples for correlative studies. Assessment of N-telopeptide of type 1 collagen (NTX), a product of mature bone collagen that reflects bone specific resorption, is planned.
Results: The median age of the 24 patients who met criteria for analysis was 50y (37 - 66y). Of these, 15 (63%) had ER+ disease, and 24 (100%) were negative for human epidermal growth factor receptor (HER2). At study entry, 17 (71%) patients had bone involvement. Following the initial eight week moratorium, 7 (29%) patients received a bisphosphonate or rank ligand inhibitor during treatment with dasatinib + paclitaxel. Patients received a median 2 months (range 1-23) of dasatinib + paclitaxel therapy. To date, 3 (13%) continue on therapy, and 21 (88%) have had progression of disease. Among patients who progressed, 18 (86%) have progressed in visceral sites and only 3 (14%) progressed in bone. Analyses of serum NTX levels are ongoing and will be compared by site of progression.
Conclusion: The potential role of serum NTX as a predictive biomarker of benefit from dasatinib and paclitaxel is being explored and updated results will be presented.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-16-12.
Abstract P2-18-06: Preservation or division of the intercostobrachial nerve in axillary dissection for breast cancer: Meta-analysis of randomised controlled trials
Authors: Warrier SK , Hwang S , Koh C , Shepherd H , Mak C , Carmalt H , Solomon M 
Published: August 2014

Abstract
Purpose: Management of the ICBN during axillary dissection is controversial and the division of ICBN is often trivialised.The effect of dividing the ICBN, and its association with sensory disturbance, is unclear. A systemic review and meta-analysis was performed to evaluate the effect of preserving the ICBN during axillary dissection.
Methods: A systemic literature review and meta-analysis was performed according to the PRISMA and Cochrane Collaboration guidelines. Two authors (SW and SH) independently searched Medline, Pubmed, Embase, Cochrane Database of Systemic Reviews and the Cochrane Controlled Trials Register from 1950 to December 2012 for studies comparing preservation or division of the ICBN in axillary dissection for breast cancer. The primary outcome of this meta-analysis was sensory disturbance, defined as objectively assessed change in sensation in the distribution of the ICBN after axillary dissection. The nature of sensory disturbance was assessed as a secondary outcome, categorised into two types: “hypersensitivity” and “hyposensitivity”.
Results: Three RCTs and four non-RCTs were reviewed. A meta-analysis demonstrated that the incidence of sensory disturbance was significantly lower with preservation of ICBN compared to division of the ICBN with Mantel-Haenzel combined odds ratio 0.31 (0.17-0.57, 95% CI). There was relatively low level of heterogeneity (I2 = 19%, c2 = 2.48, df = 2).
The sensory disturbance was more likely to be hyposensitivity when compared to hypersensitivity (p &lt;0.0001). No difference on number of lymph nodes dissected or operating time was noted.
Conclusion: This meta-analysis demonstrates that division of the ICBN is associated with higher risk of sensory disturbance, and that the nature of this sensory disturbance is more likely to be hyposensitivity, attributable to reduced nerve function.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-18-06.
Abstract P2-18-07: Nipple sparing mastectomy-infectious complication risk. A preliminary assessment of the American Society of Breast Surgeons nipple sparing mastectomy registry
Authors: Mitchell SD , Feldman SM , Beitsch PD , Willey SC , Manasseh DME , Unzeitig GW 
Published: August 2014

Abstract
Objectives: The American Society of Breast Surgeons (ASBS) Nipple Sparing Mastectomy Registry (NSMR) is a prospective, IRB approved, non-randomized, multi-institutional registry assessing surgical techniques, utilized metrics, oncologic outcome, and aesthetic outcome of nipple sparing mastectomies. The registry has been open for enrollment for 26 months. The target accrual is 1000 individuals. This abstract specifically analyzes rates of post-operative infection in NSMs.
Methods: Fifty two investigators from 41 institutions are participating in the ASBS NSMR. A total of 373 patients underwent 631 mastectomies, with indications of prophylaxis (365), cancer (248), and unknown (18). We assessed a sub group of 449 mastectomies, with indications of prophylaxis (253) and cancer (196) that had all data sets completed. We assessed infection rates(characterized as needing oral or iv antibiotics with or without removal of implant/expander and/or debridement) in the entire group as well as by indication (cancer vs. prophylaxis). Factors such as smoking history, previous radiation therapy, previous surgery, incision type, reconstruction technique, and flap dissection technique were analyzed.
Results: In a subgroup of 449 mastectomies (253 prophylactic and 196 cancer):
Post operative infections were reported in 22 (4.9%) of patients: 7 (3.6%) of mastectomies with an indication of cancer and 15 (5.9%) of prophylactic mastectomies (p-value 0.3140). Infections were characterized as: treatment with oral antibiotics alone, treatment with i.v. antibiotics alone, iv antibiotics with washout or debridement, or antibiotics and implant/ tissue expander removal. No correlation was found in smoking history (p-value 1.000), previous breast surgery (p-value 0.1277) or previous radiation (p-value 0.6024). No correlation was found in incision utilized, reconstruction technique, or method of flap dissection either.
Conclusion:
The rate of postoperative infections in nipple sparing mastectomies is comparable if not lower than non-nipple sparing mastectomies. No statistically significant difference in infection rate was found between mastectomies completed for prophylaxis or cancer. No correlation was found between factors such as smoking history, history of radiation therapy, prior breast surgery, incision utilized, reconstruction technique, or method of flap dissection. Improved aesthetics with a nipple sparing approach (technically more demanding and typically through a smaller incision) does not come at the cost of a higher rate of infectious complications.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-18-07.
Abstract P2-18-10: High risk of late in-breast tumour recurrence after BRCA1/2-associated breast cancer
Authors: Nilsson M , Hartman L , Kristoffersson U , Olsson H , Borg Å , Henriksson K , Lanke E , Loman N 
Published: August 2014

Abstract
Background: In the general population, partial mastectomy followed by postoperative radiotherapy (PMRT) reduces the risk of local recurrences of breast cancers to a level comparable to the risk after mastectomy (M). However, for BRCA1/2 mutation carriers, a potentially increased risk of a new primary breast cancer in the ipsilateral breast must be taken into account when recommendations about type of surgery are given. To address this question, we conducted a retrospective study on the risk of in-breast tumor recurrence (IBTR) after PMRT in BRCA1/2 mutation carriers.
Methods: Women with invasive breast cancer from families with a pathogenic mutation in BRCA1 or BRCA2 identified at a single institution were included in the study (n = 174). Median age at diagnosis was 43 years and median follow-up was 10.8 years for patients alive at end of follow-up. Patients who were treated with PMRT (n = 45) were compared with patients who had M as primary surgery (n = 118). Endpoints were local recurrence as first failure (LR [IBTR or thoracic wall recurrence]), overall survival (OS), breast cancer-specific survuval (BCSS) and distant disease-free survival (DDFS). LR, OS, BCSS and DDFS were estimated using the Kaplan-Meier method and compared by the log-rank test. For calculation of hazard ratios and for multivariable analysis, the Cox proportional hazards model was used.
Results: In univariate analysis, no difference in OS, BCSS or DDFS was seen between the PMRT and M groups (HR 0.9 [95% CI 0.5-1.4], HR 0.9 [CI 0.5-1.7] and HR 0.8 [CI 0.5-1.5], respectively). In multivariable analysis, adjusting for tumor stage, age and use of adjuvant chemotherapy, the hazard ratios were lower (HR 0.8 [95% CI 0.4-1.3], HR 0.6 [CI 0.3-1.3] and HR 0.6 [CI 0.3-1.1], respectively), but remained inconclusive.
Compared to M, PMRT was associated with an increased risk for LR in univariate analysis (HR 4.0 [CI 1.6-9.8]). In the M group, all local recurrences were seen in the first 5 years. As opposed to this, in the PMRT group the rate of IBTR was rather constant over 15 years of follow-up. The cumulative risk for IBTR in the PMRT group was 19%, 32% and 43% after 5, 10 and 15 years, respectively.
Conclusion: BRCA1/2 mutation carriers treated with PMRT have a high risk for IBTR, many of which are new primary breast cancers. This must be thoroughly discussed with the patient and is an example of how rapid treatment-focused genetic testing already could influence choice of treatment.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-18-10.