bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P4-12-03: Towards a risk prediction model for breast cancer that utilizes breast tissue risk features
Authors: Pankratz VS , Degnim AC , Visscher DW , Frank RD , Vierkant RA , Ghosh K , Aziza N , Vachon CM , Frost M , Radisky DC , Hartmann LC 
Published: August 2014

Abstract
Background: Optimal early detection and prevention strategies for breast cancer are predicated on our ability to accurately identify women at increased risk for disease. Current breast cancer risk prediction models rely on clinical and epidemiologic features. As demonstrated with other cancers, such as those of the cervix and colon, cancer risk assessment is enhanced when the tissue at risk is examined for evidence of premalignant abnormalities. Here, we present a multivariate model for individualized breast cancer risk prediction that incorporates tissue features identified from biopsies from women with benign breast disease (BBD).
Methods: We used our cohort of more than 9000 women diagnosed with BBD at the Mayo Clinic from 1967–1991, and identified a nested case:control series of 377 women who developed cancer (cases) matched with 734 women who did not (controls). We identified a set of variables that either alone or in two-way interactions contributed to a multivariable risk prediction model. We combined this relative risk model with the baseline incidence of breast cancer and the baseline hazard of death from our full BBD cohort to develop a risk prediction tool that computes absolute risk estimates for breast cancer. We calculated 5-year risk predictions for these cases and controls using our model and using the Gail model and compared c-statistics from these risk predictions. We validated our model using an independent set of 378 breast cancer cases and 728 matched controls drawn from our BBD cohort.
Results: Cases and controls in the model development data set differed significantly on a number of features when examined individually. Those included in a multivariable relative risk model for breast cancer among women with BBD are shown below.

After including interactions between lobular involution, and histologic impression, with age at first live birth/number of children, and degree of involution with sclerosing adenosis, we devised a model that predicts the absolute risk of breast cancer. Predicted five-year risks in the model development series, we observed a c-statistic of 0.66, higher than the c-statistic of 0.61 for the Gail model. With risk prediction estimates from our validation series of cases and matched controls, the c-statistic of our model decreased to 0.59 and the c-statistic for the Gail model was 0.55.
Conclusion: We have identified an initial risk prediction model for breast cancer in women with BBD. The identified model includes basic demographic information as well as a number of histologic features of the tissue samples. Its initial performance is promising, providing improved discrimination over the Gail model in our replication data set. Further work is needed to identify features which might provide additional predictive information for breast cancer risk.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-12-03.
Abstract P4-12-04: Association of single-strand breaks (SSBs) in normal breast DNA with estimates of breast cancer risk
Authors: Chatterton RT , Sahadevan M , Heinz RE , Sukumar S , Stearns V , Fackler MJ , Lee O , Sivaraman I , Kenney K , Khan SA 
Published: August 2014

Abstract
Background: Formation of single strand breaks in DNA is a constant process, estimated to occur 10,000 times per day in each cell, either from endogenous biosynthetic errors or from interference by endogenous or exogenous agents. Base excision repair in some cases may be impaired or may be exceeded by the rate of DNA damage, leading to cancer. Nick translation of with labeled nucleotides can be used as a quantitative indicator of SSBs.
Methods: Healthy women were recruited through the Love-Avon Army of Women and breast clinics of Northwestern and John Hopkins Universities. Digital or digitized mammograms were evaluated for percent density using Cumulus software. The medians (ranges) were age 51 (36 to 60); BMI 28.2 (18.7 to 51.3); life-time Gail estimate 12.5 (5.6 to 28.3); % breast density 16.5 (2.4 to 52.5); Masood score 13 (0 to 18). Breast tissue was obtained by random fine needle aspiration (rFNA). Specimens were rinsed into ice-cold phosphate buffered saline and were stored at −80°C. Thawed samples were centrifuged at 2200 g for 60 min. A kit from Norgen Inc., was used to separate DNA, RNA, and protein from the pellet. The lipids were extracted with ethyl acetate-hexane (3:2) from the supernatant fluid, and triglycerides were precipitated from cold 90% methanol, leaving a purified lipid fraction containing the steroids. Steroids were then fractionated by HPLC on a C18 column, and estradiol was analyzed by a radioimmunoassay. Blood was obtained at the same time as the rFNA samples and was frozen prior to analysis. An aliquot containing 200 ng of DNA (260/280 ratio 1.3 to 2.3) was taken for the nick translation assay. Incorporation of free nucleotides at SSBs with dCTP labeled with3H was catalyzed by Polymerase I from E. coli. A quality control preparation prepared from calf thymus DNA and a reagent blank without DNA was included with each set of 6 samples. Incorporation of3H-dCTP was linear with dose of DNA and reached a maximal at 30 min. Separation of free from incorporated3H-dCTP was accomplished by gel chromatography on an 80 × 15 mm column. The concordance of interassay values was 0.96.

Results: Incorporation of nucleotides into DNA ranged from 0.03 to 8.59 pmol/μg, median 0.63 pmol/μg DNA. The association with other factors associated with breast cancer is shown in the Table. A significant correlation, was found with % breast density, life-time risk by the Gail model, but not serum estradiol concentrations.
Conclusions: Assessment of SSBs by the nick translation procedure may be a useful indicator of breast cancer risk. Future studies will relate this method with actual risk as assessed by analysis of pre-diagnosis specimens with subsequent occurrence of breast cancer.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-12-04.
Abstract P4-12-07: Diabetes Increases the Risk of Breast Cancer
Authors: Hardefeldt PJ , Edirimanne S , Eslick GD 
Published: August 2014

Abstract
Background: The hyperinsulinaemia associated with type 2 diabetes and the known proliferative effects of insulin lead to the hypothesis that diabetes mellitus increases the risk of breast cancer. The aim of this meta-analysis was to collate and analyse all primary observational studies investigating the risk of breast cancer associated with diabetes. In addition, we aimed to complete sub group analyses by both type of diabetes and gender of study participants to further clarify the origin of any such association between the two.
Method: Studies were obtained from a database search of MEDLINE, EMBASE, PubMed, Current Contents Connect and Google Scholar with additional cross checking of reference lists. Databases were searched using subject headings, keyword searches and text word searches wherever possible using the search terms ‘diabetes’ AND ‘breast cancer’ OR ‘breast carcinoma’ OR ‘breast neoplasm’. Inclusion criteria required a confirmed diagnosis of both diabetes and breast cancer, reporting of an odds ratio or data to calculate an unadjusted odds ratio (and 95% confidence interval) and the use of an internal control group as the comparator. Collated data was assessed for heterogeneity and a pooled odds ratio calculated.
Results: 34 studies were included in the meta-analysis with 31 studies investigating breast cancer in women and 5 studies investigating breast cancer in men. Overall, we found a significantly increased risk of breast cancer associated with diabetes in both women (OR 1.25, 95% CI 1.13–1.38) and men (OR 1.40, 95% CI 1.10–1.79). The pooled odds ratio was consistent across both case control studies (OR 1.25, 95% CI 1.06–1.46) and cohort studies (OR 1.26, 95% CI 1.09–1.45). Heterogeneity was significant (I2 = 73.40, p &lt; 0.001) and publication bias was present (p = 0.03). The 31 studies investigating breast cancer in women were sub grouped by type of diabetes with the association strengthened by a diagnosis of type 2 diabetes (OR 1.32, 95% CI 1.09–1.61) but nullified with gestational diabetes (OR 1.06, 95% CI 0.79–1.40). There were insufficient studies to calculate a pooled odds ratio of the risk of breast cancer associated with type 1 diabetes.
Conclusion: Diabetes increases the risk of breast cancer in both women and men. This association is strengthened in women with type 2 diabetes and supports the hypothesis that diabetes is an independent risk factor for breast cancer.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-12-07.
Abstract P4-13-02: Comparing data quality of client intake forms by interview mode: results of a pilot study on the use of audio computer-assisted self-interview (ACASI) in the Avon Breast Health Outreach Program
Authors: Hallum-Montes R , Senter L , D'Souza R , Hurlbert M , Gates-Ferris K , Anastario M 
Published: August 2014

Abstract
Background: Numerous studies have documented the relative advantages that computer assisted self-interview (CASI) technology holds over traditional interviewing methods in collecting research data on stigmatized and/or risky health behaviors. However, few studies have explored the broader implications of using CASI to collect basic client-level data during routine health promotion and disease prevention screenings.
Aims: The present study aims to address this gap in research by comparing the quality of client-level data collected via audio-computer assisted self-interview (ACASI) with data collected via face-to-face and self-administered paper-based interviews among a sample of clients served through the Avon Breast Health Outreach Program (Avon BHOP).
Methods: A total of 303 clients served through the Avon BHOP were sampled from three U.S. sites between November 2011 and March 2012. Clients were randomly assigned to complete the Avon BHOP client intake form (CIF) via one of three interview modes: face-to-face interview (FFI), self-administered paper-based interview (SAPI), or ACASI. We conducted logistic regression and determined odds ratios with 95% confidence intervals to test our hypothesis that use of ACASI would result in significantly higher rates of CIF completion than either FFI or SAPI. We compared rates of completion of the entire CIF, as well as completion of each of the three CIF sections: Demographics, Breast Health Information, and Correlates of Breast Health.
Results: Clients were significantly more likely to complete the entire CIF via ACASI than either FFI or SAPI interview modes. The greatest differences were observed when comparing rates of completion between ACASI and SAPI, as clients were almost five times more likely to complete the CIF via ACASI as opposed to SAPI (OR = 4.7, p &lt; 0.001). Additionally, when comparing rates of completion of the three CIF sections on Demographics, Breast Health Information (e.g. mammogram history), and Correlates of Breast Health (e.g., smoking behavior, alcohol consumption), we found that clients were between 3.2 and 7.2 times more likely to complete the sections via ACASI as opposed to SAPI.

Discussion: Overall, we found that use of ACASI resulted in significantly higher rates of overall form completion and lower rates of missing data than use of SAPI or FFI, with the greatest identified disparity in form completion between ACASI and SAPI. This study has important implications for breast health specialists or any health practitioners who regularly rely on self-administered questionnaires and/or face-to-face interviews to collect important health information. We recommend that where feasible, ACASI be utilized as an effective means of collecting high quality client-level data.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-13-02.
Abstract P4-13-12: Identifying women at increased risk for breast cancer using the electronic health record in an integrated health system
Authors: Leader JB , Bengier A , Darer J , Stark A , Vogel VG 
Published: August 2014

Abstract
Women at increased risk for breast cancer (BC) are eligible to take selective estrogen receptor modulators (SERMs) to reduce their risk; Food and Drug Administration (FDA) approval of tamoxifen or raloxifene for BC risk reduction and American Society of Clinical Oncology (ASCO) guidelines for the use of SERMs recommend the two drugs for any woman over the age of 35 years with a 5-year risk of 1.67% or greater, but identifying those women can be both challenging and costly. We used an electronic database (Centricity RIS-IC) from the Geisinger Health System (GHS) Department of Radiology with 77,000 women ages 35–90 years to calculate 5-year and lifetime risks of developing invasive BC using National Cancer Institute's (NCI) Breast Cancer Risk Assessment Macro (BrCa RAM). BrCa RAM calculates risk based on patient age, number of biopsies, did a biopsy ever display atypical hyperplasia (Yes/No), age at menarche, age at first live birth, number of first degree relatives with breast cancer, and patient race. Demographic information (age, race, sex) was obtained from the electronic health record (EpicCare), pathology information (number of biopsies, atypical hyperplasia) was obtained from the pathology application (CoPath), and personal history (number of first degree relatives with breast cancer) were obtained from RIS. Age at menarche and age at first live birth could not be obtained, but makes a small relative contribution to the risk of BC. Sensitivity analysis explored implications of missing data; imputing ages for age at first live birth and age at menarche showed that the absence of this data did not overestimate the five-year and lifetime risks. There were 5,897 patients with calculated 5-year breast cancer risk 2; mean age was 65.8 years, mean 5-yr risk of BC = 3.05% (max 18.2%). The number of patients by 5-year risk score category were: risk 2–2.5% (n = 1728); 2.5%–3% (n = 3188); 3%+ (n = 981). There were 4,196 patients with a GHS primary care physician (PCP); 5,086 patients had seen any Geisinger physician within the past year; 4,113 women had seen their PCP in the past year. Only 239 patients ever received a prescription for tamoxifen or raloxifene, and some received raloxifene for prevention or treatment of osteoporosis and not for BC risk reduction. Only 40 were currently taking tamoxifen or raloxifene. These data from an integrated health system with an electronic health record validate the under-utilization of SERMs for primary BC risk reduction. Strategies are being designed to increase their use in GHS by using the risk score to identify the population and attempt to intervene using a risk modification clinical program.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-13-12.
Abstract P4-13-14: Lung cancer after treatment of breast cancer:retrospective study from Curie Institut
Authors: Sebbagh S , Cosquer M , Kirova YM , Livartowski A 
Published: August 2014

Abstract
Background: Few studies have evaluated the effects of adjuvant radiotherapy (RT)of breast cancer(BC). The relation between the risk of lung carcinoma and radiotherapy have been controversial.
Methods and materials: We retrospectively studied 127 patients treated at the Institut Curie with non metastatic breast cancer and lung carcinoma between 2000 and 2011(2/3 of BC apperead befor lung). Confirmation Diagnosis bronchial cancer obtained by: biopsy: histological data:architecture, IHC (HR, HER 2, TTF1), EGFR, Kras statut clinical and radiological Correlation. Comparison with breast tumor
Results: BC: median age at diagnosis 54 years, predominatly invasive ductual carcinoma(IDC), lumpectomy 78%, mastectomy 21%. Lung cancer: median age at diagnosis: 63 years, 67 smokers. histology: 52 % Adenocarcinoma, 18.1 % scamous cell carcinoma, 18.1% large cell carcinoma, 13.4 % small cell carcinoma. EGFR mutation in 4.3%. 109 patients underwent RT (3 cases of lung cancer befor BC):Region: internal mammary chain: 46, supracalvicular: 42, axillary: 21. Technique: lateral decubitus position: 44, dorsal decubitus position: 57. Interval between breast and lung cancer: 0–3 years: 24.4%, 3–5 years: 15%, 6–10years: 16.5%, 11–20 years: 28%, &gt;20 years: peak of incidence of lung cancer in the 3 years of diagnosis of breast cancer: 24.4 %. There was no apparent relation between treatment of BC and relative risk of developing lung carcinoma. 2nd peak between 11–20 years: 32 % patients, suggest that RT may increase risk of lung carcinoma (latency period for radiation induced second malignancy).
Conclusion: This study suggest that adjuvant RT is associated with a real but small risk of developing lung carcinoma.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-13-14.
Abstract P4-14-03: Nipple-sparing mastectomy and intra-operative nipple biopsy: To freeze or not to freeze?
Authors: Guth AA , Blechman K , Samra F , Shapiro R , Axelrod D , Choi M , Karp N , Alperovich M 
Published: August 2014

Abstract
Background: Advances in breast cancer screening and treatment have fostered the use of surgical procedures that increasingly optimize cosmetic outcome, while ensuring oncologic safety remains the primary concern of the oncologic surgeon. The role of nipple-sparing mastectomy (NSM) for risk-reducing surgery and breast cancer is evolving. It can be difficult to demonstrate involvement of the nipple-areolar complex (NAC) preoperatively, and and in this report we examine the utility of intraoperative subareolar frozen section (FS).
Methods: Records of patients undergoing NSM at the NYU Langone Medical Center from 2006–2011 were reviewed retrospectively. Use of subareolar FS was at surgeon's discretion.
Results: 237 NSM were performed (146 prophylacytic, 91 theraputic). FC was not utilized in 58 mastectomies (28 prophylactic), with 2 (+) on paraffin. Among the remaining 180 mastectomies, 11 biopsies were (+)(7.2%); 5 subareolar biopsies were (+) on FS and paraffin histologic slides (PS)(2.8%); 6 were negative on FS and (+) on PS. Among the 3 prophylactic NSM with (+) subareolar biopsies there was 1 (+) FS, 1 (−) FS, and 1 with no FS performed. There were no false (+) FS. Four of the 5 patients with (+)FS underwent simultaneous excision of the NAC. The 5th patient had atypia on FS and DCIS on PS, and returned to the OR during the same hospitalization for removal of NAC. The remaining patients underwent subsequent excision of the NAC either during planned 2nd stage reconstruction or following completion of chemotherapy. 8 NAC were free of disease and 5 were positive for in situ or invasive disease. There has been no local recurrence in these patients to date.
Conclusions: The rate of NAC involvement is low, 5.5% in this series, and FS, while utilized in the majority of these cases, detected only 46% of subareolar disease. While FS can direct intraoperative decision making, the predictive power is low, and these considerations must be addressed in preoperative patient discussions. Furthermore, among those patients with (+) subareolar biopsies, only 39% had residual disease on NAC excision. Thus, optimal oncologic management of the NAC must still be considered an unresolved issue.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-14-03.
Abstract P4-14-05: Skin sparing mastectomy – thorough breast tissue removal leads to a low local recurrence rate of breast cancer
Authors: Paily AJ , Drabble EH 
Published: August 2014

Abstract
Introduction: Skin sparing mastectomy (SSM) has the dual advantage of being an acceptable treatment for breast cancer as well as preserving a skin envelope for better aesthesis and cosmesis. However, SSM and immediate breast reconstruction for early breast cancer is not based on level-1 evidence. Even though oncological recurrence is equivalent to that with skin removing mastectomies, most studies have only short term follow-ups. Local Recurrence (LR) or the threat of it is becoming an increasing issue for us as 1 in 4 will succumb from local recurrence. We present local recurrence (LR) and systemic recurrence (SR) rates and the aesthetic results following SSM with or without immediate reconstruction.
Methods and materials: Over a period of 10 years, 249 patients undergoing SSM with or without immediate reconstruction were identified from a prospectively recorded database and complete details of all their treatments and outcomes were assessed. The reconstructive methods employed included Transverse Rectus Abdominus Myocutaneous (TRAM) flap, Latissimus Dorsi (LD) flap in isolation or along with an implant and subpectoral implant insertion. LR and SR rates were determined. Pathological examination of biopsies from the skin flaps after SSM, were also analysed.
Results: Of the 249 patients who underwent SSM, only 34 did not have immediate breast reconstruction. The overall LR and SR rates were 0.4% and 4.4% respectively. 76 patients underwent SSM and TRAM flap reconstruction (1 LR and 5 SR). 33 patients had LD flap reconstruction (no LR and 1 SR). 61 patients were given LD flap reconstruction with implants (no LR and 4 SR). SSM and insertion of sub-pectoral implants was performed on 45 patients (no LR and no SR). 34 patients underwent SSM without immediate reconstruction (no LR, 1 SR). All 249 patients had no evidence of residual breast tissue in subcutaneous flap biopsies. Of the 215 patients who underwent immediate reconstruction, 140 had a good aesthetic result (65%). Individually, TRAM flap and LD flap with implant insertion each produced the best aesthetic result (74%). While reconstructions with LD flaps alone did result in a good aesthetic result in 70% of patients, it also had the poorest aesthetic result (12%) compared to the other three groups.
Conclusion: SSM with or without immediate breast reconstruction performed in our unit has shown a very low rate of LR compared to that in literature. In addition, flap biopsies have shown no residual breast tissue in our patients highlighting that thorough removal of breast tissue at skin sparing mastectomy leads to low LR rates. Our systemic recurrence rates are much higher than local recurrence rates, but are still as expected or slightly lower than expected. Our approach therefore achieves thorough removal of breast tissue and we believe that this leads to a low local recurrence rate, but with good aesthetic results.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-14-05.
Abstract P4-14-06: Contralateral Prophylactic Mastectomy and Survival: Selection Bias or True Survival Benefit?
Authors: Yao Katharine , Du Hongyan , Tomasz Czechura , Winchester David P , Winchester David J , Hou Ningi , Huo Dezheng 
Published: August 2014

Abstract
Withdrawn by Author
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-14-06.