bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P1-06-02: A force-sensitive organoid assay to quantify regenerative potential of single primary human mammary cells
Authors: Scheel CH , Linnemann JR , Miura H , Meixner LK , Irmler M , Kloos UJ , Hirschi B , Bartsch HS , Sass S , Beckers J , Theis FJ , Gabka C , Sotlar K 
Published: May 2016

Abstract
We have developed an organoid regeneration assay to quantify the ability of freshly isolated, single human mammary epithelial cells to generate complex branched ductal structures with basal and luminal features.
For this purpose, cells are cultured in adherent or floating collagen gels, corresponding to a rigid or compliant matrix. In both conditions, single luminal progenitors form spheres, whereas basal cells generate branched ductal structures. In compliant but not rigid collagen gels, branching ducts in multicellular structures generated by basal cells develop a lumen and alveoli at their tips. Importantly, branched structures generated by single basal cells express basal and luminal markers at correct positions, thereby demonstrating bi-potential. Functionally, basal cells in branched structures display cellular contractility, which we reveal to be required for alveologenesis. In conclusion, branched structures generated by single basal cells in compliant collagen gels resemble terminal ductal-lobular units (TDLU), the functional units of the mammary gland.
To prospectively isolate basal cells with regenerative potential, we added the membrane metallo-endopeptidase CD10 as a cell surface marker to existing sorting protocols, thereby enriching for TDLU-formation and enabling rigorous quantification of regenerative potential by extreme limiting dilution assay (ELDA). Moreover, the use of CD10 as a cell surface marker reveals the presence of stromal cells with endothelial qualities within the CD49fhi/EpCAM– population, previously labeled basal. In summary, we describe a defined in vitro assay system to quantify primary human mammary epithelial cells with regenerative potential and systematically investigate their interaction with the physical environment at distinct steps of morphogenesis.
Citation Format: Scheel CH, Linnemann JR, Miura H, Meixner LK, Irmler M, Kloos UJ, Hirschi B, Bartsch HS, Sass S, Beckers J, Theis FJ, Gabka C, Sotlar K. A force-sensitive organoid assay to quantify regenerative potential of single primary human mammary cells. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-06-02.
Abstract P1-06-08: Stem cell markers CD44+CD24- and ALDH1 in primary breast cancers and metastatic sentinel and non-sentinel lymph nodes
Authors: Kim W , Kim Y-M , Kim W , Lee J-S 
Published: May 2016

Abstract
Background and Aim
Studies of Aldehyde dehydrogenase 1 (ALDH-1) and CD44+/24- have suggested them as cancer stem cell (CSC) markers in breast cancers and the clinicopathologic and prognostic significance of these CSC markers have been widely investigated. However, expressions of CSC in metastatic axillary lymph nodes (ALN) of breast cancers have not yet been the center of interest. Therefore, the object of this study is to explore breast CSC markers CD44+CD24- and ALDH-1 in the primary breast tumor and metastatic ALNs by retrospectively analyzing the CSC expressions on metastatic tumor cells within ALN.
Method
180 surgically resected breast cancers were selected and among them 165 cases had undergone sentinel lymph node (SLN) with or without non-sentinel lymph node (NSLN) dissections. 50 SLNs (30.3%) and 43 NSLNs (30.9%) had metastatic tumor cells and total of 74 cases were involved with axillary lymph node metastasis. Double immunohistochemistry of CD44/CD24 and single immunohistochemical staining of ALDH-1 were applied on paraffin embedded breast tissue specimens and lymph node specimens to evaluate the CSC phenotypes of primary tumor and metastatic lymph nodes.
Results
The prevalence of CD44+/CD24- and ALDH-1(+) tumor cells in primary breast cancer was 76.7% and 45.0%. In triple negative breast cancers (TNBC) contained significantly higher percentage (49.2%) of ALDH-1 positive tumor cells (p=0.001). CD44+/CD24- phenotype was present in 65.2% and 40.0% in metastatic SLNs and NSLNs, respectively. The analysis of metastatic sentinel lymph nodes and breast cancers with CSCs indicated that there are significant relationships with ALDH-1(+) (p&lt;0.001) and CD44+/CD24- (p&lt;0.001) phenotypes. CSC expression in metastatic NSLNs and breast tumors also showed significant association (p=0.001). However, CSCs in metastatic SLNs and NSLNs did not show any significant relationships to the intrinsic molecular subtypes.
Conclusions
This study investigated the impact of the stem/progenitor phenotype defined by CD44 positivity/CD24 negativity and ALDH-1 positivity in sentinel lymph nodes (SLN) on non-sentinel lymph node (NSLN) metastases. CSC phenotypes expressed in metastatic SLNs and NSLNs, independently showed significant association with the primary breast tumors. However, in future, the authors recommend that the exploration of a much larger study including a vast amount of pool will provide a more reliable result.
Citation Format: Kim W, Kim Y-M, Kim W, Lee J-S. Stem cell markers CD44+CD24- and ALDH1 in primary breast cancers and metastatic sentinel and non-sentinel lymph nodes. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-06-08.
Abstract P1-07-18: Breast cancer in young patients, twelve years of experience in a single institution
Authors: Morante ZD , Pacheco C , Limón RS , Neciosup S , Gomez HL 
Published: May 2016

Abstract
Breast cancer is very rare in young women and has a more aggressive biological behavior and a worse prognosis than in older premenopausal women. This study was designed to determine and evaluate the features of breast cancer in young patients less than 35 years old at the Instituto Nacional de Enfermedades Neoplásicas, Lima - Perú.
Medical records of 115 patients less than 35 years old with breast cancer, whom were diagnosed and received a kind of treatment, even surgery, chemotherapy, radiotherapy or all of them at the Instituto Nacional de Enfermedades Neoplásicas Lima-Perú, between January 2000 and December 2012, were reviewed.
Triple negative breast cancer (38.3%) is the most common subtype cancer and its presentation is in a lower age compared with the others subtypes (27.1 years vs 28.5 years p: 0.047). The high histological grade was more frequent in triple negative and HER2 subtypes (80% both vs 30% and 48% for luminal A and luminal B p: 0.001). The 2 yr and 5 yr overall survival was 75.0% and 59.3% for luminal A, 71.4% and 55.1% luminal B, 67.7% and 54.9% triple negative, 58.3% and 41.7% HER2 (p: 0.434). The 2 yr progression free survival was 81.6%, 72.6%, 61.5% and 59.4% for each group respectively (p: 0.522).
As conclusion, the breast cancer in 35 yr old or less women is uncommon; the triple negative subtype is more common, also in relation with high histological grade and in lower age. The overall survival and the progression free survival are worse in patients with lower age.
Citation Format: Morante ZD, Pacheco C, Limón RS, Neciosup S, Gomez HL. Breast cancer in young patients, twelve years of experience in a single institution. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-07-18.
Abstract P1-07-22: Infectious disease hospitalization in breast cancer patients: Risk and impact on prognosis
Authors: Brand JS , Colzani E , Johansson A , Giesecke J , Clements M , Bergh J , Hall P , Czene K 
Published: May 2016

Abstract
Background: Infection-related hospitalizations are a serious complication in breast cancer patients, resulting in treatment delay, prolonged hospitalization and future morbidity and mortality. Little, however, is known about the actual risk, clinical characteristics and outcomes of infection-related hospitalizations in this patient population.
Methods: We conducted a prospective population-based study including 7071 women diagnosed with primary invasive non-metastatic breast cancer between 2001 and 2008 in the Stockholm-Gotland region (Sweden), with complete follow-up until 2010. Standardized incidence ratios (SIRs) for infection-related hospitalizations (overall and by site) were estimated using background rates from the general female population, matched on age and calendar period. Associations with clinical characteristics and breast cancer outcomes (breast cancer death, distant metastasis and locoregional recurrence) were analysed using flexible parametric survival models.
Results: During a medium follow-up of 5.3 years, 657 hospital admissions with infections were observed and 1,2 and 5-year cumulative risks were 3.4, 4.7 and 8.1% respectively. Rates of infection-related hospitalizations were increased compared to the general female population (SIR = 2.12; 95% CI = 1.96-2.29) and site-specific SIRs were most pronounced for sepsis (SIR = 3.65; 95% CI = 3.13-4.26) and skin infections (SIR = 2.93; 95% CI = 2.35-3.64). The overall risk of infections was highest during the first year (SIR = 5.06; 95% CI, 4.46-5.74), and recurrent disease contributed to the long-term risk observed. Older age at diagnosis, chemotherapy, axillary radiotherapy, comorbidities and markers of tumor aggressiveness (large tumors, estrogen receptor negative tumors and lymph node positive tumors) were independent predictors of infectious disease risk. Analyses evaluating the prognostic impact of infections revealed an independent effect on breast cancer death and distant metastasis, associations that were mainly driven by sepsis (HR = 4.53; 95% CI, 3.25-6.33 and 1.69; 95% CI, 1.04-2.79 respectively). No association was found with future risk of locoregional recurrence.
Conclusions: Physicians and patients should be aware of the risk of serious infections which persists beyond the initial treatment period. Infection-related hospitalizations are an independent marker of poor prognosis. Further research is needed to elucidate the role of sepsis in breast cancer progression.
Citation Format: Brand JS, Colzani E, Johansson A, Giesecke J, Clements M, Bergh J, Hall P, Czene K. Infectious disease hospitalization in breast cancer patients: Risk and impact on prognosis. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-07-22.
Abstract P1-07-26: Marital status and overall mortality in breast cancer patients: Differences by socioeconomic status and race/ethnicity
Authors: Martinez ME , Anderson K , Schwab R , Hurley S , Canchola AJ , Keegan THM , Cheng I , Clarke C , Glaser S , Gomez SL 
Published: May 2016

Abstract
Background: Results of several studies show that married cancer patients have lower mortality than unmarried patients. However, data on differences by race/ethnicity are lacking. We assessed the risk of overall mortality associated with marital status among patients with breast cancer according to neighborhood socioeconomic status (SES) and race/ethnicity.
Methods: We used data from the population-based California Cancer Registry to include breast cancer cases diagnosed between 2000 and 2009 with follow-up through December 31, 2012 and identified 175,154 women with invasive breast cancer. We estimated hazard rate ratios (HR) and 95% confidence intervals (CI) for overall mortality by neighborhood SES and race/ethnicity.
Results: Among all cases, 42.6% were unmarried at the time of diagnosis. In adjusted models, the HR for all-cause mortality (95% CI) for unmarried compared to married women was 1.20 (1.17-1.22). There was no significant difference by SES. However, significant variation was observed by race/ethnicity. The HRs (95% CI) were 1.23 (1.20-1.26), 1.20 (1.11-1.30), 1.12 (1.04-1.21), and 1.05 (0.99-1.11) for NH Whites, NH Asians/Pacific Islanders (API), NH Blacks, and Hispanics, respectively. Among API subgroups, Chinese (HR=1.35; 95% CI, 1.12-1.62) and Filipinas (HR=1.25; 95% CI, 1.09-1.44) were the only groups with significantly higher risk of total mortality associated with unmarried status.
Conclusions: Our results show that not being married at the time of breast cancer diagnosis is associated with worse overall survival compared to being married. Significant variation in risk of mortality was shown by race/ethnicity but not by neighborhood SES. Targeted, culturally-appropriate interventions to support unmarried breast cancer patients through their cancer treatment and survivorship need to be developed to improve their survival.
Citation Format: Martinez ME, Anderson K, Schwab R, Hurley S, Canchola AJ, Keegan THM, Cheng I, Clarke C, Glaser S, Gomez SL. Marital status and overall mortality in breast cancer patients: Differences by socioeconomic status and race/ethnicity. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-07-26.
Abstract P1-08-04: Sources of polycyclic aromatic hydrocarbons associated with gene-specific promoter methylation in women with breast cancer
Authors: White AJ , Chen J , McCullough LE , Xu X , Cho YH , Conway K , Beyea J , Stellman SD , Steck SE , Mordukhovich I , Eng SM , Terry MB , Engel LS , Hatch M , Neugut AI , Hibshoosh H , Santella RM , Gammon MD 
Published: May 2016

Abstract
Tobacco smoke, diet, and indoor and outdoor air pollution, all major sources of polycyclic aromatic hydrocarbons (PAHs), have been associated with breast cancer incidence. Aberrant methylation may be an early event in carcinogenesis, but whether PAHs influence the epigenome is unclear. Few studies have evaluated whether PAHs are associated with methylation, particularly in breast tumors where methylation changes are particularly relevant. In a population-based case-control study, we measured promoter methylation of 13 breast cancer-related genes in breast tumor tissue (n=765-851 cases) and global methylation in peripheral blood (1,055 cases/1,101 controls). PAH sources (current active smoking, residential environmental tobacco smoke (ETS), vehicular traffic, synthetic log burning, and grilled/smoked meat intake) were evaluated separately. Logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). When comparing methylated versus unmethylated genes, synthetic log use was associated with increased ORs for CDH1 (OR=2.28, 95%CI=1.07-4.83), HIN1 (OR=2.11, 95%CI=1.32-3.38) and RARβ methylation (OR=1.82, 95%CI=1.18-2.83) and decreased ORs for BRCA1 methylation (OR=0.44, 95%CI=0.30-0.65). Residential ETS was associated with decreased ORs for ESR1 (OR=0.74, 95%CI=0.56-0.99) and CCND2 methylation (OR=0.65, 95%CI=0.44-0.96). Current smoking and vehicular traffic were associated with decreased ORs for DAPK (OR=0.53, 95%CI=0.28-0.99) and increased ORs for TWIST1 methylation (OR=2.79, 95%CI=1.24-6.30), respectively. In controls, synthetic log use was inversely associated with LINE-1 methylation (OR=0.60, 95%CI=0.42-0.87). PAH sources were associated with hypo- and hypermethylation at multiple promoter regions in breast tumors and LINE-1 hypomethylation in blood of controls. Methylation may be a potential biologic mechanism for the association between PAHs and breast cancer incidence.
Citation Format: White AJ, Chen J, McCullough LE, Xu X, Cho YH, Conway K, Beyea J, Stellman SD, Steck SE, Mordukhovich I, Eng SM, Terry MB, Engel LS, Hatch M, Neugut AI, Hibshoosh H, Santella RM, Gammon MD. Sources of polycyclic aromatic hydrocarbons associated with gene-specific promoter methylation in women with breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-08-04.
Abstract P1-08-07: Predisposing germline mutations in a clinic based breast cancer (BC) population
Authors: Garber JE , Tung NM , Elkin EP , Allen BA , Singh NU , Wenstrup R , Hartman A-R , Winer EP , Lin NU 
Published: May 2016

Abstract
Background: Evaluation of women with BC for germline mutations associated with hereditary breast and ovarian cancer (HBOC) has become increasingly common due to its impact on management. Guidelines for genetic evaluation indicate testing for cases with early onset, triple negative disease or family cancer history. However, the majority of breast cancer occurs in patients without these high risk characteristics. The prevalence of mutations associated with HBOC has not been well characterized in this population.
Methods: We performed a cross sectional study using DNA from blood samples from consecutive new invasive BC patients seen at the Dana-Farber Cancer Institute (01/01/2010 to 07/31/2102) who consented to research. Subjects were otherwise unselected. Mutations in 25 cancer genes were identified using a next generation sequencing based panel. Germline sequence variations and large rearrangements were classified for pathogenicity.
Results: 456 samples from eligible subjects were included. The mean age of BC diagnosis was 50 years. Mutations were found in 51 women, 49 of which were associated with breast cancer (10.8%, 95% CI 8.1-14.0). BRCA1/2 mutations were found in 6.6% [95% CI 4.5-9.2%] while mutations in other BC-associated genes were found in 4.4% [95% CI 2.7-6.7%], particularly CHEK2 (2.2%, 95% CI 1.1, 4.0). Of the 49 women with BC-related mutations, 21 (43%) had BC diagnosed after age 45. In univariate analyses, age at diagnosis, Ashkenazi Jewish ancestry, triple negative histology and family BC/ovarian cancer (OC) history were associated with BRCA1/2 mutations, but no factors were significantly associated with mutations in other genes. Among 261 women with no FDR/SDR with BC/OC, 26 (10.0%) had a mutation. Nineteen mutations (10 BRCA1/2) were found in the 256 women (7.4%) who had not had previous genetic testing.
Conclusions: In a single academic institution, 11% of new breast cancer patients had a germline mutation in a breast cancer predisposition gene: 6.6% were in BRCA1/2. The elevated prevalence compared to population-based series may reflect the practice composition of academic centers, which often attract women younger at BC diagnosis. In an academic practice with an active cancer genetics program, 10 women with BRCA1/2 and 9 with other mutations had not had genetic testing. Expanded testing identifies additional predisposing mutations, the utility of which are being defined for the care of breast cancer patients and their families.
Citation Format: Garber JE, Tung NM, Elkin EP, Allen BA, Singh NU, Wenstrup R, Hartman A-R, Winer EP, Lin NU. Predisposing germline mutations in a clinic based breast cancer (BC) population. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-08-07.
Abstract P1-09-02: Higher incidence of second cancers in African American (AA) patients compared to Caucasian patients with a primary breast cancer
Authors: Diab N , Clark G , Hamlington B , Brzeskiewicz L , Langer L , Diab S 
Published: May 2016

Abstract
Background: AA women with breast cancer have lower survival rates compared to Caucasian women. Since this lower survival rate may be related to genetic mutations, and environmental/socioeconomically factors, we hypothesize that the same factors may lead to a higher risk of secondary cancers after an initial diagnosis of breast cancer.
Method: Analysis of the Surveillance, Epidemiology, and End Results (SEER) Program data using Multiple Primary - Standardized Incidence Ratio parameters. The incidence of second cancer diagnoses in AA and Caucasian women previously diagnosed with breast was compared to the incidence of cancer in the general population matched by age, race, and year of diagnosis. Results are reported as the observed risk divided by the expected risk (O/E).
Results: For the 43,688 AA pts, the overall O/E and excess risks were 1.48 and 51.2 compared to 1.11 and 14.7 for the 428,103 Caucasian patients. The mean ages of diagnoses of initial breast cancer diagnosis and second cancer were 57.2 and 65 years for AA patients compared to 61.8 and 70.2 years for Caucasian patients. The following is a summary of statically significant (p &lt;0.05) selected O/E by the site of second cancer :
O/E for AA and white by site of second cancerSiteAAWhiteOral Cavity and Pharynx1.651.41Digestive System1.181Respiratory System1.271.13Skin excluding Basal and Squamous1.931.33Breast1.671.18Female Genital System1.110.95Urinary System1.561.18Endocrine System1.521.38All Lymphatic and Hematopoietic Diseases1.261.05
This higher risk of second cancers occurred despite the lower relative survival rate for AA compared to Caucasian patients with a 5-year relative survival rate of 68.6% for AA and 78.3% for Caucasian patients.
Conclusions: To our knowledge, this is the first report of the incidence of second cancers in AA patients with breast cancer compared to caucasian. More research to understand the biological, genetic, therapeutic, and environmental factors leading to this higher risk of second cancers is warranted.
Citation Format: Diab N, Clark G, Hamlington B, Brzeskiewicz L, Langer L, Diab S. Higher incidence of second cancers in African American (AA) patients compared to Caucasian patients with a primary breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-09-02.