bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P1-06-04: Bisphenol A treatment induces hyperplasia in primary and stem cell-generated mammary glands from pregnant mice
Authors: Bouamar H , Zhang F , Gu X , Dong Q , Sun L-Z 
Published: May 2016

Abstract
Breast cancer is a commonly diagnosed cancer of pregnancy. However, how endogenous and exogenous endocrine factors may contribute to the development of pregnancy-associated mammary tumorigenesis is not clear. There is growing evidence that mammary stem cells (MaSCs) may initiate neoplastic transformation when dysregulated in mouse models. We investigated the effect of the environmental endocrine disruptor bisphenol A (BPA) on mouse mammary gland morphology, epithelial cell composition, pre-neoplastic lesions, and the regenerative function of MaSCs. Pregnant FVB mice with GFP transgene on Day E8.5 were implanted with osmotic pumps that constantly release BPA at 0, 25 or 250 ng/kg/day for 28 days and the mice were euthanized one month after weaning. In agreement with the literature, we observed an abnormality of the morphology of the mammary gland after BPA treatment characterized by higher duct density and abnormal secondary and tertiary branching. Quantification of percent hyperplastic mammary ducts in H&E-stained tissue slides revealed a significant increase of ducts with hyperplastic lesions after BPA treatment, particularly with the low dose. To investigate the effects of BPA treatment on MaSCs, we used enzyme digestion to isolate the CD24hi/CD49f+ luminal epithelial cells (also termed as colony forming cell or CFC) and the CD24+/CD49fhi basal epithelial cells (also termed as mammary repopulating unit or MRU) from mammary gland tissues by FACS and found no significant difference in percent of luminal or basal cell population after BPA treatment. Because the basal cells are enriched with MaSCs that can form mammospheres in suspension culture and subsequently form solid 3D organoids when cultured in Matrigel, we transplanted the solid 3D organoids into cleared mammary fat pads of syngeneic FVB mice and immune-compromised nude mice to examine how BPA treatment might alter MaSC function. Significantly, similar to the results from the primary mammary glands, the regenerated mammary glands by MaSCs from mice treated with the low dose of BPA showed increased duct density, secondary and tertiary branching, and a significantly greater number of hyperplastic lesions. Taken together, our study demonstrated that BPA exposure at very low dose could induce pre-neoplastic lesions in the mammary gland of pregnant mice, apparently by directly targeting MaSCs and implicates BPA as an exogenous endocrine factor that may promote pregnancy-associated mammary tumorigenesis.
Citation Format: Bouamar H, Zhang F, Gu X, Dong Q, Sun L-Z. Bisphenol A treatment induces hyperplasia in primary and stem cell-generated mammary glands from pregnant mice. [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 P1-06-04.
Abstract P1-06-07: Msi1 in maintaining breast cancer stem cell involves the AKT/PI3K pathway
Authors: Nahas GR , Sinha GA , Sherman LS , Walker ND , Rameshwar P 
Published: May 2016

Abstract
Musashi1 (Msi1) was originally described in neural stem cells in a role influencing neural differentiation in the Numb/Notch pathway. Due to its role in neural stem cells, there has been much interest in the role of Msi1 in the breast cancer (BC) stem cell population. In this vein, with we have demonstrated a possible feedback loop between the stem cell marker OCT4 and Msi1, in addition to other stem cell-associated genes. Flow cytometry analyses demonstrated that the subset of BC cells (BCCs) that we previously identified as those with high Oct4 was also enriched for Msi1. Msi1 knockdown BCCs showed decreased doubling time and with limited ability to be passaged, indicating the loss of the self-renewal subset needed for cell passaging. These in vitro findings were consistent with the inability of the Msi1 knockdown BCCs to undergo serial passages in vivo. We therefore examined the Msi1 knockdown BCCs for intracellular proteins that could explain the reduced cell growth and the reduced initiating cells. We selected the AKT/PI3K pathway due to its recent connection to the maintenance of BC stem cells. Msi1 knockdown repressed several molecules within the AKT/PI3K pathway: PTEN, AKT, and PI3K. There were no significant differences found however, in the apoptotic factors, BCL-2 and Caspase-3. Upon further investigation, we observed increases in molecules that are linked to decreased cell proliferation and senescence, p16, p53 and p21. Since Msi1 is an RNA binding protein, it is possible that its loss could leave RNAs for binding to miRNAs and this might be partly responsible for the decrease in key intracellular molecules needed for the survival and proliferation of the Msi1 knockdown BCCs. Further studies are needed to investigate how miRNAs and Msi1 interact to maintain the survival of BCCs. Finally, Msi1 KD positively affects the expression of the immune checkpoint inhibitor PD-1L, suggesting increased PD-1L expression in cells that are not of the CSC phenotype. The studies may identify Msi1 or its associated molecules as a potential therapeutic intervention for BC.
Citation Format: Nahas GR, Sinha GA, Sherman LS, Walker ND, Rameshwar P. Msi1 in maintaining breast cancer stem cell involves the AKT/PI3K pathway. [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 P1-06-07.
Abstract P1-07-10: Increasing population rates of in-situ breast cancer [DCIS] are associated with reduced breast cancer (BrCa) mortality. A case for screening mammography and "overdiagnosis" linked to outcome benefits
Authors: Ragaz J , Qian H , Shakeraneh S , Fox J , Wilson KS , Simpson JS , Yoon J-Y , Wong H 
Published: May 2016

Abstract
INTRODUCTION:
Following the first phase of this project [Ref 1], we correlate here the rates of DCIS with BrCaMOR, in two regions of Canada - British Columbia [BC] and Atlantic Provinces [Atl.P].
We previously reported higher compliance in screening mammography [ScreenMam] and therapeutic [TH*] guidelines [GUIDELINES] for both DCIS and invasive BrCa in BC compared with Atl.P [Ref. 2].
METHODS: Annual age-specific rates [cases / 100,000 population] of DCIS, and BrCaMOR between BC vs Atl.P, were obtained for 17 age groups of 5 years (years 0-4 to 85+) and averaged each 5-year period from 1975-1979 up to 2005-2009. To compare age distribution, DCIS rates and BrCaMOR between the two regions, we selected four birth cohorts, age 30-34, 35-39, 40-44 and 45-49 in 1975-1979. From those, we tabulated the DCIS incidence and BrCaMOR for each birth cohort when they reached ages 50-54 and 60-64. We assumed that the rates of DCIS reflect annual ScreenMam practices.
Data were obtained from the Public Health Agency of Canada based on the Canadian Cancer Registry database at Statistics Canada.
RESULTS [N/100,000 population]British ColumbiaAtlantic ProvincesAge / years DCISBrCaMORDCISBrCaMORAge 50 â– 54 1980-8413.152.24.056.41985-8921.246.68.056.11990â–9429.244.421.449.91995â–9945.543.830.050.1Age 60â – 64 1990-9428.072.123.186.21995-9949.361.935.276.62000-0449.365.845.669.42005â–0951.453.141.059.4
CONCLUSIONS:
1. Our study shows across all age cohorts higher rates of DCIS and lower BrCaMOR in BC compared to Atl.P - results consistent with higher ScreenMam rates in BC than Atl.P.
2. These data are compatible with the concept that a higher diagnostic rate for early lesions such as DCIS [i.e. frequently designated as "Overdiagnosis"] by ScreenMam, and subsequent earlier Guideline TH*, contributes to lower BrCaMOR.
*TH Guidelines: surgery, radiation, Tamoxifen for DCIS; and the same + chemotherapy for early invasive disease.
Citation Format: Ragaz J, Qian H, Shakeraneh S, Fox J, Wilson KS, Simpson JS, Yoon J-Y, Wong H. Increasing population rates of in-situ breast cancer [DCIS] are associated with reduced breast cancer (BrCa) mortality. A case for screening mammography and "overdiagnosis" linked to outcome benefits. [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 P1-07-10.
References:
1. J. Ragaz, H. Wong, H. Qian, J.Fox, K. Wilson, A. Coldman: Cancer Research, May 1, 2015 75; P3-07-28
2. J. Ragaz, H. Wong, H. Qian: Cancer Research Feb 2010; 69(24 Supplement):2063-2063.
Abstract P1-07-17: Breast cancer presentation in the over 70s
Authors: Murray J , Smith L , Lannigan A 
Published: May 2016

Abstract
Aims:
Life expectancy of the population in rising, and the risk of breast cancer increases with age. Older patients with breast cancer generally present later with more advanced disease for a variety of factors. We aimed to explore the presentation of the over 70s with breast cancer, along with their attitudes towards screening.
Methods:
A questionnaire was sent to patients aged over 70 at the time of their breast cancer surgery within the three hospitals across NHS Lanarkshire. This detailed reasons and timing of presentation, in addition to thoughts about screening.
Results:
Three hundred and fifty-two questionnaires were sent to women with a mean age of 76 years, 230 were returned (65%). Sixty-four percent routinely examined their breasts with more identifying a lump themselves (70%). Knowledge of signs and symptoms beyond a lump was explored, explicitly asking about nipple inversion, nipple discharge and skin changes with all three having similar degrees of awareness (40%, 35%, 25% respectively). Distressingly only 36% of our patients were aware of any of these signs, with only 9% being aware of all three. The majority of women sought medical attention early after identifying a problem, with 39% seeing someone within days and only 6% waiting over 6 months. Personal concern was the greatest prompt for women to see a doctor (68%) followed by family or friend concern (10%). With regard to screening, 83% routinely attended screening when they were invited. Ninety percent also said they would attend if the service was routinely offered to the over 70s. Although the majority (60%) were not aware that they could opt into the screening service once over 70.
Conclusions:
Despite the belief that most older women are felt to be less breast aware than younger most of our patients routinely examined themselves and identified the pathology, before promptly seeking medical advice (70% within weeks). This is the case despite most women having no knowledge of other signs and symptoms of breast cancer. Our cohort have also shown that they are keen to continue screening over the age of 70 if it was routinely offered.
Citation Format: Murray J, Smith L, Lannigan A. Breast cancer presentation in the over 70s. [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 P1-07-17.
Abstract P1-07-23: Prognostic impact of HER2 overexpression/amplification in women with pT1a N0 M0 breast cancer with known screening status: Results from a multicenter population-based cancer registry study
Authors: Musolino A , Michiara M , Boggiani D , Sikokis A , Rimanti A , Pellegrino B , Silini EM , Campanini N , Barbieri E , Sgargi P , Falcini F , Pinto C 
Published: May 2016

Abstract
Introduction: Outcomes for women with pT1aN0M0 breast cancers (BC) may vary by biologic subtype. A higher proportion of HER2-positive BCs diagnosed in the interval between scheduled screening rounds has been proposed to account for the more aggressive behaviour of interval cancers (IC) compared with screen-detected (SD) tumors. No data are available on the prognostic role of HER2-positive status in a general population of pT1aN0M0 breast tumors with known screening status.
Methods: All incident pT1aN0M0 BCs (n=874), systematically collected by the Cancer Registries of Emilia Romagna Region (northern Italy) and diagnosed in women aged 50-69 from 2003 to 2009 were evaluated. Screening status was ascertained by reference to the Emilia Romagna Breast Cancer Screening Program (ERBSP) database. Patients unexposed to screening, with HER2 unknown primary tumor and/or who received adjuvant chemotherapy or trastuzumab were excluded from analysis.
Results: Twenty percent of patients had HER2-positive tumors. Fifty-three percent of the entire study population were SD cancers, while 18% were ICs. Tumors with high histologic grade, high proliferative rate, negative estrogen receptor status, or HER2-positive status were more likely to be diagnosed in the interval between screening. At a median follow-up of 84 months, the 5-year invasive disease-free survival (IDFS) rates were 89% and 95% in patients with HER2-positive and HER2-negative tumors, respectively (P = 0.025). Notably, HER2-positive ICs showed poorer IDFS than HER2-positive SD tumors (84% vs. 95%, respectively; P = 0.04). No difference in IDFS rates were observed between HER2-positive SD cancers and HER2-negative SD cancers. Multivariable analysis of candidate prognostic factors for IDFS will be reported.
Conclusions: In a general population of pT1aN0M0 early BCs with known screening status, IC detection may identify patients with HER2-positive pT1aN0M0 tumors in whom the rate of recurrence justifies consideration for systemic, anti-HER2, adjuvant therapy.
Citation Format: Musolino A, Michiara M, Boggiani D, Sikokis A, Rimanti A, Pellegrino B, Silini EM, Campanini N, Barbieri E, Sgargi P, Falcini F, Pinto C. Prognostic impact of HER2 overexpression/amplification in women with pT1a N0 M0 breast cancer with known screening status: Results from a multicenter population-based cancer registry study. [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 P1-07-23.
Abstract P1-08-03: Association analysis of single-nucleotide polymorphisms in FANCD2-DNA damage repair pathway genes with breast cancer risk
Authors: Chen F , Tang L , Huang J 
Published: May 2016

Abstract
Purpose: The aim of the study was to estimate breast cancer risk conferred by individual single-nucleotide polymorphisms (SNPs) of breast cancer susceptibility genes in the monoubiquitinated FANCD2–DNA damage repair pathway.
Methods: We selected 48 tagging SNPs (tSNPs) from eight breast cancer susceptibility genes (TP53,PTEN,NBS1,BRIP1,PALB2,ATM,CHEK2 and RAD50) involved in the monoubiquitinated FANCD2–DNA damage repair pathway.The 48 tSNPs were genetyped by SNPscan in 734 women with breast cancer(534 sporadic cases and 200 early-onset and familial cases) and 672 sex- and age-matched healthy controls from Hunan and Sichuan Province of China.The odds ratio were calculated by logistic regression analysis under co-dominant model ,dominant model and recessive model respectively.
Results: Forty-five tSNPs were successfully genotyped by SNPscan, and the call rates for each tSNP were above 98.9%. We found that 13 tSNPs of five genes (PALB2, TP53, NBS1, PTEN, and BRIP1) were significantly associated with breast cancer risk. A total of five tSNPs (rs2299941 of PTEN, rs2735385, rs6999227, rs1805812, and rs1061302 of NBS1) were tightly associated with breast cancer risk in sporadic cases, and five other tSNPs (rs1042522 of TP53, rs2735343 of PTEN, rs7220719, rs16945628, and rs11871753 of BRIP1) were tightly associated with breast cancer risk in early-onset and familial cases. We have not found significant tSNPs in the other three genes (ATM, RAD50, and CHEK2).Three tSNPs of TP53(rs12951053, rs1042522 and rs8064946),three tSNPs of BRIP1(rs16945628, rs7220719 and rs11871753) and rs2735343 of PTEN can significantly increase the risk of breast cancer,and most of these were under the analysis of early-onset and familial cases.Four tSNPs of NBS1(rs2735385, rs6999227, rs1805812 and rs1061302),rs2299941 of PTEN and rs513313 of PALB2 can significantly decrease the risk of breast cancer,and most of these were under the analysis of sporadic cases.
Conclusions: Some of the tSNPs of five breast cancer susceptibility genes (PALB2, TP53, NBS1, PTEN, and BRIP1) involved in the monoubiquitinated FANCD2–DNA damage repair pathway were significantly associated with breast cancer risk in women from Hunan and Sichuan Province of China.Some locuses can increase breast cancer risk,and others can decrease breast cancer risk.But the majority of the tSNPs are located in the intron domain and their functions are unknown, so larger studies are needed to research the functions of these genes further.
Citation Format: Chen F, Tang L, Huang J. Association analysis of single-nucleotide polymorphisms in FANCD2-DNA damage repair pathway genes with breast cancer risk. [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 P1-08-03.
Abstract P1-08-08: Heterozygous germline mutations in RAD50 among Korean patients with high-risk breast cancer negative for BRCA1/2 mutation
Authors: Kim H , Cho D-Y , Choi DH , Jung GH , Shin I , Park W , Huh SJ , Nam SJ , Lee JE , Gil WH , Kim SW 
Published: May 2016

Abstract
Background: The MRE11-RAD50-nibrin (MRN) complex participates in pathways of double-strand break induced DNA repair and cell cycle checkpoint control. RAD50 interacts with the MRE11 and NBS proteins, is involved in the maintenance of genomic integrity. The association of RAD50 mutation and breast cancer susceptibility has been reported in European patients. However, the impact of RAD50 mutation on a breast cancer predisposition among Koreans remains uncertain. In the current analysis, we evaluated the incidence of RAD50 mutations among Korean patients with non-BRCA1/2 high-risk breast cancer.
Materials and Methods: A total of 247 Korean patients with high-risk breast cancer who tested negative for BRCA1/2 mutation were enrolled. The criteria for high-risk breast cancer were as follows: having a family history of breast or ovarian cancer in any relative; diagnosed at age 40 years or younger; bilateral breast cancer; and male breast cancer. All participants were screened for BRCA1/2 mutations using fluorescent-conformation sensitive capillary electrophoresis (F-CSCE) and traditional sequencing. The entire RAD50 gene of each patient was sequenced using F-CSCE. In silico analyses of the RAD50 variants was performed using PolyPhen-2 and SIFT.
Results: There were two novel deleterious mutations in RAD50 (p.Q426X, p.E1271del). These mutations were found in two patients, including one with p.Q426X and the other with p.E1271del. Besides, five sequence variants in RAD50 were identified: four exonic variants (p.I118T, p.R486C, p.L1264F, and p.R1279H) and one intronic variant (c.1246-11T&gt;C). Among the four missense variants, p.R486C and p.L1264F were variants predicted to be deleterious by in silico analyses.
Conclusions: We found protein-truncating mutations in RAD50 gene in a small proportion of Korean patients with high-risk breast cancer. The contribution of the mutation to the development of breast cancer should be clarified in further researches.
Citation Format: Kim H, Cho D-Y, Choi DH, Jung GH, Shin I, Park W, Huh SJ, Nam SJ, Lee JE, Gil WH, Kim SW. Heterozygous germline mutations in RAD50 among Korean patients with high-risk breast cancer negative for BRCA1/2 mutation. [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 P1-08-08.
Abstract P1-10-19: Skin, and nail, infections associated with the addition of pertuzumab to trastuzumab-based chemotherapy
Authors: Mortimer JE , Yuan Y , Jung J , Kruper L , Stewart D , Chung S , Yu WK , Mendelsohn M , D'Apuzzo M , Tegtmeier B , Dadwal S 
Published: May 2016

Abstract
Objectives: We have maintained a local registry of skin and nail infections in patients receiving pertuzumab and trastuzumab as treatment for HER2 positive breast cancer. Over the past 16 months, we have continued to observe an increase in infectious complications in patients receiving the combination of pertuzumab and trastuzumab with or without chemotherapy. We expand a series of prospectively identified patients who developed infections while on these regimens. Methods: We became concerned about an increased incidence of infections shortly after the FDA approval of pertuzumab, and created an IRB approved registry of these patients. Results: Twenty-eight women were identified to have 32 separate infections (often at more than one site); 9 after cycle 1; 6 after cycle 2, 9 after cycle 3 and 8 after 4 or more cycles. The median age was 51 (Range 25-67); 14 received pertuzumab, trastuzumab, carboplatin, and docetaxel (PTCH), 5 pertuzumab, trastuzumab, and docetaxel, 7 pertuzumab, trastuzumab, and nab-paclitaxel, and 2 pertuzumab and trastuzumab. Folliculitis of the scalp, abdomen, and/or buttocks was observed in 19 patients, abscesses in 8 patients (4 of whom required incision and drainage) and cellulitis in 2. Severe paronychial infections involving one to 16 digits were observed in 4; 2 pt required surgical removal of 2 nails. Quantitative immunoglobulins were found to be low in 8 of 17 women tested; 2 patient had low total protein but did not have an assessment of quantitative immunoglobulins. All patients were initially treated with oral antibiotics, and 6 required hospitalization. Cultures were obtained in 10 patients; Staphylococcus aureus was identified in 4, methicillin resistant Staphylococcus aureus (MRSA) in 5, Enterococcus faecalis in 1. A 57 year old pt receiving neoadjuvant PTCH died on cycle 2 day 7. Autopsy was consistent with sepsis and gram positive cocci were identified. A 62 year old became septic and developed renal failure. Skin biopsies were performed in 3 patients and are consistent with changes associated with EGFR inhibition.
Conclusions: We believe these infections are a result of combining pertuzumab with trastuzumab as 2 pts received no concurrent chemotherapy. An awareness of this complication is critical as some infections may be life-threatening. We have initiated patient education to ensure awareness of this potential complication.
Citation Format: Mortimer JE, Yuan Y, Jung J, Kruper L, Stewart D, Chung S, Yu WK, Mendelsohn M, D'Apuzzo M, Tegtmeier B, Dadwal S. Skin, and nail, infections associated with the addition of pertuzumab to trastuzumab-based chemotherapy. [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 P1-10-19.