bluuebunny/crossref_metadata_2025_split huggingface dataset:
EGFR/K-ras mutations in lung adenocarcinoma and atypical adenomatous hyperplasia (AAH)
Authors: Matsumoto S. , Takuwa T. , Kondo N. , Okumura Y. , Fukuoka K. , Nakano T. , Hasegawa S. , Tanaka F. 
Published: March 2020

21074 Background: Mutations in the epidermal growth factor receptor (EGFR) gene and k-ras gene are found in 10–30% of non-small cell lung cancer, and are useful to predict the efficacy of EGFR-tyrosine kinase inhibitors. Such mutations are also onco- developmentally important especially in lung adenocarcinoma, but the exact incidences of such mutations in adenocarcinoma/AAH and surrounding normal lung. Methods: A total of 45 consecutive patients with lung adenocarcinoma and/or AAH (18 females; mean age, 65 years) who received thoracotomy from August 2005 through December 2006. In each case, EGFR/k-ras mutations were examined in specimens cut from adenocarcinoma/AAH and normal lung; in the present study, pure bronchioalveolar carcinoma (BAC) was reviewed separately from adenocarcinoma. Results: As 12 (27%) of all 45 patients had multiple adenocarcinoma/BAC/AAH lesions, mutations were examined in 59 lesions (41 adenocarcinomas, 7 BACs, 11 AAHs) and 45 normal lung tissues. EGFR and k-ras mutations were documented in 37% (15/41) and 2% (1/41) of adenocarcinomas, and no EGFR/k-ras mutation was documented in any BAC, AAH, or normal lung tissue. Next, clinical characteristics of patients were compared between patients with solitary adenocarcionma/BAC/AAH lesion and those with multiple lesions; non-smoker were more frequently documented in multiple-lesions group (42%) than in solitary-lesion group (15%), and there was no significant difference in other characteristics such as sex and age. Conclusions: EGFR mutation was not documented in non-invasive (BAC) or pre-neoplastic (AAH) lesion in this series, which may suggest that EGFR mutation play a critical role in the development of invasive adenocarcinoma. No significant financial relationships to disclose.
Expression of vascular endothelial growth factor (VEGF), p53 in Molecular breast cancer subtypes of pre-menopausal African-American women
Authors: Ihemelandu C. U. , Leffall L. D. , Naab T. J. , Frederick W. A. 
Published: March 2020

21084 Background: Tumor growth and metastasis have been shown to be dependent on angiogenesis. With the current classification of breast tumors into molecular subtypes with distinct prognosis and response to treatment, we sort to analyze the expression of the angiogenesis markers in molecular subtypes and determine their association with clinicopathologic variables of prognostic significance. Methods: A retrospective analysis of women diagnosed with breast cancer from 1998–2005, who had assessable data for ER, PR, and Her-2/neu status. The molecular subtypes were defined as: luminal A, luminal B, basal-like , and Her-2/neu. Results: All molecular breast cancer subtypes overexpressed VEGF, with no statistically significant difference noted between the subtypes: - luminal A (69.8%) basal-like (71.1%), luminal B (70.0%), Her-2/neu (71.0%) (p=.99). Subtypes differed significantly in expression of p53 (p<.000), with the basal-like and Her-2/neu subtypes more likely to be associated with p53 mutations (51.7%) and (54.1%) respectively. No statistically significant association between p53 protein and increased VEGF expression was noted (p=.176) Statistically significant associations between p53 protein and prognostic factors ER (p<.000), PR (p>.000), histologic grade (p<.000), S-phase fraction (p<.001) were noted. A significant inverse correlation was noted between p53 expression and thrombospodin for the age-group <35 years (rho -.810; p=.003). VEGF showed no significant association with the prognostic factors ER, PR, histologic grade and S-phase fraction. A tendency not reaching statistical significance was found between VEGF and angiogenesis (p=.09). A direct correlation between VEGF and thrombospodin was noted in the age- group < 35 years (rho .800; p=.01). Expression of VEGF and thrombospodin did not correlate with survival outcome; however angiogenesis seemed to correlate with survival outcome. Survival outcome was influenced by molecular subtypes with the basal-like and Her-2/neu subtypes having a poorer outcome (p=.01). Conclusions: VEGF expression is not related to p53 status or survival outcome in molecular breast cancer subtypes of pre-menopausal African-American women. No significant financial relationships to disclose.
VEGF-Trap (V-T) overcomes defects in dendritic cell (DC) differentiation without improvement in antigen-specific immune responses
Authors: Sosman J. A. , Fricke I. , Mirza N. , Dupont J. , Lockhart A. C. , Jackson A. , LaFleur B. , Gabrilovich D. 
Published: March 2020

21087 Background: Induction of antitumor immune responses requires adequate DC function. Well-documented DC defects in cancer mediated through tumor-derived vascular endothelial growth factor (VEGF) may lead to tumor escape and limit efficacy of cancer vaccines. V-T with extracellular domains of VEGFR 1/ 2 coupled to Fc IgG1 binds all VEGF-A isoforms. Methods: To determine if inhibition of VEGF signaling improves immune responses, we evaluated 15 cancer pts treated with V-T (2.0–7.0 mg/kg) IV over 1 hr Q 2 wks on a phase I trial. To evaluate immune parameters, PBMC were collected prior to, days 15, 29, and 57 of V-T treatment. Ligand blockade was achieved in all patients. Mature DCs (myeloid and plasmacytoid subsets), and regulatory T cells (T regs) were characterized by expression pattern of CD11c, CD86, CD40, CCR7, CD83, CD123, CD4, CD25, and GITR. T cell function was assessed by allogeneic mixed leukocyte reaction (MLR) and proliferation to tetanus toxoid, influenza, or PHA. Results: V-T treatment did not affect the presence of the total population of DCs, myeloid or plasmacytoid subsets, or myeloid-derived suppressor cells (MDSC). It significantly increased the proportion of mature DCs expressing CD86, CD40, CD83, and CCR7R (p<0.05) without overall improvement in T cell immunity. At 8 wks, 11 pts had either stable disease (SD) or partial response (PR) to the therapy and 4 pts had progressive disease (PD), both with no significant differences in the proportion of MDSC or total DCs. The proportion of mature DCs was significantly increased in pts with SD and PR (p<0.025), but remained unchanged in PD pts. However, functional tests were similar in both groups. Another subset analysis revealed significant improvement in immune responses in 6 pts who had stable or decrease in the MDSC proportion, but not in 9 pts with increases in MDSC. During V-T treatment, Tregs further increased above baseline in pts (p=0.048). Conclusions: These data demonstrate that inhibition of VEGF signaling improves differentiation of DCs in cancer patients, while alone it was not sufficient to improve immune responses. These data illustrates the multifaceted nature of immune deficiency in cancer pts and points to a need for complex approaches to modulation of immune reactivity. No significant financial relationships to disclose.
Does triple-negative breast cancer (TNBC) have distinct clinicopathologic characteristics and prognostic significance?
Authors: Rhee J. , Oh S. , Oh D. , Im S. , Lee S. , Kim D. , Heo D. , Park I. , Bang Y. , Kim T. 
Published: March 2020

21088 Background: Studies have suggested that TNBC, defined by estrogen receptor-negative, progesterone receptor-negative, and HER2-negative, may represent the subset of breast cancer(BC) with different biologic behavior. Here we investigated the clinicopathologic characteristics of TNBC and its prognostic significance in Korean BC patients. Methods: Patients diagnosed as invasive BC and underwent curative surgery at Seoul National University Hospital between Jan. 2000 and Jun. 2003, were reviewed, retrospectively. We excluded the patients whose immunohistochemistry for hormone receptor nor HER2 status had not been evaluated, and who had been treated with adjuvant trastuzumab or neoadjuvant chemotherapy (CT). Clinicopathologic variables (age, T and N stage, endovascular or lymphatic tumor emboli, nuclear and histologic grade, p53, bcl2, Ki67) and 3 year relapse free survival (3YRFS) rate of TNBC were compared with those of non- TNBC. Results: 1,136 patients were eligible for analysis. The median follow-up was 48.7 months. 341 patients underwent breast conserving surgery followed by adjuvant radiotherapy. 249 patients were TNBC and 62.1% of those were node negative. 86.4% of node negative TNBC, 88.3% of node positive TNBC, 53.9% of node negative non-TNBC, and 90.2% of node positive non-TNBC received adjuvant CT. Compared with non-TNBC, TNBC was correlated with younger age (age<35,14.1% vs. 8.2%, p=0.013), higher nuclear and histologic grade(62.2% vs. 23.6%, p=0.001;60.2% vs. 24.6%, p=0.001, respectively); positive staining for p53 (p=0.001) and higher positivity for Ki67 (p=0.001), suggesting the biologic aggressiveness of TNBC. During the follow-up periods, 17.3% of TNBC were relapsed. In particular, 3YRFS in node negative TNBC and non-TNBC were 86% and 96%, respectively (p<0.001). But, in node positive BC, 3YRFS was not different between TNBC and non-TNBC (80.6% vs. 83%, p=0.99). Conclusions: We confirm that TNBC shows more aggressive clinicopathologic characteristics and in particular, higher relapse in node negative BC. Thus, triple-negativity(TN) may be integrated into risk factor analysis in node negative BC. Final results of more detailed molecular analysis for TNBC would be available in the meeting. No significant financial relationships to disclose.
Null allele polymorphisms in the GSTT1 and GSTM1 genes in 705 women from a mammographic breast cancer screening program (NMPOA) in southern Brazil
Authors: Aguiar E. , Giacomazzi J. , Palmero E. I. , Kalakun L. , Schuler-Faccini L. , Duarte Filho D. , Skonieski G. , Caleffi M. , Giugliani R. , Ashton-Prolla P. 
Published: March 2020

21091 Background: Several genetic polymorphisms in genes related with metabolism have been associated with breast cancer (BC) risk. Among these, the gluthatione-S-transferase M1 and T1 null genotypes have been associated with slightly increased BC risk in some populations. In Brazil, BC is a significant public health problem, due to its high incidence and mortality rates. In Porto Alegre, Brazil`s southernmost capital, a multidisciplinary BC Prevention Project - the Nucleo Mama Porto Alegre Cohort (NMPOA)- was started in 2004 and includes a mammographic screening program for women ages 40–69 years. Goal:Determine the allelic and genotypic frequencies of GSTM1 and GSTT1 null alleles in women undergoing annual mammographic screening and correlate its presence with mammography results and presence of additional BC risk factors at baseline and after 10 years. Methods: A sample of 705 women from the NMPOA BC screening program was consecutively enrolled from November/2005 until March/2006. Mammography results (BIRADS categories) and BC risk information (5-yr and vital estimates using the Gail model, family history of BC, body mass index) were obtained by chart review. Genotyping was performed by multiplex polymerase chain reaction (PCR). Results: Of the 705 patients studied, 145 (20.6%) and 314 (44.5%) had the GSTT1 and GSTM1 null alleles, respectively. Genotypically, 67 (9,5%) were null homozygous for both genes (GSTM1- and GSTT1- ); 78 (11,1%) were GSTT1- and non-null for GSTM1 (GSTT1- and GSTM1+); 247 (35%) were GSTT1+ and GSTM1- and 313(44,4%) were GSTM+ and GSTT+. There was a statistically significant association of the GSTT1+ allele with low-risk mammographic findings (category BIRADS 1; p<0,05). Conclusions: The genotypic and allelic frequencies of the GSTT1 and GSTM1 null alleles were not significantly different from those reported previously for other populations. The non-null GSTT1 allele was associated with lower category mammographic findings. Prospective clinical evaluation of the women followed in this program and correlation of genotype with clinical findings may elucidate additional risks associated with the presence of these polymorphisms. No significant financial relationships to disclose.
In vivo and in vitro efficacy of capecitabine (X) + tamoxifen (TAM) in breast cancer (BC)
Authors: Mori K. , Yamaguchi Y. , Sawada N. , Kondoh K. , Hayashi S. 
Published: March 2020

21092 Background: In vitro studies in BC cell lines suggested antagonism between TAM and 5-FU. Thymidine phosphorylase (TP) activates X to 5-FU in tumors. X activity correlates with tumor TP concentrations in vivo. Methods: We studied antitumor efficacy of X + TAM in vivo and in vitro in human BC models. Nude mice were inoculated s.c. with estradiol, then MCF-7 cells 1 day later. When tumors were ∼300 mm3, mice received 6 weeks’ oral vehicle (control), X (d1–14 q21d) at MTD (539 mg/kg) or 2/3 MTD, and/or TAM at 100 or 30 mg/kg/d. We also analyzed impact of 5-FU and doxifluridine (5'-DFUR, an intermediate of X) + TAM on estrogen receptor (ER) signals in an in-vitro culture system. ER signals were monitored by expression of green fluorescent protein (GFP) in MCF-7 BC cells transfected with the estrogen-responsive element (ERE)-GFP gene (MCF-7-E10). GFP expression was induced in MCF-7-E10 cells in the presence of estradiol at 3 pM or BC tissue supernatant. Results: X at 2/3 MTD + TAM 30 mg/kg were significantly more active than the highest dose of X or TAM alone. Tumor TP concentrations were significantly higher in TAM- than vehicle-treated mice. In the ER signal system, GFP expression of MCF-7-E10 was reduced by 4-hydroxytamoxifen (4-OHT, active form of TAM) at 0.01 and 0.1 nM. When added to 4-OHT, 5-FU 0.3–30 μM or 5'-DFUR 3–10 μM reduced GFP expression more than either agent alone. In vitro, 5-FU and 5'-DFUR inhibited proliferation of MCF-7-E10 cells regardless of 4-OHT. Additive effects could not be confirmed as 4-OHT alone showed only marginal anti- proliferative activity at 0.01–0.1 nM. Conclusion: X and TAM are not antagonistic in this model. TAM may augment X activity via TP upregulation in BC tissues. TAM and X intermediates showed no clear antagonism in vitro in an ER signal system. All-oral X + TAM merits evaluation as combination therapy in breast cancer. [Table: see text]
Genetic testing in young women with breast cancer: Results from a web-based survey
Authors: Shin J. A. , Gelber S. , Garber J. , Rosenberg R. , Przypyszny M. , Winer E. , Partridge A. 
Published: March 2020

21093 Background: Young women with breast cancer have an increased risk of harboring a BRCA1/2 mutation. The frequency of genetic testing in this population is not well described. We evaluated the reported frequency and factors associated with genetic testing among young breast cancer survivors identified through the Young Survival Coalition (YSC), an international advocacy group for young women with breast cancer. Methods: Items regarding family history and genetic testing were included in a large web-based survey addressing quality of life and fertility issues for young women with breast cancer. All YSC members were invited by email in March 2003 (N= 1,703 women) to participate in this cross-sectional survey. Results: 657 women completed the on-line survey; 622 were eligible for this analysis (age <40, no metastatic or recurrent disease). Mean age at breast cancer diagnosis was 33 years; mean age when surveyed 35.5 years. Stages included: 0 (10%), I (27%), II (49%), III (12%), missing (3%). 90% of women were white; 64% married; 49% with children; 78% had at least a college education; 42% of women reported a 1st or 2nd degree relative with breast or ovarian cancer, and 13% considered themselves high-risk for harboring a genetic mutation at the time of diagnosis. At the time of the survey, 23% of women had undergone genetic testing, and 26% of those tested reported that a mutation was found. In a multivariate model, women who were younger (age 36–40 vs. age =30, O.R. 2.26, p=0.004), more educated (< college vs. > college education, O.R. 2.62, p=0.0009), had a family history of breast or ovarian cancer (O.R. 3.15, p<0.0001), and had had a mastectomy (O.R. 1.99, p=0.001) were more likely to have undergone genetic testing. Non-significant covariates included: age at survey, stage, time since diagnosis, race, marital status, employment, finances, insurance, number of children, comorbidities, baseline anxiety and depression, and fear of recurrence. Conclusion: The majority of women diagnosed with breast cancer age 40 and younger do not undergo genetic testing. Younger, more educated women with a family history of breast or ovarian cancer are more likely to get tested. Further research to define the appropriateness of genetic testing in this relatively high-risk population is warranted. No significant financial relationships to disclose.
Topoisomerase-2alpha (T-2a), Ki67, Her-2 and response to neoadjuvant anthracycline-containing chemotherapy in breast cancer. A prospective, correlation study
Authors: Bari M. , Sartori D. , Zambenedetti P. , Tacchetti G. , Sicari U. , Rosetti F. , Iop A. , Pappagallo G. L. , Vinante O. 
Published: March 2020

21094 Background: T-2a creates a reversible double-strand DNA break allowing DNA doubling. Anthracyclines (A) stabilize the DNA double-strand breaks, and T-2a is probably the primary molecular target of A. Due to the close location of T-2a and Her-2 genes on chromosome 17, T-2a gene aberrations are mainly associated with Her-2 gene amplification; while a correlation exists between Her-2 amplification and protein overexpression this is not true for T-2a. A linear correlation between T-2a and Ki67 labeling indices was found, suggesting that both essentially reflect cellular proliferation. The correlation between T-2a overexpression and both Her-2 and Ki67 was investigated in a series of consecutive patients undergone neoadjuvant A-containing chemotherapy for locally-advanced breast cancer. Material and Methods: T-2a expression was measured by means of monoclonal antibody Ki-S1; thresholds (ts) for immunopositivity were tested at 10%, 15% and 20%, respectively. Both the anti-c-erb-B2 primary antibody (clone CB11) and the Dako test were employed to recognize c-erb-B2 protein. Ki67 was measured using the MIB-1 antibody, with ts for positivity at 10%. Patients were required to have a cT>2cm breast cancer. The neoadjuvant chemotherapy included Adriamycin 60mg/m2 or Epirubicin 75mg/m2, in combination with Paclitaxel (175 mg/m2), every 3 weeks for 4 cycles. Bivariate correlations were performed according to Pearson. Results: 38 patients were enrolled until August, 2006. A significant correlation between T-2a and Ki67 was found (r=.598; P<.000); the T-2a positivity rate within Ki67 positive patients was of 90% (10% ts), 86% (15% ts), and 67% (20% ts). No correlation appeared between T-2a and Her-2 labeling indices (r=.150; P=.391); the T-2a positivity rate within Dako +++ patients was 75% (for both 10% and 15% ts) and 50% (for 20% ts). The overall response rate by T-2a overexpression was 61% (10% ts), 70% (15% ts), and 72% (20% ts). Conclusions: We provide a further evidence of the correlation between T-2a and Ki67. We can also generate the hypothesis that a 20% ts for T-2a correlate with a better prediction of response to A-containing chemotherapy; at the same ts, no correlation with Her-2 status was found. No significant financial relationships to disclose.
A comparison of tumor characteristics between ER+/PR+ and ER+/PR- breast tumors in Chinese women
Authors: Zhou L. , Yin W. , Lu J. , Shi D. , Liu G. , Di G. , Wu J. , Shen K. , Lu H. , Shen Z. , Shao Z. 
Published: March 2020

21097 Background: Although breast caner patients with any one of the two sex hormone receptors positive can be treated with endocrine therapy, many clinical data showed that there was different response to endocrine therapy for patients with ER+/PR+ and with ER+/PR- tumors. The aim of this study was to find out the factors related to PR expression by comparing the ER+/PR+ tumors and ER+/PR- tumors clinically and biologically. Methods: Between January 1990 to August 2006, 5,191 female breast cancer patients with known ER/PR expression status who received operation in our hospital were enrolled onto this retrospective study. Clinical and biological features of 2,227 patients with ER+/PR+ tumors were compared with those of 909 patients with ER+/PR- tumors. χ2 test was used for univariate analysis and logistic regression for multivariate analysis. Disease-free survival (DFS) and overall survival (OS) was calculated using Kaplan-Meier analyses, and all statistical tests were two-sided. Results: The peak onset age of patients with ER+/PR+ tumors and ER+/PR- tumors was 50, and it was significantly higher than that of patients with ER- tumors, which is 48(P=0.001). Univariate analysis showed that ER+/PR- tumors were larger in size, had more lymph nodes of metastasis, were higher in tumor grade than ER+/PR+ tumors. Furthermore, the expression of ER and CathepsinD was significantly lower, and CerbB-2 expression was higher in ER+/PR- tumors than in ER+/PR+ tumors. Multivariate analysis indicated that positive PR expression was associated with the level of ER(OR=1.792, P=0.000), CathepsinD(OR=1.380, P=0.035)and CerbB-2(OR=0.639, P=0.007). DFS(P=0.004) and OS(P=0.009) were higher among patients with PR-expressing tumors than with PR- negative tumors. Conclusions: ER+/PR+ tumors and ER+/PR- tumors may have the same etiology which is different from that of ER- tumors. Because of low ER level and changes of the expression of CerbB-2 and CathepsinD, the tumors that lacked PR expression display more aggressive features and have worse prognosis. According to these differences, new target of therapy and endocrine regimen may provide the possibility of improving the response and prognosis of endocrine therapy for patients with ER+/PR- tumors. No significant financial relationships to disclose.
The rule of mortality risk in young women (≤35 years) with primary breast cancer
Authors: Yin W. , Lu J. , Liu G. , Di G. , Wu J. , Shen K. , Shen Z. , Shao Z. 
Published: March 2020

21098 Background: The prognosis of young women (=35 years) is poorer than that of women over 35 years, which may indicate that they bear different biologic characteristics. However, such data is still not available at home and abroad as the rule of mortality risk in young women and its distinction from that in women over 35 years. We sought to investigate the clinical characteristics, prognosis and the rule of mortality risk in young women (=35 years) with primary breast cancer. Methods: We performed a retrospective study of 2331 female unilateral breast cancer patients undergoing surgery in our hospital from January 1990 to October 2005.They were divided into two groups with the cut-off of 35 years. Selection criteria included complete data on the following: age, tumor size, axillary nodal status, estrogen receptor (ER) status, menopausal status.Overall survival curve was estimated by Kaplan-Meier method and annual mortality hazard by hazard function. Their clinicopathologic indices, overall survival curve and annual mortality hazard were analyzed. Results: There was statistical significance between =35 years and >35 years group in terms of tumor size( P =0.0231), axillary nodal status( P <0.001) and estrogen receptor status( P =0.064). 10-year overall survival was 72% and 79% ( P = 0.0081), respectively, for =35 years and >35 years group. Although annual mortality hazard curve for both groups showed double-peaked pattern, there also exist some differences. Mortality surges for =35 years patients appeared earlier than those for >35 years counterparts. Moreover, =35 years group showed a minor increase between double peaks, which cannot be found in >35 years group. Conclusions: Between the two groups, different tumor biology leads to the discrepancy of overall survival and mortality pattern, which might indicate distinct principles and measures in the follow-up and treatment for young patients to provide the possibility of improving the therapeutic effect and reducing the mortality hazard. No significant financial relationships to disclose.