bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P1-07-12: Kaiso is a novel regulator of epithelial-to-mesenchymal transition in triple negative breast cancer cells
Authors: Bassey BI , Crawford C , Daniel JM 
Published: August 2014

Abstract
Introduction:
Breast cancer (BC) is the most frequent form of female cancer and a principal cause of female deaths worldwide. Most BC deaths are attributed to tumor metastasis to vital organs, and many studies have proposed a role for epithelial-to-mesenchymal transition (EMT) in BC metastasis especially the Triple Negative BC (TNBC) subtype. This theory is further strengthened by the observation that many triple-negative tumors display low E-cadherin expression, which is a hallmark of EMT. The TNBC subtype lack expression of the estrogen-receptor (ER), progesterone-receptor (PR) and human epidermal growth factor receptor-2, HER2. These tumors are highly aggressive with limited treatment options or targeted-therapies, and consequently TNBC patients have poor outcomes. Recently, increased nuclear expression of the transcription factor Kaiso was significantly correlated with high grade, BRCA1-related and basal/TNBCs. Kaiso is a novel transcription factor that we originally identified as a binding partner of p120-catenin (p120), a Src Kinase substrate and regulator of E-cadherin stability and turnover.
Rationale and Research Objective:
Though not much is known about the function of Kaiso in breast tumor progression and metastasis, Kaiso has been implicated in regulating E-cadherin expression, which raised the possibility that Kaiso might play a role in EMT. Thus we sought to elucidate the role of Kaiso in EMT and TNBC metastasis.
Results:
To achieve this goal, we created a stable Kaiso-depleted TNBC cell line (MDA-MB-231) to analyze the consequences of Kaiso-depletion on features attributed to metastasis, using immunoblot, wound healing and Matrigel invasion assays among other techniques. Interestingly, Kaiso-depletion led to reduced transcript and expression levels of the EMT markers Snail, Slug, ZEB1/2, TGFbRII, vimentin, and up-regulation of E-cadherin. Kaiso-depleted MDA-MB-231 cells also showed a gradual change in morphology from a mesenchymal to an epithelial phenotype referred to as mesenchymal to epithelial transition (MET). Loss of Kaiso further resulted in reduced cell motility and invasion. Ongoing studies seek to evaluate the effect of Kaiso-depletion on metastasis in vivo. Since there is evidence that the TGFβ signaling pathway drives EMT, and Kaiso-depletion resulted in reduced transcript levels of TGFβRII, future studies will determine if Kaiso plays a role in EMT/MET via promotion of the TGFβ signaling pathway.
Overall Significance:
Our study is the first to demonstrate a link between Kaiso and EMT/MET of TNBC cells and suggest that Kaiso may be a novel regulator of EMT in TNBC. Consequently, Kaiso might be useful as a therapeutic or prognostic tool in the treatment of TNBC.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-07-12.
Abstract P1-08-02: Chemosensitivity and endocrine sensitivity of MammaPrint and BluePrint in the prospective neo-adjuvant breast registry symphony trial (NBRST)
Authors: Whitworth P , Gittleman M , Akbari S , Stork-Sloots L , de Snoo F , Gibson J , Beitsch P 
Published: August 2014

Abstract
Background
Classification into molecular subtypes may be important for the selection of therapy for patients with early breast cancer. Previous analyses had shown that breast cancer subtypes have distinct clinical outcome (Sorlie, PNAS 2001; Esserman, BCRT 2011). The aim of the prospective NBRST study is to measure chemosensitivity as defined by pathological Complete Response (pCR), or endocrine sensitivity as defined by partial response (PR) and metastasis-free survival in molecular subgroups using MammaPrint and BluePrint.
Methods
The study includes women aged 18–90 with histologically proven breast cancer, who are scheduled to start neo-adjuvant chemotherapy (CT) or neo-adjuvant endocrine therapy (ET), and who provide written informed consent. Additional inclusion criteria include no excision biopsy or axillary dissection, no confirmed distant metastatic disease, and no prior therapy for breast cancer. Treatment is at the discretion of the physician adhering to NCCN approved regimens. pCR is defined as no invasive or noninvasive residual disease in the breast or axillary lymph nodes.
Results
191 Patients (median age 53, range 22-82), T1-4 N0-3, had definitive surgery and the overall pCR rate was 18%.
31 (16%) patients are classified as Luminal A-type (BluePrint Luminal/MammaPrint Low Risk) of whom 24 received neo-adjuvant CT; 1 patient (4%) had a pCR. While 7 patients received neo-adjuvant ET and 5 (71%) had a PR. 64 (34%) Patients are classified as Luminal B-type (BluePrint Luminal/MammaPrint High Risk). All but 1 patient received neo-adjuvant CT and 2 (3%) had a pCR. 30 (16%) Patients are classified as BluePrint HER2-type and all received neo-adjuvant CT and trastuzumab (except for 3 patients who did not receive trastuzumab); 11 (37%) had a pCR. 66 (31%) Patients are classified as BluePrint Basal-type and received neo-adjuvant CT; 19 (29%) had a pCR.
Comparison of IHC/FISH classification with molecular subtyping:
24/102 (24%) IHC/FISH ER+/Her2- patients are not classified as Luminal-type by BluePrint (4 Her2, 20 Basal). 22/48 (46%) IHC/FISH Her2+ patients are not Her2-type by BluePrint (4 Luminal A, 11 Luminal B, and 7 Basal). All IHC/FISH triple negative patients are BluePrint Basal-type.
Conclusions
Molecular subtyping using MammaPrint and BluePrint leads to a reclassification of 24% (46/191) of tumors. We observed differences in pCR to neo-adjuvant treatment in groups stratified by BluePrint and MammaPrint. Patients with Luminal A-type breast cancer have a high response to neo-adjuvant endocrine therapy (71% PR) and low pCR (4%) to neo-adjuvant CT. While patients with BluePrint HER2-type and Basal-type breast cancer have a high pCR rate to neo-adjuvant CT.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-08-02.
Abstract P1-08-03: Prediction of response to neoadjuvant chemotherapy in estrogen receptor positive (ER+) breast cancer by IHC4 or Ki67 alone
Authors: Sheri A , Smith IE , A'Hern R , Jones R , Parton M , Johnston SRD , Dowsett M 
Published: August 2014

Abstract
Aims To determine whether IHC4 score assessed on pre-treatment core biopsies (i) predicts response to neoadjuvant chemotherapy in ER positive breast cancer; (ii) provides more predictive information than Ki67 alone.
Background The IHC4 score, a composite of ER, PgR, Ki67 and HER2 scores provides prognostic information similar to the OncotypeDx 21-gene Recurrence Score in ER + primary breast cancer treated with endocrine therapy but it is unknown if it also predicts response to chemotherapy. Pathological complete response (pCR) following neoadjuvant chemotherapy is established as an intermediate marker of long-term outcome. More recently the residual cancer burden (RCB) has also been shown to be prognostic, with those patients with minimal residual disease (RCB1) following neoadjuvant chemotherapy having a similar prognosis to those with a pCR (RCB0). The development of these intermediate markers provides an opportunity to study the predictive role of pre-treatment biomarkers for benefit to a particular therapy.
Methods A total of 114 ER+ patients treated with neoadjuvant chemotherapy at the Royal Marsden Hospital between 2002-2010 were included in the study.
An assessment of the excision specimen was made for residual disease. IHC4 was determined on pre-treatment core biopsies, blinded to clinical outcome, by immunohistochemistry using quantitative scoring of ER (H-score), PgR (%) and Ki67 (%). Determination of HER2 status was made by immunohistochemistry and fluorescent in situ hybridization for 2+ cases. IHC4 and Ki67 scores were tested for their association with pCR rate and RCB score.
Results 19 (17%) of the 114 patients and 9 (10%) of the 90 HER2-ve cases showed a pCR. Ki67 and the IHC4 score were both positively associated with achievement of pCR (P&lt;10-7 and P&lt;10-9 respectively) and RCB0+1 (P&lt;10-5 and P&lt;10-9 respectively) following neoadjuvant chemotherapy in all patients. Rates of RCB0+1 were 45% and 66% in the highest quartiles of Ki67 and IHC4 scores respectively. In ER + HER2-ve cases pCR and RCB0+ 1 rates were 35% and 39%, respectively in the highest quartile of IHC4 and 30% and 39%, respectively in the highest quartile of Ki67 (Table 1). There were no pCRs in the lower half of IHC4 or Ki67 scores.
Conclusions A high IHC4 was strongly predictive of a pCR or near pCR in ER + breast cancers following neoadjuvant chemotherapy. Ki67 was an important component of this predictive ability.
Response according to IHC4 and Ki67 quartile in HER2 negative, ER+ breast cancersIntermediate endpointpCRpCRRCB0+RCB1RCB0+RCB1ScoreIHC4Ki67IHC4Ki67Quartile 10% (0/22)0% (0/22)5% (1/22)9% (2/22)Quartile 20% (0/23)0% (0/23)4% (1/23)0% (0/23)Quartile 35%(1/22)9% (2/23)9% (2/22)9% (2/23)Quartile 435% (8/23)30% (7/23)39% (9/23)39% (9/23)
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-08-03.
Abstract P1-08-07: High tumor CD68 mRNA content (intratumoral macrophages) predicts response to neoadjuvant chemotherapy
Authors: Wirtz RM , Aigner J , Marme F , Eidt S , Altevogt P , Sinn P , Schneeweiss A 
Published: August 2014

Abstract
Background
Immune cell infiltrates have been shown to play a prominent role with regard to prognosis of node negative breast cancer (Schmidt et al 2008). Moreover, it has been shown that B-cells and T-Cells are of particular importance for the response to chemotherapy (Schmidt et al. 2012). However, the role of macrophages remains unclear. It has been assumed, that tumor-associated macrophages play a role in promoting tumorigenesis. Still their role with regard to therapy prediction is unknown. Here we tested wether the infiltration of macrophages is associated with the response to neoadjuvant chemotherapy.
Materials and Methods
Pretreatment core cut biopsies from n = 100 patients with PBC treated within a randomized phase II trial (1) of anthracyline/taxane based NAC were examined. RNA from formalin-fixed, paraffin embedded (FFPE) routine biopsies were extracted using a bead-based extraction method (STRATIFYER XTRAKT kits). CD68 and ESR1, PGR, HER2, Ki67 as well as CALM2 as a house keeping gene were measured via a multiplex quantitative RT-PCR (RT-qPCR). Correlation analyses and partitioning tests were performed using the SAS JMP® 9.0.0 software.
Results
CD68 mRNA exhibited a normal data distribution (Median expression 40-DCT 34,66) in the core needle biopsies of advanced breast tumors. CD68 mRNA correlated strongly with Ki67 mRNA levels (Spearman r = 0,46; p&lt;0,001), whereas there is virtually no correlation with other classical biomarkers such as ESR1, PGR and HER2. Partitioning analysis revealed that CD68 mRNA levels are superior to the previously and prospectively validated response markers ESR1 mRNA and HER2 mRNA. When using the median mRNA expression as an objective cut-off measurement no tumor having low CD68 mRNA expression did respond to chemotherapy, while 22% of the CD68 positive tumors responded by pathological complete response (ypT0ypN0). Based on molecular subtyping into Luminal, HER2 positive and Triple-Negative with predefined Cut-Off values for ESR1mRNA and HER2 mRNA levels, high CD68 were particularly informative within luminal tumors (22% pCR versus 0% pCR rate) and Triple negative tumors (38% pCR versus 0% pCR rate).
Conclusion
The presence of macrophages indicates tumors being sensitive to chemotherapy beyond the prospectively validated ESR1 and HER2 mRNA determinations (2), both in luminal and triple negative tumors. The mRNA expression levels of CD68 provide additional information beyond conventional subtyping and might therefore be useful for early assessment of non-response to chemotherapy und subsequent treatment planning.
1) Schneeweiss et al, Ann Oncol 2011
2) Denkert et al, Ann Oncol 2013.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-08-07.
Abstract P1-08-22: The impact of obesity on response to neoadjuvant chemotherapy in operable breast cancer patients
Authors: Lee HY , Jung SP , Kim S , Kim HY , Bae JW , Lee JB 
Published: August 2014

Abstract
Background
The association between obesity and response to neoadjuvant chemotherapy in breast cancer patients is not clear. We evaluated the impact of obesity on response to neoadjuvant chemotherapy in patients with operable breast cancer.
Methods
From May 2008 to December 2010, 104 patients were diagnosed with invasive breast cancer at Korea University Anam Hospital and received neoadjuvant chemotherapy before surgery. Patients were classified into those of normal (BMI of 18.5 to &lt;25kg/m2), overweight (BMI of 25 to &lt;30kg/m2), or Obese (BMI≥30kg/m2). The association between body mass index and pathologic response (pathologic complete response(pCR) and pathologic partial response(pPR)) to neoadjuvant chemotherapy was examined using logistic regression.
Results
Median age was 45 years. Mean BMI was 24.8 kg/m2; 53.8% had a normal BMI, 35.6% overweight, and 10.6% of patients was obese. BMI did not show a significant association with ER status, PR status, HER-2 status, lymph node involvement and neoadjuvant chemotherapy regimen. In univariate analysis, overweight and obese patients were significantly less likely to have a pCR compared with normal weight patients (odds ratio [OR] = 0.300; 95% CI, 0.115 to 0.784; p = 0.010). In multivariate analysis, ER negativity was significantly associated with a pCR and pPR to neoadjuvant chemotherapy (OR = 2.987; 95% CI, 1.128 to 7.907; p = 0.028), And there was significant difference in pCR for overweight and obese compared with normal weight patients (OR = 0.304;95% CI, 0.115 to 0.803; p = 0.016).
Conclusion
This study suggests that higher BMI should be considered to be a factor of worse response to neoadjuvant chemotherapy in patients with operable breast cancer.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-08-22.
Abstract P1-08-39: Tumor-infiltrating CD8+ lymphocytes as an independent predictive factor for pathologic complete response to primary systemic therapy in breast cancer
Authors: Seo AN , Lee HJ , Kim EJ , Kim HJ , Lee HE , Kim YJ , Kim JH , Park SY 
Published: August 2014

Abstract
Background: Tumor infiltrating lymphocytes (TILs), stem cell phenotype and epithelial-mesenchymal transition (EMT) are known to be associated with response to primary systemic therapy (PST) in breast cancer. However, these markers are strongly correlated with triple negative breast cancer, which shows high pathologic complete response (pCR) to PST. This study was conducted to evaluate clinical implication of these markers as predictive factor for pCR after PST in breast cancer and to find independent predictive factors, irrespective of breast cancer subtype.
Methods: The pre-chemotherapeutic biopsy specimens of 153 breast cancer patients who underwent surgical resection after anthracycline-or anthracycline/taxane-based PST were enrolled. TILs (CD4, CD8, and FOXP3), breast cancer stem cell phenotype (CD44+/CD24-, and ALDH1), expression of EMT markers [vimentin, smooth muscle actin (SMA), osteonectin, E-cadherin, and N-cadherin] were evaluated by immunohistochemistry and were correlated with pCR after PST.
Results: High infiltration of TILs (CD4+, CD8+, and FOXP3+), expression of stem cell markers (CD44+/CD24-, ALDH1+) and expression of EMT markers (expression of vimentin, SMA and osteonectin; loss of E-cadherin) were significantly associated with high histologic grade and triple negative breast cancer. Of them, high TILs (CD4+, CD8+, and FOXP3+) and expression of ALDH1, vimentin and osteonectin were associated with pCR. In multivariate analysis, CD8+ TILs and a conventional predictive marker, Ki67 were found to be independent predictors for pCR. In subgroup analyses, high CD8+ TILs was remained as a predictive factor for pCR, irrespective of PST regimen and tumor subtype.
Conclusion: CD8+ TILs could therefore be used as a reliable predictor of response to PST in breast cancer.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-08-39.
Abstract P1-09-14: Relationship between socioeconomic status, race, and breast cancer clinical stage at presentation
Authors: Wray CJ , Nguyen BC , Wiatrek RL , Robinson EK , Ko TC , Kao LS 
Published: August 2014

Abstract
Introduction: Racial and ethnic minority breast cancer patients present with later clinical stage at diagnosis, which may be due to lack of access to care due to poor socioeconomic status (SES). Our hypothesis was that the racial gap in clinical stage at breast cancer presentation would be eliminated after adjustment for SES.
Methods: Retrospective review was performed of breast cancer (excluding ductal carcinoma in situ) patients from 10 hospitals in Harris County Texas between 2002 and 2011. Demographic and clinical information was recorded. Clinical stage was calculated based on data from the institutional tumor registry and electronic medical record. Zip code-based SES data, including mean household income and percentage of households receiving social support, were downloaded from www.census.gov. A multivariate ordered logistic regression clustered by hospital was used to identify predictors of clinical stage.
Results: Of 3084 breast cancer patients, the mean age at diagnosis was 59 ± 14 years. The cohort included 1873 Caucasian (61%), 519 African-Americans (17%), 353 Hispanics (11%), and 339 Asian/others (11%). Age, race, mean household income, and percentage of household receiving social support were predictive of clinical stage at presentation (p&lt;0.05).
Ordered Logistic RegressionVariableOdds RatioSEp-value95% CIMean Income0.998.2 e-060.0010.98 - 0.99% Social Support1.010.0020.0021.00 - 1.01Age0.980.0020.0410.97- 0.99Race African-American4.581.220.0002.72 - 7.72Hispanic1.991.260.2730.58 - 6.89Asian/other1.450.760.4730.52 - 4.04Caucasian = referent value for Race, SE = standard error, CI = confidence interval
The largest racial gap was observed between African-Americans and Caucasians. African Americans from areas with a mean income up to $180K still had a lower predicted probability of presenting with clinical stage 1a disease than the Caucasians from the poorest mean income areas (&lt;$5K). African Americans from the highest mean income areas (&gt; $305K) still had a higher probability of presenting with clinical stage 4 disease as Caucasians from areas with a mean income as low as $100K.
Conclusion: Both African-American race and residence in a low SES zip code contribute independently to late clinical stage at presentation among breast cancer patients. Both genetic and social factors may play a role in this disparity. Addressing factors related to just race or low SES status alone is unlikely to improve outcomes for African-Americans from low SES zip codes.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-09-14.
Abstract P1-09-16: Factors affecting disparities in advanced stage breast cancer
Authors: Samiian L , Kraemer D , Butterfield R , Osian SR , Lukens-Bull K , Wood D 
Published: August 2014

Abstract
BACKGROUND:
African American women have a lower incidence of breast cancer than white American women. However, black women in the US are 40% more likely to die of breast cancer. Compared to white women, Black women in Florida have among the highest additional breast cancer deaths. Within Florida, Duval County has one of the highest rates of breast cancer. Furthermore, breast cancer mortality is significantly higher for black women (36.7 per 100,000) in Duval County, than for white women (24.0 per 100,000). Therefore, we evaluated breast cancer disparities in Duval County as a representative population to identify factors influencing breast cancer mortality.
METHODS:
Data on female breast cancer cases from 2004-2010 was extracted using the Florida Cancer Data System (FCDS). Classifications included health zones within Duval County, race, insurance, and age. Insurance categories included Medicare, Medicaid, Uninsured, and Tricare/commercial which were combined in one group. The primary outcome was late stage (Stage 4) at diagnosis versus other stages. Multivariable logistic regression was used to assess the association between late stage at diagnosis and insurance, race, age, and place of residence (health zone).
RESULTS:
Using the FCDS, 6,502 new breast cancers were identified in Duval County from 2004 – 2010. Of these women, 73% were white, 24% black, 5% Hispanic, 2% Asian, and 2% unknown/other. Health Zone 1 which represents the urban core has the largest population of Black women with breast cancer (76%), although the incidence of breast cancer was not higher in this group. Health Zone 1 has the highest volume of uninsured, and Medicaid breast cancer patients (10% and 8% vs. 4% average for all other zones), and the lowest number of breast cancer patients with Tricare/commercial insurance (33% vs. 56% average for all other zones). Black women overall had a higher percentage of advanced stage IV disease than any other race (8% vs. 4%, p&lt; .001). Women in Health Zone 1 are more likely to present with stage IV breast cancer than any other health zone in Duval County (10% vs. 5%, p&lt;0.01). Medicaid patients, followed by the uninsured had the highest rate of stage IV at diagnosis than those with commercial insurance (20% and 12% vs. 4%, p&lt;.001). Using multivariable logistic regression analysis, only Medicaid insurance (OR = 5.3; 95% CI = (3.6, 7.9)) and living in the urban core (OR = 4.02; 95% CI = (1.9, 8.4)) was significantly associated with stage IV disease. After adjustment for insurance and place of residence, black race did not remain a significant factor (p = 0.1722).
CONCLUSION:
Living in the urban core, and lack of insurance or Medicaid funding was significantly associated with advanced stage at diagnosis in Duval County, Florida. These results suggest that socioeconomic factors are a major contributor to breast cancer mortality, irrespective of race.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-09-16.