bluuebunny/crossref_metadata_2025_split huggingface dataset:
Standardized uptake value (SUV) by positron emission tomography/computed tomography (PET/CT) as a prognostic variable in metastatic breast cancer (MBC).
Authors: Jhaveri K. L. , Ulaner G. , Fazio M. , Eaton A. , Patil S. , Evangelista L. , Serna-Tamayo C. , McArthur H. L. , Hudis C. , Morris P. G. 
Published: February 2017

3 Background: The accurate prediction of outcome from MBC could be useful if it could guide more effective therapies. Because PET/CT combines anatomical with functional imaging it could enable greater individualization of treatment. However, there is substantial SUV variation by anatomic site. In this retrospective, single-institution study, we examine baseline SUV on PET/CT as a predictor of outcome from MBC. Methods: Patients (Pts) with ≥1 metastatic lesion on PET/CT performed ≤60 days of diagnosis of MBC from 01/01/2001-12/31/2008 were identified through institutional databases. Pts who rcvd chemotherapy within 30 days prior to PET/CT were excluded. Electronic medical record reports were reviewed and maximum SUV (SUV-MAX) by site for lesions in bone, liver, lung and lymph node (LN) was recorded. In a secondary analysis, PET/CT scans were reviewed and SUV-MAX recalculated. Relationships between SUV-MAX and OS were assessed using Cox regression by site. Results: We identified 285 pts, median (med) age 57 yrs (range 27-90) who had PET/CT at med of 2.3 yrs (range 0–41) from primary BC (67% ER+ and 21% HER2+). Med time between PET/CT and MBC diagnosis was -9 days (range -58–59). At med follow-up of 53 mths, 163 pts have died. Med OS is 41 mths (95%CI 34-48). The SUV-MAX by site was; bone (N=159) med 7.0 (range 2.1–29.6); liver (N=55) med 8.2 (range 2.9–51.2); lung (N=89) med 4.7 (range 1.1–24.0); LN (N=180) med 6.9 (range 1.2–34.0). On univariate analysis, higher SUV in bone was associated with shorter survival (p<0.001; table). This was maintained in multivariate analyses after adjusting for known prognostic variables (p=0.02). A similar trend for shorter survival for higher SUV was noted in liver (p=0.07). However, no relationship between SUV and OS was noted in lung (p =0.34) and LN (p=0.6). Conclusions: This large retrospective study of pts with chemotherapy-naïve MBC suggests that SUV-MAX in bone strongly correlates with prognosis. [Table: see text]
HOXB9, a gene promoting tumor angiogenesis and proliferation, as a prognostic factor in breast cancer.
Authors: Seki H. , Hayashida T. , Jinno H. , Hirose S. , Takahashi M. , Mukai M. , Kitagawa Y. 
Published: February 2017

33 Background: We demonstrated that HOXB9, a member of homeobox genes, expression promoted tumor neovascularization and metastasis in vitro and in vivo assay. These findings imply that overexpression of HOXB9 contributes to tumor progression through activation of signaling pathways that alter both tumor-specific cell fates and tumor-stromal microenvironment, leading to increased invasion and metastasis. (Hayashida et al., PNAS 2010) We sought to determine whether these results could be extended to the clinical application. In this study, we evaluated the correlation between HOXB9 expression, clinical outcomes, and the clinicopathological variables in breast cancer patients, and the contribution of HOXB9 expression to tumor cell proliferation and angiogenesis. Methods: A consecutive series of 141 patients with invasive ductal carcinoma who underwent surgical treatment were examined. HOXB9 protein expression was analyzed immunohistochemically using the anti-human HOXB9 polyclonal antibody. Immunostaining of Ki-67, CD31, and CD34 were performed to evaluate the association of proliferation and tumor angiogenesis with HOXB9 expression. Results: Of 141 tumor specimens immunostained for HOXB9, 69 specimens (48.9%) were positive staining. Univariate logistic regression revealed ER and PgR negativity, HER2 positivity, high nuclear grade, and large pathological tumor size as significant variables associated with HOXB9 expression. Moreover, 12 (92.3%) out of 13 triple negative breast cancer showed HOXB9 expression. The disease-free survival (DFS) and the overall survival were significantly different between the HOXB9 positive and negative group; HR=20.714, p=0.001, HR 9.206, p=0.003, respectively. A Multivariate analysis indicated that HOXB9 expression was the only independent prognostic factor for DFS (HR=15.532, p=0.009). In subgroup analysis, HOXB9 positive tumors showed a significant increase in the number of vasculature and the Ki-67 ratio in comparison with HOXB9 negative. Conclusions: Our results suggest that HOXB9 expression promoting the tumor proliferation and the angiogenesis is a significant prognostic factor in breast cancer.
The effect of statins on overall survival of breast cancer.
Authors: Mozayen M. , Omaira M. , Kanaan M. , Ahmad A. , Katato K. 
Published: February 2017

34 Background: Observational studies have raised the possibility that use of statins may reduce the incidence and overall risk of cancer. In contrast, some randomized trials have consistently shown no effect of statins at cancer incidence or mortality. However, data about the potential effect of statins on overall survival of breast cancer are limited. We intend to examine the role of statins at overall survival of women diagnosed with breast cancer. Methods: A retrospective observational study was conducted from 1993 to 2007, using data from McLaren Regional Medical Center in Flint, Michigan on women diagnosed with breast cancer. Patient's characteristics including age at diagnosis, race, stage and use of statin with dosage were recorded. Patients with coronary artery disease were excluded to eliminate the confounding effect. The three-year overall survival was considered the primary outcome. Results:s A total of 392 women diagnosed with breast cancer were identified. 146 patients were on statins therapy prior to diagnosis (group 1), and 246 patients were not on statins (group 2). African American percentage was 7%. Mean age at diagnosis was 65 for both groups. Atorvastatin was the most used treatment with a dose of 20 mg daily. Patients were classified according to the TNM staging system of breast cancer as stage I, II, III, IV (58%, 31%, 8%, 3%) for group 1, and (62%, 32%, 4%, 2%) for group 2 respectively. The 3-year stage-specific survivals were calculated and compared between the two groups using Fisher's exact test (Table). Overall survival was not statistically significant between the two groups. Conclusions: Our study did show that statins do not affect the three-year overall survival of breast cancer at early stages, but it may improve the outcome at advanced stages. A larger national data review is warranted. [Table: see text]
Frequency distribution of SPARC in triple-negative breast cancer patients.
Authors: Basu G. , Van Vickle G. , Ghazalpour A. , Ashfaq R. , Gatalica Z. , Blevins R. , Arguello D. , Brisbin L. , Roberts C. , Loesch D. , Bender R. 
Published: February 2017

37 Background: SPARC (secreted protein acid rich in cysteine) belongs to a group of extracellular matrix proteins and promotes adhesion of cells from the matrix. It plays an important role in tumor development in breast cancer and has a significant bearing on patient prognosis and long term survival. It is also known to predict response to nab-paclitaxel in certain tumor types including breast cancer. In 2005, FDA approved a solvent free formulation of paclitaxel for the treatment of metastatic breast cancer that utilizes albumin bound (nab) technology (nab-paclitaxel). Clinical studies have shown that nab-paclitaxel is significantly more effective than paclitaxel. Our study evaluated the frequency distribution of SPARC among triple negative breast cancer patients in which identification of a novel therapeutic target is warranted. Methods: In a total of 951 breast cancer patients, we analyzed tumor SPARC expression by immunohistochemistry (IHC) using a monoclonal (R&D Systems) and a polyclonal antibody (Exalpha Biologicals). Immunoreactivity was assessed by scoring the percentage of cells stained in each field and by the intensity of staining. A cutoff point of 2+ and >30% stained tumor cells were considered as positive. Results: From our analysis of 951 breast cancer patients profiled, a total of 165 patients (17%) were triple negative for ER, PR and HER2. Within this pathologic subtype, 29% patients stained positive with SPARC monoclonal antibody and 21% stained positive with SPARC polyclonal antibody. The correlation of SPARC tumor staining with hormone receptor status will be presented in detail. Conclusions: We conclude that SPARC over-expression is a functionally important feature of a subset of triple negative breast cancer patients. The triple negative subset of tumors generally has a more aggressive clinical course and does not benefit from conventional targeted therapies. Our study suggests that nab-paclitaxel may serve as a therapeutic agent for the subset of triple negative patients that over-express SPARC. To the best of our knowledge, this is the first study involving a large patient pool in which SPARC has been investigated in a single clinical laboratory using standardized IHC with two different SPARC antibodies.
Re-evaluating the efficacy of axillary ultrasound in the detection of nodal metastasis and its impact on clinical practice.
Authors: Lee B. , Lim A. , Krell J. , Satchithananda K. , Lewis J. S. , Stebbing J. , Meric-Bernstam F. 
Published: February 2017

4 Background: Recent reports have indicated a lack of overall survival benefit for axillary node dissection versus sentinel lymph node biopsy in early breast cancer. To study this further, we wished to assess the accuracy and effectiveness of ultrasound guided fine needle aspiration (FNA) cytology in detecting lymph node involvement in breast cancer patients, in order to refine and evaluate our current clinical pathways as newly diagnosed invasive breast cancer patients routinely undergo pre-surgical axillary ultrasound. Methods: An FNA was taken from nodes of consecutive patients, which appeared abnormal on ultrasonography based on size, morphology, fatty hilum and cortical thickness measurements. Ultrasound and FNA cytological findings were correlated with histology following axillary node dissection. Of 260 cases, 123 (47.3%) had metastatic nodal involvement. Of these cases, only 66 (53.7%) were reported as positive on US findings. Results: The overall positive predictive value (PPV) of ultrasound for detecting metastatic nodal involvement measured 0.82, and the negative predictive value (NPV) was 0.60. The sensitivity was 0.54, specificity measured 0.85 and the accuracy was 0.68. The ultrasound morphological nodal features with the greatest correlation with malignancy were absence of a fatty hilum (p=0.003) and an increased cortical thickness (p=0.03). Cases with a metastatic nodal burden density of a least 20% were also more likely to be detected as abnormal on axillary ultrasound. (p=0.009). Conclusions: Axillary ultrasound has a low NPV and negative sonographic results do not exclude node metastases with sufficient sensitivity in most cases, to justify its routine clinical use. [Table: see text]
Combined use of MammaPrint and molecular subtyping profile (BluePrint) to identify subgroups with marked differences in response to neoadjuvant treatment.
Authors: Stork-Sloots L. , De Snoo F. , Roepman P. , Krijgsman O. , Bernards R. , Glas A. 
Published: February 2017

42 Background: Concordance between the IHC receptor status and the molecular subtype suggests that molecular profiles represent oncogenic processes that are driven by pathways in which ER, PR and HER2 play pivotal roles. It is, therefore, likely that the use of gene expression arrays will enable the identification of previously unappreciated subtypes of breast cancer that differ in clinical outcomes. Methods: The cohort consists of 133 (T1-4, N0-3) breast cancer patients treated with T/FAC neoadjuvant chemotherapy. Genome wide expression data was publicly available and downloaded from bioinformatics.mdanderson.org/pubdata.html. The data was used to determine the response to T/FAC neoadjuvant chemotherapy for patients stratified by MammaPrint and molecular subtype (BluePrint). The MammaPrint and BluePrint result were used to subtype the patients into 4 groups: MammaPrint Low-risk/Luminal-type, MammaPrint High-risk/Luminal-type, Basal-type and ERBB2-type. Results: Within this patient cohort, 20% (n=27) were classified as Basal-type, 62% (n=82) as Luminal-type, and 18% (n=24) as ERBB2-type. The overall pCR of this patient cohort was 26% and differed substantially among the subgroups. pCR was observed in 9% of all Luminal-type samples (i.e. 3% of MammaPrint Low Risk/Luminal-type and 11% of MammaPrint High Risk/Luminal-type), in 50% of the ERBB2-type samples and in 56% of the Basal-type samples. The pCR rates observed for the ERBB2-type and Basal-type patient groups were higher compared to classification based on IHC/CISH assessed ER and HER2 receptor status: 50% for ERBB2-type versus 39% for HER2+ and 56% for Basal-type versus 47% for ER-/HER2- samples. Conclusions: We observed marked differences in response to neo-adjuvant treatment in groups stratified by MammaPrint and BluePrint. These findings confirm differences in chemotherapy response among molecular subgroups and indicate that the BluePrint profile described here will help to further establish a clinical correlation between molecular subtyping and treatment response.
Does mammography affect the nodal status at presentation in 40- to 49-year-old breast cancer patients?
Authors: Hopkins L. , Chang S. H. , Kirstein L. J. , Fulop T. , Malamud S. C. , Chadha M. , Boolbol S. K. 
Published: February 2017

55 Background: It has previously been demonstrated that mammographically-detected breast cancers present as earlier stage disease than those detected as a palpable finding. In addition, it is well known that the single most important prognostic indicator in breast cancer is lymph node status. The benefit of screening mammography in women age 40-49 has been questioned recently, and has led to a change in the recommendations by the United States Preventative Services Task Force (USPSTF) to begin screening mammography in the average risk woman at age 50, rather than 40. In this study, we sought to determine whether detection of breast cancer in 40-49 year old women by screening mammography is associated with negative nodal status at presentation. Methods: A prospectively collected database was reviewed to identify 460 women ages 40-49 diagnosed with invasive breast cancer from 2003-2008. The method of detection of the breast cancer was noted, and the lymph node status at presentation was identified. Results: There were 460 eligible patients with invasive breast cancer for whom information regarding nodal status was available. Of these, 205 patients were diagnosed with a mammographic finding, and 255 patients presented with a palpable abnormality. In the group whose cancers were detected on mammography, 18% presented with lymph node metastases. This is significantly lower than the 41% who presented with a palpable finding (p<0.0001). For 40-49 year old women with invasive breast cancer, the likelihood of having a positive lymph node at presentation is 3.2 times higher if her cancer is detected as a palpable abnormality rather than on mammography (odds ratio) (CI: 2.1-5.0) (Table). Conclusions: Our analysis demonstrates that a patient diagnosed with invasive breast cancer in her 40s is more likely to present with lymph node metastases if her cancer is detected as a palpable mass, compared to those detected on mammography. This has certain prognostic importance, and provides an additional rationale for performing screening mammography in women of this age group. [Table: see text]
Responsiveness of adjacent ductal carcinoma in situ and changes in HER2 status after neoadjuvant chemotherapy/trastuzumab treatment in early breast cancer: Results from the GeparQuattro study (GBG 40).
Authors: Von Minckwitz G. , Darb-Esfahani S. , Loibl S. , Huober J. B. , Tesch H. , Solbach C. , Holms F. , Eidtmann H. , Diedrich K. , Just M. , Clemens M. , Hanusch C. , Schrader I. , Henschen S. , Hoffmann G. , Tiemann K. , Diebold K. , Untch M. , Denkert C. 
Published: February 2017

6 Background: Adjacent ductal carcinoma in situ (DCIS) is in found in approximately 45% of invasive ductal carcinomas (IDC) of the breast. Pure DCIS overexpresses HER2 in approximately 45%. There is uncertainty whether adjacent DCIS impacts on the response to neoadjuvant chemotherapy and trastuzumab as well as whether HER2 expression in IDC component or adjacent DCIS changes throughout treatment. Methods: Core biopsies and surgical tissue from participants of the GeparQuattro study with HER2-positive IDC were centrally examined for the area of invasive ductal component and adjacent DCIS before and after receiving neoadjuvant anthracycline-taxane-trastuzumab containing chemotherapy. HER2 overexpression in IDC and adjacent DCIS was quantified separately by immunohistochemistry using the Ventana automated staining system. Pathological complete response (pCR) was defined as no residual invasive or non-invasive tumor tissue. Results: Fifty nine (37.3%) of 158 IDCs presented with adjacent DCIS at diagnosis. These tumors showed lower regression grades than pure IDC (p=0.033). Presence of adjacent DCIS was an independent negative predictor of pCR (odds ratio 0.42 [95% CI 0.2-0.9], p=0.027). Adjacent DCIS area decreased from pre-treatment to surgery (r=0.205) with 30 (50.8%) IDCs with adjacent DCIS showing complete eradication of adjacent DCIS. HER2 status of adjacent DCIS was highly correlated with HER2 status of IDC component before (r=0.892) and after treatment (r=0.676). Degree of HER2 overexpression of the IDC component decreased in 16 (33.3%) out of 49 patients without a pCR. These 16 IDCs showed lower RGs compared to the 33 IDCs with unchanged HER2 expression (p=0.055). Conclusions: HER2-positive IDCs with adjacent DCIS is less responsive to neoadjuvant chemotherapy and trastuzumab compared to pure IDC. However, complete eradication of adjacent DCIS is frequently observed. HER2-overexpression of the invasive ductal component decreases in a subset of tumors, which showed less tumor regression.
Loss of B-cell translocation gene 2 in estrogen receptor–positive breast cancer and tamoxifen resistance.
Authors: Hayashida T. , Jinno H. , Takahashi M. , Kitagawa Y. 
Published: February 2017

63 Background: The expression analysis in ER positive human breast cancer already demonstrated the loss of nuclear expression of BTG2, the cell cycle regulator, in 46% of tumors and showed a significant inverse correlation with cyclinD1 expression. Our analysis of Oncomine database suggested that BTG2 expression might be related to the clinical outcome in patients with tamoxifen treatment. Methods: The examinations to evaluate whether BTG2 expression affects the sensitivity against tamoxifen were conducted both in vitro and in vivo. Results: In vitro cellular proliferation assay using tamoxifen against ER positive cell lines revealed that T47D expressing high level of endogenous BTG2 showed more drug sensitivity than MCF7 expressing low level of BTG2. (MCF7; IC50=4.48uM, T47D; =1.31uM) Tetracycline-inducible BTG2 expression model was developed in MCF7 and the cellular proliferation was strongly inhibited by the concomitant administration of tetracyclin and tamoxifen in vitro. Then, the cell line was injected into the mammary fat pad of immunodeficient mice. After the tumors grew more than 125mm3, these tumor bearing mice were administered the water including tetracyclin and/or tamoxifen pellet for 3 weeks. Tumor growth ratio was significantly suppressed in the concomitant administration of tetracyclin and tamoxifen in comparison with the animal treated with single agent. (p=0.044) Consistently, tumor weight and Ki67 expression were also significantly suppressed in the mice administered both tamoxifen and tetracyclin. (BW; p=0.034, Ki67; p=0.039) The cohort of 60 patients treated with adjuvant tamoxifen monotherapy was available online. Comparison of disease-free survival (DFS) of patients with positive BTG2 expression versus patients with loss of BTG2 expression revealed an univariate association in the dataset (log-rank probability, p=0.029). Multivariate analysis indicated that BTG2 expression resulted an independent prognostic factor for DFS (HR, 0.69; 95% CI, 0.495 to 0.963; p=0.029). Conclusions: Despite further validation studies need to be conducted, BTG2 expression may be useful biomarker to identify patients appropriate for tamoxifen treatment.
A noninvasive multimodal sono-contrast NIR spectroscopy system for breast cancer diagnosis: Clinical trial.
Authors: Yan K. , Yu Y. , Liao L. 
Published: February 2017

68 Background: A noninvasive multimodal sono-constrast spectroscopy system was developed to detect breast cancer from benign mass. An IRB approved clinical study has been carried out to evaluate its diagnostic power. Fourteen patients with histologically-proven cancer and 26 with benign mass were enrolled with informed consent. Methods: This system combines three modules: diffuse reflectance spectroscopy, ultrasonography and low intensity focused ultrasound (LIFU). It reports the optical functional difference in cancer and benign mass after transient LIFU interaction with vascular flow. The optical intensity and LIFU signals were collected during each study. The ratio of optical intensities at wavelengths 685 nm and 830 nm was decomposed into low frequency and high frequency components using wavelet analysis. Results: Comparison of the high frequency component showed that LIFU stimulated transitory fluctuation in benign mass, but not in malignant tissue, as quantified by mean absolute deviation (MAD). The ratios of MAD during LIFU vs. baseline in cancer and benign mass are [mean (max/min/std)] 2.04 (3.27/1.41/0.43) and 3.00 (4.29/1.86/0.62). This suggests that high frequency fluctuation was amplified in benign mass during LIFU stimulation. There are a few outliers due to poor patient setup or patient movement during procedure. The MAD ratios are significantly different in cancer vs. benign mass (p<<0.01). An ROC curve was generated by varying threshold MAD values. The area under ROC curve (AUC) was calculated to be 0.91. With threshold 2.3, sensitivity of 92.8% and specificity of 80.8% can be achieved. Backward stepwise regression study reveals that system performance is not affected by patient age (hormone status), tumor depth and tumor size. Conclusions: Current results demonstrate the effectiveness of the multimodal system in characterizing breast cancer vs. benign mass. LIFU appears to exert more pronounced influence on blood flow in benign mass than in tumor. This lack of response to LIFU in breast cancer is possibly due to its abnormal blood vasculature. The analysis is ongoing to incorporate ultrasound imaging parameters with spectroscopy to further improve the diagnostic power.