bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early breast cancer response to neoadjuvant chemotherapy: Defining the optimal timing and response rate using clinical tumor measurement.
Authors: Boudreau Dominique , Santos Fabiano , Robidoux Andre , Boileau Jean-Francois 
Published: February 2017

121 Background: Breast cancer pathological complete response (pCR) following neoadjuvant therapy (NAT) is associated with better survival in some tumor subtypes. There is interest in identifying methods to increase early prediction of pCR during NAT. A simple and inexpensive technique such as early clinical breast examination has been shown to correlate with pCR during NAT in some studies. However, the optimal timing of the measurement and the best tumor response (TR) rate to predict pCR still need to be defined. Methods: We conducted a retrospective cohort study of patients prospectively enrolled in the following NSABP trials in one academic center (Montreal, Canada): B-40, B-41, FB-AX-003, FB-4, FB-5 and FB-6. Patients with T4 disease or disease progression were excluded. Clinical tumor measurements were recorded before each cycle of NAT. TR was measured as the percentage decrease in the largest tumor diameter. ROC curves for TR measurements at each time point were generated, comparing areas under the curve using the DeLong method. P-value ² 0.05 was considered significant. Results: We analyzed data of 155 patients recruited from Aug. 2005 to May 2011. Results are presented in Table 1. The best time point to predict pCR was after cycle 2. At this time point, a TR of 46% was the best cutoff value to predict for pCR. Among hormone receptor positive (HR+) and HER-2 positive (HER-2+) breast cancer patients, a TR of 47% after cycle 2 was significantly predictive for pCR. These findings were similar using a 50% TR cutoff after 2 cycles. Conclusions: Observing a 50% reduction in largest tumour diameter on clinical breast examination after cycle 2 of NAT is predictive for pCR in HR+ and HER-2+ breast cancer patients. We recommend using this definition of clinical response in future trials evaluating novel methods to improve early prediction of pCR during NAT. [Table: see text]
How to reduce Ki67 variability jointly evaluating histological grade.
Authors: Izquierdo Maxim , Rodriguez Ignacio , Tresserra Fransec , Fabregas Rafael 
Published: February 2017

127 Background: Proliferative tumor activity measured immunohistochemically by Ki67 has high variability. Clinical use can be improved if it is considered together with the histological grade. Methods: Ki67 value has been studied in 566 breast cancers between 2007 and 2013 at our Institution using MIBI monoclonal antibody. The histological grade and hormonal receptor status were also evaluated. Results: Histological grade was I in 293 (51.7%) tumors, II in 219 (38.7%) and III in 54 (16.8%) tumors. Estrogen receptor was positive in 166 (29.5%) tumors and progesterone receptor was positive in 95 (16.8%) tumors. None of the tumors with Ki 67 value lower than 10% had histological grade III. Only 7% of tumors with histological grade I had a Ki 67 higher than 25%. Conclusions: It has to be considered to repeat or confirm the values of Ki67 higher than 25% with histological grade I, and Ki67 values lower than 10% in tumors with histological grade III.
Distant recurrence risk with prospective use of the 21-gene assay at a single institution.
Authors: Mullinax John , Carr Danielle , Vera Nora , Sun Weihong , Lee M. Catherine , Hoover Susan , Fulp William J. , Acs Geza , Laronga Christine 
Published: February 2017

131 Background: Distant recurrence (DR) is the cause of most breast cancer deaths. The 21-gene assay (ODX) Recurrence Score (RS) result predicts both 5 and 10-yr DR risk and can guide adjuvant chemotherapy (CT) recommendations to mitigate this risk. This study analyzed the use of the RS result to guide adjuvant treatment decisions in a large single-institution, prospective cohort of patients (pts). Methods: This is an IRB-approved review of a prospective database of pts receiving ODX on an initial primary breast cancer. Data collected included demographics, primary operation, margin status, receptor status, RS, adjuvant treatment, recurrence, and survival. Pts were stratified as low risk (RS < 18), intermediate risk, or high risk (RS > 30). The primary analysis computed Kaplan-Meier estimates for rate of DR at 5 yrs when pts were stratified by RS. Results: From 2003 to 2009, a RS result was obtained on 606 pts. Median follow up was 2.9 yrs (0.1-9.7) and median age was 58 yrs (27-84). Median RS result was 16 (0-63); 344(57%) pts were low, 212(35%) intermediate, 50(8%) high. Endocrine therapy was given to 92.4%, 94.3%, and 87.5% low, intermediate, and high risk pts, respectively. Adjuvant CT was given to 8.6%, 47.6%, and 70.8% low, intermediate, and high risk pts, respectively. There were 8 DR events with 1.8% 5-yr estimated risk of DR. The 5-yr estimated risk of DR was 0.7% for low risk (344) pts, 3.4% for intermediate risk (211) pts, and 2.6% for high risk (50) pts. Among node negative [N(-)] pts (502), the 5-yr estimated risk of DR was 0.8% for low risk (287) pts, 3.7% for intermediate risk (174) pts, and 3.3% for high risk (41) pts. Among node positive [(N+)] pts (54) there was only 1 DR, which was in a high risk pt. Of pts with unknown nodal status (50), there were no DRs. Conclusions: The RS result is predictive of DR at 5 yrs as shown in historical datasets (Table). The use of ODX to guide adjuvant treatment recommendations in our contemporary, prospective cohort resulted in a much lower 5-year DR rate and thus supports its use to guide adjuvant treatment decisions. [Table: see text]
Racial/ethnic disparities in HER2-positive breast cancer in the era of adjuvant trastuzmab.
Authors: Caggiano Vincent , Parise Carol 
Published: February 2017

139 Background: Racial/ethnic disparities in breast cancer survival have been well-documented. Trastuzumab was FDA approved for adjuvant treatment of HER2-positive breast cancer in November, 2006 and has improved survival in these patients. The purpose of this study is to determine if racial disparities have changed in patients who were diagnosed with HER2 positive breast cancer in 2007-2012 when compared with patients who were diagnosed in 2000-2006. Methods: Using the California Cancer Registry, we identified 32,597 cases of first primary female invasive HER2-postive breast cancer. Cases were divided into two cohorts: Early - diagnosed in 2000-2006; Late - diagnosed in 2007-2012. Kaplan-Meier 6-year survival and Cox regression analysis was conducted to assess risk of mortality of African Americans, Hispanics, Asian/Pacific Islanders, and American Indians when compared with whites. Analyses were conducted separately for each cohort and adjusted for stage at diagnosis, grade, age, and socioeconomic status. Hazard ratios and 95% confidence intervals were reported. Use of trastuzumab was not documented. Results: When combining all HER2-positive subtypes (ER+/PR+/HER2+, ER-/PR+/HER2+, ER+/PR-/HER2+, ER-/PR-/HER2+), blacks had an increased risk of mortality (HR = 1.32; 95% CI: 1.16-1.49), in the early cohort but there were no differences for any other race. There were no differences in mortality by race/ethnicity in the late cohort. Separation of the HER2-positive subtypes showed that African Americans with the ER+/PR+/HER2+ subtype had higher mortality than whites (HR = 1.43; 95% CI: 1.17-1.75) in the early cohort but there was no difference in the late cohort. There were no racial disparities within either of the cohorts for the ER-/PR-/HER2+ subtype. Conclusions: Although we were unable to document use of anti-HER2 treatment, the era of adjuvant trastuzumab appears to have attenuated the black/white disparity in HER2 positive breast cancer.
Early detection of mammary tumors in vivo using a highly specific tumor antibody.
Authors: Dréau Didier , Moore Laura Jeffords , Das Roy Lopamudra , Wu Shu-ta , Puri Rahul , Mukherjee Pinku 
Published: February 2017

14 Background: Earlier detection of abnormal cells using target-specific techniques holds great promise. One of those targets Mucin-1 (MUC1) is expressed as a hypo-glycosylated form (i.e., tMUC1) in 95% of breast tumors and plays a crucial role in cancer progression. We have developed Tab004, a monoclonal antibody highly specific to a protein sequence accessible in tMUC1. Here we present data assessing the specificity and sensitivity of Tab004 in vitro and in genetically engineered mice in vivo overtime. Methods: We have developed human MUC1 Tg mice that were bred to mice that carry the oncogene, polyoma middle T antigen driven by the MMTV promoter. These mice designated MMT develop mammary gland tumors spontaneously and expresses the human form of tMUC1. PyVMT and C57Bl/6 served as controls. Mice develop mammary gland hyperplasia between 8-10 weeks of age that progresses to ductal carcinoma in situ by 12-14 weeks and adenocarcinoma by 18-24 weeks. Approximately 40% of the mice develop metastasis to the lung and other organs. The tumor progression appropriately mimics the human disease. MMT mice (n = 20) were injected twice monthly retro-orbitally with 12.5ug (100uL) of Tab004-conjugated to indocyanine green (ICG) and imaged thereafter from 8 to 22 weeks of age. Fluorescence was assessed 4 and 24 hrs post injection using the IVIS system. At euthanasia, tissue was collected for further analyses. Further, human breast tumor and normal mammary epithelial tissues were evaluated by immunohistochemical staining. Results: Tab004 specifically recognizes tMUC1 and not normal MUC1. In MMT mice, ICG-conjugated Tab004 allowed early detection of tumors in vivo sparing recognition of normal mammary epithelia in the C57BL/6 mice or in the PyV MT tumors. Detection with ICG-conjugated Tab004 allowed monitoring of tumor progression overtime. Importantly, ICG-conjugated Tab004 permitted significantly earlier detection than physical examination. Conclusions: The data highlight the specificity and the sensitivity of Tab004 in detecting tMUC1 in vitro, in situ and in relevant murine models in vivo. Thus, Tab004 will have significant clinical relevance for development as a targeted imaging agent and in the future for targeted drug delivery.
Investigation of potential salivary biomarkers for the diagnosis of breast cancer.
Authors: Jinno Hiromitsu , Murata Takeshi , Sunamura Makoto , Sugimoto Masahiro 
Published: February 2017

145 Background: Saliva is an easily accessible and informative biological fluid which has high potential for the early diagnosis of diseases. Saliva-based diagnostics, particularly those based on metabolomics technology, offer a promising clinical strategy by characterizing the association between salivary analysts and a particular disease. The aim of this study is to investigate potential biomarkers in human saliva to facilitate the early diagnosis of breast cancer. Methods: We conducted a comprehensive metabolite analysis of saliva samples obtained from 60 breast cancer patients and 20 healthy controls, using capillary electrophoresis time-of-flight mass spectrometry (CE-TOF-MS). Statistical analyses were performed by using a nonparametric Mann-Whitney U test, multiple logistic regression and the receiver operating characteristics (ROC) to evaluate the predictive power of biomarkers. Results: Forty-nine patients (81.7 %) had invasive ductal carcinoma (IDC) and 9 patients (15.0 %) had ductal carcinoma in situ. In 33 patients receiving neoadjuvant treatment, saliva samples were obtained just before surgery. After removing the concomitantly observed peaks and noise peaks, an average of 205 peaks were derived from the metabolites. Among these peaks, five potential salivary biomarkers demonstrated significantly higher concentrations in breast cancer patients comparing with healthy individuals (p < 0.05). Especially, salivary biomarkers obtained from patients with IDC before neoadjuvant treatments tended to be higher concentrations than those obtained after treatment. In these metabolites, the area under the ROC curves (AUCs) were 0.765 for substance A, 0.716 for substance B, 0.809 for substance C, 0.819 for substance D and 0.850 for substance E. Conclusions: Salivary metabolites are promising biomarkers for the early diagnosis of breast cancer.
Elevated neutrophil to lymphocyte ratio to predict survival outcome after recurrence for patients with triple-negative breast cancer.
Authors: Iwase Toshiaki , Sangai Takafumi , Sakakibara Masahiro , Nagashima Takeshi , Miyazaki Masaru 
Published: February 2017

24 Background: Recent studies show that obesity plays a major role in causing chronic inflammation by producing several inflammatory cytokines. On the other hand, there is limited research focusing on the effect of obesity in recurrent breast cancer treatments. Therefore, we set out to clarify the impact of obesity related inflammation by Neutrophil to Lymphocyte ratio (N/L ratio) in recurrent breast cancer treatment. Methods: From January 2005 to December 2014, 93 patients with recurrent breast cancer after surgery were included. World Health Organization body mass index (BMI) classification was used for evaluating the degree of obesity. Muscle mass amount was also analyzed. Lumber skeletal muscle index (LSMI, cm2/m2) was generated by standardizing each patient’s muscle area (m2) at the third lumber vertebrae level in axial CT data. Less than 50m2 in LSMI was defined as pre-sarcopenia. N/L ratio was calculated from the laboratory data, and more than 3.0 was defined as high N/L group. Results: Patient background showed there were 20 overweight patients and 2 obese patients. Twenty-eight cases had pre-sarcopenia. In univariate analysis, N/L ratio had no significant differences among BMI categories. However, triple negative (TN) type demonstrated significantly high N/L ratio compared to other subtypes (p < 0.05). LMSI had significant negative correlation to N/L ratio (p < 0.05). In survival analysis, Overweight/Obese group showed significantly shorter OS (p < 0.05). High N/L ratio group also showed similar results (p < 0.05). When stratified by intrinsic subtypes, TN type demonstrated significantly shorter OS (p < 0.05). Additionally, Overweight/Obese groups in TN type had notably shorter OS (p < 0.05). In multivariate analysis, subtype and N/L ratio were independently related to OS (Hazard ratio: 3.3 in TN type, 2.9 in High NL ratio group). Conclusions: Present study did not show any significant relationship between obesity and chronic inflammation in recurrent breast cancer setting. On the contrary, intrinsic subtype was significantly related to inflammation, leading to pre-sarcopenia and worse OS. Whether obesity promotes inflammation in TN type needs more investigation.
Human insulin to increase breast cancer risk in Taiwanese women with type 2 diabetes.
Authors: Tseng Chin-Hsiao 
Published: February 2017

26 Background: To investigate whether human insulin use may be associated with risk of breast cancer in Taiwanese women with type 2 diabetes. Methods: The reimbursement databases of all Taiwanese diabetic patients from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2004 and a total of 482,065 women with type 2 diabetes were followed up for breast cancer incidence until the end of 2009. Incidences for ever-users, never-users and subgroups of human insulin exposure (using tertile cutoffs of time since starting insulin, cumulative dose and cumulative duration of insulin) were calculated and the multivariable-adjusted hazard ratios were estimated by Cox regression. Results: There were 59,830 ever-users and 422,235 never-users, with respective numbers of incident breast cancer of 559 (0.93%) and 4,711 (1.12%), and respective incidence of 207.7 and 215.1 per 100,000 person-years. The overall adjusted hazard ratios (95% confidence intervals) did not show a significant association with insulin [1.098 (0.994-1.212)]. However, significant trends for the different categories of the dose-responsive parameters were observed. Patients in the third tertiles consistently showed a significantly higher risk of breast cancer while compared to never-users: 1.263 (1.093-1.458), 1.339 (1.164-1.540) and 1.331 (1.158-1.531) for ≥ 67 months for time since starting insulin, ≥ 39,000 units for cumulative dose of insulin, and ≥ 21.8 months for cumulative duration of insulin, respectively. Conclusions: This study discloses a significantly higher risk of breast cancer associated with the use of human insulin, demonstrating a significant dose-responsive relationship.
Age-related variations: A retrospective analysis of 851 prospectively collected patient samples to determine the benefit of combining combinatorial protein biomarker assay for risk assessment in women with dense breast.
Authors: Reese David Emery , Silver Michael , Henderson Meredith C. , Borman Sherri , Corn Christa , Mulpuri Rao , Benson Kasey 
Published: February 2017

27 Background: Clinicians often experience difficulty in differentiating benign lesions from invasive breast cancers in patients designated as dense breast. A major limitation of radiological breast cancer screening methods involves a decrease in sensitivity and specificity in women with dense breast. Thus, we sought to test whether Klarify Breast, a combinatorial protein-based biomarker panel could improve early detection of significant breast lesions in a controlled fashion. Clearly, a diagnostic assay that would provide biochemical evidence in the patient’s clinical course is greatly needed. Methods: We have conducted two independent, multi-center, prospective clinical trials to establish the clinical validity of Klarify Breast – an assay that uses multiple Serum Protein Biomarkers (SPBs), Tumor-Associated Autoantibodies (TAAbs), patient specific clinical data and develop a score to differentiate patients with benign breast disease from those with invasive breast cancer. Independent panels of biomarkers and associated algorithms were developed using prospectively collected samples from women under age 50 (n = 351) and from women ages 25-75 (n = 500). Here, we present the benefit of integrating the results of Klarify Breast test with patient imaging to best assess risk in women with dense breast. Results: While performance of the assay was somewhat age dependent (women under the age of 50 demonstrated a higher sensitivity and specificity than women over the age of 50). Here we present data that both groups of women clearly benefit from the addition of a biomarker assay combined with standard of care imaging in identifying invasive breast lesions. Conclusions: Clearly, in women with dense breast, where radiologic studies alone do not permit full assessment in women with a dense breast finding. The biomarker test here, comprised of TAAbs and SPBs, offers a clear advantage in terms of NPV, PPV, Sensitivity and specificity. The results argue strongly for the use of appropriate biomarkers to augment imaging based breast cancer screening in women with dense breast or those who are at high risk. Clinical trial information: NCT01839045, NCT02078570.
Concordance of preoperative US-guided tattooing of axillary lymph nodes to sentinel lymph nodes and comparison of their pathologic results according to imaging modalities in breast cancer patients.
Authors: Kim Hye Jung , Jung Jin Hyang , Park Ho Yong , Park Ji-young 
Published: February 2017

28 Background: We wanted to know the concordance of preoperative ultrasound (US)-guided tattooing of axillary lymph nodes (ALNs) to sentinel lymph node and to correlate MR and PET-CT findings with the final histologic results. Methods: Axillary US examination was performed for all breast cancer patients before sentinel lymph node biopsy. The detected lymph nodes in US were classified as negative (group I, enlarged but image-benign) or positive (group II, image-suspicious) finding for metastases based on US, MRI and PET-CT findings. US-guided tattooing for ALNs was performed preoperatively by injection of 3cc of activated charcoal into the cortex of lymph node and the adjacent soft tissue. We evaluated their concordance to sentinel lymph node and correlated the histologic results of US tattooed LN according to each imaging modality. Results: Forty ALNs were tattooed and sentinel nodes corresponded to tattooed nodes in all except one patient with a tattooed non-sentinel node. Ten in group I and 30 in group II on US, 18 in group I and 22 in group II on MR, and 19 in group I and 21 in group II on PET-CT. Eight cases had evidence of metastases in final histology, 2 (20.0%) in group I and 6 (20.0%) in group II on US, 4 (22.2%) in group I and 4 (18.1%) in group II on MR, and 6 (31.6%) in group I and 2 ( 9.5%) in group II on PET-CT. Conclusions: US-guided tattooing is a feasible method for marking ALNs. In addition, tattooed lymph nodes correlate well with sentinel nodes, which may obviate the need for additional localization for axillary staging.
Group visits for women at high risk for breast cancer: Facilitated education and support sessions.
Authors: Trotter Kathryn , Seewaldt Victoria , Riley Stephanie 
Published: February 2017

30 Background: Women at increased risk for breast cancer frequently have anxiety and stress. They often have questions and concerns that are not discussed at their medical appointment. Methods: The Duke High-Risk Breast Clinic consists of over 1,110 women undergoing high-risk screening due to 1) BRCA-mutation, 2) familial pattern of breast cancer inheritance, 3) prior abnormal biopsy, or 4) > 20% lifetime risk of breast cancer. Approximately 31% of clinic participants are African-American and 65% are European-American. Women participating in the Duke High-Risk Breast Clinic were offered a monthly, hour-long education and support session at no charge. The goal was to help women answer key questions and provide a supportive environment. A five-month pilot was initiated in 02/2015. The NP adapted the Centering Healthcare Institute’s group visit model (www.centeringhealthcare.org). Attendees completed a Self-Assessment Sheet (SAS) on arrival. A clinic conference room was used, with chairs arranged in a circle, and refreshments available. After an icebreaker opening, the NP led a facilitated discussion on timely topics, which the patients actively prioritized. Guest experts (radiologist, geneticist, gynecologist, mental health provider) also participated. A participant or the team navigator led the closing activity, and then a brief patient satisfaction survey was completed. Patient support persons were welcomed. Results: 100% of the participants (N = 38) strongly agreed that the educational session was a resourceful way of addressing healthcare concerns, and 92% agreed that they would attend more educational sessions. Several women came at least 3 of the sessions with 30% traveling 1-3 hours. Comments were positive. Common topics on the SAS were: genetic risk/testing, risk factors for breast cancer, screening tests/tools, and nutrition. Further topics requested: “When to be concerned about aches, pains, ‘lumps’, and how not to over react”, research updates, 3D imaging, and stress. Conclusions: Women found this group visit model highly informative and helpful. Several commented they would like the sessions to be longer, or be offered in the evening. Further commitment to this group visit format is warranted.