bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrative oncology from the patient advocate perspective.
Authors: Fonfa Ann 
Published: February 2017

133 Background: As a 20+ year breast cancer survivor I sought to find and offer information on natural cancer strategies. At first I needed them for my own cancer protocol, then to help others Integrative Oncology refers to the simple, natural and non-toxic approaches that can reduce toxicity, possibly enhance the efficacy of conventional treatment, and create feelings of well-being and control in people dealing with cancer. Many studies, some from long ago, have pointed to the strong patient interest in Integrative Oncology (formerly known as CAM). Yet the professional oncology community’s knowledge has failed to keep up. Trained to seek level 1 studies, they have failed to note the preponderance of all the other evidence available supporting natural approaches. Due to cost, most natural products/substances are not reviewed at level 1 and probably will never be. Methods: We’ve created a simple program we call 3 Steps 4 Health, which offers anyone in cancer treatment a guide to improved health. We will present the research that backs up these simple ideas that can be incorporated into anyone’s protocol. We also have a handout to reduce toxicities that is evidence-based to help with those adverse effects that plague modern cancer patients. So many suffer from neuropathy – there are quite a few methods to protect or treat this with complementary therapies that can be integrated into conventional treatment. Results: ASCO has pointed to the value of Yoga, of ginger, and other natural approaches but oncology professionals have been slow to adopt or recommend. Conclusions: We will provide evidence-based information on integrative oncology and the 3 Steps 4 Health program.
HER2 amplification and overexpression between primary and liver metastatic breast cancer: Significance and implication.
Authors: Williams Casey B. , De Pradip , Klein Jessica , Williams Kirstin Anne , Cyr Brigitte , Small Misty , King Michelle , Carlson Jennifer , Sun Yuliang , Young Brandon Michael , Willis Scooter , Dey Nandini , Krie Amy K. , Leyland-Jones Brian 
Published: February 2017

150 Background: The systemic management of metastatic breast cancer (MBC) is mostly based on the ER or HER2 status of the primary tumor. However, the hormonal status or the amplificaction/overexpression HER2 may change in every metastatic site because of the effects of the long-term treatment of metastatic cancer with endocrine therapy, chemotherapy, or targeted agents. The purpose of this study was to investigate the frequency of change in HER2 expression in primary and distant metastatic tumors (especially in liver) in HER2+ breast cancer patients. Methods: We retrospectively analyzed the results of 31 consecutive metastatic breast cancer patients that were seen in our center over 4 months from February 2014 through May 2014. All patients were rebiopsied after consultation and samples were sent for standard immunohistochemistry (IHC) for ER, PR, and HER2 and formalin-fixed, paraffin-embedded (FFPE) samples were sent for genomic (Foundation Medicine) and proteomic analysis (Theranostics). All results from the metastatic samples were compared to the baseline IHC and/or FISH results for HER2. Results: A change in HER2 status was observed in 26% of the cases. 16% of cases underwent a negative to positive conversion in HER2 status while 10% of cases underwent a positive to negative conversion. It is notable that all 5 patients that underwent a negative to positive conversion in HER2 status had biopsies taken from metastatic disease in the liver. Overall, 45% of patients with metastatic disease in the liver had a negative to positive conversion in HER2 status. Conclusions: The results of this study emphasize the significance of confirming HER2 expression in a recurrence lesion. This discordance may be due to the increasing level of genetic instability occurring throughout disease progression that can significantly influence the alterations of the HER2 gene. If feasible, HER2 reassessment in metastatic lesions should be carefully taken into account, especially for metastases coming from non-HER2 amplified breast cancer. Although HER2 status is usually appraised in primary tumor, knowledge of the HER2 status in metastases may be of potential value for therapeutic decision making.
The basal phenotype as a clinically relevant indicator of trastuzumab resistance in HER2+ breast cancer.
Authors: Choi Michael Phillip , Chung Alice P. , Bose Shikha , Han Bingchen , Qu Ying , Zhang Xiao , Cui Xiaojiang , Giuliano Armando E. 
Published: February 2017

154 Background: Trastuzumab (Herceptin) resistance remains a clinical challenge but the mechanism is not well understood. Recently, studies have identified a subset of Her2+ breast cancer called basal HER2 that expresses basal genes. We investigated the effect of basal gene expression on Herceptin response in HER2+ breast cancer cell lines and on prognosis in HER2+ breast cancer patients. Methods: Non-basal (BT474, SKBR3) and basal (HCC1569, HCC1954, JIMT-1) HER2+ cell lines were chosen based on basal cytokeratin expression. Cell proliferation was assessed after treatment with vehicle, Herceptin (H), Paclitaxel (P), H+P, Akt Inhibitor (AI), and H+AI. HER2 signaling was examined using immunoblotting of p-Akt and p-ERK. Because breast cancer stem cells (BCSC) are linked to basal breast tumors and treatment resistance, we assessed BCSC activity using mammosphere formation and aldehyde dehydrogenase (ALDH) positivity. Immunohistochemical staining of HER2+ breast cancers for basal markers CK5/6, CK14, and EGFR was correlated with clinicopathologic features and survival in 88 patients with Stage 1-3 HER2+ breast cancer treated with Herceptin. Results: Basal HER2 cells were resistant to Herceptin compared to non-basal HER2 cells but this resistance was overcome by Akt inhibition. Immunoblotting showed that non-basal HER2 cells had decreased p-Akt after Herceptin treatment which was not seen in basal HER2 cells. There was no difference in p-ERK levels after Herceptin therapy in all cell lines. Basal HER2 cells had increased mammosphere formation and ALDH positivity suggesting higher stem cell activity compared to non-basal HER2 cells. Of the HER2+ patients, 33/88 (37.5%) expressed at least one basal marker. Basal Her2 tumors were associated with higher grade (p = 0.04) and more ER/PR negativity (p < 0.01). CK14 expression correlated with worse overall survival by log-rank test (p = 0.02), while EGFR showed a similar trend (p = 0.06). Conclusions: Basal HER2 breast cancer cell lines have Herceptin resistance which may be due to constitutively active Akt signaling and increased stem cell activity. Clinically, basal marker expression predicts Herceptin resistance and worse outcomes in HER2+ breast cancer patients.
Incidence of germline BRCA mutation in patients with ER-low positive/PR negative/HER-2 neu negative tumors.
Authors: Sanford Rachel Ann , Song Juhee , Gutierrez-Barrera Angelica M. , Litton Jennifer Keating , Bedrosian Isabelle , Albarracin Constance T. , Valero Vicente , Arun Banu 
Published: February 2017

2 Background: The 2011 ASCO/CAP guidelines recommend that breast cancers with estrogen receptor (ER) staining as low as 1% on immunohistochemistry be considered ER-positive. In practice, there remains significant variability in what clinicians consider ER-positive versus ER-negative. Current NCCN guidelines recommend that patients under age 60 with triple-negative breast cancer (TNBC) be referred for genetic counseling and consideration of germline BRCA mutation testing. With the 2011 ASCO/CAP guidelines, the definition of TNBC has changed to exclude patients with ER low-positive (1-9%) tumors; hence patients with ER-low positive tumors (formerly considered ER negative) may not be referred for genetic counseling and BRCA testing. This may lead to “undertesting” of appropriate patients. The incidence of BRCA germline mutations in patients with ER-low positive versus ER-negative (0%) tumors is unknown. We sought to identify whether the incidence of BRCA mutation differed between patients with ER-negative/PR-negative/HER-2 neu negative tumors and patients with ER-low positive/PR-negative/HER-2 neu negative tumors. Methods: We performed a review of a prospectively maintained research database of all patients with ER < 10%, PR 0% and HER-2 neu–negative breast cancers who were referred for genetic risk assessment and testing for BRCA mutation at UT MD Anderson Cancer Center. Results: Of 144 patients who underwent BRCA mutation testing, 22 (15%) had ER-low positive tumors while 122 (85%) had ER-negative tumors. Among patients with ER-low positive tumors, 7 of 22 (31.8%) were found to have a deleterious BRCA 1/2 mutation, while 33 of 122 (27%) with ER-negative tumors were found to have a deleterious BRCA 1/2 mutation. The incidence of deleterious BRCA 1/2 mutation in patients with ER-low positive tumors versus those with ER-negative tumors was not statistically significantly different (p = 0.6457). Conclusions: The rate of deleterious BRCA 1/2 germline mutations in ER-negative versus ER-low positive (1-9%) breast cancer is similar. Therefore, we strongly recommend that BRCA testing continue to be offered to women under age 60 with tumors that are ER-low positive/PR-negative/HER-2 neu negative.
Use of serum biomarkers to differentiate benign breast lesions from invasive breast cancer in women with a BI-RADS 3 or 4.
Authors: Henderson Meredith C. , Silver Michael , Yeh Susan , Corn Christa , Borman Sherri , Reese David Emery 
Published: February 2017

20 Background: The Provista Biomarker Assay (PBA) combines multiple serum biomarkers, measured at high sensitivity, in order to determine the likelihood of an invasive breast tumor at the time of testing. PBA, when paired with traditional breast imaging technologies, provides a biochemical tool that can help guide additional imaging or biopsy decisions. As part of our ongoing efforts to characterize clinical performance, we conducted a proof-of-concept study wherein PBA assay performance was tested in prospectively enrolled BI-RADS 3 and 4 patients. Methods: To maximize performance and sensitivity, we utilized the Meso Scale Discovery ELISA-based system to analyze a randomized cohort of 350 prebiopsy serum samples from women under the age of 50. Enrollment in the trial required a BI-RADS 3 or 4 radiologic assessment utilizing multiple imaging modalities. Serum proteins and autoantibodies were measured for each patient and applied to a proprietary statistical algorithm. Results: We were able to obtain statistically significant differentiation using the Provista Biomarker Assay in women under age 50 who were characterized as BI-RADS 3 or 4. The majority of patients in the study were diagnosed with a benign breast lesion, consistent with prior studies. However, the data indicate that PBA, when used in combination with imaging techniques, more accurately informs clinical decision-making. Conclusions: The Provista Biomarker Assay provides a powerful tool for physicians to more accurately assess patients with a BI-RADS 3 or 4 classification. With more clinical evidence, the assay may translate into changes in clinical treatment decisions for women under the age of 50 with a BI-RADS 3 or 4 classification. Clinical trial information: NCT01839045.
Next-generation sequencing for inherited cancer risk assessment: Under the hood at Counsyl.
Authors: Maguire Jared Robert 
Published: February 2017

22 Background: Next-generation DNA sequencing (NGS) is the universal nucleic acid assay technology, with the capability to replace nearly all existing DNA assay technologies. In most cases it is more affordable, more accurate, more flexible, and less subject to human error than prior assay technologies such as capillary electrophoresis or genotyping arrays. In the last year especially, NGS utilization in the clinic has increased. The use of NGS to detect single nucleotide polymorphisms (SNPs) and short insertions/deletions (indels) is well established. However, primarily due to novelty, NGS for has not yet often been used in the clinic for the detection of larger copy number variants (CNVs). Instead, supplementary technologies such as multiplex ligation-probe amplification (MLPA) and quantitative PCR (qPCR) have been used to probe large CNVs. Methods: Counsyl’s Family Prep and Inherited Cancer Screens use NGS for detecting SNPs and indels, and also CNV analysis in the genes of interest. Here we present the technical details of the platform and our validation results showing that CNV analysis by NGS meets or exceeds the performance of such analysis by MLPA or endpoint TaqMan. Only two discordant CNV genotypes were found out of 20,086 calls; both discordances are errors in the control assay, and are attributable to technical limitations. Results: See Table. Conclusions: CNVs account for a significant proportion of BRCA1 and BRCA2 associated cancer risk. Our NGS methodology achieves analytical performance previously obtained only by multiple assays, decreasing testing costs and thereby potentially widening access. [Table: see text]
Association of single-nucleotide polymorphisms of USP7 gene with breast cancer suscepbility in Chinese women.
Authors: Jiang Huangang , Zhou Fuxiang , Wang You , Wei Yuehua , Xu Hui , Hu Liu , Wang Wenbo , Zhao Hong 
Published: February 2017

27 Background: The tumor suppressor p53 pathway plays a crucial role in preventing carcinogenesis. It was reported that activity of p53 was regulated by USP7 (Ubiquitin Specific Peptidase 7) and TSPYL5 (Testis-specific Y-encoded-like protein 5). This study was carried out to assess the association between single nucleotide polymorphisms (SNPs) in P53, USP7, TSPYL5 genes and the breast cancer susceptibility in Chinese Han women. Methods: DNA was extracted from the peripheral blood samples of breast cancer patients and age-matched controls. In the first stage, tag SNPs of P53, USP7, and TSPYL5 genes were selected with Hapmap database and Haploview program. The matrix-assisted laser desorption/ionization time-of-flight mass spectrometry assay was used for genotyping. Then, two positive SNPs were determined by polymerase chain reaction- restricted fragment length polymorphisms assay (PCR-RFLP) in the second stage. The ethics committee of Zhongnan Hospital of Wuhan University authorized this study. Results: In the first stage, 23 SNPs were selected and detected in 192 cases and 192 controls. The results demonstrated that the distribution of genotype of rs12924995, rs2304467 in USP7 gene was different in cases and controls (p = 0.026, 0.037, respectively). In the second stage, these two SNPs were determined. A total of 975 cases and 910 controls enrolled in the present study. Hardy-Weinberg equilibrium of rs2304467 and rs12924995 in the control group was tested (p = 0.979, 0.111). Multivariate analysis showed that breast cancer risk of women with C allele (CC or CG genotype) increased (p < 0.001, odds ratio = 1.87, 95% confidence interval, 1.44-2.44), compared with rs2304467 GG carriers. Besides, women with rs12924995A allele (AA or AC genotype) had higher risk of breast cancer than those with CC genotype (P=0.002, odds ratio=1.36, 95% confidence interval, 1.21-1.65). Breast cancer risk of women carried rs2304467C allele and rs12924995A allele also increased (p < 0.001, odds ratio = 2.05, 95% confidence interval, 1.54-2.73). Conclusions: SNPs rs2304467 and rs12924995 in USP7 gene are associated with breast cancer susceptibility in Chinese Han women.
Race, Oncotype DX, and other characteristics in a highly screened population.
Authors: Chun Jennifer , Schnabel Freya Ruth , Schwartz Shira , Billig Jessica , Kern Elizabeth , Hiotis Karen , Axelrod Deborah M. , Guth Amber 
Published: February 2017

32 Background: Oncotype DX breast cancer 21 gene assay recurrence score (RS) is used to predict disease recurrence and response to chemotherapy in order to offer patients the highest treatment benefit to risk ratio. There is a dearth of literature on the relationship of Oncotype RS and race in women with hormone receptor positive and node negative/positive disease. The purpose of this study was to investigate the relationship of race and clinical characteristics (including Oncotype RS) in an insured population of highly screened women with newly diagnosed breast cancer. Methods: The Breast Cancer Database of our institution was queried for patients who were newly diagnosed with breast cancer. We looked at demographics, risk factors, tumor characteristics, and Oncotype RS. Statistical analyses included Pearson’s Chi-Square and Fisher’s Exact Tests. Results: A total of 1,767 women were diagnosed with breast cancer from 1/2010 to 4/2014. The median age was 59 years. There was a total of 1327 (75%) Whites, 162 (9%) Blacks, 163 (9%) Asians, and 108 (6%) Hispanics. Majority of patients had a college-level education (83%), had annual/biannual screening mammography (78%), and clinical breast exams (89%). Majority of patients had invasive ductal carcinoma (61%), early stage (0, I, II) tumors (94%), ER+ (85%), PR+ (72%), Her2-negative (86%), and node-negative disease (80%). Compared to Whites, there was a significantly higher proportion of later stage disease among Blacks (p = 0.001) and Asians (p = 0.003), more triple negative breast cancers among Blacks (p < 0.0001) and higher Ki-67 scores among Blacks (p < 0.001) and Asians (p < 0.001). Oncotype RS was not significantly different among the race categories and a majority of patients had a low Oncotype RS (57%). These results did not change after stratifying for nodal status. Conclusions: In a population of women who had health insurance and were highly screened, we found clinical differences among races with respect to tumor histology. However, we did not find a statistically significant difference among race and Oncotype RS, even after stratifying for nodal status. Further studies are warranted to determine which tumor proliferation markers are contributing to ethnic differences in breast cancer mortality.
Surgical outcome of lobular neoplasia diagnosed in core biopsy: Prospective study of 316 cases.
Authors: Susnik Barbara , Day Deborah , Krueger Janet , Abeln Ellen , Bowman Tara , Lillemoe Tamera J 
Published: February 2017

4 Background: Recommendations for management of lobular neoplasia (LN) including lobular carcinoma in situ (LCIS) or atypical lobular hyperplasia (ALH) diagnosed in core biopsy specimens (CB) are controversial. The aim of our prospective study is to identify subset of patients with LN diagnosed in CB who do not require subsequent surgical excision (SE). Methods: All patients with a diagnosis of ALH or LCIS on CB were referred for SE. Cases with coexistent DCIS or invasive breast carcinoma were excluded. Cases with coexistent ductal atypia including FEA or ADH (LN-DA) and LCIS variants including pleomorphic or necrotic LCIS (LN-V) were separated from classic LN (LN-C). Dedicated breast pathologists and radiologists reviewed all cases with careful imaging/pathology (IP) correlation. Results: From June 2008 to December 2013, 13,772 percutaneous breast CB procedures were performed. A total of 370 patients with LN diagnosed on CB were referred to SE. 302 (82%) patients with 316 lesions underwent SE within 2 months after initial diagnosis. Average age was 55.3, 27% had positive family history and 4% had previous breast carcinoma. After patients with synchronous ipsilateral CB showing cancer were excluded (20 patients) from upgrade analysis, the diagnostic groups included 228 LN-C, 15 LN-V and 53 LN-DA. In the LN-C group I/P discordance represented 6/228 cases (2.6%). Upgrade to carcinoma of LN-C varied between discordant (6/6) and concordant cases (8/222=3.6%). In comparison, upgrades were seen in 26.7% LN-V (4/15), and 28.3% LN-DA (15/53). For concordant LN-C, the imaging target was calcifications in 176/222 cases (81%); 7 were associated with upgrade (3.9%). Upgrades were rare for MRI targeted lesions (0/14) and mass lesions (1/32). Overall, upgrades were similar for ALH and LCIS (3.4% vs. 4.5 %). Conclusions: While LN with nonclassic morphology or with associated ductal atypia requires SE, this can be avoided in classic LN diagnosed on CB targeting calcifications when careful imaging/pathology correlation is applied; the likelihood of unsuspected cancer diagnosis is minimal and limited to coincidental cases. Until larger numbers are studied, excising classic LN diagnosed as masses or MRI detected lesions may be prudent.
Axillary ultrasonographic criteria to predict chemotherapy response in breast cancer patients receiving neoadjuvant chemotherapy.
Authors: Yoo Koun Joy , Kim Sun Mi , Kim Sung-Won , Park So Yeon , Choi Seung-Hee , Lee Jieun , Jang Mi Jung , Yun Bo La 
Published: February 2017

48 Background: The purpose of the study is to evaluate ultrasonographic criteria to predict response of axillary LNs in patients with breast cancer receiving neoadjuvant chemotherapy. Methods: We retrospectively reviewed data of 402 patients who underwent neoadjuvant chemotherapy from August 2003 to December 2012. Of these, 202 breast cancers in 199 patients (bilateral in 2 patients) in whom axillary LN metastasis was confirmed using axillary ultrasonography (US) and US-guided fine-needle aspiration biopsy (FNAB) were included in the study. US evaluation was done for the long and short axes, and cortical thickening before and after chemotherapy. The ratio of decreased long and short axes and cortical thickening on prechemotherapy US was also calculated. Statistical analysis with receiver operating characteristic (ROC) curve was used to determine the valuable ultrasonographic criteria for predicting pathologic complete remission (CR) using Medicalc program. Results: Final pathologic diagnoses of LNs were yNo in 57, yN1 in 76, yN2 in 50 and yN3 in 19 cases. The mean size of LNs were 1.8cm in long axis, 1.0cm in short axis and 0.9cm in cortical thickening on prechemotherapy US and 1.1cm in long axis, 0.6 cm in short axis and 0.4 cm in cortical thickening on postchemotherapy US. The area under the ROC curve (AUC) was 0.578 for cortex thickening, 0.523 for the long axis, and 0.523 for the short axis of LN on postchemotherapy US. The AUC was 0.643 for the decreased cortex thickening ratio, 0.585 for the long axis ratio, and 0.585 for the short axis ratio. The most significant criteria was decreased cortex thickening ratio to the long and short axes (p < 0.05). The sensitivity and specificity of the decreased cortex thickening ratio for predicting CR were 43.7% and 80.7%, respectively, with a 0.5 cut off value. Conclusions: The most significant criteria for predicting CR was decreased cortex thickening ratio to the long and short axes. It is applicable for selecting sentinel LN biopsy candidates from among breast cancer patients who have undergone neoadjuvant therapy.