bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P1-07-21: Relationship between hereditary cancer syndromes and oncotype DX recurrence score
Authors: Toltzis S , Casasanta N , Lipinski S , Marino A , McHenry A , Denduluri N , Rodriguez P , Kaltman R 
Published: February 2018

Abstract
Background
Oncotype DX Recurrence Score (RS) is used to stratify breast tumors into those likely to respond to cytotoxic chemotherapy. Women and men with hereditary cancers tend to have tumors that are chemosensitive. We hypothesize that a high RS may harbor a signal of potential hereditary risk. This analysis aims to identify whether breast cancer patients with hereditary cancer syndromes have a disproportionate amount of high RS compared to sporadic cases.
Methods
Individuals with a personal history of breast cancer who received treatment at participating research facilities and had hormone receptor positive breast cancer, Oncotype DX testing and hereditary cancer mutation testing were included. Oncotype DX RS was recorded along with the type of genetic testing and the genetic testing results. RS was categorized as low (0-17), intermediate (18-30), and high (31+). Those with deleterious mutations in any known hereditary cancer gene were considered positive. Individuals with a variant of uncertain significance (VUS) or negative genetic testing result were considered negative. Difference in distribution of tumors with low, intermediate, and high Oncotype DX results in those with hereditary breast cancers compared to those with sporadic breast cancers was determined with Chi-square.
Results
419 patients with Oncotype DX testing from two clinical sites were collected from 2013. Of those, 123 underwent genetic risk assessment. Mutations identified included the following genes: BRCA1 (1), BRCA2 (5); CHEK2 (3); BRIP1 (3); NBN (2); MSH6 (1). Of those testing positive for a deleterious mutation, the number of patients with RS results in each category were 5, 4 and 6 for low, intermediate and high, respectively. For those considered negative on hereditary cancer panel testing, the RS results were 76, 52 and 8, respectively. Of those with high RS, 43% had deleterious mutations. Chi square test was statistically significant for a difference between the RS of those with deleterious hereditary mutations versus those with sporadic cancers (p = 0.000086).
Conclusions
High RS may indicate a higher likelihood of harboring a hereditary cancer syndrome. Further investigation with larger numbers and multivariate analysis is needed to validate if a high RS serves as an independent predictor of benefit from genetic counseling and testing.
Citation Format: Toltzis S, Casasanta N, Lipinski S, Marino A, McHenry A, Denduluri N, Rodriguez P, Kaltman R. Relationship between hereditary cancer syndromes and oncotype DX recurrence score [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-07-21.
Abstract P1-12-02: Clinical efficacy of a humanized monoclonal antibody against the Lewis-Y antigen (Ley): Results of a phase II clinical trial
Authors: Testa L , Serrano SV , Arai RJ , Zorzetto MC , Freitas-Junior R , Maletz O , Mano MS , Hoff PM 
Published: February 2018

Abstract
Background. The Lewis-Y (Ley) antigen is a blood group-related antigen expressed in over 70% of epithelial cancers. It is expressed in 44% of breast cancers.
Objectives. The primary endpoint was to evaluate the clinical efficacy of hu3S193, a humanized monoclonal antibody against the Lewis-Y antigen, in advanced hormone positive breast cancer after failure of at least one line of endocrine therapy.
Methods. This multicenter, single arm, phase II trial enrolled eligible patients to receive hu3S193 weekly at a dose of 20 mg/m2 intravenously. Efficacy was measured as clinical benefit rate (objective response or stable disease for at least 24 weeks).
Results. Of 49 patients screened, 27 (55%) were Ley positive. Of these 27, only 20 were eligible for efficacy analysis. No complete or partial responses were observed. Five patients had stable disease for 24+ weeks (clinical benefit rate 25%). One patient remains on study drug maintaining stable disease for over 2 years. This patient had high expression of Ley. The most common treatment-related adverse events were headache (50%), cough (45,5%) and nausea/vomiting (31,8%).
Conclusions. Hu3S193 lacked sufficient activity in is trial and the investigators stopped accrual at the first interim analysis. High expression of Ley might play a role in selecting patients to this strategy.
Citation Format: Testa L, Serrano SV, Arai RJ, Zorzetto MC, Freitas-Junior R, Maletz O, Mano MS, Hoff PM. Clinical efficacy of a humanized monoclonal antibody against the Lewis-Y antigen (Ley): Results of a phase II clinical trial [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-12-02.
Abstract P2-02-03: Assessment of an immune response panel of serum protein biomarkers for the non-invasive detection of breast cancer
Authors: McQuary PR , Copeland KAF , Sheibani NM , Friedman LA , Korn RL , Fiorica JV , Lourenco AP , Struthers SE , Hesterberg LK 
Published: February 2018

Abstract
Background: Breast cancer screening guidelines (ACS) recommend annual mammography for asymptomatic women ages 45 to 54 and once every two years for women age 55 and older. Women with suspicious screening mammograms are recommended for a diagnostic mammogram and may also undergo MRI or ultrasound. Ultimately, unresolved suspicious findings frequently result in the recommendation of a breast biopsy. Approximately 10% of suspicious diagnostic mammograms are recommended for breast biopsies and a large majority of these biopsies yield benign results. We conducted a screen for serum protein biomarkers and identified a novel panel for the non-invasive detection of breast cancer with the goal of developing a diagnostic test that can reduce the number of patients with benign pathology undergoing invasive biopsies.
Methods: Serum samples were collected at 4 US sites from women with suspicious diagnostic mammogram findings (primarily BI-RADS category 4 and breast composition b/c) undergoing biopsy for evaluation of a potential malignancy. Serum samples from 136 patients (87 benign pathology and 49 malignant pathology) were evaluated on the olink® Proteomics Immune Response Panel (92 analytes). Statistical screening methodologies, such as individual t-tests with control for false discovery, were used to identify markers with the potential to distinguish benign from malignant pathology. The candidate markers were further studied and combined using generalized linear modeling to develop potential diagnostic models.
Results: A 19-marker model resulted in an AUC of 0.94 with a sensitivity of 90% and a specificity of 80%. A 12-marker model resulted in an AUC of 0.93, yielding a sensitivity of 90% with a specificity of 77%.
Conclusions: This study reveals a novel panel of serum protein biomarkers that may allow for the non-invasive and sensitive detection of breast cancer in patients presenting with suspicious findings on mammography, thus reducing the need for invasive biopsies.
Citation Format: McQuary PR, Copeland KAF, Sheibani NM, Friedman LA, Korn RL, Fiorica JV, Lourenco AP, Struthers SE, Hesterberg LK. Assessment of an immune response panel of serum protein biomarkers for the non-invasive detection of breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-02-03.
Abstract P2-05-07: Whole exome sequencing of extreme responders reveals low mutation burden in metastatic breast cancer
Authors: Sohn J , Lim SM , Kim E , Kim S , Koo JS , Kim SI , Park S , Park HS , Kwon N-J , Kim GM , Kim S 
Published: February 2018

Abstract
Background: Extreme responders to anticancer therapy are rarely encountered in the treatment of advanced breast cancer patients, but their treatment response have not been investigated on the whole exome level. We performed whole exome analysis to characterize genomic landscape of extreme responders in metastatic breast cancer patients.
Methods: Clinical samples were obtained from patients who showed exceptional response to anti-HER2 therapy or hormonal therapy. Non-responders were selected among those who did not respond. Matched breast tumor tissue (somatic DNA) and blood samples (germline DNA) were collected from a total of 18 responders (12 ER+, 6 HER2+) and 8 non-responders (6 ER+, 1 HER2+, 1 TNBC). Whole exome sequencing using Illumina HiSeq2500 was performed on the 26 patients (52 samples). Somatic single nucleotide variants (SNVs), indels and copy number variants (CNVs) were identified for each patient genome. Group specific somatic variants and mutation burden were statistically analyzed.
Findings: Cancer exomes were characterized by 1,455 somatic single-nucleotide variants (1,327 missense, 80 nonsense, 36 splice-site, 12 start/stop-lost), 149 insertions/deletions (108 frameshift, 41 inframe), with a median of 1 mutations per Mb (0.2 to 2.7 mutations per Mb) in all patients. Responders harbored a significantly lower non-synonymous mutation burden than non-responders (median, 27 vs. 90.5, P=0.01), and copy number variation burden was also lower (median 23 vs. 31, P=0.14). Multivariate analyses of factors influencing progression-free survival showed that high mutation burden and visceral metastases were significantly related with progression.
Interpretation: Extreme responders of metastatic breast cancer are characterized by low nonsynonymous mutational burden.
Citation Format: Sohn J, Lim SM, Kim E, Kim S, Koo JS, Kim SI, Park S, Park HS, Kwon N-J, Kim GM, Kim S. Whole exome sequencing of extreme responders reveals low mutation burden in metastatic breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-05-07.
Abstract P2-07-08: Prognostic relevance of claudins 4 and 7 in invasive breast carcinoma (NOS) subtypes: A large tissue microarray study
Authors: Logullo AF , Rocha RM , Stiepcich M , Soares FA , Pasini FS , Nonogaki S , Brentani MM 
Published: February 2018

Abstract
Molecular phenotyping has improved the understanding of a wide range of breast cancer disease. Recently, a new molecular subtype denominated “claudin-low” (CL) was described in breast cancer and correlated to worse prognosis and to CD44+/24- stem cell profile. Among 19 known claudin proteins, isotypes 4 (CL4) and 7 (CL7) are the most common in the breast biology. Objective: To verify differences in CL4 and CL7 immunoexpression between Luminal A, HER-2, and triple negative breast cancer phenotypes; and their association to CD44/24 status and tumor prognosis. Design: Estrogen and progesterone receptor status (ER/PR), HER-2, CL4 and CL7 expression and CD44/24 profiles were evaluated in 803 invasive ductal breast carcinomas arranged into four tissue microarrays (TMA) and results were correlated with prognosis and important clinical data. Results: 503 (62.6%) cases were positive for CL4 and 369 (46.0%) cases for CL7. The majority (199/283, 70.3%) of CL4 negative cases were clustered in the luminal A subtype whereas 63 (22.3%) showed triple negative profile and the remaining 21 cases (7.4%) exhibited positive HER-2 expression (p&lt;0.001). Claudin 7 negative samples (44.2%) tended to follow the same pattern. CL4 positive expression was significantly associated to HER-2 expression, presence of lymph nodes and increased tumor grades and inversely correlated to ER and PR expression. However, there was no association between CL7 expression and any of these features. Both CL4 and CL7 did not show correlation to the stem cell markers (CD44+/CD24-) or worse prognosis (survival and disease-free interval). Conclusion: Claudins 4 and 7 immunoexpression did not provide additional prognostic information within breast cancer subtypes.
Citation Format: Logullo AF, Rocha RM, Stiepcich M, Soares FA, Pasini FS, Nonogaki S, Brentani MM. Prognostic relevance of claudins 4 and 7 in invasive breast carcinoma (NOS) subtypes: A large tissue microarray study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-07-08.
Abstract P2-09-26: Frequency and mechanisms of elevated somatic mutation burden in metastatic breast cancer and response to immune checkpoint blockade
Authors: Cobain EF , Robinson DR , Wu Y-M , Lonigro R , Vats P , Rabban E , Kumar-Sinha C , Schott AF , Smerage JB , Morikawa A , Burness ML , Van Poznak CH , Griggs J , Wicha M , Hayes DF , Chinnaiyan AM 
Published: February 2018

Abstract
Background: Immune checkpoint blockade (ICB) is effective in the treatment of various malignancies. Thus far, however, results in breast cancer have been mixed. Elevated tumor mutational load, and subsequent increased likelihood of forming immunogenic neoantigens, has been correlated with response to ICB. Mutational load observed in breast cancers varies widely. However, most studies have assessed mutational load using primary tumors. Few studies have explored the frequency of high mutational load, molecular mechanisms accounting for this phenomenon, and its potential impact on response to ICB in metastatic breast cancer (MBC).
Methods: From 2011-2016, 124 patients (pts) with MBC of varying subtypes underwent research biopsy of their metastatic disease for whole genome, exome and transcriptome sequencing of tumor and matched normal sample through the Michigan Oncology Sequencing Center (Mi-OncoSeq). Those pts with elevated somatic mutation load were defined as having greater than 10 mutations per megabase of targeted sequencing and mutational signatures accounting for high mutation load were noted. Pts treated subsequently with ICB were followed to assess response.
Results: Twelve MBC pts had high mutation load (10% of cohort). Eight pts had estrogen receptor (ER) positive MBC and 4 pts had metastatic triple negative breast cancer (TNBC). In 5 cases, a clear mutational signature accounting for high mutation load was evident. Two TNBC cases harbored an APOBEC mutational signature in addition to 1 TNBC and 2 ER positive tumors displaying a microsatellite instability signature (MSI-H). Among the tumors with MSI-H signature, 1 case was associated with a pathogenic germline alteration in MLH1. Two pts were subsequently treated with ICB on a clinical trial. One pt came off study after 3 months due to progressive brain metastases and another had partial response to therapy lasting 7 months.
Conclusions: Elevated somatic mutation burden in MBC is observed in approximately 10% of pts, and is detected in both ER positive and TNBC. Since high mutation burden has been associated with increased likelihood of response to ICB, identification of this genomic feature could have important therapeutic implications for MBC pts.
Citation Format: Cobain EF, Robinson DR, Wu Y-M, Lonigro R, Vats P, Rabban E, Kumar-Sinha C, Schott AF, Smerage JB, Morikawa A, Burness ML, Van Poznak CH, Griggs J, Wicha M, Hayes DF, Chinnaiyan AM. Frequency and mechanisms of elevated somatic mutation burden in metastatic breast cancer and response to immune checkpoint blockade [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-09-26.
Abstract P2-10-01: Validation that a histone gene signature predicts anthracycline response in early breast cancer
Authors: Spears M , Kornaga E , Lyttle N , Liao L , Bayani J , Quintayo M-A , Yao CQ , D'Costa A , Boutros PC , Twelves CJ , Pritchard KI , Levine MN , Nielsen TO , Shepherd L , Bartlett JMS 
Published: February 2018

Abstract
Background: The use of anthracycline-based chemotherapies has improved overall and disease free survival in breast cancer. However, anthracyclines can have significant toxicities including cardiotoxicity and leukemia. It is, therefore, imperative to identify those patients who will benefit from adjuvant anthracycline treatment and patients who could be spared unnecessary toxicities and be considered for alternative adjuvant therapy. Previous work performed by our laboratory identified a histone gene expression signature as a predictive marker of anthracycline benefit in the BR9601 clinical trial. In this study we validate the 18 histone gene signature in the MA.5 clinical trial and examine the role of the signature in individual intrinsic subtypes of breast cancer.
Methods We analysed the CCTG MA.5 clinical trial in a prospectively planned retrospective biomarker approach to validate this signature and tested the role of intrinsic subtyping as predictive markers of anthracycline benefit. RNA was extracted from patients in the MA.5 adjuvant trial evaluating the addition of epirubicin (E) to CMF and analysed using NanoString technology. Log-rank analyses validated the predictive values of the signature on distant relapse-free survival (DRFS). Cox-regression models tested independent predictive value on DRFS in the presence of treatment, age, tumour size, nodal status, HER2, ER status and grade, and treatment by marker interactions.
Results Analysis of the MA.5 clinical cohort revealed that patients whose tumour had low histone gene signature expression experienced increased DRFS (HR: 0.54, 95% CI 0.38-0.76, p=0.001) when treated with CEF compared with patients treated with CMF alone. Conversely, there was no apparent benefit of CEF vs CMF in patients with high histone gene expression signature (HR: 1.01, 95%CI 0.66-1.55, p=0.963). After multivariate analysis and adjustment for HER2, nodal status, age, grade and ER, the treatment by marker interaction for the gene signature was 0.54 (95%CI 0.31-0.94, p=0.030) for DRFS.
The predictive impact of the histone signature was independent of intrinsic subtype.
Conclusion The histone gene expression signature is an independent predictor of anthracycline benefit and could be a potential candidate diagnostic assay for patients with early breast cancer.
Citation Format: Spears M, Kornaga E, Lyttle N, Liao L, Bayani J, Quintayo M-A, Yao CQ, D'Costa A, Boutros PC, Twelves CJ, Pritchard KI, Levine MN, Nielsen TO, Shepherd L, Bartlett JMS. Validation that a histone gene signature predicts anthracycline response in early breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-10-01.
Abstract P2-12-08: Rates of re-excision surgery after implementation of consensus guidelines on margins for breast- conserving surgery in stage I and II invasive breast cancer: A Nova Scotian experience
Authors: Drohan AE , Helyer LK 
Published: February 2018

Abstract
Background: In Canada, most women with early invasive breast cancer will be treated with breast-conserving surgery (BCS). The proportion of patients requiring re-excision surgery after BCS varies province to province. Until recently, there was no universally accepted definition for adequate margin width following BCS. The Society of Surgical Oncology (SSO) and American Society for Radiation Oncology (ASTRO) published consensus guidelines in 2014 to help regulate practice. The objective of this study was to determine the proportion of patients undergoing re-excision surgery before and after guideline implementation at our institution.
Methods: We performed a retrospective review of all patients with invasive breast cancer and/or ductal carcinoma in situ (DCIS) who underwent re-excision surgery between October 1, 2010- October 31, 2011 (pre-guideline) and October 1, 2014- May 30, 2016 (post-guideline). The proportion of patients requiring re-excision surgery was calculated for each time period and patient characteristics and clinical outcomes were compared.
Results: There were 188 patients identified who underwent BCS in the pre-guideline time period and 411 patients in the post-guideline time period. The proportion of patients undergoing re-excision surgery significantly decreased from 13.8 % to 7.8 % after guideline implementation (p = 0.02). Patient characteristics were similar between those who underwent re-excision before and after guideline implementation. In patients requiring re-excision surgery, histological and pathological features were similar between time periods. Margin width and indication for re-excision surgery varied between time periods. Among women who had re-excision surgery in the pre-guideline group, most (50%) had an invasive cancer margin &gt; 1 mm. However, after guideline implementation, a frankly positive invasive cancer margin was the most common indication for re-excision surgery (65%). No significant differences in clinical outcomes were observed between patients who underwent re-excision surgery before and after guideline implementation.
Conclusion: The proportion of patients undergoing re-excision surgery after BCS has significantly decreased after SSO-ASTRO guideline implementation at our institution. This data suggests that among women with invasive breast cancer and/or DCIS, the implementation of SSO-ASTRO guidelines has led to a 43.5% decline in re-excision surgery.
Citation Format: Drohan AE, Helyer LK. Rates of re-excision surgery after implementation of consensus guidelines on margins for breast- conserving surgery in stage I and II invasive breast cancer: A Nova Scotian experience [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-12-08.