bluuebunny/crossref_metadata_2025_split huggingface dataset:
Updated results of tucatinib versus placebo added to trastuzumab and capecitabine for patients with pretreated HER2+ metastatic breast cancer with and without brain metastases (HER2CLIMB).
Authors: Curigliano Giuseppe , Mueller Volkmar , Borges Virginia F. , Hamilton Erika P. , Hurvitz Sara A. , Loi Sherene , Murthy Rashmi Krishna , Okines Alicia Frances Clare , Paplomata Elisavet , Cameron David A. , Carey Lisa A. , Gelmon Karen A. , Hortobagyi Gabriel N. , Krop Ian E. , Loibl Sibylle , Pegram Mark D. , Slamon Dennis J. , Ramos Jorge , Zhang Chiyu , Winer Eric P. 
Published: June 2021

1043 Background: Tucatinib (TUC) is an oral tyrosine kinase inhibitor (TKI) highly specific for HER2. TUC is approved for use in combination with trastuzumab (T) and capecitabine (C) in patients (pts) with and without brain metastases (BM) who have received 1 or more prior anti-HER2–based regimens in the metastatic setting. In the primary analysis from the pivotal HER2CLIMB trial, the addition of TUC to T and C in pts with HER2+ metastatic breast cancer showed a statistically significant and clinically meaningful prolongation of progression-free (PFS) (HR = 0.54 [95% CI: 0.42, 0.71]; P < 0.001) and overall survival (OS) (HR = 0.66 [95% CI: 0.50, 0.88]; P = 0.005) (Murthy, et al. NEJM 2020). TUC in combination with T and C was well tolerated with few discontinuations other than for disease progression. Based on these data, the protocol was amended for unblinding of sites to treatment assignment to allow for crossover from the placebo arm to receive TUC in combination with T and C. Methods: HER2CLIMB (NCT02614794) is a global, randomized, double-blind, placebo-controlled trial in pts with unresectable locally advanced or metastatic HER2+ breast cancer previously treated with T, pertuzumab, and T-emtansine (T-DM1), including pts with untreated, treated stable, or treated and progressing BM. Overall 612 pts were randomized 2:1 to receive TUC 300 mg BID or placebo, each in combination with T and C. Randomization was stratified by BM, ECOG performance status, and geographic region. Protocol prespecified analysis of OS, PFS (by investigator assessment) and safety in the total study population will be performed at approximately 2 years from the last patient randomized. Results: Updated Kaplan-Meier time-to-event analysis of OS and PFS with hazard ratios and 95% confidence intervals for TUC arm vs placebo arm will be presented overall, as well as for OS in the prespecified subgroups reported previously (Murthy, et al. NEJM 2020). Safety and tolerability assessments will include frequency of adverse events by severity, dose modifications and discontinuation of study medications. Conclusions: Conclusions will be presented in the presentation. Clinical trial information: NCT02614794 .
68Ga-HER2 affibody PET/CT imaging as an option in patients whose HER2 status of any tumor in the body needs to be deciphered.
Authors: Miao Haitao , Sun Yuyun , Hu Xichun , Song Shaoli , Zhang Jian 
Published: June 2021

1045 Background: Anti-HER2 targeted agents are standard of care for HER2 positive patients with either early or advanced breast cancer. Determination of tumor HER2 status helps diagnosing and treating breast cancer. In any tumor which required this biological information, we used a novel 68Ga-NOTA-MAL-MZHER2 (68Ga-HER2) affibody PET/CT to differentiate HER2 status of each lesion in the patient body. Methods: 68Ga-HER2 affibody PET/CT was performed in breast cancer patients if HER2 status of any lesions in the patient body remained to be determined. Results: Twenty-four patients were enrolled. 68Ga-HER2 affibody PET/CT was requested by physicians due to the following reasons: 6 with multiple primary cancers (including patients who harbored two primary breast malignancies but with different HER2 status, and patients who had at least another non-breast primary other than HER2-positve breast cancer), 13 with metastases inaccessible for biopsy or repeated biopsy, 6 with inconsistent HER2 status between the primary and metastatic lesions, and 4 with different HER2-status within metastases (ICH ranging from 0-3+). Assessment report showed that the 68Ga-HER2 affibody tumor uptake was considered positive in 16 patients, negative in 7 patients, and equivocal in one patient. In 11 lesions which was pathological-confirmed HER2-positivity, 100% of the tumors were also positive with this PET/CT. The heterogeneity of 68Ga-HER2 affibody uptake was obvious, with a maximal 8.5-fold difference within one patient and a maximal 11-fold difference among patients. Conclusions: 68Ga-HER2 affibody PET/CT imaging is a valuable tool if HER2 status of any tumor needs to determined. We are now evaluating the 68Ga-HER2 affibody PET/CT imaging as a non-invasive approach to classify the molecular subtype of metastatic breast cancer, and its potential application in the dynamic surveillance of anti-HER2 therapies.
Ancestrally unbiased polygenic breast cancer (BC) risk assessment.
Authors: Hughes Elisha , Tiemeny Placede , Gallagher Shannon , Meek Stephanie , Eng Charis , Gary Monique , Gordon Ora , Klemp Jennifer R. , Olopade Olufunmilayo I. , Pederson Holly Jane , Weitzel Jeffrey N. , Whitworth Pat W. , Yehia Lamis , Wagner Susanne , Slavin Thomas Paul , Gutin Alexander , Lanchbury Jerry 
Published: June 2021

10502 Background: BC risk is influenced by single-nucleotide polymorphisms (SNPs) with small effects that can be aggregated into polygenic risk scores (PRSs). PRSs have primarily been developed and validated for populations of European descent. To make a PRS available for all women, we developed and validated a novel global PRS (gPRS) that utilizes individual ancestral genetic composition. Methods: Ancestry-specific PRSs corresponding to 3 continental ancestries were developed from 149 SNPs (93 BC and 56 ancestry-informative): an African PRS was developed using a cohort of 31,126 self-reported African American patients referred for hereditary cancer testing; an East Asian PRS was developed based on published data from the Asia Breast Cancer Consortium; and a European PRS was developed using data from the Breast Cancer Association Consortium and 24,259 European hereditary cancer testing patients. For each patient, ancestry-informative SNPs were used to calculate the fractional ancestry attributable to each of the 3 continents. The gPRS was the sum of ancestry specific PRSs weighted according to genetic ancestral composition. In an independent validation cohort (N = 62,707), we evaluated discrimination and calibration of gPRS, and compared performance against a previously described 86-SNP PRS for women of European ancestry. Associations of SNPs and PRSs with BC were analyzed using logistic regression adjusted for personal and family cancer history, age, and ancestry. Odds ratios (ORs) are reported per standard deviation within the corresponding patient population. P-values are reported as two-sided. Results: The gPRS was strongly associated with BC in the full validation cohort and in sub-cohorts defined by self-reported ancestry (Table). 95% (88/93) of BC SNPs had ≥1% frequency of risk alleles within each of the self-reported populations. Compared to the aforementioned 86-SNP PRS, the gPRS showed improved discrimination overall, and within each sub-cohort, with the exception of the Asian population where the sample size was too small to show superiority of either score. The 86-SNP PRS was calibrated for white non-Hispanic women but mis-calibrated for non-European ancestries. The gPRS was properly calibrated for all women. Conclusions: The 149-SNP gPRS is validated and calibrated for women of all ancestries. Combined with clinical and biological risk factors, this approach may offer improved risk stratification for all women, regardless of ancestry.[Table: see text]
Underdiagnosis of germline genetic prostate cancer: Are genetic testing guidelines an aid or an impediment?
Authors: Esplin Edward D. , Cahn David J , Mazzarella Brian , Pieczonka Christopher Michael , Gazi Mukaram , Belkoff Laurence H. , Heron Sean , Modh Rishi , Berger Aaron D. , Morris David , Jayram Gautam , Idom Charles , Veys Joseph , Engelman Alexander , Bevan-Thomas Richard , Hardwick Mary Kay , Hatchell Kathryn E. , Nielsen Sarah M. , Nussbaum Robert Luke , Shore Neal D. 
Published: June 2021

10504 Background: Pathogenic/likely pathogenic (P/LP) germline genetic variants are estimated to occur in 10-15% of all prostate cancer (PCa) patients. However, genetic testing for PCa patients is underutilized, partially due to complicated and restrictive testing guidelines developed at a time when the cost of testing was high. We conducted a study based in community urology clinics to determine the incidence of P/LP variants in PCa patients who met and did not meet the NCCN 2019 PCa germline genetic testing criteria. Methods: An IRB-approved, multicenter, prospective registry was initiated with 15 community and academic urologists nationwide. Eligibility criteria included patients with a PCa diagnosis unselected for personal or family history, stage or histology who had not been previously tested. Consecutive patients ages 18-90 were consented and underwent an 84-gene germline panel test. HIPAA-compliant electronic case report forms distributed to clinician collected information on patient diagnoses, NCCN testing criteria, and results-based recommendations. Results: To date, 640 enrolled patients have genetic testing results available. Overall, 69 (10.8%) patients had 72 P/LP variants detected, 15% of which were in BRCA1/2. Of the 532 patients for whom we have clinician-reported data, 293 (55%) met NCCN criteria and 239 (45%) did not. Median age was 70 (range 44-90). Overall, 11.1% (59/532) of patients with clinician-reported data had a P/LP variant. 36 (12.3%) of patients who met NCCN criteria and 23 (9.6%) of patients who did not meet criteria had a P/LP variant. The difference in P/LP rate between the two groups was not statistically significant (p=0.33). If only a conservative 12-gene PCa panel was considered, P/LP yield was 5.5% (29/532), with 8 (28%) of these patients missed by guidelines. Stratification by self-reported ethnicity was: 76% White/Caucasian (52 patients w/ P/LP), 18% Black/African American (2 patients w/ P/LP), and <5% each of Hispanic or Asian. Conclusions: There was no statistically significant difference in the yield of P/LP variants between patients who met and those who did not meet NCCN PCa guidelines, reinforcing that a significant number of P/LP variants are missed if NCCN guidelines are required for genetic testing. Expanded panel testing yields more medically actionable P/LP variants than testing BRCA1/2 alone or PCa panels with 12 genes. While 18% of the cohort was Black/African American, there was a lower P/LP rate (2%) relative to other groups, indicating that more research is needed to understand genetic variation in underrepresented populations with PCa.
Trends in cancer screening volumes at an urban health center during the COVID-19 pandemic.
Authors: Khan Mahir , Wright Margaret , Watson Karriem , Jain Shikha 
Published: June 2021

10551 Background: The Coronavirus-19 (COVID-19) pandemic has disrupted cancer screening for reasons including healthcare resource preservation, infection control efforts, and patient factors. There is limited literature quantifying this interruption of care, particularly in vulnerable and racial/ethnic minorities. Methods: We compared the volume of cancer screening at the University of Illinois Hospital & Health Sciences System before and during the COVID-19 pandemic using data obtained from the electronic medical record. Modalities included mammogram, ultrasound, and MRI for breast; Pap test for cervical; colonoscopy, CT colonography, and flexible sigmoidoscopy for colorectal; low-dose CT for lung; and prostate-specific antigen test for prostate. Of note, screening and diagnostic tests could not be distinguished for colorectal cancer. We examined percent changes in cancer screening counts for each month from February 2020-August 2020, using January 2020 as a reference. Results were stratified by gender, race, and ethnicity. Results: Screening volume declined rapidly after January 2020, with the nadir for each cancer site occurring in April 2020: breast ( n = 0, -100%), cervical ( n = 169, -84%), colorectal ( n = 35, -89%), lung ( n = 0, -100%), and prostate ( n = 108, -72%). Values recovered by August 2020 for most cancer sites except cervical cancer, which remained decreased (-23%). There were no differences in screening trends by gender. With respect to race, breast screening volume in Black patients decreased earlier and exhibited slower recovery compared to White patients. White patients had poorer cervical screening recovery than Black patients by August 2020 (-60% vs. -23%). Hispanics had poorer recovery of breast screening compared to non-Hispanics by August 2020 (-23% vs. 6%). Conclusions: We observed widely decreased cancer screening attributable to COVID-19. Breast cancer screening data specifically showed persistent disparities affecting Black and Hispanic patients. Despite the reassuring recovery of multiple screening methods by August 2020, an increase above baseline is needed to compensate for initial declines. Further studies will likely reveal long-term consequences of this unprecedented situation.[Table: see text]
Adverse consequences of the COVID-19 pandemic on breast cancer stage distribution and breast cancer disparities.
Authors: Fasano Genevieve A. , Chen Yalei , Bayard Solange , Davis Melissa , Bea Vivian , Drotman Michele B. , Kagan Arleo Elizabeth , Marti Jennifer , Malik Manmeet , Simmons Rache M. , Swistel Alexander J. , Tamimi Rulla , Newman Lisa A. 
Published: June 2021

10555 Background: The COVID-19 surge in March 2020 resulted in a hiatus placed on screening mammography programs in support of shelter-in-place mandates and diversion of medical resources to pandemic management. The COVID-related economic recession and ongoing social distancing policies continued to influence screening practices after the hiatus was lifted. We evaluated the effect of the hiatus on breast cancer stage distribution on the diverse patient population of a health care system in New York City, the first pandemic epicenter in the United States. Methods: Breast cancer patients diagnosed January 1, 2019 to December 31, 2020 were analyzed, with comparisons of stage distribution and mammography screen-detection for three intervals: Pre-Hiatus, During Hiatus (March 15, 2020 to June 15, 2020), and Post-Hiatus. Results were stratified by African American (AA), White American (WA), Asian (As) and Hispanic/Latina (Hisp) self-reported racial/ethnic identity. Results: A total of 894 patients were identified; of these, 549 WA, 100 AA, 104 As, and 93 Hisp comprised the final race/ethnicity-stratified study population. Overall, 588 patients were diagnosed Pre-Hiatus, 61 During-Hiatus, and 245 Post-Hiatus. Nearly two-thirds (65.5%) of the Pre-Hiatus cases were screen-detected versus 49.2% During-Hiatus and 54.7% Post-Hiatus (p = 0.002). Frequency of tumors diagnosed < 1 cm declined from 41.9% Pre-Hiatus to 31.7% Post-Hiatus (p = 0.035). WA patients were more likely to have screen-detected disease compared to AA in the Pre-Hiatus period (69.1% vs. 56.1%; p = 0.05) but non-significantly more likely to have screen-detected disease compared to As and Hisp patients (66.2% vs. 56.9%; p = 0.08). In the Post-Hiatus period, the frequency of screen-detected disease was highest among WA patients (63.0%) compared to all other racial/ethnic groups (AA; 48.1%, As-33.3%, and Hisp-40%; p = 0.007). Similar patterns were observed for frequency of tumors diagnosed ≤1cm Pre-Hiatus (WA-44.3% vs AA-26%, p = 0.02; and vs. As-41.3%, Hisp-48%; p = 0.09), and Post-Hiatus (WA-37.7% vs. AA-18.2%, As-30.8%, Hisp-23.5%; p = 0.25). Conclusions: The 3-month pandemic-related mammography screening hiatus resulted in a more advanced stage distribution for New York City breast cancer patients, and worsened pre-existing race/ethnicity-associated disparities, especially for AA pts.
Validation of a high performing blood test for multiple major cancer screenings.
Authors: Xu Linhao , Wang Jun , Ma Weifeng , Liu Xin , Li Sihui , Chen Siyu , Hu Qian , Yang Ting , Ye Zhujia , Chen Zhiwei , Fan Jianbing 
Published: June 2021

10561 Background: Early detection at the localized stage is pivotal for the successful treatment of various cancer types. Although several cancers already have routine screening approaches, the comprehensive utilities are impeded for various reasons, e.g., low accuracy, high cost, limited availability of required facilities, especially in the developing countries. Therefore, an accurate, cost-effective, and non-invasive test for multiple major cancer screening is in high demand. We previously reported a cfDNA methylation test, which can detect five major cancer types with high specificity and sensitivity, especially at the early stage (stage I). These five major cancers, including lung cancer (LC), breast cancer (BC), colorectal cancer (CRC), gastric cancer (GC), and esophageal cancer (EC), account for 56% of new cancer cases and 60% of cancer-related deaths yearly in China. Here, we report the result in an independent cohort as a further validation of this multi-cancer screening test. Methods: The high-throughput targeted methylation profiling platform, Aurora, was used to analyze the plasma samples from an independent retrospective cohort containing 505 healthy controls and ̃200 cases for each cancer type. A locked model based on our previous pilot study (reported in AACR 2020 and 2021) was applied to this data set to assess the overall performance. Results: The Area Under Curves (AUC) of the classifier for LC, BC, CRC, GC and EC are 97.3%, 96.2%, 92.0%, 94.0% and 93.5%, respectively. At a fixed specificity of 99%, the sensitivities for LC, BC, CRC, GC and EC are 84%, 75%, 82%, 85% and 78%, respectively. Conclusions: A methylation blood test for five major cancer screening has been validated in a large retrospective cohort. Its high sensitivity for each cancer type, especially at the early stage (stage I), and easy to use suggests it can be implemented in real clinical world. A large prospective clinical trial is undergoing to further validate this test in asymptomatic populations.
Prior tonsillectomy and subsequent risk of breast cancer in females: Systematic review and meta-analysis.
Authors: Kacimi Salah Eddine Oussama , Ould Setti Mounir , Benmelouka Amira Yasmine , Aloulou Mohammad , Sekkal Hanane Zoubida , Shamseldin Laila Salah , Vidovic Jovana , Klouche-Djedid Selma Nihel , Shah Jaffer , Yasmin Farah , Riffi Omar , Afifi Ahmed M , Ghozy Sherief 
Published: June 2021

10568 Background: Exposure to recurrent infections in childhood was linked to an increased risk of cancer in adulthood. There is also evidence that a history of tonsillectomy, a procedure often performed in children with recurrent infections, is linked to an increased risk of leukemia, and Hodgkin lymphoma. Tonsillectomy could be directly associated with cancer risk or it could be a proxy for another risk factor such as recurrent infections and chronic inflammation. Nevertheless, the role of recurrent childhood infections and tonsillectomy on the one hand, and the risk of breast cancer (BC) in adulthood remain understudied. Our study aims to verify whether a history of tonsillectomy increases the risk of BC in women. Methods: A systematic review was conducted using PubMed, Google Scholar, Scopus, Embase and Web of Science databases from inception through November 2020 to identify the studies which explored the association between history of tonsillectomy and BC in females. The Newcastle Ottawa Scale was used to assess the quality of included studies. Odds ratio (OR) was used to measure effect size. The Random/Fixed effects model was applied to synthesize the associations between tonsillectomy and BC risk based on heterogeneity. Heterogeneity was assessed using the I-squared statistic. A forest plot was generated, and publication bias was assessed. The leave-one-out sensitivity analysis was performed to check if results were driven by a single study. Results: Seven studies with a total of 7259 patients were included in our analysis; out of them, 2200 patients were diagnosed with BC. Patients with a history of tonsillectomy (n = 2843) showed higher subsequent risk of developing BC (OR = 1.252; 95% CI = 1.115 - 1.406; P < 0.001; I2 = 9%) as compared to patients without a history of tonsillectomy (n = 4416). Using the leave-one-out sensitivity analysis to iteratively remove one study at a time, we confirmed that no single study had a substantial influence on the overall effect size. Conclusions: Our study supports and confirms the evidence that a history of tonsillectomy is associated with an increased risk of breast cancer. These findings are also an argument in support of the hypothesis that recurrent childhood infections are linked with adulthood breast cancer.
Identification of potential germline (GL) variants by routine clinical comprehensive genomic profiling (CGP) and confirmatory GL testing in 24 tumor types.
Authors: Hanson Kristen , Mullane Michael , Schnettler Erica , Pavlick Dean C. , Frampton Garrett M. , Cooper Maureen , Wham Deborah , Thompson Michael A. , Godden Jennifer , Walters Mary , Venstrom Jeffrey Michael , McGregor Kimberly 
Published: June 2021

10596 Background: Tumor CGP may identify both somatic and GL variants, though confirmatory testing is required to verify which variants originate from the GL. Studies have shown CGP can identify patients who both do and do not meet criteria for genetic counseling (GC). Ideally, improved annotation from tumor CGP could more appropriately direct GC referrals. We explore how a computational algorithm might be used to influence GC and confirmatory GL testing for variants in inherited cancer predisposition genes. Methods: 849 patients from the Aurora Oncology Precision Medicine Program who had routine hybrid-capture based CGP by Foundation Medicine from 8/2018-8/2020 were eligible. A previously published algorithm, SGZ (Sun et al PMID 29415044) which incorporates allele frequency, aneuploidy, and admixed copy number modeling was used to predict whether each single nucleotide variant (SNV) was GL or somatic. SGZ predictions for SNVs in 24 actionable inherited cancer predisposition genes were available to Aurora for review as part of standard screening to identify appropriate GC referrals. For patients who had GL testing, variants in genes on both assays were compared. Results: 76 pathogenic (P) or likely pathogenic (LP) variants predicted to be GL by SGZ were detected in 73/849 (9%) patients: ATM (7), BAP1 (2), BRCA1 (13), BRCA2 (8), BRIP1 (1), CHEK2 (18), FH (0), FLCN (2), MLH1 (1), MSH2 (0), MSH6 (3), MUTYH (12), PALB2 (3), PMS2 (1), POLE (0), RAD51C (1), RAD51D (0), RET (1), SDHA/B/C/D (0,0,0,0), TSC2 (0), and VHL (3). 27/73 (37%) patients had GL testing. 25/26 (96%) variants were confirmed to be GL in origin and 1 additional variant was detected by CGP in a region not interrogated by the GL assay: ATM (2/2), BRCA1 (6/6), BRCA2 (2/2), BRIP1 (1/1), CHEK2 (9/9), FLCN (0*/1), MSH6 (1/1), MUTYH (2/2), PALB2 (1/1), RAD51C (1/1), and VHL (0/1). Variants were confirmed in bladder, breast, CRC, glioma, NSCLC, ovary, pancreas, prostate, sarcoma, and gastric cancer. The VHL variant was discordant in a leiomyosarcoma. Conclusions: We identified the potential real-world clinical impact of computationally screening solid tumor patients undergoing routine CGP for potential P/LP GL variants. Predicting GL results with SGZ for 24 inherited cancer predisposition genes was highly concordant with confirmatory GL testing independent of tumor type. CGP annotations can facilitate GC referral and GL testing for at-risk patients, particularly in tumor types which may not typically meet guidelines for GL testing.[Table: see text]