bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gemcitabine plus paclitaxel and gemcitabine plus docetaxel in first- or second-line metastatic breast cancer: A phase II randomized trial
Authors: Boccia R. V. , Vaughn L. , Zeigler H. , Wang Y. , Gill J. , Melemed A. , Shonukan O. 
Published: March 2020

1046 Background: The combination of gemcitabine (G) with paclitaxel (P) has proven efficacy in the first-line treatment of metastatic breast cancer (MBC). In addition, the combination of G with docetaxel (D) has shown activity in several nonrandomized, Phase II, MBC trials. This randomized Phase II trial was conducted to assess the efficacy and safety of G plus P and G plus D combination regimens in previously treated patients with MBC. Methods: Patients with locally advanced or metastatic breast cancer were randomized equally into two groups to receive either GP (G 1,250 mg/m2 IV on Days 1 and 8 plus P 175 mg/m2 IV on Day 1) or GD (G 1,000 mg/m2 IV on Days 1 and 8 plus D 75 mg/m2 IV on Day 1). Treatment was administered every 21 days and continued until disease progression or undue toxicity. Planned enrollment was 112 patients (56 per group). The primary study objective was tumor response assessed using RECIST criteria. Toxicities were assessed using the NCI Common Toxicity Criteria, Version 2.0. Results: Twenty-five patients were enrolled in each treatment group and accrual was stopped due to slow enrollment. In the GP group, only 23 patients were evaluable for response and 24 patients were monitored for safety. One patient did not receive study medication and was not assessed for efficacy or safety. A second patient was determined to have nonmeasurable disease at baseline and was not assessed for response. Overall response rate was 39% (95% CI 20, 61) for the GP group and 40% (95% CI 21, 61) for the GD group. The median number of cycles administered was 6.5 in the GP group and 6.0 in the GD group. Detailed study results are summarized in the table below. Conclusions: These results show that GP and GD combination regimens are both efficacious in the treatment of MBC, with similar response rates and manageable toxicity profiles. [Table: see text] No significant financial relationships to disclose.
Elevated stem cell marker CD133 mRNA in peripheral blood predicts colon cancer recurrence
Authors: Lin E. H. , Hassan M. , Li Y. , Zhao H. , Nooka A. , Xie K. , Champlin R. , Wu X. , Li D. 
Published: March 2020

10504 Background: CD133 is a specific stem cell marker that enriches cancer stem cells of many tumor types including colon cancer as well as circulating endothelial progenitors (CEP). CEP is vital in postnatal angiogenesis and elevated CEP is a proven favoable prognositic marker for heart disease but a potentially poor prognostic marker for cancer. We examined whether elevated CD133 mRNA expression levels in peripheral blood mononuclear cells (PBMC) predict recurrence in colon cancer patients. Methods: We developed and validated a semi-quantitative real-time RT-PCR to quantify CD133 mRNA levels relative to GADPH mRNA. Sixty-six colon cancer patients were enrolled between February 2002 and December 2003. The protocol excluded patients with history of cardiac disease or surgery < 4 weeks from the enrollment and were followed for recurrence for a median 30 months. A central statistician performed multivariate unconditional logistics regression analysis. Results: Among the patients without recurrence, 93% had a CD133 mRNA level < 4.79, whereas 7% had a CD133 mRNA value ≥ 4.79 (p = 0.029). Among patients with a CD133 mRNA value ≥ 4.79, 85% had experienced recurrence compared to 15% of the patient who had no recurrence (p = 0.03). Elevated CD133 mRNA levels at a cut-off point ≥ 4.79 versus < 4.79 were associated with an odd ratio of 22.6 for recurrence (95% CI, 1.7–291.2; p = 0.02); in comparison, the odds ratio for recurrence was 17.2 (95% CI, 1.8–164; p = 0.01) for stage IV patients versus stage I-III patients. No other predictive variables for recurrence were identified including age, race, sex, tumor differentiation, smoking, and diabetes etc. We also observed an trend of association with elevated carcinoma embryonic antigen (CEA) levels (p = 0.03, one sided) and a decreased survival (p = 0.035, one sided) with elevated CD133 mRNA level at a cutoff point ≥ 4.79. Conclusions: Elevated CD133 mRNA levels at a cutoff ≥ 4.79 in PBMC predict colon cancer recurrence independent of stage IV disease. The current assay has certain advantages over flow cytometry for wider clinical application. CD133+ cells measured by CD133 mRNA may contain both CEP and cancer stem cells, leading to increased risks of recurrence. No significant financial relationships to disclose.
Validation of genomic markers that predict distant recurrence risk via FISH assays in women with early stage breast carcinoma
Authors: Williams T. M. , Budd G. T. , Gunter M. , Hines R. , Masood S. , Pawloski P. , Schwartzberg L. , Wei F. , Tubbs R. R. 
Published: March 2020

10506 Background: Biomarkers offer the potential to better predict recurrence risk in early stage invasive breast cancer, especially if adaptable to common assays such as fluorescent in situ hybridization (FISH). We studied the ability of tumor copy numbers (CN) of 3 genes, BIRC5, CYP24, and PDCD6IP, to predict distant recurrence in women with breast cancer. Methods: We conducted a blinded, multi-site study of 350 women with lymph node negative, estrogen/progesterone receptor positive (ER/PR+), invasive ductal carcinomas with archived paraffin-embedded biopsy specimens available. Eligible women received local surgical and radiation treatment only (93) (LTO) or local treatment and tamoxifen therapy only (257), and had distant metastases or no evidence of distant recurrence with at least 5 years follow-up (FU). Tumors were subjected to FISH with DNA probes for the 3 genes to assess CN. A prognostic index (PI) was calculated for each patient based on the 3 genes’ CN. A predetermined threshold (3.0) was used to categorize PI's as low or high. Data were assessed by Fisher's exact analysis and by categorical and continuous Cox modeling. Results: The study included 350 women with Stage I (288) and II (62) disease. FU averaged 7.3 years. Distant recurrence occurred in 32 women (9.1%) overall and in 5.2% of women with Stage I disease. In a multivariate Cox analysis including continuous PI, age, tamoxifen treatment, grade, and tumor size, PI remained a significant predictor of recurrence for Stage I patients: OR=1.56, p=0.019, and Stage I/LTO patients: OR=6.02, p=0.00007. Using the PI as a categorical classifier, the high/low recurrence rates were significantly different: OR=2.24, p= 0.045. Similar results were seen in Stage I patients: OR=3.53, p=0.021 with recurrence rates of 3.5% and 11.5% in the low and high risk groups, respectively, and for the Stage I/LTO patients: OR=5.33, p=0.041. Conclusions: FISH analysis of 3 genes allows metastasis risk prediction in women with early stage ER/PR+ cancers. This may be particularly useful for Stage I cancers traditionally considered low risk. The markers are prognostic in that they predict metastasis in patients receiving only local therapy. No significant financial relationships to disclose.
Real-time optical biopsy and analysis of breast cancer using clinical optical coherence tomography
Authors: Boppart S. A. , Zysk A. M. , Nguyen F. T. , Chaney E. J. , Bellafiore F. J. , Kotynek J. G. , Johnson P. A. , Rowland K. M. 
Published: March 2020

10508 Background: Advances in high-resolution, real-time, optical imaging have enabled optical coherence tomography (OCT) for non-excisional optical biopsies of breast tissue. OCT is the optical analogue to ultrasound imaging, with resolution approaching that of histology. In breast tissue, regions of tumor, tumor margins, abnormal ducts, and foci of tumor cells can be identified based on increased scattering and morphological appearance. We have developed a portable clinical OCT system along with image criteria for identifying breast cancer in real-time during needle-biopsy and surgical-biopsy procedures. Methods: Over 4,000 depth-resolved OCT axial scans were extracted from over 50 cross-sectional OCT images from 9 ex vivo specimens of ductal carcinoma in situ (DCIS) of the human breast. OCT image data was acquired in real-time within 6 hours of surgical resection using a state-of-the-art OCT system with micron resolution. Imaged sites were marked for registration with hematoxylin and eosin-stained histology. Axial scan data was analyzed using frequency-domain analysis techniques to classify regions as tumor, stroma, or adipose tissue. OCT images of tissue types were compared with histological observations. Results: Real-time OCT images of microscopic breast cancer morphology showed strong correlations with corresponding histology, including regions of tumor, tumor margins, ducts, and adipose tissue. Computational frequency-domain analysis of depth-resolved axial scan data classified tissue types as tumor, stroma, and adipose with 91% sensitivity and 87% specificity. Conclusions: Optical biopsy of breast cancer with OCT is feasible for imaging at resolutions approaching histology. Frequency- domain analysis of axial scan data can be used to classify breast tissue types with a sensitivity and specificity that are comparable to or surpasses that of conventional mammography and ultrasound imaging of human DCIS. Clinical OCT imaging has the potential for real-time guidance and diagnostics in needle- or surgical-biopsy of breast cancer. No significant financial relationships to disclose.
Breast cancer and DNA epair gene SNPs in a family cancer registry population
Authors: Langer L. R. , Papp J. , Sinsheimer J. S. , Kwan L. , Seldon J. , Reed E. F. , Dandekar S. , Korin Y. , Zhang Z. F. , Ganz P. A. 
Published: March 2020

10514 Background: Alterations in the DNA double-strand break repair (DSBR) pathway are associated with cancer risk. Mutations in the genes BRCA1/2 disrupt DNA DSBR. Variations in breast cancer penetrance among BRCA1/2 mutation carriers, and familial patterns among women without known BRCA1/2 mutations may be related to polymorphisms of genes in the DNA-DSBR pathway. Methods: Using a case-control study design with individuals in the UCLA Family Cancer Registry (FCR), we examined the independent effects of 100 SNPs in 19 DNA-DSBR genes. SNPs were assayed using the Applied Biosystems SNPlex™ assay. Results: 630 consecutive females from 508 families in the UCLA FCR selected for familial risk of breast cancer were included in the study. Table 1 describes select subject characteristics. Preliminary association analysis of the Caucasian subset using a nonparametric permutation method, which controls for Ashkenazi Jewish heritage and dependencies among relatives, suggests that polymorphisms within RAD21 (p=0.0044, p=0.0005), XRCC2 (p = 0.0069), XRCC4 (p =0.0511), and BRIP1 (p =0.0107) may be associated with a change in risk of breast cancer. Using only unrelated Caucasian subjects in a logistic regression analysis with covariates such as age, BMI, and Ashkenazi Jewish heritage, the effects of these polymorphisms remain significant, with 32% to 74% change in the odds of breast cancer. Conclusions: We have identified five potential SNPs in genes in the DNA-DSBR pathway that appear to be associated with a change in risk of breast cancer. This hypothesis generating study lends support to a role for polymorphisms of the DNA-repair pathway in breast carcinogenesis. Assessment of gene-environment and gene-gene interactions will help to elucidate carcinogenic mechanisms. Further validation in similar populations is warranted. (Funded by the Breast Cancer Research Foundation and NIH/NCI CA87949 R25 Career Development Program.) [Table: see text] No significant financial relationships to disclose.
Efficacy of oral vinorelbine (NVBo), capecitabine (X) and trastuzumab (H) triple combination (NVBoXH) in HER2-positive metastatic breast cancer (MBC): First results of an international phase II trial
Authors: Chan A. , Ganju V. , Becquart D. , Conte P. , Petruzelka L. , Aubert D. , Villanova G. , Tubiana-Mathieu N. 
Published: March 2020

1052 Background: Chemotherapy (CT) plus H is the standard first-line treatment for HER2-positive MBC. H plus vinorelbine is an active and well-tolerated regimen in this setting. The all-oral combination of NVBo and X also appears active and well-tolerated in MBC. We report efficacy and safety results from the first 34 patients (pts) included in an international trial evaluating NVBoXH in HER2-positive MBC. Methods: In this multicenter trial, main eligibility criteria included: HER2-positive disease (IHC 3+ or FISH+), documented measurable MBC previously untreated by CT, relapse 6 months after completing neoadjuvant or adjuvant CT, Karnofsky PS = 70, age =18 years. Pts received 3-weekly cycles of NVBo 60 mg/m2 (cycle 1) escalating to 80 mg/m2 (from cycle 2) days 1 and 8; × 1,000 mg/m2 bid (750 if = 65 years) days 1–14; H 4 mg/kg day 1 as a loading dose then 2 mg/kg i.v. weekly starting on day 8. Treatment was continued until progression or unacceptable toxicity. Primary endpoint is overall response rate. Results: Baseline characteristics: median age 54 years (20% = 65); prior (neo)adjuvant CT 21 pts (62%); type of CT: anthracycline 52%, anthracycline + taxane 29%, CMF 14%, taxane 5%; visceral involvement 29 pts (85%), >2 metastatic sites 13 pts (38%). Treatment administered: median 8 cycles, median relative dose intensity: NVBo 77%, X 81%, H 95%; NVBo dose escalation to 80 mg/m2 in 91% of pts. Safety (n=34, G3/4 NCI CTC v2 adverse events): neutropenia 22 pts (65%), diarrhea 4 pts (12%), febrile neutropenia 3 pts (9%), vomiting 3 pts (9%), hand-foot syndrome 3 pts (9%), asthenia 3 pts (9%), infection without neutropenia 2 pts (6%), LVEF decline 2 pts (6%), stomatitis 1 pt (3%), nausea 1 pt (3%), constipation 1 pt (3%). Efficacy (n=31 evaluable pts): objective response rate (RECIST) 71% (95% CI [52–86]), CR 13%, PR 58%, SD 23%, PD 6%, disease control (CR+PR+ SD for =6 months) 84%. Progression-free survival, overall survival and duration of response data are not yet mature. Conclusions: This is the first trial, in pts with HER2-positive MBC, to show high efficacy with first-line NVBoXH therapy. This regimen can be safely administered in this pt population. No significant financial relationships to disclose.
Cancer penetrance of Lynch syndrome for MSH2 A636P mutation carriers
Authors: Moreno V. , Rennert G. , Gruber S. B. 
Published: March 2020

10528 Background: Mutations in mismatch repair genes are responsible for Lynch syndrome. Estimating the penetrance of cancer related to MSH2 A636P, a founder mutation identified in Ashkenazi Jewish population, has clinical implications. Methods: The mutation was genotyped in all subjects of the MECC study, a population-based case-control study carried out in North Israel during 1998–2004 that included 2,112 cases of pathology-confirmed colorectal cancer (CRC) and 2,060 population controls. Approximately 50% of the subjects were of Ashkenazi Jewish origin. Family history of cancer (among first and second degree relatives) was obtained by personal interview. Penetrance of MSH2 A636P was estimated from relatives using a kin-cohort approach by the marginal maximum likelihood method, estimating cumulative risk among carriers and noncarriers. Results: Thirteen MSH2 A636P carriers were identified, all among CRC cases. Their relatives formed a cohort of 138 subjects contributing 8,802 person years (py); 14 of 138 had CRC (173 per 100,000) and 5 endometrial cancer (112 per 100,000). The cohort of relatives of noncarriers summed 46,257 subjects contributing 2.8M py; 582 had CRC (20 per 100,000) and 142 endometrial cancer (EC)(10 per 100,000). For carriers, the cumulative risk to age 70 of CRC was 0.44 (0.19–0.90) and that of EC was 0.29 (0–0.84). The cumulative risk of any cancer related with Lynch syndrome was 0.66 (0.47–0.93). These estimates of penetrance were not substantially modified if the cohorts were restricted to first degree relatives, to Ashkenazi Jews, or when relatives of controls were excluded. Compared to noncarriers, the hazard ratios were 28.7 (2.8–112) for CRC, 9.1 (0–181) for EC and 19 (6.4–50) for Lynch syndrome cancers. Conclusions: The MSH2 A636P missense mutation is highly penetrant, with a cumulative risk of cancers related to Lynch syndrome that is similar to other truncating mutations in mismatch repair genes. These results have implications for the tailored management of patients with this Ashkenazi founder mutation. No significant financial relationships to disclose.
Correlation among [18-F] FDG-PET/CT, tumor marker CA 27.29, and circulating tumor cells in metastatic breast cancer
Authors: Saad A. A. , Rikhye S. , Kanate A. , Sehbai A. , Marano G. , Hobbs G. , Abraham J. 
Published: March 2020

10533 Background: Both tumor marker CA 27.29 and combined [18-F]-fluorodeoxyglucose-positron emission tomography/computed tomography scan (PET/CT) are used to follow up response to treatment and disease progression in patients with metastatic breast cancer (MBC). Recently, circulating tumor cell testing (CTC) has been used in this context. It is not known if one of the three tests can be a surrogate for the other 2 tests. Methods: We analyzed the database of 35 patients with MBC. There were 173 time points (at least 6 weeks apart), when at least 2 of these tests were done. CA 27.29 test (chemiluminescent immunoassay by Bayer Advia Centaur) was either high or normal (< 38.6 U/ml). Circulating tumor cells cell test (Cell Search by Quest Diagnostics, Nichols Institute, Chantilly, VA) was either high or normal (0 cells detected). Results: PET/CT scan results were compared to CA 27.29 at 163 time points. There was statistically significant correlation between both groups (P value: 0.02), however, sensitivity of CA 27.29 to detect metastatic disease seen in PET/CT scan was 59%. The positive predictive value (PPV) of CA 27.29 was 90%, while the negative predictive value (NPV) was only 24%. PET/CT scan results were compared to CTC at 100 events, where there was statistically significant correlation between both groups (P value: 0.0002), however, sensitivity of CTC to detect metastatic disease shown in PET/CT scan was 55%. The positive predictive value of CTC was 98% while the negative predictive value was only 33%. CTC test was more specific (94% Vs 67%) than CA 27.29 to rule out metastatic disease that is seen in PET/CT scan. CA 27.29 results were also compared to CTC at 93 events, where there was statistically significant correlation between both groups (P value: 0.0002). However, only 64 % of those with high CA 27.29 had abnormal CTC. Conclusion: Our data shows correlation among PET/CT scan, CA 27.29, and CTC. However, both CA 27.29 and CTC had poor sensitivity and negative predictive value to detect metastatic disease seen in PET/CT scan. Normal CA 27.29 test or CTC has to be interpreted cautiously in patients with MBC. No significant financial relationships to disclose.
Loss of heterozygosity at the BRCA2 locus is a common finding in prostate cancer in men with a germline BRCA2 mutation
Authors: Dawson S. , Willems A. , Thorne H. , Samaratunga H. , Antill Y. C. 
Published: March 2020

10539 Background: The prevalence of prostate cancer (PC) is higher in men with a germline mutation in BRCA2 and to a lesser extent BRCA1. It is unclear as to whether a causal relationship exists between these mutations and PC tumorigenesis. The primary aim of this pilot study was to examine for loss of heterozygosity (LOH) in PC samples from men with a known BRCA1/2 mutation. Secondary aims included assessment of the clinical and pathological features of PC in these individuals. Methods: Subjects were male carriers of a germline BRCA1/2 mutation enrolled in kConFab with a diagnosis of PC. LOH analysis was performed using multiplex ligation-dependent probe amplification and confirmed using PCR and sequencing. Clinical data was obtained on all individuals together with histopathology review. Results: In total, 134 pedigrees from BRCA1/2 mutation positive families known to include = 1men with PC were reviewed; 192 men were identified as having PC, however, only 26 were found to carry a pathogenic family specific mutation. Of these, 14 were ineligible as prostate tissue was unavailable. LOH was therefore assessed in 12 subjects (3 BRCA1 and 9 BRCA2). LOH at the BRCA2 locus was seen in 8/9 (89%) subjects with a BRCA2 mutation whilst the ninth showed no LOH. None of the samples from BRCA1 carriers were found to have LOH at the BRCA1 locus. For samples showing LOH, sequencing confirmed loss of the wild-type allele. No unique clinical or histopathological subtype was identified. Conclusions: LOH appears to occur very frequently at the BRCA2 locus in PC arising in men known to carry a germline BRCA2 mutation with LOH heavily biased towards loss of the wild-type allele. Whilst the cohort studied is small, these two results strongly indicate that BRCA2 is a tumour suppressor of PC and is the first gene shown to have this property. In contrast, failure to identify LOH in the BRCA1 samples suggests that BRCA1 is unlikely to be integral in the development of PC. These results should be confirmed in a larger cohort and further research into the mechanisms of BRCA2 induced prostate tumorigenesis is warranted. No significant financial relationships to disclose.
An international phase II study of an all-oral combination of oral vinorelbine (NVBo) and capecitabine (X) in HER2-negative metastatic breast cancer (MBC)
Authors: Tubiana-Mathieu N. , Bougnoux P. , Becquart D. , Chan A. , Majois F. , Espie M. , Aubert D. , Villanova G. , Conte P. F. 
Published: March 2020

1056 Background: Oral chemotherapy (CT) is attractive for patients (pts) with MBC. The all-oral regimen of NVBo and X is active with good tolerability in MBC. We report efficacy and safety data from an international phase II study of NVBo plus X. Methods: Main eligibility criteria included: measurable HER2-negative, CT-naive MBC, relapse ≥6 months after completing (neo)adjuvant CT, Karnofsky PS ≥70%, age ≥18 years. Study treatment: 3-weekly cycles of NVBo 60 mg/m2 (cycle 1) or 80 mg/m2 (from cycle 2) d1 and d8, plus X 1,000 (750 if ≥ 65 years) mg/m2 twice-daily d1–14. Treatment was continued until progression or unacceptable toxicity. Results: 55 pts were enrolled: median age: 58.5 years (41% ≥65); prior (neo)adjuvant CT in 63%; type of CT: anthracycline 67%, anthracycline + taxane 18%, CMF 15%; visceral involvement in 78%; >2 metastatic sites in 46%. Median 6 cycles; median relative dose intensity: NVBo 88%, X 87%; NVBo dose escalated to 80 mg/m2 in 94% of pts. G3/4 NCI CTC v2 adverse events (n=54): neutropenia 44% of pts, vomiting 9%, febrile neutropenia 7%, stomatitis 7%, asthenia 7%, infection with G3/4 neutropenia 4%, nausea 4%, diarrhea 4%, hand-foot syndrome 4%, thrombosis/embolism 4%. Efficacy (n=48 evaluable pts): objective response rate (RECIST) 44% (95% CI [29–59]), CR 2%, PR 42%, SD 35%, PD 21%, disease control (CR+PR+SD ≥6 months) 56%. Median time to objective response was 2.9 months. Because of short follow-up, progression-free survival, overall survival and duration of response data are not yet available. Conclusion: The all-oral combination of NVBo and X is an effective and well-tolerated first-line therapy for MBC. Based on these results and the high convenience of oral CT, evaluation of this regimen vs i.v. combinations in a randomized trial is ongoing. [Table: see text]