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PurposeOncotype DX (ODX) recurrence score (RS) breast cancer (BC) assay is costly, and performed in only ~1/3 of estrogen receptor (ER)-positive BC patients in the USA. We have now developed a user-friendly nomogram surrogate prediction model for ODX based on a large dataset from the National Cancer Data Base (NCDB) to assist in selecting patients for which further ODX testing may not be necessary and as a surrogate for patients for which ODX testing is not affordable or available.MethodsSix clinicopathologic variables of 27,719 ODX-tested ER+/HER2−/lymph node-negative patients with 6–50 mm tumor size captured by the NCDB from 2010 to 2012 were assessed with logistic regression to predict high-risk or low-risk ODXRS test results with TAILORx-trial and commercial cut-off values; 12,763 ODX-tested patients in 2013 were used for external validation. The predictive accuracy of the regression model was yielded using a Receiver Operator Characteristic analysis. Model fit was analyzed by plotting the predicted probabilities against the actual probabilities. A user-friendly calculator version of nomograms is available online at the University of Tennessee Medical Center website (Knoxville, TN).ResultsGrade and progesterone receptor status were the highest predictors of both low-risk and high-risk ODXRS, followed by age, tumor size, histologic tumor type and lymph-vascular invasion (C-indexes-.0.85 vs. 0.88 for TAILORx-trial vs. commercial cut-off values, respectively).Conclusion This is the first study of this scale showing confidently that clinicopathologic variables can be used for prediction of low-risk or high-risk ODXRS using our nomogram models. These novel nomograms will be useful tools to help physicians and patients decide whether further ODX testing is necessary and are excellent surrogates for patients for which ODX testing is not affordable or available.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-017-4170-3) contains supplementary material, which is available to authorized users.

Objectives: Oncotype DX (ODX), 21-gene breast cancer (BC) assay, predicts risk of recurrence and benefits of addition of chemotherapy to hormonal therapy for early-stage BC. We previously published a nomogram/calculator that could predict ODX results without performing the test by using clinicopathologic characteristics of BC available from pathology reports. Patients with intermediate-risk (11e25) ODXRS (RS) were excluded from that nomogram. This update tests the predictive value of clinicopathologic variables for forecasting the ODXRS while including intermediate-risk-ODXRS patients and stratifying ODXRS based on recently published TAILORx clinical trial results (0e25 ¼ low-risk, 26 e100 ¼ high-risk-ODXRS; intermediate-risk-ODXRS belongs to the low-risk category). Material and methods: The nomogram was built on 65,754 ODX-tested ERþ/HER2-/lymph-node-negative patients with 6e50 mm tumor, captured by the National Cancer Data Base (NCDB) from 2010 to 2014.Five clinicopathologic variables (age, tumor size, grade, progesterone-receptor status (PR) and BChistologic type) were assessed with logistic regression to predict for a low-risk (0e25) or a high-risk (26e100) ODXRS. Results were validated on a separate 18,585 ODX-tested cohort from 2015. Results: Grade and PR were the highest significant predictors of both low-risk and high-risk-ODXRS, followed by histologic type, tumor size and age. The Receiver Operator Characteristic (ROC) curve showed strong statistical model for both low-risk and high-risk-ODXRS prediction outcomes (cindex ¼ 0.81). Conclusions: An updated nomogram is now developed/validated on the entire population of ODX-tested patients (84,339) captured by the NCDB. The nomogram/calculator, available on-line at the UTMCK/Shiny website (https://utgsm.shinyapps.io/OncotypeDXCalculator/), will continue serving as a surrogate for BC patients for which ODX testing is not affordable, available or necessary.

Estrogen receptor (ER), progesterone receptor (PR), and epidermal growth factor receptor 2 (HER2) status are well-established prognostic markers in breast cancer management. The triple negative breast carcinoma subtype (ER-/PR-/HER2-) has been associated with worse overall prognosis in comparison with other subtypes in study populations consisting of ethnic minorities and young women. We evaluated the prognostic value of breast cancer subtypes, Ki-67 proliferation index (Ki-67PI), and pathologic tumor characteristics on breast cancer survival in Caucasian women in our institution, where greater than 90% of the total patient population is white. From 628 new invasive breast cancer cases in our data base (2000-late 2004), 593 (94%) were identified in Caucasian women. ER/PR/HER2 breast cancer subtypes were classified based on St. Gallen International Expert Consensus recommendations from 2011. ER/PR/HER2 status and its effect on survival were analyzed using a Kaplan-Meier curve. ER/PR/HER2 status, grade, tumor-node-metastasis status (TNM)/anatomic stage, and age were analyzed in terms of survival in a multivariate fashion using a Cox regression. Ki-67PI was analyzed between ER/PR/HER2 groups using the Kruskal-Wallis, Mann-Whitney U-tests, and 2 × 5 ANOVA. Our results showed that patients with stage IIB through stage IV breast carcinomas were 2.1-16 times more likely to die than patients with stages IA-B and IIA disease, respectively (95% CI 1.17-3.81 through 9.68-28.03, respectively), irrespective of ER/PR/HER2 subtype. Similar effect was seen with T2, N2/N3, or M1 tumors in comparison with T1, N0/N1, and M0 tumors. Chances of dying increase approximately 5% for every year increase in age. There was a significant main effect of Ki-67PI between ER/PR/HER2 subtypes, p < .001, but Ki-67PI could not predict survival. In summary, TNM status/anatomic stage of breast carcinomas and age are predictive of survival in our patient population of Caucasian women, but breast carcinoma subtypes and Ki-67 proliferation index are not.

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The aim of our study is to investigate patient selection for the 21-gene recurrence score assay (RS) for breast cancer (BC) and the RS impact on chemotherapy administration (Chemo) in clinical practice across the United States through the retrospective observational study of National Cancer Data Base (NCDB) patients from 2010 to 2012. NCDB captures ~70 % of all newly diagnosed malignancies in the USA annually. The 2010–2012 period depicts data from the beginning of the NCDB that required recording of molecular assays and their data release in April 2015. De-identified demographic and clinical variables of patients that had RS results were analyzed. 513,080 patients had BC; 406,525 were estrogen receptor-positive (ER+). 74,334/91,651 patients with RS recorded as a numerical value (0–100) were analyzed (18.2 % of ER+). Patients’ ages ranged from 18 to 90 (mean = 58.8, median = 59); 99.1 % were females. Patients of Caucasian race, from regions with <7 % having no high school education, and >$63,000 median household income were more likely to be tested than patients of other races, education, or income (p < 0.001). 58.1 % of tests were performed in ER+/lymph node-negative/>1 cm tumors; 16.4 % included ≥N1 disease; 9.9 % included T1a, T3, Stage III and IV, or HER2-positive cancers. Low-risk RS result had 92.2 % negative predictive value for no Chemo. Intermediate-risk RS result had 40.1 % positive predictive value (PPV); high-risk RS had 81.2 % PPV for Chemo. RS is obtained in ~1/5 of ER + BC patients across the USA. Further studies investigating influence and implementation of the newest evidence-based management guidelines regarding patients’ selection for RS test and chemotherapy administration upon obtaining of test results are warranted.

Nuclear pore complexes are large, elaborate macromolecular structures that mediate the bidirectional nucleocytoplasmic traffic. In vertebrates, nuclear pore complexes comprise 50 to 100 proteins termed nucleoporins (Nup). An 88-kd nucleoporin (Nup88) has been recently cloned and characterized, and found to be associated in a dynamic subcomplex with the oncogenic nucleoporin CAN/Nup 214. We have produced a polyclonal antiserum to Nup88, and found that it immunoreacts convincingly in conventional tissue sections of 214 samples of malignant tumors of many types. All carcinomas were stained irrespective of site or line of differentiation; the majority of cases reacted strongly and extensively. In situ carcinomas and highly dysplastic epithelia were similarly reactive. Samples of malignant mesotheliomas, gliomas, sarcomas, and lymphoreticular tumors were also stained. Substantial reactions were also found in certain fetal tissues. Focal reactions were noted in some reactive-proliferative processes. In 1993, a monoclonal antibody directed against Candida krusei cytochrome c was shown to react with a cytoplasmic fraction protein of a human lung carcinoma cell line. Independently, it was reported that monoclonal antibody C6, generated against Candida albicans mannoproteins, reacted specifically with a M r 43,000 molecule from samples of human ovarian carcinoma but not with nonneoplastic counterpart cells.2 Subsequently, we showed that this monoclonal antibody recognized in immunoblots an additional protein of M r 88,000.3 Using a cDNA library, we recognized the mammalian molecule as nucleoporin (Nup) 88 3 ; and, identified it as a protein located at the nuclear membrane known to be involved in nuclear-cytoplasmic transport. 4,5 In turn, Nup88 had been found to be associated with the central domain of CAN/Nup214, a nuclear pore complex component putatively implicated in nuclear protein import, nuclear mRNA export, and the regulation of the cell cycle.6 Notably, the CAN/Nup214 proto-oncogene is involved in chromosomal rearrangements related to two variants of leukemia. 7,8 As part of the investigation that led to the recognition that the molecule bound by monoclonal antibody C6 corresponded to Nup88, a polyclonal antiserum directed to the pertinent recombinant protein was generated. By immunohistochemistry, this antiserum was shown to recognize several human tumor cell lines as well as ovarian carcinomas in tissue sections; parallel results were obtained by immunoblot analysis. 3 We now report that this antiserum immunostains richly and extensively conventional histological sections of 214 samples representing a wide spectrum of malignant tumors including carcinomas and sarcomas of diverse sites, lineages, and differentiation as well as some mesotheliomas, gliomas, melanomas, and lymphoreticular neoplasms. Certain fetal tissues were similarly stained. Notably, benign neoplasms and reparative processes showed only focal and less intense reactions whereas normal adult cells reacted only sporadically and weakly. Immunoblots ...

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