The role of the canonical NF-kB pathway in mammary tumorigenesis was investigated using a transgenic (TG) mouse expressing a dominant-negative inhibitor of kB (IkBa SR (S32A/S36A) ) in the mammary gland under the control of the mouse mammary tumor virus promoter (MMTV). TG and control mice were subjected to a chemical carcinogenesis protocol. Hyperkeratinized squamous metaplasias (cytokeratinÀ6 þ /p63 þ ) sometimes with a basaloid island component, were found in both TG and control mice whereas luminal (cytokeratin-19 þ / MUC1 þ ) ErbB2 þ papillary and adenomatous lesions developed almost exclusively in control mice. p65/RelAand NF-kB DNA-binding activity were detected in mammary luminal lesions, but rarely in squamous metaplasias. Analysis of NF-kB family proteins and target genes using microarray data from a cohort of human mammary tumors revealed the expression of a canonical NF-kB pathway, but not non-canonical pathway proteins in HER2 þ luminal cancers. HER2 þ tumors also showed differential regulation of specific NF-kB target genes relative to basal and ER þ luminal cancers. Isolation of mammary cell populations enriched for stem and progenitor cell characteristics from an NF-kB-EGFP reporter mouse by fluorescence-activated cell sorting demonstrated that luminal progenitors contain activated NF-kB whereas the mammary stem cell-enriched population, does not. Together these data suggest that the canonical NF-kB pathway is active in normal luminal progenitor cells before transformation and is required for the formation of mammary luminal-type epithelial neoplasias.

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Our findings show that PICD accounted for 1.15% of all patients attending the contact clinic over the study period. Diverse occupations and materials were implicated. The most common cause of PICD was low humidity due to air-conditioning, which caused dermatitis of the face and neck in office workers due to drying out of the skin.

Background: The Oncotype DX Recurrence Score (ODX) is commonly used to estimate recurrence risk and chemotherapy benefit in ER positive, node negative breast cancer but is associated with significant cost. The Magee score (MS), a free online calculation using numerical values of commonly assessed pathological features (ER, PR, Her2/neu, and Ki-67), has been validated as an ODX surrogate. This includes the MS using classic H scores (HMagee) or Surrogate H scores derived from total % positive cells and average intensity or our use of Surrogate H scores derived from Allred scores (SMagee). Also Gage et al (2015) used a simple algorithm based on tumor grade, PR >1% and ER>20%. Here we compare three methods of predicting ODX scores. Design: 61 patients from The Ottawa Hospital with ER positive HER2/neu negative invasive ductal carcinoma (IDC), known ODX were assessed. Classic H scores (CH) were assessed using Image analysis. All cases had Ki67 (1000 cell hot spot score), tumor size, grade, and Allred scores available. Surrogate H scores (SH) were derived (average reported intensity x midpoint of reported Allred positive score range or absolute percentage if between 1-10%). The three MS were calculated with CH giving classic MS (HMagee) and with SH giving surrogate scores (SMagee). Each case was also categorized using rules published by Gage (2015): LOW predicted if Low Grade and PR positive (>1%), HIGH predicted if High Grade or Low ER (<20%). Agreement with classic ODX categories of low (<18), intermediate (18-30) and high risk (≥ 31) was assessed. Results: ODX included 35 low, 20 intermediate and 6 high risk (Mean 17.4, sd=10). There was a good correlation between corresponding HMagee and SMagee 1-3(0.820, 0.73, 0.84). Concentrating on the theoretically best MS1 that includes Ki67 and all clinical variables (Table 1); HMagee1 predicted 32 cases as low grade with 78% accuracy and SMagee1 predicted 26 low grade with 92.3% accuracy. Of note, all intermediate ODX predicted low by MS were ODX 18-20. None of the MS falsely predicted high risk in low risk ODX. The one case of high ODX which MS predicted low (false negative) is controversial as an Allred ER&PR 8 tumor gave low ODX PR score. Using SMagee1 in this population would safely leave 32 (52.5%) in the intermediate category. Of note, all intermediate ODX predicted low by MS were borderline ODX 18-20. The Gage algorithm in our population is less useful with higher discordance rate and left 69% in the intermediate category. Table 1TestMagee RiskNODX LowODX IntermediateODX High%DiscordantHMagee1Low (<18)3225/78%7/22%07/22% Moderate(≥18-30)2810/36%15/54%3/11%13/46% High (≥31)1001/1.6%0SMagee1Low (<18)2624/92%1/4%1/4%2/8% Moderate(≥18-30)3211/33%19/58%3/9%14/44% High (≥31)2002/100%0GageLow108/80%1/10%1/10%2/20% Moderate4225/60%16/38%1/2.4%26/62% High92/22%3/33%4/44%5/56% Conclusions: In IDC, while simpler algorithms without proliferation markers do not perform as well; SMagee1 based on Allred, performs at least as well in prediction of ODX as an MS based on classic H score and can potentially save considerable time and money. In our hands the simpler Gage algorithm does not perform as well. Citation Format: Robertson SJ, Petkiewicz SL, Arnaout A, Clemons M, Gravel DH, Pond GR. Comparing surrogates of oncotype Dx recurrence scores in invasive ductal carcinoma: How complicated does it have to be?. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-16.