Estrogens have an important role in the progression of breast cancer. The 17B-hydroxysteroid dehydrogenase (17HSD) family has been identified to be of significance in hormonedependent tissues. 17HSD1 and 17HSD2 are the main 17HSD enzymes involved in breast cancer investigated this far, but it is possible that other hormone-regulating enzymes have a similar role. 17HSD5 and 17HSD12 are associated with sex steroid metabolism, and 17HSD14 is a newly discovered enzyme that may be involved in the estrogen balance. The mRNA expression of 17HSD5, 17HSD12, and 17HSD14 were analyzed in 131 breast cancer specimens by semiquantitative real-time PCR. The results were compared with recurrencefree survival and breast cancer-specific survival of the patients. The breast cancer cell lines MCF7, SKBR3, and ZR75-1 were transiently transfected with 17HSD14 to investigate any possible effect on estradiol levels. We found that high 17HSD5 was related to significantly higher risk of late relapse in estrogen receptor (ER)-positive patients remaining recurrence-free later than 5 years after diagnosis (P = 0.02). No relation to 17HSD12 expression was found, indicating that 17HSD12 is of minor importance in breast cancer. Patients with ER-positive tumors with high expression levels of 17HSD14 showed a significantly better prognosis about recurrence-free survival (P = 0.008) as well as breast cancerspecific survival (P = 0.01), confirmed by multivariate analysis (P = 0.04). Transfection of 17HSD14 in the human breast cancer cells MCF7 and SKBR3 significantly decreased the levels of estradiol, presenting an effect of high expression
Background Several validated molecular subtyping tests for breast cancer based on gene expression profiling are now routinely used in clinical practice.The Prosigna® breast cancer (BC) prognostic gene signature assay identifies a gene-expression profile that permits the classification of tumors into subtypes and gives a score for the risk of recurrence (ROR) at 10 years. The assay uses the 50-gene expression profile, weighted together with clinical variables, to generate a risk category and numerical score. The score is reported on a 0-100 scale, for hormone receptor positive BC. Prosigna test results classified tumors according to intrinsic subtypes (Lum A, Lum B, HER2-enriched, basal-like) and ROR risk groups (low risk, 0-40; intermediate risk, 41-60; and high risk, 61-100). For node-positive patients, the weight given to the node status is similar when considering pN1mi ([0.2-2mm]) or pN1 (>2mm, 1-3 positive lymph nodes). Our aim was to characterize the Prosigna test classification of the pN1mi subgroup in the French national registry for molecular signatures in ER+ BC. Methods Since 2018, four French laboratories using Prosigna test in clinical practice retrospectively implement a national registry for molecular prognostic signatures in ER+ BC. We analyzed the pN1mi subgroup with regards to their clinico-pathological characteristics, Prosigna test results and ROR risk score. Using the definition formula of the prosigna algorithm, we could calculate a hypothetical score if the pN1mi has been considered as pN0 and redefine risk categories for pN1mi breast cancers. Results The database included 886 tests performed in routine practice, including 91 (10.3%) pN1mi. The pN1mi BC were ER+ HER2- (88/91, 96.7%), invasive carcinoma of no special type in 81/91 (89%), with a median tumor size of 23 mm (range 12-60). Among these, the median ROR score was 44, and 51/91 tumors (56%) were classified as LumA tumors, 34/91 (41%) as LumB, two asHER2-enriched and one as basal-like. Interestingly, the probability of distant recurrence was 26% if pN1mi BC were considered as N+ but lowered to 10% if considered as pN0. Among the different molecular subtypes, the change from pN1 top N0 has different weight: in Lum A tumors, the switch in the probability of distant recurrences was 13 to 6% according to pN categorization of the pN1mi BC, and the median ROR score moved from 27 to 6 with 15/51(29%) of Lum A tumors considered as high risk if pN1 but only 1/51 if pN0; 31/51 (61%) versus 14/51 (27.5%) were in the intermediate risk group, and only 5/51 (10%) versus 34 (67%) in the low risk group. For LumB tumors, the switch in the probability of distant recurrences was 29% to 17% according to pN categorization and and the median ROR score moved from 60 to 15 with 36/37(97.3%) of Lum B tumors considered as high risk if pN1but only 13/37(35%) ifp N0; 1/37 versus 20/37 (54%) were in the intermediate risk group, and none of the 37 LumB versus 1 in the low risk group. Conclusion With regards to Prosigna test in pN1mi BC - and the persistent debate as to whether they should bear the same weight as pN1 pN0 tumors - categorization in ROR risk group is likely to be impacted by the node factor weight, and more importantly among Lum B tumors. Citation Format: Charafe-Jauffret E, Duprez-Paumier R, Berghian A, Penault-Llorca F, Dauplat MM, Boucraut A, Cohen M, Houvenaeghel G, Maroc C, Pradines A, Cayre A, Etancelin P, Lacroix-triki M. Prosigna prognostic signature in pN1mi, estrogen receptor-positive breast cancer:the pN categorization impacts the BC risk stratification [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-11-10.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.