Discordance du phénotype immunohistochimique hormonal et du récepteur du facteur de croissance épidermique de type 2 [HER2] des métastases cérébrales de cancer du sein comparativement à leurs primitifs

International audienceINTRODUCTION: Phenotype changes between primary tumor and the corresponding brain metastases are recent reported data. Breast cancer, with biological markers predicting prognosis and guiding therapeutic strategy remains an interesting model to observe and evaluate theses changes. The objective of our study was to compare molecular features (estrogen receptor [ER], progesterone receptor [PR], and human epidermal growth factor receptor type 2, [HER2]) between brain metastases and its primary tumor in patients presenting with pathologically confirmed breast cancer.MATERIAL AND METHODS: This retrospective study was based on the immunohistochemical analysis of the brain metastases paraffin embedded samples stored in our institutional tumor bank, after surgical resection. The level of expression of hormonal receptors and HER2 on brain metastases were centrally reviewed and compared to the expression status in primary breast cancer from medical records.RESULTS: Forty-four samples of brain metastases were available for analysis. Hormonal receptor modification status was observed in 11/44 brain metastases (25%) for ER and 6/44 (13.6%) for PR. A modification of HER2 overexpression was observed in brain metastases in 6/44 (13.6%). Molecular subtype modification was shown in 17 cases (38.6%). A significant difference was demonstrated between time to develop brain metastases in cases without status modification (HER2, ER and PR) (med=49.5months [7.8-236.4]) and in cases in which brain metastases status differs from primary tumor (med=27.5months [0-197.3]), (P=0.0244, IC95=3.09-51.62, Mann and Whitney test).CONCLUSION: the main interest of this study was to focus on the molecular feature changes between primary tumor and their brain metastases. Time to develop brain metastases was correlated to phenotypic changes in brain metastases.Introduction:La modification phénotypique entre une tumeur primitive et sa métastase cérébrale correspondante est une donnée récente. Le cancer du sein, de part ses biomarqueurs impactant le pronostic et la stratégie thérapeutique, constitue une pathologie d’intérêt pour observer et évaluer ce type de modification. L’objectif était de comparer les caractéristiques moléculaires (récepteurs aux estrogènes [RE], à la progestérone [PR], et récepteur au facteur de croissance épidermique humain type 2 [HER2]) des métastases cérébrales et des tumeurs primitives correspondantes de patients porteurs d’un adénocarcinome mammaire.Matériels et méthodes:Cette étude rétrospective, utilisait des échantillons tumoraux issus des métastases cérébrales réséquées, inclus en paraffine, conservés en tumorothèque. Le niveau d’expression des récepteurs hormonaux et de HER2, sur chaque couple primitif/métastase cérébrale correspondante était analysé par immunohistochimie.Résultats:Quarante-quatre échantillons de métastases cérébrales étaient exploitables. La conversion des récepteurs hormonaux a été observée pour 11/44 métastases cérébrales (25 %) pour RE et pour 6/44 cas (13,6 %) pour RP. L’expression de HER2 était modifiée au sein de la métastase cérébrale dans 6/44 cas (13,6 %). Le changement de sous-type moléculaire était montré dans 17 cas (38,6 %). Il existait une différence significative pour le délai de survenue de la métastase cérébrale entre le groupe ne présentant pas de modification pour RE, RP ou HER2, (med = 49,5 mois [7,8–236,4]) et le groupe dont le phénotype de la métastase cérébrale différait du primitif (med = 27,5 [0–197,3]), (p = 0,0244, IC95 = 3,09–51,62, test de Mann et Whitney).Conclusion:L’intérêt de ce travail était la mise en évidence de modification de signature moléculaire entre la tumeur primitive et la métastase cérébrale correspondante. Le délai de survenue de la métastase cérébrale apparaissait corrélé à la modification de statut phénotypique de la métastase cérébrale

Lymphovascular invasion has a significant prognostic impact in patients with early breast cancer, results from a large, national, multicenter, retrospective cohort study

International audienceBackground: We determined the prognostic impact of lymphovascular invasion (LVI) in a large, national, multicenter, retrospective cohort of patients with early breast cancer (BC) according to numerous factors.Patients and methods: We collected data on 17 322 early BC patients treated in 13 French cancer centers from 1991 to 2013. Survival functions were calculated using the Kaplan-Meier method and multivariate survival analyses were carried out using the Cox proportional hazards regression model adjusted for significant variables associated with LVI or not. Two propensity score-based matching approaches were used to balance differences in known prognostic variables associated with LVI status and to assess the impact of adjuvant chemotherapy (AC) in LVI-positive luminal A-like patients.Results: LVI was present in 24.3% (4205) of patients. LVI was significantly and independently associated with all clinical and pathological characteristics analyzed in the entire population and according to endocrine receptor (ER) status except for the time period in binary logistic regression. According to multivariate analyses including ER status, AC, grade, and tumor subtypes, the presence of LVI was significantly associated with a negative prognostic impact on overall (OS), disease-free (DFS), and metastasis-free survival (MFS) in all patients [hazard ratio (HR) = 1.345, HR = 1.312, and HR = 1.415, respectively; P < 0.0001], which was also observed in the propensity score-based analysis in addition to the association of AC with a significant increase in both OS and DFS in LVI-positive luminal A-like patients. LVI did not have a significant impact in either patients with ER-positive grade 3 tumors or those with AC-treated luminal A-like tumors.Conclusion: The presence of LVI has an independent negative prognostic impact on OS, DFS, and MFS in early BC patients, except in ER-positive grade 3 tumors and in those with luminal A-like tumors treated with AC. Therefore, LVI may indicate the existence of a subset of luminal A-like patients who may still benefit from adjuvant therapy