Specific aspect of utilization of the prognostic multigene assay for invasive lobular carcinoma at early stage: Oncotype Dx in the prospective French cohort PONDx

Abstract Introduction: Invasive lobular carcinoma (ILC) differs from invasive ductal carcinoma (IDC) in a number of biological features with possible implication in treatment choice particularly for adjuvant chemotherapy. Multigene assay are being used increasingly to guide therapy for endocrine responsive breast cancer without HER2 overexpression or amplification at early stage. But if their interest is well defined for IDC, there are few data for ILC. Our study examine the impact of a multigene assay, Oncotype Dx (ODx), for the population of lobular breast cancer. Patients and methods: It was a retrospectively analysis of a French prospective cohort of patients (PONDx), with use of ODx (n= 882 patients). We studied and compared the specifics aspects of the use and the results of ODx for the ILC ( n= 125 (14,2%)) and IDC patients (n= 691 (78.3%)). We took account of the clinicopathological features, the Recurrence Score (RS), resulting of ODx and its impact on decision making. Results: In our cohort ILC were more frequently grade 2 tumours, had a significantly larger size, and lower Ki67 than IDC. RS distribution was lower for ILC (p<0,007): 66,4% of ILC had RS<18, 28,8% had RS from 18 to 30 and 4,8% had RS>30 ; whereas for IDC RS<18 for 52,2%, RS 18-30 for 36,8% and RS>30 for 11%. But there was a similar overall rate of change in treatment decision for ILC (46,4%) and IDC (43%) and a de-escalation of treatment (for no adjuvant chemotherapy) for 67,7% of ILC and 57,1% of IDC with initial indication of adjuvant chemotherapy. On the other hand, about 10% of patients with no initial indication of chemotherapy had an escalation of treatment after ODx for adjuvant chemotherapy. The analysis of the whole population shows a correlation of the lobular histologic type with low RS in univariate or multivariate analysis. Conclusion: RS is clearly prognostic for ILC and IDC. The predictive value of chemotherapy benefit was prospectively demonstrated for IDC, but not so clearly for ILC. In the PONDx cohort, despite a larger size of tumors, the RS of ILC was lower showing different biological features among the gene studied by ODx. The impact on decision making of ODx was similar for ILC and IDC, showing the interest of genomic assay in decision making independently from histologic subtypes (between ILC and IDC). Citation Format: Gaëlle Douchet, Elsa Curtit, Hugues Bourgeois, Sandrine Richard, Sonia Zilberman, Younes Mahi, Joseph Gligorov. Specific aspect of utilization of the prognostic multigene assay for invasive lobular carcinoma at early stage: Oncotype Dx in the prospective French cohort PONDx [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-11-13.