Abstract

Abstract Background: Positive lymphovascular invasion (LVI) is a negative prognostic factor for women with early-stage ER+ breast cancer. LVI, along with other clinicopathologic factors such as larger tumor size, higher grade and positive nodal status, increase a patient's risk of late (post-5y) recurrence. Breast Cancer Index (BCI) is a validated gene expression-based assay for patients with early-stage HR+ breast cancer that reports an individualized risk of late distant recurrence based on a combination of the HOXB13/I17BR ratio and the molecular grade index (MGI). The correlation of LVI and individualized risk stratification by genomic analysis is not well characterized. Therefore, this study evaluated risk stratification by BCI based on the presence or absence of LVI. Methods: A population of 2,613 patients with known LVI status were identified in the Breast Cancer Index Clinical Database for Correlative Studies, an IRB-approved de-identified database which contains clinicopathologic and molecular variables of more than 19,000 clinical cases submitted for BCI testing. LVI was recorded as either positive or negative based on pathology report review. BCI results based on LVI status from LN- (n=2035) and LN+ patients (n=578) were evaluated separately. Chi-squared tests were used to compare BCI results between LVI groups. Results: In analyses of 2,613 patients with LVI data available (median age 59.1 y; range 28-89y; 74% ≥50y), 18.3% of patients showed evidence of LVI (LVI-pos). In comparison to the LVI-neg tumors submitted for BCI testing, the LVI-pos tumors had a higher proportion of grade 3 tumors (33% vs 16%, p<0.0001), more LVI-pos tumors were 2.0 cm or greater (45% vs 23%, p<0.0001), a higher percentage LVI-pos patients had node-positive disease (51% vs 16%, p<0.0001), and a higher proportion of LVI-pos tumors showed high Ki67 (Ki67 ≥14%; 64% vs 51%, p=0.004). A correlation between LVI positivity and high BCI prognostic risk was observed, with a higher proportion of LVI-pos patients classified as high risk of late distant recurrence in both the LN- (68% vs 49%, p<0.0001) and LN+ subsets (84% vs 70%, p<0.0001) compared to LVI-neg patients. LVI-pos patients had a higher median molecular proliferative status (MGI) compared to LVI-neg patients regardless of nodal status (p<0.0001 for both). In contrast to the categorical LVI prognostic factor, the wide distribution of BCI individual risk scores provides additional resolution that identifies a substantial subset of LVI positive tumors (32%) that that have a low risk of late recurrence by genomic analysis. Conclusion: While BCI Prognostic stratification correlated with LVI status, BCI identified a subset of patients with LVI positivity as having a low risk of late distant recurrence that otherwise would have an unfavorable prognosis based on LVI and/or LN positivity. These findings help to characterize differential patient stratification based on an individualized assessment of tumor biology versus LVI for patients considering EET. Citation Format: Vulchi M, Sagalnik M, Schnabel CA, Abraham J. Correlation of breast cancer index (BCI) results to lymphovascular invasion in early stage HR+ breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-06-09.

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