Abstract P4-07-13: An exploratory case-control study of perineural invasion in breast cancer
Authors: Cox Solange Erlyn , Bassett Roland , Yi Min , Sahin Aysegul , Teshome Mediget , Hunt Kelly , Akay Catherine 
Published: March 2022

Abstract
Background: There is great interest in determining prognostic indicators in cancer as they enable more informed treatment decisions and patient counseling. Perineural invasion (PNI) has been established as a poor prognostic indicator in many types of cancer, however its significance in breast cancer is not clear. Research Objectives: The objective of this study was to explore the prognostic importance of PNI in breast cancer and identify clinicopathologic variables associated with PNI in breast cancer. Methods: A prospectively maintained database was used to identify patients treated at a single institution for stage I-III unilateral breast cancer from 2006-2014. PNI-positive cases included all patients whose tumors were reported to contain PNI in either the needle biopsy specimen or the surgical pathology, and each case was matched with two PNI-negative control patients on age, clinical stage, ER, PR, and HER2 status. A total of 492 patients were included in the analysis, including 164 PNI-positive patients and 328 control patients. Distributions of age, race, lymphovascular invasion, multifocality, clinical tumor size and pathologic tumor size were compared using Fisher’s exact test (categorical variables) or Wilcoxon rank-sum test (continuous variables). The method of Kaplan and Meier was used to estimate the distribution of overall survival, disease-free survival, and time to locoregional recurrence from the diagnosis date. All statistical tests used a significance level of 5%. No adjustments for multiple testing were made. Results: The median follow up was 6.26 years (6.3 years versus 6.2 years for PNI-positive and controls, respectively). The number of reported PNI-positive cases increased over the study period, with 76 cases reported during the 6-year period 2006-2011 and 88 cases reported during the last two years, 2013-2014. There was no statistical difference noted in overall survival, disease-free survival, or time to recurrence by clinical stage for PNI-positive patients compared to controls. It was noted that clinical stage 3 disease showed a trend toward poorer disease-free survival in PNI-positive patients although this did not reach statistical significance. Median pathologic tumor size was significantly higher in the PNI-positive patients compared to controls (2.2 cm versus 1.6 cm, respectively, p&lt;0.0001). In the subset of patients treated with neoadjuvant chemotherapy, median tumor size was also significantly higher in the PNI-positive patients compared to controls (2.8 cm versus 1.5 cm, p=0.0087). Pathologic node-positive status was more likely in the PNI-positive patients (47% versus 41%, p=0.019). Analysis of non-matched variables including race, lymphovascular invasion, multifocality and nuclear grade showed no statistically significant difference between the PNI and control groups.Conclusion: Perineural invasion was not found to be a statistically significant prognostic indicator of survival or locoregional recurrence. PNI is associated with larger pathologic tumor size, and this finding persists among patients treated with neoadjuvant chemotherapy. PNI is also associated with lymph node metastasis. This analysis is limited by small sample sizes and likely under reporting of PNI. Additional research is needed to evaluate the significance of PNI in breast cancer.
Table 1.Patient CharacteristicsVariableLevelsPNI (%)Control (%)P-ValueAge≤ 5047 (28.7)94 (28.7)p = 1.00&gt; 50117 (71.3)234 (71.3)RaceAsian10 (6.1)24 (7.3)p = 0.22Black9 (5.5)30 (9.2)Hispanic22 (13.4)51 (15.6)White122 (74.4)214 (65.2)Lymphovascular invasionY53 (32.3)80 (24.4)p = 0.07Lymphovascular invasionN111 (67.7)248 (75.6)p = 0.07MultifocalityN123 (75.0)206 (69.8)p = 0.28Y41 (25.0)89 (30.2)Nuclear Grade129 (18.4))47 (14.8)p = 0.28288 (55.7)166 (52.4)341 (25.9)104 (32.8)Clinical StageIA55 (33.5)110 (33.5)p = 1.00IIA59 (36.0)118 (36.0)IIB23 (14.0)46 (14.0)IIIA6 (3.7)12 (3.7)IIIB14 (8.5)28 (8.5)IIIC7 (4.3)14 (4.3)Pathologic N StageNx2 (1.2)1 (0.3)p = 0.019N083 (51.5)193 (59.0)N149 (30.4)88 (26.9)N217 (10.6)22 (7.0)N310 (6.2)23 (7.0)ERNeg11 (6.7)22 (6.7)p = 1.00Pos153 (93.3)306 (93.30PRNeg19 (11.6)38 (11.6)p = 1.00Pos145 (88.4)290 (88.4)HER2Neg155 (94.5)310 (94.5)p = 1.00Pos9 (5.5)18 (5.5)Neoadjuvant ChemotherapyN121 (73.3)240 (73.2)p = 1.00Y44 (26.7)88 (26.8)Clinical tumor sizeRange (cm)0.15 - 9.800.50-10.00p = 0.0013Median (cm)2.453.00Pathologic tumor sizeRange (cm)0.02-15.000.00 - 20.00p &lt; 0.0001Median (cm)2.201.60Pathologic tumor size after neoadjuvant chemotherapyRange (cm)0.02-120.00-20p = 0.0087Median (cm)2.751.47
Citation Format: Solange Erlyn Cox, Roland Bassett, Min Yi, Aysegul Sahin, Mediget Teshome, Kelly Hunt, Catherine Akay. An exploratory case-control study of perineural invasion in breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-07-13.