Abstract

Abstract Background Oncotype Dx Recurrence Score (ODX-RS) is a 21-gene assay used to predict recurrence in early stage breast cancer and guide chemotherapy decisions. Invasive lobular carcinomas (ILC) represent approximately 10-15% of all breast cancers. Many prior studies have shown that they have unique clinicopathologic features when compared to other histological subtypes. Therefore, the aim of this study was to first assess whether ODX-RS can be predicted using clinicopathologic factors in ILC and secondly, to compare these factors in invasive ductal carcinoma (IDC) and invasive carcinoma with mixed ductal and lobular features (IMC). Materials and Methods With IRB approval, the CoPath pathology database was queried for patients who were newly diagnosed with either IDC, ILC or IMC from 2010-2018 and had available Oncotype scores. For ILC cases, the subtype and presence or absence of LCIS was documented. The original pathology report was reviewed, and a chart review was performed to assess treatment decisions, locoregional and or distant recurrences and duration of follow-up. Patients with hormone receptor negative, HER2 positive or lymph node macrometastatic disease were excluded. Results A total of 582 patients were identified. The mean age was 60.1 years (range, 25-80 years). The median follow-up was 49 months (range, 0-145 months). There were 414 (71%), 102 (18%) and 66 (11%) cases of IDC, ILC and IMC, respectively. For ILC, there was a statistically significant relationship between ODX-RS and tumor grade, tubule formation, nuclear pleomorphism, mitotic count, modified Magee score (MME) and associated LCIS (Table 1). When compared to IDC and IMC, ILC had the lowest percentage of Grade 3 tumors, PR expression and high-risk patients by ODX. Factors predictive of high-risk ODX-RS in ILC were nuclear pleomorphism, mitotic count, ER H-score, PR H-score and MME, while for IDC, predictive factors included tumor grade, PR H-score, and MME using TAILORx cutoffs (Table 2). The rate of locoregional recurrences was similar between ILC and IDC (Table 1). No statistically significant correlation was found between ILC variants and RS. Disease free survival (DFS) was best in patients with IMC compared to IDC and ILC. DFS was also significantly better in patients with classic variant of ILC compared to pleomorphic variant.Conclusion We found that although ILC was similar to IDC and IMC based on tumor stage, tumor grade, risk category distribution, they demonstrated different predictors of high-risk ODX. Overall DFS was best in patients with IMC and patients with ILC, classic variant, however, when stratified based on RS scores the results were variable. Table 1. Clinicopathologic features of patients with ILC based on risk categories. ODX based on TAILORx<1111-25>25Totalp-valueAge0.534<502 (14)12 (86)014>5018 (20)65 (74)5 (6)88Race, n (%)0.551Caucasian20 (23)62 (72)4 (5)86African American012 (92)1 (8)13Asian02 (100)02Not reported01 (100)01T stage, n (%)0.187111 (21)35 (69)5 (10)51 27 (16)36 (84)04332 (25)6 (75)08Tumor Grade, n (%)<0.000113 (22)11 (78)014216 (19)66 (78)3 (3)8531 (33)02 (67)3Tubule formation, n (%)<0.0001Not reported3 (50)2 (33)1 (17)61000020011317 (18)75 (79)3 (3)95Nuclear pleomorphism, n (%)<0.0001Not reported3 (50)2 (33)1 (17)612 (14)12 (86)014214 (19)58 (80)1 (1)7331 (11)5 (56)3 (33)9Mitotic count, n (%)<0.0001Not Reported32161167018721539ER %, mean (SD)95 (4)92.6 (10)95.6 (1.3)93.2 (8.5)0.426PR %, mean (SD)74.3 (31.6)54.6 (37)62.2 (19)58.8 (36)0.09Modified Magee Score, mean (SD)13 (6.5)17.3 (5)16.7 (9.8)16.4 (5.8)0.010ILC Variants, n (%)0.169Classic18 (20)68 (77)3 (3)89Pleomorphic2 (15)9 (70)2 (15)13Associated LCIS Variants, n (%)<0.0001Classic15 (19)62 (79)2 (2)79Solid001 (100)1Pleomorphic08 (80)2 (20)10Mixed Pleomorphic and Classic5 (42)7 (58)012Locoregional RecurrenceYes0 (0)3 (75)1 (25)40.12No20 (20)74 (76)4 (4)98Distant recurrenceYes03 (100)030.605No20 (20)74 (75)5 (5)99 Table 2. Demographic data.AgeILCIDCIMCTotalp-value<3003 (0.7)030.00631-402 (2)14 (3.4)1 (1.5)1741-5012 (11.8)67 (16.2)10 (15.2)8951-6021 (20.6)140 (33.8)12 (18.2)17361-7039 (38.2)132 (31.9)31 (47)20271-8028 (27.5)58 (14)12 (18.2)98Total10241466582T stage, n (%)<0.0001T151 (50)303 (73)48 (73)402T243 (42)109 (26)18 (27)170T38 (8)2 (1)0 (0)10Tumor Grade, n (%)<0.0001114 (14)84 (20)9 (14)107285 (83)236 (57)50 (76)37133 (3)94 (23)7 (10)104ER, mean (SD)93 (8)91 (15)93 (7)0.883PR, mean (SD)59 (36)67 (37)62 (38)0.451Oncotype risk categories, n (%)Low risk (<11)20 (20)95 (23)13 (20)128<0.0001Intermediate risk (11-25)77 (75)230 (56)46 (70)353High risk (>25)5 (5)89 (21)7 (11)101Locoregional recurrence0.266Yes4 (4)16 (4)0 (0)20No98 (96)398 (96)66 (100)562Distant Recurrence0.927Yes3 (3)10 (2)2 (3)15No99 (97)404 (98)64 (97)567Predictors of High-risk ODX-RS, p-valueTumor gradeNS<0.00010.045Nuclear pleomorphism0.0060.004NSMitotic count0.003NSNSER H score0.047NSNSPR H score<0.00010.014NSModified Magee score (MME)0.019NSNSMME based on TAILORx cutoffsNS0.024NS Citation Format: Akisha Glasgow, Haley Sechrist, Phillip Bomeisl, Hannah Gilmore, Aparna Harbhajanka. Can oncotype Dx risk categories be predicted in invasive lobular carcinoma? [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS2-12.

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