Abstract

Abstract Background: It is unknown whether molecular subtype is associated with axillary lymph node (ALN) status (ypN) after neoadjuvant therapy (NAT) in breast cancer patients who achieved breast pathological complete remission (pCR), especially for patients with different clinical stage. Our study aimed to investigate the association of clinical stage and molecular subtype with ALN status (ypN) after NAT in breast cancer patients. Patients and methods: Breast cancer patients receiving ≥ 4 cycles of NAT with complete clinicopathological data were retrospectively included between January 2009 to January 2020. Status of ypN according to breast pCR status was compared in cT1-2N0, cT1-2N1, and local advanced breast cancer (LABC) patients with different molecular subtype. Univariate and multivariate analyses were conducted to identify potential predictive factors for ypN status. Results: A total of 1999 patients were included. cT1-2N0, cT1-2N1, and LABC disease were found in 457 (22.86%), 884 (44.22%) and 658 (32.92%) patients, whose ypN+ rate was 24.5%, 60.3%, and 66.4%, respectively (P < 0.001). Compared with cT1-2N0 patients, ypN+ rate was significantly higher in cT1-2N1 (OR = 5.48, 95%CI = 3.77-7.97, P < 0.001) and LABC (OR = 10.90, 95%CI = 7.12-16.70, P < 0.001). Moreover, ypN+ rate varied across different molecular subtypes, which was 60.0% in Luminal A subtype, 61.4% in Luminal B (HER2-) subtype, 47.6% in Luminal B (HER2+) subtype, 42.2% in HER2-amplified subtype and 52.5% in TNBC (P < 0.001). Patients achieving breast pCR also had a significantly lower ypN+ rate than those without breast pCR (23.9% vs 62.5%, univariate P < 0.001; OR =0.14, 95%CI = 0.09-0.21, P < 0.001). Furthermore, in breast pCR patients, multivariate analyses showed that clinical stage and molecular subtype were substantially related to ypN+ rate: the ypN+ rate was significantly higher in cT1-2N1 (OR = 5.64, 95%CI = 2.31-13.76, P < 0.001) and LABC (OR = 9.80, 95%CI = 3.88-24.77, P < 0.001), compared with cT1-2N0 patients; while it was significantly lower in Luminal B HER2+ (OR =0.20, 95%CI = 0.05-0.82, P = 0.025) and HER2-amplified (OR = 0.19, 95%CI = 0.05-0.83, P = 0.026) subtype, compared with Luminal A subtype. In the cT1-2N0 subgroup, all patients with breast pCR with Luminal B HER2+ or HER2-amplified subtype achieved ALN pCR. Conclusion: Clinical stage and molecular subtype were significantly associated with ypN status in breast pCR patients after NAT. Patients with cT1-2N0 and HER2-positive patients who achieved breast pCR had low ypN+ rate, which possibly guides further clinical ALN management after NAT. Key words: Breast pathological complete remission; Neoadjuvant therapy; Molecular subtype; Clinical stage; Nodal residual burden. Table. Pathological node status stratified by clinical stage between patients with breast pCR and non-pCR.Response in breastpCRnon-pCRypN0 (N, %)ypN+ (N, %)ypN0 (N, %)ypN+ (N, %)Whole population331(76.1)104(23.9)586(37.5)978(62.5)cT1-2N088(93.6)6(6.4)257(70.8)106(29.2)cT1-2N1159(74.3)55(25.7)192(28.7)478(71.3)LABC84(66.1)43(33.9)137(25.8)394(74.2)Luminal A like9(69.2)4(30.8)37(36.3)65(63.7)cT1-2N06(85.7)1(14.3)19(73.1)7(26.9)cT1-2N13(50.0)3(50.0)12(27.9)31(72.1)LABC0(0.0)0(0.0)6(18.2)27(81.8)Luminal B like (HER2-)112(70.4)47(29.6)220(31.4)480(68.6)cT1-2N033(89.2)4(10.8)85(59.0)59(41.0)cT1-2N159(71.1)24(28.9)75(23.8)240(76.2)LABC20(51.3)19(48.7)60(24.9)181(75.1)Luminal B like (HER2+)89(83.2)18(16.8)140(42.4)190(57.6)cT1-2N019(100.0)0(0.0)70(83.3)14(16.7)cT1-2N146(83.6)9(16.4)43(30.5)98(69.5)LABC24(72.7)9(27.3)27(25.7)78(74.3)HER2 amplified66(82.5)14(17.5)97(48.0)105(52.0)cT1-2N014(100.0)0(0.0)42(82.4)9(17.6)cT1-2N125(78.1)7(21.9)32(42.1)44(57.9)LABC27(79.4)7(20.6)23(30.7)52(69.3)TNBC55(72.4)21(27.6)92(40.0)138(60.0)cT1-2N016(94.1)1(5.9)41(70.7)17(29.3)cT1-2N126(68.4)12(31.6)30(31.6)65(68.4)LABC13(61.9)8(38.1)21(27.3)56(72.7)Abbreviations: LABC, locally advanced breast cancer; HER2, human epidermal growth factor receptor 2; TNBC, triple negative breast cancer; pCR, breast pathological complete response. Citation Format: Jin Hong, Yiwei Tong, Ou Huang, Jiayi Wu, Li Zhu, Jianrong He, Weiguo Chen, Yafen Li, Xiaochun Fei, Xiaosong Chen, Kunwei Shen. Molecular subtype and clinical stage influenced axillary lymph node response in breast cancer patients with breast pathological complete remission after neoadjuvant therapy [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 PS1-33.

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