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Chinese Journal of Breast Disease(Electronic Edition) ›› 2023, Vol. 17 ›› Issue (04): 203-209. doi: 10.3877/cma.j.issn.1674-0807.2023.04.002

• Original Article • Previous Articles     Next Articles

Clinical significance of tumor-infiltrating lymphocytes in HER-2-positive early breast cancer

Yaping Wang, Jing Fan, Niuniu Hou, Rui Ling()   

  1. Department of Thyroid, Breast and Vascular Surgery, First Affiliated Hospital of Air Force Medical University, Xi’an 710032, China
  • Received:2023-01-30 Online:2023-08-01 Published:2023-09-28
  • Contact: Rui Ling

Abstract:

Objective

To evaluate the role of tumor-infiltrating lymphocytes (TIL) in predicting the prognosis of HER-2 positive breast cancer patients.

Methods

We retrospectively analyzed the clinicopathological data of 176 patients with HER-2 positive breast cancer treated with neoadjuvant therapy (NAT) in the First Affiliated Hospital of Air Force Medical University from January, 2013 to June 2018. According to the pathological results of surgically removed specimens after NAT, the patients were divided into pCR group (n=84) and non-pCR group (n=92).Using the TIL counting method recommended by the international TIL working group, we assessed TIL level in the area between the borders of invasive tumor and adjacent normal tissues. The overall survival (OS) and recurrence-free survival (RFS) curves were plotted using the Kaplan-Meier method and the values were compared using log-rank test. The influencing factors of OS and RFS were analyzed by Cox proportional hazards regression model. The Mann-Whitney U test was used to analyze the change of TIL level before and after NAT.

Results

(1) The TIL level before NAT (pre-TIL) presented a significant difference between pCR group and non-pCR group (χ2=12.140, P<0.001). (2) Survival analysis showed that pre-TIL was related to OS and RFS (OS: χ2=14.243, P<0.001; RFS: χ2=3.881, P=0.049). Subgroup analysis showed that pre-TIL was related to OS and RFS (OS: χ2=5.272, P=0.022; RFS: χ2=6.033, P=0.014) in non-pCR patients, while TIL level after NAT (post-TIL) was not related to OS and RFS (OS: χ2=0.174, P=0.677; χ2=0.074, P=0.786). The pre-TIL was significantly lower than post-TIL in 92 non-pCR patients [6.0% (5.0%, 25.0%) vs 30.0% (11.3%, 63.8%), Z=-5.474, P<0.001]. The change of TIL level before and after NAT in non-pCR was not significantly related to OS and RFS (OS: χ2=2.342, P=0.126; RFS: χ2=3.853, P=0.051). (3) The Cox univariate analysis showed that the patients with lower pre-TIL had lower OS (HR=2.556, 95%CI: 1.458-4.482, P=0.001), but pre-TIL was not related to RFS (HR=1.362, 95%CI: 0.996-1.862, P=0.053); multivariate analysis showed that pre-TIL was an independent factor of OS (HR=2.556, 95%CI: 1.458-4.482, P=0.001). Among the patients with non-pCR, the patients with low pre-TIL had lower OS (HR=1.878, 95%CI: 1.058-3.333, P=0.031) and RFS (HR=1.670, 95%CI: 1.090-2.559, P=0.019). Post-TIL was not significantly related to OS (HR=1.534, 95%CI: 0.202-11.673, P=0.679) and RFS (HR=0.905, 95%CI: 0.438-1.866, P=0.786) in patients with non-pCR. The change of TIL level before and after NAT was not an independent factor of OS(HR=3.020, 95%CI: 0.681-13.396, P=0.146) and RFS (HR=3.152, 95%CI: 0.939-10.576, P=0.063).

Conclusion

Pre-TIL is a potential prognostic factor for HER-2 positive early breast cancer, and the predictive value of TIL change before and after NAT in non-pCR patients is worth of further exploration.

Key words: Breast neoplasms, Receptor, ErbB-2, Neoadjuvant therapy, Tumor infiltrating lymphocytes, Pathologic complete response

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