HER2 阴性乳腺癌新辅助化疗后 HER2、ER、PR 与 Ki-67 的变化：病例对照研究

Purpose : This study investigates receptor status changes following neoadjuvant chemotherapy (NAC) in breast cancer, aiming to identify new therapeutic opportunities and improve human epidermal growth factor receptor 2 (HER2) detection and categorization methods. Methods : This retrospective analysis was conducted on patients with breast cancer who underwent NAC and surgery between July 2022 and June 2024. Chi-square tests and logistic regression models were applied to assess the associations between HER2 status changes and clinicopathological features. Results : Among 508 patients, the receptor discordance rates after NAC were 5. 3% for estrogen receptor (ER), 21. 3% for progesterone receptor (PR), and 43. 7% for HER2. Ki-67 expression decreased in 64. 6% of cases and increased in 6. 8%. Of the 103 patients with HER2-0, 47 (45. 6%) transitioned to IHC 1+, 9 (8. 7%) to IHC 2+/ISH-, and 1 (1. 0%) to IHC 2+/ISH+.

Among 256 patients with HER2 IHC 1+, 58 (22. 7%) transitioned to IHC 2+/ISH-, 36 (14. 1%) to IHC 0, and 9 (3. 5%) to IHC 2+/ISH+. For 149 patients with HER2 IHC 2+/ISH-, 50 (33. 6%) transitioned to IHC 1+, 6 (4. 0%) to IHC 2+/ISH+, 5 (3. 4%) to IHC 0, and 1 (0. 7%) to IHC 3+. Univariate analysis revealed that, when compared to grade III tumors, grade I-II tumors exhibited a higher rate of HER2-0 to HER2-low conversion (66. 7% vs. 36. 8%, p = 0. 027).

HER2-low to HER2-0 conversion was associated with ER negativity ( p = 0. 028), PR negativity ( p = 0. 021), HER2 IHC 1+ (vs. IHC 2+, p = 0. 001), and TIL >10% ( p = 0. 049). Multivariate analysis revealed that tumors with HER2 IHC 1+ were more likely to convert to HER2-0 after NAC than those with HER2 IHC 2+ ( p = 0. 020). Conclusions : Following NAC, ER gain, PR loss, and Ki-67 reduction were common. HER2 and ER status changes predominantly occurred within adjacent expression intensity levels.