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ObjectiveThis study aimed to analyze the expression levels of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), and Ki-67 proliferation index in the brain metastatic lesions and primary lesions in Chinese patients with breast cancer brain metastasis (BCBM) and determine the correlation between their changes and patients' survival.MethodsA retrospective analysis was performed on patients with BCBM. The clinical characteristic of these patients was collected. The differences in the expression levels of the ER, PR, HER-2, and Ki-67 index between the primary lesions and brain lesions were evaluated, and the association between the differences and survival was analyzed.ResultsThe conversion rate of anyone receptor (ER, PR, or HER2) between the primary lesions and brain metastatic lesions was 45.0% (18/40), of which the ER inconsistency rate was 25.0%, the PR inconsistency rate was 22.5%, and the HER-2 inconsistency rate was 15.0%, and the receptor conversion resulted in a subtype conversion of 27.5% (11/40). The patients with HER-2 expression discordance between the primary lesions and the brain metastatic lesions had significantly longer survival times (58.9 vs. 26.4 months, P = 0.04) after diagnosis of brain metastases.ConclusionIn this study, 45.0% of breast cancer patients developed biomarker-conversion between the primary lesions and brain metastatic lesions, and the differences in the expression levels of the ER, PR, and HER-2, the change in Ki-67 index between the primary lesions and brain lesions may predict patients' survival.

CDK4/6 inhibitors combined with endocrine therapy are standard first- or second-line treatment for patients with HR-positive and HER2-negative advanced breast cancer, however, there is currently no optimal recommendation for therapeutic strategies after progression on CDK4/6i. The aim of this study is to analyze the efficacy and safety of HDAC inhibitor Tucidinostat combined with endocrine therapy in patients after prior CDK4/6 inhibitor progression. The pathological and clinical data of 44 HR-positive and HER2-negative breast cancer patients treated with tucidinostat after progression on CDK4/6i at the Breast Oncology Department of the Fifth Medical Center of the PLA General Hospital from July 2019 to October 2021 were retrospectively analyzed. Observation indexes included progression-free survival (PFS), overall survival (OS), clinical benefit rate (CBR), objective response rate (ORR) and adverse events. At the same time, we attempted to identify potential genomic predictors using available next-generation sequencing (NGS). A total of 44 patients were enrolled in this study. Median follow-up was 10 months (1–26 months) by the data cutoff date (February 2022). The CBR was 6.8% (3/44), the median PFS was 2.0 months (95% CI 1.9–2.1), and the median OS was 14 months (95% CI 6.3–21.7). The mPFS was 4.1 months (95%CI: 0–8.2) in patients with 1 metastatic site, and the mPFS was 4.5 months (95%CI: 4.2–4.8) in patients who received sequential tucidinostat after CDK4/6i failure. Multivariate analysis showed that patients with 1 metastatic site or sequential tucidinostat treatment after failure of CDK4/6i were more likely to benefit from tucidinostat combined with endocrine therapy. Preliminary data showed PIK3CA mutation may be associated with resistance of tucidinostat therapy. No grade 4 adverse events and no treatment-related deaths were recorded in the study. Dose reductions because of adverse events occurred in 4 (9.1%) patients. This study preliminarily shows that tucidinostat combined with endocrine therapy may be an optional sequential strategy for patients with HR+/HER2-advanced breast cancer that has progressed on CDK4/6 inhibitor, especially for these with lower tumor burden and fewer prior palliative treatment. • CDK4/6 inhibitor became standard treatment for HR-positive MBC patients. • There is no optimal treatment strategy after progression on CDK4/6i. • Tcucidinostat was the only HDAC inhibitor approved in solid tumors worldwide. • The mPFS of Tcucidinostat was 4.5 months when used sequentially after prior CDK4/6i. • PIK3CA mutation may be associated with resistance of tucidinostat. [ABSTRACT FROM AUTHOR]

Background: At present, local therapy, such as surgery and radiotherapy, is the mainstay treatment for brain metastasis and anti-human epidermal growth factor receptor type 2 (HER2)-targeted therapy has been shown to be efficacious for HER2 + breast cancer (BC) patients with brain metastasis. However, Clinical studies comparing the combined effects of the two treatments are lacking. This study sought to investigate the efficacy and safety of pyrotinib and radiotherapy versus pyrotinib-based therapy in treating HER2 + BC patients with brain metastasis., Methods: This retrospective, observational study collected data from 79 HER2 + BC patients with brain metastasis who received pyrotinib-based therapy from May 2018 to December 2021. Among these patients, 35 received pyrotinib-based therapy concurrently with, or within 3 months before or after, brain radiotherapy (Group A), and 44 received pyrotinib-based therapy as the primary regimen (with no restriction as to whether they had received brain radiotherapy previously or not, the interval between receiving radiotherapy and receiving pyrotinib was >3 months) (Group B). Patient information was collected by the Electronic Medical Records System. The primary endpoints were progression-free survival (PFS) and overall survival (OS). The secondary endpoints were the objective response rate (ORR), the clinical benefit rate (CBR), and safety. The assessment of adverse effects was based on CTCAE5.0., Results: The intracranial ORRs were 48.6% in Group A and 20.5% (9/44) in Group B (P=0.015). The intracranial CBRs were 80.0% in Group A and 65.9% in Group B. The median intracranial PFS times (IC-PFS) were 15.0 months and 9.0 months in Group A and Group B, respectively (P=0.385). There was no statistically significant difference in OS between the 2 groups (95.0 vs . 98.0 months, P=0.872). The subgroup analysis showed that patients with active brain metastasis who received pyrotinib and radiotherapy had a longer IC-PFS time than those who received pyrotinib-based therapy(P=0.056). No serious adverse reactions (e.g., acute brain edema, cognitive dysfunction, or treatment-related death events) were observed., Conclusions: Pyrotinib combined with radiotherapy is recommended for HER2 + breast cancer active brain metastasis patients who can tolerate radiotherapy and pyrotinib. Pyrotinib-based therapy may be considered for patients who cannot tolerate radiotherapy and pyrotinib., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-5352/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Background: Neoadjuvant therapy is a standard treatment for patients with large, nonmetastatic breast cancer and may allow breast-conserving surgery after tumor downsizing while decreasing the risk of subsequent relapse. Dynamic changes of circulation tumor cells (CTCs) have a role in predicting treatment efficacy of breast cancer. However, the relationship between CTC enumeration before neoadjuvant therapy and pathologic complete response rate is still uncertain., Methods: The study was exploratory. A total of 50 breast cancer patients were enrolled in a phase II clinical study of neoadjuvant therapy for HER-2-positive early breast cancer. They were enrolled for blood draws before and after neoadjuvant therapy. We used two methods ( CellSearch and TUMORFISH ) to detect CTCs. We compared the sensitivity of the two systems and investigated the correlation of the enumeration on baseline CTCs with the diagnosis, prognosis, and efficacy of neoadjuvant therapy of the patients with HER-2-positive early breast cancer. We also explored the dynamic change of CTCs after neoadjuvant therapy., Results: The sensitivity of TUMORFISHER (27/50) method was significantly higher than that of the CellSearch system (15/50, p =0.008). The CTC numbers detected by the two detection systems were not significantly correlated with lymph node status, clinical stage, ki-67 level and hormone receptor status. Patients with ≥1 CTC before neoadjuvant therapy measured by the TUMORFISHER system had a significant high pCR rate (74.1% vs. 39.1%, p = 0.013); whereas, there was no predictive effect on pCR by CellSearch system (73.3% vs. 51.4%, p = 0.15). Patients with a decrease in CTCs enumeration after neoadjuvant therapy were more likely to achieve pCR than those with no change or increase in CTCs enumeration (87.5% vs 50.0%, p = 0.015) by the TUMORFISHER method. Unfortunately, there was no predictive value of CTCs enumeration for EFS before and after neoadjuvant therapy by two methods., Conclusions: Our study demonstrates that the new CTCs detection method TUMORFISHER system has a higher checkout rate in early breast cancer than the CellSearch system, and shows the opportunity of CTC enumeration as a novel assistant biomarker to predict the response of neoadjuvant therapy in patients with HER-2-positive early breast cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhou, Wu, Hao, Li, Zhang, Wu, Chen, Liu, Xiao, Zhang, Jiang, Yang, Hu and Wang.)