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Purpose: we used the real-world data of Chinese patients to describe clinicopathological characteristics of patients with breast cancer brain metastases (BCBM) and to investigate survival after diagnosis of brain metastases (BM). Methods: The clinicopathological characteristics of 700 patients with BCBM at the fifth Medical Center of Chinese PLA General Hospital between 2003 and 2021 were retrospectively reviewed. Information was collected from the electronic medical records, including patient demographics, tumor characteristics, and dates of diagnosis of original breast carcinoma and subsequent metastases. Sites and number of metastatic lesions were also recorded, along with data on treatments and outcomes. The prognostic and predictive effects of these clinicopathological variables in BCBM were analyzed. Results: The median age at diagnosis of primary breast cancer was 44 years (range, 22-80 years) and all patients were female. Among the 700 patients with BCBM, 30.0%, 49.7%, 18.9%, 1.4% had Luminal, HER2 positive, triple-negative and unknown subtypes, respectively. Based on available clinical information, the proportions of extracranial metastasis at diagnosis included bone (63.7%), lymph nodes (61.6%), lung (55.1%), liver (50.1%), the soft tissues of the thoracic wall (26.1%) and bone marrow (4.9%).The median time from the diagnosis of breast cancer to the development of BM was 52.0 months [95% confidence interval (CI), 44.3-59.7], 36.0 months (95%CI, 31.9-40.1), and 29.0 months (95%CI, 22.4-35.6) for patients with Luminal, HER2 positive and triple-negative, respectively (p Table 1.patient characteristics (n=700)Parametern (%)Mean age, y, at diagnosis (range)44(22-80)Stage at initial diagnosis of cancerI89(12.7)II342(48.9)III167(23.9)IV69(9.9)unknown33(4.7)Molecular subtypesLuminal A/B211(30.0)HER2-positive347(49.7)TNBC132(18.9)Unknown10(1.4)Site of first metastasisBrain128(18.3)Others572(81.7)Number of BM at time of BM diagnosis1189(27.0)248(6.9)≥3454(64.9)Unknown9(1.3)Visceral metastases at diagnosis of BMliver351(50.1)lung386(55.1)bone446(63.7)lymph nodes431(61.6)the soft tissues of the thoracic wall183(26.1)bone marrow34(4.9) Citation Format: Tao Wang, Huiqiang Zhang, Feng Li, Xia Wu, Jinmei Zhou, Shao hua Zhang, Li Bian, Ze fei Jiang. The real word study on clinical features and prognostic factors of Chinese breast cancer patients with brain metastasis [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-21-04.

BackgroundNeoadjuvant 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.MethodsThe 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.ResultsThe 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.ConclusionsOur 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.

Breast cancer is the most commonly diagnosed cancer among women, causing 15% of patient deaths. The metastasis of breast cancer cells is the leading cause of death for patients. Several studies have shown that Discoidin Domain Receptor 1 (DDR1) was highly expressed in breast cancer and could influence tumor cell behaviors. However, the specific role of DDR1 in breast cancer metastasis is still elusive. In this study, we uncovered that DDR1 is significantly increased in breast cancer and inversely correlated with the prognosis of patients. Knockdown of DDR1 suppressed the migration and invasion of breast cancer cells. Additionally, overexpression of DDR1 enhanced the metastatic capacity of cancer cells. Immunoblotting revealed that activation of Src and FAK, which are involved in cancer cell metastasis, were correlated with the expression level of DDR1. Co-immunoprecipitation experiments showed that DDR1 could bind to Src and FAK. Finally, the inhibition of FAK and Src could attenuate DDR1 enhanced migration ability of breast cancer cells. In summary, our study revealed that DDR1 was highly expressed in breast cancer and negatively correlated with the prognosis of breast cancer patients. DDR1 facilitates migration and invasion in breast cancer cells via activation of the Src-FAK signaling. Accordingly, blocking DDR1/Src/FAK axis is a promising therapeutic strategy for breast cancer treatment.

Rationale: Breast cancer has become the leading cause of cancer mortality in women. Although immune checkpoint inhibitors targeting programmed death-1 (PD-1) are promising, it remains unclear whether PD-L1 expression on circulating tumor cells (CTCs) has predictive and prognostic values in predict and stratify metastatic breast cancer (MBC) patients who can benefit from anti-PD-1 immunotherapy. Methods: Twenty six MBC patients that received anti-PD-1 immunotherapy were enrolled in this study. The peptide-based Pep@MNPs method was used to isolate and enumerate CTCs from 2.0 ml of peripheral venous blood. The expression of PD-L1 on CTCs was evaluated by an established immunoscoring system categorizing into four classes (negative, low, medium, and high). Results: Our data showed that 92.3% (24/26) of patients had CTCs, 83.3% (20/26) of patients had PD-L1-positive CTCs, and 65.4% (17/26) of patients had PD-L1-high CTCs. We revealed that the clinical benefit rate (CBR) of patients with a cut-off value of ≥ 35% PD-L1-high CTCs (66.6%) was higher than the others (29.4%). We indicated that PD-L1 expression on CTCs from MBC patients treated with anti-PD-1 monotherapy was dynamic. We demonstrated that MBC patients with a cut-off value of ≥ 35% PD-L1-high CTCs had longer PFS (P< 0.05) and OS (P< 0.01) compared with patients with a cut-off value of < 35% PD-L1-high CTCs. Conclusion: Our findings suggested that PD-L1 expression on CTCs could predict the therapeutic response and clinical outcomes, providing a valuable predictive and prognostic biomarker for patients treated with anti-PD-1 immunotherapy. Citation Format: Ying Zhou, Jinmei Zhou, Haoyuan Shi, Zhiyuan Hu, Yanlian Yang, Zefei Jiang, Tao Wang. Prognostic relevance of PD-L1 expression on circulating tumor cells in metastatic breast cancer patients treated with anti-PD-1 immunotherapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-02-12.

Recently, female breast cancer (BC) has surpassed lung cancer to occupy the first place of the most commonly diagnosed cancer. The unsatisfactory prognosis of endocrine therapy for breast cancer might be attributed to the discordance in estrogen receptor (ER) status between primary tumors and corresponding metastases, as well as temporal and spatial receptor status heterogeneity at point-in-time between biopsy and treatment. The purpose of this study was to evaluate the prognostic and predictive value of ER status in circulating tumor cells (CTCs) in BC patients. We analyzed ER expression on CTCs isolated using the Pep@MNPs method in 2.0 ml of blood samples from 70 patients with BC and 67 female controls. The predictive and prognostic value of ER expression in CTCs and immunohistochemistry results of biopsies for progression-free survival (PFS) and overall survival (OS) of patients in response to therapies were assessed. The detection rate for CTCs was 95.71% (67/70 patients), with a median of 8 CTCs within 2 ml of peripheral venous blood (PVB). A concordance of 76.56% in ER status between CTCs and corresponding primary tumor and 69.23% between CTCs and corresponding metastases was observed. We also found that patients with ER-positive CTCs (CTC ER+) had longer PFS and OS than those without ER-positive CTCs (CTC ER-). Our findings suggested that ER status in CTCs of BC patients may provide valuable predictive and prognostic insights into endocrine therapies, although further evaluation in larger prospective trials is required.

e14558 Background: PD-1/PD-L1 checkpoint blockade immunotherapy is revolution- izing the therapeutic strategy of malignancies. Tumor PD-L1 levels have predictive value in PD-1/PD-L1 checkpoint blockade therapies. Whether PD-L1 expression on circulating tumor cells (CTCs) could serve as an alternative biomarker is of great interest, especially in breast cancer. Methods: We established an immunofluorescence assay for semi-quantitative assessment of the PD-L1 expression levels on CTCs with four categories (PD-L1negative, PD-L1low, PD-L1medium and PD-L1high). 20patients with advanced breast cancerwere enrolled who took PD-1 inhibitortherapy. The CTC numeration and the PD-L1 expression levels were analyzedat the begining and ending of treatment . Results: 20 patients were enrolled, 85%(17/20) were triple-negative breast cancer. 65% of patients had visceral metastases, 60% of patients had ≥3 lines of treatment. Prior the treatment of PD-1 inhibitor, 95% (19/20) patients had CTCs, ranging from1 to 53(median 5). 90% (18/20) had PD-L1positive CTCs, and 75% (15/20) had at least one PD-L1high CTCs. The clinical benefit rate(CBR) rate in PD-L1high patients (26.7%) is much higher than the others (0%). we examined the proportion of PD-L1high CTCs relative to total CTCs. The median proportion of PD-L1high CTCs was 33.3%. Patients with ≥33% PD-L1high CTCs had a significantly longer PFS (median 2.6 vs. 1.4 months( P = 0.027). 100% patients with CBR had PD-L1highCTCs decreased and 46.7% of patients without CBR decreased. Further analysis showed that the mean proportion of PD-L1highCTCs at baseline and after treatment was 56.8±20.7%, 19.0±23.7%, p = 0.005. There was no significant difference in the mean proportion of PD-L1highCTCs before and after treatment in the non-CBR group (28.0±26.2%, 30.3±31.5%, p = 0.846). Conclusions: We revealed that the abundance of PD-L1high CTCs at baseline might serve as a predictor to screen patients for PD-1/PD-L1 blockade therapies and measuring the dynamic changes of PD-L1high CTCscould indicate the therapeutic response at early time.

This study was initiated to evaluate the clinical significant of HER2 extracellular domain (ECD) in the real-time management of breast cancer patients.Five-hundred forty-six eligible breast cancer patients were divided according to their clinical background. The correlation between ECD, tissue HER2, and clinical outcome of the patients were analyzed.Receiver operating characteristic analysis revealed that ECD measured before receiving neoadjuvant therapy yielded the highest area under the curve (0.9185; P0.0001), indicating that ECD and tissue HER2 levels are consistent in untreated tumor-bearing patients. At cut-off of 15.0ng/ml, the prognostic value of ECD was demonstrated using univariate (HR=1.664, P0.0001) and multivariate (HR=1.547, P=0.011) Cox regression analysis. Kaplan-Meier survival curves revealed that patients with elevated ECD had shorter progression-free survival (PFS) (4.0 vs. 6.1months, P0.0001). Elevated ECD was also an adverse predictor for PFS in response to anti-HER2 therapy (4.3 vs. 10.2months, P=0.0155). In contrast, ≥20%, decreased ECD was associated with longer PFS in patients who received anti-HER2 therapy (10.9 vs. 2.4months, P=0.0164) and overall (10.7 vs. 2.8months, P=0.0034).A patient's clinical history can help determine whether ECD could provide added value for breast cancer management.

e12084Background: Circulating tumor cell (CTC) and serum HER2 ECD can reflect tumorous biological information in different aspects, however their clinical significance for HER2-positive advanced breast cancer receiving anti-HER2 therapy remain unclear. We performed this prospective, monocenter, double-blinded study to investigate the potential clinical significance of detection of CTC and serum HER2 ECD for advanced breast cancer patients with histological HER2-positivity. Methods: A total of 155 eligible patients were enrolled in the present study from April 2012 to October 2015. We used Cell search system and ADVIA Centaur System to detect CTC and serum HER2 ECD respectively. Patients received systemic treatment according to national and international guidelines. Results: Forty nine (31.6%) patients had ≥ 5 CTC, One hundred and twenty three (79.4%) patients had serum HER2 ECD values of at least 15ng/ml, forty seven (30.3%) patients had both elevated CTC and ECD values, thirty (19.4%) patients had both n...

Background: Circulating tumor cell (CTC) and serum HER2 ECD can all reflect an aggressive tumor behavior. We performed this prospective, monocenter, double-blinded study to investigate the potential clinical significance of combined detection of CTC and serum HER2 ECD for advanced breast cancer patients with histological HER2-positivity. Methods: A total of 88 eligible patients were enrolled in the present study from April 2012 to October 2013. We used Cell search system and ADVIA Centaur System to detect CTC and serum HER2 ECD respectively. Patients received systemic treatment according to national and international guidelines. Results: Twenty nine (33%) patients had ≥5 CTC, seventy three (83%) patients had serum HER2 ECD values of at least 15ng/ml, twenty seven (30.7%) patients had both elevated CTC and ECD values and fourteen (15.9%) patients had both normal CTC and ECD values. Patients with both normal CTC and serum HER2 ECD values exhibited a significantly longer median PFS than patients with both elevated values (9.0 months versus 2.8 months, p=0.023) and exhibited a trend toward longer PFS compared with patients with elevated CTC or ECD values (9.0 months versus 4.2 months, p=0.065), patients with both or one elevated values showed similar median PFS (2.8 months versus 4.2 months, p=0.211) (Figure1). Conclusions: The combined detection of CTC and serum HER2 ECD showed prognostic significance for HER-2 positive advanced breast cancer patients, patients with both normal values exhibited longer median PFS than others. Citation Format: Zefei Jiang, Jinmei Zhou, Tao Wang, Yi Liu, Lei Li, Huiqiang Zhang, Shaohua Zhang, Li Bian, Santai Song. The combined detection of CTC and serum HER2 ECD predict PFS for HER2-positive advanced breast cancer patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-01-19.

e12006 Background: The percentage of breast cancer patients exposed to anthracyclines and taxanes in the adjuvant or neoadjuvant chemotherapy is increasing, in metastatic stage using again is limit...