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Background: HER2-targeted agents combined with endocrine therapy (ET) has been recommended as an optional therapeutic strategy for hormone receptor (HR)/human epidermal growth factor receptor 2 (HER2) co-positive metastatic breast cancer (MBC). Pyrotinib is an oral irreversible pan-ErbB receptor tyrosine kinase inhibitor targeting EGFR, HER2 and HER4, with proven efficacy in combination with chemotherapy in HER2-positive MBC. This multicenter, single-arm phase 2 trial aimed to investigate the efficacy and safety of pyrotinib plus letrozole in patients with estrogen receptor (ER)-positive, HER2-positive MBC (NCT04407988). Methods: Pre-/perimenopausal or postmenopausal women with histologically confirmed HER2-positive (immunohistochemistry [IHC] 3+ or 2+ with fluorescence in situ hybridization positive) and ER-positive (the percentage of ER+ cells ≥ 10% by IHC) MBC were enrolled. Prior treatment for metastatic disease was not allowed. Eligible patients received pyrotinib (400 mg, po, qd) plus letrozole (2.5 mg, po, qd) until disease progression or unacceptable toxicity. For pre-/perimenopausal patients, additional treatment with ovarian function suppression (OFS) was required. The primary endpoint was clinical benefit rate (CBR), defined as the rate of patients with complete response (CR), partial response (PR), or stable disease (SD) for at least 24 weeks per RECIST 1.1. Secondary endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Results: Between December 3, 2019 and April 2, 2021, 26 patients were enrolled. As of July 5, 2021, CBR was 76.9% (20 of 26; 95% CI 56.4% to 91.0%) and ORR was 57.7% (15 of 26; 95% CI 36.9% to 76.6%). One of the 26 patients (3.8%) had CR, 14 (53.8%) had PR, 5 (19.2%) had SD, 5 (19.2%) had progressive disease, and 1 (3.8%) had not evaluable disease. The benefits in CBR and ORR were observed across all subgroups. The most common any grade AEs were diarrhea (25 of 26, 96.2%), vomiting (8 of 26, 30.8%), nausea (6 of 26, 23.1%), and oral ulceration (6 of 26, 23.1%). Diarrhea was the only reported grade 3 AE that occurred in 5 patients (19.2%). No grade 4 or 5 AEs occurred during this study. Conclusions: Pyrotinib combined with letrozole showed an encouraging antitumor activity with good tolerance in patients with ER/HER2 co-positive MBC, promising as an alternative treatment option for this disease. The study is ongoing. Citation Format: Quchang Ouyang, Huihua Xiong, Min Yan, Jincai Zhong, Li Ran, Ting Luo, Liping Liu, Jing Li, Xiaohong Yang, Huawu Xiao, Ning Xie, Hui Wu, Jianxiang Gao, Jun Lu, Xuming Hu, Zheyu Hu, Can Tian, Zhengrong Shui, Min Cao. Pyrotinib in combination with letrozole for estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer: A multicenter, single-arm, phase II trial [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 P2-13-32.

Breast cancer is the most commonly diagnosed malignant tumor and the leading cause of cancer-related death in women worldwide. Previous studies have demonstrated that patients with human epidermal growth factor receptor 2 (HER2)-positive/hormone receptor (HR)-positive metastatic breast cancer can benefit from HER2-targeted therapy. Pyrotinib, an irreversible tyrosine kinase inhibitor (TKI), has been demonstrated to be effective and safe in treating HER2-positive breast cancer patients. Letrozole is an aromatase inhibitor (AI) which has shown better clinical efficacy when combined with HER2 inhibitors in treating patients with HER2-positive and HR-positive breast cancer than has hormonal therapy alone. However, the effect of combination therapy with pyrotinib plus letrozole in HER2-positive/HR-positive metastatic breast cancer patients has not yet been investigated. In this case report, a 57-year-old female patient with HER2-positive/HR-positive breast cancer received modified radical mastectomy and experienced subsequent relapse and metastasis. She was diagnosed with relapsed right breast cancer, a right chest bone mass accompanied by bone destruction, and metastases in the chest wall and both lungs. She was then enrolled in a phase II clinical trial and was treated with pyrotinib plus letrozole, and achieved a durable clinical response. Our case shows that combination therapy with pyrotinib plus letrozole may provide significant clinical benefit for patients with HER2-positive/HR-positive metastatic breast cancer, with tolerable adverse events.

Background: Metastatic breast cancer (MBC) has poor prognosis, and the 5 yr-OS is less than 20%. Maintaining treatment post the chemotherapy could improve the OS and the life quality. However, we lack clinical consensus for the maintaining treatment. In this study, we aim to investigate the treatment outcome of capecitabine maintaining treatment. Methods: The study recruited 669 consecutive MBC patients who received chemotherapy from January 2016 through August 2019. 256 patients received capecitabine maintaining treatment after chemotherapy, including 163 patients with maintaining treatment after the first-line chemotherapy and 67 patients with maintaining treatment after the second-line chemotherapy. 413 patients did not receive capecitabine maintaining treatment after capecitabine-based chemotherapy. Kaplan-Meier curves were plotted and COX proportional hazards models with candidate risk factor analyses stratified by chemotherapy lines and maintaining treatment were assessed the impact of each candidate on progression-free survival (PFS). Circulating tumor DNA (ctDNA) analysis was performed to screen genetic aberrations that might lead to maintaining treatment response. Results: Capecitabine maintaining treatment group showed a significant improvement in PFS compared with non-maintaining group [hazard ratio = 0.53 (95% confidence interval = 0.41-0.68); log-rank test p Citation Format: Quchang Ouyang, Zhe-Yu Hu, Xiaohong Yang, Liping Liu, Jing Li, Huawu Xiao, Jianxiang Gao, Jun Lu, Hui Wu, Ning Xie, Xuming Hu, Can Tian, Zhengrong Shui, Min Cao. Capecitabine maintaining treatment improves progression-free survival in metastatic breast cancer: A prospective observational study of 669 cases [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 PS13-17.

1094 Background: Eribulin mesylate is a structurally simplified, synthetic, macrocyclic ketone analogue of Halichondrin B. We investigated the efficacy and safety of eribulin monotherapy versus eribulin plus the oral anti-angiogenesis inhibitor anlotinib in patients with advanced or metastatic breast cancer. Methods: This Phase II study included adult Chinese patients with locally advanced or metastatic breast cancer previously treated with at least two chemotherapy regimens, including both anthracycline- and taxane-based therapy (NCT05206656). Patients were randomized (1:1) to receive eribulin (1.4 mg/m2, intravenously, on days 1−8), alone or in combination with anlotinib (12 mg orally once daily), in 21-day cycles. The primary endpoint was investigator-assessed disease control rate (DCR), per RECIST version 1.1. Key secondary endpoints included objective response rate (ORR), progression-free survival (PFS) and safety. Results: Between February 12, 2020, and July 22, 2021, 56 patients were randomized to eribulin (n=32) or eribulin plus anlotinib (n=24) (Table). Sites of metastasis were: bone (60.7%), lung (52.7%), liver (53.6%), lymph nodes (73.2%) and soft tissue (7.1%). Among all patients, the DCR was 66.7% versus 100% (treatment difference, 33.3%; P=0.007), the ORR was 37.0% versus 38.9%, and the median PFS was 3.7 months versus 9.7 months (adjusted hazard ratio, 0.20; 95% CI, 0.04 to 0.91; P=0.04) for patients receiving eribulin versus eribulin plus anlotinib, respectively. Among 36 (64.3%) patients with triple-negative breast cancer, the DCR was 55.6% versus 72.2% (treatment difference, 16.7%; P=0.300) and the median PFS was 3.6 months versus 9.7 months (log rank P=0.030) with eribulin alone versus eribulin plus anlotinib, respectively. The most frequent grade 3-4 adverse events in the eribulin and eribulin plus anlotinib groups were decreased neutrophil count (25.0% [n=8] vs. 29.2% [n=7]) elevated transaminase (6.3% [n=2] vs. 0.0%) and decreased thrombocyte count (3.1% [n=1] vs. 0.0%), respectively. Conclusions: Eribulin plus anlotinib was associated with a significantly better DCR, ORR and PFS than eribulin monotherapy in patients with locally advanced or metastatic breast cancer previously treated with anthracyclines and taxanes. Clinical trial information: NCT05206656. [Table: see text]

Supplemental material, Table_S4_FGFR for FGFR aberrations increase the risk of brain metastases and predict poor prognosis in metastatic breast cancer patients by Ning Xie, Can Tian, Hui Wu, Xiaohong Yang, Liping liu, Jing Li, Huawu Xiao, Jianxiang Gao, Jun Lu, Xuming Hu, Min Cao, Zhengrong Shui, Yu Tang, Xiao Wang, Jianbo Yang, Zhe-Yu Hu and Quchang Ouyang in Therapeutic Advances in Medical Oncology

Supplemental material, Table_S3 for FGFR aberrations increase the risk of brain metastases and predict poor prognosis in metastatic breast cancer patients by Ning Xie, Can Tian, Hui Wu, Xiaohong Yang, Liping liu, Jing Li, Huawu Xiao, Jianxiang Gao, Jun Lu, Xuming Hu, Min Cao, Zhengrong Shui, Yu Tang, Xiao Wang, Jianbo Yang, Zhe-Yu Hu and Quchang Ouyang in Therapeutic Advances in Medical Oncology

Supplemental material, Table_S2 for FGFR aberrations increase the risk of brain metastases and predict poor prognosis in metastatic breast cancer patients by Ning Xie, Can Tian, Hui Wu, Xiaohong Yang, Liping liu, Jing Li, Huawu Xiao, Jianxiang Gao, Jun Lu, Xuming Hu, Min Cao, Zhengrong Shui, Yu Tang, Xiao Wang, Jianbo Yang, Zhe-Yu Hu and Quchang Ouyang in Therapeutic Advances in Medical Oncology

Supplemental material, Table_S5-brain for FGFR aberrations increase the risk of brain metastases and predict poor prognosis in metastatic breast cancer patients by Ning Xie, Can Tian, Hui Wu, Xiaohong Yang, Liping liu, Jing Li, Huawu Xiao, Jianxiang Gao, Jun Lu, Xuming Hu, Min Cao, Zhengrong Shui, Yu Tang, Xiao Wang, Jianbo Yang, Zhe-Yu Hu and Quchang Ouyang in Therapeutic Advances in Medical Oncology

This study aims to detect the prognostic value of circulating tumour cell (CTC) in patients with metastatic breast cancer. In this study, 38 patients with metastatic breast cancer were enrolled. The in vivo CellCollector® method was used to detect the number of CTC in patients. Single CTC and CTC clusters were counted, and the expression of plakoglobin was also analysed. At baseline, 73.7% (28/38) of the patients were positive for ≥ 1 CTC (range, 1–14 cells). No CTC-like events were observed in the control group. Among the CTC-positive patients, 21.4% (6/28) of patients had CTC clusters, and 42.9% (12/28) of patients had plakoglobin-positive CTC. After chemotherapy, 48.6% (17/35) of the patients were positive for ≥ 1 CTC (range, 1–3 cells), of which 3 patients had CTC clusters, and 35.3% (6/17) had plakoglobin-positive CTC. Additionally, we found that the number of CTC clusters in plakoglobin-positive patients was much greater than that in plakoglobin-negative patients, and the number of CTC was associated with the number of sites of metastases. We also found that patients with ≥ 3 CTC at baseline had shorter progression-free survival (PFS) and overall survival (OS), and pre-chemotherapy CTC detection was associated with PFS (P = 0.0001) and OS (P = 0.0091). CTC plakoglobin expression was associated with PFS (P = 0.02) but not OS (P = 0.22). CTC collected by the in vivo CellCollector method in Chinese patients with metastatic breast cancer have prognostic significance. CTC plakoglobin expression may be associated with CTC clusters, and more in-depth studies are needed.

Background: The survival status of patients with breast cancer and brain metastasis (BCBM) receiving current treatments is poor. Method: We designed a real-world study to investigate using patients’ clinical and genetic aberrations to forecast the prognoses of BCBM patients. We recruited 146 BCBM patients and analyzed their clinical features to evaluate the overall survival (OS). For genetic testing, 30 BCBM and 165 non-brain-metastatic (BM) metastatic breast cancer (MBC) patients from Hunan Cancer Hospital, and 86 BCBM and 1416 non-BM MBC patients from the Geneplus database who received circulating tumor DNA testing, were compared and analyzed. Results: Ki67 >14% and >3 metastatic brain tumors were significant risk factors associated with poor OS, while chemotherapy and brain radiotherapy were beneficial factors for better OS. Compared with non-BM MBC patients, BCBM patients had more fibroblast growth factor receptor ( FGFR) aberrations. The combination of FGFR, TP53 and FLT1 aberrations plus immunohistochemistry HER2-positive were associated with an increased risk of brain metastasis (AUC = 77.13%). FGFR aberration alone was not only a predictive factor (AUC = 67.90%), but also a significant risk factor for poor progression-free survival (Logrank p = 0.029). FGFR1 aberration was more frequent than other FGFR family genes in BCBM patients, and FGFR1 aberration was significantly higher in BCBM patients than non-BM MBC patients. Most FGFR1-amplified MBC patients progressed within 3 months of the late-line (>2 lines) treatment. Conclusion: A group of genetic events, including FGFR, TP53 and FLT1 genetic aberrations, and HER2-positivity, forecasted the occurrence of BM in breast cancers. FGFR genetic aberration alone predicted poor prognosis.