291P HER2-low metastatic breast cancer (MBC): Management and prognosis of a new breast cancer entity in a real-world setting

Abstract

Background: Trastuzumab emtansine (T-DM1) has shown great effectiveness in treating HER2-positive metastatic breast cancer, but therapies after T-DM1 progression are still controversial. Here, we report the real-world data of tyrosine kinase inhibitors (TKIs) based therapy in T-DM1 resistant HER2-positive metastatic breast cancer.Methods: From August 2019 to April 2021, 48 HER2-positive metastatic breast cancer patients received TKIs-based therapy after T-DM1 progression in Jiangsu Province Hospital. We evaluated the efficacy and safety of TKIs in treating T-DM1 resistant HER2-positive metastatic breast cancer.Results: 48 patients received TKIs-based therapies as a second or later line therapy. 46 (95.8%) patients received a combined therapy, including TKIs plus capecitabine, vinorelbine or trastuzumab. 2 (4.2%) patients received TKIs alone. The median progression-free survival (PFS) was 10.5 months (95%CI 5.432-15.568). Objective response rate (ORR) was 17.4%, and clinical benefit rate (CBR) was 73.9%. For patients who had brain metastasis (n¼11), the median PFS was 10.5 months ) and intracranial ORR was 27.3%. No difference was observed between lapatinib (n¼32) and pyrotinib (n¼16) groups (8.0 months vs. 13.3 months, P¼0.243). The most common adverse events were hand-foot syndrome (11, 22.9%) and thrombocytopenia (10, 20.8%).Conclusions: TKIs-based therapy could improve the survival of T-DM1 resistant HER2positive metastatic breast cancer patients, including those with brain metastasis. This provides a new therapeutic option for HER2-positive breast cancer treatments.Legal entity responsible for the study: The authors.

HER2 expression, copy number variation and survival outcomes in HER2-low non-metastatic breast cancer: an international multicentre cohort study and TCGA-METABRIC analysis

“…This study on HER2-low BCs evaluated the largest real-world cohort to date. We found that HER2-low BCs were more frequent in hormone receptor-positive tumours, similar to other studies [ 11 , 15 , 35 ]. RFS and OS were superior for HER2-low compared to HER2-zero non-metastatic BC.…”

“…Interestingly, in early ER-positive BCs with high genomic risk (OncotypeDx risk score > 25), Mutai et al observed more favourable outcomes of HER2-low compared to HER2-zero tumours [ 36 ]. It is worth noting that in advanced BC, a modestly superior OS (HR 0.95, 95% CI 0.91 to 0.99) was also observed by Frenel et al ( n = 15,054) for HER2-low BC in a preliminary report [ 35 ], particularly for the hormone receptor-negative subgroup, although smaller studies have not detected significant differences [ 15 – 17 ].…”

Hormone Receptor-Positive/HER2-Positive Breast Cancer: Hormone Therapy and Anti-HER2 Treatment: An Update on Treatment Strategies

“…No significant difference in RFS and OS was described between HER2 IHC score 2+/ISH-negative and HER2 IHC score 0 [101]. In the advanced setting, a better OS has been evidenced for HER2-low BC in comparison with HER2-0 BC in a cohort of 15.054 patients with HER2negative BC, and the findings were seen in the HR-negative subgroup, although smaller cohorts have not demonstrated a significant difference [90,101,102]. Gampenrieder et al studied 1729 patients with metastatic BC and highlighted that low HER2 expression did not significantly influence OS in the HR-positive or triple-negative subgroups [92].…”

“…The level of expression of ER seems to impact the prognosis of HER2-low BC. A significant positive association between ER expression and HER2-low expression was found in a cohort of 5235 patients with early HER2-low BC at the Dana-Farber Brigham Center; HER2-low expression did not seem to play a distinct prognostic role, and the authors found no statistically significant difference in the pCR rate and in OS between HER2-low and HER2-0 tumors, regardless of HR+ status [91,101,102]. An Italian Cancer Registry study evaluated 3633 HER2low BC and divided ER status into low (1-9%), moderate (10-79%), and high (80-100%).…”

Classification of HER2-negative breast cancers by ERBB2 copy number alteration status reveals molecular differences associated with chromosome 17 gene aberrations

“… 11 , 12 In addition, identification of the HER2 status may be complicated by intra-patient heterogeneity. 13 Consequently, studies investigating survival outcomes in HER2-low versus HER2-zero breast cancers have demonstrated mixed results, 8 , 14 – 20 leading to uncertainty as to whether the current definition of HER2-low breast cancer has any biological or prognostic implications.…”