scholarly journals Current approaches to the treatment of HER2‑positive breast cancer with brain metastases

2021 ◽  
Vol 17 (1) ◽  
pp. 27-34
Author(s):  
T.  Yu. Semiglazova ◽  
S.  M. Sharashenidze ◽  
S.  N. Kerimova ◽  
V.   V. Klimenko ◽  
A. Yu. Malygin ◽  
...  

The article discusses modern approaches in the treatment of HER2-positive breast cancer (BC) with brain metastases (BM).The patients are subject to multidisciplinary, comprehensive and biologically – oriented treatment, with the involvement of a neurosurgeon and a radiation therapist to make a decision considering local treatment of BM, as well as a clinical oncologist to choose systemic drug therapy. Local treatment of HER2+ BC with BM patients includes surgical treatment and/or radiotherapy. Use of targeted anti-HER2 therapy changes “biology” of the disease from aggressive to indolent.In the prospective KAMILLA trial, clinically significant antitumor activity of trastuzumab emtansine was found for the first time both in patients with HER2+ BC with BM, who were previously treated with radiotherapy, and without radiotherapy in the anamnesis, which suggests the validity of further use of trastuzumab emtansine in this category of patients.The antitumor activity of trastuzumab emtansine in patients with HER2+ BC with BM was also confirmed in preclinical models. Despite the similar drug distribution in the tissues, trastuzumab emtansine, in contrast to trastuzumab, significantly slowed the growth of metastases, causing the induction of apoptosis in HER2+ BC models with BM in mice.

2020 ◽  
Vol 16 (14) ◽  
pp. 899-909 ◽  
Author(s):  
Alexandra S Zimmer ◽  
Seth M Steinberg ◽  
Dee Dee Smart ◽  
Mark R Gilbert ◽  
Terri S Armstrong ◽  
...  

Brain metastases occur in up to 25–55% of patients with metastatic HER2-positive breast cancer. Standard treatment has high rates of recurrence or progression, limiting survival and quality of life in most patients. Temozolomide (TMZ) is known to penetrate the blood–brain barrier and is US FDA approved for treatment of glioblastoma. Our group has demonstrated that low doses of TMZ administered in a prophylactic, metronomic fashion can significantly prevent development of brain metastases in murine models of breast cancer. Based on these findings, we initiated a secondary-prevention clinical trial with oral TMZ given to HER2-positive breast cancer patients with brain metastases after recent local treatment in combination with T-DM1 for systemic control of disease. Primary end point is freedom from new brain metastases at 1 year. (NCT03190967).


2016 ◽  
Vol 157 (2) ◽  
pp. 307-318 ◽  
Author(s):  
William Jacot ◽  
Elvire Pons ◽  
Jean-Sébastien Frenel ◽  
Séverine Guiu ◽  
Christelle Levy ◽  
...  

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Matthew N. Mills ◽  
Chelsea Walker ◽  
Chetna Thawani ◽  
Afrin Naz ◽  
Nicholas B. Figura ◽  
...  

Abstract Background Due to recent concerns about the toxicity of trastuzumab emtansine (T-DM1) with stereotactic radiation, we assessed our institutional outcomes treating HER2-positive breast cancer brain metastases (BCBM) with T-DM1 and stereotactic radiation. Methods This is a single institution series of 16 patients with HER2-positive breast cancer who underwent 18 stereotactic sessions to 40 BCBM from 2013 to 2019 with T-DM1 delivered within 6 months. The Kaplan-Meier method was used to calculate overall survival (OS), local control (LC), distant intracranial control (DIC), and systemic progression-free survival (sPFS) from the date of SRS. A neuro-radiologist independently reviewed follow-up imaging. Results One patient had invasive lobular carcinoma, and 15 patients had invasive ductal carcinoma. All cases were HER2-positive, while 10 were hormone receptor (HR) positive. Twenty-four lesions were treated with stereotactic radiosurgery (SRS) to a median dose of 21 Gy (14–24 Gy). Sixteen lesions were treated with fractionated stereotactic radiation (FSRT) with a median dose of 25 Gy (20-30Gy) delivered in 3 to 5 fractions. Stereotactic radiation was delivered concurrently with T-DM1 in 19 lesions (48%). Median follow up time was 13.2 months from stereotactic radiation. The 1-year LC, DIC, sPFS, and OS were 75, 50, 30, and 67%, respectively. There was 1 case of leptomeningeal progression and 1 case (3%) of symptomatic radionecrosis. Conclusions We demonstrate that stereotactic radiation and T-DM1 is well-tolerated and effective for patients with HER2-positive BCBM. An increased risk for symptomatic radiation necrosis was not noted in our series.


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