Prognostic factors of brain metastasis and survival among HER2-positive metastatic breast cancer patients: a systematic literature review

Abstract

Background Patients with breast cancer who overexpress the human epidermal growth factor receptor 2 (HER2) and subsequently develop brain metastasis (BM) typically experience poor quality of life and low survival. We conducted a comprehensive literature review to identify prognostic factors for BM and predictors of survival after developing BM, and the effects of therapies with different mechanisms of action among patients with HER2+ breast cancer (BC). Methods A prespecified search strategy was used to identify research studies investigating BM in patients with HER2+ BC published in English during January 1, 2009–to June 25, 2021. Articles were screened using a two-phase process, and data from selected articles were extracted. Results We identified 25 published articles including 4097 patients with HER2+ BC and BM. Prognostic factors associated with shorter time to BM diagnosis after initial BC diagnosis included younger age, hormone receptor negative status, larger tumor size or higher tumor grade, and lack of treatment with anti-HER2 therapy. Factors predictive of longer survival after BM included having fewer brain lesions (< 3 or a single lesion) and receipt of any treatment after BM, including radiosurgery, neurosurgery and/or systemic therapy. Patients receiving combination trastuzumab and lapatinib therapy or trastuzumab and pertuzumab therapy had the longest median survival compared with other therapies assessed in this review. Conclusions More research is needed to better understand risk factors for BM and survival after BM in the context of HER2+ BC, as well as the assessment of new anti-HER2 therapy regimens that may provide additional therapeutic options for BM in these patients.

Pyrotinib combining with radiotherapy on breast cancer with brain metastasis

“…In this study, the prognosis of active BM was explored through multivariate Cox regression analysis incorporating all clinicopathological indexes of patients. The results illustrated that the size and number of BM lesions were OS-related factors in BM, which was consistent with the report in Hackshaw et al 36 Moreover, presence or absence of hepatic metastasis and combination mode of radiotherapy and targeted therapy were revealed to be independent risk factors for BM prognosis.…”

HER2-Positive Gastroesophageal Cancers Are Associated with a Higher Risk of Brain Metastasis

“…In addition to GOCs, HER2 is an established biomarker for breast cancer. Evidence in patients with breast cancer demonstrates that HER2-positive breast cancers had higher rates of brain metastasis [ 47 , 48 , 49 ]. HER2 expression appears to be an important pathway in the development of brain metastasis from HER2-expressing tumours.…”

Outcomes and Prognostic Factors in HER2-Positive Metastatic Breast Cancer Patients Who Had Developed Brain Metastasis in the Treatment Process

“…Scoring systems based on clinical and pathological data, such as the modified breast GPA score and prognostic assessment index, have been developed to predict the prognosis in patients with brain mBC [16]. In a review published by Hackshaw et al [17] and examining the related articles in the literature, the risk factors for the development of brain metastasis were determined as young age, larger tumor size, high tumor grade, hormone receptor status, and not receiving anti-HER2 therapy, while the factors affecting the prognosis after the development of brain metastasis were determined as fewer brain metastases and using anti-HER2 therapy. In a study published by Lu et al [18], it was stated that five hub genes (PHLPP1, ACACB, UBC, TGFB1, and ACTB) are related to the development of brain metastasis in HER2-positive BC and that these genes may be a potential biomarker for prognosis.…”