HER2‐positive breast cancer brain metastasis: A new and exciting landscape

HER2 positive breast cancer is an aggressive breast cancer followed by brain metastasis, which emerges at the later stage of breast cancer or after a few years of treatment. HER2+ breast cancer brain metastasis is a complex fatal disease with short survival and resistance to first-line drugs such as Trastuzumab, lapatinib, etc. The resistance can be due to the upregulation/downregulation of various proteins of downstream pathways mainly PI3K/AKT pathway and MAPK pathway. In addition, the Blood-brain Barrier (BBB) and Blood Tumor Barrier (BTB) also hinder the delivery to brain metastases. Thus controlling the altered proteins of the downstream pathway can be a targeted approach to control breast cancer and its brain metastasis. At the same time, targeted delivery to metastatic sites can give a synergistic effect in controlling brain metastasis and increasing the survival period. Various type of targeted nanocarriers such as single, dual, or multitargeted, pH specific, or stimuli sensitive nanocarriers can be employed for providing specific delivery to HER2+ cancer cells. Furthermore, combinations such as Trastuzumab with tyrosine kinase inhibitors (lapatinib, neratinib, afatinib), chemotherapeutic drugs (paclitaxel, doxorubicin, capecitabine), or some natural compounds (curcumin, Lycorine, berberine) with anti-apoptotic activity can provide an additional effect in the management of HER2 positive breast cancer and its metastasis.

Download Full-text

RADT-03. OUTCOMES OF PATIENTS WITH HER2-POSITIVE BREAST CANCER METASTATIC TO BRAIN TREATED WITH HER2-TARGETED SYSTEMIC THERAPY AND STEREOTACTIC RADIOSURGERY

Neuro-Oncology ◽

10.1093/neuonc/noab196.161 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi41-vi41

Author(s):

John Shumway ◽

Marina Torras ◽

Katherine Reeder-Hayes ◽

Trevor Jolly ◽

Elizabeth Dees ◽

...

Keyword(s):

Breast Cancer ◽

Brain Metastasis ◽

Stereotactic Radiosurgery ◽

Systemic Therapy ◽

Survival Outcomes ◽

Maximal Dimension ◽

Her2 Positive ◽

Intracranial Metastasis ◽

Her2 Positive Breast Cancer ◽

Positive Breast Cancer

Abstract OBJECTIVE For patients with HER2-positive breast cancer metastatic to brain, HER2-directed systemic therapies are increasingly used with stereotactic radiosurgery (SRS). These include monoclonal antibodies such as trastuzumab (H) and pertuzumab (P), antibody-drug conjugates such as ado-trastuzumab emtansine (T-DM1), and tyrosine kinase inhibitors such as lapatinib. Limited data exist regarding appropriate timing with SRS and outcomes of this treatment regimen. METHODS A single-institution retrospective review collected clinical data on patients with breast cancer metastatic to brain who were treated with SRS from 2009-2020. Statistical analyses were performed using the Kaplan-Meier method and chi-square statistic. RESULTS Of 82 patients with breast cancer metastatic to brain treated with SRS, 33 (40%) were HER2-positive, 18 of whom were hormone receptor-positive. At brain metastasis diagnosis, 15 patients (45%) had >1 intracranial metastasis (range 2-7), and the median brain metastasis maximal dimension was 2.0 cm. Fifteen patients had uncontrolled extracranial disease. After brain metastasis diagnosis, 9 patients (27%) were treated with systemic therapy first (T-DM1+/-HP, lapatinib+HP, chemotherapy+/-HP) followed by SRS at a median of 18.6 months after starting systemic therapy. Seven patients (21%) were treated with SRS first, followed by systemic therapy in 6 of these patients (multi-agent regimens, 4 including T-DM1 or lapatinib). Seventeen (52%) received concurrent systemic therapy and SRS (T-DM1+/-chemotherapy, lapatinib, HP, hormone therapy, chemotherapy). Median follow-up time was 21.1 months. Median overall survival was 24.8 months and not statistically different between treatment groups. Four patients (12%) developed symptomatic radionecrosis; 3 were on T-DM1 concurrent with SRS. CONCLUSION In this small patient sample, we noted favorable survival outcomes for patients with HER2-positive breast cancer metastatic to brain when treated with HER2-targeted therapies together with SRS. The sequence of systemic therapy and SRS does not appear to impact survival outcomes. Concurrent treatment with T-DM1 and SRS may be associated with higher rates of radionecrosis.

Download Full-text