Brain metastases in breast cancer

Abstract

Despite therapeutic advances, the development of breast cancer brain metastases (BCBM) is still the harbinger of a dismal prognosis. Patient outcomes vary depending on factors, including tumor phenotype, extent of disease within and outside the brain, as well as patient performance status. Treatment includes surgery, radiation therapy and systemic therapy determined by patient and tumor characteristics. Despite these approaches, novel treatments are needed and there is growing interest in systemic therapies. However, the efficacy of pharmacologic agents is hampered by poor penetration of drugs across the blood–brain barrier. Therefore, there is a pressing need for a greater understanding of the natural history of BCBM to guide the development of further therapies. This review analyzes prognosis and treatment of BCBM by tumor phenotype and discusses ongoing research into new therapies.

Keywords::

• brain metastases
• breast cancer
• systemic therapy
• treatment of breast cancer brain metastases

Authors contributions

M Khasraw designed the review and performed the literature search with HW Sim. HW Sim and S Patil performed analysis of the studies. All authors contributed to the writing and final approval of the manuscript.

Acknowledgements

The authors like to thank Fiona Russell from Deakin University Faculty of Health library for her assistance with the development of the literature search.

Financial & competing interests disclosures

M Khasraw has served on advisory boards of Roche and Novartis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Breast cancer brain metastases (BCBM) represent a devastating clinical problem associated with significant morbidity and limited survival.

• The biological heterogeneity of breast cancer is increasingly recognized with important implications for BCBM.

• Tumors that lack expression of the estrogen receptor (ER), progesterone receptor and HER2 are associated with the highest risk of brain metastases.

• Brain metastases represent a late complication of ER-positive breast cancer.

• Surgical resection should be considered for patients with single brain metastases, good systemic disease control and good performance status.

• Stereotactic radiosurgery may be an alternative to surgery for single metastases in inaccessible areas or in some patients who are otherwise not fit for surgery.

• Whole brain radiation therapy remains an important approach for patients who are not candidates for surgical resection.

• In retrospective series, many cytotoxic chemotherapy agents have shown activity in BCBM.

• For patients with HER2-positive tumors, the use of anti-HER2 therapies may be effective in BCBM.

• Novel systemic therapies are being investigated, which will hopefully lead to improvements in outcome following diagnosis of BCBM.