Evidence from trial or study results

A Cancer Australia systematic review⁷ on the management of CNS metastases in women with metastatic breast cancer was undertaken, with available evidence published between January 2001 and April 2012.

A systematic literature search was conducted in Medline, Embase and Pubmed to identify relevant studies which addressed the inclusion criteria. A search of conference websites was also conducted, including the American Society of Clinical Oncology and San Antonio Breast Cancer Symposium. The search undertaken for the systematic review identified a conference abstract on the LANDSCAPE study; a full paper for this study was published in February 2013³⁶ and was included in the systematic review and is referred to in these guidelines.

The systematic review focused on evidence for the management of CNS metastases in women with metastatic breast cancer not CNS metastases from various primary tumours. However, some studies included in the systematic review had patient populations with mixed primary tumours and where available, the results specific to the breast cancer populations of these studies were reported. The systematic review included evidence reported for metastases in the brain and in the spinal cord (including metastatic spinal cord compression), and for both parenchymal and meningeal (leptomeningeal) metastases.

A total of 1315 citations were identified. Following application of the exclusion criteria, a total of 108 citations and one abstract were identified as eligible for the current review.

Fifty-seven citations addressed the primary research questions:

1. What is the effectiveness of surgery in the management of CNS metastases from breast cancer?
2. What is the effectiveness of radiotherapy in the management of CNS metastases from breast cancer?
3. What is the effectiveness of systemic therapies in the management of CNS metastases from breast cancer?
4. What is the effectiveness of combinations of the above treatments in the management of CNS metastases from breast cancer?
5. Are there specific requirements for the management of the sub-group of patients diagnosed with asymptomatic CNS metastases?

 

In addition, 51 citations addressed other issues:

• The incidence/prevalence of CNS metastases in breast cancer patients, specifically those with HER2-positive and triple negative breast cancer.
• The course, nature and extent of neurocognitive and psychological impairments in CNS metastases in metastatic breast cancer, and how these impairments are assessed.
• The impacts of these impairments on everyday functioning and quality of life of women with CNS metastases from breast cancer including restrictions on driving, seizures.
• The identification of effective strategies for providing supportive and palliative care to women with CNS metastases from breast cancer.
• Multidisciplinary care including involvement of allied health such as physiotherapy and rehabilitation, psychology, care coordinators, social work, speech pathology.
• Measurements of Quality of Life (QoL).
• Meningeal metastases in women with metastatic  breast cancer.
• Use of other medications including steroids and anticonvulsants.

There were few large prospective trials identified that investigated the use of surgery, radiotherapy, systemic therapies or multimodal treatment for the management of CNS metastases in women with metastatic  breast cancer, specifically from breast cancer. Most of the relevant trial data were limited to small breast cancer patient cohorts or retrospective studies.

The systematic review identified seven systematic reviews, including two Cochrane reviews. These systematic reviews included evidence for management for CNS metastases in populations of mixed primary cancers. While they were not specific to the management of CNS metastases from breast cancer, the Cochrane reviews and included primary studies have been used as primary references in the recommendations and statements of evidence of this clinical practice guideline due to the limited high quality evidence identified for the management of CNS metastases from breast cancer. Details of the Cochrane reviews and the included primary studies are outlined in Evidence from trial or study results.

Refer to the Cancer Australia systematic review⁷ for detailed evidence from studies on the management of CNS metastases in patients with metastatic breast cancer.