Clinical benefit, toxicity and cost of metastatic breast cancer therapies: systematic review and meta-analysis



Oncologists, clinical trialists, and guideline developers need tools that enable them to efficiently review the settings and results of previous studies testing metastatic breast cancer (MBC) drug therapies.


We searched the literature to identify clinical trials testing MBC drug therapies. Key eligibility criteria included at least 90% of patients enrolled in the trial having MBC, therapeutic clinical trials, and Phase II–III studies. Studies were stratified based on patients’ tumor receptor statuses and prior exposure to therapy. Survival and toxicity of each drug therapy were estimated from randomized controlled trials using network meta-analysis and from all studies using meta-analysis. These results, along with estimated drug costs, are presented in a web-based visualization tool.


We included 1865 studies containing 2676 treatment arms and 184,563 patients in the tool ( Meta-analysis-based efficacy and toxicity estimates are available for 85 HER-2-directed therapies, 84 hormonal therapies, and 442 undirected therapies. Network meta-analysis-based estimates are available for 16 HER-2-directed therapies, 26 hormonal therapies, and 131 undirected therapies.


In this era of increasing choices of MBC therapeutic agents and no superior approach to choosing a treatment regimen, the ability to compare multiple therapies based on survival, toxicity and cost would enable treating physicians to optimize therapeutic choices for patients. For investigators, it can point them in research directions that were previously non-obvious and for guideline designers, enable them to efficiently review the MBC clinical trial literature and visualize how regimens compare in the key dimensions of clinical benefit, toxicity, and cost.

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Data Availability

The datasets analyzed during the current study are available online at


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    Assistance in the literature review and data extraction was provided by former MIT graduate students Allison O’Hair and Stephen Relyea and by MIT and Wellesley undergraduate students Emily Chen, Michael Chen, Shahrin Islam, Siva Nagarajan, David Sukhin, Pei Tao, Roza Trilesskaya, Victoria Wang, Mimi Williams, and Joanna Yeh.


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Correspondence to John Silberholz.

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Conflict of interest

Linda Vahdat has performed consulting for Berg Pharma, Seattle Genetics, Athenex, and Eisai and has received clinical trial research funding from Genentech and Immunomedics. Dimitris Bertsimas and John Silberholz declare that they have no conflict of interest.

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Silberholz, J., Bertsimas, D. & Vahdat, L. Clinical benefit, toxicity and cost of metastatic breast cancer therapies: systematic review and meta-analysis. Breast Cancer Res Treat 176, 535–543 (2019).

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  • Metastatic breast cancer
  • Network meta-analysis
  • Overall survival
  • Dose-limiting toxicity