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Methods

We used a mixed-methods approach to our landscape analysis of MBC research, including
both quantitative aspects (classification and quantification of clinical trials and grants) and
qualitative aspects (KOL interviews). The Alliance used 2 leading frameworks about cancer
development and metastasis (Figure 1 and Figure 2) in order to categorize and group MBC
research information. The Hallmarks of Cancer framework, recently updated by Hanahan
and Weinberg, includes 8 hallmarks of cancer and 2 enabling characteristics that describe
biological capabilities acquired during the multistep development of human tumors and takes
into account the tumor microenvironment . The second framework, the “Steps in Metastasis,”
[5]
describes the mechanistic insights of tumor metastasis [6, 7] . This framework describes the
steps necessary for tumor metastasis—including invasion outside of the primary tumor and
into nearby tissues, entering of the lymphatics or bloodstream (called intravasation), surviving,
avoiding immune attack and eventually arresting the circulation, entering a new organ site
[6]
(called extravasation), and then growing in the new organ (called metastatic colonization) .
These frameworks encompass understanding the period of tumor dormancy, the need for
angiogenesis, and tumor–host cell interactions. Clinical trials were assigned to the Hallmarks of
Cancer framework, when applicable, and funded research grants were assigned to the Steps
in Metastasis framework, where sufficient information was available in research summaries for
this purpose.

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