This author interview is by Dr Xin Jin, of Broad Institute of MIT and Harvard. Dr Jin's full paper, Targeting Breast Cancer Metastasis, is available for download in Breast Cancer: Basic and Clinical Research.

Please summarize for readers the content of your article
This review article summarizes recent breakthroughs in breast cancer research with a special focus on metastasis, which remains to be the biggest challenge for breast cancer treatment. This article discusses in depth genes, pathways and programs that contribute to the metastasis process, their applicability for therapeutic targeting, and possible challenges when pushing such therapies into the clinic. I hope this review will provide a clear picture of what metastasis is, why it is important, how it can be targeted, and whether we can eventually combat it with the advancement of basic and clinical science.

How did you come to be involved in your area of study?
I did my graduate research on breast cancer at Memorial Sloan-Kettering Cancer Center, NY, USA. My research topic was to investigate the origins of metastatic traits in breast cancer. This is how I became involved in this area.

What was previously known about the topic of your article?
Breast cancer may develop metastasis in multiple organs, including bone, lung, brain, liver and etc. Despite recognition of their molecular differences from primary tumors, breast cancer metastases are largely targeted based on their primary tumor characteristics. Estrogen receptor (ER)-positive tumors and HER2-positive tumors are treated with hormonal therapy and anti-HER2 therapy respectively. These targeted therapies can be combined with chemotherapy to increase the treatment potency for some cases. Triple-negative breast tumors are mainly treated with chemotherapy because effective targeted therapy is not yet available for the majority of this molecular subtype. Even though these first-line treatments have demonstrated their efficacies in controlling disease progression and extending patient survival, in many cases, resistance eventually develops and patients succumb to the metastatic disease.

How has your work in this area advanced understanding of the topic?
One important question that remains unanswered in the field is how molecular traits that contribute to metastasis arise from the primary tumor. Here we present a conceptual framework of metastatic trait evolution, which systematically explains how different features of primary tumors may serve as driving forces for certain metastatic traits and predispose cancer clones adaptable to the distant tissue. Built upon this framework, this work further discusses how these findings can be incorporated into the design of new combination therapy for breast cancer.

What do you regard as being the most important aspect of the results reported in the article?
Combination therapy via concurrent targeting of multiple molecular targets is the future trend of breast cancer therapy. This review summarizes key molecular targets of breast cancer and their inhibitors currently tested in clinical trials. This is a useful resource for combination therapy design. To circumvent many existing complications in targeting full-fledged metastasis, an alternative strategy for therapeutic intervention is targeting latent metastasis. Our discussions highlight the attractiveness of such therapy, its practicality concern and some foreseeable challenges. These perspectives add to our current understanding of the latency biology and may provide novel insights in guiding the design of next-generation adjuvant therapy.

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