“Patients do not die from their primary breast tumor but as a consequence of metastases,” wrote the authors of a Nature Genomics study published in September 2019.1 It’s a no-frills statement that highlights the urgent need for research that could help practitioners better understand the biology of metastatic breast cancer, and could pave the way for increasingly sophisticated treatments.

“We learned that metastatic breast cancer is different from primary breast cancer regarding the number of mutations, mutational signatures, and affected genes,” said Lindsay Angus, lead author of the study, and a PhD candidate in medical oncology at Erasmus University Medical Center in Rotterdam, Netherlands. “Since the metastatic lesions can substantially differ from the primary tumor, genomic characterization of the metastatic lesions will better reflect the current genomic make-up and will give insight into which molecular targets are currently present in the patient’s tumor.”

The study relied on whole-genome sequencing (WGS) to get a more granular view of metastatic breast cancer, to see how it differs from primary breast cancer. The study, which included 442 patients, found that in metastatic breast cancer, “tumor mutational burden doubles, the relative contributions of mutational signatures shift, and the mutation frequency of 6 known driver genes increases in metastatic breast cancer.” It also found that pretreatment significantly affected health outcomes for patients with metastatic breast cancer.

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Because the genome of metastasis can differ so much from the primary tumor — due to tumor evolution and the influence of treatment — it’s important to gain a more detailed understanding of metastatic growths in their own right. And as the most common cancer in women, a better overall understanding of the genomics of breast cancer could have a big impact on global health.

Many prior studies of metastatic breast cancer looked only at whole-exome sequencing and showed results suggesting that the same gene drivers are responsible for both primary and subsequent tumors. But this study — which looked more closely at the genome of the metastases and found otherwise — moved the needle by relying on WGS, a tool that until recently was not widely accessible.

The authors of another Nature Medicine letter focused on WGS — but in triple-negative breast cancers (TNBCs), specifically — are also acutely aware that taking the whole-genome approach was not always feasible across prior studies.2