Inherited DNA May Hold Key to Breast Cancer Metastasis

New research challenges the long-held belief that cancer metastasis is solely driven by mutations within tumor cells. A study published in Cell suggests that a patient's inherited DNA may play a crucial role in breast cancer spread, offering a fresh perspective on metastasis as a partially hereditary disorder.

The Tavazoie lab at Rockefeller University identified a common variant of the PCSK9 gene present in 70% of white women, associated with reduced breast cancer survival. When mice were engineered with this human PCSK9 variant, metastasis rates increased. A large Scandinavian cohort study further validated these findings, revealing that patients with the PCSK9 variant had a 22% risk of metastasis within 15 years, compared to only 2% for those without it.

The PCSK9 variant appears to promote metastasis by degrading the LRP1 receptor on cancer cells, triggering a cascade of gene activation favorable for metastatic initiation. This mechanism aligns with previous findings on melanoma metastasis, where APOE alleles affecting LRP1 were also implicated.

While these results are significant, Sohail Tavazoie emphasizes that patients with the variant should not be alarmed, as the majority will still not develop metastasis. However, the study opens up potential therapeutic avenues. Preliminary work suggests that an existing antibody approved for high cholesterol treatment could suppress the PCSK9 variant's activity.