New research shows how genes can identify risks of breast cancer
Not only can young cancer cells look different from healthy cells—cancer cells often also look very different from each other. Polyak’s work showed high levels of molecular and genetic variation within a single breast tumor in an individual woman. Tumor cells were not identical clones of each other but could vary widely both in the genes they carried and their physical characteristics. This means that treatment like hormone therapy wouldn’t necessarily wipe out tumor cells: some cells can survive and seed a fully resistant, triple negative breast tumor that is more aggressive and has few treatment options, Polyak says.
Breast cancer forecasts
Scientists have known about the importance of inherited mutations in genes like BRCA1 and BRCA2 in impacting cancer development since the 1980s, Curtis says. Individuals carrying certain versions of these two genes have an extremely high risk of developing breast, ovarian, and other cancers. But many individuals who have inherited an increased risk for breast cancer don’t have these two variants, leaving scientists to ask where this risk comes from.
What Curtis and her postdoctoral fellow Kathleen Houlahan wanted to know was how inherited immune differences could help explain why some women develop breast cancers that were readily treatable, and others relapse decades after seemingly successful treatment.
This type of investigation required lots of data, so Houlihan and Curtis stitched together information from a range of datasets, including tumor cell atlases and cancer registries. Their analysis of over 6,000 breast tumors showed that cells varied in what scientists call their “germline epitope burden,” which could help predict how aggressive a cancer might form.
What they found is that that women with higher germline epitope burdens (i.e. more flashy neon signs) were more likely to catch and eliminate cancer cells early and prevent it from becoming invasive. However, if women had cancer with flashy signs and escaped immune surveillance, “the pattern flips,” Houlahan said in a report for Stanford University. The cancer would be more likely to become aggressive, learning to outsmart the the immune system. It could become invasive, affecting nearby tissue, or spread and metastasize to distant parts of the body.