The hunt for mutations … and treatment targets
The most common targets include the estrogen receptor (ER-positive cancers feed on estrogen) and the human epidermal growth factor receptor 2 (HER2-positive breast cancers produce too much of this protein), but there are many more.
Oncologists utilize these targets when they treat a cancer, often shrinking the tumor. But a few genes may mutate in response to the treatment, allowing the cancer to become resistant and continue to grow. A new treatment may kill most of the cancer again until there’s another mutation, another resistance.
Gralow said this cycle of mutation, resistance and metastatic spread means there can be a mix of many mutations within one patient, i.e., a HER2-positive met in the lung and a HER2-negative met in the liver. It also means your tumors can acquire mutations in cancer-driving genes like BRCA1 or 2.
"Even if you didn't inherit a BRCA mutation from your parents, your tumor can acquire a BRCA1 or 2 mutation,” she said. “The list is getting longer and longer at all the things we're looking for in breast cancer.”
Gralow demonstrated her point by sharing slides of a patient’s genomic profiling — delineating all of the gene amplifications or deletions that might point to possible therapies — as well a multitude of DNA repair genes beyond BRCA1 or 2, that might contribute to cancer’s growth. The list reads like a deadly alphabet soup: CHEK2, ATM, P53, PALB2, RAD51D, BARD1, ATR, FAM175, etc.