Breast cancer research has revealed that using estrogen-deprivation therapy on estrogen receptor-positive (ER-positive) tumors causes changes in the mutation population, leading to results that can be used for improving treatment.
In a study published in the journal Nature Communications, Matthew Ellis and colleagues from the Baylor College of Medicine, Mayo Clinic, MD Anderson Cancer Center and the Washington University School of Medicine, said that simply examining the genetic makeup of tumors at diagnosis will not suffice if effective cancer treatment is desired.
Rather, the researchers suggest that a periodic scan using several biopsy samples will be necessary to fully observe how a tumor is changing, which could guide the next treatment strategy that will be prescribed to a patient.
"The majority of ER-positive breast cancers are not a single tumor but more like a family of related tumors referred to as ‘sub-clones,'" said Ellis.
He explained that a family originate from the same genes, but every member still features distinct genetic characteristics. The same is true with tumors. When the researchers applied estrogen-deprivation therapy by using aromatase inhibitors, they created a situation wherein some members of a tumor family die while others keep growing. It's important to keep tabs on the "survivors" because they are likely to be the ones to cause problems in the future with recurrence.
In their work, Ellis and colleagues found that new mutations or progression in mutations are usually low in numbers before the use of aromatase inhibitors like exemestane, anastrozole and letrozole. But when treatment is applied, the stress causes new sub-clones to not only spawn but survive and thrive. With the tumor inherently still growing (no thanks to these new sub-clones), this is what makes treating ER-positive cases of breast cancer difficult.
The researchers, however, also discovered that while most breast cancer tumors have sub-clones from the same origin, there are some tumors that have different origins.
Called collision tumors, think of them as two different families living so close together that they are first identified as a single family. When tumors are not diagnosed to be of this kind, they lead to unexpected relapse after surgery even though the initial prognosis was good.
As such, the researchers recommended treating tumors with aromatase inhibitors first prior to surgery to track their behavior. This will allow for the potential detection of sub-clones that may lead to relapse in the future, as well as tumor shrinkage that can encourage patients to undergo breast-conserving surgical procedures.
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