Estrogen receptor (ER)-positive breast cancers are often not a single tumor but a composite of related tumors, referred to as sub-clones, which contributes to treatment resistance, according to a multicenter study published in the journal Nature Communications.1

Although estrogen suppression therapy is successful in treating ER-positive breast cancer, therapy resistance is common and accounts for most breast cancer deaths. Little is known about the effect of aromatase inhibitors (eg, letrozole, anastrozole, and exemestane) on the genetic diversity of breast cancer tumors; therefore, researchers sought to better understand the affects of endocrine therapy on the genetic diversity of breast cancer tumors.

For the study, researchers from Baylor College of Medicine, Washington University School of Medicine, MD Anderson Cancer Center, and the Mayo Clinic studied 22 human breast cancer tumors in patients scheduled for surgery. The tumors were treated with estrogen deprivation therapy for 4 months prior to surgical resection.

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After removal, the entire genomic structure of each tumor was analyzed and compared with the genomic structure of their respective biopsy samples obtained before hormone therapy. Compared with pretreatment biopsy samples, new mutations or enrichment of mutations present in low levels were seen in the respective posttreatment samples. Some cases originally diagnosed as a single tumor were found to be 2 separate tumors growing closely together, referred to as collision tumors.

In one case, ER-negative cancer cells were found in a mostly ER-positive tumor. After 4 months of aromatase inhibitor therapy, the ER-positive tumor had shrunk enough to enable diagnosis of the ER-negative tumor and initiation of appropriate treatment.

These results suggest that genomic analysis at diagnosis is not enough, reported the researchers. Periodic analyses of biopsy samples can help clinicians evolve treatment strategies to match changes in tumors.

In addition, because aromatase inhibitor therapy shrinks the tumor, breast-conserving surgery is more likely to be an option for patients.


1. Miller CA, Gindin Y, Lu C, et al. Aromatase inhibition remodels the clonal architecture of estrogen-receptor-positive breast cancers. Nat Commun. 2016 Aug 9. doi: 10.1038/ncomms12498. [Epub ahead of print]