Hormone therapy, which reduces estrogen levels in a woman’s body, has long served as an effective way to reduce tumor size and, in turn, reduce the recurrence of cancer in women with breast cancer. However, a new study has found evidence to suggest that some tumors are actually able to build a resistance to this therapy and continue to grow and spread despite efforts to stop them.

In a new analysis of 22 breast cancer tumors, researchers from Washington University School of Medicine found that aromatase inhibitors hormone-reduction therapy brought about genetic mutations in some tumors that caused them to not only survive the treatment, but also grow. The results show the extreme genetic complexity of these types of breast cancer tumors and reveal that even single tumors are able to evolve very quickly in response to therapy. The study also reinforces past research suggesting that mutations in a gene called ESR1 are associated with resistance to aromatase inhibitor therapy.

"In the post-treatment tumor samples, we found many new mutations or enrichment of mutations already seen in the pre-treatment samples," said co-senior author Matthew J. Ellis, in a recent statement. "This means that under the environmental stress of the treatment, the tumors are spawning new sub-clones that subsequently can survive and grow despite therapy, and that is why we are having difficulty in the end treating estrogen-receptor-positive breast cancer. We found this result in the majority of tumors we studied."

Aromatase inhibitors are commonly given in order block the body’s remaining production of estrogen in postmenopausal women with breast cancer whose ovaries no longer produce estrogen. For the majority of women with breast cancer, this treatment is highly effective in shrinking tumor size so that it can eventually be removed with surgery. However, the variety of responses to estrogen-deprivation treatments as shown in this study suggest that this approach should be further investigated and tailored to each individual patient.

These findings could have implications for how doctors plan to treat breast cancer patients following the surgical removal of tumors. Co-author Elaine Mardis suggested that patients who undergo aromatase inhibitor therapy for several months prior to surgery should be re-evaluated immediately before their operation to determine exactly how their tumors have changed in response to the therapy.

“Such information can help indicate whether further estrogen suppression treatment is likely to contribute to a lower risk of relapse," concluded Mardis.

Source: Miller CA, Gindin Y, Lu C, et al. Aromatase inhibition remodels the clonal architecture of estrogen-receptor-positive breast cancers. Nature Communications . 2016.

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