Breast tumors evolve in response to hormone therapy

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Breast tumors evolve in response to hormone therapy

Many breast tumors grow in response to female hormones, especially estrogen.

Drugs that reduce estrogen levels in the body often are effective in reducing tumor size and preventing recurrence of the cancer.

But some tumors become resistant to these therapies and continue to grow and spread.

A new analysis of breast tumors, before and after hormone-reduction therapy, reveals the extreme genetic complexity of these tumors and the variety of responses that are possible to estrogen-deprivation treatments.

The study, led by researchers from Washington University School of Medicine in St. Louis and Baylor College of Medicine, appears Aug. 9 in the journal Nature Communications.

The researchers analyzed 22 breast tumors before and after 4 months of treatment with aromatase inhibitors, drugs commonly given to post-menopausal women with breast cancer.

The majority of the tumors analyzed — 18 of 22 — had complex genetic landscapes and dynamic responses to hormone deprivation therapy, meaning that many of the gene mutations present in the tumors before and after treatment were different.

For example, in one patient, certain mutations present in 92% of the initial tumor were totally absent in samples taken after four months of aromatase inhibitor therapy.

The researchers analyzed only one tumor that had a complex but stable genetic landscape, meaning it was largely unchanged by aromatase inhibitor therapy.

Another tumor had very simple and stable genetics before and after treatment. And two patient samples indicated evidence of two independent but intertwining tumors with separate genetic origins.

The result showed that successful treatment reduces the size of a tumor before it is surgically removed. The therapy has been shown to improve long-term outcomes for patients.

The researchers suggest that reducing estrogen levels in estrogen-receptor-positive breast cancer can change the genetics of the tumor.

These changes may be important for deciding how best to treat a patient after the surgical removal of the tumor.

In addition, analyzing a single sample of the breast tumor is insufficient for understanding how a patient should best be treated.

The study also reinforced past research suggesting that mutations in a gene called ESR1 are associated with resistance to aromatase inhibitor therapy, but the analysis did not identify any new genes that may also be responsible for conferring resistance to these drugs.

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Citation: Miller CA, et al. (2016). Aromatase inhibition remodels the clonal architecture of estrogen-receptor-positive breast cancers. Nature Communications. Published online. DOI:10.1038/ncomms12498.
Figure legend: This Knowridge.com image is credited to M.J. Ellis.