Gene Mutations May Predict Breast CA Treatment Response

For women with estrogen receptor-positive breast cancer, mutations ID aromatase inhibitor response

MONDAY, June 11 (HealthDay News) -- Genetic mutations present in women with breast cancer may be able to predict whether the tumor will respond to treatment, according to a study published online June 10 in Nature.

Matthew J. Ellis, Ph.D., from Washington University in St. Louis, and colleagues sequenced pretreatment tumor DNA from 77 postmenopausal women with estrogen receptor-positive breast cancer from two neoadjuvant aromatase inhibitor clinical trials.

The researchers identified 18 significantly mutated genes in the tumors, including five genes which had already been associated with hematopoietic disorders. Using data from 240 additional cases, mutant MAP3K1 was associated with low-grade histology, low Ki67 proliferation index, and luminal A status, indicating a favorable response to aromatase inhibitors. Tumors with mutant TP53 had higher histological grade and luminal B status; these tumors were mostly aromatase-inhibitor resistant. Tumors with mutant GATA3 were associated with slower growth after treatment.

"In conclusion, the genomic information derived from unbiased sequencing is a logical new starting point for clinical investigation, where the mutation status of an individual patient is determined in advance and treatment decisions are driven by therapeutic hypotheses that stem from knowledge of the genomic sequence and its possible consequences," Ellis and colleagues write.

The study received clinical trial support from Novartis and Pfizer. Institutional support was received in the form of a productive partnership with Illumina Inc.

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