two genes predict risk of recurrence in tamoxifen treated ER+ breast cancer patients

[Lani]

from the Mayo Clinic--again, her2 status is not discussed in the abstracts. Will try to read the whole article

Mayo Clinic researchers report that the expression of two novel genes within the tumors of women with early stage breast cancer may allow identification of women who are and are not at risk for early relapse or cancer-related death. Results: of the study are published in the April 1 issue of Clinical Cancer Research.

"The HOXB13 and IL17BR gene profile was previously discovered as a potential marker of relapse in hormone-receptor positive breast cancer treated with tamoxifen," says Matthew Goetz, M.D., who co-led the project with James Ingle, M.D. and Fergus Couch, Ph.D. "Our new study shows that the marker is only useful for identifying women with a higher risk in the setting of lymph node-negative breast cancer."

The study, which was conducted by researchers at Mayo Clinic, Harvard Medical School and Arcturus Bioscience, tested whether the expression levels of two genes within women with early stage breast cancer affected the outcomes of women with estrogen receptor-positive breast cancer. The research team examined tissue from 206 postmenopausal women enrolled in a prospective study conducted by the North Central Cancer Treatment Group (NCCTG). They tested the level of gene expression of HOXB13 and IL17BR from paraffin-embedded tumors and found that the 2-gene expression ratio was an independent marker of early breast cancer relapse or death in lymph node-negative breast cancer.

"We believe that these findings are clinically important and corroborate the accumulating laboratory data which suggests that the HOXB13 gene is critically involved in breast cancer metastases," says Dr. Goetz. "Further research is needed to determine whether more aggressive or additional treatments will improve the outcomes of women identified to be at high risk by means of this marker."

Breast cancer is diagnosed in approximately one million women each year, and claims the lives of over 40,000 in the United States. More than two-thirds of all breast cancers are hormone positive, and most of these are early stage (lymph node-negative).


ABSTRACT: A Two-Gene Expression Ratio of Homeobox 13 and Interleukin-17B Receptor for Prediction of Recurrence and Survival in Women Receiving Adjuvant Tamoxifen [Clinical Cancer Research; Subscribe]
Purpose: In the adjuvant treatment of estrogen receptor (ER)-positive breast cancer, additional markers are needed to identify women at high risk for recurrence.

Experimental Design: We examined the association between the ratio of the homeobox 13 (HOXB13) to interleukin-17B receptor (IL-17BR) expression and the clinical outcomes of relapse and survival in women with ER-positive breast cancer enrolled onto a North Central Cancer Treatment Group adjuvant tamoxifen trial (NCCTG 89-30-52).

Results: Tumor blocks were obtained from 211 of 256 eligible patients, and quantitative reverse transcription-PCR profiles for HOXB13 and IL-17BR were obtained from 206 patients. The cut point for the two-gene log 2(expression ratio) that best discriminated clinical outcome (recurrence and survival) was selected and identified women with significantly worse relapse-free survival (RFS), disease-free survival (DFS), and overall survival (OS), independent of standard prognostic markers. The cut point differed as a function of nodal status [node negative (59th percentile) versus node positive (90th percentile)]. In the node-positive cohort (n = 86), the HOXB13/IL-17BR ratio was not associated with relapse or survival. In contrast, in the node-negative cohort (n = 130), a high HOXB13/IL-17BR ratio was associated with significantly worse RFS [hazard ratio (HR), 1.98; P = 0.031], DFS (HR, 2.03; P = 0.015), and OS (HR, 2.4; P = 0.014), independent of standard prognostic markers.

Conclusion: A high HOXB13/IL-17BR expression ratio is associated with increased relapse and death in patients with resected node-negative, ER-positive breast cancer treated with tamoxifen and may identify patients in whom alternative therapies should be studied.