AKT PHOSPHORYLATION PREDICTS PACLITAXEL BENEFIT IN BREAST CANCER

NEW YORK (Reuters Health) Jun 18 - Women with node-positive breast cancer that shows Akt phosphorylation (pAkt) will likely benefit from paclitaxel, according to findings published online May 17th in the Journal of Clinical Oncology.

Knowing a tumor's pAkt status "would help physicians to make treatment decisions and allow patients with pAkt-positive tumors to elect taxane-based chemotherapy," said lead author Dr. Sherry X. Yang from the National Cancer Institute, Bethesda, Maryland, in e-mail to Reuters Health.

On the other hand, she continued, knowing the pAkt status can also spare patients with pAkt-negative tumors from taxane therapy and toxicity and allow them to start other therapies that are more effective.

For their study, Dr. Yang and colleagues used tissue microarray findings from 1581 women who were enrolled in a National Surgical Adjuvant Breast and Bowel Project trial. The women had all received four cycles of doxorubicin-cyclophosphamide chemotherapy (AC); roughly half had also received four cycles of paclitaxel afterward.

Six hundred and six tumors (38%) expressed pAkt, including 279 of 760 (37%) in the AC-only group and 327 of 821 (40%) of the group that received sequential AC and paclitaxel.

At a median follow-up of 9 years, the women with pAkt-negative tumors had no difference in disease-free survival with AC only or AC plus paclitaxel.

But for women with pAkt-positive tumors, disease-free survival was significantly longer with the sequential combination. Multivariate analysis using the Cox proportional hazards model showed that patients with pAkt-positive tumors had a significant 26% increase in disease-free survival (p = 0.02) and a nonsignificant 20% increase in overall survival (p = 0.17) with paclitaxel treatment versus AC alone.

The interaction between paclitaxel treatment and pAkt status persisted after stratification for estrogen receptor status and HER2 status, the investigators say, although the statistical power was reduced.

"The application of this biomarker in clinical practice may potentially tailor chemotherapy and reduce the cost of cancer care," Dr. Yang said. But before it can be used in the clinic, "it is important that other Phase III studies such as CALGB9344 trial validate our data" - and the results of these studies may not be available for several years yet, she added.

http://jco.ascopubs.org/cgi/content/abstract/JCO.2009.26.1602v1

J Clin Oncol 2010.