Two studies published in 2006 and a major clinical trial launched by the National Cancer Institute (NCI) are moving breast cancer specialists closer to understanding a cutting-edge test’s value in customizing cancer care. Many oncologists have been looking for more proof that a two-year-old genetic test helps make good treatment decisions. The test (Oncotype DX) looks at 21 genes to measure a patient’s genetic risk of cancer recurrence after early-stage breast cancer. In many cases, the resulting score also predicts the likelihood of response to chemotherapy.

Tailoring chemotherapy decisions
The lab test holds promise for a more personalized approach to cancer treatment, but medical professionals have been waiting for further evidence from long-term studies that point to the test’s clinical utility. The test was first shown to be highly accurate in a study published in December 2004 in the New England Journal of Medicine (see Breast Cancer Test Predicts Chances of Recurrence). In May 2006, the NCI launched a first-of-its-kind clinical trial using the genetic test. The trial’s primary goal is to help determine which women will benefit from chemotherapy and which can be spared difficult, unnecessary treatment. This ten-year clinical trial will involve thousands of patients and may provide the additional data health care providers are looking for as confirmation of the test’s merit.

The NCI noted that a study published in the May 23, 2006 issue of the Journal of Oncology—the B-20 chemotherapy benefit study of the National Surgical Adjuvant Breast and Bowel Project (NSABP)—“provides strong evidence for the value of using [the test] to help women with this form of breast cancer determine whether they will benefit by adding chemotherapy to hormonal therapy.” The study randomly assigned 227 patients to tamoxifen treatment and 424 to tamoxifen treatment plus chemotherapy. Researchers found that patients with a high recurrence score (RS) on the genetic test benefited most from chemotherapy. Those patients with low-RS tumors had low or no benefit from chemotherapy. The NCI said the NSABP study of 651 patients and several other similar studies in recent years “provided the basis” for the launch of this landmark, individualized treatment trial.

Also in May, results of a study using the test in a community hospital setting were published in Breast Cancer Research. Researchers sought to demonstrate that the 21-gene assay is predictive of recurrence for breast cancer patients, whether treated or untreated with tamoxifen. None of the patients received adjunct chemotherapy. The large study, involving 4,964 women from 14 California hospitals and clinics again demonstrated clinical utility, helping predict the likelihood of breast cancer survival.

FDA wants to regulate
In September, the U.S. Food and Drug Administration (FDA) announced it would like to regulate this and similarly complex genetic tests (tests it calls “multivariate index assays”). Tests of this type, the FDA noted, are some of the most promising developments in diagnostics to date. The agency issued a draft of its regulatory guidelines for the category and asked for public comment.

According to a New York Times article of September 6, some experts fear that the costs and time required to obtain regulatory approval will impair companies seeking to develop genetic tests. The burden of regulation at this point, some argue, deters both development of new products and improvements in existing ones. Others say oversight is appropriate to protect consumers from tests of questionable value.

Patients wanted
The NCI trial using the cancer test is known as TAILORx—the Trial Assigning IndividuaLized Options for Treatment (Rx). Study sites across the country are enrolling 10,000 women ages 18 to 75 with estrogen receptor (ER) positive and/or progesterone receptor (PR) positive breast cancer that has not spread to the lymph nodes and can be surgically removed. For a list of sites involved in the 10-year study, visit http://www.cancer.gov/clinicaltrials/ECOG-PACCT-1 or call (800) 422-6237.

Sources
S1
Genomic Health. 31 May 2006. Genomic Health announces publication of Kaiser Permanente study demonstrating Oncotype DX helps predict likelihood of survival in early-stage breast cancer (press release). On the Internet: http://www.shareholder.com/visitors/print_release.cfm?releaseid=199059. Accessed 8 Sep 2006.

S2
Genomic Health. 23 May 2006. Genomic Health announces “early release” of NSABP study confirming Oncotype DX predicts chemotherapy benefit in certain breast cancer patients; study findings pave way for landmark NCI TAILORx trial (press release). On the Internet: http://www.shareholder.com/visitors/print_release.cfm?releaseid=198167. Accessed 8 Sep 2006.

S3
Habel, LA, Shak S, Jacobs MK, et al. 2006. A population-based study of tumor gene expression and risk of breast cancer death among lymph node-negative patients. Breast Cancer Research. 2006, 8:R25. On the Internet: http://breast-cancer-research.com. Accessed 8 Sep 2006.

S4
National Cancer Institute. 23 May 2006. Personalized treatment trial for breast cancer launched (news release). On the Internet: http://www.cancer.gov/newscenter/pressreleases/TAILORxRelease. Accessed 26 Aug 2006.

S5
Pollack, A. F.D.A. seeks to regulate new types of diagnostic tests. 6 Sep 2006. New York Times.

S6
U.S. Food and Drug Administration. 5 Sep 2006. FDA Drafts Regulatory Guidance to Industry and Labs for Group of Medical Tests (FDA News). On the Internet: http://www.fda.gov/bbs/topics/NEWS/2006/NEW01445.html. Accessed 11 Sep 2006.