Individualized Therapy and OncoType DX By Musa Mayer A very important validation study and accompanying editorial appear today (free full text in PDF format) on the website of the New England Journal of Medicine. In this study, the OncoTypeDX multigene test, created by Genomic Health, has been shown to accurately predict recurrence rates in a large group of women with node-negative, invasive primary breast cancers whose tumors are ER+ and/pr Pgr+ a group representing as many as 50% of all patients. Earlier studies had already characterized certain patterns, or algorithms, in the expression of 21 genes that could be associated with low, medium or high risk of recurrence in ER+ and/or PgR+ breast cancer treated with tamoxifen. For this method of testing, a technique is used called RT-PCR, which permits analysis of RNA samples taken from paraffin-embedded tumor blocks of the kind that are commonly used for cancer patients. To accomplish this validation study, researchers studied 675 archived tumor specimens from patients treated with tamoxifen in the B-14 study, a large randomized trial from the cooperative oncology research group, NSABP. The B-14 trial had already been completed and the outcomes in terms of recurrences and survival were known. Researchers who were "blinded" regarding the outcome of patients in the trial, were able to use the OncoTypeDX test to predict recurrence scores with a degree of accuracy greater than existing methods, such as patient age, tumor size and tumor grade. A numerical "Recurrence Score," was used to assign patients to low and high risk groups, and turned out to be a strong independent predictor of recurrence. This represents the first large-scale, multicenter validation of a multi-gene assay. Researchers estimate that as many as 50% of patients will be reclassified from low risk to high risk, or from higher risk to low risk, using this test. According to Steve Shak, the chief medical officer of Genomic Health, their test has now been evaluated in about 2,600 patients, including those in this validation study, with consistent results. To read the study and editorial in the New England Journal, look for the "Early Release" red flag at the top of the home page at http://content.nejm.org/ ORIGINAL ARTICLE: A Multigene Assay to Predict Recurrence of Tamoxifen-Treated, Node-Negative Breast Cancer EDITORIAL: Individualized Care for Patients with Cancer ­ A Work in Progress I would suggest reading the editorial first, then the study. You will be hearing a lot about this test tonight in the news media, but this is actually not because of this validation study alone--which was presented last year in San Antonio and at ASCO in June. The news today comes from both additional validation data and additional uses for this test. This morning, at the San Antonio Breast Cancer Symposium, Dr. Soonmyung Paik, also the principle investigator in the NEJM validation study, presented new data to demonstrate that OnctoTypeDX has been able not only to accurately predict recurrence, but also to identify which patients will respond to chemotherapy and to a lesser extend, hormonal therapy. These new data come from an analysis of tissue samples from the NSABP B-20 study of 651 patients randomized to get either tamoxifen alone, or tamoxifen plus CMF chemotherapy. This study demonstrates that patients with the highest Recurrence Scores on OncoTypeDX had a large absolute benefit from chemotherapy (absolute distant disease-free survival of 27.6%) , while patients with the lowest Recurrence Scores derived no benefit from chemotherapy (absolute distant disease-free survival of -1.1%). In addition, an analysis of 645 patients in the B-14 study who were randomized to get tamoxifen only or placebo, found that not all patients with ER+ tumors benefited equally from tamoxifen. The largest benefits from tamoxifen were found in patients with high ER expression and low Recurrence Scores. "Our study discloses that the same 21-gene panel that we demonstrated could quantify breast cancer recurrence, can also predict response to chemotherapy," according to Dr. Norman Wolmark, chair of the NSABP. Oncologists have long known that they are overtreating some patients and undertreating others, but have had no very good way to discriminate between patients--hence the prescription for offering chemotherapy to all patients with tumors over 1 cm. So, the results of this study confirms and quantifies what oncologists have long observed, that high-risk breast cancer patients seem to benefit more from chemotherapy than low-risk patients, but it also identifies those patients at lowest risk. Two other studies presented in San Antonio about OncoTypeDX found that the test performed better in predicting recurrence than two important guideline sets, from NCCN and St. Gallen; and that in a large case-control population-based study from Kaiser Permanente, in a representative sample of all breast cancer patients diagnosed at 14 Northern California hospitals between1985-94, the test accurately identified patients at low and high risk for recurrence and death. Advocates here at the San Antonio meeting are of course excited at the idea that this test may spare a very sizable number of patients the toxicities of chemotherapy, not to mention sparing society the costs. We're also pleased that we may be able to really locate the high-risk patients who are likeliest to benefit from very aggressive chemo protocols. There are, of course, many implications to this test, having to do with cost effectiveness (current cost is $3,640), impact on oncology practice, insurance and Medicare reimbursement, etc.. Is it ready for "prime time" now, to become a standard part of clinical care? Will these test results be clinically relevant for patients, and truly help them decide on treatment--especially, will lower risk patients who stand to gain smaller benefits be able to refuse chemotherapy? How can this test be improved, to apply to other groups of patients, and predict for response to other forms of treatment? Will the data be updated, to reflect current standards of care and choices that women must make today? Will these test results be used to deny patients choice by insurers? At the press briefing after the presentation today, which was attended by many top research oncologists and department heads like Larry Norton, Cliff Hudis, Eric Winer, Kathy Albain and others, earlier cautions seem to have been replaced by a growing respect for the very consistent data and the thoughtful process by which this assay has been validated and revalidated. I think we are seeing the beginnings of something very revolutionary in breast cancer treatment--truly individualized treatment, based on the biology of the tumor. All in all, a VERY interesting day... Musa Ann's NOTE: This strikes to the heart of a major issue in cancer treatment. We KNOW going in that only a small percentage of people will respond to chemotherapy. But we have never KNOWN who as an individual. This test and similar ones that are sure to be under development, may really be able to change that. Having to undergo chemotherapy when there is no benefit means that one experiences the unwanted effects (and we all know they are HUGE and awful) for no reason. Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.