SAN ANTONIO — The Oncotype DX 21-gene recurrence score assay can identify a sizeable subgroup of postmenopausal women with node-positive, estrogen receptor–positive breast cancer who are at such low risk of recurrence that they are unlikely to benefit from adding chemotherapy to 5 years of adjuvant tamoxifen, a study showed.
The 21-gene test is already widely ordered to help physicians select breast cancer patients with axillary node–negative disease who need adjuvant chemotherapy, an application endorsed in American Society of Clinical Oncology guidelines since 2007 (J. Clin. Oncol. 2007;25:5287–312).
The new study is the first to show that the test is also prognostic for patients with positive lymph nodes, Dr. Kathy S. Albain noted in presenting the results at the San Antonio Breast Cancer Symposium.
Such patients now routinely receive adjuvant chemotherapy as standard practice. The new study challenges that approach by demonstrating that patients with a low 21-gene recurrence score—irrespective of their number of positive nodes—appear able to safely forego chemotherapy, with its toxicities and other costs, said Dr. Albain, professor of medicine at Loyola University, Maywood, Ill.
Conversely, patients with a high recurrence score on Oncotype DX showed marked clinical benefit from subsequent adjuvant chemotherapy in this new retrospective analysis of prospectively collected data from the phase III Southwest Oncology Group (SWOG)-8814 study.
Dr. Albain reported on 367 participants in SWOG-8814, all of whom were postmenopausal with node-positive, estrogen receptor–positive disease. This analysis included the 148 women randomized to 5 years of adjuvant tamoxifen and the 219 assigned to chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil followed by tamoxifen (CAF-T) whose stored tumor specimens contained sufficient RNA for analysis using Oncotype DX.
Of the 367 women in the study, 40% were at low risk, with a recurrence score of less than 18. In this group, CAF-T offered no advantage over the 60% 10-year disease-free survival rate among the patients who were assigned to tamoxifen alone (hazard ratio 1.02). Nor did CAF-T provide significant benefit over the 49% 10-year disease-free survival with tamoxifen alone in patients who had an intermediate recurrence score of 18–30 (HR 0.72).
In contrast, in the 32% of subjects who had a recurrence score of 31 or more, the 10-year disease-free survival rate was 55% with CAF-T, significantly greater than the 43% rate with tamoxifen alone (HR 0.59).
The same trends were seen in terms of 10-year overall survival: no significant advantage for the addition of adjuvant chemotherapy in patients with a low or intermediate recurrence score, but pronounced benefit in the high-score subgroup (68% in the CAF-T group vs. 51% in the tamoxifen alone group).
Similarly, 10-year breast cancer–specific survival in women with a high recurrence score was 73% in the CAF-T group and 54% with tamoxifen alone, but didn't differ according to the assigned adjuvant regimen in patients with low or intermediate recurrence scores.
Larger prospective randomized studies using state-of-the-art chemotherapy and aromatase inhibitors are needed to definitely establish the prognostic role of Oncotype DX and other multigene assays, according to Dr. Albain.
Dr. Eric P. Winer said the SWOG-8814 analysis, while retrospective and involving a relatively small number of patients, is reassuringly consistent with other study findings.
“I personally think that for the vast majority of patients who have a low recurrence score—even those who have larger tumors and positive lymph nodes—the benefit of chemotherapy is likely to be extremely small,” Dr. Winer said at a subsequent satellite continuing medical education symposium supported by AstraZeneca, Genentech, and Genomic Health.
“That being said, faced with a 55-year-old woman who has a 6-cm cancer and nine positive lymph nodes, in late 2009 I still find it difficult not to use chemotherapy,” admitted Dr. Winer, chief of the division of women's cancers at the Dana-Farber Cancer Institute and professor of medicine at Harvard University, both in Boston.
Dr. Joyce O'Shaughnessy said she orders the Oncotype DX assay selectively, mainly for confirmation in women she's already disinclined to treat with adjuvant chemotherapy. “I like to handpick the patients. The patient who is over age 60, with an estrogen receptor/progesterone receptor–positive, HER2-negative tumor that is slowly proliferative—that's somebody I'd be comfortable ordering the recurrence score for, and if it were low I'd be comfortable just going with endocrine therapy,” explained Dr. O'Shaughnessy of US Oncology, Dallas.
The SWOG-8814 analysis was funded by the National Cancer Institute and Genomic Health, which markets the Oncotype DX test. Dr. Albain disclosed serving on the speakers bureau for Genomic Health, as well as receiving research funding from the company.
Simultaneous with her San Antonio presentation, the study results were published online in Lancet Oncology (doi:10.1016/S1470-2045(09)70314-6