[Skip to Content]
[Skip to Content Landing]
Views 3,285
Citations 0
Original Investigation
January 9, 2020

Association Between 21-Gene Assay Recurrence Score and Locoregional Recurrence Rates in Patients With Node-Positive Breast Cancer

Author Affiliations
  • 1Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston
  • 2Cancer Research and Biostatics, Seattle, Washington
  • 3Department of Radiation Oncology, University of Michigan, Ann Arbor
  • 4Department of Pathology, Genomic Health Inc, Redwood City, California
  • 5Department of Pathology, University of California San Francisco, San Francisco
  • 6Department of Medicine, McMaster University, Hamilton, Ontario, Canada
  • 7Division of Medical Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania
  • 8Division of Medical Oncology, Fred Hutchinson Cancer Research Center, Seattle, Washington
  • 9Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester, Minnesota
  • 10Department of Surgery, Dana-Farber Cancer Institute, Boston, Massachusetts
  • 11Department of Medicine, Cancer Therapy & Research Center, University of Texas Health Science Center, San Antonio
  • 12Department of Medicine, Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, Texas
  • 13Department of Breast Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston
  • 14Department of Medicine, Division of Hematology and Oncology, University of Arizona, Tucson
  • 15Department of Medicine, Division of Oncology, University of Washington/Seattle Cancer Care Alliance, Seattle
  • 16Department of Breast Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston
  • 17Department of Internal Medicine, University of Michigan, Ann Arbor
  • 18Department of Medicine, Division of Hematology/Oncology, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois
JAMA Oncol. Published online January 9, 2020. doi:10.1001/jamaoncol.2019.5559
Key Points

Question  Does an association exist between the 21-gene expression assay recurrence score and locoregional recurrence in postmenopausal women with a node-positive, estrogen receptor– or progesterone receptor–positive breast cancer treated with either adjuvant chemotherapy followed by tamoxifen or tamoxifen alone?

Findings  In this cohort study of 316 women with breast cancer who were participants in the Southwest Oncology Group S8814 randomized clinical trial, an intermediate or high recurrence score was associated with a significantly increased risk of locoregional recurrence; the same results were found in a subset of this cohort who underwent a mastectomy without radiotherapy.

Meaning  These findings suggest that the recurrence score may provide valuable prognostic information on locoregional recurrence that may aid in decision-making about radiotherapy for postmenopausal women with breast cancer.


Importance  The 21-gene assay recurrence score is increasingly used to personalize treatment recommendations for systemic therapy in postmenopausal women with estrogen receptor (ER)– or progesterone receptor (PR)–positive, node-positive breast cancer; however, the relevance of the 21-gene assay to radiotherapy decisions remains uncertain.

Objective  To examine the association between recurrence score and locoregional recurrence (LRR) in a postmenopausal patient population treated with adjuvant chemotherapy followed by tamoxifen or tamoxifen alone.

Design, Setting, and Participants  This cohort study was a retrospective analysis of the Southwest Oncology Group S8814, a phase 3 randomized clinical trial of postmenopausal women with ER/PR-positive, node-positive breast cancer treated with tamoxifen alone, chemotherapy followed by tamoxifen, or concurrent tamoxifen and chemotherapy. Patients at North American clinical centers were enrolled from June 1989 to July 1995. Medical records from patients with recurrence score information were reviewed for LRR and radiotherapy use. Primary analysis included 316 patients and excluded 37 who received both mastectomy and radiotherapy, 9 who received breast-conserving surgery without documented radiotherapy, and 5 with unknown surgical type. All analyses were performed from January 22, 2016, to August 9, 2019.

Main Outcomes and Measures  The LRR was defined as a recurrence in the breast; chest wall; or axillary, infraclavicular, supraclavicular, or internal mammary lymph nodes. Time to LRR was tested with log-rank tests and Cox proportional hazards regression for multivariate models.

Results  The final cohort of this study comprised 316 women with a mean (range) age of 60.4 (44-81) years. Median (interquartile range) follow-up for those without LRR was 8.7 (7.0-10.2) years. Seven LRR events (5.8%) among 121 patients with low recurrence score and 27 LRR events (13.8%) among 195 patients with intermediate or high recurrence score occurred. The estimated 10-year cumulative incidence rates were 9.7% for those with a low recurrence score and 16.5% for the group with intermediate or high recurrence score (P = .02). Among patients who had a mastectomy without radiotherapy (n = 252), the differences in the 10-year actuarial LRR rates remained significant: 7.7 % for the low recurrence score group vs 16.8% for the intermediate or high recurrence score group (P = .03). A multivariable model controlling for randomized treatment, number of positive nodes, and surgical type showed that a higher recurrence score was prognostic for LRR (hazard ratio [HR], 2.36; 95% CI, 1.02-5.45; P = .04). In a subset analysis of patients with a mastectomy and 1 to 3 involved nodes who did not receive radiation therapy, the group with a low recurrence score had a 1.5% rate of LRR, whereas the group with an intermediate or high recurrence score had a 11.1% LRR (P = .051).

Conclusions and Relevance  This study found that higher recurrence scores were associated with increased LRR after adjustment for treatment, type of surgical procedure, and number of positive nodes. This finding suggests that the recurrence score may be used, along with accepted clinical variables, to assess the risk of LRR during radiotherapy decision-making.

Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words