21-Gene recurrence score and locoregional recurrence in lymph node-negative, estrogen receptor-positive breast cancer

Breast Cancer Res Treat. 2017 Nov;166(1):69-76. doi: 10.1007/s10549-017-4381-7. Epub 2017 Jul 12.

Abstract

Background/purpose: The 21-gene recurrence score (RS) assay evaluates the likelihood of distant recurrence and benefit of chemotherapy in lymph node-negative, estrogen receptor (ER)-positive, HER2-negative breast cancer patients. The RS categories are associated with the risk of locoregional recurrence (LRR) in some, but not all studies.

Methods: We reviewed the institutional database to identify consecutive female patients with node-negative, ER+/HER2- breast carcinoma tested for the 21-gene RS assay and treated at our center from 2008 to 2013. We collected data on clinicopathologic features, treatment, and outcome. Statistical analysis was performed using SAS version 9.4 or R version 3.3.2.

Results: Of 2326 patients, 60% (1394) were in the low RS group, 33.4% (777) in the intermediate RS group, and 6.6% (155) in the high RS group. Median follow-up was 53 months. A total of 44 LRRs were observed, with a cumulative incidence of 0.17% at 12 months and 1.6% at 48 months. The cumulative incidence of LRR at 48 months was 0.84%, 2.72% and 2.80% for low, intermediate, and high RS groups, respectively (p < 0.01). Univariate analysis showed that the risk of LRR was associated with the RS categories (p < 0.01), T stage (p < 0.01) and lymphovascular invasion (LVI) (p = 0.009). There was no difference in LRR rates by initial local treatment (total mastectomy vs. breast-conserving surgery plus radiation therapy). The RS remained significantly associated with LRR after adjusting for LVI and T stage. Compared to patients with low RS, the risk of LRR was increased more than 4-fold (hazard ratio: 4.61, 95% CI 1.90-11.19, p < 0.01), and 3-fold (hazard ratio: 2.81, 95% CI 1.41-5.56, p < 0.01) for high and intermediate risk categories, respectively.

Conclusions: Our study confirms that RS is significantly associated with the risk of LRR in node-negative, ER+/HER2- breast cancer patients. Our findings suggest that in addition to its value for prognostic stage grouping and decision-making regarding adjuvant systemic therapy, the role of the RS in identifying patients not requiring radiotherapy should be studied.

Keywords: 21-Gene recurrence score assay; Breast cancer; Locoregional recurrence; Recurrence score.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / therapy
  • Combined Modality Therapy
  • Computational Biology / methods
  • Female
  • Gene Expression Profiling
  • Humans
  • Incidence
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Prognosis
  • Receptors, Estrogen / genetics*
  • Receptors, Estrogen / metabolism
  • Transcriptome*
  • Treatment Outcome
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Receptors, Estrogen