MammaPrint Scoring and Indolent Node-Negative Breast Cancer

Key Points

  • A MammaPrint ultralow risk was associated with 20-year breast cancer–specific survival of 97% in tamoxifen patients and 94% in those receiving no treatment.
  • Those with a MammaPrint low or high risk had a 4.5-fold greater risk of breast cancer mortality at 20 years.

In an analysis reported in JAMA Oncology, Esserman et al found that an ultralow-risk designation using the 70-gene MammaPrint assay is capable of identifying patients with node-negative disease who have a very low long-term risk of death from breast cancer after surgery without systemic therapy.

Breast cancer screening has contributed to a reduction in the risk of breast cancer mortality. However, there is evidence that screening contributes disproportionately to the diagnosis of biologically indolent forms of disease, with increasing diagnosis of low-risk disease being associated with an increased risk of overtreatment.

Study Details

In a previous study, the investigators identified a MammaPrint score threshold below which no breast cancer deaths in women with node-negative disease were observed at 15 years with no systemic therapy in a series of patients with 25-year follow-up.

The current analysis involved postmenopausal women with clinically detected node-negative tumors ≤ 3 cm randomized to receive tamoxifen vs no adjuvant therapy after mastectomy or lumpectomy and radiation who were enrolled in the Stockholm tamoxifen (STO-3) trial between 1976 and 1990 (ie, before the screening era). In the trial, patients received 2 years of tamoxifen or no systemic therapy regardless of hormone receptor status; those without relapse were eligible to reconsent to further randomization to 3 additional years of tamoxifen or no further treatment. MammaPrint risk scoring was performed using formalin-fixed paraffin-embedded primary tumor blocks. Risk thresholds for the 70-gene assay were ultralow (≥ 0.355), low but not ultralow (> 0, < 0.355), and high risk (< 0).

Identification of Low Long-Term Risk

Among 652 women with MammaPrint scoring available (median age = 62.8 years of age), the MammaPrint risk level was high for 275 (42%), low for 377 (58%), and ultralow for 98 (15%). At 20 years, compared with women at ultralow risk, those at high risk (hazard ratio [HR] = 4.73, 95% confidence interval [CI] = 1.38–16.22) and those at low risk (HR = 4.54, 95% CI = 1.40–14.80) had an increased risk of breast cancer mortality. In the ultralow-risk group, no breast cancer deaths had occurred among tamoxifen recipients at 15 years. At 20 years, breast cancer–specific survival in the ultralow-risk group was 97% among tamoxifen recipients and 94% among those receiving no treatment.

Additional analysis indicated that MammaPrint ultralow risk was the most significant predictor of good outcome. For tumors in other risk categories, tumor size > 2 cm was the most significant predictor of poorer outcome.

The investigators concluded: “The ultralow-risk threshold of the 70-gene MammaPrint assay can identify patients whose long-term systemic risk of death from breast cancer after surgery alone is exceedingly low.”

The study was supported by the California Breast Cancer Research Program, the Swedish Research Council, the Gösta Milton Donation Fund, and the Breast Cancer Research Foundation.

Laura J. Esserman, MD, MBA, of Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, is the corresponding author of the JAMA Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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