What is Mammaprint?

MammaPrint: A Gene Expression Profiling Test for Breast Cancer

MammaPrint is a 70-gene signature test that stratifies early-stage breast cancer patients into low and high risk of distant recurrence, providing valuable prognostic information to complement pathology assessment and predict the benefit of adjuvant chemotherapy. 1

Overview and Technical Details

• MammaPrint analyzes the expression of 70 genes to predict the risk of cancer recurrence in patients with early-stage breast cancer 2
• It was cleared by the U.S. Food and Drug Administration (FDA) in 2007 for use as a prognostic test to be used along with other clinicopathologic factors 1
• MammaPrint is intended for women 61 years of age or younger with primary invasive (Stage I or II) breast cancer who are lymph node-negative and have a tumor ≤5 cm, regardless of estrogen receptor (ER) status (positive or negative) 1
• Results are reported as either low risk ("13% chance to develop distant metastases at 10 years without adjuvant treatment") or high risk ("56% chance to develop distant metastases at 10 years without adjuvant treatment") 1

Clinical Applications and Evidence

• MammaPrint has achieved a Level of Evidence (LoE) and Grade of Recommendation (GoR) of [I, A] through the prospective MINDACT trial for its prognostic value and clinical utility in chemotherapy decision making 1
• It is the only gene expression test designed for both ER-positive and ER-negative early breast cancer, while other tests (Oncotype DX, Prosigna, Endopredict, Breast Cancer Index) were designed primarily for ER-positive disease 1
• The test can identify patients with an ultra-low risk of death from breast cancer at 10 or 20 years 1
• Further stratification of MammaPrint risk results identifies four risk subgroups: ultra-low, low, high 1, and high 2, each with specific prognostic and predictive outcomes 2

Clinical Utility and Decision Making

• MammaPrint helps determine which patients might benefit from adjuvant chemotherapy versus those who can safely avoid it 3
• The MINDACT trial demonstrated that women with clinically high-risk but genomically low-risk results on MammaPrint could potentially avoid chemotherapy 1
• The test has been shown to be cost-effective, with the OPTIMA Prelim Trial showing an 86% probability of molecular tests being cost-effective 1
• MammaPrint has demonstrated significant prognostic performance at both 5 and 10 years of follow-up 4

Special Considerations for Different Breast Cancer Types

• MammaPrint has shown independent prognostic value for patients with early-stage invasive lobular breast cancer (ILC), with hazard ratios up to 11 in multivariate analyses for lymph node-negative ILC breast cancers 5
• The test captures all 10 hallmarks of cancer in early breast cancer patients, reflecting important biological processes that might guide treatment decisions 2

Limitations and Practical Considerations

• The MammaPrint report states that "its performance characteristics and clinical utility in the United States Population have not been established" 1
• The test requires adequate tissue sampling and RNA quality; in some studies, up to 45% of samples have failed quality control after RNA extraction 4
• Unlike some other tests, MammaPrint is not intended "to predict or detect response to therapy, or to help select the optimal therapy for patients" according to FDA clearance 1
• The test can be performed on both fresh and formalin-fixed paraffin-embedded (FFPE) tissue samples, with an excellent correlation of 0.93 between the two tissue types 6

MammaPrint offers valuable prognostic information for early-stage breast cancer patients and has been validated in multiple clinical trials. When considering its use, clinicians should evaluate the patient's specific clinical characteristics and understand that the test is meant to complement, not replace, traditional clinicopathologic risk assessment.