The National Comprehensive Cancer Network (NCCN) has updated its Clinical Practice Guidelines in Oncology for breast cancer to recognize that MammaPrint and BluePrint can help identify a specific subset of patients with hormone receptor–positive, HER2-negative early-stage breast cancer who are most likely to benefit from anthracycline-based chemotherapy.1,2
The guideline update was supported by the 3-year analysis of the prospective, real-world observational FLEX study (NCT03053193), which were presented at the 2025 San Antonio Breast Cancer Symposium.1,3 In the FLEX study analysis, at a median follow-up of 3.2 years, patients with MammaPrint High Risk 1 or High Risk 2 scores received either an adjuvant taxane with cyclophosphamide (n = 289 and n = 51, respectively) or anthracycline and taxane-based chemotherapy (n = 289 and n = 51, respectively). The results indicated that patients with High Risk 2 and BluePrint Luminal B disease derived the most benefit from anthracycline-based therapy. Those treated with a taxane plus cyclophosphamide had a significantly worse 3-year invasive disease–free survival (iDFS) rate of 89.3% (95% CI, 80.8%-98.7%), compared with 100% (95% CI, 100%-100%) for those treated with an anthracycline plus taxane-based chemotherapy, translating to an absolute benefit rate of 10.7% (HR, 0.16; 95% CI, 0.02-1.29; P = .048).
Additionally, patients with High Risk 1 and Luminal B disease did not derive meaningful benefit from the addition of anthracyclines. The 3-year iDFS rate was 95.6% (95% CI, 93.1%-98.1%) with an anthracycline plus taxane-based chemotherapy vs 94.6% (95% CI, 92.0%-97.3%) with a taxane plus cyclophosphamide (HR, 1.01; 95% CI, 0.57-1.80; P = .98).
Furthermore, a multivariate Cox regression analysis demonstrated that among patients with High Risk 1 disease, treatment with an anthracycline plus taxane-based chemotherapy was not associated with improved IDFS compared with a taxane plus cyclophosphamide (HR, 0.99; 95% CI, 0.52-1.67; P = .812).3 However, among patients with High Risk 2 disease, a trend toward improved outcomes with this regimen vs a taxane plus cyclophosphamide was observed, although this benefit was not statistically significant (HR, 0.18; 95% CI, 0.02-1.57; P = .12).
“I am delighted that oncologists finally have a way to identify [patients with] HR-positive/HER2-negative early breast cancer who will benefit from anthracycline therapy,” Joyce A. O’Shaughnessy, MD, principal investigator for the FLEX Study, as well as co-chair of Breast Cancer Research and chair of Breast Cancer Prevention Research at the Texas Oncology-Baylor Charles A. Sammons Cancer Center and The US Oncology Network in Dallas, stated in a news release.1 “The biologic rationale and the data underpinning the observation that [patients with] High Risk 2 Luminal (by BluePrint) breast cancer benefit from anthracycline therapy are quite strong.”
NCCN Guidelines Update: MammaPrint in Hormone Receptor–Positive, HER2-Negative Breast Cancer
- The NCCN Clinical Practice Guidelines have been updated to recognize MammaPrint and BluePrint as tools to identify specific patients with hormone receptor–positive, HER2-negative early-stage breast cancer who are most likely to benefit from anthracycline-based chemotherapy.
- Findings from the FLEX study demonstrated that patients with MammaPrint High Risk 2 and BluePrint Luminal B disease derived a significant clinical benefit from anthracycline-based regimens compared with those treated with a taxane plus cyclophosphamide.
- In contrast, patients classified with High Risk 1 and Luminal B disease did not experience a meaningful benefit from the addition of anthracyclines.
What was the design of the FLEX study in breast cancer?
The FLEX Study is a large-scale, real-world study that followed patients for a median of 3.2 years. Researchers used propensity score matching to balance differences in age, tumor size, and nodal status between the taxane/cyclophosphamide- and anthracycline/taxane-treated cohorts within the High Risk 1 and High Risk 2 groups. The study aimed to provide clear evidence to reduce uncertainty regarding the selection of optimal chemotherapy regimens by tailoring treatment to underlying tumor biology.
“The NCCN guideline update is based on the strongest real-world evidence to date that MammaPrint can help identify which patients are most likely to benefit from anthracycline-based therapy,” William Audeh, MD, MS, chief medical officer at Agendia, added in the news release. “This recent evidence from FLEX underscores the power of precision genomics to guide more effective, individualized care, and reinforces the value of large-scale, real-world-studies that speak directly to how treatments can be tailored to underlying tumor biology.”
References
- Agendia announces NCCN guideline update recognizing MammaPrint to guide personalized anthracycline use in HR+/HER2- early‑stage breast cancer. News release. Agendia, Inc. January 20, 2026. Accessed January 23, 2026. https://agendia.com/agendia-announces-nccn-guideline-update-recognizing-mammaprint-to-guide-personalized-anthracycline-use-in-hr-her2-early-stage-breast-cancer/
- NCCN. Clinical Practice Guidelines in Oncology. Breast cancer, version 1.2026. Accessed January 23, 2026. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf
- O’Shaughnessy J,Brufsky A, Graham CL, et al. Improved 3-year IDFS with anthracycline-based therapy for patients with 70-gene signature High 2, luminal B, HR+HER2- early-stage breast cancer. Presented at: 2025 San Antonio Breast Cancer Symposium. December 9-12, 2025. San Antonio, Texas. Abstract PS2-07-03.
