Details

Autor(en) / Beteiligte

• Pellicane, James V.
• Beitsch, Peter D.
• Rock, David T.
• Budway, Raye J.
• Dul, Carrie L.
• Kelemen, Pond R.
• Ashikari, Andrew Y.
• Baron, Paul L.
• Weinstein, Paul D.
• Mislowsky, Angela
• Lee, Laura A.
• Beatty, Jennifer
• Murray, Mary K.
• Dupree, Beth B.
• Finn, Christine
• Corcoran, Kate
• Wang, Shiyu
• Menicucci, Andrea R.
• Yoder, Erin B.
• Blumencranz, Lisa E.
• Dauer, Patricia
• Audeh, William
• Whitworth, Pat W.

Titel

Combined 70- and 80-gene signatures identify tumors with genomically luminal biology responsive to neoadjuvant endocrine therapy and are prognostic of 5-year outcome in early-stage breast cancer

Ist Teil von

• Surgical oncology, 2022-12, Vol.45, p.101885-101885, Article 101885

Ort / Verlag

Oxford: Elsevier Ltd

Erscheinungsjahr

2022

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• As more patients with early-stage breast cancer receive neoadjuvant endocrine therapy (NET), there is a need for reliable biomarkers that can identify patients with HR+ HER2- tumors who are likely to benefit from NET. NBRST (NCT01479101) compared the prognostic value of the 70-gene risk classification and 80-gene molecular subtyping signatures with conventional pathological classification methods in response to neoadjuvant therapy. We evaluated the association of these signatures with clinical response and 5-year outcome of patients treated with NET. 1091 patients with early-stage breast cancer scheduled to receive neoadjuvant therapy were prospectively enrolled into NBRST, and a sub-analysis of 67 patients treated with NET was performed. Patients received standard of care genomic testing using the 70-gene and 80-gene signatures and were treated with NET, per physician's discretion. The primary endpoint was pathologic partial response (pPR) and secondary endpoints were distant metastasis-free survival (DMFS) and overall survival (OS). Clinical benefit was defined as having a pPR or stable disease (SD) with NET. Overall, 94.4% of patients with genomically (g) Luminal A-Type (50.0% pPR and 44.4% SD) and 95.0% with Luminal B-Type tumors (55.0% pPR and 40.0% SD) exhibited clinical benefit. At 5 years, patients with gLuminal B tumors had significantly worse DMFS (75.6%, 95% CI 50.8–89.1) than patients with gLuminal A (91.1%; 95% CI 74.8–97.1; p = 0.047), with a similar trend for OS, albeit not significant (81.0%, 95% CI 56.9–92.4 and 91.1%, 95% CI 74.8–97.1, respectively; p = 0.13). Genomic assays offer a broader understanding of the underlying tumor biology, which adds precision to pathology as a preoperative risk classifier. Patients with 70-gene signature Low Risk, gLuminal A tumors treated with endocrine therapy alone have excellent 5-year outcomes. Most patients with genomically-defined Luminal A- and B-Type tumors respond well to NET, suggesting these patients may be safely treated with NET, while those with gLuminal B tumors will also require post-operative chemotherapy or CDK4/6 inhibitors to improve long-term outcomes. Overall, these findings demonstrate that genomic classification, defined by the combined 70- and 80-gene signatures, is associated with tumor response and prognostic of long-term outcomes. •MammaPrint and BluePrint are prognostic for patients treated with NET.•BluePrint Luminal tumors respond well to NET and may safely delay surgery.•MammaPrint Low Risk tumors have excellent 5-year outcomes with NET.•MammaPrint High Risk, Luminal B tumors would benefit from adjuvant chemotherapy.•Genomic stratification adds precision to IHC and better corresponds with outcomes.