Early-stage TNBC

Early-stage TNBC: overview

This algorithm covers early-stage triple-negative breast cancer and branches first on tumor size and nodal status, then on pathologic response after neoadjuvant therapy.

For tumors under 2 cm and node negative, surgery comes first. Tumors under 1 cm (T1a) may be observed or treated with chemotherapy, while tumors 1 to 2 cm receive chemotherapy after surgery. For tumors 2 cm or larger or node-positive disease, the preferred high-risk approach is neoadjuvant paclitaxel plus carboplatin (TC) then AC, with pembrolizumab throughout, supported by KEYNOTE-522, which improved pathologic complete response and event-free survival in stage II to III TNBC regardless of PD-L1 status. After surgery, patients with a pathologic complete response continue pembrolizumab. Patients with residual disease continue pembrolizumab and add capecitabine if BRCA wild type (KEYNOTE-522, CREATE-X) or olaparib if they carry a germline BRCA mutation (KEYNOTE-522, OlympiA). CREATE-X showed improved disease-free and overall survival with adjuvant capecitabine for residual disease, and OlympiA showed improved invasive disease-free and overall survival with 1 year of olaparib.

Step by step

• Under 1 cm, node negative: surgery, then observation (T1a) or chemotherapy.
• 1 to 2 cm, node negative: surgery, then chemotherapy.
• 2 cm or larger or node positive: neoadjuvant paclitaxel plus carboplatin (TC) then AC, with pembrolizumab, then surgery (KEYNOTE-522).
• Pathologic complete response: continue pembrolizumab (KEYNOTE-522).
• Residual disease, BRCA wild type: pembrolizumab plus capecitabine (KEYNOTE-522, CREATE-X).
• Residual disease, germline BRCA: pembrolizumab plus olaparib (KEYNOTE-522, OlympiA).

Trials behind this algorithm

• KEYNOTE-522 Schmid P et al, NEJM, 2022; PMID: 35139274
• CREATE-X Masuda N et al, NEJM, 2017; PMID: 28564564
• OlympiA Tutt AN et al, NEJM, 2021; PMID: 34081848

Background reading: Breast Cancer (Part 2): DCIS, Early-Stage and Metastatic Treatment board review notes.