August 2021: Utility of the CPS + EG scoring system in TNBC patients treated with neoadjuvant chemotherapy

Neoadjuvant chemotherapy offers the unique opportunity to directly monitor response to therapy in primary breast cancer. Post-neoadjuvant treatment strategies make use of the response evaluation after neoadjuvant chemotherapy to only select patients without a pathological complete response (pCR) who are at high-risk of recurrence for treatment escalation.

In luminal breast cancer, where the association between pCR and survival is less pronounced compared to other subtypes (von Minckwitz et al. J Clin Oncol 2012; Cortazar et al. Lancet 2014), a score based on pre-treatment clinical stage (CS) post-treatment pathologic stage (PS), estrogen receptor status (E) and grade (G), the CPS+EG score, leads to a refined estimate of prognosis after neoadjuvant chemotherapy in all-comers and hormone receptor-positive/HER2-negative patients. The CPS+EG score thus provides additional prognostic information beyond clinical and pathologic stage alone in this cohort (Marmé et al Eur J Cancer 2016) and was recently successfully used to select patients with luminal breast cancer for the Penelope-B trial (Loibl et al. J Clin Oncol 2021).

Since the performance of the CPS+EG score has not been evaluated in triple-negative breast cancer (TNBC) patients, this study was designed to investigate the potential of the CPS+EG score to refine prognostic estimation specifically in TNBC beyond pCR. With respect to post-neoadjuvant treatment strategies, the primary question was if the CPS+EG score would be able to identify patients with a favorable prognosis despite not having a pCR, who might forgo post-neoadjuvant treatment escalation and vice versa patients with a detrimental prognosis despite a pCR that might warrant additional therapies.

The CPS+EG score was calculated for 1795 patients with TNBC from eight prospective German trials. Patients could obtain scores between 1 and 6 receiving points for each fulfilled category as previously described (Mittendorf et al. J Clin Oncol 2011; Jeruss et al. J Clin Oncol 2008). Median age was 48 (21-75) years and the median follow-up time was 63.6 (62.3-64.8) months. The pCR rate (ypT0is ypN0) was 45.8% and the estimated 5-year disease-free survival (DFS) and overall survival (OS) rates were 68.2% (95% CI, 65.8%–70.6%) and 77.2% (95% CI, 75.0%–79.4%), respectively. Patients with pCR had a 5-year DFS of 86%, whereas patients with residual AJCC-stage I (n=383; 21.3%) had a 5-year DFS of 77.5%. CPS+EG led to superior prognostic information compared to clinical stage but was inferior to the prognostic information provided by pathologic stage (c-index statistics p<0.001). CPS+EG did not discriminate prognosis within the two best prognostic groups (score 1 and 2; n=362; 37.2%). In contrast, pCR status added prognostic information beyond CPS+EG. Patients with a CPS+EG score of 3 had a 5-year DFS rate of 64% overall, those with pCR had a 5-year DFS rate of 84%, and those without pCR had a 5-year DFS rate of only 49.7%.

In conclusion, in TNBC CPS+EG scoring provided inferior prognostic information compared to pathological stage and was unable to identify non-pCR patients with a sufficiently good prognosis, to avoid post-neoadjuvant therapy. pCR remains the strongest and most clinically useful prognostic factor after neoadjuvant chemotherapy. This analysis is the first to specifically address the clinical usefulness of the CPS+EG score in TNBC and is based on a large series of patients treated in prospective randomized trials.

Marmé F, Solbach C, Michel L, et al. Utility of the CPS + EG scoring system in triple-negative breast cancer treated with neoadjuvant chemotherapy. Eur J Cancer. 2021; 153:203-212.

• PubMed Link https://pubmed.ncbi.nlm.nih.gov/34186505/