According to the World Health Organization, breast cancer has become the most common cancer worldwide, accounting for 12% of new cases. Clinical classification still relies largely on the TNM system (tumor size, nodal involvement, metastases), a major limitation of which is that it does not take into account the patient's antitumor immune response. Yet patients with identical TNM stages can experience markedly different outcomes following neoadjuvant chemotherapy. The presence of tumor-infiltrating lymphocytes (TILs) has long been recognized as a favorable prognostic factor, particularly in triple-negative breast cancer (TNBC). It is in this context that the authors evaluated the prognostic value of the Immunoscore for Clinical Research (ISCR), an objective, computer-assisted digital method. Derived from the Immunoscore validated in localized colon cancer, this tool quantifies the densities of CD3+ cells (total T lymphocytes) and CD8+ cells (cytotoxic T lymphocytes) both in the tumor center (CT) and in its invasive margin (IM), yielding a five-level classification (0 to 4).
The study included 103 patients with early-stage breast cancer treated with neoadjuvant chemotherapy: 53 triple-negative cases, 32 luminal cases, and 18 HER2-positive cases. Pretreatment tumor biopsies underwent immunostaining of CD3+ and CD8+ cells, followed by quantitative analysis using computer-assisted imaging according to their location within the tumor. The endpoint was pathological complete response (pCR) after chemotherapy.
The pathological complete response rate was 44%. In univariate analysis, several variables were found to be associated with a high pCR: tumor size, estrogen and progesterone receptor negativity, molecular subtype, high Ki-67, as well as high CD3+ and CD8+ densities both in the tumor center and in the margin. The ISCR was also associated with pCR, with a linear relationship between score and response. The negative predictive value of the ISCR (60.4% positive predictive value and 92.6% negative predictive value for scores 0-1 versus 2-3-4) proved numerically superior to that of the cell densities considered individually. The authors emphasize that this is, to their knowledge, the first study distinguishing tumor center and margin to analyze the influence of TILs on prognosis after neoadjuvant chemotherapy in early breast cancer, suggesting that the spatial distribution of lymphocytes matters more than their mere presence.
This work thus highlights a significant prognostic role of the spatial distribution of CD3+ and CD8+ lymphocytes, as well as of the ISCR, with respect to pathological complete response. The authors acknowledge, however, several limitations—small sample size, insufficient statistical power, patient selection, and the retrospective nature of the data—and call for adequately powered prospective studies to confirm these observations.