A high CD8 to FOXP3 ratio in the tumor stroma and expression of PTEN in tumor cells are associated with improved survival in non-metastatic triple-negative breast carcinoma.

BACKGROUND: Triple-negative mammary carcinoma (TNBC) is an aggressive breast cancer subtype associated with dismal prognosis. The interaction between the immune system and the cancer cells plays a crucial role in tumor development and progression. However, it is still unclear how each diverse cell of the immune system contributes to the prognosis of patients with breast cancer. In this study, we investigated how the cell composition of the immune cell infiltrated modifies the survival of patients with resected TNBC. METHODS: Retrospectively, we collected data from 76 patients diagnosed with non-metastatic TNBC with available tissue blocks for tissue micro-array (TMA) construction. The TMA was constructed using two cores from each tumor block. The expression of CD4, CD8, FOXP3, CD20, CD68, CD163, PD-1, PD-L1, PTEN and phospho-STAT1 was determined by immunohistochemistry. RESULTS: We observed that the inflammatory infiltrate in TNBC is enriched for M2 macrophages and T lymphocytes (CD4+, CD8+). PD-L1 expression in the stroma was associated with the percentage of TILs (p = 0.018) as, PD-L1 expression in the tumor was associated with the percentage of TILs (p = 0.049). We found a correlation between TILs and PD-L1 expression in stroma cells (p = 0.020) and in tumor cells (p = 0.027). In our cohort, we observed a trend for improved survival associated with higher CD8+ (p = 0.054) and CD4 + (p = 0.082) cell counts, but the results were not statistically significant. Conversely, the expression of PTEN in tumor cells and a low number of FOXP3+ cells in tumor stroma were both associated with improved OS. The CD8 to FOXP3 ratio and the CD4 to FOXP3 ratio were associated with better OS as well, however, only the CD8 to FOXP3 ratio had its prognostic impact confirmed in the METABRIC TNBC cohort. There was no association between PD-L1 expression and OS. CONCLUSION: TNBC tumor microenvironment is enriched for lymphocytes and macrophages. FOXP3 expression and the CD8 to FOXP3 ratio in the tumor stroma as well as the loss of PTEN expression in tumor cells are prognostic factors in non-metastatic TNBC.

Prognostic value of response evaluation based on breast MRI after neoadjuvant treatment: a retrospective cohort study.

OBJECTIVE: To investigate the impact of response evaluation after neoadjuvant chemotherapy (NAC) in breast cancer patients, assessed by both magnetic resonance imaging (MRI) and pathology, on disease-free survival (DFS). METHODS: This single-center, retrospective cohort study included consecutive breast cancer patients who underwent NAC and preoperative breast MRI. Resolution of invasive carcinoma in the breast and axilla was defined as complete pathological response (pCR). Radiological complete response (rCR) was defined as the absence of abnormal enhancement in the tumor site. Kaplan-Meier estimator was used to estimate the disease-free survival on 60 months. Cox regression analysis was used to estimate hazard ratio (HR) values. RESULTS: In total, 317 patients were included with a mean age of 47.3 years and a mean tumor size of 39.8 mm. The most common immunophenotype was luminal (44.9%), followed by triple-negative (26.8%). Overall, 126 patients (39.7%) had an rCR, while 119 (37.5%) had pCR; the radiological and pathological responses agreed in 252 cases (79.5%). During follow-up, patients who had rCR and pCR had a better DFS curve compared to patients with non-rCR and non-pCR, while those who had rCR or pCR presented an intermediate curve (Log-rank p = 0.003). Multivariate analysis showed a higher risk of recurrence in patients with non-rCR and non-pCR (HR: 5,626; p = 0.020) and those who had a complete response on MRI or pathology only (HR: 4,369; p = 0.067), when compared to patients with rCR and pCR. CONCLUSIONS: The association of MRI and pathological responses after NAC might better stratify the risk of recurrence and prognosis in breast cancer patients. KEY POINTS: • Association of response evaluation after neoadjuvant chemotherapy by pathology and MRI allows better stratification of prognosis. • Complete response to neoadjuvant chemotherapy on pathology and MRI was related to better disease-free survival. • Complete response on MRI or pathology only had a greater risk of recurrence.