The following article is part of conference coverage from the 17th St. Gallen International Breast Cancer Symposium, which is being held virtually from March 7-21, 2021. The team at Cancer Therapy Advisor will be reporting on the latest research conducted by leading experts in breast cancer. Check back for more from the 17th St. Gallen International Breast Cancer Symposium.

The presence of FOXP3 expression on tumor-infiltrating lymphocytes (TILs) in estrogen receptor-positive (ER+) breast cancer has been found to be significantly associated with a trend toward a lower overall survival rate, according to research presented at the 17th St. Gallen International Breast Cancer Conference 2021.

A. Tseluiko, from the N.N. Petrov National Medical Research Center of Oncology, Saint Petersburg, Russian Federation, and colleagues sought to determine the significance of the immunologic aspects of the antitumor response by analyzing cases with PD, PD-L1, and FOXP3. They also tested CD3, CD4, and CD8 as response markers.

The investigators assessed TILs in 1152 cases and found the level to be low in 67%, moderate in 25%, and severe in 8%. A total of 296 patients had a CD4+ percentage equal to or less than 20%. The 10-year overall survival rate of patients in this group reached 93%, which is considered favorable (P <.05) for early breast cancer (stages T1-T2, N0). In 98 patients, the CD4+ percentage was greater than 20%, and the 10-year overall survival of these patients was significantly lower than 82% (P <.05).

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The investigators observed no significant correlation between the degree of CD4+ lymphoid infiltration and disease-free survival rates (P =.27). However, in cases with a high CD4+ level (>20%), 10-year overall survival rates were noted to be decreased.

“The presence of FOXP3 expression on TILs in estrogen receptor-positive (ER+) breast cancer is significantly associated with a trend toward a lower overall survival rate (P =.06),” stated the investigators. “FOXP3-regulatory TILs are a poor prognostic indicator in ER+ breast cancer, but a favorable prognostic factor in HER2+/ER-subtype breast cancer.”

The predictive value of FOXP3 TILs differs depending on the expression and status of ER and HER2, as well as and CD8+ T-cell infiltration, noted the study authors.

“Particular importance is attached to the study of CD8+ and FOXP3,” the researchers commented. “It is believed that the co-expression of these markers has prognostic value and depends on the status, especially in the ER+ and HER2+ subgroups.”

A low degree of TILs (0%-10%) was observed with the luminal A subtype, and approximately 80% of patients with breast cancer have low tumor infiltration rates of CD8+ cytotoxic T lymphocytes and CD3+ TILs, according to the investigators.

PD-L1 is more frequently detected in patients with triple-negative breast cancer, occurs 1.5 times less often in HER2+ breast cancer, and is “extremely rarely” found in luminal A subtype, noted the researchers. The simultaneous expression of PD, PD-L1, and FOXP3 is associated with a poor prognosis and was found in 11.59% of patients. In addition, a high CD8+/ FOXP3 ratio (≥1.0) indicates a good prognosis of the disease.

“The percentage of CD4+ T lymphocytes less than 20% indicates a good prognosis and a high 10-year survival rate,” stated the study authors. “A high level (more than 10%) of CD8+ lymphoid infiltration increases 10-year survival (80%) and overall survival (92%) in patients with pT1-2N0.” Relapse-free, 10-year survival rates were reported to be 70% in the group without PD-L1 expression vs 41% for the group with PD-L1 expression (P = .02).

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Tseluiko AI, Semiglazov VF, Kudaibergenova AG, Artemieva AS, Gigolaeva LP, Krivorotko PV. The role of tumor-infiltrating lymphocytes (TILs), prognostic and predictive value in breast cancer. Poster presentation at: 17th. St Gallen International Breast Cancer Conference 2021; March 17-20, 2021. Abstract P118.