Abstract P3-05-17: The numbers of Foxp3 positive cells in simultaneous bilateral breast cancer
Authors: Goto R , Hirota Y , Aruga T , Horiguchi S , Tazawa S , Nakamura S , Takimoto M 
Published: February 2018

Background

Evasion of the immune system is one of the hallmarks of malignant tumors, and recently blocking of such evasion has been used in clinical practice for the treatment of some types of cancers. Recruitment of regulatory T cells (Tregs), which express the specific marker Foxp3, is an established mechanism of escaping from the immune system. In breast cancer, it has been reported that the number of Tregs differs widely among breast cancer subtypes, and that patients who have many Tregs around the tumor tend to have a poor prognosis. However, the factors that are important for the recruitment of Tregs are not well known. Thus, factors that depend on the host (e.g., age or comorbidity), on the tumor (e.g., subtype, grade, or stage), or on measurement error might be the cause of the observed differences in the number of Tregs. In this study, we investigated the numbers of Tregs in simultaneous bilateral breast cancer patients in order to determine the factors that influence the recruitment of Tregs, while excluding differences in individuals as much as possible.

Material and methods

Patients who had breast cancer in both breasts and who underwent simultaneous surgery between January 2005 and September 2015 at two institutions were enrolled in this study. Patients who underwent primary systemic therapy who were diagnosed with ductal carcinoma in situ, or who were stage IV were excluded. The average numbers of Foxp3-positive (Foxp3+cells) were determined from scores of five high-power fields (HPFs). The association between the difference in Foxp3+ cell number between each breast in a single individual and clinicopathological features was examined.

Results

Seventy patients were included in this study. Their ages ranged from 39-85 (median 54) years old. Ninety five percent of the tumors were invasive ductal carcinoma non-special type. Eighty eight (62.9%), 43 (30.7%), and 9 (6.4%) of the tumors were T1, T2, and ≥T3, respectively, and 102 (72.9%) of the tumors were node-negative. Regarding nuclear grade (NG), 104 (74.3%), 21 (22.1%), and 7 (5%) of the tumors were NG1, 2, and 3, respectively. As for subtype, 124 (88.6%), 9 (6.4%), and 7 (5%) were ER-positive and HER2-negative(ER+/HER2-), ER-positive or negative and HER2-negative(ER±/HER2+), and ER-negative and HER2-negative(ER-/HER2-), respectively. The numbers of Foxp3+ cells ranged from 0 to 39.8 (median 3.3)/HPF, and difference in Foxp3+ cell number between each breast in a single individual ranged from 0 to 34 (median 3.9)/HPF.

Differences in tumor size and node status in individuals did not impact on the number of Foxp3+ cells. However, the number of Foxp3+ cells in tumors that were NG3 (P=0.00098) or ER±/HER2+ or ER-/HER2- type (P=0.00586) were statistically significantly increased compared with tumors that were NG1/2 or ER+/HER2- type in the same host.

Furthermore, the difference of Foxp3+ cells between each tumor in a single individual were quite small regarding tumor size and node status in 53 patients who had similar NG and subtype tumors in both breasts.

Conclusions

The number of Foxp3+ cells showed no relationship with tumor size, or lymph node status in simultaneous bilateral breast cancer patients. High NG, ER±/HER2+ or ER-/HER2- type of the tumor were involved with enhancement of the recruitment of Tregs.

Citation Format: Goto R, Hirota Y, Aruga T, Horiguchi S, Tazawa S, Nakamura S, Takimoto M. The numbers of Foxp3 positive cells in simultaneous bilateral breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-05-17.