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Purpose: Emojis are commonly used for daily communication and may be useful in assessing patient-reported outcomes (PROs) in breast cancer. The purpose of this study is to develop and validate an Emoji Sticker Scale (ESS) as a new PRO measurement. Methods: Eighteen original ESS items were developed from the PRO-CTCAE. In cohort one, the ESS validity and reliability were examined in patients with breast cancer, using a semi-structured five-question survey to investigate content validity. PROs with PRO-CTCAE and ESS were examined twice to determine criteria validity and test-retest reliability. In cohort two, the responsiveness of the scales were examined in patients treated with anthracycline, docetaxel, paclitaxel, and endocrine therapy. PROs with PRO-CTCAE and ESS were investigated two or three times, depending on the therapy. Results: Patients were enrolled from August 2019 to October 2020. In cohort one (n=70), most patients had no difficulties with the ESS, but 16 patients indicated that it was difficult to understand severities in the ESS. For criterion validity, Spearman rank correlation coefficients (rs) between PRO-CTCAE and ESS items were ≥0.41, except for “Decreased appetite.” For test-retest reliability, κ coefficients of the ESS were ≥0.41 for 16/18 items (88.9%). Response time was significantly shorter for the ESS than for PRO-CTCAE (ps≥0.41. Conclusion Parts of the original ESS developed from PRO-CTCAE require updating. However, this study provides a comprehensive confirmation of the validity, reliability, and responsiveness of the ESS.

Background It is unclear what interventions can sustain long-term higherphysical activity (PA) to improve breast cancer outcomes. Thus, this study aimed to evaluate the long-term effects of interventions on PA after breast cancer treatment. Methods This was an open-label randomized controlled trial for patients with stage 0-III breast cancer evaluating the efficacy of exercise and educational programs on long-term PA compared with usual care. The primary endpoint was proportion of patients with recreational PA (RPA) ≥5 metabolic equivalents(METs)/week at 1 year after registration. Results From 01/03/2016 to 15/03/2020, breast cancer patients were registered in the control (n = 120), education (n = 121), or exercise (n = 115) group. There were no significant differences in proportion of RPA ≥5 METs/week at 1 year between the exercise and control groups (54% and 53%, P = 0.492) and between the education and control groups (62% and 53%, P = 0.126). Significant difference in reductions from baseline at 1 year were noted on body weight (P = 0.0083), BMI (P = 0.0034), and body fat percentage (P = 0.0027) between education and control groups. Similarly, the exercise group showed significant difference in reduction in body fat percentage (P = 0.0038) compared to control group. Conclusions Although there were no significant effects on RPA 1 year after exercise and educational programs for breast cancer survivors, both interventions reduced body composition. Future studies on PA should investigate appropriate interventions to improve overall survival. Trial registration UMIN000020595 at UMIN Clinical Trial Registry Date of first registration: 01/03/2016

Background Elucidating the unique immunoregulatory mechanisms in breast cancer microenvironment may help develop new therapeutic strategies. Some studies have suggested that hormone receptors also have immune regulatory functions, but their mechanisms are not fully understood. In this study, we have comprehensively analyzed the relationship between the expressions of estrogen (ER), progesterone (PgR), and androgen receptors (AR), and the immunological profile in breast cancer. Methods Using publicly available gene expression profile datasets, METABRIC and SCAN-B, the associations between the expressions of hormone receptors and the immune cell compositions in breast cancer tissue, estimated by CIBERSORTx algorithm, were analyzed. We histologically evaluated tumor-infiltrating lymphocytes (hTIL), PD-L1 (hPD-L1) expression, and the infiltration of 11 types of immune cells by flow cytometry (FCM) for 45 breast cancer tissue samples. The relationships between them and the expressions of ER, PgR, and AR of tumor tissues, evaluated immunohistochemically, were analyzed. Results Expressions of ESR1, PGR, and AR were negatively correlated with overall immune composition. Expressions of ER and AR, but not that of PgR, were inversely associated with hTIL and hPD-L1 expression. FCM analysis showed that the expressions of ER and AR, but not that of PgR, were associated with decreased total leukocyte infiltration. Both CIBERSORTx and FCM analysis showed that ER expression was associated with reduced infiltration of macrophages and CD4+ T cells and that of AR with reduced macrophage infiltration. Conclusion Hormone receptor expression correlates with specific immunological profiles in the breast cancer microenvironment both at the gene and protein expression levels.

Background The HORSE-BC study previously demonstrated that second-line endocrine therapy (ET) for patients with acquired endocrine-resistant metastatic breast cancer (MBC) still provided a clinically meaningful benefit. Herein, we investigated the health-related quality of life (HR-QOL) in the HORSE-BC study. Methods Patients with acquired endocrine-resistant MBC who were scheduled for second-line ET were recruited. The HR-QOL was assessed at baseline, and 1 and 3 months after second-line ET initiation. To investigate the minimally important difference (MID) in the Functional Assessment of Cancer Therapy-Endocrine Symptoms (FACT-ES), we evaluated the means and standard deviations for the distribution-based method, and differences in the change in HR-QOL for the anchor-based method. We also investigated the association between FACT-ES total scores and clinical benefit. Results Overall, 56 patients were enrolled. Of these, 47 were analyzed. When defined as 1/3 standard deviation estimates based on the distribution method, the calculated MID was 5.9. The MIDs of the FACT-ES total scores based on the anchor method were 7.7 for decline and 4.1 for improvement. The MID decline proportions were 6.1% and 14.7% lower in patients who experienced clinical benefits than in those who did not at 1 and 3 months, respectively. The ratios of MID improvement in patients who experienced clinical benefits were 18.3% and 3.2% higher, respectively; the mean change in the FACT-ES total score from baseline improved in patients who experienced clinical benefits. Conclusions Maintaining the HR-QOL as determined by FACT-ES may be associated with clinical benefits in patients with acquired endocrine-resistant MBC treated with ET.

Background. A better understanding of tumor immunology can facilitate the development of new treatment strategies for various malignancies. Histologically assessed tumor-infiltrating lymphocytes (hTILs) and programmed cell death 1 ligand 1 (hPD-L1) have been established as prognostic or predictive biomarkers in certain subsets of breast cancer. However, the complexity of multiple types of immune cells is not fully understood. In this study, the immune cell fractions in breast cancer tissue and blood were evaluated to analyze their association with hTILs and hPD-L1. Methods. In total, 45 tumor and 18 blood samples were collected from breast cancer patients. The total leukocyte counts, proportions of 11 types of immune cells in the samples, and PD-L1 expression in each fraction were evaluated using multicolor flow cytometry for both the tumor and blood samples. The hTILs and hPD-L1 were evaluated with hematoxylin and eosin staining and immunohistochemistry respectively. Results. The immune cell composition of the blood showed a partial correlation with that of the tumor tissue; however, no significant association was found between the blood immune cell compositions and hTIL or hPD-L1 expression. A higher hTIL was associated with increased leukocyte infiltration as well as a higher proportion of CD4+ and CD8+ T cells and lower proportion of natural killer cells and natural killer T cells. PD-L1 was highly expressed in the monocyte/macrophage (Mo/Mφ), nonclassical monocyte (CD16+ Mo), myeloid-derived suppressor cell (MDSC), dendritic cell (DC), and myeloid dendritic cell (mDC) fractions in the tumor tissues. hPD-L1 positivity was associated with increased leukocyte infiltration in the tumor tissues and PD-L1 expression in Mo/Mφ, CD16+ Mo, MDSC, DC, and mDC fractions. Conclusion. There was a partial correlation in the composition of immune cells at the tumor site and that in the peripheral blood. A high proportion of hTILs reflects not only higher immune cell infiltration but also differences in the immune responses in the tumor microenvironment. Non-B-cell antigen-presenting cell fractions such as Mo/Mφ, CD16+ Mo, MDSC, DC, and mDC fractions are involved primarily in the PD-L1 pathway in the breast cancer microenvironments.

Purpose The HORSE-BC study previously demonstrated that 2nd-line endocrine therapy (ET) for metastatic breast cancer (MBC) patients with acquired endocrine resistance still provided a clinically meaningful benefit. Herein, we investigated health-related quality of life (HR-QOL) in HORSE-BC. Methods MBC patients with acquired endocrine resistance who were scheduled for 2nd-line ET were recruited. HR-QOL was assessed at baseline and 1 and 3 months after initiation of 2nd-line ET. To investigate the minimally important difference (MID) in the Functional Assessment of Cancer Therapy-Endocrine Symptoms (FACT-ES), we evaluated the means and standard deviations (SDs) for the distribution-based method, and differences in the change in HR-QOL for the anchor-based method. We also investigated the association between FACT-ES total scores and clinical benefit. Results Overall, 56 patients were enrolled. Of these, 47 were analyzed. When defined as 1/3 SD estimates based on the distribution method, the calculated MID was 5.9. The MIDs of the FACT-ES total scores based on the anchor method were 7.7 for decline and 4.1 for improvement. The proportions of MID decline were 6.1% and 14.7% lower in patients who experienced clinical benefits than in those who did not at 1 month and 3 months, respectively. The respective ratios of MID improvement in patients who experienced clinical benefits were 18.3% and 3.2% higher, respectively; mean change in FACT-ES total score from baseline was improved in patients who experienced clinical benefits. Conclusion Maintaining HR-QOL as determined by FACT-ES may be associated with clinical benefits in patients with acquired endocrine-resistant MBC treated with ET.