As an aggressive subtype of breast cancer, triple-negative breast cancer (TNBC) is associated with poor prognosis and lack of effective therapy, except chemotherapy. In recent years, immunotherapy based on immune checkpoint (IC) inhibition has emerged as a promising therapeutic strategy in TNBC. TNBC has more tumor-infiltrating lymphocytes (TILs) and higher rate of mutation and programmed cell death ligand-1 (PD-L1) expression than other subtypes of breast cancer have. However, previous studies have shown that monotherapy has little efficacy and only some TNBC patients can benefit from immunotherapy. Therefore, it is important to identify biomarkers that can predict the efficacy of IC inhibitors (ICIs) in TNBC. Recently, various biomarkers have been extensively explored, such as PD-L1, TILs and tumor mutational burden (TMB). Clinical trials have shown that PD-L1-positive patients with advanced TNBC benefit from ICIs plus chemotherapy. However, in patients with early TNBC receiving neoadjuvant therapy, PD-L1 cannot predict the efficacy of ICIs. These inconsistent conclusions suggest that PD-L1 is the best to date but an imperfect predictive biomarker for efficacy of ICIs. Other studies have shown that advanced TNBC patients with TMB ≥10 mutations/Mb can achieve clinical benefits from pembrolizumab. TILs also have potential predictive value in TNBC. Here, we select some biomarkers related to ICIs and discuss their potential predictive and prognostic value in TNBC. We hope these biomarkers could help to identify suitable patients and realize precision immunotherapy.

Background: Pyrotinib, a novel irreversible epidermal growth factor receptor 2 (EGFR)/HER2 dual tyrosine kinase inhibitor, has shown promising antitumor efficacy with tolerable toxicity in HER2‐positive metastatic breast cancer (MBC) in several clinical trials. However, the clinical trials do not usually well reflect the patients in real clinical settings. Despite several small‐sample studies in real world, the data on pyrotinib as first‐line and third‐or‐later‐line treatment and the efficacy comparison of pyrotinib combined with different regimens are still lacking. Therefore, this study aimed to investigate the efficacy and safety of pyrotinib for the HER2‐positive MBC in real world to replenish more comprehensive data.Methods: A total of 172 HER2‐positive MBC patients treated with pyrotinib‐based therapy were recruited from multiple centers in nonclinical trial settings from September 2017 to June 2020.Results: The median progression‐free survival (mPFS) of 172 patients was 8.83 months. The patients, receiving first‐line pyrotinib treatment, had the longest mPFS (20.93 months) compared with those receiving second‐line (8.67 months, p = 0.0339) and third‐or‐later‐line (7.13 months, p = 0.0075) treatments, respectively. Prior treatment with lapatinib (p = 0.012) and site of metastasis (visceral vs. nonvisceral) (p = 0.033) were the independent prognostic factors for PFS. The prior treatment with lapatinib compared with lapatinib‐native treatment (5.96 vs. 10.97 months, p = 0.0036) and those with visceral metastasis compared with nonvisceral metastasis (8.40 vs. 23.70 months, p = 0.0138) had worse mPFS. Among 146 patients evaluated for efficacy, 2.1%, 58.9%, and 32.9% showed complete response, partial response, and stable disease, respectively. Adverse events occurred in 92.4% of the patients with 33.3% Grade 3 and higher adverse events and diarrhea (57.0%), anemia (44.8%), and leukopenia (40.7%) as the most frequent ones.Conclusions: Pyrotinib‐containing regimen could effectively treat HER2‐positive MBC with acceptable toxicity, including the patients who progressed after lapatinib treatment and with brain metastasis.

Introduction: Neoadjuvant trastuzumab plus chemotherapy may affect programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs) in HER2-positive breast cancer. Discordant results were shown on the correlation between PD-L1 expression or TILs and the effectiveness of neoadjuvant therapy in HER2-positive breast cancer patients. This study aimed to clarify the predictive value of PD-L1 expression and TILs in neoadjuvant therapy in patients with HER2-positive breast cancer.Methods: HER2-positive breast cancer cases receiving neoadjuvant treatment (NAT; n = 155) were retrospectively collected from July 2013 to November 2018. Histopathologic analysis of TILs was performed on hematoxylin and eosin (H&E)-stained sections from pre- and post-NAT specimens. The TIL score as a categorical variable can be divided into high (≥30%) and low (<30%) categories. The expression of PD-L1 was detected by immunohistochemistry, and the percentage of positive membranous staining (at least 1%) in tumor cells (PD-L1+TC) and TILs (PD-L1+TILs) was scored.Results: In our study, 87 patients received neoadjuvant chemotherapy alone and 68 received neoadjuvant trastuzumab plus chemotherapy. Multivariate logistic regression analysis confirmed that lymph node metastasis, high TILs, and PD-L1+TILs in pre-neoadjuvant therapy specimens were independent predictors of pathological complete response (pCR) in neoadjuvant therapy (p < 0.05, for all). Among all patients, TILs were increased in breast cancer tissues post-neoadjuvant therapy (p < 0.001). Consistent results were found in the subgroup analysis of the trastuzumab plus chemotherapy group and the chemotherapy alone group (p < 0.05, for both). In 116 non-pCR patients, PD-L1+TC was decreased in breast cancer tissues post-neoadjuvant therapy (p = 0.0219). Consistent results were found in 43 non-pCR patients who received neoadjuvant trastuzumab plus chemotherapy (p = 0.0437). However, in 73 non-pCR patients who received neoadjuvant chemotherapy, there was no significant difference in PD-L1+TC expression in pre- and post-neoadjuvant therapy specimens (p = 0.1465). On the other hand, in the general population, the neoadjuvant trastuzumab plus chemotherapy group, and the neoadjuvant chemotherapy group, PD-L1+TILs decreased after treatment (p < 0.05, for both).Conclusion: Higher TIL counts and PD-L1+TILs in pre-neoadjuvant therapy specimens and lymph node metastasis are independent predictors of pCR in patients with HER2-positive breast cancer treated with neoadjuvant therapy. TIL counts, PD-L1+TC, and PD-L1+TILs changed before and after neoadjuvant trastuzumab plus chemotherapy for HER2-positive breast cancer, which may suggest that, in HER2-positive breast cancer, neoadjuvant trastuzumab plus chemotherapy may stimulate the antitumor immune effect of the host, thereby preventing tumor immune escape.

Objective: To assess fear of progression (FoP)'s relationship with symptom burden and disease and social/family factors, as well as, determine the status of FoP in women with stage‐IV breast cancer in Shandong, China.Methods: Two hundred and sixteen women were recruited from the department of breast cancer internal medicine, Shandong Cancer Hospital and Institute. Data for this observational study were collected between October 2020 and January 2021 using the MD Anderson Symptom Inventory, the Fear of Progression Questionnaire‐Short Form (FoP‐Q‐SF) and a participant information scale. SPSS 23.0 was used for statistical analysis.Results: After excluding invalid responses, the data of 200 participants were analysed. The average total FoP‐Q‐SF score was 29.39 ± 9.39 (95% confidence interval, 21.81–27.64). The FoP level among the participants was relatively low. For disease and social/family factors, FoP statistically significantly differed by satisfaction with family emotional support and the Eastern Cooperative Oncology Group (ECOG) score. The ECOG score was positively correlated with FoP. Furthermore, symptom burden was positively correlated with FoP.Conclusions: Among patients with stage‐IV breast cancer, satisfaction with family emotional support, ECOG score and symptom burden play key roles in FoP. Interventions, including providing appropriate emotional support from family, improving physical fitness and relieving symptom burden, must be considered in future studies, which may improve patients' overall physical and mental status and provide a supportive therapeutic environment.

Background: Limited data are available on applying circulating tumor DNA (ctDNA) in metastatic triple-negative breast cancer (mTNBC) patients. Here, we investigated the value of ctDNA for predicting the prognosis and monitoring the treatment response in mTNBC patients.Methods: We prospectively enrolled 70 Chinese patients with mTNBC who had progressed after ≤2 lines of chemotherapy and collected blood samples to extract ctDNA for 457-gene targeted panel sequencing.Results: Patients with ctDNA+, defined by 12 prognosis-relevant mutated genes, had a shorter progression-free survival (PFS) than ctDNA− patients (5.16 months vs. 9.05 months, p=0.001), and ctDNA+ was independently associated with a shorter PFS (HR, 95% CI: 2.67, 1.2–5.96; p=0.016) by multivariable analyses. Patients with a higher mutant-allele tumor heterogeneity (MATH) score (≥6.316) or a higher ctDNA fraction (ctDNA%≥0.05) had a significantly shorter PFS than patients with a lower MATH score (5.67 months vs.11.27 months, p=0.007) and patients with a lower ctDNA% (5.45 months vs. 12.17 months, p<0.001), respectively. Positive correlations with treatment response were observed for MATH score (R=0.24, p=0.014) and ctDNA% (R=0.3, p=0.002), but not the CEA, CA125, or CA153. Moreover, patients who remained ctDNA+ during dynamic monitoring tended to have a shorter PFS than those who did not (3.90 months vs. 6.10 months, p=0.135).Conclusions: ctDNA profiling provides insight into the mutational landscape of mTNBC and may reliably predict the prognosis and treatment response of mTNBC patients.Funding: This work was supported by the National Natural Science Foundation of China (Grant No. 81902713), Natural Science Foundation of Shandong Province (Grant No. ZR2019LZL018), Breast Disease Research Fund of Shandong Provincial Medical Association (Grant No. YXH2020ZX066), the Start-up Fund of Shandong Cancer Hospital (Grant No. 2020-PYB10), Beijing Science and Technology Innovation Fund (Grant No. KC2021-ZZ-0010-1).