Breast density reduction as a predictor for prognosis in premenopausal women with estrogen receptor-positive breast cancer: an exploratory analysis of the updated ASTRRA study.

BACKGROUND: While the relationship between mammographic breast density reduction (MDR) and endocrine therapy efficacy has been reported in estrogen receptor (ER)-positive breast cancer, it is still unclear in premenopausal women, especially in the case of adding ovarian function suppression (OFS) to antihormone therapy. The authors investigated the impact of MDR on prognosis stratified by treatment based on the updated results of the ASTRRA trial. MATERIALS AND METHODS: The ASTRRA trial, a randomized phase III study, showed that adding OFS to tamoxifen (TAM) improved survival in premenopausal women with estrogen receptor-positive breast cancer after chemotherapy. The authors updated survival outcomes and assessed mammography before treatment and the annual follow-up mammography for up to 5 years after treatment initiation. Mammographic density (MD) was classified into four categories based on the Breast Imaging-Reporting and Data System. MDR-positivity was defined as a downgrade in MD grade on follow-up mammography up to 2 years after randomization, with pretreatment MD grade as a reference. RESULTS: The authors evaluated MDR in 944 of the 1282 patients from the trial, and 813 (86.2%) had grade III or IV MD. There was no difference in the MDR-positivity rate between the two treatment groups [TAM-only group (106/476 (22.3%)) vs. TAM+OFS group (89/468 (19.0%)); P =0.217). MDR-positivity was significantly associated with better disease-free survival (DFS) in the TAM+OFS group (estimated 8-year DFS: 93.1% in MDR-positive vs. 82.0% in MDR-negative patients; HR: 0.37; 95% CI: 0.16-0.85; P =0.019), but not in the TAM-only group ( Pinteraction =0.039). MDR-positive patients who received TAM+OFS had a favorable DFS compared to MDR-negative patients who received only TAM (HR: 0.30; 95% CI: 0.13-0.70; P =0.005). CONCLUSION: Although the proportion of MDR-positive patients was comparable between both treatment groups, MDR-positivity was independently associated with favorable outcomes only in the TAM+OFS group.

Navigating the microbial community in the trachea-oropharynx of breast cancer patients with or without neoadjuvant chemotherapy (NAC) via endotracheal tube: has NAC caused any change?

Background: We compare the diversity and niche specificity of the microbiome in the trachea-oropharynx microbiome of malignant breast neoplasm with or without neoadjuvant chemotherapy (NAC) via NGS analysis. Methods: We prospectively collected a total of 40 endotracheal tubes intubated from subjects, of whom 20 with NAC treated breast cancer (NAC group) and 20 with breast cancer without NAC (Non-NAC group). We generated 16S rRNA-based microbial profiles in IlluminaTM platform and alpha diversity indices were compared between groups. For the comparison of taxa abundance, linear discriminant analysis effect size method with Kruskal-Wallis test was used. The distribution of variables between the two groups was compared using the Mann-Whitney test. For beta diversity analysis, PERMANOVA was used. Results: Among the diversity indices, the NAC group showed significantly lower Chao1, Inverse Simpson, and Shannon indices than the Non-NAC group. The three most frequent taxa of all two groups were Streptococcus (20.4%), followed by Veillonella (11.9%), and Prevorella (10.4%). This order was the same in NAC and non-NAC groups. Conclusion: Here, we provide the first comparison data of the respiratory tract microbiome of breast cancer patients with or without NAC via NGS analysis. This study ultimately seeks to contribute to future studies on the lower respiratory tract in cancer patients with cytotoxic chemotherapy by establishing reliable control data.

An observational, prospective, open label, multicenter study to evaluate the safety and effectiveness of pegfilgrastim as secondary prophylaxis to decrease the incidence of febrile neutropenia in Korean female patients with breast cancer.

PURPOSE: Pegfilgrastim is a widely used long-acting granulocyte colony-stimulating factor (G-CSF) that prevents febrile neutropenia (FN) in patients with breast cancer receiving chemotherapy. This study aimed to evaluate the incidence of chemotherapy-related FN events and other adverse events (AEs) during chemotherapy in Korean patients with breast cancer treated with pegfilgrastim as secondary prophylactic support. MATERIALS AND METHODS: This was a multicenter, open-label, prospective, observational study. A total of 1255 patients were enrolled from 43 institutions. The incidence of FN was evaluated as the primary endpoint. The secondary endpoints included (1) incidence of bone pain, (2) proportion of patients with a relative dose intensity (RDI) of ≥85%, and (3) proportion of patients with AE. RESULTS: Pegfilgrastim administration reduced FN by 11.8-1.6%. The highest incidence of bone pain was observed at the time point of the 1st day after the administration and mild bone pain was the most common of all bone pain severity. The mean RDI was 98.5 ± 7.3%, and the proportion of the patients with and RDI≥85% was 96.9% (1169/1233). AEs were reported in 52.6% of the patients, and serious drug reactions occurred in only 0.7%. CONCLUSION: The use of pegfilgrastim as secondary prophylaxis was effective and safe for preventing FN in patients with breast cancer who were treated with chemotherapy.

Hypofractionated Radiotherapy for Early-Stage Breast Cancer: A Propensity Score Matched Analysis.

BACKGROUND: In patients with early-stage breast cancer, the treatment results of hypofractionated radiation therapy (RT) and conventional RT are evaluated in efficacy and cost. METHODS: We retrospectively evaluated 280 patients with early-stage (Tis-2N0M0) breast cancer (including 100 hypofractionated RT patients) with regards to treatment outcomes according to the RT schedule. The median whole-breast RT dose was 42.56 Gy/16 fractions for hypofractionated RT and 50.4 Gy/28 fractions for conventional RT. Most patients (n = 260, 92.9%) additionally received a tumor bed boost RT. We used propensity score matching (PSM) analysis to balance the baseline risk factors for recurrence. The co-primary endpoints of this study were disease-free survival (DFS) and ipsilateral breast tumor recurrence (IBTR). DFS or IBTR was analyzed using the Kaplan-Meier survival curve and log-rank test. RESULTS: Total 89 pairs of matched patients (1:1 matching, n = 178) were finally evaluated. The median follow-up was 23.6 months. After matching, the 3-year DFS was 100% in the hypofractionated RT group and 98.4% in the conventional RT group; there was no significant difference in DFS between the groups (P = 0.374). Furthermore, the IBTR did not differ between the hypofractionated RT and conventional RT groups (P = 0.374) after matching. The 3-year overall survival was not different between two groups (both 100%). Hypofractionated RT saved 26.6% of the total cost of RT compared to conventional RT. Additionally, the acute skin toxicity rate (≥ grade 2) was also not significantly different between the groups (hypofractionated RT: 10.1% vs. conventional RT: 2.2%). CONCLUSION: Hypofractionated RT showed good IBTR and DFS, which were compatible to those in conventional RT in breast cancer. Hypofractionated RT is expected to be used more widely because of its low cost and convenience.

Combined treatment with anti-HER2/neu and anti-4-1BB monoclonal antibodies induces a synergistic antitumor effect but requires dose optimization to maintain immune memory for protection from lethal rechallenge.

Human epidermal growth factor receptor type 2 (HER2)-positive breast cancer that is treated with anti-HER2/neu monoclonal antibody (mAb) is not free from late recurrences. Addition of anti-4-1BB mAb to anti-HER2/neu mAb has been demonstrated to strengthen the cytotoxic antitumor response. Our study expands on this by revealing the influence of anti-4-1BB mAb addition on the immune memory of anti-HER2/neu mAb. We designed murine breast cancer models by implanting TUBO and TUBO-P2J cell lines in mice, which were then treated with anti-HER2/neu and/or anti-4-1BB mAb. After complete surgical and/or chemical regression of the tumor, the mice were rechallenged with a second injection of cancer cells. Notably, anti-HER2/neu and anti-4-1BB mAb combination therapy had a synergistic antitumor effect at the initial treatment. However, the combination therapy did not evoke immune memory, allowing the tumors to thrive at rechallenge with reduced CD44+ expression in CD8+ T cells. Immune memory was also impaired when anti-4-1BB mAb was administered to naive CD8+ T cells but was sustained when this was administered to activated CD8+ T cells. In an attempt to resist the loss of immune memory, we controlled the dose of anti-4-1BB mAb to optimize the stimulation of activated CD8+ T cells. Immune memory was achieved with the dose regulation of anti-4-1BB mAb to 1 mg/kg in our model. Our study demonstrates the importance in understanding the adaptive immune mechanism of anti-HER2/neu and anti-4-1BB mAb combination therapy and suggests a dose optimization strategy is necessary to ensure development of successful immune memory.

Synergism of a novel MCL­1 downregulator, acriflavine, with navitoclax (ABT­263) in triple­negative breast cancer, lung adenocarcinoma and glioblastoma multiforme.

Myeloid cell leukemia sequence 1 (MCL­1), an anti­apoptotic B­cell lymphoma 2 (BCL­2) family molecule frequently amplified in various human cancer cells, is known to be critical for cancer cell survival. MCL­1 has been recognized as a target molecule for cancer treatment. While various agents have emerged as potential MCL­1 blockers, the present study presented acriflavine (ACF) as a novel MCL­1 inhibitor in triple­negative breast cancer (TNBC). Further evaluation of its treatment potential on lung adenocarcinoma and glioblastoma multiforme (GBM) was also investigated. The anticancer effect of ACF on TNBC cells was demonstrated when MDA­MB­231 and HS578T cells were treated with ACF. ACF significantly induced typical intrinsic apoptosis in TNBCs in a dose­ and time­dependent manner via MCL­1 downregulation. MCL­1 downregulation by ACF treatment was revealed at each phase of protein expression. Initially, transcriptional regulation via reverse transcription­quantitative PCR was validated. Then, post­translational regulation was explained by utilizing an inhibitor against protein biosynthesis and proteasome. Lastly, immunoprecipitation of ubiquitinated MCL­1 confirmed the post­translational downregulation of MCL­1. In addition, the synergistic treatment efficacy of ACF with the well­known MCL­1 inhibitor ABT­263 against the TNBC cells was explored [combination index (CI)<1]. Conjointly, the anticancer effect of ACF was assessed in GBM (U87, U251 and U343), and lung cancer (A549 and NCI­H69) cell lines as well, using immunoblotting, cytotoxicity assay and FACS. The effect of the combination treatment using ACF and ABT­263 was estimated in GBM (U87, U343 and U251), and non­small cell lung cancer (A549) cells likewise. The present study suggested a novel MCL­1 inhibitory function of ACF and the synergistic antitumor effect with ABT­263.

Metabolomics-guided global pathway analysis reveals better insights into the metabolic alterations of breast cancer.

Accurate metabolome measurements are critical for improved insights into breast cancer metabolic disturbances and enhanced exploration of novel therapeutic targets. Nevertheless, conventional functional interpretation is limited by metabolite identification capacity, which diminishes the scientific value of untargeted metabolomics analyses. In this study, we conducted a metabolomics-guided global pathway meta-analysis to investigate the metabolic alterations of breast cancer. Metabolic features were directly investigated in the pathway meta-analysis to identify breast cancer-associated metabolic processes. Conventional pathway analysis was also conducted involving identified metabolites alone. Comparison of the two strategies revealed that the global pathway meta-analysis approach could avoid the loss of functionally relevant information, relative to the conventional analysis findings. Furthermore, the pathway meta-analysis accurately captured alterations in the following components of the breast cancer metabolome: central carbon metabolism, oxidative glutamine metabolism, purine metabolism, nonessential amino acid metabolism, and glutathione metabolism. There were also substantial alterations of fatty acyl carnitine species and fatty acid ß-oxidation processes. These pathways contribute to breast cancer initiation, progression, metastasis, and drug resistance. In conclusion, we suggest that global pathway analysis and the conventional approach with identified metabolites should be employed together to maximize the exploration of breast cancer's metabolic landscape.

Postpartum Galactocele in Augmented Breast after Using Breast Pump Mimicking Breast Implant-Associated Anaplastic Large Cell Lymphoma: A Case Report.

Post-partum galactocele is a common benign disease among breastfeeding women, whereas retromammary and peri-implant galactocele are relatively rare conditions. Herein, a 34-year-old, 1 month-postpartum female, who had augmentation mammoplasty and a 1-month history of breast pump use, presented with left breast enlargement for 2 weeks. An initial left breast US revealed hyperechoic peri-implant fluid collection. Additional US-guided fine needle aspiration was done using a 21G-needle, draining the milk component in the process, and cytologic results revealed numerous crystals, suggestive of galactocele. Various diseases, especially breast implant-associated anaplastic large cell lymphoma, can cause peri-implant fluid collection in an augmented breast. Thus, correlating imaging features with clinical information and cytologic analysis plays an important role in appropriate management.

Enlightening the Immune Mechanism of the Abscopal Effect in a Murine HCC Model and Overcoming the Late Resistance With Anti-PD-L1.

PURPOSE: The establishment of a preclinical model of the abscopal effect on hepatocellular carcinoma (HCC) and evaluation of whether the hypofractionated radiation therapy (RT) multitumor Hepa1-6 mouse HCC model could be used to suppress nonradiated tumor mass was performed in this study. METHODS AND MATERIALS: Hepa1-6 mouse liver cancer cell lines were used to form tumors. Immunogenicity was analyzed using ELISpot and immune cell labeled antibody. Interferon (IFN) ß expression was confirmed through polymerase chain reaction. RESULTS: After investigation, the intratumoral transcription of type Ⅰ IFN increased by 2-fold. The antitumor immune response to Hepa 1-6 cells induced by radiation was increased. Moreover, the influx of activated CD8+ T cells was increased in nonirradiated tumors. The number of dendritic cells and activation status were evaluated by flow cytometry on the second day after irradiation. Flow cytometry revealed a significantly increased dendritic cell population expressing the CD11c molecule in tumor-draining lymph nodes. Furthermore, because irradiation leads to adaptation of immune resistance of tumor cells against RT, we sought to elucidate a potent tool to overcome the resistance and confirm the ability of PD-L1 antibody to survive late RT resistance. CONCLUSIONS: The immunologic mechanism of the abscopal effect was revealed and the application of PD-L1 inhibitor successfully performed as a breakthrough in late RT resistance in the Hepa1-6 tumor model.

Cordyceps militaris Induces Immunogenic Cell Death and Enhances Antitumor Immunogenic Response in Breast Cancer.

Cordyceps militaris has been widely used as a traditional medicine in East Asia. Its effects against breast cancer have been reported previously. However, whether C. militaris-induced breast cancer cell death is immunogenic remains unelucidated. This study aimed to determine whether ethanolic extracts of C. militaris (CM-EE) could induce immunogenic cell death (ICD) in breast cancer immunotherapy to improve the efficacy of immune checkpoint inhibitors. Human and mouse breast cancer cells were treated with various concentrations of CM-EE for 72 h, and cytotoxicity was measured using the sulforhodamine B assay. Flow cytometry was used to assess cell death with annexin V/7-AAD staining and measure the surface exposure of damage-associated molecular pattern (DAMP) molecules including calreticulin, HSP70, and HSP90. Western blot for cleaved poly (ADP-ribose) polymerase (PARP) was used to confirm apoptotic cell death. The immunogenicity of CM-EE-induced dead cells was evaluated using the CFSE dilution assay. CM-EE reduced the viability of human (MCF7, MDA-MB-231, HS578T, and SKBR3) and mouse (4T1-neu-HA, TUBO-HA, and TUBO-P2J-HA) breast cancer cells. The IC50 was 25-50 µg/ml in human breast cancer cells and 10-50 µg/ml in mouse breast cancer cells at 72 h. CM-EE-treated breast cancer cells were positively stained by annexin V, cleaved PARP, and cleaved caspase 3/7 which were increased upon CM-EE treatment. Surface exposure of DAMP molecules was increased in dose- and time-dependent manners. The CFSE dilution assay revealed that dendritic cells fed with CM-EE-treated breast cancer cells successfully stimulated tumor-specific T cell proliferation without inhibiting DC function and T cell proliferation. The expression of PD-L1 mRNA and protein level was increased in dose-dependent manners. In addition, CM-EE also potentiated the cytotoxic activity of tumor-specific T cells. CM-EE can induce immunogenic and apoptotic cell death in breast cancer cells, and it is a good candidate for cancer immunotherapy and may improve the efficacy of immune checkpoint inhibitors.

Bilateral Triple Negative Invasive Ductal Breast Carcinoma in a BRCA1 Mutation Carrier with Discrepant Pathologic Response to Neoadjuvant Chemotherapy.

Herein, we report a case of synchronous bilateral triple negative invasive ductal breast carcinoma in a patient with discrepant pathologic response to neoadjuvant chemotherapy. Right and left breast cancer stages at the initial diagnosis were T1cN0M0 and T4dN3aM0, respectively. The patient was identified as a BRCA1 mutation carrier and treated with four cycles of adriamycin and cyclophosphamide, followed by four cycles of docetaxel. Bilateral breast cancer stages decreased with the first regimen. However, the bilateral breast cancers showed discrepant responses to chemotherapy with docetaxel. The right breast cancer showed a continuous tumor volume reduction while the left breast cancer showed marked progression. Finally, the tumor size was 0.3 cm and 12 cm in the right and left mastectomy specimens, respectively. As bilateral breast cancers of the same subtype may show discrepant responses to neoadjuvant chemotherapy, close monitoring and follow-up imaging are required to avoid delayed surgery.

Erratum: Bilateral Triple Negative Invasive Ductal Breast Carcinoma in a BRCA1 Mutation Carrier with Discrepant Pathologic Response to Neoadjuvant Chemotherapy.

[This corrects the article on p. 428 in vol. 81.].

BRCA1/BRCA2 Pathogenic Variant Breast Cancer: Treatment and Prevention Strategies.

Hereditary breast cancer is known for its strong tendency of inheritance. Most hereditary breast cancers are related to BRCA1/BRCA2 pathogenic variants. The lifelong risk of breast cancer in pathogenic BRCA1 and BRCA2 variant carriers is approximately 65% and 45%, respectively, whereas that of ovarian cancer is estimated to be 39% and 11%, respectively. Therefore, understanding these variants and clinical knowledge on their occurrence in breast cancers and carriers are important. BRCA1 pathogenic variant breast cancer shows more aggressive clinicopathological features than the BRCA2 pathogenic variant breast cancer. Compared with sporadic breast cancer, their prognosis is still debated. Treatments of BRCA1/BRCA2 pathogenic variant breast cancer are similar to those for BRCA-negative breast cancer, mainly including surgery, radiotherapy, and chemotherapy. Recently, various clinical trials have investigated poly (adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor treatment for advanced-stage BRCA1/BRCA2 pathogenic variant breast cancer. Among the various PARP inhibitors, olaparib and talazoparib, which reached phase III clinical trials, showed improvement of median progression-free survival around three months. Preventive and surveillance strategies for BRCA pathogenic variant breast cancer to reduce cancer recurrence and improve treatment outcomes have recently received increasing attention. In this review, we provide an information on the clinical features of BRCA1/BRCA2 pathogenic variant breast cancer and clinical recommendations for BRCA pathogenic variant carriers, with a focus on treatment and prevention strategies. With this knowledge, clinicians could manage the BRCA1/BRCA2 pathogenic variant breast cancer patients more effectively.

Plasma metabolites as possible biomarkers for diagnosis of breast cancer.

Metabolomic approaches have been used to identify new diagnostic biomarkers for various types of cancers, including breast cancer. In this study, we aimed to identify potential biomarkers of breast cancer using plasma metabolic profiling. Furthermore, we analyzed whether these biomarkers had relationships with clinicopathological characteristics of breast cancer. Our study used two liquid chromatography-mass spectrometry sets: a discovery set (40 breast cancer patients and 30 healthy controls) and a validation set (30 breast cancer patients and 16 healthy controls). All breast cancer patients were randomly selected from among stage I-III patients who underwent surgery between 2011 and 2016. First, metabolites distinguishing cancer patients from healthy controls were identified in the discovery set. Then, consistent and reproducible metabolites were evaluated in terms of their utility as possible biomarkers of breast cancer. Receiver operating characteristic (ROC) analysis was applied to the discovery set, and ROC cut-off values for the identified metabolites derived therein were applied to the validation set to determine their diagnostic performance. Ultimately, four candidate biomarkers (L-octanoylcarnitine, 5-oxoproline, hypoxanthine, and docosahexaenoic acid) were identified. L-octanoylcarnitine showed the best diagnostic performance, with a 100.0% positive predictive value. Also, L-octanoylcarnitine levels differed according to tumor size and hormone receptor expression. The plasma metabolites identified in this study show potential as biomarkers allowing early diagnosis of breast cancer. However, the diagnostic performance of the metabolites needs to be confirmed in further studies with larger sample sizes.

The Role of Neutrophil-lymphocyte Ratio and Platelet-lymphocyte Ratio in Predicting Neoadjuvant Chemotherapy Response in Breast Cancer.

PURPOSE: The role of the host immunologic environment is crucial in cancer progression. Recent studies revealed that neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR), are possible surrogate markers of outcome in various cancers. In breast cancer, the therapeutic effect of neoadjuvant chemotherapy (NAC) differs in patients, and higher response rate reflects better outcomes. This study aimed to determine the predictive value of peripheral blood NLR and PLR for NAC response along with their prognostic role in breast cancer. METHOD: A total of 105 patients with breast cancer treated with NAC between 2009 and 2017 were analyzed retrospectively. NAC response and prognosis (disease-free-survival [DFS], progression-free-survival [PFS] and overall survival [OS]) according to NLR and PLR were evaluated. According to the optimal cut-off values for NAC response obtained from receiver operating characteristic (ROC) curves, patients satisfying both low NLR and PLR levels (low-ratio group) were compared to those who did not (high-ratio group). RESULTS: The NLR cut-off value was ≤ 2.21 (area under the ROC curve [AUC], 0.617; 95% confidence interval [CI], 0.517-0.710; p=0.030) with 94.1% sensitivity and 38.0% specificity. The PLR cut-off value was ≤ 143.36 (AUC, 0.618; 95% CI, 0.518-0.711; p = 0.040) with 85.3% sensitivity and 39.4% specificity. The low-ratio group demonstrated a better NAC response (p = 0.006) in multivariate analysis than the high-ratio group. The low-ratio group showed better DFS and PFS (p = 0.046 and p = 0.040, respectively) and longer OS (p = 0.078) in univariate survival analysis than the high-ratio group. In multivariate analysis, the low-ratio group had significantly better PFS (p = 0.049) and higher DFS (p = 0.054) than the high-ratio group. CONCLUSIONS: The combination of NLR and PLR showed improved prediction of NAC response, revealing their potential as screening tools, significant prognostic role in breast cancer patients who receive NAC. Further studies with subgroup analysis, larger population and longer follow up duration are required.

Diabetes as a prognostic factor in HER-2 positive breast cancer patients treated with targeted therapy.

PURPOSE: Recent studies revealed that metabolic stress influences the outcomes of breast cancer treatment. We sought to evaluate the prognostic effect of type 2 diabetes and find the molecular mechanism of relapses in postoperative HER-2+ breast cancer patients treated with HER-2 targeted therapy. MATERIALS AND METHODS: We evaluated 190 HER-2+ breast cancer patients (pT1-4N0-2M0) who were treated with surgical resection and trastuzumab (HER-2 targeted therapy) between 2006 and 2015. Survival outcomes and failure patterns were compared between such patients with (n = 12) and without (n = 178) type 2 diabetes. RESULTS: The median follow-up period was 42.4 months (range 12.0-124.7 months). Twenty-one patients (11.1%) showed relapse (including nine patients with locoregional failure), and three patients (1.6%) died as a result of cancer relapse. One-third of the patients with diabetes experienced relapse (4/12, 33.3%). The 3-year disease-free survival (DFS) and overall survival (OS) rates were 90.7% and 98.6%, respectively. Diabetic patients showed shorter DFS compared with non-diabetic patients (p = 0.006, 74.1% vs. 91.9%). OS was also shorter in diabetic patients compared with non-diabetic patients (p = 0.017, 91.7% vs. 99.1%). Of our interest, the levels of HER-3 and its ligand neuregulin-1 were significantly increased in the tumor specimen in HER-2+ breast cancer patients suffering with type 2 diabetes than that in the euglycemic control group. CONCLUSIONS: Type 2 diabetes was associated with detrimental effects on survival in postoperative HER-2+ breast cancer patients who were treated with trastuzumab. The poor prognostic effect of diabetes in HER-2+ breast cancer patients could be associated with the high levels of HER-3 and neuregulin 1, thus it should be considered and evaluated more.

Effect of anthracycline and taxane on the expression of programmed cell death ligand-1 and galectin-9 in triple-negative breast cancer.

This study identified chemotherapeutic agents that up-regulate programmed cell death ligand-1 (PD-L1) and galectin-9 (Gal-9) in breast cancer cells. Immunohistochemical (IHC) staining was used to evaluate changes in PD-L1 and Gal-9 expression in the tumor tissue of triple-negative breast cancer (TNBC) patients who received anthracycline- and taxane-based neoadjuvant chemotherapy. To determine whether PD-L1 and Gal-9 expression changes were attributable directly to chemotherapeutics, MDA-MB-231 cells and HS578T cells were treated with different concentrations of anthracycline and taxane. Expression levels of PD-L1 and Gal-9 were evaluated and the activation status of NFκB in MDA-MB-231 and HS578T cells was determined to identify the PD-L1 and Gal-9 up-regulation mechanism. Three cases of increased PD-L1 expression and two of increased Gal-9 expression were observed among the TNBC patients. PD-L1 and Gal-9 expression were up-regulated by anthracycline and taxane in MDA-MB-231 cells, but not in HS578T cells. Increased nuclear levels of NFκB were observed in MDA-MB-231 cells treated with 0.5 µM epirubicin. Anthracycline and taxane up-regulated PD-L1 and Gal-9 expression in some subtypes of TNBC. This study provides useful reference data for clinical trials investigating combination treatments with immune checkpoint inhibitors and chemotherapy.