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Purpose Triple-negative breast cancer (TNBC) is challenging to treat with traditional “standard of care” therapy due to the lack of targetable biomarkers and rapid progression to distant metastasis. Methods We synthesized a novel combination regimen that included chemotherapy and photothermal therapy (PTT) to address this problem. Here, we tested a magnetic nanosystem (MNs-PEG/IR780-DOX micelles) loaded with the near-infrared (NIR) photothermal agent IR780 and doxorubicin (DOX) to achieve chemo-photothermal and boost antitumor immunity. Intraductal (i.duc) administration of MNs-PEG/IR780-DOX could increase the concentration of the drug in the tumor while reducing systemic side effects. Results We showed more uptake of MNs-PEG/IR780-DOX by 4T1-luc cells and higher penetration in the tumor. MNs-PEG/IR780-DOX exhibited excellent photothermal conversion in vivo and in vitro. The release of DOX from MNs-PEG/IR780-DOX is pH- and temperature-sensitive. Facilitated by i.duc administration, MNs-PEG/IR780-DOX displayed antitumor effects and prevented distant organs metastasis under NIR laser (L) irradiation and magnetic field (MF)while avoiding DOX-induced toxicity. More importantly, MNs-PEG/IR780-DOX alleviated tumor immunosuppressive microenvironment by increasing tumor CD8 + T cells infiltration and reducing the proportion of myeloid-derived suppressor cells (MDSCs) and Tregs. Conclusion Intraductal administration of pH- and temperature-sensitive MNs-PEG/IR780-DOX with L and MF had the potential for achieving minimally invasive, targeted, and accurate treatment of TNBC.

Background: Chemically induced animal models of breast cancer (BC) using N-methyl-N-nitrosourea (MNU) have been widely used in preclinical research. The conventional approach entails intraperitoneal (i.p) or intravenous injection of a carcinogen, leading to tumor induction at unpredictable locations. This study aimed to establish a modified MNU-induced rat mammary tumor model using intraductal (i.duc) administration and to evaluate its biological behavior, morphology, and response to chemotherapy drugs.Methods: In a pilot experiment, female Sprague-Dawley (SD) rats were injected with either i.duc MNU or vehicle to test the feasibility of this approach. We explored the appropriate dosage for stable tumor formation in pubescent female SD rats by testing a single i.duc dose of MNU (0.5, 1.0 and 2.0 mg) or vehicle.Results: An i.duc injection of 20 μL (1 mg/per duct) MNU in the fourth rat mammary gland induced stable carcinomas in situ. Immunohistochemical (IHC) analysis showed positive expression of estrogen receptor (ER), negative expression of human epidermal growth factor receptor 2 (Her-2), and low expression of Ki-67. Histopathology revealed atypical hyperplasia in the mammary gland 4 weeks after carcinogen injection, developing into carcinoma in situ 5-6 weeks after treatment, with loss of α-SMA and calponin expressions during tumor progression. Albumin-bound paclitaxel (nab-PTX) was injected i.duc and intravenously (i.v) 5 weeks after administration of MNU. The tumor growth rate of the nab-PTX i.duc-treated group was lower than in the i.v and control groups. The number of TUNEL-positive apoptotic cells was significantly higher in the nab-PTX i.duc-treated group.Conclusions: Using i.duc MNU (20 μL, 1 mg) to establish a rat mammary tumor model resulted in a predictable location in the rat mammary gland and exhibited better consistency; i.duc administration of nab-PTX permitted a smaller drug dose, but produced a better drug response, than i.v injection.

Background The purpose of this study was to determine the effect of hepatitis B virus (HBV) infection on the clinicopathological features and survival outcomes of breast cancer (BC) patients. Methods Patients diagnosed with BC at the Breast and Thyroid Center, Renmin Hospital, Wuhan University between January 2013 and December 2017 were included in the study. Among these patients, 100 (8.4%) were infected with HBV (case group), while 237 (19.9%) had never come into contact with HBV (control group). Chi-square tests for analyses of clinicopathological features, Kaplan-Meier survival analyses, the log-rank test for disease-free survival (DFS) between the case and control group, along with the factors correlated with prognosis, were evaluated using univariate and multivariate analyses. Results The median follow-up of the patients in the case and control groups was 34.5 months. The clinicopathological features revealed that patients with HBV tended to have smaller tumors compared with the control group (case vs. control: 53.0% vs . 65.8%, P<0.05). In addition, more grade 3 tumors were observed in patients with HBV (case vs . control: 55.0% vs . 37.6%, P<0.01). The 3-year DFS was 94.3% in the case group and 89.4% in the control group patients (P=0.212). In multivariate analysis, nodal status [hazard ratio (HR) =5.033, P=0.003] and estrogen receptor (ER) status (HR =0.216, P=0.023) were both independent prognostic risk factors for DFS. However, HBV infection had no association with the DFS of BC. Conclusions BC patients in central China have a higher incidence rate of HBV infection than the general population does. BC patients with chronic HBV infection tend to have an earlier tumor stage and higher histological grade, but there is no association with the DFS of BC.

Background This study had the purpose of examining the incidences, risk factors, and survival outcome of developing subsequent acute non-lymphocytic leukemia (ANLL) among a large group of breast cancer survivors. Methods We analyzed data from the Surveillance, Epidemiology, and End Results (SEER) program for standardized incidence ratio (SIR), risk factors, and survival of subsequent ANLL, focusing on the period between 2000 and 2014. Results There was an increased SIR among breast cancer patients for subsequent ANLL (SIR: 2.41; 95% CI: 2.26–2.58). Risk factors of subsequent ANLL were age at first cancer diagnosis (40+ vs. 15–39 years, aHR =1.572, P=0.003), tumor size (21–50 vs. ≤20 mm, aHR =1.332, P=0.003; 50+ vs. ≤20 mm, aHR =1.735, P<0.001), chemotherapy exposure (yes vs. no, aHR =1.692, P<0.001), and radiation exposure (yes vs. no, aHR =1.232, P=0.002). Meanwhile, following subsequent ANLL, survivors had an adverse overall survival (OS) compared with patients who did not develop ANLL (aHR =3.359, P<0.001). Conclusions Breast cancer survivors have a higher risk of developing subsequent ANLL compared to the general population. Increased vigilance should be shown towards the potential development of ANLL due to older age, larger tumor size, chemotherapy, and radiation exposure in survivors.