Hypothesis: Toremifen is effective in reducing breast pain and does not increase the incidence of adverse events as a therapy for moderate to severe mastalgia. Design and Patients:In a double-blind randomized controlled trial, patients with moderate to severe mastalgia received toremifen citrate, 30 mg daily, or a placebo tablet for 3 menstrual cycles and were followed up for breast pain score and adverse events. The serum levels of estradiol, progesterone, and prolactin were examined before treatment and correlated with the response rate to toremifen treatment.Results: Seventy-two (69.2%) of 104 patients receiving toremifen and 29 (31.9%) of 91 receiving placebo responded to the treatment, with reduction in breast pain score of more than 50% (PϽ.001). Among the patients with cyclical mastalgia, the response rate for toremifen was 76.7% (59/77), whereas the response rate for pla-cebo was 34.8% (23/66; PϽ.001). In contrast, the response rate of patients with noncyclical mastalgia was 48.1% (13/27) for toremifen and 24.0% (6/25) for placebo (P=.09). Adverse events were observed in 44 (42.9%) of 104 patients receiving placebo and 46 (50.5%) of 91 patients receiving toremifen (P=.45). A positive correlation between baseline breast pain score and serum estradiol level was observed in patients with cyclical mastalgia (r =0.35, P=.003).Conclusions: Toremifen effectively relieves moderate and severe cyclical mastalgia and tends to exert a positive therapeutic effect on noncyclical mastalgia. In addition, toremifen therapy does not increase the incidence of intolerable adverse event. Therefore, it is a feasible therapy for mastalgia, especially cyclical mastalgia.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor outcome and lacks of approved targeted therapy. Overexpression of epidermal growth factor receptor (EGFR) is found in more than 50% TNBC and is suggested as a driving force in progression of TNBC; however, targeting EGFR using antibodies to prevent its dimerization and activation shows no significant benefits for TNBC patients. Here we report that EGFR monomer may activate signal transducer activator of transcription-3 (STAT3) in the absence of transmembrane protein TMEM25, whose expression is frequently decreased in human TNBC. Deficiency of TMEM25 allows EGFR monomer to phosphorylate STAT3 independent of ligand binding, and thus enhances basal STAT3 activation to promote TNBC progression in female mice. Moreover, supplying TMEM25 by adeno-associated virus strongly suppresses STAT3 activation and TNBC progression. Hence, our study reveals a role of monomeric-EGFR/STAT3 signaling pathway in TNBC progression and points out a potential targeted therapy for TNBC.

Background To summarize the clinical experience of ultrasound-guided minimally invasive surgery for granulomatous lobular mastitis (GLM), and explore the feasibility of this technique for treating GLM. Methods This retrospective study reviewed the clinical features and treatment outcome of 30 patients who were diagnosed pathologically as GLM from 2016.3 to 2019.5 in the Department of Breast Surgery, Women's and Children's Hospital, Xiamen University. These patients weretreated with ultrasound-guided Mammotome minimally invasive surgery, and we tried to classified the lesion into four distinct patterns (diffuse abscess mixed type, sheet hypoechoic type, localized abscess type, localized hypoechoic mass type) according to the sonographic findings and clinical symptoms to find out if these patterns correlated with treatment and recurrence rate. Results After a median follow-up of 12 months on average (4–42 months), 26 cases (86.7%) were cured without acute or chronic complications such as disseminated inflammation and bleeding. Post-operative bleeding occurred in 1 case, and 3 cases (10.00%) relapsed. The ultrasound classification had 0 cases of diffuse abscess mixed type, 17 cases (56.7%) of sheet hypoechoic type, 9 cases (30%) of localized abscess type, and 4 cases (13.3%) of localized hypoechoic mass type. All 3 recurrent cases were sheet hypoechoic type, which were cured after another open surgical resection and showed no recurrence during an average follow-up of 20 months (11–40 months). Conclusions In treating GLM patients with minimally invasive rotary cutting, ultrasound classification helps to select suitable patients, especially those with localized abscess and localized hypoechoic mass types with low recurrence rate, which is one of the safe and effective treatment methods.

What Is Known and Objective: Drug-induced neutropenia is the main reason for the dose limitation of docetaxel in patients with breast cancer. The area under the drug concentration-time curve (AUC) of docetaxel is associated with neutropenia. However, the optimal exposure to docetaxel for receiving postoperative adjuvant chemotherapy remains unclear. Therefore, we aimed to evaluate the relationship between the docetaxel AUC and neutropenia, identify potential influencing factors, and explore the best monitoring target for docetaxel when treating patients with earlystage breast cancer using a population pharmacokinetic (PopPK) model.Methods: Docetaxel plasma concentration, demographics, clinical data, and related laboratory data were collected. PopPK analyses were performed using a nonlinear mixed-effect modelling program. The docetaxel AUC was determined using the maximum a posteriori Bayesian (MAPB) method. The docetaxel exposure-toxicity threshold measured from the AUC for neutropenia was determined using the receiver operating characteristic (ROC) curve. The correlation between docetaxel exposure and neutropenia was analysed using multivariable logistic regression.Results: Among the 70 participants, 47 (67.1%) developed severe neutropenia. The PopPK analysis showed that the typical drug clearance (CL) rate was 37.4 L/h. Age was a significant covariate of CL rate, and aspartate aminotransferase and albumin levels were covariables of the volume of distribution. The multivariable regression analysis showed that AUC >3.0 mg.h/L (odds ratio [OR], 5.940; 95% confidence interval [CI], 1.693-20.843; P = 0.005), platinum use (OR, 0.156; 95% CI, 0.043-0.562; P = 0.005) and baseline haemoglobin level (OR, 0.938; 95% CI, 0.887-0.993; P = 0.027) were significant factors influencing the occurrence of grade 3/4 neutropenia. The AUC of first cycle may not predict the occurrence rates of grade 3/4 neutropenia in later cycles. What Is New and Conclusion:We developed a docetaxel PopPK model for patients with early-stage breast cancer. Age and AST and ALB levels were significant covariates. AUC estimated using the MAPB method can predict the toxicity of docetaxel in patients with breast cancer. Docetaxel AUC >3.0 mg.h/L, absence of platinum use and low baseline haemoglobin level were risk factors for docetaxel-induced grade 3/4 neutropenia.

Background: Although taxane-containing chemotherapy is widely used to treat solid tumors, genetic polymorphisms can influence the chemotherapeutic response. This meta-analysis was conducted to determine the correlation between two polymorphisms in ABCB1 , rs1045642 and rs1128503, and survival of patients administered taxane-containing chemotherapy. Methods: PubMed, Web of Science, Embase, Wanfang database, VIP database, and China National Knowledge Infrastructure database were used to obtain articles published up to August 2019 describing the association between the ABCB1 rs1045642 and rs1128503 polymorphisms and survival. A meta-analysis was conducted using R 3.6.1 software to determine the pooled hazard ratio (HR) and 95% confidence intervals (95% CI). Furthermore, publication bias was assessed, and sensitivity analysis was performed to validate the analysis. Results: Fifteen studies involving 3320 patients were included in the meta-analysis. The summary results showed that the effect of the C1236T polymorphism on progression-free survival remained significant in the heterozygote model (HR 0.81; 95% CI: 0.67–0.98) and homozygote model (HR 0.71; 95% CI: 0.58–0.88). Compared to the C1236 TT phenotype, the CC genotype was associated with a poor overall survival (HR 0.72; 95% CI: 0.53–0.97). Finally, subgroup analysis suggested that different areas, tumor types, and treatment regimens influence patient survival. Conclusions: Patients who are ABCB1 rs1045642 and rs1128503 T gene carriers show a survival benefit with taxane-containing chemotherapy.