Risk factors for early postoperative psychological problems in breast cancer patients after axillary lymph node dissection Abstract Background The purpose of this study was to investigate the factors related to early postoperative psychological conditions in breast cancer patients with axillary lymph node dissection 3 months after the surgery. Methods The subjects of this study were 200 consecutive patients who underwent axillary lymph node dissection for breast cancer at our hospital. Age, body mass index, surgical side, work, marriage, presence of children, presence of co-resident household members, resection of the pectoralis minor muscle, preoperative chemotherapy, postoperative chemotherapy, postoperative hormonal therapy, postoperative radiotherapy, shoulder range of motion, upper limb function (Disabilities of the Arm, Shoulder and Hand; DASH), and psychological conditions were evaluated. In this study, a Distress and Impact Thermometer was used to classify patients with adjustment disorders, depression, or major depression and suicidal ideation into a group with psychological problems and the remaining patients into a group with no psychological problems. Results Logistic regression analysis showed that only DASH was statistically significantly associated with psychological conditions (p < 0.05). Using receiver operating characteristic curve analysis, a DASH score of 18 or greater was found to be very specific for predicting psychological conditions. Conclusions The observation that somatic symptoms and disability of upper limb function are related to psychological conditions may indicate the importance of postoperative rehabilitation in breast cancer patients with axillary lymph node dissection.

RETRACTED ARTICLE: Association of insulin-like growth factor 1 receptor and estrogen receptor with pathological complete response to neoadjuvant chemotherapy in HER2-negative breast cancer

Mean platelet volume may not be an independent prognostic factor in breast cancer patients with type 2 diabetes mellitus

Acknowledgements to reviewers 2019

MicroRNA-138-5p inhibits cell migration, invasion and EMT in breast cancer by directly targeting RHBDD1 Abstract Background Accumulating studies have identified that microRNAs (miRNAs) are novel regulators acting as tumor suppressors or oncogenes in tumor progression. The aim of the study is to investigate the functional roles of miR-138-5p in breast cancer (BC) cells and explore the underlying mechanisms by identifying its target gene. Methods and results Our results first showed that miR-138-5p expression was remarkably decreased in BC tissues and cells using quantitative real-time PCR analysis. Forced expression of miR-138-5p significantly suppressed cell migration and invasion ability of BC using transwell assay. Moreover, miR-138-5p overexpression suppressed cell epithelial–mesenchymal transition (EMT) phenomenon of BC by upregulating E-cadherin expression, but downregulating N-cadherin and Vimentin expression. More importantly, rhomboid domain-containing protein 1 (RHBDD1) was predicted as the direct target of miR-138-5p by TargetScan and miRanda, which was subsequently confirmed by luciferase reporter assay in BC cells. RHBDD1 was up-regulated in BC tissues and negatively correlated with miR-138-5p expression. Furthermore, forced expression of miR-138-5p could down-regulate the expression of RHBDD1, but overexpression of RHBDD1 reversed the suppressive effects of miR-138-5p in BC cell migration, invasion and EMT. Conclusions Our findings revealed the tumor-suppressive role of miR-138-5p in regulating BC migration by targeting RHBDD1, suggesting that miR-138-5p negatively regulating EMT might be a therapeutic target in BC.

Reproductive history and breast cancer survival: a prospective patient cohort study in Japan Abstract Background Reproductive factors may influence breast cancer progression and patient survival; however, evidence has been limited. Methods The associations of reproductive factors with tumor characteristics and patient survival were analyzed among 1468 breast cancer patients diagnosed during 1997–2013 at a single institute in Japan. The patients were followed until 2016. During a median follow-up period of 8.6 years, 272 all-cause and 199 breast cancer deaths were documented. Results In case–case comparisons, later age at menarche was inversely associated with advanced tumors. Nulliparous patients tended to have receptor-positive [estrogen receptor (ER)+ or progesterone receptor (PR)+] tumors. Conversely, the Cox proportional-hazards model including adjustment for tumor characteristics revealed U-shaped relationship between parity number and the risk of all-cause death among the patients overall [hazard ratio (HR) = 2.10 for nulliparous, 1.28 for 2, and 1.50 for ≥ 3 vs. one child]. According to hormone receptor, later age at menarche and later age at last birth were positively associated with the risk of all-cause death among patients with ER– and PR– cancer (menarche, HR = 2.18 for ≥ 15 vs. ≤ 12 years, ptrend = 0.03; last birth, HR = 3.10 for ≥ 35 vs. ≤ 29 years, ptrend = 0.01). A shorter time since last birth was associated with the risk of death among receptor-positive patients (HR = 5.72 for ≤ 4 vs. ≥ 10 years, ptrend = 0.004). Conclusion The results indicate that the timing of menarche and parity have significant effects on patient survival, providing clues for understanding the association between women’s life course and breast cancer outcome.

Knockdown of FAM64A suppresses proliferation and migration of breast cancer cells Abstract Background FAM64A is a mitotic regulator promoting cell metaphase–anaphase transition, and it is frequently reported to be highly expressed in cancer cells. However, the role of FAM64A in human breast cancer (BrC) is poorly studied. Methods The expression of FAM64A mRNA in BrC samples was determined by RT-qPCR assay and TCGA database mining. Kaplan–Meier plotter was used to analyze whether FAM64A expression impacted prognosis. Then, the expression of FAM64A was silenced using RNA interference. Cell-counting assay, colony formation assay and flow cytometry assay were conducted to detect proliferation; transwell migration assay, EMT-related proteins expression (E-cadherin, N-cadherin and vimentin), and EMT-related transcription factors mRNA expression (Snail, Twist, Slug) were conducted to evaluate the migration ability. Results FAM64A was highly expressed in human BrC samples, which was negatively associated with poor survival time. Analysis of FAM64A expression in BrC cell lines demonstrated that the expression of FAM64A was significantly correlated with the proliferation rate and migration ability of BrC cells. Indeed, knockdown of FAM64A suppressed the proliferation of MDA-MB-231 and MCF-7 cells. Importantly, we also found that silencing of FAM64A inhibited the migration of BrC cells via impeding epithelial–mesenchymal transition. Conclusions Our findings suggest that FAM64A plays an important role in the proliferation and migration of BrC cells, which might serve as a potential target for BrC treatment.

Cardiorespiratory fitness predicts cardiovascular health in breast cancer survivors, independent of body composition, age and time post-treatment completion Abstract Background Breast cancer treatment may increase non-cancer related mortality risk due to unintended cardiovascular consequences. The aim of this study was to investigate the strongest correlate of cardiovascular health (CVH) in female breast cancer survivors, cardiorespiratory fitness or fatness. Methods Fifty-one women (59 ± 9 years, BMI 26.4 ± 4.8 kg/m2) previously diagnosed and treated for primary breast cancer were assessed using pulse wave analysis to determine central arterial wave reflection (augmentation index, AIx) and central systolic blood pressure (cSBP). A composite Z score calculated which incorporated central double product and AIx, as an indicator of CVH. Dual energy X-ray absorptiometry was used to obtain total body fat percentage (BF%). Cardiorespiratory fitness was determined using the single-stage walk test to predict maximal oxygen uptake ( \(V{\text{O}}_{2\hbox{max} }\) ). Results Linear regression analysis revealed that fitness was associated with AIx after adjusting for BF %, age and time post-treatment completion (β = − 0.271, p = 0.010). A significant association between BF% and AIx after adjusting for fitness and age was found (β = 0.166, p = 0.0005); however, this association was lost when time post-treatment was included in the model (β = 0.166, p = 0.167). Both fitness (β = − 0.347, p = 0.0005) and BF% (β = 0.333, p = 0.013) were independently associated with CVH in the fully adjusted model. Conclusions This study provides evidence for an association between cardiorespiratory fitness and cardiovascular health in female breast cancer survivors. While fatness may be associated with cardiovascular health, it appears to be more strongly associated with age.

A novel nipple–areola complex involvement predictive index for indicating nipple-sparing mastectomy in breast cancer patients Abstract Background Nipple-sparing mastectomy (NSM) is increasingly used in breast cancer patients, as it offers better cosmetic outcomes and improves quality of life. Nipple–areola complex (NAC) involvement must be accurately determined to identify which patients may be candidates for NSM. We aimed to identify the predictors of NAC involvement and develop a clinical predictive model to determine the patients for whom NAC preservation may be considered. Patients and methods Patients (n = 168) with primary operable breast cancer who underwent subcutaneous mastectomy for breast reconstruction at Saitama Medical Center from July 2013 to December 2017 were selected from the hospital’s surgical database. Results The clinicopathological factors of tumor size ≧ 4 cm (p < 0.001), nipple-to-tumor distance (NTD) < 1 cm by mammography (p = 0.002), NTD < 1 cm by magnetic-resonance imaging (MRI) (p < 0.001), nipple contrast findings by MRI (p < 0.001), tumor in central portion (p < 0.001), multicentric/focal lesion (p < 0.001), and clinical node involvement (p = 0.014) were significantly associated with the presence of NAC involvement. Each predictor was scored 0 or 1. A score of 0–3 points was defined as low risk, 4 points as intermediate risk, and 5–7 points as high risk. Using these classification criteria, NAC involvement rate was determined to be 3.5% in low-risk, 68.7% in intermediate-risk, and 90.0% in high-risk specimens. A significant correlation was observed between the risk group and NAC involvement (p < 0.001). Conclusion This nipple–areola complex involvement predictive index can be used to determine the appropriate indication for NSM in breast cancer patients who request NAC preservation with more oncological safety.

Simultaneous comparison between strain and shear wave elastography of breast masses for the differentiation of benign and malignant lesions by qualitative and quantitative assessments Abstract Purpose To compare the addition of diagnostic strain elastography (SE) and shear wave elastography (SWE) values to the conventional B-mode ultrasonography in differentiating between benign and malignant breast masses by qualitative and quantitative assessments. Materials and methods B-mode ultrasound, SE, and SWE were simultaneously performed using one ultrasound system in 148 breast masses; 88 of them were malignant. The breast imaging reporting and data system category in the B-mode, Tsukuba score (SETsu), Fat-Lesion-Ratio (SEFLR) in SE, and five-point color assessment (SWEcol) and elasticity values (SWEela) in SWE were assessed. The results were compared using the area under the receiver-operating characteristic curve (AUC). Result The AUC for B-mode and each elastography were similar (B-mode, 0.889; SETsu, 0.885; SEFLR, 0.875; SWEcol, 0.881; SWEela, 0.885; P > 0.05). The combined sets between B-mode and either of the elastography technique showed good diagnostic performance (B-mode + SETsu, 0.903; B-mode + SEFLR, 0.909; B-mode + SWEcol, 0.919; B-mode + SWEela, 0.914). B-mode + SWEcol and B-mode + SWEela showed a higher AUC than B-mode alone (P = 0.026 and 0.029), and B-mode + SETsu and B-mode + SEFLR showed comparable AUC to B-mode alone (P = 0.196 and 0.085). There was no significant difference between qualitative and quantitative assessments for the combined sets of B-mode and elastography (P > 0.05). Conclusion The addition of both SE and SWE to B-mode ultrasound improved the diagnostic performance with increased AUC, and especially SWE was more useful than SE, and no significant difference was found between qualitative and quantitative assessments.