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Background: The current research aims to elucidate the interplay between the anatomical distribution of spinal metastases, MRI features, and the intensity of bone pain in patients with breast cancer. Methods: A retrospective analysis was used on a cohort of 45 breast cancer patients with verified spinal metastases, examining the relationship between metastatic locations, MRI-derived metrics, and bone pain scores. The Visual Analogue Scale (VAS) was conducted to measure the severity of bone pain. Results: The results revealed a significant association between lumbar spine metastases and elevated pain scores, outpacing those observed in thoracic and cervical regions. Furthermore, a strong correlation was found between the multiplicity of metastatic sites and the ratio of high-intensity areas on MRI, both of which were predictive of increased pain severity. Conclusions: The study's outcomes indicate that distinct MRI profiles, including the number and location of spinal metastases, can serve as prognostic indicators of bone pain intensity in breast cancer patients. Our data highlighted the need for personalized pain management strategies and targeted interventions tailored to specific imaging characteristics. Ultimately, this research underscores the dual role of MRI in both detecting spinal metastases and informing symptom management, with the potential to augment the overall well-being of breast cancer patients with spinal involvement., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

To promote the generalization ability of breast tumor segmentation models, as well as to improve the segmentation performance for breast tumors with smaller size, low-contrast and irregular shape, we propose a progressive dual priori network (PDPNet) to segment breast tumors from dynamic enhanced magnetic resonance images (DCE-MRI) acquired at different centers. The PDPNet first cropped tumor regions with a coarse-segmentation based localization module, then the breast tumor mask was progressively refined by using the weak semantic priori and cross-scale correlation prior knowledge. To validate the effectiveness of PDPNet, we compared it with several state-of-the-art methods on multi-center datasets. The results showed that, comparing against the suboptimal method, the DSC and HD95 of PDPNet were improved at least by 5.13% and 7.58% respectively on multi-center test sets. In addition, through ablations, we demonstrated that the proposed localization module can decrease the influence of normal tissues and therefore improve the generalization ability of the model. The weak semantic priors allow focusing on tumor regions to avoid missing small tumors and low-contrast tumors. The cross-scale correlation priors are beneficial for promoting the shape-aware ability for irregular tumors. Thus integrating them in a unified framework improved the multi-center breast tumor segmentation performance.

Breast cancer was the fourth leading cause of cancer-related death worldwide, and early mammography screening could decrease the breast cancer mortality. Artificial intelligence (AI)-assisted diagnose system based on machine learning (ML) methods can help improve the screening accuracy and efficacy. This study aimed to systematically review and make a meta-analysis on the diagnostic accuracy of mammography diagnosis of breast cancer through various ML methods. Springer Link, Science Direct (Elsevier), IEEE Xplore, PubMed and Web of Science were searched for relevant studies published from January 2000 to September 2021. The study was registered with the PROSPERO International Prospective Register of Systematic Reviews (protocol no. CRD42021284227). A Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used to assess the included studies, and reporting was evaluated using the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). The pooled summary estimates for sensitivity, specificity, the area under the receiver operating characteristic curve (AUC) for three ML methods (convolutional neural network [CNN], artificial neural network [ANN], support vector machine [SVM]) were calculated. A total of 32 studies with 23,804 images were included in the meta-analysis. The overall pooled estimate for sensitivity, specificity and AUC was 0.914 [95% CI 0.868-0.945], 0.916 [95% CI 0.873-0.945] and 0.945 for mammography diagnosis of breast cancer through three ML methods. The pooled sensitivity, specificity and AUC of CNN were 0.961 [95% CI 0.886-0.988], 0.950 [95% CI 0.924-0.967] and 0.974. The pooled sensitivity, specificity and AUC of ANN were 0.837 [95% CI 0.772-0.886], 0.894 [95% CI 0.764-0.957] and 0.881. The pooled sensitivity, specificity and AUC of SVM were 0.889 [95% CI 0.807-0.939], 0.843 [95% CI 0.724-0.916] and 0.913. Machine learning methods (especially CNN) show excellent performance in mammography diagnosis of breast cancer screening based on retrospective studies. More rigorous prospective studies are needed to evaluate the longitudinal performance of AI., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Phyllodes tumor (PT) is a solid fibroepithelial breast lesion with proliferation of stromal and epithelial elements, usually presents with a rapidly expanding feature. Venous thromboembolism (VTE) have been reported to increase the burden in terms of mortality and morbidity of malignant tumor, and associate with worsened survival. However, benign PTs with silent thromboembolism that have not yet been reported, we report an unusual case of massive benign PT that grew on the left side of the breast in a cauliflower-shaped form and presented severe chronic blood loss and deep VTE., Case: A 37-year-old woman with uncontrolled pain presented a rapidly enlarging left breast mass, measuring approximately 30 × 20 × 15 cm 3 that first started 25 years ago. color Doppler ultrasound showed a large mass lesion on the left breast and deep VTE, several enlarged lymph nodes in the left axilla and mediastinum, which presented a malignant character. However, the biopsies of the mass did not show evidence of malignancy and the pathology result was considered to be benign PT. The patient was treated with an inferior vena cava and anticoagulation, the operation was arranged according to the surgical procedure, the patient recovered very well after mastectomy., Conclusion: This case is unique in that the giant breast mass presented with malignant character, was eventually pathologically confirmed to be benign PT, and it's rare that the benign tumor accompanied with silent thromboembolism. This finding describes the atypia features of giant benign PT and reminds the surgeon to consider the factor of VTE and risk when encountering ulcerative benign breast tumor and avoid excessive treatment., (© 2023 The Authors. Cancer Reports published by Wiley Periodicals LLC.)

During disease progression and bone metastasis, breast tumor cells interact with various types of bystander cells residing in the tumor microenvironment. Such interactions prompt tumor cell heterogeneity. We used successive co-culture as an experimental model to examine cancer-bystander cell interaction. RMCF7-2, a clone of the human breast cancer MCF-7 cells tagged with a red fluorescent protein, was tracked for morphologic, behavioral, and gene expression changes. Co-cultured with various types of hematopoietic cells, RMCF7-2 adopted stable changes to a rounded shape in suspension growth of red fluorescent cells, from which derivative clones displayed marked expressional changes of marker proteins, including reduced E-cadherin and estrogen receptor α, and loss of progesterone receptor. In a successive co-culture with bone marrow-derived mesenchymal stem/stromal cells, the red fluorescent clones in suspension growth changed once more, adopting an attachment growth, but in diversified shapes. Red fluorescent clones recovered from the second-round co-culture were heterogeneous in morphology, but retained the altered marker protein expression while displaying increased proliferation, migration, and xenograft tumor formation. Interaction with bystander cells caused permanent morphologic, growth behavioral, and gene expressional changes under successive co-culture, which is a powerful model for studying cancer cell heterogeneity during breast cancer progression and metastasis.

Objective: To determine the ability of conventional ultrasound (US) combined with shear wave elastography (SWE) to reveal axillary status after neoadjuvant chemotherapy (NAC) in breast cancer patients., Methods: From September 2016 to December 2021, 201 patients with node-positive breast cancer who underwent NAC were enrolled in this prospective study. Conventional US features of axillary lymph nodes and SWE characteristics of breast lesions after NAC were analyzed. The diagnostic performances of US, SWE, and their combination were assessed using multivariate logistic regression and receiver operator characteristic curve (ROC) analyses., Results: The area under the ROC curve (AUC) for the ability of conventional US features to determine axillary status after NAC was 0.82, with a sensitivity of 85.23%, a specificity of 67.39%, and an accuracy of 76.11%. Shear wave velocity (SWV) displayed moderate performance for predicting axilla status after NAC with SWV mean demonstrating an AUC of 0.85. Cortical thickness and shape of axillary nodes and SWV mean of breast tumors were independently associated with axillary nodal metastasis after NAC. Compared to conventional US, the combination of conventional US of axillary lymph nodes with SWE of breast lesions achieved a significantly higher AUC (0.90 vs 0.82, p < 0.01, Delong's test) with a sensitivity of 87.50%, improved specificity of 82.61% and accuracy of 85.00%., Conclusions: Breast SWE was independently associated with residual metastasis of axillary node after NAC in patients with initially diagnosed positive axilla. Combining SWE with conventional US showed good diagnostic performance for axillary node disease after NAC., Key Points: • Breast SWE can serve as a supplement to axilla US for the evaluation of the axilla after NAC. • The combination of axilla US with breast SWE may be a promising method to facilitate less-invasive treatment in patients receiving NAC., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

The tumor-adipose microenvironment (TAME) is a universal microecosystem, that is characterized by the dysfunction of lipid metabolism, such as excessive free fatty acids (FFAs). Macrophages are the most abundant immune cell type within TAME, although their diversity in the TAME is not clear. We first reveal that infiltration of M2-like macrophages in the TAME is associated with poor survival in breast cancer. To explore lipid-associated alterations in the TAME, we also detected the levels of FFAs transporters including fatty acid binding proteins (FABPs) and fatty acid transport protein 1 (FATP1). The results indicated that expression of fatty acid transporters in the TAME is tightly linked to the function of macrophages and predicts survival in breast cancer. To explore the impact of FFAs transporters on the function of macrophages, we performed single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics. Consequently, we identified a special subpopulation of macrophages defined as lipid-associated macrophages (LAMs), highly expressed macrophage markers (CD163, SPP1 and C1QC), genes involved in lipid metabolism (FABP3, FABP4, FABP5, LPL and LIPA) and some lipid receptors (LGALS3 and TREM2). Functionally, LAMs were characterized by a canonical functional signature of M2-like macrophages, lipid accumulation and enhancing phagocytosis, and they were mostly distributed in tumor-adipose junctional regions. Finally, the allograft cancer mouse models confirmed that LAMs depletion in the TAME synergizes the antitumorigenic effects of anti-PD1 therapy. In summary, we defined a novel subtype of macrophages in the TAME, that has unique features and clinical outcomes., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Aerobic glycolysis (the Warburg effect) has been demonstrated to facilitate tumor progression by producing lactate, which has important roles as a proinflammatory and immunosuppressive mediator. However, how aerobic glycolysis is directly regulated is largely unknown. Here, we show that ectopic Zeb1 directly increases the transcriptional expression of HK2, PFKP, and PKM2, which are glycolytic rate-determining enzymes, thus promoting the Warburg effect and breast cancer proliferation, migration, and chemoresistance in vitro and in vivo. In addition, Zeb1 exerts its biological effects to induce glycolytic activity in response to hypoxia via the PI3K/Akt/HIF-1α signaling axis, which contributes to fostering an immunosuppressive tumor microenvironment (TME). Mechanistically, breast cancer cells with ectopic Zeb1 expression produce lactate in the acidic tumor milieu to induce the alternatively activated (M2) macrophage phenotype through stimulation of the PKA/CREB signaling pathway. Clinically, the expression of Zeb1 is positively correlated with dysregulation of aerobic glycolysis, accumulation of M2-like tumor-associated macrophages (TAMs) and a poor prognosis in breast cancer patients. In conclusion, these findings identify a Zeb1-dependent mechanism as a driver of breast cancer progression that acts by stimulating tumor-macrophage interplay, which could be a viable therapeutic target for the treatment of advanced human cancers., (© 2022. The Author(s).)

Circulating adiponectin has some association with the risk of osteoporosis and cancers, but their causal relationships remains elusive. Mendelian randomization (MR) study was used to explore the causal roles of circulating adiponectin in osteoporosis and cancers by using genome-wide association studies (GWASs) associated with circulating adiponectin, osteoporosis and cancers. Fifteen single nucleotide polymorphisms (SNPs) were used as instrumental variables for circulating adiponectin. Genetic predisposition to high circulating adiponectin was strongly associated with low femoral neck bone mineral density (FN-BMD, beta-estimate: -0.015, 95% CI: -0.023 to -0.006, SE: 0.004, P-value = 0.001), low forearm BMD (FA-BMD, beta-estimate: -0.027, 95% CI: -0.050 to -0.004, SE: 0.012, P-value = 0.023) and increased risk of breast cancer (beta-estimate: 0.011, 95% CI: 0.001 to 0.022, SE: 0.005, P-value = 0.031). There was limited evidence of the associations between circulating adiponectin and other outcomes (i.e. lumbar spine BMD [LS-BMD], colorectal cancer, liver cancer, lung cancer, bone cancer and prostate cancer). This study provides robust evidence that high circulating adiponectin is causally associated with low FN-BMD, low FA-BMD and increased risk of breast cancer, which may provide new insight to prevent and treat osteoporosis and breast cancer., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Zinc finger E-box binding homeobox 1 (Zeb1) has been demonstrated to participate in the acquisition of the properties of cancer stem cells (CSCs). However, it is largely unknown how signals from the tumor microenvironment (TME) contribute to aberrant Zeb1 expression. Here, we show that Zeb1 depletion suppresses stemness, colonization and the phenotypic plasticity of breast cancer. Moreover, we demonstrate that, with direct cell-cell contact, TME-derived endothelial cells provide the Notch ligand Jagged1 (Jag1) to neighboring breast CSCs, leading to Notch1-dependent upregulation of Zeb1. In turn, ectopic Zeb1 in tumor cells increases VEGFA production and reciprocally induces endothelial Jag1 in a paracrine manner. Depletion of Zeb1 disrupts this positive feedback loop in the tumor perivascular niche, which eventually lessens tumor initiation and progression in vivo and in vitro. In this work, we highlight that targeting the angiocrine Jag1-Notch1-Zeb1-VEGFA loop decreases breast cancer aggressiveness and thus enhances the efficacy of antiangiogenic therapy.

Purpose: Breast cancer is responsible for high morbidity and mortality across the globe. Studies are focusing to develop novel systemic therapies for the treatment of this disease. The present study was designed to examine the anticancer effects of Shionone against human breast cancer cells along with the underlying mechanism of its action., Methods: The breast cancer SK-BR-3 and normal breast MB-157 cell lines were used in the study. CCK8 assay was used for cell viability assessment. DAPI was used for the assessment of nuclear morphology. Acridine orange (AO)/ ethidium bromide (EB) and annexin V/propidium iodide (PI) assays were used for detection of apoptosis. Cell cycle analysis was done by flow cytometry. Protein expression was examined by western blot analysis., Results: The results showed that in vitro administration of Shionone led to decline of proliferation of breast cancer cells. The reduction of proliferative rates was attributed to the induction of apoptosis of breast cancer cells. Shionone caused cleavage of caspase-3 and 9. The expression of Bax was increased and that of Bcl-2 was decreased upon Shionone treatment. The transwell assays showed that Shionone suppressed the migration and invasion of breast cancer cells in a dose-dependent manner. Finally, western blot analysis showed that Shionone blocked the Ras/Raf/MEK/ERK and STAT3 signaling pathways in breast cancer cells., Conclusion: Taken all together, the study established the anticancer role of triterpenoid Shionone in restricting the growth and proliferation of human breast cancer cells.

Objective: To explore the effects of pedicled rectus abdominis myocutaneous (PRAM)flap combined with free deep inferior epigastric artery perforator (DIEAP) flap carrying inguinal lymphatic flap in breast reconstruction and upper limb lymphedema treatment post radical mastectomy. Methods: From October 2014 to September 2016, 9 patients with upper limb lymphedema after mastectomy were treated with PRAM flap combined with free DIEAP flap carrying inguinal lymphatic flap for breast reconstruction and upper limb lymphedema treatment in Hunan Province Cancer Hospital. The patients were all females, aged 34-66 (44±7) years. The location of deep inferior epigastric artery perforator was detected by audible Doppler ultrasound blood stream detector and computed tomography angiography for designing combined tissue flap, with length of (25.32±0.27) cm, width of (13.14±0.76) cm, and thickness of (3.55±0.34) cm. The donor site of combined tissue flap was closed by suturing, and two or more tubes for negative pressure drainage were placed according to the situation of donor site and recipient site. Operation time and average placing time of negative pressure drainage tube, postoperative condition of combined tissue flap and the donor site, reconstructed breast condition, recovery of upper limb lymphedema were documented and followed up. Results: The operation time was 290-420 (396±55) min. The average retaining time of negative pressure drainage tube in breast was 5.9 d, while the average retaining time of negative pressure drainage tube in abdomen was 4.3 d. Ecchymoma occurred in DIEAP flap of one patient and in the flap donor site of another patient. Delayed healing was also seen in the rectus abdominis myocutaneous flap of a patient, which healed eventually after dressing change, and the other flaps survived well. The appearance of reconstructed breast was good with good elasticity, and no contracture or deformation occurred in the tissue flap. The upper limb lymphedema in 7 patients was alleviated in varying degrees, with 2.0-4.0 cm reduction in circumference. During follow-up of 12-24 months of 9 patients, averaged 17.5 months, with 6 patients received long term bandage pressure therapy and physical therapy to the affected limbs after operation and all patients were satisfied with appearances of the affected limbs. Neuropathic pain in affected limbs was significantly relieved in 2 patients and stopped aggravating in the other 2 patients. Only linear scar was seen in the donor site of abdomen without affecting obviously the function of abdomen. Conclusions: The PRAM flap combined with free DIEAP flap carrying inguinal lymphatic flap is an effective way for breast reconstruction and upper limb lymphedema treatment post mastectomy.

Objective: Current conclusions on the potential influence of the single nucleotide polymorphism (SNP) of Matrix metalloproteinase-2 (MMP)-2-1306 C>T on Breast cancer (BCa) susceptibility remain controversial. This study aims to accurately clarify their relation., Materials and Methods: The relevant literature on the relation between genetic variation of MMP-2 and BCa susceptibility was searched in PubMed, Web of School, VIP, and CNKI published before March 2019. The keywords used were as follows: "MMP-2, breast/mammary cancer/carcinoma/tumor" or "SNPs of MMP-2, breast/mammary cancer/carcinoma/tumor". Odds ratio (OR) and 95% CI of extracted data from eligible literature were calculated., Results: A total of 7 studies involving 1823 BCa patients and 1899 healthy controls were included. All control genes were consistent with HWE (p>0.05). Different genetic models were utilized to clarify the potential influence of MMP-2-1306 C>T (rs243865) on BCa susceptibility. No significant correlation was identified between the SNP of MMP-2-1306 C>T and BCa susceptibility based on the calculated OR and 95% CI in different genotypes: CC vs. CT&TT: p=0.54, OR=0.88 (95% CI=0.58-1.33); TT vs. CC&CT: p=0.67, OR=1.07 (95% CI=0.79-1.44); CC vs. TT: p=0.73, OR=0.95 (95% CI=0.70-1.29); C Allele vs. T Allele: p=0.93, OR=1.02 (95% CI=0.70-1.47)., Conclusions: The SNP of MMP-2-1306 C>T did not correlate to the susceptibility to BCa.

Objective: To explore the clinical effects of free deep inferior epigastric perforator flap carrying lymphatic groin flap for treatment of upper limb lymphedema after radical mastectomy and breast reconstruction. Methods: From October 2014 to December 2016, 10 female patients, aged 37-60 (48±8) years, who had lymphedema in the upper limb after radical mastectomy, were admitted to Department of Oncology Plastic Surgery of Hunan Cancer Hospital. Three patients suffered recurrent erysipelas infections, and 4 patients suffered consistent neuropathic pain in the upper limb. Free deep inferior epigastric perforator flap carrying lymphatic groin flap was used for breast reconstruction and lymphedema treatment. Operation was performed by 2 surgeon groups including recipient site prepare group and flap harvest group. In the 10 patients, the length of the flaps was (26.2±0.3) cm, the width of the flaps was (13.4±0.4) cm, and the thickness of the flaps was (3.4±0.3) cm. All the donor sites in the abdomen were closed directly. The choices of vascular pedicles and vessels in the recipient sites, operation time, complications, operation effects, and follow-up were recorded. Results: (1) Bilateral vascular pedicle was adopted in flaps of 5 patients. Unilateral vascular pedicle was adopted in flaps of 5 patients. The recipient vessels were proximal and distal ends of internal thoracic vessels in 4 cases, the proximal end of thoracodorsal vessels in 3 cases, the proximal end of internal thoracic vessels in 2 cases, and the proximal end of internal thoracic vessels and thoracodorsal vessels in 1 case. (2) The operation time of the patients was 330-480 (406±55) min. (3) Subcutaneous edema was observed in flaps of 2 patients and donor site of 1 patient, which were all healed by dressing change therapy. The other flaps survived successfully. The reconstructed breasts were in good shape and elasticity. Nine patients had different degrees of relief in lymphedema in the upper limb. All 10 patients were followed up for 6 to 28 months, no one had recurrent erysipelas infections, and neuropathic pain in the upper limb was relieved in 2 patients. Only linear scar was left in the donor sites of 10 patients, and the function of abdomen was not affected without related complications. Conclusions: Free deep inferior epigastric perforator flap carrying lymphatic groin flap can simultaneously accomplish breast reconstruction and upper limb lymphedema treatment, which is worthwhile to be popularized in clinic.

Objective: To summarize the application progress of indocyanine green (ICG) angiography in breast reconstruction., Methods: The literature about the application of ICG angiography in breast reconstruction was reviewed and analyzed, including its history, chemical composition, principles, usages, and attentions., Results: ICG is a kind of fluorescent substance used in medical diagnosis and various surgical fields, especially in intraoperative vascular angiography. ICG angiography and SPY system are gradually applied in breast reconstruction, including both prosthesis/tissue expander reconstruction and autologous reconstruction. Compared to clinical judgment, portable Doppler devices, tissue oximetry, and fluorescein angiography, ICG angiography obviously has more benefits and usages., Conclusion: ICG angiography can reveal the perfusion of flaps during the operation instantly and accurately, which refines the intraoperative strategy in order to decrease the incidence of flap-related complications. Besides, it has some economic benefits to some extent.

Objectives: To explore factors affecting the quality of quasistatic ultrasound elastograms of the breast and to evaluate their accuracy in distinguishing benign and malignant breast lesions., Methods: A total of 663 patients with 702 breast lesions were recruited. All patients received both conventional ultrasonography and quasistatic elastography. Patients' breast lesions were divided into A and B groups according to satisfactory and unsatisfactory elastographic examinations. Group A included 590 satisfactory elastograms, whereas Group B included 112 unsatisfactory elastograms. Various factors-maximum depth of the lesion, maximum transverse diameter of the lesion, thickness of the adipose layer, thickness of the glandular layer, thickness of the breast, distance between the nipple and lesion, age, body mass index, and menopausal status-were analyzed and compared between the groups to gauge their effects on the quality of the elastograms., Results: Significantly deeper lesions, higher maximum transverse lesion diameters, thicker adipose layers, thicker glandular layers, and thicker breasts were identified in group B patients compared to group A patients (P < .05). Multivariate logistic regression analyses showed that the maximum depth of the lesion, thickness of the adipose layer, and thickness of the breast were independent factors in the quality of elastograms. The area under the curve for the maximum depth of the lesion was 0.986 with the optimal cutoff threshold of 2.5 cm., Conclusions: Quasistatic elastography can be a supplementary approach to conventional ultrasonography in helping improve the diagnostic accuracy of breast lesions. The depth and size of breast lesions are correlated with the quality of elastograms., (© 2017 by the American Institute of Ultrasound in Medicine.)

Background: We have previously demonstrated the anticancer effect of anthocyanins. In this study, we explored the biological activities of delphinidin, the most common of the anthocyanidin monomers, that were related to autophagy in HER-2 positive breast cancer MDA-MB-453 and BT474 cells., Methods: The effects of various doses of delphinidin on the proliferation and apoptosis of MDA-MB-453 and BT474 cells were analysed. Autophagy was identified as a critical factor that influenced chemotherapy, and the autophagic mechanism in delphinidin-treated cells was investigated. The autophagy inhibitors, 3-MA and BA1, were used to analyse the effects of autophagy inhibition., Results: Delphinidin inhibited proliferation, promoted apoptosis, and induced autophagy in MDA-MB-453 and BT474 cells in a dose-dependent manner. The inhibition of autophagy enhanced the delphinidin-induced apoptosis and antiproliferative effect in both HER-2 positive breast cancer cells. In addition, delphinidin induced autophagy via suppression of the mTOR signalling pathway and activation of the AMPK signalling pathway in HER-2 positive breast cancer cells., Conclusions: Collectively, the results showed that delphinidin induced apoptosis and autophagy in HER-2 positive breast cancer cells and that autophagy was induced via the mTOR and AMPK signalling pathways. The suppression of autophagy promoted the anticancer effects of delphinidin.

The aim of this study was to explore whether intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) can probe pre-treatment differences or monitor early response in patients with locally advanced breast cancer receiving neoadjuvant chemotherapy (NAC). Thirty-six patients with locally advanced breast cancer were imaged using multiple-b DWI with 12 b values ranging from 0 to 1000  s/mm(2) at the baseline, and 28 patients were repeatedly scanned after the second cycle of NAC. Subjects were divided into pathologic complete response (pCR) and nonpathologic complete response (non-pCR) groups according to the surgical pathologic specimen. Parameters (D, D*, f, maximum diameter [MD] and volume [V]) before and after 2 cycles of NAC and their corresponding change (Δparameter) between pCR and non-pCR groups were compared using the Student t test or nonparametric test. The diagnostic performance of different parameters was judged by the receiver-operating characteristic curve analysis. Before NAC, the f value of pCR group was significantly higher than that of non-pCR (32.40% vs 24.40%, P = 0.048). At the end of the second cycle of NAC, the D value was significantly higher and the f value was significantly lower in pCR than that in non-pCR (P = 0.001; P = 0.015, respectively), whereas the D* value and V of the pCR group was slightly lower than that of the non-pCR group (P = 0.507; P = 0.676, respectively). ΔD was higher in pCR (-0.45 × 10(-3)  mm(2)/s) than that in non-pCR (-0.07 × 10(-3)  mm(2)/s) after 2 cycles of NAC (P < 0.001). Δf value in the pCR group was significantly higher than that in the non-pCR group (17.30% vs 5.30%, P = 0.001). There was no significant difference in ΔD* between the pCR and non-pCR group (P = 0.456). The prediction performance of ΔD value was the highest (AUC [area under the curve] = 0.924, 95% CI [95% confidence interval] = 0.759-0.990). When the optimal cut-off was set at -0.163 × 10(-3)  mm(2)/s, the values for sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were up to 100% (95% CI = 66.4-100), 73.7% (95% CI = 48.8-90.9), 64.3% (95% CI = 35.6-86.0), and 100% (95% CI = 73.2-99.3), respectively. IVIM-derived parameters, especially the D and f value, showed potential value in the pre-treatment prediction and early response monitoring to NAC in locally advanced breast cancer. ΔD value had the best prediction performance for pathologic response after NAC., Competing Interests: The authors have no conflicts of interest to disclose.

Purpose: To evaluate DRAMMS, an attribute-based deformable registration algorithm, compared to other intensity-based algorithms, for longitudinal breast MRI registration, and to show its applicability in quantifying tumor changes over the course of neoadjuvant chemotherapy., Methods: Breast magnetic resonance images from 14 women undergoing neoadjuvant chemotherapy were analyzed. The accuracy of DRAMMS versus five intensity-based deformable registration methods was evaluated based on 2,380 landmarks independently annotated by two experts, for the entire image volume, different image subregions, and patient subgroups. The registration method with the smallest landmark error was used to quantify tumor changes, by calculating the Jacobian determinant maps of the registration deformation., Results: DRAMMS had the smallest landmark errors (6.05 ± 4.86 mm), followed by the intensity-based methods CC-FFD (8.07 ± 3.86 mm), NMI-FFD (8.21 ± 3.81 mm), SSD-FFD (9.46 ± 4.55 mm), Demons (10.76 ± 6.01 mm), and Diffeomorphic Demons (10.82 ± 6.11 mm). Results show that registration accuracy also depends on tumor versus normal tissue regions and different patient subgroups., Conclusions: The DRAMMS deformable registration method, driven by attribute-matching and mutual-saliency, can register longitudinal breast magnetic resonance images with a higher accuracy than several intensity-matching methods included in this article. As such, it could be valuable for more accurately quantifying heterogeneous tumor changes as a marker of response to treatment., (© 2014 Wiley Periodicals, Inc.)

Background: Centrally necrotizing carcinoma of the breast (CNC) represents a newly-identified subset of breast cancer. The clinical and pathological characteristics of this breast cancer subtype are not yet completely understood., Methods: We assessed the clinicopathological characteristics of 73 cases of CNC and 30 control cases of high-grade infiltrating ductal carcinoma (IDC) with focal necrosis based on light microscopy and immunohistochemical staining for estrogen receptor, progesterone receptor, Cerb-B2/HER2, Ki-67, epidermal growth factor receptor, cytokeratin 5/6, smooth muscle actin, S-100 protein, p63 and CD10., Results: All the tumors showed extensive central necrotic or acellular zones with different degrees of fibrotic or hyaline material surrounded by ring-like or ribbon-like residual tumour tissue which were usually high-grade IDCs. The central necrotic zone accounted for at least 30% of the cross-sectional area of the tumor. Thirty-six cases (49.3%) showed a component of ductal carcinoma in situ. The tumorous stroma around the central necrotic zone was accompanied by myxoid matrix formation in 28 cases (40%). Lymphocytic infiltration was present in 53 cases (72.6%). Granulomatous reactions were detected at the periphery of the tumors in 49 cases (67.1%). Immunohistochemistry showed greater expression of basal-like markers (72.2%, 52 cases) than myoepithelial markers (60.6%, 43 cases), both of which were significantly higher than in controls (26.7%, 8 cases) (P < 0.001). According to molecular typing, most CNCs were basal-like subtype (37 cases, 50.7%). Follow-up data were available for 28 patients. Disease progression occurred in 11 patients. The combined rate of recurrence, distant metastasis or death was significantly higher in CNC patients compared with controls (P < 0.05)., Conclusions: CNC was associated with distinctive clinicopathologic features mostly characterized as basal-like type. Its high proliferative activity, highly-aggressive biological behavior, and high rates of recurrence and metastasis, suggest that CNC should be classified as a new type of breast carcinoma.

The specific mechanism underlying the role of putative stem cell marker aldehyde dehydrogenase 1 (ALDH1) playing in development and progression of breast cancer is currently unclear. Transforming growth factor β (TGFβ) signaling pathway is reported to be activated in most cancers. Thus a study was initiated to explore possible differences and correlation of ALDH1 and TGFβ2 expression in the most common malignant and benign tumors of the breast in Chinese women. Samples of 75 breast cancer tissues, 30 paracancerous normal tissues, and 39 fibroadenoma breast tissues were investigated for the expression of ALDH1 and TGFβ2 using immunohistochemistry. The positive rates of ALDH1 and TGFβ2 protein were 62.67% and 66.67%, respectively, in breast cancer tissues, which were significantly higher than that in normal fibroadenoma breast (P<0.05) and paracancerous tissues (P<0.01). ALDH1 and TGFβ2 status were significantly associated with tumor histological grade and receptor status (P<0.05). Expression of ALDH1 was found to be positively correlative to TGFβ2 in breast cancer (r = 0.33, P<0.01). Expression of both proteins remained significantly associated with reduced overall survival (OS) by univariate analysis (P<0.05). Multivariate Cox regression analysis showed that ALDH1 expression, tumor stage, and lymph node status are independent prognostic factors in invasive breast cancer patients. Thus ALDH1 and TGFβ2 play important roles in the development of breast cancer. The ALDH1 phenotype is an independent predictor of poor prognosis, and TGFβ2 signaling pathway activation might be involved in the pathological regulation of ALDH1 in breast cancer.

Background: To validate the clinical value of the One-Step Nucleic Acid Amplification (OSNA) Breast Cancer System for the intraoperative detection of sentinel lymph node (SLN) metastases in early-stage breast cancer patients in a Chinese population, a prospective, multicenter trial, the China Breast Cancer Clinical Study Group (CBCSG)-001c trial, was conducted. The present study focused on the prospective comparison of the performance between OSNA and touch imprint cytology (TIC)., Methods: The retrieved SLNs were divided into sections. Alternate slices from the tissue blocks were subjected either to OSNA analysis or to postoperative histopathology evaluation through serial sectioning. TIC was performed on every sample surface of each tissue block and was used by the surgeon to determine whether to perform an immediate ALND., Results: A total of 552 patients qualified for the analysis. The sensitivity, specificity, and overall accuracy of OSNA were 87.8%, 89.6%, and 88.4%, respectively, on a per-patient basis compared with those of TIC, which were 81.3%, 96.9%, and 92.0%, respectively. OSNA detected more micrometastasis-involved nodes than TIC (52.8% vs. 25.0%; p = 0.029) on a per-node basis. Tissue allocation bias (TAB) was the main cause of discordant results. The performance of TIC varied significantly among the institutes, while the performance of OSNA was steady., Conclusions: Both OSNA and TIC can serve as qualified intraoperative assessments of SLNs. For institutes lacking the support of experienced cytopathologists, OSNA can be the first choice for the intraoperative assessment. In addition, OSNA can be applied as a complement to histopathology assessment. However, the results of the present study do not support the routine application of OSNA in the entire SLNs in place of pathology with serial sectioning., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Human lactoferrin (hLTF) is an 80KD iron-binding protein. It has been reported that hLTF exists anti-tumor effects. In this study Adenovirus Vectors Mediated Human Lactoferrin cDNA (ad-rhLTF) was constructed and an antitumor effects of ad-rhLTF were investigated in mice bearing EMT6 breast carcinoma. The results demonstrated that ad-rhLTF (5 x 10(8) and 25 x 10(8) pfu/ml local injection) had high expression in tumor tissues and effectively reduced the weight of EMT6 breast tumors. Compared with the control group, cell cycle assay by flow cytometry showed that ad-rhLTF increased the percentage of tumor cells in the Sub-G1 phase and G0/G1 phase and the apoptotic number reached to 23.2% in ad-rhLTF group (25 x 10(8) pfu/ml). Ad-rhLTF treatment also resulted in a decrease of Bcl-2 and an increase in Bax and caspase 3 expressions, which was demonstrated by immunohistochemical analysis and RT-PCR. These data suggest that the antitumor effects of ad-rhLTF might be associated with arresting tumor cells in the G0/G1 phase, inducing cell apoptosis and regulation of the expression of Bcl-2, Bax and activation of caspase 3.

Human lactoferrin (hLTF), an 80-kDa iron-binding glycoprotein, has antitumor activity. In this study, a recombinant adenovirus containing the human lactoferrin cDNA (ad-rhLTF) was constructed and its effect on tumor growth was investigated in mice bearing EMT6 breast cancer. Ad-rhLTF was injected seven times within 14 days into the tumor site at two concentrations (10(8) and 5 × 10(8) pfu/mL) in mice bearing EMT6 breast cancer. Injected ad-rhLTF had considerable cytotoxicity on mice breast cancer, and significantly reducing the weight of tumor produced and increasing the tumor inhibition rate up to 52.64%. The presence of apoptotic cells was confirmed using TUNEL staining and flow cytometry assays. At the same time, RTPCR and Western blot analyses demonstrated that ad-rhLTF also decreased expression of Bcl-2 and increased Bax and caspase 3 expressions. Therefore, we conclude that ad-rhLTF inhibits tumor growth by inducing tumor cell apoptosis in mice with breast cancer by triggering the mitochondrial-dependent pathway and activation of caspase 3. The results indicate that ad-rhLTF might be a promising drug for breast cancer gene therapy.