The oncological safety and long-term cosmetic effect of free dermal fat graft with epidermis removal for breast defect repair in breast conserving surgery.

BACKGROUND: Free dermal fat grafts (FDFG) are used for immediate breast defect repair in breast-conserving surgery (BCS), and have achieved satisfactory immediate postoperative cosmetic effects (Sawai et al., 2004) [1]. However, the oncologic safety and long-term cosmetic outcomes of these surgical procedures remain unknown. Therefore, t，in this study, we aim to investigate the oncological safety and long-term cosmetic outcomes of FDFG in patients with breast cancer. METHODS: This matched retrospective case-control study included patients with non-special types of breast cancer who underwent FDFG for breast defect repair after BCS or BCS alone at two breast cancer research centers in Guangxi Province, China, from January 2016 to December 2019. The patients were divided into either the FDFG or BCS group. Control cases were screened using propensity score matching, and survival analysis and cosmetic evaluations were performed. RESULTS: A total of 442 patients with breast cancer were included in the study. After 1:4 propensity score matching, 53 and 212 patients were included in the FDFG and BCS groups, respectively. The median follow-up time was 49.9 (9.0-76.0) months. The rate of local recurrence in the FDFG group (9.4 %) was significantly higher than that in the BCS group (1.9 %; p < 0.05). The total cosmetic evaluation score was significantly higher in the BCS group 18 months after surgery than in the FDFG group (p < 0.05). CONCLUSIONS: In this retrospective study, FDFG was significantly associated with an increased risk of local recurrence. Further prospective studies are required to confirm these results. No significant difference in long-term cosmetic effects were observed for FDFG than for BCS alone for immediate breast defect repair.

Expression and Clinical Significance of Origin Recognition Complex Subunit 6 in Breast Cancer - A Comprehensive Bioinformatics Analysis.

OBJECTIVE: We aimed to investigate the expression, diagnostic and prognostic values, and potential molecular mechanisms of the origin recognition complex (ORC) in breast cancer (BC). METHODS: Kaplan-Meier estimation was used to assess the prognostic value of ORC genes, and Oncomine, TCGA, GEO and ULCAN databases were used to analyze their expression in BC. Wilcoxon rank-sum tests were used to evaluate the relationship between ORC gene expression levels and BC clinicopathological features. Receiver operating characteristic (ROC) curves were used to assess the diagnostic value of ORC genes in BC. Survival analysis was performed using Kaplan-Meier estimation and Cox regression. A nomogram was constructed to predict 1-, 3-, and 5-year survival probabilities in BC. Gene set enrichment analysis (GSEA) and immune infiltration were used to investigate potential molecular mechanisms of the ORC. RESULTS: ORC1L and ORC6L were highly expressed in BC compared with healthy tissue, while ORC5L expression patterns were inconsistent; no significant differences in ORC2L, ORC3L or ORC4L expression were observed between BC and healthy tissues. ORC1L and ORC6L expression levels were significantly correlated with age, tumor (T) stage and molecular subtype; ORC5L expression was significantly correlated with age and number of nearby lymph nodes with cancer (N stage). ORC6L expression had the highest diagnostic value in BC and was an independent prognostic factor for poor overall survival (OS). ORC6L may be involved in cell cycle progression and may regulate cancer signaling pathways, including NF-κB, P53, and WNT, in BC. ORC6L expression was also associated with immune infiltration. CONCLUSION: ORC1L and ORC6L are highly expressed in BC; ORC6L has a high diagnostic value and is an independent prognostic factor for poor OS. ORC6L may be involved in the initiation and progression of BC by regulating cell cycle progression, promoting cancer signaling pathway activation, and influencing tumor immune cell infiltration.

H19 Knockdown Suppresses Proliferation and Induces Apoptosis by Regulating miR-130a-3p/SATB1 in Breast Cancer Cells.

PURPOSE: Breast cancer (BC) is the most common cancer in women. Emerging evidence has demonstrated that lncRNAs play an important role in BC. The objective of this study was to investigate the impact of the long non-coding RNA (lncRNA), H19/miRNA-130a-3P/special AT-rich sequence-binding protein-1 (SATB1) axis on BC progression. MATERIALS AND METHODS: Expression of lncRNA and RNA was quantified via RT-qPCR. CCK-8, colony formation, wound healing, transwell, and flow cytometric analyses were used to analyze the proliferation, migration, invasion and apoptosis of cells. A dual-luciferase reporter assay and a RNA immunoprecipitation (RIP) assay were used to assess molecular binding. Protein levels were measured by Western blotting. The function of the lncRNA H19 (hereafter referred to as H19) was examined by xenotransplantation. RESULTS: We demonstrated that H19 expression was higher in cancer tissues and cancer cell lines than in adjacent non-tumor tissues and normal cell lines, respectively. H19 silencing inhibited the proliferation, migration and invasion of BC cells, and induced apoptosis. In addition, H19 directly bound to miR-130a-3p and downregulated its expression. We further demonstrated that H19 sponged miRNA-130a-3p, which resulted in SATB1 upregulation, thus promoting BC progression. Silencing of H19 substantially suppressed BC tumorigenesis in vivo. CONCLUSION: Our data uncovered a novel mechanism of BC progression based on the H19-miR-130a-3p-SATB1 axis.

Determination of Serum Exosomal H19 as a Noninvasive Biomarker for Breast Cancer Diagnosis.

PURPOSE: There is an urgent need for new biomarkers for the diagnosis of breast cancer. Exosomes can communicate with cells through transport molecules, including long-chain noncoding RNA (lncRNA), which is considered as a promising noninvasive biomarker. Here, we aimed to determine the potential of long noncoding RNA (lncRNA) H19 in the circulating exosomes for the diagnosis of breast cancer (BC). MATERIALS AND METHODS: We measured the levels of lncRNA H19 in serum-derived exosomes from patients with breast cancer (BC) or benign breast disease (BBD) and healthy subjects, using quantitative real-time PCR. H19 levels were also measured for pre-operative and post-operative patients. Receiver operating characteristic curve was constructed, and the area under the curve (AUC) was calculated to determine the applicability of exosomal H19 levels as biomarkers in BC. The relationship between H19 relative expression and clinical features of BC patients was also analyzed. RESULTS: Exosomal H19 expression levels were upregulated in patients with BC compared to that in patients with BBD and healthy controls (BC vs BBD, P < 0.001; BC vs healthy subjects, P < 0.001). The median serum exosomal H19 levels were significantly lower in post-operative than that in the pre-operative patients (P < 0.001). The AUC for exosomal H19 analysis was 0.870 (95% CI: 0.774-0.966) with a sensitivity of 87.0% and specificity of 70.6%, which was higher than the AUCs for CA15-3 and CEA, ie, 0.822 and 0.811, respectively. Moreover, exosomal H19 expression levels were associated with lymph node metastasis (P = 0.039), distant metastasis (P = 0.008), TNM stages (P = 0.022), ER (P=0.009), PR (P = 0.018), and Her-2 (P = 0.021). CONCLUSION: Our results indicated that serum exosomal H19 acts as a novel biomarker for the diagnosis of BC.

Long-term comparisons of the efficacy, safety, and pregnancy outcomes of adjuvant tamoxifen plus ovarian function suppression in premenopausal Han and Zhuang Chinese patients with hormone receptor-positive early breast cancer.

OBJECTIVE: To compare the efficacy, safety, and pregnancy outcomes of tamoxifen plus ovarian function suppression (OFS) between Han and Zhuang women with hormone receptor-positive breast cancer. METHODS: A total of 236 Han and 101 Zhuang women with hormone receptor-positive breast cancer who received tamoxifen plus OFS were analyzed retrospectively. Long-term disease-free survival (DFS) and overall survival (OS) were evaluated by Kaplan-Meier analysis, and adverse events and pregnancy outcomes were assessed by χ2 and Fisher's exact-probability tests. RESULTS: There was no significant difference in DFS or OS between Han and Zhuang women (5-year DFS 74.57% and 77.23%, OS 85.59% and 90.01%, respectively). The incidences of endometrial hyperplasia, ovarian cysts, nausea and vomiting, fatty liver, retinitis, and thrombocytopenic purpura were similar in both groups, but Zhuang women had significantly more allergic reactions (6.93% vs. 2.12%). Pregnancy rates among women who attempted pregnancy were similar (Han, 7/138, 5.07%; Zhuang, 2/46, 4.35%). CONCLUSIONS: OFS plus tamoxifen resulted in similar DFS and OS among premenopausal Han and Zhuang women with hormone receptor-positive breast cancer. However, Zhuang women were more likely to experience an allergic reaction. For women with fertility concerns, OFS plus tamoxifen was associated with similar pregnancy rates in Zhuang and Han women.

Male accessory breast cancer on the abdominal wall: a case report and literature review.

BACKGROUND: Accessory breast cancer is very rare, particularly in men. Male accessory breast cancer on the abdominal wall has not been documented in the scientific literature so far. We describe a case of male accessory breast cancer on the abdominal wall. CASE PRESENTATION: We describe a male patient suffering a swelling and erosive, enlarged, and hardened abdominal wall mass with pain due to abdominal wall accessory breast cancer. The patient had no obvious disease history, and the initial clinical symptom was a small mass on the abdominal wall. B-ultrasound revealed a solid subcutaneous nodule in the right abdomen with a size of ~2.8 × 2.5 × 1.5 cm. The abdominal wall tumor resection was performed with local anesthesia. Pathological testing revealed a grade II infiltrating ductal carcinoma derived from the accessory mammary gland (right abdominal wall) with neuroendocrine characteristics, showing ER (100% strong positive), PR (100% strong positive), HER-2 (-), ki67 (40% positive), Syn (+), CgA (+), and GCDFP15 (+). CONCLUSION: Nonaxillary accessory breast cancer in males is very rare, with no obvious clinical manifestations, and could be easily ignored. This disease requires great attention from clinicians.

Comparison of the efficacy and survival analysis of neoadjuvant chemotherapy for Her-2-positive breast cancer.

PURPOSE: The objective of this research was to compare the short- and long-term efficacy of the following four neoadjuvant chemotherapy (NAC) regimens: docetaxel/carboplatin/trastuzumab (TCH), docetaxel/epirubicin/cyclophosphamide (TEC), Xeloda/epirubicin/cyclophosphamide followed by Xeloda/docetaxel (XEC-XT), and 5-fluorouracil/epirubicin/cyclophosphamide followed by docetaxel (FEC-T) in human epidermal growth factor receptor-2-positive (Her-2-positive) breast cancer. PATIENTS AND METHODS: According to treatment preferences, 139 patients with Her-2-positive breast cancer were divided into the following four groups: 39 patients in the TCH group, 35 patients in the TEC group, 33 patients in the XEC-XT group, and 32 patients in the FEC-T group. The primary end points were disease-free survival (DFS) and 5-year overall survival (5-year OS). The secondary end points were the efficacy and toxicity of NAC. RESULTS: The TCH, TEC, XEC-XT, and FEC-T groups demonstrated overall response rates of 87.1%, 74.3%, 75.8%, and 62.5% (P=0.031), respectively, and pathological complete response rates of 25.6%, 18.2%, 20.0%, and 18.2% (P=0.041), respectively. The DFS rates for the TCH, TEC, XEC-XT, and FEC-T groups were 84.6%, 62.9%, 65.7%, and 46.9% (P=0.01), respectively. The 5-year OS rates for the TCH, TEC, XEC-XT, and FEC-T groups were 87.2%, 69.7%, 71.4%, and 59.4% (P=0.069), respectively. The mean survival time was 59.3 months (TCH group), 53.5 months (TEC group), 55.3 months (XEC-XT group), and 52.4 months (FEC-T group). The difference in survival among the four groups was statistically significant (P=0.04). CONCLUSION: In four NAC regimens for the treatment of Her-2-positive breast cancer, the TCH group exhibited better DFS and 5-year OS. The TCH regimen significantly enhanced the pathological complete remission rate of NAC with similar side effects compared to the TEC, XEC-XT, and FEC-T regimens. In terms of long-term efficacy, the XEC-XT treatment was superior to the FEC-T and TEC treatment, and there was no significant difference between the FEC-T and TEC groups.

Breast cancer in postmenopausal women is associated with an altered gut metagenome.

BACKGROUND: Increasing evidence suggests that gut microbiota play a role in the pathogenesis of breast cancer. The composition and functional capacity of gut microbiota associated with breast cancer have not been studied systematically. METHODS: We performed a comprehensive shotgun metagenomic analysis of 18 premenopausal breast cancer patients, 25 premenopausal healthy controls, 44 postmenopausal breast cancer patients, and 46 postmenopausal healthy controls. RESULTS: Microbial diversity was higher in breast cancer patients than in controls. Relative species abundance in gut microbiota did not differ significantly between premenopausal breast cancer patients and premenopausal controls. In contrast, relative abundance of 45 species differed significantly between postmenopausal patients and postmenopausal controls: 38 species were enriched in postmenopausal patients, including Escherichia coli, Klebsiella sp_1_1_55, Prevotella amnii, Enterococcus gallinarum, Actinomyces sp. HPA0247, Shewanella putrefaciens, and Erwinia amylovora, and 7 species were less abundant in postmenopausal patients, including Eubacterium eligens and Lactobacillus vaginalis. Acinetobacter radioresistens and Enterococcus gallinarum were positively but weakly associated with expression of high-sensitivity C-reactive protein; Shewanella putrefaciens and Erwinia amylovora were positively but weakly associated with estradiol levels. Actinomyces sp. HPA0247 negatively but weakly correlated with CD3+CD8+ T cell numbers. Further characterization of metagenome functional capacity indicated that the gut metagenomes of postmenopausal breast cancer patients were enriched in genes encoding lipopolysaccharide biosynthesis, iron complex transport system, PTS system, secretion system, and beta-oxidation. CONCLUSION: The composition and functions of the gut microbial community differ between postmenopausal breast cancer patients and healthy controls. The gut microbiota may regulate or respond to host immunity and metabolic balance. Thus, while cause and effect cannot be determined, there is a reproducible change in the microbiota of treatment-naive patients relative to matched controls.

Clinicopathologic Factors Related to the Histological Tumor Grade of Breast Cancer in Western China: An Epidemiological Multicenter Study of 8619 Female Patients.

BACKGROUND AND PURPOSE: Breast cancer is now recognized as a clinically heterogeneous disease with a wide spectrum of epidemiological and clinicopathologic features. We aimed to evaluate whether epidemiological and clinicopathologic features are associated with the histological tumor grade of breast carcinomas in Western China. METHODS: We retrospectively collected data from the Western China Clinical Cooperation Group and assessed associations between clinicopathologic factors and histological tumor grade in 8619 female breast cancer patients. Patients were divided into two groups: Group I (tumor grade I/II) and Group II (tumor grade III). Univariable analysis and multivariable logistic regression models were used to analyze the relationships between clinicopathologic factors and tumor grade. RESULTS: Patients presenting with positive axillary lymph nodes, large tumor size (>2 cm), lymphovascular invasion, hormone receptor negativity, human epidermal growth factor receptor 2 (HER-2) positivity, and triple negativity tended to have an increased risk of a high tumor grade. However, the number of pregnancies or births was inversely correlated with the risk of a high tumor grade. In addition, patients presenting with grade III tumors were more likely to receive aggressive treatment, such as adjuvant chemotherapy, anti-HER-2 therapy, and level III axillary lymph node dissection. CONCLUSIONS: Our results suggested that several clinicopathologic factors were associated with high tumor grade of breast cancer patients in Western China.

Expression of GOLPH3 in patients with non-small cell lung cancer and xenografts models.

Increased expression of Golgi phosphoprotein 3 (GOLPH3) has been reported to be associated with several types of human cancer. Patient-derived cancer xenograft models have demonstrated great potential in preclinical studies. In the present study, the link between GOLPH3 expression and survival was examined in patients with non-small cell lung cancer (NSCLC). Patient-derived lung cancer xenograft models were established with two different methods. Lastly, the association between GOLPH3 expression and establishment of the xenograft models was explored. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry analysis were used to examine GOLPH3 expression in 60 NSCLC tissues and matched adjacent non-cancerous tissues (ANT). In addition, tumor pieces from the 60 NSCLC tissues were implanted in the subcutaneous layer and in the subrenal kidney capsule of nude mice. RT-qPCR, histopathology and immunohistochemistry were used to confirm the human origin of the xenograft tumors. RT-qPCR was also used to research the mutation status of GOLPH3 in the xenograft tumors. The results demonstrated that NSCLC tissues had higher expression of GOLPH3, at the mRNA and protein level, compared with ANT. High expression of GOLPH3 correlated with poor survival in patients with NSCLC. Successful engraftment was established for 27 tissues in the subrenal kidney capsule and for 16 in the subcutaneous layer of nude mice. The subrenal kidney capsule group demonstrated significantly higher engraftment rates than the subcutaneous layer group. In addition, higher GOLPH3 expression in the tumor tissues was significantly correlated with higher engraftment rates in mice. In both groups, few xenografts lost the GOLPH3 mutation. In summary, GOLPH3 may be an important diagnosis and prognosis indicator in patients with NSCLC. The genotype and phenotype of the xenograft tumors derived from patient lung cancer tissues exhibited significant similarities to the originating primary tumors. High GOLPH3 expression may promote the successful establishment of xenograft models for NSCLC.

Axillary ultrasound and fine needle aspiration biopsy in the preoperative diagnosis of axillary metastases in early-stage breast cancer.

The efficacy of axillary lymph node dissection (ALND) following sentinel lymph node biopsy (SLNB) has been questioned. The present study was performed to determine the sensitivity, specificity and accuracy of axillary ultrasound (US) and fine needle aspiration biopsy (FNAB) in the diagnosis of axillary metastases in patients with early breast cancer. A total of 214 patients with stage I and II breast cancer between June 2015 and January 2017 were included. All of the patients received axillary US as a primary investigation for lymph node status. US-guided FNAB was performed on suspicious lymph nodes. Those with non-suspicious and FNAB-negative axillary nodes proceeded to SLNB at the time of primary breast surgery. ALND was performed when the result of the US-guided FNAB was positive. The results of US and cytology were compared to histopathological results to determine their sensitivity, specificity, positive and negative predictive value and accuracy. A total of 76 out of 214 patients (35.5%) had axillary lymph node metastases at final histology. The sensitivity and specificity of axillary US alone were 59.2% (45/76) and 78.3% (108/138), respectively. Axillary US with FNAB identified 32 patients with positive lymph node metastases, and increased the sensitivity and specificity to 71.1% (32/45) and 100.0% (30/30). Combined with FNAB, the positive and negative predictive values were 100.0% (32/32) and 69.8% (30/43), respectively. Axillary US-alone or combined US/FNAB had a high accuracy rate and a satisfactory result as they cost less and it is easy to assess the status of axillary lymph nodes. Thus, axillary US with FNAB may avoid unnecessary SLNB in a significant number of patients.

GOLPH3: a novel biomarker that correlates with poor survival and resistance to chemotherapy in breast cancer.

The association between Golgi phosphoprotein 3 (GOLPH3) and clinical pathological characteristics, as well as the clinical outcomes of both neoadjuvant and adjuvant chemotherapies in breast cancer, remain largely unknown. In this study, we investigated the biological role and clinical significance of GOLPH3 in breast cancer. We found that GOLPH3 expression in tumor tissue was higher than that in adjacent noncancerous tissue (ANT) and fibroadenoma. GOLPH3 silencing reduced the migration, invasion, and proliferation of breast cancer cells and promoted apoptosis of the cells. Importantly, patients with high GOLPH3 expression had worse disease-free survival (DFS) and overall survival (OS), and GOLPH3 expression was correlated with clinical pathological characteristics such as molecular subtype, tumor-node-metastasis classification, and age but was not associated with surgery type. Patients with high GOLPH3 expression had poor DFS and OS in every molecular subtype, and an increase in tumor invasion and lymph node metastasis. The risk of recurrence increased with age in patients with high GOLPH3 expression, and surgery type had no influence on patient survival. This is the first study to investigate the correlation between GOLPH3 and response to chemotherapy in breast cancer. Patients with high GOLPH3 expression showed resistance to neoadjuvant and adjuvant chemotherapies, and GOLPH3 overexpression indicated a high risk of recurrence in patients who received adjuvant chemotherapy. These data suggest that GOLPH3 may be a novel biomarker that correlates with poor survival and resistance to chemotherapy in breast cancer.

Relationship between mammographic calcifications and the clinicopathologic characteristics of breast cancer in Western China: a retrospective multi-center study of 7317 female patients.

BACKGROUND AND PURPOSE: Limited information is available regarding the correlations between mammographic calcifications and the epidemiological features of patients with breast cancer living different lifestyles in Western China. Thus, this study aimed to investigate the relationship between mammographic calcifications and the epidemiological characteristics of female patients with breast cancer in Western China. METHODS: This was a hospital-based, retrospective, multi-center epidemiological study of patients with breast cancer. Using the Western China Clinical Cooperation Group (WCCCG) database, we obtained the records of 7317 patients (with mammographic data) diagnosed with breast cancer between March 2011 and June 2016. These patients were divided into Groups I (mass alone) and II (mass combined with calcification), and their clinical and pathological data were compared. RESULTS: A total of 4211 patients were enrolled in Group I, and 3106 patients were enrolled in Group II. The tumors in Group II were more likely to be larger (P < 0.0001), higher grade (P = 0.0029), estrogen receptor (ER)+/progesterone receptor (PR)- (P = 0.0319), and human epidermal growth factor receptor 2 (HER-2)-positive (P < 0.0001), and to have axillary lymph node metastasis (P = 0.0033) than those in Group I. Regarding treatment, patients in Group II were more likely to have undergone chemotherapy (P = 0.0108) and anti-HER2 therapy (P = 0.0102), whereas patients in Group I were more likely to have undergone endocrine therapy (P < 0.0001). CONCLUSIONS: In conclusion, mammographic calcifications in tumors were associated with distinct clinicopathologic characteristics and aggressive treatments.

Clinical utility of the additional use of blue dye for indocyanine green for sentinel node biopsy in breast cancer.

BACKGROUND: Indocyanine green (ICG) is widely used as a tracer in sentinel lymph node biopsy (SLNB) of patients with breast cancer. Whether SLNB performance can be improved by supplementing ICG with methylene blue dye remains controversial. This study compared the performance of SLNB when ICG was used alone or with blue dye. MATERIALS AND METHODS: Consecutive patients with T1-3 primary breast cancer at our hospital were recruited into our study and randomized to undergo SLNB with ICG alone (n = 62) or with the combination of ICG and blue dye (n = 65). We compared the two methods in terms of identification rate, number and detection time of sentinel lymph nodes (SLNs) removed. RESULTS: SLN identification rate were similar in the absence (95.2%) or presence of blue dye (98.5%, P = 0.578) but significantly, more average nodes were removed when blue dye was used (3.8 ± 1.5 versus 2.7 ± 1.2, P = 0.000), and the average time for detecting each SLN was significantly shorter (3.91 ± 1.87 versus 5.65 ± 2.95 min; P = 0.000). No patient in the study experienced severe adverse reactions or complications. Recurrence of axillary node was detected in one patient (1.6%) using ICG alone but not in any patients using ICG and blue dye. CONCLUSIONS: The efficiency and sensitivity of SLNB can be improved by combining ICG with blue dye.

ß-Glucosidase inhibition sensitizes breast cancer to chemotherapy.

The resistance to therapy is a major clinical challenge for advanced stage breast cancer. Identification of novel potential therapeutic targets is needed to overcome chemoresistance. In this work, we identified a target that was critically involved in breast cancer growth and chemoresistance. We demonstrated that ß-glucosidase expression and activity were significantly upregulated in breast cancer tissues and a panel of cell lines compared to normal adjacent breast tissues and cell lines. ß-glucosidase overexpression activated PI3K/Akt/mTOR signalling, leading to increased cell growth. In contrast, ß-glucosidase inhibition by siRNA depletion and pharmacological approach using conduritol B epoxide (selective ß-glucosidase inhibitor) suppressed growth and induced apoptosis in breast cancer cells. Importantly, ß-glucosidase inhibition significantly sensitized breast cancer cells to chemotherapy in vitro and in vivo, suggesting that inhibiting ß-glucosidase effectively targeted breast cancer cells that were resistant to elimination by chemotherapeutic agent alone. We demonstrated the positive role of ß-glucosidase in breast cancer growth and survival. Our work also suggested that inhibiting ß-glucosidase as a possible alternative therapeutic strategy to overcome chemoresistance in breast cancer.

Comparison of the effectiveness and toxicity of neoadjuvant chemotherapy regimens, capecitabine/epirubicin/cyclophosphamide vs 5-fluorouracil/epirubicin/cyclophosphamide, followed by adjuvant, capecitabine/docetaxel vs docetaxel, in patients with operable breast cancer.

The aim of this study was to compare the effectiveness and toxicity of neoadjuvant chemotherapy regimens, xeloda/epirubicin/cyclophosphamide (XEC) vs 5-fluorouracil/epirubicin/cyclophosphamide (FEC), followed by adjuvant chemotherapy regimens, capecitabine/taxotere (XT) vs taxotere (T), in axillary lymph node (LN)-positive early-stage breast cancer. In this randomized, Phase III trial, 137 patients with operable primary breast cancer (T2-0, N0-1) who were tested axillary LN positive through aspiration biopsy of axillary LNs were randomized (1:1) to four 3-weekly cycles of XEC or FEC. Patients underwent surgery within 4-6 weeks after the fourth cycle, followed by four adjuvant cycles of 3-weekly XT or T. The primary end point was tumor pathological complete response. Toxicity profiles were secondary objectives. In total, 131 patients had clinical and radiological evaluation of response and underwent surgery. Treatment with XEC led to an increased rate of pathological complete response in primary tumor (18% vs 6%, respectively, P=0.027) and objective remission rate (87% vs 73%, P=0.048) compared to FEC. Clinical complete response occurred in 20% and 7% for XEC and FEC, respectively. Compared to FEC, XEC was associated with more hand-foot syndrome (57% vs 11%, P<0.001) and 3/4 grade nausea/vomiting/diarrhea (30% vs 14%, P=0.034) but less phlebitis (3% vs 14%, P=0.035). XT and T adjuvant chemotherapy regimens were well tolerated: treatment-related 3/4 grade adverse events occurred in 28% and 17% of patients receiving XT and T, respectively.

Efficacy of vinorelbine-based neoadjuvant chemotherapy in breast cancer: A systematic review and meta-analysis of randomized controlled trials.

The present study aimed to compare the effects of vinorelbine-based neoadjuvant chemotherapy and vinorelbine-free regimens. A meta-analysis of all the relevant randomized controlled trials was performed to investigate the improvement in pathological complete response (pCR), overall response rate (ORR) and breast-conserving surgery (BCS). The PubMed and Embase databases were searched for relevant studies reporting randomized controlled trials comparing vinorelbine-based neoadjuvant chemotherapy with vinorelbine-free regimens until July 2013. Risk ratios/odds ratio and 95% confidence intervals (CIs) were used to estimate the association between vinorelbine in neoadjuvant chemotherapy and various efficacy outcomes. Fixed- or random-effect models were adopted to pool the data. Five eligible studies with a total of 1,495 patients were included in the meta-analysis. Compared to vinorelbine-free chemotherapy, vinorelbine-based regimens demonstrated no significant improvement in clinical outcomes including: pCR [relative risk (RR)=1.016; 95% CI, 0.738-1.399; P=0.922], ORR (RR=1.048; 95% CI, 0.969-1.133; P=0.239) and BCS (RR=1.764; 95% CI, 0.734-4.239; P=0.205). However, vinorelbine-based regimens were associated with a lower incidence of grade 3-4 alopecia (OR, 0.617; 95% CI, 0.448-0.848; P=0.003). In a hierarchical analysis for patients who received neoadjuvant chemotherapy, the proportion of subjects achieving pCR was significantly increased when HER2-amplified (RR=2.31; 95% CI, 1.20-4.43; P=0.01) and hormone receptor negative (RR=0.488; 95% CI, 0.263-0.908; P=0.023). The present review confirms that neoadjuvant chemotherapy vinorelbine-based regimens are unlikely to emerge as superior to pCR, ORR and BCS. Hierarchical analysis indicated that the HER2-amplified and hormone receptor-negative patients were significantly associated with a pathological response rate.

RSK4 knockdown promotes proliferation, migration and metastasis of human breast adenocarcinoma cells.

RSK4 has been shown to inhibit the growth of certain cancer cells. The aim of this study was to construct a lentiviral vector of RSK4-shRNA (Lenti-RSK4-shRNA) to specifically block the expression of RSK4 in the human breast adenocarcinoma cell line MCF-7, and investigate the effect of the RSK4 gene on cell proliferation and invasion in vitro and in vivo. Lenti-RSK4-shRNA was stably transfected into MCF-7 cells. RSK4 mRNA and protein expression were measured by fluorescence quantitative RT-PCR and western blot analysis. Cell proliferation was evaluated by MTT assays and flow cytometric analysis. Invasion was evaluated by Transwell assays and xenograft nude mouse models. The expression of RSK4 mRNA, Ki-67 mRNA, cyclin D1 mRNA, CXCR4 mRNA and E-cadherin mRNA of tumor xenografts were detected by fluorescence quantitative RT-PCR. Significant decreases in RSK4 mRNA and protein expression was detected in MCF-7 cells carrying lentiviral RSK4-shRNA vector. The cell proliferation was significantly promoted in the RSK4-shRNA group as compared to that in the negative and blank control group. In addition, the number of cells in the S phase in the RSK4­shRNA group was significantly greater than the blank and negative control groups (P<0.05). Furthermore, the number of invading cells was increased in the RSK4-shRNA (P<0.05). In vivo, we also found that the knockdown of RSK4 promoted tumorigenicity and migration in the xenograft nude mouse model. In addition, we showed that the RSK4 mRNA and E-cadherin mRNA expression were significantly lower in the RSK4-shRNA group compared to that in negative and blank control group (both P<0.05), while the Ki-67 mRNA, cyclin D1 mRNA and CXCR4 mRNA were higher in the shRNA group compared to that in negative and blank control group (both P<0.05). In conclusion, downregulation of RSK4 expression is indicated to be associated with tumor cell proliferation and invasion, and silencing of the RSK4 may be involved in the development and progression of breast cancer through the changes of Ki-67, cyclin D1, CXCR4 and E-cadherin, and suggesting that RSK4 may act as a potential cancer suppressor gene and therapeutic target for the treatment of breast cancer.

Promoter methylation and expression changes of BRCA1 in cancerous tissues of patients with sporadic breast cancer.

BRCA1 is a susceptibility gene that has a genetic predisposition for breast cancer. BRCA1 gene mutation is closely associated with familial hereditary breast cancer, but the BRCA1 gene mutation is rarely found in sporadic breast cancer. According to previous studies, decreased expression of BRCA1 was detected in certain types of sporadic breast cancer. Aberrant methylation of DNA promoter CpG islands is one of the mechanisms by which tumor suppressor gene expression and function is lost. The aim of the present study was to investigate BRCA1 gene expression, methylation status and clinical significance in sporadic types of breast cancer. Quantitative polymerase chain reaction (PCR) and bisulfite sequencing PCR were respectively used to detect expression differences of BRCA1 mRNA and BRCA1 methylation in the 49 cancerous and paired non-cancerous samples from patients with breast cancer. The associations of BRCA1 expression and methylation status with the clinicopathologic characteristics were analysed. BRCA1 mRNA expression levels in the 49 breast cancer tissues were lower than those in the paired non-cancerous tissues. There was a significant statistical difference (P=0.001). BRCA1 mRNA expression was not associated with the main clinicopathologic characteristics. Frequency of the BRCA1 promoter methylation in the breast cancerous tissues was significantly higher than that in the non-cancerous tissues (P=0.007); BRCA1 gene methylation status was negatively correlated with mRNA expression (P=0.029); and BRCA1 methylation exhibited no association with all clinicopathological features. DNA promoter hypermethylation may be the potential mechanism accounting for BRCA1 expression silence in part of sporadic types of breast cancer. Some patients with hypermethylated BRCA1 may display favorable clinicopathological status.

Periductal stromal sarcoma of the breast: A case report and review of the literature.

Periductal stromal sarcoma (PSS), spindle and epithelioid types, is a rare subtype of malignant fibroepithelial tumor. The morphological characteristics of this neoplasm are different from phyllodes tumor and stromal sarcoma. PSS exhibits biphasic histology with benign ductal elements and a sarcomatous stroma composed of spindle cells and lacking phyllodes tumor architecture. The therapeutic management of PSS is based on wide surgery with free margins, and adjuvant therapies are not required. To the best of our knowledge, the recurrence of PSS in ≤5 months has not been reported in the literature to date. This report describes a 43-year-old woman who presented to our hospital with a recurrence of nodules in the left breast. The patient had undergone lumpectomy at a different hospital 5 months previously, and a diagnosis of phyllodes tumor was pathologically confirmed. On presentation at our hospital, the patient underwent a second lumpectomy. Histological examination revealed PSS and the patient underwent a simple mastectomy of the left breast with no adjuvant treatment (such as chemotherapy or radiotherapy). After 9 months of close follow-up examinations, no recurrence was observed. PSS is an extremely rare disease with low-grade sarcomatous behavior, which may evolve into a phyllodes tumor or an entity of breast cancer. Therefore, frequent follow-up examinations are required.