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The incidence of breast cancer (BC) is the highest among women. Identification of miRNAs as biomarkers may help to improve the diagnosis of BC. The purpose of this study was to assess the expression levels of miR-1976 in plasma samples and the biological functions in the progression of BC. The expression levels of miR-1976 in plasma samples and tissues were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The associations between the expression levels and clinicopathological features were studied. Cell supernatants were used to simulate circulation. The biological functions of miR-1976 were assessed in vitro and in vivo. The expression levels of miR-1976 in plasma samples were found significantly lower in patients with BC than those in healthy controls, and were associated with Ki-67. The expression levels in BC tissues were lower than those in adjacent normal tissues, and were correlated with the number of lymph nodes and Ki-67. The expression levels in BC cell supernatants and cell lines were lower than that in normal human breast epithelial cell line HBL-100. miR-1976 knockdown promoted proliferation in vitro and in vivo. miR-1976 may serve as a promising non-invasive biomarker for the diagnosis of BC in the future.

Background: Neoadjuvant chemotherapy (NCT) is the standard treatment for patients with locally advanced breast cancer (LABC). The aim of this study was to verify this relationship, and to estimate the clinical value of aneuploid circulating endothelial cells (CECs) in LABC patients with different NCT responses. Methods: Breast cancer patients received an EC4-T4 NCT regimen. Peripheral blood mononuclear cells were obtained before NCT, and after the first and last NCT courses. A novel subtraction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) strategy was applied for detection of circulating rare cells (CRCs). CECs (CD45–/CD31+/DAPI+) and circulating tumor cells (CTCs) with different cytogenetic abnormalities related to chromosome 8 aneuploidy were analyzed in LABC patients subjected to NCT. Results: A total of 41 patients were enrolled. Firstly, CD31+/EpCAM+ aneuploid endothelial-epithelial fusion cells were observed in LABC patients. Further, aneuploid CECs in the peripheral blood showed a biphasic response during NCT, as they initially increased and then decreased, whereas a strong positive correlation was observed between aneuploid CECs and CTC numbers. Conclusion: We determined that aneuploid CEC dynamics vary in patients with different response to chemotherapy. Elucidating the potential cross-talk between CTCs and aneuploid CECs may help characterize the process associated with the development of chemotherapy resistance and metastasis.

To determine the characteristics of ultrasound (US) imaging of completely ablated cases and the effects of duration and clinical experience on accurate microwave ablation (MWA) for the treatment of benign breast tumours.With written informed consent and approval of the institutional ethics committee, patients with symptomatic or palpable benign breast tumours (longest diameter, 7-32 mm), to whom MWA (2450 MHz) was performed, were enrolled in this prospective nonrandomised study. US and contrast-enhanced US (CEUS) images were applied for follow-up and analysed.Forty-seven consecutive patients with 52 completely ablated tumours were enrolled. Of these 52 tumour ablations in US, 16 ablations were defined as concentric type, and 36 were defined as nonconcentric type. Of these 52 ablations, 7 cases were defined as nonaccurate ablation with the largest margin ≥10 mm in US. The nonaccurate ablation rate in the training group (the first consecutive 30 cases, 7/30) was significant higher than that (the last 22 cases, 0/22) in the practiced group (p = 0.016). Of 38 completely ablated cases (9 mm the longest diameter20 mm), the average largest margin in70 s group was significant larger than that in70 s group (p = 0.019).Experience was important for accurate MWA in the treatment of benign breast tumour, and at least 30 cases training was recommended. Nevertheless, clinical trials are still required to validate our findings in the future.

Non-surgical treatments for benign breast tumours have clinical goals of stopping growth and/or reducing (removing) palpable tumours effect without leaving a surgical scar. The purpose of this non-randomised prospective clinical trial was to assess imaging and clinical outcomes of microwave ablation (MWA) in the treatment of benign breast tumours regardless of the distance from the tumour to the skin and chest wall.With approval of the institutional ethics committee and written informed consent, 39 patients with 44 core-biopsy-proved benign breast tumours 3.0 cm or less in diameter assessed by using ultrasound (US) and contrast-enhanced ultrasound (CEUS) were prospectively recruited. US-guided MWA was performed under local anaesthesia. The patients were followed up with physical examination, ultrasound elastography and CEUS.The MWA procedure with a mean duration of 74.3 s ± 26.5 was well accepted and tolerated in 41 cases except for three cases. Of 41 tumours with follow-up data, 40 (97.5%; 95% confidence interval: 87.1%, 99.9%) showed complete ablation assessed by using CEUS. The mean volume of the ablated tumours decreased significantly (p = .005) during follow-up. The strain ratio 1-3 months after ablation was higher than that before ablation, and became low 6 months after ablation (p = .022). No epidermal burn was observed in all cases with a mean distance of 7.5 mm ±3.3 from the tumour to the skin.MWA is a safe and effective minimally invasive "patient-friendly" procedure with a very short duration for the treatment of benign breast tumours.

Aims: To determine the factors influencing ultrasound breast tumor size assessment accuracy.Material and methods: Five factors (tumor type, molecular subtype, histological size, histological grade, and breast density) were used to assess the measurement accuracy of breast ultrasound in tumor size. Size underestimation was defined as ultrasound index lesion diameter < histological size by at least 5 mm.Results: Breast ultrasound underestimated tumor size significantly, especially in cases with intraductal components (p=0.002). There was a tendency for higher size underestimation in breast cancer tumors with high–histological grade (p=0.03), human epidermal growth factor receptor type 2 (HER2)-overexpressing breast cancer tumors (p=0.02) and hormone receptor (HR)−/HER2+ breast cancer tumors (p=0.008). Furthermore, core biopsy revealedhigher probability of size underestimation with intraductal components (p=0.002). Size underestimation was more frequent with larger histological size (p

The aim of this study was to explore whether doxorubicin hydrochloric (DOX) combined with microwave ablation (MWA) is more effective at increasing tumour coagulation and prolonging end-point survival in a VX2 rabbit breast cancer model than each intervention individually.New Zealand white rabbits with VX2 tumours were placed into treatment groups as follows: MWA (20 W for 5 min and 40 W for 5 min), intravenous injection of 4 mg/kg DOX, and combined therapy. Tumours were analysed at 4 h and 24 h after treatment to determine the temporal quantities of cleaved caspase-3 and Hsp70 using immunohistochemical staining and Western blots. Tumour coagulation areas were compared at 24 h after treatment.No significant difference in tumour coagulation was found between DOX-MWA and 40W-MWA (mean 4.52 cm(2) ± 0.48 (SD), 4.08 cm(2) ± 0.36, respectively; P0.05). A significant difference between tumour coagulation was found for DOX-MWA and 20W-MWA (mean 4.52 cm(2) ± 0.48 (SD), 1.69 cm(2) ± 0.34 cm(2), respectively; p0.01). Cleaved caspase-3 and Hsp70 demonstrated low level expression at 4 h and 24 h in the DOX group. Cleaved caspase-3 showed low expression at the coagulation margin in the 20W-MWA group, was highly expressed in DOX-MWA group, and continued to increase with time. Hsp70 in the 20W-MWA group increased significantly at the coagulation margin but demonstrated low expression in the DOX-MWA group at 4 h and 24 h. The animals in the combined treatment group had a longer survival time (mean 78.33 days ± 8.07 SD) than the 20W-MWA group (mean 57.17 days ± 8.77, p0.01) or the DOX group (mean 35.17 days ± 7.63, p0.01).A combination of DOX and MWA could increase tumour coagulation and end-point survival better than single therapy, which had some connection with the elevated expression of cleaved caspase-3 and low Hsp70 expression at the coagulation margin.

Background Sentinel lymph node biopsy (SLNB) is well accepted to be a standard procedure in breast cancer surgery with clinically negative lymph nodes. Isosulfan blue is the first dye approved by the USA Food and Drug Administration for the localization of the lymphatic system. Few alternative tracers have been investigated. In this study, we aimed to compare the differences between 10 % fluorescein sodium and 1 % isosulfan blue in breast sentinel lymph node biopsy and to investigate the feasibility of using 10 % fluorescein sodium as a new dye for breast sentinel lymph node biopsy. Methods A total of 30 New Zealand rabbits were randomly divided into the fluorescein sodium group and the isosulfan blue group (15 rabbits per group). Fluorescein sodium or isosulfan blue was injected subcutaneously into the second pair of mammary areolas. Results The average fading time of the second lymph nodes in the isosulfan blue group was significantly shorter than that in the fluorescein sodium group. Moreover, the detection rates of SLNs were higher in the fluorescein sodium group than in the isosulfan blue group. No significant differences between the fluorescein sodium group and isosulfan blue group were observed regarding the distances between the detected sentinel lymph nodes and second pair of mammary areolas, the distances between the second lymph nodes and second pair of mammary areolas, the number of detected sentinel lymph nodes and second lymph nodes, the average dyeing time of the sentinel and the second lymph nodes, and the average fading time of the second lymph nodes. Conclusions In summary, we first reported that fluorescein sodium is a potential new tracer for breast sentinel lymph node biopsy.

Background Aldehyde dehydrogenase 1 (ALDH1) is an important marker of tumor-initiating cells. We aimed to investigate ALDH1 expression in benign breast disease and human breast cancer of different histologic stages. Methods Immunohistochemical staining of ALDH1 was applied to 21 cases with benign breast diseases, 47 ductal carcinoma in situ (DCIS) cases, 62 cases diagnosed with invasive cancer with extensive intraductal component (EIC), and 58 cases diagnosed with invasive cancer without EIC. Results ALDH1 was expressed in tumor cells in 61.0 % of 164 breast cancer cases, which was higher than that in benign breast disease (3/21) (P 0.05). However, ALDH1 positive invasive breast cancers were significantly more likely to be with large tumor size (P = 0.001), high grade (P

Background The objective of this study is to investigate the association among the polymorphisms of XRCC1 gene, smoking, drinking, family history of tumors, and the risk of colorectal cancer (CRC) in the population of Han nationality in Jiangsu Province, China. Methods A case–control study of 320 patients with CRC and 350 cancer-free subjects as a control group was conducted. The three polymorphic sites, codons 194, 280, and 399, of XRCC1 genes were analyzed by PCR-RFLP. Results We find that heavy smoking (>500 cigarettes per year) significantly increased the susceptibility of CRC (OR = 1.89, 95 % confidence interval (CI) 1.27–2.84) after stratification by total smoking amount. There was also significant difference between cases and controls when family history of tumors (OR = 2.96, 95 % CI 1.76–4.99) was considered. Comparing with individuals carrying XRCC1 399Arg/Arg genotype, the subjects with 399Arg/Gln (OR = 1.46, 95 % CI 1.06–2.01) or 399Gln/Gln genotype (OR = 1.93, 95 % CI 1.05–3.54) had a significantly increased risk for CRC. Taking smoking and drinking habits into consideration, we found that subjects with heavy smoking history and XRCC1 194Arg allele had the significantly increased risk for CRC (OR = 2.91, 95 % CI 1.35–6.24). Individuals, who carry 399Gln allele and have a heavy smoking (OR = 2.72, 95 % CI 1.52–4.89) or drinking habit (OR = 1.98, 95 % CI 1.06–3.67), also have higher risk. In smoking population, 194Arg (P = 0.491) and 399Gln (P = 0.912) had not significantly increased risk for CRC, so did 399Gln (P = 0.812) in smoking population. Conclusions Individuals carrying XRCC1 399Gln allele with a smoking or drinking habit were in increased risk, and heavy-smoking subjects with 194Arg allele also have higher risk for CRC in the Han nationality population of Jiangsu Province, which also showed a positive correlation with exposure dose of tobacco. But XRCC1 399Gln allele or 194Arg allele were not independent risk factors for CRC in smoking or drinking population.

Purpose To prospectively assess MR imaging evaluation of the ablation zone and pathological changes after microwave ablation (MWA) in breast cancer. Materials and methods Twelve enrolled patients, diagnosed with non-operable locally advanced breast cancer (LABC), were treated by MWA and then neoadjuvant chemotherapy, followed by surgery. MR imaging was applied to evaluate the effect of MWA. Hematoxylin-eosin (HE) staining and transmission electron microscopy (TEM) were applied to analyze the ablated area. Results All MWA procedures were performed successfully under local anesthesia. For a mean duration of 2.15 min, the mean largest, middle and smallest diameters in the ablated zone 24-h post-ablation in MR imaging were 2.98 cm ± 0.53, 2.51 cm ± 0.41 and 2.23 cm ± 0.41, respectively. The general shape of the ablation zone was close to a sphere. The ablated area became gradually smaller in MR imaging. No adverse effects related to MWA were noted in all 12 patients during and after MWA. HE staining could confirm the effect about 3 months after MWA, which was confirmed by TEM. Conclusions 2 min MWA can cause an ablation zone with three diameters larger than 2 cm in breast cancer, which may be suitable for the local treatment of breast cancer up to 2 cm in largest diameter. However, the long-term effect of MWA in the treatment of small breast cancer should be determined in the future.

Background Few studies have systematically reported the relationship between the risk of breast cancer and family history of other cancers. This study was designed to systematically determine the relationship between breast cancer risk and family history of other cancers in first-degree relatives. Methods Between January 2006 and June 2011, 823 women diagnosed with breast cancer were included, and age-matched women diagnosed with benign breast disease were selected as controls. Family history of other cancers in first-degree relatives was recorded by trained reviewers. Multivariate logistic regression was applied to analyze the relationships. Results A family history of esophagus cancer (OR: 2.70, 95% CI: 1.11 – 6.57), lung cancer (OR: 2.49 95% CI: 1.10 – 5.65), digestive system cancer (OR: 1.79, 95% CI: 1.14 – 2.79) and any cancer (OR: 2.13, 95% CI: 1.49 – 3.04) in first-degree relatives was directly associated with increased breast cancer risk. In subgroup analysis, the risk of hormone receptor positive breast cancer was increased in subjects with a family history of lung cancer (OR: 3.37, 95% CI: 1.45 – 7.82), while the risk of hormone receptor negative breast cancer was increased in subjects with a family history of esophagus cancer (OR: 6.19, 95% CI: 2.30 – 16.71), uterus cancer (OR: 6.92, 95% CI: 1.12 – 42.89), digestive tract cancer (OR: 2.05, 95% CI: 1.03 – 4.10) and gynecology cancer (OR: 6.79, 95% CI: 1.46 – 31.65). Additionally, a significant increase in breast cancer was observed with a family history of digestive system cancer for subjects 50 y and younger (OR: 1.88, 95% CI: 1.03 – 3.43), not for subjects 50 y older (OR: 1.67, 95% CI: 0.86 – 3.25). Conclusions Breast cancer aggregates in families with several types of cancer especially for digestive system cancer. The influence of a family history of other cancers seems more likely to be limited to hormone receptor negative breast cancer.

Background The association between family history and risk of triple negative breast cancer and ductal carcinoma in situ (DCIS) has not been well investigated, especially in Asian populations. We investigated the association between family history and risk of DCIS or triple negative breast cancer in a Han Chinese population. Methods A case–control study, comprising 926 breast cancer patients and 1,187 benign breast disease controls, was conducted in our hospital. Multivariate logistic regression was used to assess the relationships between family history and risk of DCIS or triple negative breast cancer. Results Subjects with a family history of breast cancer had higher breast cancer risk than those without a family history (odds ratio (OR) = 2.11, 95% confidence interval (CI) = 1.26 to 3.52). Family history was not significantly associated with an increased risk of DCIS (OR = 1.27, 95% CI = 0.36 to 4.46), while family history was significantly associated with an increased risk of invasive breast cancer (OR = 2.22, 95% CI = 1.32 to 3.75), irrespective of triple negative breast cancer (OR = 3.35, 95% CI = 1.43 to 7.88) or non-triple negative breast cancer (OR = 2.14, 95% CI = 1.21 to 3.80). Conclusion Our results indicate that having a family history of breast cancer is associated with an increased risk of triple negative breast cancer with a magnitude of association similar to that for non-triple negative breast cancer. Furthermore, family history is not significantly associated with an increased risk of DCIS. Future cohort studies with larger sample sizes are still needed to explore these relationships.

BACKGROUND: Previous studies provide an ambiguous picture of creatine kinase (CK) expression and activities in malignancy. The aim of this study was to investigate the role of serum CK level in breast cancer patients. PATIENTS AND METHODS: 823 female patients diagnosed with breast cancer were consecutively recruited as cases, and 823 age-match patients with benign breast disease were selected as controls. Serum CK was analyzed by commercially available standardized methods. RESULTS: Serum CK level was significantly associated with breast cancer (P = 0.005) and subtypes of breast cancer, including breast cancer with diameter>2 cm (P = 0.031) and stage IIIbreast cancer (P = 0.025). The mean serum CK level in patients with>2 cm tumor was significantly lower than that in≤2 cm (P = 0.0475), and the mean serum CK level of stage III breast cancer patients was significantly lower than that of stage I and II breast cancer patients (P = 0.0246). Furthermore, a significant difference (P = 0.004) was observed between serum CK level and ERBB2+breast cancer not other molecular subtypes. CONCLUSIONS: Serum CK levels in cases was significantly lower compared with controls. Notably, our results indicated for the first time that there was a negative correlation between serum CK levels and breast cancer stage. Serum CK level, which may reflect the status of host immunity, may be an important factor in determining breast cancer development and progression.