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ABSTRACT: Cancer/testis antigen (CTA) SSX2, which is silent in most normal adult tissues and expressed in various malignant tumors, has been identified for decades. Expression of SSX in tumors has been associated with advanced stages and worse patient prognosis. However, little is known about its role in breast cancer. The SSX2 expression plasmid constructed was stably transfected into the breast cancer cell line MCF-7. The influence of SSX2 on MCF-7 cells was assessed using MTT assay, flow cytometry, transwell invasion assay and in vivo tumorigenicity assay. A comparative proteomic approach was performed to identify and clarify the underlying molecular mechanisms. SSX2 expression was more pronounced in ERα-negative breast cancer cells compared with the positive ones. Overexpression of SSX2 induced cell growth and prompted cell invasion. Both ERα and E-cadherin expression were suppressed in the SSX2 overexpressing MCF-7 cells. Eleven known proteins were identified with significant differential expression. Among these, five were decreased, while other six were increased in the SSX2 overexpressing MCF-7 cells. These results suggested SSX2 may enhance invasiveness in MCF-7 cells both in vivo and in vitro. The regulation of ERα signaling by target proteins of SSX2 may explain the metastatic potential of breast cancer cells.
International Journal of Oncology 02/2012; 40(6):1986-94. · 2.40 Impact Factor
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ABSTRACT: Nipple discharge is a common complaint of patients with breast disease. The color of nipple discharge is always the first alarming symptom for patients. It is controversial whether the discharge color is an indicator of an underlying malignancy. The electronic database PubMed was searched for relevant articles. A meta-analysis about the association between the color of nipple discharge and breast cancer risk was conducted. Eight studies, including 3,110 patients, were eligible for this meta-analysis. Compared with patients in non-bloody nipple discharge group (179/1,478), patients in bloody nipple discharge group (404/1,632) had a markedly higher breast cancer risk (OR: 2.27, 95% CI: 1.32-3.89, P < 0.001 for heterogeneity). Compared with patients in clear/serous group (71/575), patients in bloody nipple discharge group (326/1,271) also had a higher risk (OR: 2.49, 95% CI: 1.25-4.93, P = 0.011 for heterogeneity). Furthermore, compared with patients in the colored group (55/448), patients in bloody nipple discharge group (296/1,124) (OR: 2.00, 95% CI: 0.74-5.45, P = 0.009 for heterogeneity) had no significant difference. Besides, there was no significant difference between patients in colored group (55/448) and clear/serous group (61/470) (OR: 1.35, 95% CI: 0.83-2.18, P = 0.707 for heterogeneity). Therefore, bloody nipple discharge could be a predictor of breast cancer risk among different colors of discharges. The symptom of bloody nipple discharge is helpful to the stratification of preoperative patients.
Breast Cancer Research and Treatment 09/2011; 132(1):9-14. · 4.43 Impact Factor
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ABSTRACT: Benign breast disease (BBD) is an important risk factor for subsequent breast cancer. However, it is unclear whether breast cancer risk is higher in cases of atypical ductal hyperplasia (ADH) than atypical lobular hyperplasia (ALH). Furthermore, it is unclear whether family history increases risk in women with various subtypes of BBD.
We searched the electronic database of PubMed for case-control studies about the subsequent breast cancer risk of BBD, and a meta-analysis was conducted.
Of ten inclusive studies, nine were eligible for subsequent breast cancer risk of histological subtype, including 2,340 cases and 4,422 controls, and four were eligible for investigating the influence of family history on subtypes of BBD, including 1,377 cases and 2,630 controls. Relative to non-proliferative disease (NP), all subtypes of BBD increased subsequent risk, and risk for women with ALH (OR = 5.14, 95% CI 3.52-7.52) may be higher than for women with ADH (OR = 2.93, 95% CI 2.16-3.97). Compared to women without family history and proliferative disease, women with a first-degree family history and atypical hyperplasia (AH) were at highest risk (OR = 4.87, 95% CI 2.89-8.20). Relative to women without family history, women with a first-degree family history had an increased breast cancer risk in different histological subtypes of BBD except for AH (OR = 1.39, 95% CI 0.82-2.37).
This meta-analysis strongly suggested that women with AH, especially for ALH and AH combined with a first-degree family history, were at high risk, for whom risk-reduction options should be considered.
Journal of Cancer Research and Clinical Oncology 07/2011; 137(7):1053-60. · 2.56 Impact Factor
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Tian-Song Xia,
Guo-Zhu Wang,
Qiang Ding,
Xiao-An Liu, Wen-Bin Zhou,
Yi-Fen Zhang,
Xiao-Ming Zha,
Qing Du,
Xiao-Jian Ni,
Jue Wang,
Su-Yu Miao,
Shui Wang
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ABSTRACT: In practice, investigations for bone metastasis of breast cancer rely heavily on models in vivo. Lacking of such ideal model makes it difficult to study the whole process or accurate mechanism of each step of this metastatic disease. Development of xenograft mouse models has made great contributions in this area. Currently, the best animal model of breast cancer metastasizing to bone is NOD/SCID-hu models containing human bone, which makes it possible to let the breast cancer cells and the bone target of osteotropic metastasis be both of human origin. We have developed a novel mouse model containing both human bone and breast, and proved it functional and reliable. In this study, a set of human breast cancer cell line including MDA-MB-231, MDA-MB-231BO, MCF-7, ZR-75-1 and SUM1315 were characterized their osteotropism in this model. A specific cell line SUM1315 made species-specific bone metastasis, certifying the osteotropism-identification utility of the novel mouse model. Furthermore, gene expression and microRNA expression profiling analysis were done to the two SUM1315 derived sub lines isolated and purified from the orthotopic and metastatic xenograft. In addition, to demonstrate the disparity between the "spontaneous" and "forced" bone metastasis in mouse model, MDA-MB-231 cells were inoculated into both the human implants in this model simultaneously, and then primary cultured and profiling analyzed. Supported by overall results of profiling analyses, this study suggested the novel model was a useful tool for understanding, preventing and treating bone metastasis of breast cancer, meanwhile it had provided significant information for further investigations.
Breast Cancer Research and Treatment 06/2011; 132(2):471-86. · 4.43 Impact Factor
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ABSTRACT: Prophylactic mastectomy is performed to decrease the risk of breast cancer in women at high risk for the disease. The benefit of sentinel lymph node biopsy (SLNB) at the time of prophylactic mastectomy is controversial, and we performed a meta-analysis of the reported data to assess that benefit.
We searched MEDLINE, EMBASE and the Cochrane Library databases from January 1993 to December 2009 for studies on patients who underwent SLNB at the time of prophylactic mastectomy. Two reviewers independently evaluated all the identified papers, and only retrospective studies were included. We used a mixed-effect model to combine data.
We included 6 studies in this review, comprising a total study population of 1251 patients who underwent 1343 prophylactic mastectomies. Of these 1343 pooled prophylactic mastectomies, the rate of occult invasive cancer (21 cases) was 1.7% (95% confidence interval [CI] 1.1%-2.5%), and the rate of positive SLNs (23 cases) was 1.9% (95% CI 1.2%-2.6%). In all, 36 cases (2.8%, 95% CI 2.0%-3.8%) led to a significant change in surgical management as a result of SLNB at the time of prophylactic mastectomy. In 17 cases, patients with negative SLNs were found to have invasive cancer at the time of prophylactic mastectomy and avoided axillary lymph node dissection (ALND). In 19 cases, patients with positive SLNBs were found not to have invasive cancer at the time of prophylactic mastectomy and needed a subsequent ALND. Of the 23 cases with positive SLNs, about half the patients had locally advanced disease in the contralateral breast.
Sentinel lymph node biopsy is not suitable for all patients undergoing prophylactic mastectomy, but it may be suitable for patients with contralateral, locally advanced breast cancer.
Canadian journal of surgery. Journal canadien de chirurgie 06/2011; 54(5):300-6. · 1.05 Impact Factor
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ABSTRACT: Compared to tamoxifen, the efficacy and side effects of toremifene in adjuvant endocrine therapy for breast cancer were not very clear. This meta-analysis was conducted to give a more precise estimation of the efficacy and severe side effects of toremifene given in the adjuvant setting in comparison to tamoxifen. The electronic database PubMed was searched for randomized trials comparing toremifene with tamoxifen as adjuvant therapies. Four randomized trials published in three articles were eligible, including 1,890 pooled cases treated with toremifene and 1,857 cases treated with tamoxifen. Compared to patients in tamoxifen group, patients in toremifene group did not have a significantly different overall survival rate (risk ratio (RR): 1.07, 95% confidence interval (CI): 0.97-1.19, P = 0.994 for heterogeneity) or a disease-free survival (DFS) rate (RR: 1.05, 95% CI: 0.95-1.17, P = 0.431 for heterogeneity) at the end of the follow-up time. The rates of thromboembolic events in toremifene group, including deep vein thrombosis (odds ratio (OR): 0.68, 95% CI: 0.40-1.17, P = 0.926 for heterogeneity), cerebrovascular accident (OR: 0.59, 95% CI: 0.32-1.09, P = 0.438 for heterogeneity), and pulmonary embolism (OR: 0.91, 95% CI: 0.42-2.01, P = 0.618 for heterogeneity), were not significantly different from those in tamoxifen group. The rates of endometrial polyps and endometrial cancer between the two groups were almost the same. This meta-analysis suggested that toremifene was as effective as tamoxifen in the adjuvant setting for both perimenopausal and postmenopausal breast cancer patients with similar severe adverse effects to tamoxifen. Toremifene was a convincing and safe change for tamoxifen in adjuvant endocrine therapy.
Breast Cancer Research and Treatment 05/2011; 128(3):625-31. · 4.43 Impact Factor
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ABSTRACT: Zoledronic acid (ZOL) is widely used for preventing bone loss in early breast cancer patients. However, the adverse effects caused by ZOL itself should not be neglected. Musculoskeletal disorders were common after ZOL administration and distressing to the patients. Up to now, no precise estimation of musculoskeletal disorders has been made.
Relevant randomized clinical trials were selected by searching the electronic database PubMed, and a meta-analysis was conducted.
Four trials reported musculoskeletal disorders of ZOL treatment versus no ZOL, including 2684 patients treated with ZOL and 2712 patients without ZOL treatment. Compared to patients without ZOL treatment, patients treated with ZOL had a significantly higher risk of arthralgia (risk ratio (RR): 1.162, 95% confidence interval (CI): 1.096-1.232, P = 0.466 for heterogeneity) and bone pain (RR: 1.257, 95% CI: 1.149-1.376, P = 0.193 for heterogeneity). Three clinical trials reported the complications of upfront versus delayed ZOL treatment, including 1091 patients with upfront ZOL and 1110 patients with delayed ZOL. The rate of bone pain in upfront group (119/824) was significantly higher than that in delayed group (74/836) (RR: 1.284, 95% CI: 1.135-1.453, P = 0.460 for heterogeneity).
Our meta-analysis suggested that treatment with ZOL was significantly associated to the occurrence of arthralgia and bone pain. Moreover, higher rate of bone pain was observed in patients treated with upfront ZOL compared with delayed ZOL treatment. More attentions should be paid to patients treated with ZOL, especially for immediate ZOL. For patients with low risk of osteoporosis, immediate ZOL may be not needed due to additional musculoskeletal disorders and little benefit. Or it can be stopped after the occurrence of these adverse events.
Journal of Experimental & Clinical Cancer Research 01/2011; 30:72. · 2.15 Impact Factor
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Wen-Bin Zhou,
Hong Yin,
Xiao-An Liu,
Xiao-Ming Zha,
Lin Chen,
Jun-Cheng Dai,
Ai-di Tao,
Ling Chen,
Jing-Jing Ma,
Li-Jun Ling,
Shui Wang
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ABSTRACT: The rates of chemotherapy-induced amenorrhea (CIA) associated with docetaxel-based regimens reported by previous studies are discordant. For navelbine-based chemotherapies, rates of CIA have seldom been reported.
Of 170 premenopausal patients recruited between January 2003 and September 2008, 78 were treated with fluorouracil plus epirubicin and cyclophosphamide (FEC), 66 were treated with docetaxel plus epirubicin (TE), and 26 were treated with navelbine plus epirubicin (NE). Patient follow-up was carried up every 3-4 months during the first year, then every 9-12 months during subsequent years.
In univariate analysis, the rates of CIA were 44.87% for the FEC regimen, 30.30% for the TE regimen and 23.08% for the NE regimen (P = 0.068). Significant differences in the rates of CIA were not found between the FEC and TE treatment groups (P > 0.05), but were found between the FEC and NE treatment groups (P < 0.05). Furthermore, no significant differences were found between the TE and NE regimens (P > 0.05). Tamoxifen use was a significant predictor for CIA (P = 0.001), and age was also a significant predictor (P < 0.001). In multivariate analysis, age (P < 0.001), the type of chemotherapy regimens (P = 0.009) and tamoxifen use (P = 0.003) were all significant predictors.
Age and administration of tamoxifen were found to be significant predictive factors of CIA, whereas docetaxel and navelbine based regimens were not associated with higher rates of CIA than epirubicin-based regimen.
BMC Cancer 01/2010; 10:281. · 3.01 Impact Factor
