Background and purpose:Triple-negative breast cancer (TNBC) possesses high risk of relapse and metastasis. Clinically, there are no speciifc targeted-therapies to TNBC except chemotherapy. Therefore, studying the mechanism of relapse and metastasis has signiifcance to improve the patients’ survival rate. This experiment aimed to study the effect of MAPK activation on migration and invasion of triple-negative breast cancer cells. Methods:Difference of migration and invasion between lung-high metastasis breast cancer cell line 231-HM and its parental cell line 231-p were first examined by cell scratch and transwell;Then, metastasis-associated proteins and MAPK-associated molecules were detected by Western blot; Last, 231-p cells were treated with P38/MAPK inhibitor and used to determine cell migration, invasion, and metastasis-associated proteins thereafter. Results:Compared with the parental cell line 231-p, 231-HM cells displayed obviously higher ability of migration and invasion. With the increased expression of Caveolin-1and β-catenin, the phosphorylation of MAPK-associated molecules including P38, Erk1/2, and MEK was highly decreased. Treatment of 231-p cells with low concentration (10 μmol/L) of the P38/MAPK inhibitor SB202190 increased the migration and invasion of 231-p cells, and the expression of Caveolin-1 andβ-catenin. Conclusion:Activation of MAPK signaling inhibits the migration and invasion of triple-negative breast cancer.

Objective To discuss the design of pedicled thoracodorsal artery perforator flap (TDAP flap),and to evaluate the aesthetic results and donor-site complications for immediate partial breast reconstruction (IPBR) after breast conserving surgery (BCS) for breast cancer patients.Method Clinical data of 13 breast cancer cases treated with BCS + IPBR using TDAP flap from November 2004 to November 2010 were retrospectively analyzed.Perforators were identified with Doppler preoperatively in all patients.Results All perforators originated within a median distance of 8.0 cm ( range,7.5 to 9.5 cm) from axillary plica at the posterior line of axilla.Median area of the flaps was 6.0 × 8.0 cm ( range,5.0 × 7.0 cm to 8.0 × 10.0 cm).One flap was muscle-sparing,while a small muscle strip was left embedding the perforators in other twelve flaps to increase the reliability of the vascular pedicle.Postoperatively patients were followedup from 4 to 71 months.Median follow-up time was 41 months.Flap necrosis and seroma in the donor-site were not found in all patients.Aesthetic results were graded as excellent or good in 9 patients,fair in 3,and poor in one.Conclusions TDAP flap is a good choice for IPBR after BCS for breast cancer patients whether lesions in outer quadrants or inner quadrants,especially for those patients with excisional biopsy.Preoperative mini-Doppler is helpful for determining the precise location of the main perforators,and decreasing the risk of vessels injury.

Objective The present study was to explore association of PvuⅡand XbaⅠpolymorphism in ER-?gene with genetic susceptibility for breast cancer without BRCAl/2 gene mutation. Methods 113 BRCA1/2 negative hereditary breast cancer patients from independent families and 113 agematched healthy control subjects were analyzed. Genotype analysis was conducted by polymerase chain reaction (PCR) and then DNA direct sequencing. The odd-ratios (OR) and 95% confidence intervals (CI) was calculated by unconditional logistic regression model. Results The frequency of PvuⅡpolymorphism CC(PP) ,CT(Pp) ,TT(pp) genotype in patients was found in 16 cases(14.2% ), 58 cases(51. 3% ) , and 39 cases (34. 5% ). The distribution of AA (xx) , AG (Xx) , GG (XX) genotype of XbaⅠpolymorphism were found in 76 cases ( 67. 2% ) , 34 cases ( 30. 1% ), and 3 cases ( 2. 7% ) among patients. Among premenopausal women, CT genotype of PvuⅡconfered a significantly increased risk for breast cancer compared with CC genotype ( adjusted OR = 2. 07; 95% CI, 0. 68 - 6. 30) ; Carriers of GG of XbaⅠhad a decreased risk for breast cancer (adjusted OR =0. 11; 95 % CI, 0. 01 - 1. 27) compared with AA genotype. Furthermore, combined analysis of two polymorphisms indicated individuals carrying PvuⅡCT and XbaⅠAA genotype were at increased risk for breast cancer as compared with those with PvuⅡCC and XbaⅠGG genotype (Oft = 11.43, 95% CI, 1.12-116.7) among premenopausal women. Conclusions PvuⅡand XbaⅠpolymorphisms in ER-?gene could be a candidate locus for low penetrance breast cancer susceptibility in Chinese population, especially among premenopausal women.

Objective: To investigate the effect of cinobufacini on proliferation, celly cycle distribution, invasion capability of MDA-MB-231 breast cancer cell line in vitro and possible mechanism. Methods: The effect of cinobufacini on cell growth was measured by CCK-8 reagent kit. Cell cycle distribution was determined by flow cytometry. The invasion capability in vitro was detected by Transwell chamber assay. The mRNA expressions of cell cycle related factors (cyclin) and p21 were tested by RT-PCR. Results: Cinobufacini inhibited proliferation of MDA-MB-231 cells. The half inhibition concentration (IC50) was 0.31 mg/mL. The inhibitory effect was timE-dependent (P<0.05). Cinobufacini significantly decreased invasion capability of MDA-MB-231 cells in vitro compared with control group (P<0.05). Cinobufacini induced S-phase arrest of MDA-MB-231 cells in a concentration-dependent manner (P<0.000 1). Cinobufacini down-regulated the expression levels of cyclin A1, cyclin D1, and cyclin E1, while up-regulated that of p21 in MDA-MB-231 cell line. However, there was no marked change in the expression of cyclin B1. Conclusion: Cinobufacini inhibits cell proliferation and influences the cell cycle distribution in vitro by regulating the expression of cyclin A1, cyclin D1, cyclin E1 and p21 in breast can-cer cells.

Objective To explore the influencing factors for postoperative adjuvant chemotherapy effects in elderly patients with breast cancer. Methods Five hundred and ninety female patients aged 65 years or older with invasive breast cancer were treated in our hospital, and the influencing factors for postoperative adjuvant chemotherapy effects were analyzed by chi-square test and logistic regression. Results Two hundred and thirty-one (39.2%) patients received postoperative adjuvant chemotherapy. The results showed that diabetes, age, patterns of operation and pathological characteristics of tumor had significant influences on postoperative adjuvant chemotherapy effects (χ2=4.49,88. 27,23.49 and 9.40, all P<0.05). Logistic regression analysis showed that age, tumor size, lymph node status(pN) and estrogen receptor (ER) status were related to postoperative adjuvant chemotherapy effects(χ2=68.857,15. 284,43. 540 and 7.009 ,all P<0.01). Forty-four patients (66.7%) with pN(+)/ER(-) received adjuvant chemotherapy. Conclusions Age, tumor size, lymph node status and ER status were independent predictive factors for postoperative adjuvant chemotherapy effects in elderly patients with breast cancer.

Background and purpose:Rabs are members of Ras-related small GTPase superfamily. Rab27A is a unique member in the Rab family and has specific implications in human genetic diseases. We studied the potential role of Rab27A in proliferation, distribution of cell cycle, apoptosis and invasion of breast cancer cells and its mechanism(s). Methods:The eukaryotic expression vector containing Rab27A open reading frame (ORF) pcDNA3.1(+) - Rab27A was constructed and transfected into MDA-MB-231 breast cancer cells. Then we detected the changes in terms of cell growth, cell cycle distribution, apoptosis and in vitro invasion capability before and after transfection. We also applied RT-PCR to investigate the molecular basis.Results:① The expression of Rab27A was increased as invasive and metastatic ability increased in four human breast cancer cell lines. ② Overexpression of Rab27A can promote breast cancer cells to grow faster, increase the proportion of S phase cells, avoid apoptosis and invade in vitro. ③ Rab27A transfectants constitutively enhanced the expression of Cyclin D1, MMP-7 and MMP-9 in MDA-MB-231 cell lines, on the contrary, that of p16 were down-regulated constitutively. Reduced Rab27A expression by RNAi down-regulated the expression of Cyclin D1, MMP-7 and MMP-9, and up-regulated p16 expression.Conclusions:Rab27A can stimulate breast cancer cells to proliferate, increase the proportion of cells in S phase,avoid apoptosis and invade in vitro by regulating the expression of Cyclin D1, MMP-7, MMP-9 and p16.

Background and purpose: Many factors have impacts on the surgery approach of breast cancer. The purpose of this study was to analyze the influence factors of breast reconstruction for patients with breast cancer, focusing on the relationship between travel distance and breast reconstruction. Methods: Retrospective review of all female breast cancer patients staging 0-Ⅱ who underwent unilateral or bilateral mastectomy with or without breast reconstruction at Fudan University Shanghai Cancer Center from 1999 to 2015 was conducted in the study. Analysis of travel distance and breast reconstruction rate was performed. Results: Non-Shanghai patients have higher breast reconstruction rate after mastectomy compared with Shanghai patients (6.1％ vs 4.5％, P＜0.001). Travel distance may have an influence on the breast reconstruction rate (P=0.035). Univariate regression analysis showed that the increase of travel distance was the predictor of breast reconstruction, and that the increase of age or body mass index (BMI), or the later TNM stage had a negative correlation with breast reconstruction (P＜0.001). Multiple regression analysis demonstrated that the increase of age or BMI, or the later TNM stage was the independent predictor of the refusal of breast reconstruction (P＜0.001), but travel distance was not (P＞0.05). No significant correlation between the travel distance and breast reconstruction types was indicated. Negative correlation was observed between age and travel distance (P＜0.001). Conclusion: Age, BMI and tumor stage are the main influence factors of breast reconstruction, while travel distance shows a linear correlation with it.

OBJECTIVETo evaluate the role of germline mutations of TP53 gene among a Chinese population with high risk for breast cancer.

METHODSA total of 81 BRCA-negative breast cancer probands from cancer families were analyzed using targeted capture and next-generation sequencing. Candidate mutations were verified with Sanger sequencing. Co-segregation analyses were carried out to explore the likely pathogenicity of the mutation.

RESULTSOf the 81 BRCA-negative patients, 3 exonic mutations in the TP53 gene were identified in 3 breast cancer patients. Of these, 2 mutations were previously reported and 1 was novel. One family with TP53 mutation has met the criteria for Li-Fraumeni syndrome (LFS) and accounted for 9.1% of all families who fulfilled the diagnostic criteria for LFS. Two of the carriers were diagnosed with breast cancer under the age of 30, and have accounted for 11.8% (2/17) of all very young (≤30 years) breast cancer patients in our study.

CONCLUSIONThe TP53 germline mutation is more common in Chinese population with a high risk for breast cancer than previously thought. TP53 gene mutation screening should be considered particularly for patients with a family history of LFS and very young age of onset.

Adult ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Breast Neoplasms ; ethnology ; genetics ; China ; DNA Mutational Analysis ; Exons ; Family Health ; Female ; Genetic Predisposition to Disease ; ethnology ; genetics ; Germ-Line Mutation ; Heterozygote ; Humans ; Li-Fraumeni Syndrome ; ethnology ; genetics ; Male ; Middle Aged ; Pedigree ; Risk Factors ; Tumor Suppressor Protein p53 ; genetics ; Young Adult