Feasibility study of immediate breast reconstruction with fusion fascia combined with implants / 中华肿瘤杂志

Objective: To investigate the oncologic and surgical safety of the fused fascia method for immediate breast reconstruction with implants. Methods: The clinical data of 343 patients with immediate breast reconstruction with implants in Tianjin Medical University Cancer Hospital from 2014-2017 were retrospectively analyzed to compare the 5-year local recurrence-free survival, 5-year disease-free survival and 5-year overall survival of patients with breast reconstruction by fusion fascia and other methods, and to analyze the complication incidences of implant removal between different implant groups. Results: Of the 343 patients with breast reconstruction, 95 were in the fused fascia group (fascia group) and 248 were in the non-fascia group (25 in the bovine pericardial patch group and 223 in the muscle flap group). At a median follow-up of 49 months, the differences in 5-year local recurrence-free survival (90.1% and 94.9%, respectively), 5-year disease-free survival (89.2% and 87.6%, respectively), and 5-year overall survival (95.2% and 95.1%, respectively) between patients in the fascial and non-fascial groups were not statistically significant (P>0.05). The complication incidence of implant removal was 24.0% (6/25) in the patch group and 2.1% (2/95) and 2.2% (5/223) in the fascia and muscle flap groups, respectively. Conclusion: Immediate breast reconstruction with fused fascial combined with implant is safe and feasible, less invasive than muscle flaps, more economical and with fewer complications than patches.

Effect of gefitinib on the migration of triple-negative breast cancer cell line MDA-MB-231 cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the effect of gefitinib on the migration of triple-negative breast cancer cell line MDA-MB-231 cells.</p><p><b>METHODS</b>Gefitinib was used in concentrations of 0 micromol/L, 0.1 micromol/L, 1 micromol/L, 10 micromol/L and 20 micromol/L, respectively. Phosphorylation levels of EGFR and Akt were analyzed by Western blot. The capability of migration was measured by scratch test and Boyden chamber assay. Microfilaments (cell skeleton ) remolding and polarization were evaluated by immunofluorescence microscopy.</p><p><b>RESULTS</b>Comparing with the control group (0 micromol/L gefitinib), gefitinib effectively inhibited the phosphorylation of EGFR and its downstream key proteins, and the effect displayed an obvious dose-effect relationship. At 24 hours after wound scratch, the cell migration distance of each group with 0, 0.1, 1, 10, 20 micromol/L gefitinib was (36.3 +/- 4.0) microm, (30.3 +/- 3.8) microm, (26.8 +/- 3.3) microm, (17.0 +/- 2.6) microm, and (11.0 +/- 2.5) microm, respectively. At 3.5 hours after Boyden chamber assay, the cell count of each group with 0, 0.1, 1, 10, 20 micromol/L gefitinib was 69.2 +/- 7.0, 51.8 +/- 7.5, 43.8 +/- 8.7, 30.6 +/- 4.8, and 28.4 +/- 3.4, respectively. Compared with the control group (0 micromol/L gefitinib), gefitinib could significantly prolong the wound-healing time and decrease the migrating cell count (P < 0.05), and significantly inhibit the lamellipodium formation, cell skeleton remolding and changes of the cytoskeleton polarization.</p><p><b>CONCLUSIONS</b>Gefitinib can reduce the migration capacity of triple-negative breast cancer cells through inhibiting phosphorylation of EGFR/PI3K/Akt pathway, suppressing the cell skeleton (microfilaments) remolding and changes of its polarization.</p>

Mammographic and pathological features of triple-negative breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To retrospectively evaluate the mammographic imaging findings and pathologic changes of the so-called "triple-negative" breast cancer (ER(-)/PR(-)/HER-2(-) breast cancer), and to compare them with the ER(+)/PR(+)/HER-2(-) and ER(-)/PR(-)/HER-2(+) breast cancer patients.</p><p><b>METHODS</b>Five hundred cases of breast cancer treated in Cancer Institute and Hospital of Tianjin University from January to June of 2010 were included in this study. There were 112 cases of triple-negative breast cancer, 310 cases of ER(+)/PR(+)/HER-2(-) breast cancer, and 78 cases of ER(-)/PR(-)/HER-2(+) breast cancer. Their pathological and mammographic data were reviewed and analyzed. The pathological and mammographic features of the three groups were compared.</p><p><b>RESULTS</b>Compared with the ER(+)/PR(+)/HER-2(-) breast cancer group, the triple-negative group had a higher histological grade (P < 0.001). Compared with the ER(+)/PR(+)/HER-2(-) and ER(-)/PR(-)/HER-2(+) groups, the triple-negative group was more likely to have a tumor mass (simple mass accounted for 58.0%, and tumor mass with calcification accounted for 19.6%). Moreover, compared with the ER(+)/PR(+)/HER-2(-) group (47.1% vs. 9.8%, P = 0.032)and the ER(-)/PR(-)/HER-2(+) group (47.1% vs. 0, P = 0.028), the tumor mass of triple-negative cancer was more likely to have a smooth margin. Triple-negative breast cancer seldom represented as calcification (simple calcification only accounted for 13.4%, and a mass with calcification accounted for 19.6%), and most of them were benign calcification (70.3%), significantly higher than that in the ER(+)/PR(+)/HER-2(-) group (23.1%, P = 0.002) and ER(-)/PR(-)/HER-2(+) group (10.2%, P < 0.001).</p><p><b>CONCLUSIONS</b>Different types of breast cancer have different biological characteristics and mammographic features. Analysis of the mammographic features may help us to predict the type of breast cancer and its prognosis, and to select an optimal treatment plan for patients with different types of breast cancer.</p>

Bcl-2 inhibitor ABT-737 enhances the cisplatin-induced apoptosis in breast cancer T47D cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the effect of ABT-737 combined with cisplatin on apoptosis of breast cancer cell line T47D cells.</p><p><b>METHODS</b>T47D cells cultured in vitro was used for this experiment. Cell proliferation was measured by MTT assay. The expression of apoptosis-related protein was determined by Western blot. Morphological changes of apoptotic cells were observed by fluorescence microscopy. The apoptosis rate was examined by flow cytometry.</p><p><b>RESULTS</b>The MTT assay showed that ABT-737 significantly decreased the IC(50) of cisplatin in T47D cells [(26.00 ± 1.41) µmol/L of single cisplatin vs. (13.00 ± 1.11) µmol/L of combination (ABT-737 + cisplatin)]. As a single agent, ABT-737 did not inhibit the proliferation of T47D cells, but enhanced the inhibitory effect of cisplatin in a dose-dependent manner. The detection of the cleavage of PARP showed that ABT-737 lowered the doses of cisplatin to induce apoptosis and shortened the induction time of apoptosis in T47D cells. Compared with the single use of cisplatin, the combination of ABT-737 and cisplatin accelerated the cleavage of PARP and caspase3, but did not alter the expression levels of Bcl-2, Bcl-X(L), and Bax. Both flow cytometry and fluorescence microscopy showed that ABT-737 combined with cisplatin significantly increased the apoptosis induction in T47D cells (2.3% ± 0.1 % in the control, 30.0% ± 0.8% in the cisplatin alone, and 49.0% ± 0.5% in the cisplatin + ABT-737 groups, P < 0.05).</p><p><b>CONCLUSION</b>The Bcl-2 inhibitor ABT-737 can significantly enhance cisplatin-induced apoptosis in human breast cancer T47D cells in vitro.</p>

Association of FGFR2 gene polymorphism with estrogen receptor positive breast cancer detected by fluorescent quantitative PCR / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association of fibroblast growth factor receptor 2 gene (FGFR2) rs2981582 polymorphism with breast cancer in Chinese women.</p><p><b>METHODS</b>A case-control study was performed in 936 breast cancer patients and 471 patients with benign breast diseases by using a novel fluorescent quantitative PCR method.</p><p><b>RESULTS</b>The numbers and frequencies of genotypes CC, CT, and TT in the control group were 234(49.68%), 181(38.43%) and 56(11.89%) respectively. The numbers and frequencies of genotypes CC, CT, and TT in the breast cancer group were 426(44.56%), 400(41.84%) and 130(13.60%) respectively. And no significant difference was found between the two groups (P=0.183). However, stratified analysis found that the numbers and frequencies of genotypes CC, CT, TT in the estrogen receptor(ER) positive subgroup of breast cancer patients were 189(41.27%), 202(46.12%) and 67(14.63%) respectively, and significant difference was observed compared with control group (P=0.035).</p><p><b>CONCLUSION</b>Association was found in the single nucleotide polymorphism(SNP) of the rs2981582 locus of intron 2 in FGFR2 gene between the ER positive breast cancer patients and control patients with benign breast diseases. The fluorescent quantitative PCR is a specific, easy-to-operate, low-expense method and is suitable for SNP detection in large scale samples.</p>

Clinical impact of extracapsular extension of axillary lymph node metastases in breast cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the clinical significance of extracapsular extension (ECE) of axillary lymph node metastases in breast cancer.</p><p><b>METHODS</b>The clinicopathological data of 1230 cases of nodal positive breast cancer treated in our department from 1989 to 1995 were analyzed retrospectively.</p><p><b>RESULTS</b>486 (39.5%) from the 1230 cases were ECE positive. There was a higher incidence of ECE in postmenopausal women than premenopausal ones (47.5% versus 35.5%, respectively, P < 0.001). The patients in ECE positive group had a larger tumor size (5.11 +/- 2.53 cm versus 3.90 +/- 1.80 cm, P < 0.001). 18.3% of patients with stage T1 were ECE positive, stage T2 were 36.4%, and stage T3 were 54.4%, and the difference was significant (P < 0.001). ECE was correlated with the number of positive axillary lymph nodes. The ECE positive group had more positive nodes than ECE negative group (16.96 +/- 12.16 versus 5.24 +/- 6.60, P < 0.001). 6.1% of patients with 1 positive node were ECE positive, 13.5% with 2 - 3, 35.8% with 4 - 9, 62.3% with 10 - 19, and 84.0% with more than 20 positive axillary nodes, and there was a significant difference among those groups (P < 0.001). ECE had no association with ER/PR status (P = 0.706). ECE was a risk factor of local-regional recurrence, but the relapse time had no significant difference (P = 0.559). ECE was also a risk factor of distant metastasis, and the relapse time had a significant difference (P < 0.001). The median metastasis free time was 30.0 (2 approximately 172) months in ECE positive group, while 37.5 (2 approximately 170) months in ECE negative group (P = 0.006). CE occurred in 60.4% of the patients with firstly diagnosed bone, skin and distant lymph node metastasis, but in 42.0% of the patients with firstly diagnosed visceral metastasis (P = 0.001). The metastasis-free survival rate, locoregional recurrence-free survival rate and overall survival rate of the ECE positive group were much shorter than that of the ECE negative group. COX proportional hazard regression single factor analysis and multi-factor analysis suggested that ECE is an independent factor of metastasis-free survival, locoregional free recurrence and overall survival.</p><p><b>CONCLUSION</b>The presence of ECE in breast cancer is positively related with tumor size and the number of positive lymph nodes. It is also a risk factor of locoregional recurrence and distant metastasis. ECE positive group has a much shorter metastasis-free survival, locoregional recurrence-free survival and overall survival. ECE is a risk factor of those three indexes.</p>

Research on the postoperative complications and its risk factors of breast reconstruction with abdominal flaps / 中华外科杂志

<p><b>OBJECTIVE</b>To study the postoperative complications and its risk factors in patients underwent breast reconstruction with abdominal flaps.</p><p><b>METHODS</b>The clinical data of 115 cases underwent breast reconstructions with abdominal flaps from May 2001 to October 2008 was reviewed. The postoperative complications included total flap necrosis, partial flap necrosis, fat necrosis, hernia, bulge, fat liquefaction and infection. The risk factors of complication rates were also evaluated.</p><p><b>RESULTS</b>The total postoperative complications rate was 17.4% (20/115). No severe complications was found, such as total flap necrosis, hernia and bulge. The most common complications of flap was fat necrosis which occurred in 6 cases (5.2%), partial flap necrosis in 5 cases (4.3%) and infection in 1 case (0.9%). The donor-site complications included fat liquefaction which occurred in 8 cases (7.0%) and infection in 3 cases (2.6%). No significant relation was found between patient's age, body mass index (BMI), timing of surgery and the postoperative complication rate. The postoperative complications occurred more frequently in active smokers, patients with radiotherapy history, or reconstructions with pedicled transverse rectus abdominis myocutaneous (TRAM) flaps. But no significant difference was found in those factors.</p><p><b>CONCLUSIONS</b>Fewer complications happens in patients with a reconstruction with deep inferior epigastric perforator (DIEP) flap. Abdominal flap should be performed with more consideration in active smokers or patients with a radiotherapy history. Age and obesity should not be contraindications to breast reconstruction with abdominal flaps.</p>

Relationship between the expression of matrix metalloproteinase-13 protein and other biomarkers, prognosis in invasive breast cancer / 中华病理学杂志

<p><b>OBJECTIVE</b>The study was designed to investigate the expression patterns of metalloproteinase (MMP)-13 protein in invasive breast carcinoma and to determine the clinicopathological and prognostic values of its various localization and relation to the tumor phenotypes.</p><p><b>METHODS</b>Immunohistochemistry was performed on paraffin-embedded tissue array from 263 invasive breast carcinomas to investigate the protein expressions of MMP-13, estrogen receptor, progesterone receptor, HER2, MMP-2, MMP-9 and tissue inhibitor of matrix metalloproteinases (TIMP)-1, TIMP-2.</p><p><b>RESULTS</b>MMP-13 protein was detected in the cytoplasm of carcinoma cells and peritumoral fibroblasts. High level expression of MMP-13 protein in tumor cells was associated with more lymph node involvement and higher tumor grade (both P < 0.01), and positively correlated with HER2 (P = 0.015) and TIMP-1 protein (P < 0.01) expression in carcinoma cells. Moreover, high expression of MMP-13 was associated with shortened overall survival for the entire patient population and the patient group with positive lymph node. Tumor cell derived MMP-13 had different impact on patients with different HER2 status. Peritumoral fibroblasts derived MMP-13 protein, although correlated with tumor cell derived MMP-13 and associated with lymph node stage and HER2 expression, was found having less prognostic impact. Univariate survival analysis showed that the tumor size, grade, lymph node status, PR status, HER2 expression, tumors TIMP-1 and MMP-13 expression were prognostic factors. However, multivariate survival analysis showed that only tumor size, lymph node status, HER2 expression, tumors TIMP-1 and MMP-13 were independent prognostic factors.</p><p><b>CONCLUSION</b>MMP-13 protein expressed by tumor cells correlates with the invasion and metastasis of breast carcinoma, and therefore, may serve as a poor prognostic marker for the patient.</p>

Intra-operative frozen section diagnosis of breast lesions: a retrospective analysis of 13,243 Chinese patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Although cytological methods for breast oncology have been used in recent decades, intra-operative frozen section has been playing a vital role in making therapeutic decisions. We analyzed a large series of frozen section diagnoses for Chinese cases of breast lesion within the last 15 years. The experience was expected to increase the diagnostic accuracy of cases with breast lesions.</p><p><b>METHODS</b>The data from consecutive 13243 cases of breast lesions diagnosed with intra-operative frozen sections between 1988 to 2002 were compared with paraffin sections in a case by case manner. The causes of false negative and positive diagnoses as well as delayed diagnoses were analyzed.</p><p><b>RESULTS</b>One hundred and seventeen cases (0.9%) were falsely diagnosed, with one false positive case and 116 false negative cases. The diagnosis of 47 cases (0.4%) was delayed. The proportion of several lesions had the features of the patients' ages. Six types (false invasion, peri-papilloma, adenoma of nipple duct, florid adenosis, sclerosing adenosis, and granulose cell tumor) of lesions may lead to false positive, and four types (morphological changes responding chemotherapy, well differentiated papillary carcinoma, invasive lobular carcinoma, and tubular carcinoma) to a false negative. Gross and microscopic findings may be inconsistent in two types of lesions (radial scar and florid adenosis) microscopic and clinical findings in three types (ganulomatous mastitis mammary, duct ectasia, and fat necrosis), and three types (abundant fat or sclerous tissues; borderline lesions and changes of post-chemotherapy) were likely wrongly classified.</p><p><b>CONCLUSIONS</b>Intra-operative frozen section can accurately identify breast lesions in many instances, leading to fewer errors on account of more diagnostic experience and understanding of diagnostic limitations.</p>