In recent years, studies have found that breast microbiota differs between breast cancer tissue and normal breast tissue. Breast microbiota is closely related to the occurrence and development of breast cancer, and its mechanism includes affecting estrogen levels, lipid metabolism, immune regulation, and inflammatory response. Adjusting diet, rational use of antibiotics and oral probiotics can regulate breast microbiota, which is a new direction for the prevention and treatment of breast cancer.

Targeted therapy for breast cancer can significantly improve the prognosis, quality of life and survival of breast cancer patients, but the emergence of primary or acquired drug resistance will eventually lead to disease progression, recurrence or metastasis. Tumor microenvironment (TME) is a complex environment for breast cancer cells to survive. Breast cancer cells and TME are currently known to be a functional whole, and the crosstalk between them plays a key role in breast cancer progression and resistance to targeted therapies. Therefore, clarifying TME abnormalities is important to reveal the underlying mechanisms of targeted therapy resistance and to develop therapeutic strategies against targeted therapy-resistant malignancies.

Objective:To investigate the effects of myeloid differentiation protein-2 (MD-2) on paclitaxel resistance cells in triple negative breast cancer (TNBC) through EGFR signaling pathway.Methods:Immunohistochemical method was used to detect the expression of MD-2 in cancer tissue and adjacent tissue of TNBC patients, and the relationship between MD-2 expression and clinicopathological parameters of patients was analyzed. The TNBC paclitaxel-resistant cell line was constructed and MD-2 expression in cells was interfered. Cell invasion was detected by Transwell, and cell apoptosis was detected by flow cytometry. The signaling pathways regulated by MD-2 were screened by transcriptome sequencing and verified by Western blot.Results:The expression of MD-2 was significantly enhanced in cancer tissues relative to adjacent tissues. High expression of MD-2 was closely related to clinical stage, tumor size, tumor recurrence and metastasis ( χ2=4.50, P=0.032; χ2=2.55, P=0.011; χ2=4.40, P=0.036). In cell experiments, compared with normal breast cells, the expression of MD-2 in TNBC cell lines was significantly enhanced. Compared with sh-NC group (100±11.52) (6.81±0.57), knockdown of MD-2 could inhibit the invasion (61.44±6.78) ( t=4.99, P=0.008) but promote apoptosis (15.19±1.06) ( t=12.06, P<0.001) of paclitaxel resistant TNBC cells. Transcriptome sequencing and Western blot results showed that MD-2 mainly affects the biological behavior of TNBC cells by regulating the EGFR signaling pathway. Conclusions:MD-2 promoted TNBC cell invasion and paclitaxel resistance, which may be achieved by affecting the EGFR signaling pathway. MD-2 is expected to become an effective target in TNBC treatment.

Tumor microenvironments (TMEs) are closely related to tumor resistance. TMEs are divided into cellular components and acellular components. The cellular components include tumor-associated macrophages, tumor-associated fibroblasts, mesenchymal stem cells, etc., which can enhance tumor resistance through recruitment and secretion of a variety of protective cytokines; acellular components such as extracellular matrix, hypoxia and acidification, etc., can mediate drug resistance by constructing physical barriers, affecting tumor cell growth and metabolism. Studying the mechanisms of TME-mediated drug resistance and reshaping TMEs can provide new strategies for anti-tumor therapy.

Despite the deepening of research on breast cancer,improving of treatment techniques,there are still many patients will appear local-regional recurrence after surgery.For patients with local recurrence after radical mastectomy,according to whether the postoperative radiotherapy performed,prognosis and treatment protocols are absolutely different.As for patients with local recurrence after breast-conserving surgery,more and more studies have shown that lumpectomy (secondary breast conserving surgery) combined with brachytherapy can achieve a similar effect with radical surgery in recent years,so it is a worth considering treatment protocol.

Accurate knowledge,diagnosis and treatment of breast ductal carcinoma in situ(DCIS),are crucial in controlling the development of breast cancer.In the diagnosis phase,breast ultrasound is commonly used as a screening tool,and a clear diagnosis can be made by mammography.Meanwhile,serological tests contribute to the detection of DCIS in early stages.In the treatment,the optimal surgical operation method remains debatable.It is widely acknowledged that the radiotherapy of postoperative patients should become more individualized.In addition,corresponding endocrine therapy helps those ER positive patients to reduce the recurrence.In the development of DCIS to invasive cancer,there are changes in gene and protein expressions,which may be a potential direction for further research.

Objective To investigate the impact of lack of progesterone receptor ( PR) expression on the prognosis of patients with operable ER ( estrogen receptor)?positive invasive breast cancer. Methods We retrospectively analyzed the clinicopathological features, treatment and survival data of 318 women with ER+/PR+ and ER+/PR? invasive breast cancer. Results Among the 318 patients, there were 219 PR?positive and 99 PR?negative cases. The 5?year overall survival ( OS ) rate was 92. 5%, and the 5?year disease?free survival ( DFS) rate was 87. 2% in the 318 ER?positive patients. Among them, the 5?year OS rates were significantly different between the PR?positive group (94.6%) and PR?negative group (87.8%, P=0.020), and the 5?year DFS rates were also significantly different from each other (89.8% and 81.6%, respectively, P=0.019).Univariate analysis showed that PR status, tumor size, T stage, axillary lymph node metastasis, and clinical stage were prognostic factors for OS ( P<0.05 for all) . Multivariate analysis showed that lack of PR expression, T stage ≥2, and positive axillary lymph node metastasis were independent risk factors for poor DFS and OS in ER?positive breast cancer patients ( P<0. 05 for all ) . Subgroup analysis showed that lack of PR expression was not significant in predicting poor DFS or OS when patients were in stageⅠ or with a small tumor (≤2 cm) (P>0.05 for all), and also showed that premenopausal women with PR?negative disease had poorer DFS and OS than PR?positive patients ( P<0.05 for both) . Conclusions Lack of PR expression is an independent risk factor for poor prognosis in patients with operable ER?positive invasive breast cancer, especially in patients with a large tumor (>2 cm) , advanced clinical stage ( StageⅡ or Ⅲ) or in premenopausal status.

Objective To investigate the impact of lack of progesterone receptor ( PR) expression on the prognosis of patients with operable ER ( estrogen receptor)?positive invasive breast cancer. Methods We retrospectively analyzed the clinicopathological features, treatment and survival data of 318 women with ER+/PR+ and ER+/PR? invasive breast cancer. Results Among the 318 patients, there were 219 PR?positive and 99 PR?negative cases. The 5?year overall survival ( OS ) rate was 92. 5%, and the 5?year disease?free survival ( DFS) rate was 87. 2% in the 318 ER?positive patients. Among them, the 5?year OS rates were significantly different between the PR?positive group (94.6%) and PR?negative group (87.8%, P=0.020), and the 5?year DFS rates were also significantly different from each other (89.8% and 81.6%, respectively, P=0.019).Univariate analysis showed that PR status, tumor size, T stage, axillary lymph node metastasis, and clinical stage were prognostic factors for OS ( P<0.05 for all) . Multivariate analysis showed that lack of PR expression, T stage ≥2, and positive axillary lymph node metastasis were independent risk factors for poor DFS and OS in ER?positive breast cancer patients ( P<0. 05 for all ) . Subgroup analysis showed that lack of PR expression was not significant in predicting poor DFS or OS when patients were in stageⅠ or with a small tumor (≤2 cm) (P>0.05 for all), and also showed that premenopausal women with PR?negative disease had poorer DFS and OS than PR?positive patients ( P<0.05 for both) . Conclusions Lack of PR expression is an independent risk factor for poor prognosis in patients with operable ER?positive invasive breast cancer, especially in patients with a large tumor (>2 cm) , advanced clinical stage ( StageⅡ or Ⅲ) or in premenopausal status.

Objective To study the clinical characteristics,pathology,and treatment for papillary carcinoma of the breast.Methods The clinical data of 17 patients of papillary carcinoma of the breast admitted in the First Affiliated Hospital of Wen Zhou Medical College were retrospectively analyzed.Results Papillary carcinoma of the breast accounted for 0.64％ of all breast cancer cases hospitalized during last 10 years.All cases had palpable lumps in the breast.12 cases received modified radical mastectomy,2 cases received simple mastectomy,2 cases underwent breast conservation therapy,1 case underwent simple mastectomy plus sentinel lymph node biopsy.15 patients received postoperative chemotherapy,among those 5 cases also received radiotherapy.During a 32.5-month median follow-up ( 1 month to 8 years),one case with bone metastases died 2 years postoperatively and another one died of multimetastases 7 years later.Conclusions The prognosis of papillary carcinoma of the breast is closely related with its pathology type.For intraductal papillary carcinoma low-traumatic therapy is applicable,while in case of infiltrating papillary carcinoma or invasive micropapillary carcinoma ( IMPC ),more aggressive therapies like that adopted for infiltrating ductal carcinoma are recommended.

Objective To analyse the frequeney and pattern of lymph node metastasis in bilateral papillary thyroid microcarcinoma (PTMC), and establish the optimal surgical strategy for patients. Methods From March 2006 to August 2008, 58 bilateral PTMC patients received surgical treatment and the tumour characteristics, the frequency and pattern of lymph node metastasis and surgical management of these patients were retrospectively analysed. Results Forty-four patients received total thyroideetomy and 14 patients received near-totsl thyroideetomy, 47 patients received central compartment (level VI ) dissection and cervical level Ⅱ,Ⅲ, IV node exploration by internal jugular vein exposure,10 patients received level Ⅵdissection and unilateral cervical dissection and 1 patient received bilateral cervical dissection. The mean tumor diameter was (6.28 + 2.23) mm and 26 patients (44.8%) had node involvement, 88.5%(23/26) pa-tients had only level Ⅵ node involvement. Only 1 patient had node involvement in the jugular chain without level Ⅵ node involvement, 2 patients with level Ⅵ node involvement were associated with another cervical compartment nodes involvement. Conclusions Bilateral PTMC has high incidence of lymph node metasta-sis. The cervical level Ⅵ is the most common site of node involvement for bilateral PTMC and the surgical strategy for bilateral PTMC should include the cervical level Ⅵ dissection routinely.