Troponin T1 silencing inhibits paclitaxel resistance and the development of breast cancer via suppressing rat sarcoma virus/rapidly accelerated fibrosarcoma 1 pathway.

OBJECTIVE: We aimed to determine the role of Troponin T1 (TNNT1) in paclitaxel (PTX) resistance and tumor progression in breast cancer (BC). METHODS: Differentially expressed genes were obtained from the GSE4298 and GSE90564 datasets. Hub genes were isolated from protein-protein interaction networks and further validated by real-time quantitative polymerase chain reaction. The effect of TNNT1 on PTX resistance was determined using cell counting kit-8, 5-ethynyl-2'-deoxyuridine, wound healing, transwell, flow cytometry assays, and subcutaneous xenografted tumor model. Western blotting was used to detect proteins associated with PTX resistance, apoptosis, migration, invasion, and other key pathways. Hematoxylin-eosin and immunohistochemical staining were used to evaluate the role of TNNT1 in tumors. RESULTS: After comprehensive bioinformatic analysis, we identified CCND1, IGF1, SFN, INHBA, TNNT1, and TNFSF11 as hub genes for PTX resistance in BC. TNNT1 plays a key role in BC and is upregulated in PTX-resistant BC cells. TNNT1 silencing inhibited PTX resistance, proliferation, migration, and invasion while promoting apoptosis of PTX-resistant BC cells. Tumor xenograft experiments revealed that TNNT1 silencing suppresses PTX resistance and tumor development in vivo. In addition, TNNT1 silencing inhibited the expression of proteins in the rat sarcoma virus (RAS)/rapidly accelerated fibrosarcoma1 (RAF1) pathway in vivo. Treatment with a RAS/RAF1 pathway activator reversed the inhibitory effect of TNNT1 silencing on proliferation, migration, and invasion while promoting apoptosis of PTX resistance BC cells. CONCLUSION: Silencing of TNNT1 suppresses PTX resistance and BC progression by inhibiting the RAS/RAF1 pathway, which is a promising biomarker and therapeutic target for drug resistance in BC.

Correlation of radiotherapy with prognosis of elderly patients with hormone receptor-positive breast cancer according to immunohistochemical subtyping.

OBJECTIVE: The present study examined the effect of radiotherapy on recurrence and survival in elderly patients with hormone receptor-positive early breast cancer. METHODS: A retrospective analysis of 327 patients aged ≥65 years, with stage I-II, hormone receptor-positive breast cancer who underwent breast-conserving surgery and received endocrine therapy (ET) or radiotherapy plus endocrine therapy (ET+RT) was performed. Both groups were divided into luminal A type and luminal B type subgroups. Evaluation criteria were 5-year disease-free survival (DFS), local relapse rate (LRR), overall survival (OS), and distant metastasis rate (DMR). RESULTS: There were significant differences in 5-year DFS [hazard ratio (HR)=1.59, 95% confidence interval (95% CI), 1.15-2.19; P=0.005] and LRR (HR=3.33, 95% CI, 1.51-7.34; P=0.003), whereas there were no significant differences in OS and DMR between ET group and ET+RT group. In luminal A type, there was no significant difference in 5-year DFS, LRR, OS and DMR between ET group and ET+RT group. In luminal B type, there were statistically significant differences in 5-year DFS (HR=2.19, 95% CI, 1.37-3.49; P=0.001), LRR (HR=5.45, 95% CI, 1.65-17.98; P=0.005), and OS (HR=1.75, 95% CI, 1.01-3.05; P=0.048) between ET group and ET+RT group. In the ET group, there were significant differences between luminal A type and luminal B type in 5-year DFS (HR=1.84, 95% CI, 1.23-2.75; P=0.003) and OS (HR=1.76, 95% CI, 1.07-2.91; P=0.026). CONCLUSIONS: After breast-conserving surgery, radiotherapy can reduce the LRR and improve the DFS and OS of luminal B type elderly patients, whereas luminal A type elderly patients do not benefit from radiotherapy. Without radiotherapy, luminal A type patients have better DFS and OS than luminal B type patients.

[Comparative study of chemosensitivity and efficacy between pirarubicin and epirubicin in breast cancer].

OBJECTIVE: To compare the chemosensitivity of pirarubicin (THP) and epirubicin (EPI) in primary breast cancer (PBC) cells so as to examine their differential chemosensitivity to THP and EPI by CD-DST (collagen gel droplet embedded culture-drug sensitivity test) system; To detect the differences in the short-term clinical efficacy and side effects between TAC (docetaxel + pirarubicin + cyclophosphamide) and TEC (docetaxel + epirubicin + cyclophosphamide) as the neoadjuvant chemotherapy regimens and the long-term clinical efficacy of CAF (cyclophosphamide + pirarubicin + fluorouracil) and CEF (cyclophosphamide + epirubicin + fluorouracil) as the chemotherapy regimens in breast cancer; To evaluate the feasibility of THP as an adjuvant chemotherapeutic regimen in the treatment of breast cancer. METHODS: From January 2008 to January 2009, a total of 129 fresh breast cancer samples were collected. The differential chemosensitivity of cultured PBC cells to THP and EPI was measured by CD-DST test. And 139 cases of PBC patients inIIb-IIIc phase were randomly divided into two groups: TAC and TEC groups. After 4-6 cycles of neoadjuvant chemotherapy, the primary lesion, axillary lymph nodes and side effects were assessed; The clinical data and survival status of 1241 cases of PBC patients treated at our hospital from 2003 to 2006 were collected and divided into CAF and CEF groups according to their chemotherapeutic regimens. Long-term prognosis was compared between two groups. RESULTS: There was no significant difference of chemosensitivity between THP and EPI in PBC cells (P = 0.743); The overall response rate (RR) of neoadjuvant chemotherapy was 87.8%; the clinical objective responses, pathologic complete remission (pCR), clinical complete remission (cCR), clinical partial remission (cPR) and stable disease (SD) of groups TAC and TEC were 88.7%, 11.3%, 28.2%, 60.6%, 11.3% vs 86.8%, 10.3%, 26.5%, 60.3%, 13.2% respectively. There was no significant difference between two groups (P > 0.05). No significant differences existed between two groups in such side effects as leukopenia, thrombocytopenia, constipation, cardiotoxity and hepatorenal dysfunction (P > 0.05). The gastrointestinal reactions of nausea and vomiting was less frequent in the TAC group than that in the TEC group (46.5% vs 66.2%, P = 0.019); There was no significant difference in 5-year disease-free survival rate (79% vs 78%) and overall survival rate between two groups (85% vs 82%, P > 0.05). CONCLUSION: There were no significant differences in chemosensitivity, clinical efficacy of neoadjuvant chemotherapy, side effects or long-term efficacy between THP and EPI. Both pirarubicin and epirubicin may be used as conventional chemotherapy in breast cancer.

Correlation between family history and characteristics of breast cancer.

Family history is a major risk factor for breast cancer; approximately 5-10% cases of breast cancer are associated with a family history. Herein, we investigated the link between family history and breast cancer features to elucidate the importance of family history in the diagnosis and treatment of breast cancer. Data from 10,549 patients with breast cancer were collected from 2014 to 2017. Detailed information about the family history of the patients including the degree and number of relatives affected and the types of cancer was recorded. The tumors were pathologically and clinically classified based on the stage, grade, ER, PR, HER2, Ki-67 status, and subtypes, according to standard guidelines. Data were analyzed using χ2 test and multiple logistic regression. Patients with a family history of other cancer types were significantly older at diagnosis than patients with a family history of breast/ovarian cancer (p = 0.002) and those without a family history of cancer (p < 0.001). Patients without a family history of cancer were typically diagnosed at a later stage, including high frequency in N2 (p = 0.035) and TNM stage III (p = 0.015). Compared with patients with second-/third-degree relatives, those with first-degree relatives having breast/ovarian cancer had a higher median age (54.1, p < 0.001) at diagnosis and showed more advanced disease. No significant difference was found between ER, PR, and HER2 status in patients with and without a family history of cancer. Family history of breast cancer can influence the cancer characteristics of the patients at diagnosis, especially patient age, tumor stage, and grade.

Efficacy and feasibility of the immunomagnetic separation based diagnosis for detecting sentinel lymph node metastasis from breast cancer.

A purpose of this study was to establish a novel molecular diagnostic model and provide new insight into the intraoperative evaluation of the sentinel lymph node (SLN) metastasis in breast cancer. A total of 124 breast cancer patients who met the criteria of sentinel lymph node biopsy (SLNB) and underwent intraoperative biopsy were consecutively enrolled in this study. After the SLNs obtained from each patient were labeled, MOC-31 monoclonal antibody-mediated immunomagnetic separation (IMS) and flow cytometry were used to determine the expressions of breast cancer metastasis-related markers, including Mucin 1 (MUC1), CD44v6, and HER2. Alternatively, conventional intraoperative hematoxylin and eosin (HE) staining and cytokeratin immunohistochemistry (CK-IHC) were performed to detect potential SLN metastasis. The sensitivity, specificity, and false-negative rate of the three intraoperative diagnostic methods were compared and analyzed. A total of 55 positive-SLNs were found in 38 breast cancer patients using IMS, yielding a sensitivity of 86.4% (38/44), specificity of 94.7% (36/38), accuracy of 93.5% (116/124), false-positive rate of 2.5% (2/80), false-negative rate of 13.6% (6/44), positive predictive value of 95.5% (42/44), and negative predictive value of 93.0% (80/86). Patients with high expressions of CD44v6, MUC1, and HER2 in SLNs tended to have higher number of positive lymph nodes, among which the MUC1 and HER2 showed significant differences (P<0.05). Therefore, compared with conventional HE staining and CK-IHC, IMS technology has remarkably higher sensitivity and specificity and relative lower false-negative rate, thus making it an effective and feasible intraoperative detection method of SLN for breast cancer diagnosis to some extent.

BRCA1 and BRCA2 sequence variants in Chinese breast cancer families.

A series of 45 high-risk breast cancer patients, consisting of 25 affected individuals from 16 families in China with at least two cases of breast cancer and 20 cases of breast cancer diagnosed under age 35 without reported family history, were studied for germline mutations of the BRCA1 and BRCA2 genes. Thirteen of the 16 families contained at least one case diagnosed under age 50. Three distinct protein truncating sequence variants, likely to be disease-associated, were identified: two novel mutations in BRCA1 (1584G>T and 5028delC), and a previously reported mutation in BRCA2 (7883delTTAA). Additional sequence variants identified included common polymorphisms, and several variants of unknown clinical significance, including a novel BRCA1 alteration. Based on models for predictive testing using allele frequencies and risks estimated in Western populations, our results suggest that BRCA1/2 mutations account for a somewhat smaller fraction of breast cancer cases in Tianjin than in the Caucasian populations studied. This difference could be the result of a lower penetrance of BRCA1/2 mutations due to the surrounding environmental and hormonal milieu, or a lower frequency of mutations in this population. Larger, more detailed, studies will be necessary to determine which factors underlie this difference.