Background Triple-negative breast cancer (TNBC) is a type of breast cancer with a high degree of malignancy. Because of the remarkable biological characteristics of high invasion, metastasis and recurrence, TNBC is often accompanied by a poor prognosis. As a molecular characteristic of TNBC, high expression of CD147 has been confirmed by a large number of studies. However, the mechanism of CD147 expression regulation in TNBC remains elusive. In this study, we investigated the roles of miR-890 in inhibiting CD147. Methods Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) was used to detect CD147 mRNA and miR-890 level, and western blotting was used to detect CD147 protein. Bioinformatics screening and 3′-Untranslated Region (3′-UTR) luciferase assays were used to analyze the microRNAs (miRNA) binding site. Cell proliferation, apoptosis and invasion were assessed by using CCK-8, flow cytometry and transwell assays. Results The upregulation of miR-890 inhibited cell proliferation and invasion, induced apoptosis in MDA-MB-231 and HCC-70 TNBC cells by negatively regulating its target gene, CD147, and the upregulation of CD147 rescued the inhibitory effects of miR-890. miR-890 targeted CD147 by binding to its 3′-UTR. Further results showed that the upregulation of miR-890 also inhibited the expression of MMPs, the downstream genes of CD147, and promoted the cleavage of Caspase-3. The CD147 recovery experiment was further confirmed by the activity changes in the downstream MMPs of CD147. In addition, it was confirmed that the effect of CD147 in promoting TNBC cell proliferation and invasion, inhibiting apoptosis was related to the change in caspase-3 activity. Conclusion The downregulation of miR-890 is the potential cause of high CD147 expression in TNBC, which can promote the malignant transformation of TNBC.

The objective of this study was to compare the demographic characteristics, clinicopathological factors and survival outcomes between infiltrating lobular carcinoma (ILC) and infiltrating ductal carcinoma (IDC) using our single-center database. Methods: Seventeen thousand two hundred and three breast cancer patients were treated at Fudan University Shanghai Cancer Center (FUSCC) from January 2000 to December 2017. We identified 365 cases with ILC and 16,838 cases with IDC. The Pearson chi-square test was used to compare tumor characteristics, and the Kaplan-Meier methods were used to perform the survival analysis. Results: ILC had some distinctive characteristics from IDC such as older age (ranged from 61 to 80: ILC 26.8% vs IDC 19.9%, P < 0.001; over 80: ILC 1.6% vs IDC 0.8%, P < 0.001), larger tumor size (ranged from 2 to 5: ILC 45.2% vs IDC 37.1%, P = 0.011), much more hormone receptor expression (ILC 92.9% vs IDC 73.0%, P < 0.001), extremely less HER-2 expression (ILC 7.1% vs IDC 25.9%, P < 0.001). The overall survival and disease-free survival of ILC were worse than IDC (5-year OS, ILC 93.6% vs IDC 94.5%, P < 0.001; 5-year DFS, ILC 88.5% vs IDC 91.6%, P = 0.008). It was worth noting that the ILC patients had a worse overall survival than IDC patients after our propensity score matching study (P = 0.037). The univariate analysis concluded that positive HR (hormone receptor), high expression of Ki-67 and higher pathologic tumor stage were poor prognostic markers of ILC. Multivariate analysis demonstrated that tumor stage was a poor prognostic marker after adjustment for the effects of the above three factors. The most common primary site of metastasis was bone, but the proportion in the ILC group was much higher than that in the IDC group (56.25% vs 36.40%, P = 0.003). Conclusion: Compared with IDC, ILC survived worse and was more prone to bone metastasis. Therefore, a comprehensive understanding of ILC and specific treatments are needed for further research.

Background: In recent years, genetic testing (GT) has developed rapidly in China. However, the cancer genetic service system is still immature in China. Little is known about the opinions around genetic counseling (GC) and GT in Chinese individuals at high risk of breast cancer. This work aims to understand the changes in awareness, attitudes, and willingness of high-risk populations before and after GT, as well as the possible barriers to GC/GT. Methods: Several questionnaires for the high-risk populations of breast cancer were completed. Then, some patients were selected for free single/multi-gene testing as well as further survey and statistical analysis.Results: Despite low levels of awareness, Chinese high-risk breast cancer groups hold positive attitudes about GC/GT. There were differences in the willingness of different groups of high-risk people. After GT, different testing results led to different views and choices for the patients than before GT. Lack of genetic knowledge of breast cancer, misunderstanding, cost, fear of adverse effects, and policy market factors are obstacles to accepting GC/GT for the participants.Conclusions: Chinese doctors need to communicate according to the specific situation of high-risk individuals in pre-test counseling and post-test counseling. The national policy and GT market also need to be improved to support the hereditary breast cancer families' follow-up service system.

Background To summarize the clinicopathological characteristics, prognosis, and management of breast adenosquamous carcinoma (ASC). Methods A population-based study was performed using retrospectively extracted data from the Surveillance, Epidemiology, and End Results database for breast cancer patients with histological diagnoses of ASC, infiltrating duct carcinoma (IDC) and squamous cell carcinoma (SCC) from 2004 to 2016. Results ASC presented similar tumor size but low histological grade and less lymph node metastasis compared to IDC. ASC expressed less positive rate of hormone receptors and barely HER2, which was similar with SCC. ASC patients underwent the similar surgical and systematic treatment as IDC, only with less radiotherapy. Median follow-up data of 78 months showed that the prognosis of IDC patients was better than that of ASC patients (all p < 0.05 for BCSM and OS). ASC was not an independent prognosis factor of breast cancer. After propensity score matching (PSM), no significant difference in BCSM nor OS was observed between ASC and IDC groups. In HR-negative patients, the prognosis of ASC was similar with that of IDC, and both were superior to SCC. In HR-positive patients, the 5-year survival rate of ASC was 63.5%, which was far less than that in ASC of HR-negative (81.0%). Multivariate analysis showed that older age (age > 60) and advanced AJCC-stage were independent factors of poor prognosis in ASC, breast-conserving surgery was also ideally suited for ASC. Conclusions ASC has unique clinicopathological characteristics and prognosis. It is imperative to focus on a more precise and personalized treatment management of ASC patients.

Background: Triple-negative breast cancer has become an intricate part and hotspot in the clinical and experimental research. Connexins, serving as functional proteins in gap junctions, play an important role in tumorigenesis, cell proliferation and metastasis. Methods: We constructed and employed the Connexin 43 (Cx43) overexpression lentiviral vectors and Cx43 siRNA in paclitaxel-treated MDA-MB-231 cells. We performed the experiments of clonal formation and flow cytometry to gauge the effect of paclitaxel on cellular behaviors and immunofluorescence and subsequent quantitative RT-PCR and Western blot to examine the expression of genes and corresponding proteins. Experiments of scrape loading/dye transfer were utilized to explore the gap junctions. The targets of Cx43 were identified via the experiments of co-immunoprecipitation (Co-IP), GST pull-down assays and proximal ligation assay (PLA). Results: The results showed that Cx43 hindered cell proliferation and promoted apoptosis in the paclitaxel-treated MDA-MB-231 cells. Overexpressed Cx43 suppressed the expression of resistance genes such as BRCP, Txr-1, α-tubulin and β-tubulin and promoted the expression of apoptosis gene as TSP-1 and Bcl-2. Cx43 was also positively related to ITGα9 and negatively related to ITGαV and ITGα11. The gap junctions altered magnificently under different expressions of Cx43, which indicated that Cx43 could promote the number of intercellular gap junctions. The immunofluorescent experiment revealed that both of Cx43 and β-tubulin were mainly localized in the cytoplasm. The assays of Co-IP and GST pull-down demonstrated that there existed a direct interaction between Cx43 and β-tubulin. Furthermore, the result of PLA also showed that Cx43 interacts with β-tubulin in MDA-MB-231 cells. Conclusion: Overexpression of Cx43 could modulate the cellular resistance to paclitaxel via targeting β-tubulin in triple-negative breast cancer.

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Objective: The present study is aimed at summarizing the clinicopathological characteristics, prognosis, and management of breast adenosquamous carcinoma (ASC). Introduction: ASC is a rare and unique form of invasive mammary carcinoma with poorly understood clinicopathological characteristics and disease progression, so identification of the features associated with ASC patient survival is warranted. Methods: A population-based study was performed using retrospectively extracted data from the Surveillance, Epidemiology and End Results (SEER) database for breast cancer patients with histological diagnoses of ASC, infiltrating duct carcinoma (IDC) and squamous cell carcinoma (SCC) from 2004 to 2016. End-points were overall survival (OS) and breast cancer-specific mortality (BCSM). Propensity Score Matching (PSM) was employed to minimize selection bias of baseline characteristics. Univariable and multivariable analyses were used for identifying valuable prognostic factors. Results: The average age at onset of ASC was close to that of IDC. ASC presented similar tumor size but low histological grade and less lymph node metastasis compared to IDC. ASC expressed less positive rate of hormone receptors and barely HER2 receptor, which was similar with SCC (estrogen receptor (ER): ASC 27.74% and SCC 21.53%, progesterone receptor (PR): ASC 18.06% and SCC 12.85%, HER2: ASC 4.44% and SCC 7.53%). ASC patients underwent the same treatment as IDC (chemotherapy 36.99% vs. 41.86%, BCS 50.58% vs 52.83%, P &gt;0.05), only with less radiotherapy (39.88% vs. 48.34%, P&lt;0.05). Median follow-up data of 78 months showed that the prognosis of IDC patients was better than that of ASC patients (all P &lt;0.05 for BCSM and OS). After adjustment for clinicopathological and therapeutic factors in Cox proportional hazards models, ASC was no longer an independent poor prognosis factor. In matched groups, no significant difference in BCSM nor OS was observed between ASC and IDC groups. In HR-negative patients, the prognosis of ASC was similar with that of IDC, and both were superior to SCC. In HR-positive patients, the five-year survival rate of ASC was only about 60%, which was far less than that in ASC of HR-negative, the poor prognosis of ASC was closer to that of SCC. Multivariate analysis showed that older age (age≥60) and advanced AJCC stage (III and IV) were independent factors of poor prognosis in ASC, breast-conserving surgery was also ideally suited for ASC. Conclusion: ASC have unique clinicopathological characteristics and prognosis. To improve the clinical and biological understanding of ASC can make breast cancer patients get more individualized treatment. Keywords: adenosquamous carcinoma, infiltrating duct carcinoma, squamous cell carcinoma, prognosis, SEER database Citation Format: Zhangyuan Gu, Cheng Xu, Zhigang Zhuang. Adenosquamous carcinoma of the breast: A population-based study using the SEER database [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-60.

Background: The present study is aimed at summarizing the clinicopathological characteristics, prognosis, and management of breast adenosquamous carcinoma (ASC). Methods: A population-based study was performed using retrospectively extracted data from the Surveillance, Epidemiology and End Results database for breast cancer patients with histological diagnoses of ASC, infiltrating duct carcinoma (IDC) and squamous cell carcinoma (SCC) from 2004 to 2016. End-points were overall survival (OS) and breast cancer-specific mortality (BCSM). Propensity Score Matching (PSM) was employed to minimize selection bias of baseline characteristics. Univariable and multivariable analyses were used for identifying valuable prognostic factors. Results: ASC presented similar tumor size but low histological grade and less lymph node metastasis compared to IDC. ASC expressed less positive rate of hormone receptors and barely HER2, which was similar with SCC (estrogen receptor (ER): ASC 27.74% and SCC 21.53%, progesterone receptor (PR): ASC 18.06% and SCC 12.85%, HER2: ASC 4.44% and SCC 7.53%). ASC patients underwent the same treatment as IDC (chemotherapy 36.99% vs. 41.86%, BCS 50.58% vs 52.83%, P >0.05), only with less radiotherapy (39.88% vs. 48.34%, P<0.05). Median follow-up data of 78 months showed that the prognosis of IDC patients was better than that of ASC patients (all P <0.05 for BCSM and OS). After adjustment for clinicopathological and therapeutic factors in Cox proportional hazards models, ASC was no longer an independent poor prognosis factor. In matched groups, no significant difference in BCSM nor OS was observed between ASC and IDC groups. In HR-negative patients, the prognosis of ASC was similar with that of IDC, and both were superior to SCC. In HR-positive patients, the five-year survival rate of ASC was only about 60%, which was far less than that in ASC of HR-negative, the poor prognosis of ASC was closer to that of SCC. Multivariate analysis showed that older age (age≥60) and advanced AJCC stage (III and IV) were independent factors of poor prognosis in ASC, breast-conserving surgery was also ideally suited for ASC. Conclusions: ASC has unique clinicopathological characteristics and prognosis. To improve the clinical and biological understanding of ASC can make breast cancer patients get more individualized treatment.