Treatment of breast cancer with low expression of human epidermal growth factor receptor 2 (HER2; HER2-low) has drawn much attention in recent years. With the proven therapeutic effect of trastuzumab ...deruxtecan (T-DXd) in patients with HER2-low (immunohistochemistry IHC 1+, or IHC2+/in situ hybridization ISH-) breast cancer, HER2-low may become a new subtype of targeted therapy for breast cancer. The expert committee formulated this consensus based on the current clinical studies and clinical medication experience. The current consensus is the collaborative work of an interdisciplinary working group, including experts in the fields of pathology and oncology. The purpose of this consensus was to guide the clinical diagnosis and treatment of HER2-low breast cancer, thereby prolonging the overall survival of patients.
Breast cancer is one of the most common cancers. Although the present molecular classification improves the treatment effect and prognosis of breast cancer, the heterogeneity of the molecular subtype ...remains very complex, and the applicability and effectiveness of treatment methods are still limited leading to poorer patient prognosis than expected. Further identification of more refined molecular typing based on gene expression profile will yield better understanding of the heterogeneity, improving treatment effects and prolonging prognosis of patients. Here, we downloaded the mRNA expression profiles and corresponding clinical data of patients with breast cancer from public databases and performed typical molecular typing using PAM50 (Prediction Analysis of Microarray 50) method. Comparative analyses were performed to screen the common and specific differentially expressed genes (DEGs) between cancer and corresponding para-cancerous tissues in each breast cancer subtype. The GO and KEGG analyses of the DEGs were performed to enrich the common and specific functional progress and signaling pathway involved in breast cancer subtypes. A total of 38 key common and specific DEGs were identified and selected based on the validated results, GO/KEGG enrichments, and the priority of expression, including four common DEGs and 34 specific DEGs in different subtypes. The prognostic value of these key common and specific DEGs was further analyzed to obtain useful potential markers in clinic. Finally, the potential roles and the specific prognostic values of the common and specific DEGs were speculated and summarized in total breast cancer and different subtype breast cancer based on the results of these analyses. The findings of our study provide the basis of more refined molecular typing of breast cancer, potential new therapeutic targets and prognostic markers for different breast cancer subtypes.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most leading causes of cancer-related death. Cancer stem cell is responsible for tumor initiation, metastasis and relapse. Sox9 is a pancreatic ...stem cell marker. PI3K/PTEN/Akt/mTORC is an important signal for maintaining stem cells. The purpose of this study is to determine the expression pattern of Sox9 and p-Akt in human PDAC and its correlation with prognosis. Immunohistochemical analysis was used to explore the expression of Sox9 and p-Akt in 88 human PDAC patients. The Pearson’s test was used to compare the clinicopathological parameters between negative and positive expressors. The Pearson’s correlation analysis was used to explore the relationship between Sox9 and p-Akt expression. Kaplan–Meier’s method and Cox regression analysis were used to analyze patients’ survival. The results showed that Sox9 and p-Akt overactivated in PDAC (
p
= 0.011,
p
= 0.008). Sox9-positive expression is significantly associated with distant metastasis (
p
= 0.046). p-Akt-positive expression is significantly associated with distant metastasis (
p
= 0.000), TNM stage (0.001) and PCNA expression (
p
= 0.000). Sox9 expression is positively correlated with p-Akt expression (
r
= 0.314,
p
= 0.003). In 54 patients with survival information, both Sox9- and p-Akt-positive expressions are associated with unfavorable prognosis (
p
= 0.002,
p
= 0.000). Sox9 and p-Akt double-positive expressor showed much poorer prognosis (
p
= 0.000). Cox regression analysis showed that Sox9- or p-Akt-positive expression and LN metastasis were independent prognostic factors. This study provides the first evidence that Sox9 and p-Akt are both relevant to distant metastasis and proliferation. Our data suggest the potential of Sox9 and p-Akt as prognostic biomarkers for PDAC.
The association of CYP19 gene polymorphisms with breast cancer has been widely reported, but results of previous studies were somewhat contradictory and underpowered. In order to overcome the ...limitations of individual study and to understand the real situation, we conducted a systematic review and meta-analysis including three CYP19 gene polymorphisms R264C polymorphism, CYP19_630 3-bp del/Ins polymorphism, and CYP19_681 (TTTA)n polymorphisms. A total of 22 studies with 10,592 cases and 11,720 controls were identified, and the results showed that R264C polymorphism was not associated with breast cancer risk in overall (T vs. C: OR = 1.061, 95% CI = 0.929-1.212) or race-based populations (T vs. C for Asian: OR = 1.169, 95% CI = 1.002-1.363; for Caucasian: OR = 0.787, 95% CI = 0.597-1.037); meanwhile, for Asian individuals, 3-bpDel/Ins polymorphism showed a significantly association with breast cancer susceptibility (for allele Del vs. allele Ins: OR = 1.278, 95% CI = 1.066-1.532) while the carriers of allele (TTTA)₁₂ can significantly decrease breast cancer risk (OR = 0.752, 95% CI = 0.603-0.939). Furthermore, the carriers of allele (TTTA)₁₀ were significantly associated with breast cancer susceptibility (OR = 1.515, 95% CI = 1.115-2.058). It can be concluded that potentially functional CYP19_630 3-bp del/Ins polymorphism and CYP19_681 (TTTA)n polymorphisms may play a low penetrance role in breast cancer susceptibility in an ethnicity-specific manner.
The objective of the study is to investigate the CXCR5 and MMP-13 expression in colorectal cancer and explore its correlation between the clinicopathological characteristics and prognosis. The ...expressions of CXCR5 and MMP-13 proteins in 236 paired specimens of colorectal cancer and incisal edge normal tissues as well as 62 samples of colorectal adenoma tissues were analyzed by immunohistochemistry. The CXCR5 and MMP-13 positive expression rate in colorectal cancer tissues was 43.6 and 80.5 %, respectively. Both rates were higher than those in the incisal edge healthy intestinal mucosal tissues (4.2 and 13.1 %) and colorectal adenoma tissues (24.2 and 64.5 %),
P
< 0. 05 in both cases. The expressions of the CXCR5 and MMP-13 proteins were positively related to the lymph node and distal metastasis, tumor stage and relapse,
P
< 0. 05. The expression of the CXCR5 protein was positively related to MMP-13,
P
< 0. 05. The median and overall survival in the patients with positive CXCR5 and MMP-13 expression were significantly shorter than those with negative expression: median survival, 20.5 months (CXCR5 +) versus 30.8 months (CXCR5 −), 20.3 months (MMP-13 +) versus 24.6 months; overall survival, 26.5 months (CXCR5 +) versus 47.5 months (CXCR5 −), 22.7 months (MMP-13 +) versus 29.3 months. The expression of CXCR5 and MMP-13 could promote the pathogenesis, development, metastasis, and relapse of colorectal cancer. It could also serve as a valuable indicator for the prediction of metastasis and relapse of colorectal cancer.
Background
Breast cancer (BRCA) is the most common malignant tumor among women worldwide. Despite advances in treatment, many patients still die from a lack of effective diagnostic and prognostic ...markers and powerful therapeutic targets. LIM homeobox genes (LHXs) play vital roles in regulating the development of various organisms. However, there are limited reports regarding their roles in the diagnosis, prognosis, and treatment of BRCA.
Methods
UALCAN, Kaplan–Meier plotter, cBioPortal, GeneMANIA, STRING, DAVID 6.8, TRRUST v2, LinkedOmics, and TIMER were utilized to analyze differential expression, prognostic value, genetic alteration, neighbor gene network, transcription factor targets, kinase targets, and immune cell infiltration of LHXs in BRCA patients.
Results
LHX gene expression patterns are clear in BRCA and its different subtypes. Further analyses indicated that this altered expression is possibly affected by genetic and/or epigenetic changes. The prognostic and diagnostic values of certain LHXs are unique to different BRCA subtypes. LHXs are mainly involved in the regulation of differentiation and development, and their neighbor genes are primarily involved in cancer‐related pathways. Moreover, most LHXs are closely correlated with immune cell infiltration. Furthermore, LHXs may exert their functions by regulating a series of transcription factor and kinase targets.
Conclusions
LHXs are unique diagnostic and prognostic markers and participate in cancer through different signaling pathways and/or regulatory mechanisms in BRCA. This study provides potential applications of LHXs for the diagnosis, prognosis, and treatment of BRCA and its different subtypes.
LHXs are potential and unique diagnostic and prognostic markers in BRCA, and possibly participate in the development and progression of BRCA in different manners through various signaling pathways and/or regulatory mechanisms.
The association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and breast cancer risk has been widely reported, but results were inconsistent and underpowered. To clarify the ...effects of MTHFR polymorphisms on the risk of breast cancer, an updated meta-analysis of all available studies relating C677T and/or A1298C polymorphisms of MTHFR gene to the risk of breast cancer was conducted. Eligible articles were identified by search of databases including MEDLINE, PubMed, Web of Science, EMBASE and Chinese Biomedical Literature database (CBM) for the period up to January 2010. Finally, a total of 41 studies with 16,480 cases and 22,388 controls were included, all for C677T polymorphism and 20 with 12,170 cases and 15,865 controls for A1298C polymorphism. The pooled ORs were performed for the allele contrasts, additive genetic model, dominant genetic model, and recessive genetic model, respectively. Subgroup analyses were also performed by ethnicity and menopausal status. With respect to C677T polymorphism, significantly elevated breast cancer risk was found in overall analysis (T vs. C: OR = 1.041, 95% CI = 1.009-1.073; TT vs. CC: OR = 1.132, 95% CI = 1.019-1.259; TT vs. CC + CT: OR = 1.119, 95% CI = 1.014-1.236); in the subgroup analysis by ethnicity, significantly increased risk was found in East Asian population (T vs. C: OR = 1.121, 95% CI = 1.016-1.237; TT vs. CC: OR = 1.331, 95% CI = 1.073-1.650; TT vs. CC + CT: OR = 1.265, 95% CI = 1.058-1.513) but not in Caucasian population; in the subgroup analysis by menopausal status, no statistically significant association was found. With respect to A1298C polymorphism, no significant association with breast cancer risk was demonstrated in overall, ethnicity- and menopausal status-based population. It can be concluded that potentially functional MTHFR C677T polymorphism may play a low penetrance role in the development of breast cancer.
The objective of this multicenter, single‐arm trial (ChiCTR1900022293) was to explore the efficacy and safety of neoadjuvant therapy with epirubicin, cyclophosphamide, and pyrotinib followed by ...docetaxel, trastuzumab, and pyrotinib (ECPy‐THPy) in the treatment of patients with stage II–III HER2‐positive breast cancer. The present study enrolled patients with stage II–III HER2‐positive breast cancer. Epirubicin and cyclophosphamide were administrated for four 21‐day cycles, followed by four cycles of docetaxel and trastuzumab. Pyrotinib was taken orally once per day throughout the treatment period. The primary endpoint was total pathological complete response (tpCR, ypT0/is ypN0) rate in the modified intention‐to‐treat (mITT) population. In total, 175 patients were included. The tpCR rate was 68.6% (95% CI, 60.7–75.8%), while the objective response rate was 89.1%. In the post‐hoc subgroup analysis, no association between clinical characteristics and the tpCR rate was observed. The most common grade ≥3 adverse events were diarrhea (54.3%), followed by white blood cell count decreased (5.1%), and neutrophil count decreased (4.6%). In conclusion, the neoadjuvant regimen with ECPy‐THPy showed promising pathological response and clinical benefits with an acceptable safety profile in patients with stage II–III HER2‐positive breast cancer.
In this multicenter, single‐arm trial, we investigated the efficacy and safety of the ECPy‐THPy regimen (epirubicin, cyclophosphamide, and pyrotinib followed by docetaxel, trastuzumab, and pyrotinib) as neoadjuvant therapy for patients with stage II–III HER2‐positive breast cancer. Our results revealed that tpCR was achieved in 107 (68.6%) out of 156 patients, which was in line with our previous pilot study and numerically higher than the tpCR rate in previous phase III KRISTINE trial and the phase III POENY trial.
Emerging research has indicated that circular RNAs (circRNAs), a novel class of non‐coding RNAs, play a vital role in human tumorigenesis and progression. Our previous results suggested that ...hsa_circ_0006528 (circ_0006528), a circRNA with an unknown function, mediates adriamycin resistance in human breast cancer cells. However, the role of circ_0006528 in breast cancer progression remains unknown. Here, we investigated the probable involvement of circ_0006528 in breast cancer. We analyzed a cohort of 97 patients and found that circ_0006528 expression was significantly upregulated in human breast cancer tissues compared with that in adjacent non‐tumorous tissues and was significantly associated with advanced tumor‐node‐metastasis (TNM) stage and poor prognosis. In addition, we found that in breast cancer cells, circ_0006528 could promote DNA synthesis and cell proliferation, invasion, and migration. Downregulating circ_0006528 induced G2 phase arrest and cell apoptosis. Further mechanistic studies revealed that circ_0006528 could sponge endogenous miR‐7‐5p and inhibit its activity. We also identified Raf1, which activates the MAPK/ERK signaling pathway, as a target of miR‐7‐5p and determined that circ_0006528 promotes breast cancer growth, invasion, and migration by promoting the expression of Raf1 and activates the MAPK/ERK pathway. Thus, this study provides the first evidence of the circ_0006528/miR‐7‐5p/Raf1/MEK/ERK regulatory network in the development of breast cancer and suggests that circ_0006528 is a potential therapeutic target and prognostic predictor for breast cancer.
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