Abstract P1-04-10: Using the allele specific copy number profile to predict the poor prognosis breast cancer patients of Taiwanese

Abstract Background: Breast cancer is one of the most common cancers among females with high morbidity and mortality. MicroRNAs (miRNAs) have been reported to play important roles in the development of cancers. However, the prognostic value of microRNA-421 (miR-421) in breast cancer have not been extensively explored.Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the relative expression of miR-421 in breast cancer tissue samples. Relationships between miR-421 expression and clinicopathological factors were analyzed by chi-square test. The effects of several variables on survival status were tested by Kaplan-Meier curve and Cox proportional hazards regression analyses.Results: MiR-421 expression was significantly decreased in breast cancer tissues, compared with adjacent noncancerous tissues (P<0.001). Moreover, abnormal miR-421 expression was closely correlated with lymph node metastasis (P<0.001), TNM stage (P=0.021), and differentiation (P=0.044) of breast cancer patients. Kaplan-Meier analysis revealed that patients with low miR-421 expression had a shorter overall survival time than those with high miR-421 expression (P=0.001). Furthermore, multivariate analysis demonstrated that miR-421 (P=0.014, HR=2.000, 95%CI: 1.149-3.480) was an independent prognostic indicator in breast cancer patients, as well as lymph node metastasis (P=0.016, HR=1.987, 95%CI: 1.137-3.474).Conclusion: The reduced expression of miR-421 may predict the poor prognosis of breast cancer and miR-421 may be involved in the progression of breast cancer.

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Lymphocyte-to-Monocyte Ratio is Associated with the Poor Prognosis of Breast Cancer Patients Receiving Neoadjuvant Chemotherapy

Cancer Management and Research ◽

10.2147/cmar.s292048 ◽

2021 ◽

Vol Volume 13 ◽

pp. 1571-1580

Author(s):

Youzhao Ma ◽

Jingyang Zhang ◽

Xiuchun Chen

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Cancer Patients ◽

Poor Prognosis ◽

Breast Cancer Patients ◽

Lymphocyte To Monocyte Ratio ◽

The Poor

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Effect of Wnt5a on drug resistance in estrogen receptor-positive breast cancer

Breast Cancer ◽

10.1007/s12282-021-01241-0 ◽

2021 ◽

Author(s):

Ai Amioka ◽

Takayuki Kadoya ◽

Satoshi Sueoka ◽

Yoshie Kobayashi ◽

Shinsuke Sasada ◽

...

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Cancer Patients ◽

Poor Prognosis ◽

Breast Cancer Patients ◽

Mtor Signaling Pathway ◽

The Poor ◽

Er Positive ◽

Mcf 7 ◽

Positive Breast Cancer

Abstract Background Previously, we reported that Wnt5a-positive breast cancer can be classified as estrogen receptor (ER)-positive breast cancer; its prognosis is worse than that of Wnt5a-negative breast cancer. This study aimed to investigate the mechanisms underlying the poor prognosis in Wnt5a-positive breast cancer patients. Methods In total, 151 consecutive ER-positive breast cancer patients who underwent resection between January 2011 and February 2014 were enrolled. DNA microarray and pathway analyses were conducted using MCF-7 cells stably expressing Wnt5a [MCF-7/Wnt5a (+)]. Based on the outcomes, cell viability/drug sensitivity assays, and mutation analysis were performed using cell cultures and breast cancer tissues. The relationship between Wnt5a and the PI3K–AKT–mTOR signaling pathway was also examined. Results The relapse-free survival rate in patients with Wnt5a-positive breast cancer was significantly lower than that in patients with Wnt5a-negative breast cancer (P = 0.047). DNA microarray data suggest that only the cytochrome P450 (CYP) pathway was significantly upregulated in MCF-7/Wnt5a (+) cells (P = 0.0440). Additionally, MCF-7/Wnt5a (+) cells displayed reduced sensitivity to the metabolic substrates of CYP, tamoxifen (P < 0.001), paclitaxel (P < 0.001), and cyclophosphamide (P < 0.001). Of note, PIK3CA mutations were not associated with the expression of Wnt5a in breast cancer tissue and culture cells. Conclusions In ER-positive breast cancer, Wnt5a upregulates the CYP metabolic pathway and suppresses tamoxifen, paclitaxel, and cyclophosphamide resistance, all of the three, standard treatment methods for ER-positive breast cancer. Wnt5a is thus potentially involved in the poor prognosis of ER-positive breast cancer independently of the PI3K–AKT–mTOR signaling pathway.

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Targeting PKM2 promotes chemosensitivity of breast cancer cells in vitro and in vivo

Cancer Biomarkers ◽

10.3233/cbm-210111 ◽

2021 ◽

pp. 1-10

Author(s):

Yu Wang ◽

Han Zhao ◽

Ping Zhao ◽

Xingang Wang

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Cancer Cells ◽

Cancer Patients ◽

Poor Prognosis ◽

Breast Cancer Cells ◽

Breast Cancer Patients ◽

Cancer Tissues

BACKGROUND: Pyruvate kinase M2 (PKM2) was overexpressed in many cancers, and high PKM2 expression was related with poor prognosis and chemoresistance. OBJECTIVE: We investigated the expression of PKM2 in breast cancer and analyzed the relation of PKM2 expression with chemotherapy resistance to the neoadjuvant chemotherapy (NAC). We also investigated whether PKM2 could reverse chemoresistance in breast cancer cells in vitro and in vivo. METHODS: Immunohistochemistry (IHC) was performed in 130 surgical resected breast cancer tissues. 78 core needle biopsies were collected from breast cancer patients before neoadjuvant chemotherapy. The relation of PKM2 expression and multi-drug resistance to NAC was compared. The effect of PKM2 silencing or overexpression on Doxorubicin (DOX) sensitivity in the MCF-7 cells in vitro and in vivo was compared. RESULTS: PKM2 was intensively expressed in breast cancer tissues compared to adjacent normal tissues. In addition, high expression of PKM2 was associated with poor prognosis in breast cancer patients. The NAC patients with high PKM2 expression had short survival. PKM2 was an independent prognostic predictor for surgical resected breast cancer and NAC patients. High PKM2 expression was correlated with neoadjuvant treatment resistance. High PKM2 expression significantly distinguished chemoresistant patients from chemosensitive patients. In vitro and in vivo knockdown of PKM2 expression decreases the resistance to DOX in breast cancer cells in vitro and tumors in vivo. CONCLUSION: PKM2 expression was associated with chemoresistance of breast cancers, and could be used to predict the chemosensitivity. Furthermore, targeting PKM2 could reverse chemoresistance, which provides an effective treatment methods for patients with breast cancer.

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Single Cell Genetic Profiling of Tumors of Breast Cancer Patients Aged 50 Years and Older Reveals Enormous Intratumor Heterogeneity Independent of Individual Prognosis

Cancers ◽

10.3390/cancers13133366 ◽

2021 ◽

Vol 13 (13) ◽

pp. 3366

Author(s):

Anna-Sophie Liegmann ◽

Kerstin Heselmeyer-Haddad ◽

Annette Lischka ◽

Daniela Hirsch ◽

Wei-Dong Chen ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Copy Number ◽

Genome Instability ◽

Single Cells ◽

Gene Mutations ◽

Intratumor Heterogeneity ◽

Breast Cancer Patients ◽

Luminal A ◽

Pik3ca Mutations

Purpose: Older breast cancer patients are underrepresented in cancer research even though the majority (81.4%) of women dying of breast cancer are 55 years and older. Here we study a common phenomenon observed in breast cancer which is a large inter- and intratumor heterogeneity; this poses a tremendous clinical challenge, for example with respect to treatment stratification. To further elucidate genomic instability and tumor heterogeneity in older patients, we analyzed the genetic aberration profiles of 39 breast cancer patients aged 50 years and older (median 67 years) with either short (median 2.4 years) or long survival (median 19 years). The analysis was based on copy number enumeration of eight breast cancer-associated genes using multiplex interphase fluorescence in situ hybridization (miFISH) of single cells, and by targeted next-generation sequencing of 563 cancer-related genes. Results: We detected enormous inter- and intratumor heterogeneity, yet maintenance of common cancer gene mutations and breast cancer specific chromosomal gains and losses. The gain of COX2 was most common (72%), followed by MYC (69%); losses were most prevalent for CDH1 (74%) and TP53 (69%). The degree of intratumor heterogeneity did not correlate with disease outcome. Comparing the miFISH results of diploid with aneuploid tumor samples significant differences were found: aneuploid tumors showed significantly higher average signal numbers, copy number alterations (CNAs) and instability indices. Mutations in PIKC3A were mostly restricted to luminal A tumors. Furthermore, a significant co-occurrence of CNAs of DBC2/MYC, HER2/DBC2 and HER2/TP53 and mutual exclusivity of CNAs of HER2 and PIK3CA mutations and CNAs of CCND1 and PIK3CA mutations were revealed. Conclusion: Our results provide a comprehensive picture of genome instability profiles with a large variety of inter- and intratumor heterogeneity in breast cancer patients aged 50 years and older. In most cases, the distribution of chromosomal aneuploidies was consistent with previous results; however, striking exceptions, such as tumors driven by exclusive loss of chromosomes, were identified.

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