Abstract P1-08-05: The prognostic significance of Ki-67 expression before and after neoadjuvant anthracycline-taxane-based chemotherapy in different biological breast cancer phenotypes

Abstract Objectives Breast cancer is a common malignant tumor in women with limited treatment options and multiple side effects. Today, the anti-cancer properties of natural compounds have attracted widespread attention from researchers worldwide. Methods In this study, we treated 4T1 tumor-bearing Balb/c mice with intraperitoneal injection of Auraptene, paraffin oil, and saline as two control groups. Body weight and tumor volume were measured before and after treatment. Hematoxylin and eosin (H & E) staining and immunohistochemistry of Ki-67 were used as markers of proliferation. In addition, ELISA assays were performed to assess serum IFN-γ and IL-4 levels. Results There was no significant change in body weight in all animal groups before and after treatment. 10 days after the last treatment, Auraptene showed its anti-cancer effect, which was confirmed by the smaller tumor volume and H & E staining. In addition, Ki-67 expression levels were significantly reduced in tumor samples from the Auraptene-treated group compared to the paraffin oil and saline-treated groups. In addition, in tumor-bearing and normal mice receiving Auraptene treatment, IL-4 serum production levels were reduced, while serum levels of IFN-γ were significantly up-regulated in tumor-bearing mice after Auraptene treatment. Conclusions In the case of inhibition of tumor volume and Ki-67 proliferation markers, Auraptene can effectively inhibit tumor growth in breast cancer animal models. In addition, it might increases Th1 and CD8 + T cell responses after reducing IL-4 serum levels and IFN-γ upregulation, respectively. However, further research is needed to clarify its mechanism of action.

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Prognostic significance of Ki-67 labeling index after short-term presurgical tamoxifen in women with ER-positive breast cancer

Annals of Oncology ◽

10.1093/annonc/mdq427 ◽

2011 ◽

Vol 22 (3) ◽

pp. 582-587 ◽

Cited By ~ 59

Author(s):

A. DeCensi ◽

A. Guerrieri-Gonzaga ◽

S. Gandini ◽

D. Serrano ◽

M. Cazzaniga ◽

...

Keyword(s):

Breast Cancer ◽

Prognostic Significance ◽

Labeling Index ◽

Short Term ◽

Ki 67 ◽

Er Positive ◽

Positive Breast Cancer

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Phase II breast cancer chemoprevention study with celecoxib in women at increased risk for breast cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.1010 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 1010-1010

Author(s):

B. Arun ◽

V. Valero ◽

G. Yin ◽

G. Babiera ◽

J. L. Murray ◽

...

Keyword(s):

Breast Cancer ◽

High Risk ◽

Atypical Hyperplasia ◽

Post Treatment ◽

Short Term ◽

Ki 67 ◽

High Risk Women ◽

Before And After ◽

The Difference ◽

Er Expression

1010 Background: Short-term chemoprevention trials offer a convenient model to screen chemopreventive agents and identify endpoint biomarkers. One of the potential agents is celecoxib (C), which has antiproliferative and apoptosis inducing properties. In this prospective study, our primary aim was to evaluate changes in proliferation induced by C in breast tissue of high risk women. Here, we report changes in estrogen receptor (ER) proliferation index. Methods: 42 eligible high risk women were enrolled into the study, underwent fine needle aspiration (FNA) and started celecoxib treatment at 400 mg BID. Median age: 51.9 years. Risk factors: Gail risk > 1.67% (n=13), lobular carcinoma insitu (n=13), atypical hyperplasia (n=11), previous history of breast cancer (n=5). For ER and Ki-67 testing, thin preparations slides were incubated with primary mouse monoclonal antibody 6F11 against the ER and clone MIB-1, respectively. Appropriate negative and positive controls were included. At least 100 epithelial cells were evaluated per slide. Immunoreactivity for each marker was scored as the percentage of positive nuclei. We assessed the difference in ER and Ki-67 levels before and after treatment using a Wilcoxon signed rank test. Results: The average pre-treatment ER expression in FNA samples was 35.9% and Ki-67 was 2.4%. 19 (45%) showed hyperplasia or atypical hyperplasia. 39 patients underwent also post-treatment FNAs. The pre-and post treatment ER expression in this group was 35.7% (range 0–100%) and 27.4% (range: 0–100%), respectively. The difference in ER levels was statistically significant (p = 0.04). Twenty-six patients had Ki-67 levels measured both before and after treatment. The median difference in Ki-67 levels was 0 (range 0- 5). This change was not statistically significant (p = 0.63). Conclusions: We have completed accrual to a prospective short-term chemoprevention trial with celecoxib. We have found a significant downregulation of ER expression with 6 months celecoxib. Since ER expression is a marker of proliferation, this finding confirms celecoxibs antiproliferative properties. Currently, we have not observed a change in Ki-67; this could be partly due to the small number of samples and the fact that Ki-67 is low in normal epithelium. [Table: see text]

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P177 The prognostic significance of Ki-67 expression in patients with early invasive breast cancer

The Breast ◽

10.1016/s0960-9776(11)70119-9 ◽

2011 ◽

Vol 20 ◽

pp. S37

Author(s):

T. Utsumi ◽

N. Kobayashi ◽

M. Hikichi ◽

S. Miyajima ◽

K. Ushimado ◽

...

Keyword(s):

Breast Cancer ◽

Invasive Breast Cancer ◽

Prognostic Significance ◽

Ki 67

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Prospective Monitoring of Circulating Epithelial Tumor Cells (CETC) Reveals Changes in Gene Expression during Adjuvant Radiotherapy of Breast Cancer Patients

Current Oncology ◽

10.3390/curroncol28050302 ◽

2021 ◽

Vol 28 (5) ◽

pp. 3507-3524

Author(s):

Matthias Mäurer ◽

Katharina Pachmann ◽

Thomas Wendt ◽

Dorothea Schott ◽

Andrea Wittig

Keyword(s):

Breast Cancer ◽

Single Cell ◽

Tumor Cells ◽

Early Stage ◽

Breast Cancer Patients ◽

Ki 67 ◽

Epithelial Tumor ◽

Before And After ◽

Epithelial Tumor Cells ◽

Cell Expression

Circulating epithelial tumor cells (CETC) are considered to be responsible for the formation of metastases. Therefore, their importance as prognostic and/or predictive markers in breast cancer is being intensively investigated. Here, the reliability of single cell expression analyses in isolated and collected CETC from whole blood samples of patients with early-stage breast cancer before and after radiotherapy (RT) using the maintrac® method was investigated. Single-cell expression analyses were performed with qRT-PCR on a panel of selected genes: GAPDH, EpCAM, NANOG, Bcl-2, TLR 4, COX-2, PIK3CA, Her-2/neu, Vimentin, c-Met, Ki-67. In all patients, viable CETC were detected prior to and at the end of radiotherapy. In 7 of the 9 (77.8%) subjects examined, the CETC number at the end of the radiotherapy series was higher than before. The majority of genes analyzed showed increased expression after completion of radiotherapy compared to baseline. Procedures and methods used in this pilot study proved to be feasible. The method is suitable for further investigation of the underlying molecular biological mechanisms occurring in cells surviving radiotherapy and possibly the development of radiation resistance.

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Immunohistochemical Expressions of Senescence-Associated Secretory Phenotype and Its Association With Immune Microenvironments and Clinicopathological Factors in Invasive Breast Cancer

Pathology & Oncology Research ◽

10.3389/pore.2021.1609795 ◽

2021 ◽

Vol 27 ◽

Author(s):

Min Hui Park ◽

Jung Eun Choi ◽

Jae-Ryong Kim ◽

Young Kyung Bae

Keyword(s):

Breast Cancer ◽

Invasive Breast Cancer ◽

Molecular Subtype ◽

Prognostic Significance ◽

Disease Free Survival ◽

Luminal A ◽

Cancer Specific Survival ◽

Ki 67 ◽

Entire Cohort ◽

Secretory Phenotype

This study was undertaken to investigate immunohistochemical expression of the senescence-associated secretory phenotype (SASP) in invasive breast cancer (IBC) tissues and to determine relationships between SASP positivity and tumor microenvironments and the clinicopathological characteristics of IBC. Immunohistochemistry for senescence markers, that is, high mobility group box-1 (HMGB1), p16, p15, and decoy receptor 2 (DCR2), was performed in tissue microarrays of 1140 IBC samples. Cases positive for at least one of these four markers were considered SASP-positive. Relations between SASP and tumor characteristics, including immune microenvironments (stromal tumor-infiltrating lymphocytes [sTILs] density and numbers of intraepithelial CD103-positive [iCD103 + ] lymphocytes) and clinical outcomes were retrospectively evaluated. HMGB1, p16, p15, or DCR2 was positive in 6.7%, 26.6%, 21.1%, and 26.5%, respectively, of the 1,140 cases. Six hundred and five (53.1%) cases were SASP positive, and SASP positivity was significantly associated with histologic grade 3, high-sTIL and iCD103 + lymphocyte counts, absence of ER or PR, and a high Ki-67 index. Although SASP did not predict breast cancer-specific survival (BCSS) or disease-free survival (DFS) in the entire cohort, SASP positivity in luminal A IBC was associated with poor BCSS and DFS. However, patients with SASP-positive TNBC showed better survival than those with SASP-negative TNBC. In multivariate analysis, SASP positivity was an independent prognostic factor in both luminal A IBC and TNBC, although the effect on prognosis was the opposite. In conclusion, SASP would be involved in the modulation of immune microenvironments and tumor progression in IBC, and its prognostic significance depends on molecular subtype.

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