HOXB9, a gene promoting tumor angiogenesis and proliferation, as a prognostic factor in breast cancer.

33 Background: We demonstrated that HOXB9, a member of homeobox genes, expression promoted tumor neovascularization and metastasis in vitro and in vivo assay. These findings imply that overexpression of HOXB9 contributes to tumor progression through activation of signaling pathways that alter both tumor-specific cell fates and tumor-stromal microenvironment, leading to increased invasion and metastasis. (Hayashida et al., PNAS 2010) We sought to determine whether these results could be extended to the clinical application. In this study, we evaluated the correlation between HOXB9 expression, clinical outcomes, and the clinicopathological variables in breast cancer patients, and the contribution of HOXB9 expression to tumor cell proliferation and angiogenesis. Methods: A consecutive series of 141 patients with invasive ductal carcinoma who underwent surgical treatment were examined. HOXB9 protein expression was analyzed immunohistochemically using the anti-human HOXB9 polyclonal antibody. Immunostaining of Ki-67, CD31, and CD34 were performed to evaluate the association of proliferation and tumor angiogenesis with HOXB9 expression. Results: Of 141 tumor specimens immunostained for HOXB9, 69 specimens (48.9%) were positive staining. Univariate logistic regression revealed ER and PgR negativity, HER2 positivity, high nuclear grade, and large pathological tumor size as significant variables associated with HOXB9 expression. Moreover, 12 (92.3%) out of 13 triple negative breast cancer showed HOXB9 expression. The disease-free survival (DFS) and the overall survival were significantly different between the HOXB9 positive and negative group; HR=20.714, p=0.001, HR 9.206, p=0.003, respectively. A Multivariate analysis indicated that HOXB9 expression was the only independent prognostic factor for DFS (HR=15.532, p=0.009). In subgroup analysis, HOXB9 positive tumors showed a significant increase in the number of vasculature and the Ki-67 ratio in comparison with HOXB9 negative. Conclusions: Our results suggest that HOXB9 expression promoting the tumor proliferation and the angiogenesis is a significant prognostic factor in breast cancer.

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Comparison of the Distribution Pattern of 21-Gene Recurrence Score between Mucinous Breast Cancer and Infiltrating Ductal Carcinoma in Chinese Population: A Retrospective Single-Center Study

Cancer Research and Treatment ◽

10.4143/crt.2019.387 ◽

2020 ◽

Vol 52 (3) ◽

pp. 671-679

Author(s):

Jiayi Wu ◽

Shuning Ding ◽

Lin Lin ◽

Xiaochun Fei ◽

Caijin Lin ◽

...

Keyword(s):

Breast Cancer ◽

Distribution Pattern ◽

Ductal Carcinoma ◽

Molecular Subtype ◽

Disease Free Survival ◽

Recurrence Score ◽

Chinese Patients ◽

Ki 67 ◽

Infiltrating Ductal Carcinoma ◽

Mucinous Breast Cancer

PurposeThis retrospective study aimed to evaluate the distribution pattern and prognostic value of 21-gene recurrence score (RS) in Chinese patients with mucinous breast cancer (MC) and compared with infiltrating ductal carcinoma (IDC).Materials and MethodsPatients diagnosed with MC or IDC from January 2010 to January 2017 were retrospectively recruited. Reverse transcriptase–polymerase chain reaction assay of 21 genes was conducted to calculate the RS. Univariate and multivariate analyses were performed to assess the association between RS and clinicopathological factors. Survival outcomes including disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier method and compared by log-rank test.ResultsThe MC cohort included 128 patients and the IDC cohort included 707 patients. The proportions of patients with a low (RS < 18), intermediate (18-30), or high risk (RS > 30) were 32.0%, 48.4%, and 19.5% in MC cohort, and 26.9%, 46.8% and 26.3% in IDC cohort. The distribution of RS varied significantly according to different Ki-67 index and molecular subtype in both cohorts. Moreover, the receipt of chemotherapy was associated with RS in both cohorts. Among patients with MC, tumor stage was related to the DFS (p=0.040). No significant differences in DFS and OS were found among MC patients in different RS risk groups (OS, p=0.695; DFS, p=0.926).ConclusionRS was significantly related to Ki-67 index and molecular subtypes in MC patients, which is similar in IDC patients. However, RS was not able to predict DFS and OS in patients with MC.

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Basal-Like Breast Cancer; Clinicopathological, Molecular, and Prognostic Features

Archives of Breast Cancer ◽

10.32768/abc.20196285-91 ◽

2019 ◽

pp. 85-91

Author(s):

Sabrine Haddad ◽

Ines Zemni ◽

Irtyah Merchaoui ◽

Ilhem Bettaib ◽

Olfa Adouni ◽

...

Keyword(s):

Breast Cancer ◽

Poor Prognosis ◽

Ductal Carcinoma ◽

Disease Free Survival ◽

Distant Metastases ◽

Metaplastic Carcinoma ◽

Breast Cancers ◽

Ki 67 ◽

Prognostic Features ◽

The Mean

Background: Molecular classification of breast tumors has identified the basal-like subtype, with high heterogeneity and very poor prognosis. These tumors are mainly triple negative, characterized by the expression of basal markers CK5/6 and EGFR. In this study, we sought to investigate the features, outcome, and therapeutic modalities of basal-like breast cancers (BLBC).Methods: We retrospectively identified 90 BLBC patients diagnosed at the Department of Surgical Oncology of Salah Azaiez Institute between January 2009 and December 2013. Results: The mean age of our patients was 50 years, and 15.5% had a family history of breast cancer. The mean tumor size was 43.8 mm. Histological examination revealed invasive ductal carcinoma in 88.9% of the cases, metaplastic carcinoma in 5.6%, and medullary carcinoma and adenoid cystic carcinoma in 2.2%. BLBC was most often associated with a high tumor grade (55.3% had a grade 3 tumor) and a high Ki-67 proliferative index. Vascular invasion was found in 31.1% of the cases. Regarding lymph node involvement, 42.9% had positive lymph nodes and 7.9% featured distant metastases. Surgical treatment was provided for 85 patients. It consisted of conservative surgery in 40 cases and radical surgery in 45 cases. Neoadjuvant chemotherapy was administrated to 23 patients, with a 13% complete pathologic response. The rates of overall survival and disease-free survival at 3 years for localized BLBC were 74.4% and 75.9%, respectively. Conclusion: BLBCs are aggressive tumors associated with poor prognosis. Thus, to identify novel prognostic factors and therapeutic targets, prospective studies should investigate the epidemiological and evolutive profile of these tumors.

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Ki-67/MIB-1 as prognostic factor for locoregional recurrence after adjuvant radiation therapy in early breast cancer: A population-based study

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.20074 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 20074-20074

Author(s):

C. Mucciarini ◽

F. Giovanardi ◽

F. Masoni ◽

C. Cirilli ◽

F. Artioli ◽

...

Keyword(s):

Breast Cancer ◽

Prognostic Factor ◽

Early Breast Cancer ◽

Locoregional Recurrence ◽

Cell Activity ◽

P Value ◽

Adjuvant Radiation ◽

Significant Prognostic Factor ◽

Ki 67 ◽

Mib 1

20074 Background: Adjuvant radiotherapy (RT) has been shown to decrease the risk of locoregional recurrence (LRR) in women with infiltrating early breast cancer, with or without an associated systemic treatment. RT is more effective on high proliferating cells and we could evaluate the proliferative activity of any cancer through Ki-67/ MIB-1 antibodies. Adjuvant RT for breast cancer could show a greater efficacy to prevent LRR in the higher proliferating cancers. Methods: We conducted a retrospective analisys on all the 5004 cases of infiltrating early breast cancer diagnosed in the Province of Modena between 1989 and 2004 and registered in the Modena Cancer Registry. Beneath them we were able to find data about 1885 women who underwent adjuvant RT. We analyzed the data concerning this population on the basis of number of LRR and Ki-67 labeling index. Since the lack of a worldwide agreed Ki-67 cut off value representing an high proliferation rate of cell activity, we examinate our data in an univariate analisys establishing for the Ki-67 three different cut offs values ( 20%, 30% and 50%). Results: Between 1885 women who underwent RT, 91 ( 4.8%) had a LRR. Median follow-up was 6 years (range 1–15 years). Using a cut off for the Ki-67 of 20% to fix an high cell proliferation, 67 women had a Ki-67 < 20% and 24 ≥ 20%. The p-value was 0.176. Increasing the cut off to the 30%, 75 women had a Ki-67 < 30% and 16≥ 30%. The p-value was 0.048. Finally, considering the Ki-67 value to 50%, 87 women had a value < 50% and 4 ≥ 50%, with a p-value of 0.992. In our analisys, it doesn’t seem that an increasing Ki-67 value would be correlated with a higher LRR. We are considering in a further analisys the weight of the different sistemic therapies on our results. Conclusions: The Ki-67 expression doesn’t seem to be considered a statistically significant prognostic factor for LRR in early breast cancer after adjuvant RT. No significant financial relationships to disclose.

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Histological growth pattern as a potential prognostic factor in patients operated for breast cancer liver metastases.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e12576 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e12576-e12576

Author(s):

Ali Bohlok ◽

Lara Botzenhart ◽

Valerio Lucidi ◽

Jean Christophe Noel ◽

Pieter Demetter ◽

...

Keyword(s):

Breast Cancer ◽

Liver Resection ◽

Prognostic Factor ◽

Liver Metastases ◽

Growth Pattern ◽

Oncological Outcome ◽

Consecutive Series ◽

Significant Prognostic Factor ◽

International Consensus ◽

Breast Cancer Liver Metastases

e12576 Background: Indications for surgery in patients with breast cancer liver metastases (BCLM) remain ill-defined. Recently, the histological growth pattern (HGP), such as desmoplastic (dHGP), associated with angiogenesis and inflammation, or replacement (rHGP), associated with vessel co-option and in the absence of immune infiltrate, has been demonstrated as a significant prognostic factor in patients operated for colorectal liver metastases. In BCLM, the distribution and the prognostic value of HGP are poorly documented. We aimed to characterize HGP in a series of patients undergoing liver resection for BCLM and correlate these patterns with postoperative outcomes. Methods: A consecutive series of 58 patients undergoing liver resection for BCLM was reviewed. Clinicopathologic parameters of these patients were analyzed. HGPs were assessed in archival H&E stained tissue sections, according to international consensus guidelines. The proportions of rHGP and dHGP were determined in each metastasis. In case of multiple metastases, mean HGP was calculated for each patient. Patients were categorized as pure (100% rHGP or dHGP) or dominant phenotype ( > 50% rHGP or dHGP, on the entire tumor/normal liver interface). All these factors were correlated with overall and disease-free survivals (OS and DFS). Results: After a mean follow-up of 81 months, 5-years OS and DFS in global population were 49.7% and 22.7%, respectively. No clinicopathologic preoperative factor was found to be predictive for OS or DFS. HGPs were analyzed in a first set of 21 patients. All patients showed some rHGP component. Of these, 11 were pure rHGP (52.4%), 4 dominant-rHGP (19%) and 6 dominant-dHGP (28.6%). Five-years postoperative OS and DFS were of 19.4 and 18.2% in pure rHGP, as compared with 64.8 and 33.3% in patients with some dHGP component (p = 0.089). Conclusions: rHGP appears as the main phenotype of BCLM. First analyzes suggest that surgery for BCLM with pure rHGP is associated with a worse oncological outcome as compared to BCLM with a dHGP component.

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O18 Activated leukocyte cell adhesion molecule (ALCAM) and its intracellular linkers in assessing the outcome of patients with breast cancer

British Journal of Surgery ◽

10.1093/bjs/znab282.023 ◽

2021 ◽

Vol 108 (Supplement_5) ◽

Author(s):

Y M Yang ◽

A J Sanders ◽

E Davies ◽

R E Mansel ◽

W G Jiang

Keyword(s):

Breast Cancer ◽

Cell Adhesion ◽

Prognostic Factor ◽

Clinical Outcome ◽

Prognostic Value ◽

Family Members ◽

Prognostic Index ◽

Disease Free Survival ◽

Good Prognosis ◽

Significant Prognostic Factor

Abstract Introduction ALCAM (also known as CD166) is a membrane integral protein and said to have a role in predicting the clinical outcome of patients with breast cancer, but the pattern of the prediction value is inconsistent. ALCAM confers cell-cell adhesion via heterotypic and homotypic interactions and linked to cytoskeleton via the ERM protein family (Ezrin, Moesin, Radixin and EHM2), particularly ezrin. The present study explored if the ALCAM and its ERM linkers may assist in refining the prognostic value of ALCAM. Method Gene transcripts of ACLAM and the ERM family members were quantitatively analysed in an existing breast cancer cohort collected freshly after surgery. The relationship between ALCAM and patient’s survival (follow-up 10 years) were stratified by the ALCAM linkers. Statistical methods were Kaplan-Meier’s survival method, ROC and logistic regression. Result ALCAM significantly correlated with four ERM family members (P < 0.005). Patients with high levels of ALCAM transcripts had significantly long overall survival. Further stratification by the epithelial rich Ezrin and endothelial rich Moesin identified subgroup of patients with good prognosis. Multivariant analysis indicates that the combined power of ALCAM and ERM family serves as an independent prognostic factor (P = 0.003) together with the other two factors, namely the Nottingham Prognostic Index and Nodal status (P = 0.02). A similar prediction power for disease free survival was seen with ALCAM and ERM combination. Conclusion ALCAM and its intracellular cytoskeletal linker molecules, the ERM family, together forms a significant prognostic factor to the clinical outcome of patients with breast cancer. Take-home Message ALCAM stratified by the ERM family have prognostic value in breast cancer

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Immunohistochemical Evaluation of FGD3 Expression: A New Strong Prognostic Factor in Invasive Breast Cancer

Cancers ◽

10.3390/cancers13153824 ◽

2021 ◽

Vol 13 (15) ◽

pp. 3824

Author(s):

Tommaso Susini ◽

Giulia Saccardin ◽

Irene Renda ◽

Milo Giani ◽

Enrico Tartarotti ◽

...

Keyword(s):

Breast Cancer ◽

Prognostic Factor ◽

Invasive Breast Cancer ◽

Molecular Subtype ◽

Histological Grade ◽

Disease Free Survival ◽

Individual Risk ◽

Breast Cancer Patients ◽

Ki 67 ◽

Cox Analysis

Among new prognostic factors for breast cancer, the most promising one seems to be FGD3 (Facio-Genital Dysplasia 3) gene, whose expression improves outcome by inhibiting cell migration. The aim of the study was to evaluate the prognostic role of FGD3 in invasive breast cancer in a series of 401 women, treated at our unit, by evaluating the expression of this gene by immunohistochemistry. Patients with high FGD3 expression showed a significantly better disease-free survival (DFS) (p < 0.001) and overall survival (OS) (p < 0.001). The prognostic value of FGD3 expression was stronger than that of classical pathologic parameters such as histological grade of differentiation, Ki-67 index and molecular subtype. By multivariate Cox analysis, FGD3 expression was confirmed as significant and independent prognostic factor, ranking second after age at diagnosis (≤40 years) for DFS (p = 0.003) and the second strongest predictor of OS, after AJCC Stage (p < 0.001). Our data suggest that inclusion of FGD3 evaluation in the routine workup of breast cancer patients may result in a more accurate stratification of the individual risk. The possibility to assess FGD3 expression by a simple and cheap technique such as immunohistochemistry may enhance the spread of its use in the clinical practice.

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Clinicopathologic Characteristics of Breast Cancer According to the Infiltrating Immune Cell Subtypes

International Journal of Molecular Sciences ◽

10.3390/ijms21124438 ◽

2020 ◽

Vol 21 (12) ◽

pp. 4438 ◽

Cited By ~ 1

Author(s):

Hye Min Kim ◽

Ja Seung Koo

Keyword(s):

Breast Cancer ◽

Protein Expression ◽

Immune Cell ◽

Ductal Carcinoma ◽

Disease Free Survival ◽

Luminal A ◽

Ki 67 ◽

Cell Subtype ◽

Cd163 Expression ◽

Her 2

The clinical significance of immune cell subtypes in breast cancer remains poorly understood. To identify tumor-infiltrating immune cell subtypes in breast cancer and investigate their implications, tissue microarrays were constructed using 334 cases of invasive ductal carcinoma (luminal A type: 162 (48.5%), luminal B type: 96 (28.7%), HER-2 type: 21 (6.3%), and triple negative breast cancer: 55 (16.5%)). Hormone receptors (ER, PR, and HER-2), Ki-67, and immune cell subtype-related proteins (STAT4, STAT6, FOXP3, CD8, CD68, and CD163) were assessed immunohistochemically. The proportion of highly expressed STAT6, FOXP3, CD8, CD68, and CD163 proteins was found to be lowest in luminal A type but highest in the HER-2 type. Additionally, high-level STAT6, FOXP3, CD68, and CD163 protein expression was associated with higher histologic grade. ER negativity was associated with high STAT6, FOXP3, and CD163 expression levels, whereas PR negativity and high Ki-67 labeling index were associated with high CD163 expression. Univariate (p = 0.003) and multivariate Cox (hazard ratio: 2.435, 95% CI: 1.110-5.344, p = 0.049) analyses showed that high CD8 expression is an independent factor associated with shorter disease-free survival. Immune cell subtype-related protein expression is dependent on breast cancer molecular subtypes, and CD8 expression is associated with patient prognosis.

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The Biological and Clinical Significance of Glutaminase in Luminal Breast Cancer

Cancers ◽

10.3390/cancers13163963 ◽

2021 ◽

Vol 13 (16) ◽

pp. 3963

Author(s):

Brendah K. Masisi ◽

Rokaya El Ansari ◽

Lutfi Alfarsi ◽

Madeleine L. Craze ◽

Natasha Jewa ◽

...

Keyword(s):

Breast Cancer ◽

Patient Outcome ◽

Ductal Carcinoma ◽

Tumour Size ◽

Prognostic Significance ◽

Disease Free Survival ◽

Glutamine Metabolism ◽

Gene Copy ◽

Luminal Breast Cancer ◽

Potential Biomarker

The glutamine metabolism has a key role in the regulation of uncontrolled tumour growth. This study aimed to evaluate the expression and prognostic significance of glutaminase in luminal breast cancer (BC). The glutaminase isoforms (GLS/GLS2) were assessed at genomic/transcriptomic levels, using METABRIC (n = 1398) and GeneMiner datasets (n = 4712), and protein using immunohistochemistry in well-characterised cohorts of Oestrogen receptor-positive/HER2-negative BC patients: ductal carcinoma in situ (DCIS; n = 206) and invasive breast cancer (IBC; n = 717). Glutaminase expression was associated with clinicopathological features, patient outcome and glutamine-metabolism-related genes. In DCIS, GLS alone and GLS+/GLS2- expression were risk factors for shorter local recurrence-free interval (p < 0.0001 and p = 0.001, respectively) and remained prognostic factors independent of tumour size, grade and comedo necrosis (p = 0.0008 and p = 0.003, respectively). In IBC, GLS gene copy number gain with high mRNA expression was associated with poor patient outcome (p = 0.011), whereas high GLS2 protein was predictive of a longer disease-free survival (p = 0.006). Glutaminase plays a role in the biological function of luminal BC, particularly GLS in the early non-invasive stage, which could be used as a potential biomarker to predict disease progression and a target for inhibition. Further validation is required to confirm these observations, and functional assessments are needed to explore their specific roles.

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