Prognostic Significance of Carbonic Anhydrase IX (CA-IX), Endoglin (CD105) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) in Breast Cancer Patients

PURPOSE: To assess the frequency of expression and the prognostic significance of a hypoxia-regulated marker, carbonic anhydrase IX (CA IX), in a cohort of patients with invasive breast cancer. PATIENTS AND METHODS: CA IX expression was evaluated by immunohistochemistry with a murine monoclonal antibody, M75, in a series of 103 women treated surgically for invasive breast cancer. The majority of patients were treated with adjuvant hormonal or chemotherapy. The frequency of CA IX expression, its association with recognized prognostic factors, and the relationship with outcome was evaluated by univariate and multivariate statistical analyses. RESULTS: CA IX expression was present in 49 (48%) of 103 cases. The level of CA IX expression was found to be significantly associated with tumor necrosis (P < .001), higher grade (P = .02), and negative estrogen receptor status (P < .001). Furthermore, CA IX expression was associated with a higher relapse rate (P = .004) and a worse overall survival (P = .001). By multivariate analysis, CA IX was also shown to be an independent predictive factor for overall survival (hazard ratio, 2.61; 95% confidence interval, 1.01 to 6.75, P = .05). CONCLUSION: CA IX expression was associated with worse relapse-free survival and overall survival in an unselected cohort of patients with invasive breast carcinoma. The potential role of CA IX as a marker of hypoxia within breast carcinomas was also indicated by a significant association with necrosis. Further work assessing its prognostic significance in breast cancer is warranted, particularly interactions with radiotherapy and chemotherapy resistance.

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Role of carbonic anhydrase IX expression in prediction of the efficacy and outcome of primary epirubicin/tamoxifen therapy for breast cancer

Endocrine Related Cancer ◽

10.1677/erc.1.01216 ◽

2006 ◽

Vol 13 (3) ◽

pp. 921-930 ◽

Cited By ~ 52

Author(s):

Daniele Generali ◽

Stephen B Fox ◽

Alfredo Berruti ◽

Maria P Brizzi ◽

Leticia Campo ◽

...

Keyword(s):

Breast Cancer ◽

Multivariate Analysis ◽

Carbonic Anhydrase ◽

Cancer Patients ◽

Tamoxifen Therapy ◽

Carbonic Anhydrase Ix ◽

Breast Cancer Patients ◽

Caix Expression ◽

Er Positive

The purpose of this study is to investigate the role of carbonic anhydrase IX (CAIX) expression in predicting the response to epirubicin and disease-free survival (DFS) in breast cancer patients enrolled in a single institution trial of primary anthracycline and tamoxifen therapy. CAIX expression was assessed in 183 patients with T2–4 N0–1 breast cancer enrolled in a randomized trial comparing four cycles of single agent epirubicin versus epirubicin + tamoxifen as primary systemic treatment. All patients received postoperatively four cycles of the four weekly i.v. cyclophosphamide, methotrexate, 5-fluorouracil regimen. Patients with estrogen receptor (ER)-positive primary tumors received 5 years of adjuvant tamoxifen. Pretreatment, p53 (P = 0.007), c-erbB2 (P < 0.01), and Ki67 (P = 0.02) were directly associated with CAIX expression, while bcl2 (P < 0.000) and ER (P = 0.000) and progesterone receptor (PgR; P < 0.01) were inversely correlated. In multivariate analysis, only high p53 and low bcl2 were independently associated with CAIX positivity. CAIX immunostaining was significantly associated with poor outcome for DFS (P < 0.002) and overall survival (P = 0.001). In multivariate analysis, a significant interaction was found between CAIX and markers of hormone sensitivity, bcl2 (P = 0.01), ER (P = 0.02), PgR (P = 0.02), and lymph node involvement (P = 0.04), in predicting DFS. Presently, there are few clinical markers of resistance to tamoxifen treatment in ER-positive tumors. CAIX expression in breast cancer patients shows a negative predictive role of treatment efficacy in ER-positive patients on the adjuvant tamoxifen after primary chemo-endocrine therapy. Studies investigating the effects of pH on tamoxifen uptake and the effects of therapy with CA inhibitors are planned.

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Prognostic Significance of Isolated Tumor Cells (ITC) in the Bone Marrow (BM) of Breast Cancer Patients During Recurrence-free Follow-up and Therapeutic Intervention with Zoledronate

Zentralblatt für Gynäkologie ◽

10.1055/s-2005-921013 ◽

2005 ◽

Vol 127 (04) ◽

Author(s):

B Rack ◽

W Janni ◽

C Schindlbeck ◽

B Strobl ◽

T Blankenstein ◽

...

Keyword(s):

Breast Cancer ◽

Bone Marrow ◽

Cancer Patients ◽

Tumor Cells ◽

Therapeutic Intervention ◽

Prognostic Significance ◽

Breast Cancer Patients ◽

Isolated Tumor Cells

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Prognostic significance of axillary dissection in breast cancer patients with micrometastases or isolated tumor cells in sentinel nodes: a nationwide study

Breast Cancer Research and Treatment ◽

10.1007/s10549-015-3560-7 ◽

2015 ◽

Vol 153 (3) ◽

pp. 599-606 ◽

Cited By ~ 11

Author(s):

Tove Filtenborg Tvedskov ◽

Maj-Britt Jensen ◽

Bent Ejlertsen ◽

Peer Christiansen ◽

Eva Balslev ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Tumor Cells ◽

Axillary Dissection ◽

Prognostic Significance ◽

Breast Cancer Patients ◽

Isolated Tumor Cells ◽

Sentinel Nodes ◽

Nationwide Study

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Abstract 2697: Prognostic significance of intratumoral neutrophil lymphocyte ratio (NLR) in breast cancer patients

10.1158/1538-7445.am2021-2697 ◽

2021 ◽

Author(s):

Yoshihisa Tokumaru ◽

Masanori Oshi ◽

Vijayashree V. Murthy ◽

Eriko Katsuta ◽

Nobuhisa Matsuhashi ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Prognostic Significance ◽

Breast Cancer Patients ◽

Neutrophil Lymphocyte Ratio ◽

Lymphocyte Ratio

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A possible prognostic significance of c-Kit receptor expression and angiogenesis in early breast cancer patients: a pilot study

Annals of Oncology ◽

10.1093/annonc/mdv336.48 ◽

2015 ◽

Vol 26 ◽

pp. vi18

Author(s):

M. Ammendola ◽

I. Marech ◽

C. Leporini ◽

R. Patruno ◽

M. Luposella ◽

...

Keyword(s):

Breast Cancer ◽

Pilot Study ◽

Cancer Patients ◽

Early Breast Cancer ◽

Prognostic Significance ◽

Receptor Expression ◽

Breast Cancer Patients ◽

Kit Receptor

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Clinical significance of crown-like structures to trastuzumab response in patients with primary invasive HER2+ breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e12533 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e12533-e12533

Author(s):

Constantinos Savva ◽

Charles N Birts ◽

Stéphanie A Laversin ◽

Alicia Lefas ◽

Jamie Krishnan ◽

...

Keyword(s):

Breast Cancer ◽

Adipose Tissue ◽

Cancer Patients ◽

Metastatic Disease ◽

Cox Regression ◽

Prognostic Significance ◽

Metabolic Reprogramming ◽

Breast Cancer Patients ◽

Adjuvant Trastuzumab ◽

Her2 Breast Cancer

e12533 Background: Obesity is associated with breast cancer development and worse survival. Obesity can initiate, promote, and maintain systemic inflammation via metabolic reprogramming of macrophages that encircle adipocytes, termed crown-like structures (CLS). In breast cancer patients, CLS are present in 36-50% of patients and have been associated with anthropometric parameters. Here we focus on HER2+ breast cancer. The role of adiposity in HER2+ breast cancer is conflicting which may be attributed to the tumour heterogeneity. Adiposity has also been shown to affect the local immune environment of solid tumours. However, the prognostic significance of CLS in HER2+ breast cancer is still unknown. Methods: We investigated the prognostic significance of CLS in a cohort of 219 patients with primary HER2+ breast cancer who were diagnosed between 1982 to 2012 in Southampton General Hospital. This cohort includes 76 HER2+ trastuzumab naïve patients and 143 HER2+ patients treated with adjuvant trastuzumab. We stained FFPE tumour samples for the expression of CD68, CD16 and CD32B on CLS and correlated these to clinical outcomes. CLS were defined as CLS within distant adipose tissue, CLS within the adipose-tumour border (B-CLS) and intratumoural CLS. CLS were quantified manually in full face sections by two independent scorers and descriptive and Cox regression analysis was carried out. Results: A total of 201 tumours were suitable for CLS analyses. The median follow-up was 34.74 months (range, 0.43-299.08). In the trastuzumab naive cohort, B-CLS≤1 and B-CLS > 1 were present in 37 (52.11%) and 34 (47.89%), respectively. In the trastuzumab treated cohort, B-CLS≤1 were identified in 69 (53.08%) and B-CLS > 1 were found in 61 (46.92%) of the tumours. CLS were more commonly found in the adipose-tumour border (60.89%) rather than in the distant adipose tissue (36.14%) or intratumorally (14.36%). The presence of any CLS was significantly associated with BMI≥25 kg/m2 (p = 0.018). There was strong evidence of association between CD68+CD32B+ B-CLS and BMI≥25 kg/m2 (p = 0.007). Co-expression of CD16 and CD32B by B-CLS was more frequent in patients with BMI≥25 kg/m2 (p = 0.036). Survival analysis showed shorter time to metastatic disease in patients with CD68+ B-CLS > 1 (p = 0.011) in the trastuzumab treated cohort. Subgroup analysis revealed that in the BMI≥25 kg/m2 group, patients with CD68+ B-CLS > 1 had shorter time to metastatic disease compared to patients with B-CLS≤1 (p = 0.004). Multivariate cox regression showed that B-CLS > 1 is an independent prognostic factor for shorter time to metastatic disease in patients with primary HER2+ breast cancer that received adjuvant trastuzumab (HR 6.81, 95%CI (1.38-33.54), p = 0.018). Conclusions: B-CLS can be potentially used as a predictive biomarker to optimize the stratification and personalisation of treatment in HER2-overexpressed breast cancer patients.

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