Eduardo Armanasco

PLASMA MMP-9 (92 kDa-MMP) ACTIVITY IS USEFUL IN THE FOLLOW-UP AND IN THE ASSESSMENT OF PROGNOSIS IN BREAST CANCER PATIENTS

Previously we determined that plasma MMP‐9 activity was significantly elevated in breast cancer patients compared to benign mammary pathologies and healthy controls. Now we analyzed its potential usefulness in the follow‐up and in the prognosis of these patients. MMP‐9 activity was measured by gelatin quantitative zymography in the euglobulin plasma fraction of 46 breast cancer patients in a 38‐month follow‐up study. Blood samples were obtained before surgery (S1), 1 month after (S2) and every 3 months. The relapse‐free survival (RFS) and overall survival (OS) analysis was performed along 56 months in 113 patients using the Kaplan‐Meier curves and Cox analysis. In 63% of the S2 analyzed, MMP‐9 decreased after surgery. In 44 patients evaluated during the adjuvant period who developed a complete response, MMP‐9 decreased compared to their S1, whereas 2 patients showed an enhancement in correlation with lack of response. Further analysis indicated that in all patients who never showed evidence of recurrence, plasma MMP‐9 activity remained low, but it increased 1 to 8 months preceding the clinical detection of progression in those patients who relapsed. Kaplan‐Meier curves indicated that high levels of plasma MMP‐9 activity at the moment of breast cancer diagnosis were associated with a worse OS rate. Cox analysis showed it was not associated with tumor stage or patients age. Our results, which show a good correlation between plasma MMP‐9 activity and the clinical status of each patient, suggest its usefulness as a marker both in the follow‐up and in the prognosis of breast cancer patients.

Plasma metalloproteinase activity is enhanced in the euglobulin fraction of breast and lung cancer patients

Matrix metalloproteinases (MMP) have been implicated in tumor invasion and metastasis. We verified, by gelatin zymography, MMP activity in the euglobulin plasma fraction of 82 healthy controls, 66 patients with benign diseases and 149 patients with breast, lung, colon or brain cancer. The euglobulin fractions assayed showed 4 gelatinolytic bands of 62, 92, 120 and 200 kDa. The median (Md) value for 92 kDa‐MMP activity was significantly increased in breast (Md 1.34 arbitrary units [AU]/ml plasma, range 0.0–7.2) and lung cancer patients (Md 1.43 AU/ml, range 0.0–3.6) compared with the controls (Md 0.48 AU/ml, range 0.0–1.8). Patients with colon cancer or gliomas presented values of MMP‐9 similar to those of the healthy population. Multivariate analysis indicated that plasma MMP‐9 activity was not predicted by the known clinicopathological parameters such as age, stage, tumor size, number of positive lymph nodes, histologic grade, histologic type, nuclear grade or mitotic index. Lung cancer patients also presented high values of MMP‐9 (Md 1.43, range 0.0–3.6 [n = 26]), without association with tumor stage or histologic type. The levels of 92 kDa‐MMP activity in the plasma euglobulin fraction could be a potentially useful tumor marker in breast and lung cancer. Int. J. Cancer 89:389–394, 2000.

Abstract 1577: Levels of Fibroblast Growth Factor 21 (FGF21) in serum as diagnostic biomarker in patients with breast cancer

Epidemiological studies have suggested a close link between obesity and breast cancer. There is an immediate need to investigate the potential pathways linking obesity and breast cancer to have an early diagnosis in patients and optimize the chance of cure. FGF21 is a regulator of local and systemic metabolic homeostasis and its expression is induced in response to diverse physiological or pathological stressors. High serum levels of FGF21 were found in obese individuals, subjects with metabolic syndrome, type 2 diabetes mellitus and coronary heart disease. Up to date, the clinical implication of FGF21 in cancer was not elucidated. Our aim was to study the role of serum FGF21 as a diagnostic biomarker of breast cancer. The serum levels of FGF21 in 45 breast cancer women patients (median age 59, range 32-88 years) and 51 age-matched healthy controls were evaluated using a quantitative ELISA test (RD SII: 17; SIII: 6; ND: 5] were obtained before surgery, without any previous treatment. We included patients with carcinoma in situ (n = 2), invasive ductal (n = 31) and lobular (n = 8), special carcinoma (n = 2), ND: 2. We observed that breast cancer patients showed significantly elevated values of serum FGF21 (median 224.55 pg/ml, range 24.15-776.19) respect to the levels observed in healthy controls (76.86, 0.00-425.60) (KW and MW, p Citation Format: Maria Elena Knott, Stella Maris Ranuncolo, Myriam Nunez, Eduardo Armanasco, Lydia Ines Puricelli, Mariana Silvia De Lorenzo. Levels of Fibroblast Growth Factor 21 (FGF21) in serum as diagnostic biomarker in patients with breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1577. doi:10.1158/1538-7445.AM2015-1577

Abstract P2-01-16: Role of 18 FDG PET/CT in axillary staging in early breast cancer

OBJETIVE To evaluate the 18F-FDG PET/CT capacity for the detection of axillary metastases and compare results with sentinel lymph node biopsy (SLNB).MATERIAL AND METHODS: 99 female patients with clinical T1T2N0 breast cancer were included. Patients with recent breast or axillary surgery, T3T4 disease, ductal carcinoma in situ, inflammatory carcinoma, uncontrolled diabetes mellitus and pregnant or lactation patients were excluded. Pre-operative FDG PET-CT was performed 15 days before surgery, SLNB took place with the combined method (radioisotopes and patent blue). Pearson and Spearman correlation test were used to evaluate association of main variables with a significance level (p) of 0.05.RESULTS: Breast PET-CT results: 80 positive PET/CT. Negative PET/ CT in 19 patients (4invasive lobular carcinoma, 7 tumors Citation Format: Cristina Noblia, Eugenia Azar, Dolores Mansilla, Amilcar Osorio, Eduardo Armanasco, Diana Montoya, Martin Ipina, Gaston Berman, Eduardo Gonzalez, Christian Gonzalez, Gabriel Bruno, Patricia Parma, Carla Pulero, Ana Alvarez. Role of 18 FDG PET/CT in axillary staging in early breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-01-16.

Abstract 448: Expression of Glypican-3 (GPC3) in breast cancer tumors from Brazilian and Argentinean patients

The heparan sulfate proteoglycan Glypican-3 (GPC3) is involved in the signaling regulation of several growth factors. GPC3 is widely expressed in embryonic tissues, but disappears from most adult tissues, except for the mammary gland, among others. Several studies have involved GPC3 with cancer and some data indicate that this glypican is diminished in breast tumors. Previously, we have transfected the murine mammary tumor cell line LM3 (GPC3 negative) with the GPC3 complete cDNA sequence. We found that GPC3 reexpression is able to inhibit invasion and metastasis in vivo as well as to induce an in vitro EMT reversion, suggesting that GPC3 could act as a metastasis suppressor. The aim of the present work was to determine, in a prospective trial, whether GPC3 expression might be useful as a biomarker able to predict metastasis outcome in breast cancer patients. Our local access to a major source of breast human tissues from a representative Latin American population is an exceptional tool for the development of this new biomarker. A preliminary study was perform to analyze the expression of GPC3 at the mRNA level, by quantitative real time RT-PCR, in breast cancer samples (Brazilian n=15, Argentinean n=22) and peri-tumoral normal breast tissues (Brazilian n=16, Argentinean n=4). Even though the analyzed sample size was small, we found that both Brazilian and Argentinean tumor populations presented similar characteristics related to GPC3 expression. It was established a lower GPC3 level in tumor (n=37) than in peri-tumoral normal tissues (n=20) (p Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 448. doi:1538-7445.AM2012-448

Abstract P1-01-28: Utility of 18F-Fluoro-Deoxyglucose Emisión Tomography/Computed and Sentinel Node Biopsy for Axillary Staging in Primary Breast Cancer. Roffo PET/CT 1 Trial

Objetive 1. - To compare the capacity of the PET and the sentinel node for the detection of axillary metastasis (MTS). 2. - To evaluate sensitivity, specificity, positive and negative predictive value of the PET/CT. Inclusion criteria-Breast cancer T1 T2 NO. Palpable nodes suspicious of involvement. Exclusion criteria-Ductal carcinoma in situ, inflammatory carcinoma, recent biopsy of the breast, pregnancy or lactation, diabetes. Method 18-FDG PET/CT was made 15 days before the surgery. The sentinel node biopsy took place with the combined method (radioisotopes and patent blue) Material They were evaluated 54 patients. Age average: 59 years (37-79). T1: 36 patients (67%); T2: 18 patients (33%) Tumor size between 5 and 40 mm (average 19) clinically negative axilla 46 (85%); doubtful axilla 8 (15%). Stage I: 33 patients (61%); stage II: 21 patients (39%). Results Forty four (81%) of the tumors were invasive ductal carcinoma: 7 (13%) invasive lobular carcinoma; and 3 (6%) ductolobular. Fifteen patients had MTS in the SN (28%), of these 3 were micrometastasis. In 2 patients the PET/CT changed the stage since it was positive for bony and pulmonary MTS. Results PET in breast: Eleven negatives (FN: 20%). Four were invasive lobular carcinomas; 4 were T1a. Sensitivity 80%. VPP = 100%. False negative: 20%Result PET in axila: In 45 patients the PET was negative (83%). Six of them presented MTS in the sentinel node; 3 of them were micrometastasis. False negative: 40%. Sensitivity: 60%.VPN 87%. In 9 patients the PET were positive (17%) and the sentinel node was positive in all the cases. Specifity: 100%. VPP = 100%. In 8 patients the axilla was doubtful, of these only in one patient PET and the SN was positive. Conclusion 1.-PET/CT does not contribute advantages for the axillary staging in the initial stage because it does not manage to identify smaller MTS of 5 mm. 2.- A negative PET/CT does not replace the sentinel node biopsy. 3.- A positive PET/CT would indicate the necessity of making an axillary dissection still in clinically negative axilla. 4- In clinically doubtful axilla was coincidence between PET/CT and the SN as much in the negatives as in the positives. Key words: Occult axillary metastases. Positron emission tomography. Sentinel node biopsy. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-01-28.