Detection of disseminated tumor cells in locally advanced breast cancer patients before primary systemic therapy.

AIM: To assess the prevalence and prognostic power of disseminated tumor cells (DTC) in patients with locally advanced breast cancer (LABC) before primary systemic therapy (PST). MATERIALS AND METHODS: LABC patients attending our Breast Unit were studied between 2002 and 2012, all of them being considered for PST. To determine the presence of DTC, posterior iliac crest aspirates were obtained and marrow samples were processed by gradient separation with Ficoll (Lymphoprep(®)) and immunohistochemical staining using the antiCK A45-B/B3 (EPIMET) antibody. Clinicopathologic variables were recorded before and after PST to assess response. Disease-free survival (DFS) and overall survival (OS) were determined after follow-up. The presence of DTC as a predictor of response to PST and as a prognostic tool for OS and DSF was evaluated. RESULTS: DTC were observed in 26% of 47 patients included in the study. PST consisted of chemotherapy in 94% and hormone therapy in 6%. Breast-conserving therapy was attained in 33%. Mean follow-up was 68 months. Complete clinical response (CR) after PST was seen in 26%, disease recurrence in 38%, and cancer-related death in 8%; tumor size and negative estrogen receptors were significant predictors of CR and mastectomy was associated with DFS. Persistent axillary disease after PST and previous recurrence were predictive of OS. DTC were detected more often in patients who did not achieve CR and those who presented recurrence. DTC detection was a significant prognostic factor for a worse OS (OR = 7.62; CI95%: 1.46-39.61; p = 0.009) and a decreased survival time (62 versus 82 months, p = 0.004). CONCLUSION: Presence of DTC before PST was found in a significant number of patients with LABC. DTC were found to be a significant prognostic factor for cancer-related death. DTC could be a surrogate predictor of response to PST and also of disease recurrence in LABC patients.

Multifocal hepatic cystic mass as first manifestation of metastatic spinal hemangiopericytoma.

INTRODUCTION: Hemangiopericytomas (HPCs) are rare vascular tumors with a high malignant potential. Hepatic metastases from HPC are very infrequent and usually show a distinctive solid aspect with a surrounding pseudocapsule. PRESENTATION OF CASE: A 37-year-old man with a previous medical history of recurrent spinal hemangiopericytoma with a 9cm×7cm cystic hepatic mass detected on follow-up. Contrast enhanced US and MRI confirmed the presence the lesion showing mixed (solid and cystic) content. Parasitic and viral serology plus serum tumoral markers (CEA, ca 19.9, ca 125, AFP) tests, upper and lower endoscopy and general laboratory tests were normal and extended left lobectomy was performed. Histopathologic study confirmed the diagnosis of multifocal metastasic hemangiopericytoma with moderate CD-34, CD-99 and Bcl-2 positivity after immunohistochemical staining. After 1-year follow-up the patient does not present any evidence of abdominal recurrence but a skull base recurrence has been detected. DISCUSSION: Liver metastasis from spinal HPC are uncommon and do not have cystic appearance so radiologic diagnosis can be challenging. In spite of the presence of previously diagnosed HPC context, the presence of a liver cystic mass in a young patient makes necessary to discard a number much more frequent benign and malignant diagnosis before metastatic disease can be confirmed. CONCLUSION: The presence of a cystic hepatic mass makes it mandatory to rule out a number neoplasms other than metastasic HPC before a definitive diagnosis is made. In addition to local radiotherapy and antiangiogenic agents, surgery can be useful to treat liver dissemination.

Prognostic value of hematogenous dissemination and biological profile of the tumor in early breast cancer patients: a prospective observational study.

BACKGROUND: The aim of this study was to investigate the incidence and prognostic value of disseminated tumor cells in bone marrow of breast carcinoma patients with early disease, and to analyze this finding in relation to lymph node involvement, determined by sentinel lymph node (SLN) biopsy analysis, and to prognostic factors of interest. METHODS: 104 patients with operable (T<3 cm) breast cancer and clinically- and sonographically-negative axillary lymph nodes were scheduled for SLN biopsy. Bone marrow aspirates were collected before the start of surgery from both iliac crests, and mononuclear cell layers were separated by density centrifugation (Lymphoprep). Slide preparations were then examined for the presence of disseminated tumor cells by immunocytochemistry with anti-cytokeratin antibodies (A45-B/B3). Lymphoscintigraphy was performed 2 hours after intratumor administration of 2 mCi (74 MBq) of 99mTc colloidal albumin. The SLN was evaluated for the presence of tumor cells by hematoxylin-eosin staining and, when negative, by immunocytochemistry using anti-cytokeratin antibody (CAM 5.2). Survival analyses and comparative analyses were performed on the results of bone marrow determinations, SLN biopsy, and known prognostic factors, including breast cancer subtypes according to the simplified classification based on ER, PR and HER2. RESULTS: Lymph node and hematogenous dissemination occur in one-third of patients with early-stage breast cancer, although not necessarily simultaneously. In our study, disseminated tumor cells were identified in 22% of bone marrow aspirates, whereas 28% of patients had axillary lymph node involvement. Simultaneous lymph node and bone marrow involvement was found in only 5 patients (nonsignificant). In the survival study (60 months), a higher, although nonsignificant rate of disease-related events (13%) was seen in patients with disseminated tumor cells in bone marrow, and a significant association of events was documented with the known, more aggressive tumor subtypes: triple negative receptor status (21%) and positive ERBB2 status (29%). CONCLUSIONS: Tumor cell detection in bone marrow can be considered a valid prognostic parameter in patients with early disease. However, the classic prognostic factors remain highly relevant, and the newer breast cancer subtypes are also useful for this purpose.