Predictive and prognostic value of total tumor load in sentinel lymph nodes in breast cancer patients after neoadjuvant treatment using one-step nucleic acid amplification: the NEOVATTL study.

OBJECTIVE: To evaluate the predictive and prognostic value of total tumor load (TTL) in sentinel lymph nodes (SLNs) in patients with infiltrating breast cancer after neoadjuvant systemic therapy (NST). METHODS: This retrospective multicenter study used data from a Spanish Sentinel Lymph Node database. Patients underwent intraoperative SLN biopsy after NST. TTL was determined from whole nodes using a one-step nucleic acid amplification (OSNA) assay and defined as the total sum of CK19 mRNA copies in all positive SLNs. Cox-regression models identified independent predictive variables, which were incorporated into a nomogram to predict axillary non-SLN metastasis, and identified prognostic variables for incorporation into a disease-free survival (DFS) prognostic score. RESULTS: A total of 314 patients were included; most had no lymph node involvement prior to NST (cN0; 75.0% of patients). Most received chemotherapy with or without biologic therapy (91.7%), and 81 patients had a pathologic complete response. TTL was predictive of non-SLN involvement (area under the concentration curve = 0.87), and at a cut-off of 15,000 copies/µL had a negative predictive value of 90.5%. Nomogram parameters included log (TTL + 1), maximum tumor diameter and study-defined NST response. TTL was prognostic of disease recurrence and DFS at a cut-off of 25,000 copies/µL. After a 5-year follow-up, DFS was higher in patients with ≤ 25,000 copies/µL than those with > 25,000 (89.9% vs. 70.0%; p = 0.0017). CONCLUSIONS: TTL > 15,000 mRNA copies/µL was predictive of non-SLN involvement and TTL > 25,000 mRNA copies/µL was associated with a higher risk of disease recurrence in breast cancer patients who had received NST.

Sox2 expression in breast tumours and activation in breast cancer stem cells.

The cancer stem cell (CSC) model does not imply that tumours are generated from transformed tissue stem cells. The target of transformation could be a tissue stem cell, a progenitor cell, or a differentiated cell that acquires self-renewal ability. The observation that induced pluripotency reprogramming and cancer are related has lead to the speculation that CSCs may arise through a reprogramming-like mechanism. Expression of pluripotency genes (Oct4, Nanog and Sox2) was tested in breast tumours by immunohistochemistry and it was found that Sox2 is expressed in early stage breast tumours. However, expression of Oct4 or Nanog was not found. Mammosphere formation in culture was used to reveal stem cell properties, where expression of Sox2, but not Oct4 or Nanog, was induced. Over-expression of Sox2 increased mammosphere formation, effect dependent on continuous Sox2 expression; furthermore, Sox2 knockdown prevented mammosphere formation and delayed tumour formation in xenograft tumour initiation models. Induction of Sox2 expression was achieved through activation of the distal enhancer of Sox2 promoter upon sphere formation, the same element that controls Sox2 transcription in pluripotent stem cells. These findings suggest that reactivation of Sox2 represents an early step in breast tumour initiation, explaining tumour heterogeneity by placing the tumour-initiating event in any cell along the axis of mammary differentiation.

Myofibroblastoma of male breast: report of three cases and review of the literature.

We report three cases of male breast myofibroblastoma. This uncommon benign tumor arises from breast mesenchyma and is more frequently seen in adult men. Mammographic findings consist of a well-delimited, round to oval dense mass, variable in size but usually 1-4 cm in diameter. No microcalcifications were observed. Ultrasonography confirms the solid nature of the lesion, showing a well-circumscribed, homogeneous, hypoechoic mass, compressible with pressure. Although FNA cytology may support the diagnosis, surgical biopsy should be performed. Tumorectomy is the treatment of choice. To our knowledge, no more than 40 cases of breast myofibroblastoma have been reported. This is the first report in the literature which emphasizes the mammographic and ultrasonographic features of this tumor.

An experience with the Advanced Breast Biopsy Instrumentation (ABBI) system in the management of non-palpable breast lesions.

Our objective was to evaluate our experience with the Advanced Breast Biopsy Instrumentation system (ABBI) in non-palpable breast lesions in a prospective study from July 1998 to November 2000. The ABBI system was included in a protocol for BIRADS 4 non-palpable, small (<15 mm) breast lesions. Digital radiographs of both specimen and biopsy cavity were obtained to validate the procedure. A total of 255 ABBI biopsies were performed in 254 patients. In 251 cases the lesions were successfully removed (98.4%). Mammographic lesions consisted of 176 cases of microcalcifications (69%), 51 cases of architectural distortions (20%) and 28 cases of nodules (11%). Seventy-two carcinomas were diagnosed (28.2%). Affected margins were found in 41 cases (56.9%). Residual tumour was seen in 31 patients (43%). Seventeen borderline results and 33 benign architectural distortions obviated further procedures. The complication rate in 10 cases was as follows: 3 wound infections; 4 haematomas; and 3 vasovagal reactions. The main utility of the ABBI system is to allow a reliable diagnosis in complex lesions, such as small clusters of microcalcifications and especially architectural distortions. Surgery can be avoided for borderline cases if the lesion is completely removed and free margins are obtained in the pathology study. Therapeutic use is controversial and can be applied only in selected cases.