BCL2 in breast cancer: a favourable prognostic marker across molecular subtypes and independent of adjuvant therapy received.

BACKGROUND: Breast cancer is heterogeneous and the existing prognostic classifiers are limited in accuracy, leading to unnecessary treatment of numerous women. B-cell lymphoma 2 (BCL2), an antiapoptotic protein, has been proposed as a prognostic marker, but this effect is considered to relate to oestrogen receptor (ER) status. This study aimed to test the clinical validity of BCL2 as an independent prognostic marker. METHODS: Five studies of 11 212 women with early-stage breast cancer were analysed. Individual patient data included tumour size, grade, lymph node status, endocrine therapy, chemotherapy and mortality. BCL2, ER, progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) levels were determined in all tumours. A Cox model incorporating the time-dependent effects of each variable was used to explore the prognostic significance of BCL2. RESULTS: In univariate analysis, ER, PR and BCL2 positivity was associated with improved survival and HER2 positivity with inferior survival. For ER and PR this effect was time dependent, whereas for BCL2 and HER2 the effect persisted over time. In multivariate analysis, BCL2 positivity retained independent prognostic significance (hazard ratio (HR) 0.76, 95% confidence interval (CI) 0.66-0.88, P<0.001). BCL2 was a powerful prognostic marker in ER- (HR 0.63, 95% CI 0.54-0.74, P<0.001) and ER+ disease (HR 0.56, 95% CI 0.48-0.65, P<0.001), and in HER2- (HR 0.55, 95% CI 0.49-0.61, P<0.001) and HER2+ disease (HR 0.70, 95% CI 0.57-0.85, P<0.001), irrespective of the type of adjuvant therapy received. Addition of BCL2 to the Adjuvant! Online prognostic model, for a subset of cases with a 10-year follow-up, improved the survival prediction (P=0.0039). CONCLUSIONS: BCL2 is an independent indicator of favourable prognosis for all types of early-stage breast cancer. This study establishes the rationale for introduction of BCL2 immunohistochemistry to improve prognostic stratification. Further work is now needed to ascertain the exact way to apply BCL2 testing for risk stratification and to standardise BCL2 immunohistochemistry for this application.

[Therapeutic pathomorphism of Ewing's tumor]. / Terapevticheskii patomorfoz opukholi Iunga.

Pathomorphosis of Ewing's tumors after the combined treatment is studied with the use of light and electron microscopy, DNA-flow cytometry. Necrosis and apoptosis of tumor cells produced by the therapy are characterized. Therapeutic forms of tumor cells representing hyperaneuploid population delayed at the G2-level of the cell cycle are described.

[Clinical course, diagnosis and therapy of Ewing's sarcoma of the ribs in children]. / Klinika, diagnostika i lechenie sarkomy Iuinga reber u detei.

X-ray examination is considered to be the most effective procedure for diagnosis of Ewing's sarcoma of the rib. The extent of surgery and sequence of procedures are determined on the basis of its evidence. Treatment of infantile Ewing's sarcoma of the rib should include chemoradiation therapy and compulsory surgery.