Prediction of anthracycline cardiotoxicity after chemotherapy by biomarkers kinetic analysis.

Anthracyclines are active drugs against breast cancer, but can exert cardiotoxic effects. We analyzed the association between the kinetics of various biomarkers during chemotherapy, and the risk of subsequent cardiac toxicity. 50 patients (49 women) with early breast cancer surgically treated and eligible to anthracycline-based adjuvant chemotherapy were analyzed. The left ventricular ejection fraction (LVEF) together with the plasma concentration of several blood markers was measured at the beginning of anthracycline chemotherapy (t (0)), 5 months (t (1)), 16 months (t (2)), 28 months (t (3)), and 40 months later (t (4)). A single measured LVEF value less than 50% or a clinically overt congestive heart failure (CHF) was considered cardiotoxic effects. We tested whether the kinetics of LVEF and blood biomarkers measured during chemotherapy was predictive of subsequent cardiotoxicity and overall cardiac fitness. The left ventricular ejection fraction measured at the end of treatment as well as the rate of change of hemoglobin concentration during anthracycline-based chemotherapy predicted cardiotoxicity in a 3-year follow-up period. When LVEF at the end of chemotherapy was lower than 53% or hemoglobin blood concentration declined more than 0.33 g/dL/month during chemotherapy, the odds ratio of subsequent cardiotoxicity was 37.3 and 18, respectively. The specificity of these two tests was 93.3% and 80%, whereas the sensitivity was 90.9 and 81.2%, respectively. Testing the rate of change of hemoglobin concentration during anthracycline-based chemotherapy, as well as the left ventricular ejection fraction at the end of treatment, seems a powerful method to assess the effects of anthracyclines on cardiac fitness and identify patients at high risk of CHF. Further validation of these tests on a large cohort of patients and cost-benefit analysis should be encouraged.

Infertility and pregnancy after breast cancer: current knowledge and future perspectives.

Fertility impairment induced by adjuvant treatments and potential risk associated with pregnancy, are major concerns of young pre-menopausal patients with early breast cancer. Although current evidences suggest that pregnancy does not negatively affect prognosis, a low rate (3-8%) of pregnancy after breast cancer has been reported. Among the potential causes of such a low rate there are a high chance of spontaneous abortions (25%) as well as the fertility impairment induced by adjuvant treatments. No standard strategy to preserve fertility in breast cancer patients is available so far. Experimental approaches include cryopreservation strategies, and use of gonadotropin-releasing hormone (GnRH) agonists to render germinal epithelium quiescent and less sensitive to the chemotherapy cytotoxicity. Here, we reviewed current knowledge about incidence and risks of pregnancy after breast cancer, risks of ovarian failure after adjuvant treatments and experimental strategies aiming to preserve ovarian function and fertility in young breast cancer patients.

Sentinel lymph node biopsy in breast cancer patients: the medical oncology perspective.

Recent data indicates that the sentinel lymph node biopsy (SLNB) is a possible alternative to axillary lymph node dissection (ALND) in early breast cancer patients, with minimal risk of complications. From the medical oncologist's point of view, the impact of SLNB on the management of patients should consider if SLNB is useful to choose adjuvant treatment, if it is adequate to provide local control, and what is the significance of lymph node micrometastases on treatment and staging. Lymph node involvement has always been recognised as the most important prognostic factor in early-stage breast cancer, even if many other parameters have been evaluated in recent years. However, the lack of knowledge of nodal status in patients with false-negative SLNB seems to result in an undertreatment in a very low percentage of patients. Adjuvant chemotherapy and hormonal therapy with tamoxifen are associated with an absolute reduction of the risk of recurrence and death both in node-positive and in node-negative patients, then if patients are treated with modern adjuvant systemic therapy, any effect associated with false negative SLN should be minimised. The impact of axillary treatment on survival is still controversial, but in recent times axillary lymph node positivity is considered as an indicator for high risk of systemic diffusion of the disease rather than a possible origin of systemic metastases. The significance of occult sentinel lymph node metastases detected by immunohistochemistry (IHC) or molecular biology on prognosis is still uncertain. The new version of the staging system of breast cancer has recognised the need for a standard diagnostic approach and of a nomenclature system which also takes SLNB into account.