Reinaldo Chacón

Cardiovascular autonomic function in anthracycline-treated breast cancer patients.

SummaryPreclinical studies suggest that in addition to the well-known direct damage to the myocardium, anthracycline antineoplastic drugs exert toxic effects on the cardiovascular autonomic system as well. To investigate whether this phenomenon occurs in the clinic, we carried out noninvasive, widely used tests of cardiovascular autonomic physiology in 55 women with stage II or III breast cancer. In all, 31 were being treated with anthracycline-containing chemotherapy regimens, and 24 who were receiving CMF (cyclophosphamide, Methotrexate, and fluorouracil) served as controls. Of 279 tests conducted in anthracycline (A)-treated patients, 123 were abnormal, vs 54 of 216 tests carried out in 24 controls (44% vs 25%;P <0.005). Abnormal variations in heart rate on standing and in diastolic blood pressure during handgrip was found in 25 (81%) and 17 patients receiving A, vs 9 (37%;P <0.005) and 5 (21%;P <0.0001), respectively, in controls. The incidence of abnormal tests was significantly higher in A-treated patients >60 years of age (41%) vs 67%;P <0.05). Radionuclide ventriculography was carried out in 19 patients who showed abnormal tests of cardiovascular autonomic function after ⩾ 6 courses of a-containing chemotherapy; only 1 of them had abnormal cardiac contractility (global hypokinesia), suggesting that abnormal tests of cardiovascular autonomic function may occur in the absence of a detectable deterioration in left ventricular ejection fraction. A large number of factors may alter cardiovascular autonomic function in cancer patients, including age, radiation therapy to the chest, and multidrug treatment. Even after correcting for the most obvious of these, chemotherapy with anthracyclines is associated with a significantly higher percentage of abnormal tests for cardiovascular autonomic function. Although indirect and semi-quantitative, our results are compatible with the idea of A-induced cardiac autonomic dysfunction.

Spectrum of BRCA1/2 variants in 940 patients from Argentina including novel, deleterious and recurrent germline mutations: impact on healthcare and clinical practice

BRCA1/2 mutations in Latin America are scarcely documented and in serious need of knowledge about the spectrum of BRCA pathogenic variants, information which may alter clinical practice and subsequently improve patient outcome. In addition, the search for data on testing policies in different regions constitutes a fundamental strength for the present study, which analyzes BRCA1/2 gene sequences and large rearrangements in 940 probands with familial and/or personal history of breast/ovary cancer (BOC). In non-mutated DNA samples, Multiplex Ligation-dependent Probe Amplification assays (MLPA) were used for the analysis of large rearrangements. Our studies detected 179 deleterious mutations out of 940 (19.04%) probands, including 5 large rearrangements and 22 novel mutations. The recurrent mutations accounted for 15.08% of the total and only 2.87% of the probands analyzed, very different from a Hispanic panel previously described. In conclusion: a) this first comprehensive description of the spectrum in BRCA1/2 sheds light on the low frequency of recurrent mutations; b) this information is key in clinical practice to select adequate sequencing studies in our population, subsequently improve patient outcome and prevent damage associated to false normal reports resulting from the use of invalid population panels; c) panels of mutations from other populations should be cautiously validated before imported, even those of apparently similar origin, a concept to be considered beyond significance in Argentina.