Nucleotide Excision Repair (NER) is a critical pathway involved in breast cancer (BC). We have previously published that a low DNA repair capacity (DRC) is associated with a higher risk of BC in Puerto Rican women. Let-7b belongs to a miRNA family with tumor suppressor activity that targets oncogenes. We isolated miRNAs from plasma of 153 Puerto Rican women with and without BC. DRC was measured in lymphocytes by means of a host cell reactivation assay. These women were divided into four groups according to their DRC level: High (>3.8%) and low (<3.8%). The four groups consisted of BC patients with high (n = 35) and low (n = 43) DRC and controls with high (n = 39) and low (n = 36) DRC. Epidemiologic data were collected at initial BC diagnosis and almost five years after diagnosis. A significant difference in Let-7b expression was found in BC patients with high DRC versus the remaining groups (p < 0.001). Thus, our data reveal a possible role of Let-7b on DRC during breast carcinogenesis. Our study is innovative because it provides the first evidence that Let-7b may play role in DRC regulation (through the NER repair pathway) in BC.

Breast cancer (BC) is a heterogeneous disease which many studies have classified in at least four molecular subtypes: Luminal A, Luminal B, HER2-Enriched, and Basal-like (including triple-negative breast cancer, TNBC). These subtypes provide information to stratify patients for better prognostic predictions and treatment selection. Individuals vary in their sensitivities to carcinogens due to differences in their DNA repair capacity (DRC) levels. Although our previous case-control study established low DRC (in terms of NER pathway) as a BC risk factor, we aim to study this effect among the molecular subtypes. Therefore, the objectives of this study include investigating whether DRC varies among molecular subtypes and testing any association regarding DRC. This study comprised 267 recently diagnosed women with BC (cases) and 682 without BC (controls). Our results show a substantial variability in DRC among the molecular subtypes, with TNBC cases (n = 47) having the lowest DRC (p-value < 0.05). Almost 80 percent of BC cases had a DRC below the median (4.3%). Low DRC was strongly associated with the TNBC subtype (OR 7.2; 95% CI 3.3, 15.7). In conclusion, our study provides the first report on the variability among the molecular subtypes and provides a hypothesis based on DRC levels for the poor prognosis of TNBC.

Obesity has been shown to be associated with increased left ventricular mass (LVM) and heart sympathetic activity even in nonhypertensive subjects. These factors are predictors of cardiovascular morbidity and mortality independent of other traditional risk factors. We evaluated the effect of losartan and spironolactone on LVM and heart sympathetic activity in prehypertensive obese subjects. A 16-week blinded randomized trial was performed in middle-aged men selected from a Health Public program. Anthropometric and clinical variables were measured at baseline and after losartan (50 mg/day; n ¼ 25) or spironolactone (25 mg/day; n ¼ 25) treatment. Heart sympathetic activity was evaluated with 60-min electrocardiograph monitoring, and spectral analysis was carried out. LVM was measured by echocardiography according to Devereux and Reicheck's formula indexed for body height (m 2.7 ) to account for obesity. Anthropometric variables, systolic, and diastolic blood pressure levels decreased in both groups of treatment without statisticall difference between them. Losartan increased heart rate variability (from 70.0 to 82.3 ms; P ¼ 0.01), and decreased low frequency-high frequency index (from 6.6 to 4.9; P ¼ 0.001), and LVM (from 49.2 to 45.2 g; P ¼ 0.004). In the multiple regression analysis for factors associated with reduction in LVM; treatment with losartan, and decrease in SBP were the only factors included in the model (R 2 ¼ 0.60; P ¼ 0.003). To conclude losartan, but not spironolactone, decreased LVM and heart sympathetic overactivity in prehypertensive obese subjects after 16 weeks of treatment. Regression on LVM was associated with reduction on SBP levels.

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