Variability in DNA Repair Capacity Levels among Molecular Breast Cancer Subtypes: Triple Negative Breast Cancer Shows Lowest Repair.

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.

High DRC Levels Are Associated with Let-7b Overexpression in Women with Breast Cancer.

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.

Renal Cell Carcinoma With Tumor Thrombus: A Case Series in Puerto Rico.

INTRODUCTION:  Renal cell carcinoma (RCC) is one of the most common types of kidney cancer. While RCC tends to present as a localized tumor, a notable proportion may present with distant metastasis. In some instances, RCC may also present with intravascular tumor extension, often called tumor thrombus (TT). Its presence confers a worse prognosis and has important implications for the tumor's staging and treatment. Despite extensive documentation of RCC TT in the US, limited data exists regarding its presentation, management, and outcomes in Puerto Rico (PR). This study aims to broaden the available information on RCC TT, emphasizing surgical management and outcomes. We also provide descriptive data on patient demographics and clinical presentation to improve decision-making among clinicians caring for Puerto Rican men and women. METHODS:  In this single-center, retrospective study, we evaluated patients who underwent partial or total nephrectomy at Saint Luke's Episcopal Medical Center between 2018 and 2022. Data was abstracted from electronic health records (EHR). Patients without documented evidence of TT during the peri-operative period were excluded from the study. A total of 220 patient records were evaluated, of which 12 met the inclusion criteria for the study. Cases were categorized using the latest RCC TT guidelines. Central tendency measurements were used to describe the sample distribution. The mean was considered to make assumptions regarding the prevalent observations, and the median was considered to rule out possible outliers. Categorical data were evaluated using proportion analyses, including TT extension level and BMI variables. Fisher's exact test evaluated the association between the World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade and TT extension level. RESULTS:  Most patients lacked TT-related symptoms. The most severe presenting symptom was a pulmonary embolism (8.3%). Hypertension (83.3%), BMI greater than 25 at the time of diagnosis (75%), and type 2 diabetes mellitus (66.7%) were the most common comorbid conditions within our cohort. Nearly 75% of patients underwent laparoscopic radical nephrectomy with TT resection. One left-sided level III case was managed by laparoscopic-assisted open radical nephrectomy with a right subcostal incision. There were zero intraoperative complications and two postoperative complications. The histopathological reports of all cases were consistent with clear cell carcinoma, and half of the cases (n=6) were WHO/ISUP G4. All patients are alive and free of disease. CONCLUSION:  RCC is a common renal neoplasm in PR that can present with intravascular tumor extension. Our findings do not establish a definitive association between BMI, tumor size, WHO/ISUP grading, and TT extension level. Our study shows that laparoscopic removal of RCC TT is a safe and effective approach. However, the generalizability of our findings is limited by the study's design and sample size. Future research should focus on identifying predictive markers, establishing effective screening protocols, and determining if our hybrid approach has comparable outcomes to the standard open approach.

Association between DNA repair capacity and body mass index in women.

OBJECTIVE: Examine whether DNA repair capacity (DRC) levels are associated with body mass index (BMI) in adult women. DESIGN AND PARTICIPANTS: A nested study composed of 539 women without breast cancer (BC) from a case-control BC study in addition to 104 that were recruited later for a total of 643. MEASUREMENTS: DRC levels were measured in lymphocytes using a host-cell reactivation assay with a luciferase reporter gene damaged by UVC. This assay measures the efficiency of nucleotide excision repair (NER). Log-binomial regression model was used. The prevalence ratio (PR) was used to evaluate the magnitude of the association between the BMI and DRC levels. An assessment of interaction terms was performed with the likelihood ratio test. The confounding effect was assessed by comparing the point estimates of the crude and adjusted PR. RESULTS: The 75th percentiles of DRC levels of the women with a BMI between 18 and 25 and > 25 showed statistically significant differences. The prevalence of a DRC ≤ 5 % among women with BMI > 25 is 1.24 (95 % CI: 1.03, 1.48) times the prevalence of having a DRC ≤ 5 % among the women with BMI ≤ 25 after adjustments for different covariates. This excess was statistically significant (p < 0.05). Women with a family history of cancer had an estimated PR of 1.25 (95 % CI, 0.87-1.39; P ≥ 0.05); and women with no family history of cancer, the estimated PR was 1.6 (95 % CI, 1.14-2.22; p ≤ 0.05). CONCLUSIONS: Women with BMI > 25 tend to have lower DRC levels. When having a family history of cancer, the PR of low DRC levels in overweight/obese individuals was not statistically significant. However, the PR of low levels of DRC in overweight/obese individuals with no family history of cancer was statistically significant.