scholarly journals Substitutions of the NBS1 gene and clinicopathological characteristics of young breast cancer patients

Biologija ◽  
2021 ◽  
Vol 67 (1) ◽  
Author(s):  
Roberta Vadeikienė ◽  
Aistė Savukaitytė ◽  
Rasa Ugenskienė ◽  
Jurgita Gudaitienė ◽  
Elona Juozaitytė

The purpose of this study was to determine characteristics potentially related to NBS1 mutations and polymorphisms in young (≤50 years of age) breast cancer patients. Blood from 80 breast cancer patients was collected. NBS1 mutations c.657_661del, p.R215W, p.I171V, and polymorphisms c.8360G>C, c.30537G>C were genotyped by the PCR-RFLP method. Two-sided Chi-square test was used for univariate analysis and logistic regression analysis was used to evaluate the odds ratio. No carriers of the c.657_661del, p.R215W and p.I171V mutations were found. NBS1 c.8360G>C logistic regression analysis showed that GC and CC genotypes compared with GG genotype had decreased risk of low grade tumour, 2.885-fold (OR = 2.885, 95% CI 0.173–0.735, P = 0.005) and 2.186-fold (OR = 2.186, 95% CI 0.188–0.888, P = 0.024), respectively. 8360 CC genotype (OR = 3.034, 95% CI 0.156–0.778, P = 0.010) significantly increased the chances of HER2 amplification compared to GG genotype. NBS1 8360 GC genotype had a higher risk for breast cancer progression (OR = 1.673, 95% CI 0.233–0.915, P = 0.027). The homozygote 8360 CC carriers had approximately a six times higher risk for the disease progress (OR = 5.946, 95% CI 0.098–0.585, P = 0.002). The prevalence of triple negative breast cancer type was significantly higher in individuals with NBS1 8360 CC genotype (OR = 2.186, 95% CI 0.188–0.888, P = 0.024). Regarding c.30537G>C polymorphism, none of the genotypes had a significant influence on pathological characteristics. NBS1 gene c.8360G>C polymorphism might be associated with breast cancer aggressiveness in young breast cancer patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18354-e18354
Author(s):  
Liang Yu ◽  
Xin Lei ◽  
Ying Lin

e18354 Background: Myelosuppression during chemotherapy can lead to life-threatening infections, dose reductions, treatment delays, as well as prolonged hospitalizations, early morbidity, and early mortality. According to NCCN guideline, Pegfilgrastim 6mg per cycle is recommended for breast cancer patients receiving chemotherapy, and dosage modification based on body weight is not required. However, primary PEGylated G-CSF prophylaxis comes with significant extra cost, which has a great impact on health care resources, especially for patients without insurance coverage. Methods: We analyzed clinical data of patients, weighing between 45 and 65 kilogram, received a single subcutaneous PEGylated recombinant human G-CSF injection at fixed doses of either 3 mg or 6 mg per chemotherapy cycle approximately 24 hours after completion of each cycle of chemotherapy. Data for this retrospective study were obtained from Thyroid and Breast Surgical Department of the First Affiliated Hospital of Sun Yat-sen University between July 1, 2017, and October 31, 2017. Results: 41 cycles in 33 patients were included in 3mg PEGylated G-CSF group, and 46 cycles in 39 patients were included in 6mg PEGylated G-CSF group. Among chemotherapy cycles, the incidence of neutropenic event was19.5%and 2.2% in 3mg PEGylated G-CSF group and 6mg PEGylated G-CSF group, respectively. No patients experienced dose reductions or treatment delays in both groups. Using single-factor Logistic Regression Analysis, we found that dose of PEGylated G-CSF(3mg vs 6mg) was significantly associated with occurrence of neutropenic event(p = 0.028). Multi-factor Logistic Regression Analysis also showed that dose of PEGylated G-CSFwas significantly associated with occurrence of neutropenic event (p = 0.031). Conclusions: Our study showed that dose of prophylactic PEGylated G-CSF was significantly associated with occurrence of neutropenic events. So adequate dose of PEGylated G-CSF is important to reduce chemotherapy induced neutropenic events and to guarantee the quality of chemotherapy in patients with breast cancer.


2021 ◽  
Author(s):  
Yuko Kanbayashi ◽  
Koichi Sakaguchi ◽  
Takeshi Ishikawa ◽  
Koichi Takayama ◽  
Tetsuya Taguchi

Abstract This retrospective study aimed to identify predictors for the development of palbociclib-induced neutropenia. This study retrospectively analysed 78 breast cancer patients who had received palbociclib at our hospital between January 2018 and May 2020. For the regression analysis of factors associated with palbociclib-induced neutropenia, variables were extracted manually from medical charts. The level of palbociclib-induced neutropenia was evaluated using the National Cancer Institute’s Common Terminology Criteria for Adverse Events (version 5). Multivariate ordered logistic regression analysis was performed to identify predictors for the development of neutropenia. Optimal cut-off thresholds were determined using receiver operating characteristic (ROC) analysis. Values of P < 0.05 (2-tailed) were considered significant. Significant factors identified included concomitant use of statin (odds ratio [OR] = 0.104, 95% confidence interval [CI] = 0.018–0.598; P = 0.011] and body mass index (BMI) (OR = 1.118, 95% CI = 1.007–1.241; P = 0.037). ROC analysis revealed that neutropenia (grade 4) was more likely to occur with a BMI ≥ 22.3 kg/m2. In conclusion, no concomitant use of statins and high BMI were identified as significant predictors for the development of palbociclib-induced neutropenia.


2020 ◽  
Vol 26 (8) ◽  
pp. 1836-1842 ◽  
Author(s):  
Andrea Botticelli ◽  
Simone Scagnoli ◽  
Michela Roberto ◽  
Luana Lionetto ◽  
Bruna Cerbelli ◽  
...  

Capecitabine is an oral prodrug of 5-fluorouracil with a relevant role in the treatment of breast cancer. Severe and unexpected toxicities related to capecitabine are not rare, and the identification of biomarkers is challenging. We evaluate the relationship between dihydropyrimidine dehydrogenase, thymidylate synthase enhancer region and methylenetetrahydrofolate reductase polymorphisms, 5-fluorouracil degradation rate and the onset of G3–4 toxicities in breast cancer patients. Genetic polymorphisms and the 5-fluorouracil degradation rate of breast cancer patients treated with capecitabine were retrospectively studied. Genetic markers and the 5-fluorouracil degradation rate were correlated with the reported toxicities. Thirty-seven patients with a median age of 58 years old treated with capecitabine for stages II–IV breast cancer were included in this study. Overall, 34 (91.9%) patients suffered from at least an episode of any grade toxicity while nine patients had G3–4 toxicity. Homozygous methylenetetrahydrofolate reductase 677TT was found to be significantly related to haematological toxicity (OR = 6.5 [95% IC 1.1–37.5], P = 0.04). Three patients had a degradation rate less than 0.86 ng/mL/106 cells/min and three patients greater than 2.1 ng/mL/106 cells/min. At a univariate logistic regression analysis, an altered value of 5-fluorouracil degradation rate (values < 0.86 or >2.10 ng/mL/106 cells/min) increased the risk of G3–4 adverse events (OR = 10.40 [95% IC: 1.48–7.99], P = 0.02). A multivariate logistic regression analysis, adjusted for age, comorbidity and CAPE-regimen, confirmed the role of 5-fluorouracil degradation rate as a predictor of G3–4 toxicity occurrence (OR = 10.9 [95% IC 1.2–96.2], P = 0.03). The pre-treatment evaluation of 5-fluorouracil degradation rate allows to identify breast cancer patients at high risk for severe 5-FU toxicity.


2018 ◽  
Vol 4 (Supplement 2) ◽  
pp. 79s-79s
Author(s):  
T. Fadelu ◽  
R. Damuse ◽  
L. Pecan ◽  
L. Greenberg ◽  
S. Danjoue ◽  
...  

Background: Obesity and metabolic syndrome (MS) have been linked to increased risk of breast cancer recurrence and mortality in prospective cohorts. These studies have mostly occurred in high-income countries. Little is known about rates of obesity and what factors predict obesity in breast cancer patients from low- and low-middle income countries (LMIC). However, there are increasing rates of obesity in the general population of LMICs. Hôpital Universitaire de Mirebalais (HUM) in Haiti established the main public comprehensive cancer center in the country in 2013. The facility serves patients from all around the country. Aim: To establish the prevalence of obesity in a retrospective cohort of breast cancer patients at HUM, and evaluate the association between living in urban areas and obesity in this population. Methods: We evaluated 1035 women who had their first visit between July 1, 2013 and December 31, 2016, with a coded diagnosis of breast cancer, and who had been followed in the HUM program for ≥ 90 days. We abstracted their first recorded height, weight and blood pressure (BP). We identified individuals who met criteria for obesity (body mass index [BMI] ≥ 30 kg/m2), systolic hypertension (systolic BP [SBP] ≥ 135 mmHg), and diastolic hypertension (diastolic BP [DBP] ≥ 90 mmHg). After exclusion of missing data in the variables of interest, the final analysis cohort was 678. We classified home commune location as rural or urban based on World Bank and UN standards. We used logistic regression analysis to determine the odds of being obese for individuals living in urban areas compared with rural dwellers. Results: 179 breast cancer patients (26.4%) had BMI ≥ 30, of which 58 (8.5%) were morbidly obese (BMI ≥ 35). 309 (45.6%) patients had systolic hypertension (HTN) and 180 (26.6%) had diastolic HTN. 417 (61.5%) lived in urban areas; 125 (30%) of urban dwellers were obese while only 20.7% of rural dwellers were obese. The crude OR for obesity in urban versus rural areas was 1.64 (95% CI: 1.16-2.36). Using logistic regression analysis and controlling for age the OR for obesity in urban areas was 1.67 (95% CI: 1.15-2.40), P = 0.0162. We did a similar analysis for morbid obesity, while controlling for age, the OR in urban compared with rural patients was 2.16 (95% CI: 1.15-4.03), P = 0.0162. There were no statistically significant differences in SBP and DBP comparing rural and urban patients. Conclusion: HUM breast cancer patients from urban areas were more likely to be obese than rural dwellers. Urban patients were twice as likely to be morbidly obese. There were no differences in HTN between the groups. Higher rates of obesity in the HUM breast cancer population is partly driven by the higher proportion of urban patients. Further studies need to be done to evaluate the causes and mediators of obesity as well as its effect on patient cancer outcome in Haiti.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuko Kanbayashi ◽  
Koichi Sakaguchi ◽  
Takeshi Ishikawa ◽  
Koichi Takayama ◽  
Tetsuya Taguchi

AbstractThis retrospective study aimed to identify predictors for the development of palbociclib-induced neutropenia. This study retrospectively analysed 78 breast cancer patients who had received palbociclib at our hospital between January 2018 and May 2020. For the regression analysis of factors associated with palbociclib-induced neutropenia, variables were extracted manually from medical charts. The level of palbociclib-induced neutropenia was evaluated using the National Cancer Institute’s Common Terminology Criteria for Adverse Events (version 5). Multivariate ordered logistic regression analysis was performed to identify predictors for the development of neutropenia. Optimal cut-off thresholds were determined using receiver operating characteristic (ROC) analysis. Values of P < 0.05 (2-tailed) were considered significant. Significant factors identified included concomitant use of statin (odds ratio [OR] = 0.104, 95% confidence interval [CI] = 0.018–0.598; P = 0.011) and body mass index (BMI) (OR = 1.118, 95% CI = 1.007–1.241; P = 0.037). ROC analysis revealed that neutropenia (grade 4) was more likely to occur with a BMI ≥ 22.3 kg/m2. In conclusion, no concomitant use of statins and high BMI were identified as significant predictors for the development of palbociclib-induced neutropenia.


2021 ◽  
Vol 11 ◽  
Author(s):  
Hongwei Yu ◽  
Xianqi Meng ◽  
Huang Chen ◽  
Jian Liu ◽  
Wenwen Gao ◽  
...  

ObjectivesThis study aimed to investigate whether radiomics classifiers from mammography can help predict tumor-infiltrating lymphocyte (TIL) levels in breast cancer.MethodsData from 121 consecutive patients with pathologically-proven breast cancer who underwent preoperative mammography from February 2018 to May 2019 were retrospectively analyzed. Patients were randomly divided into a training dataset (n = 85) and a validation dataset (n = 36). A total of 612 quantitative radiomics features were extracted from mammograms using the Pyradiomics software. Radiomics feature selection and radiomics classifier were generated through recursive feature elimination and logistic regression analysis model. The relationship between radiomics features and TIL levels in breast cancer patients was explored. The predictive capacity of the radiomics classifiers for the TIL levels was investigated through receiver operating characteristic curves in the training and validation groups. A radiomics score (Rad score) was generated using a logistic regression analysis method to compute the training and validation datasets, and combining the Mann–Whitney U test to evaluate the level of TILs in the low and high groups.ResultsAmong the 121 patients, 32 (26.44%) exhibited high TIL levels, and 89 (73.56%) showed low TIL levels. The ER negativity (p = 0.01) and the Ki-67 negative threshold level (p = 0.03) in the low TIL group was higher than that in the high TIL group. Through the radiomics feature selection, six top-class features [Wavelet GLDM low gray-level emphasis (mediolateral oblique, MLO), GLRLM short-run low gray-level emphasis (craniocaudal, CC), LBP2D GLRLM short-run high gray-level emphasis (CC), LBP2D GLDM dependence entropy (MLO), wavelet interquartile range (MLO), and LBP2D median (MLO)] were selected to constitute the radiomics classifiers. The radiomics classifier had an excellent predictive performance for TIL levels both in the training and validation sets [area under the curve (AUC): 0.83, 95% confidence interval (CI), 0.738–0.917, with positive predictive value (PPV) of 0.913; AUC: 0.79, 95% CI, 0.615–0.964, with PPV of 0.889, respectively]. Moreover, the Rad score in the training dataset was higher than that in the validation dataset (p = 0.007 and p = 0.001, respectively).ConclusionRadiomics from digital mammograms not only predicts the TIL levels in breast cancer patients, but can also serve as non-invasive biomarkers in precision medicine, allowing for the development of treatment plans.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 1078-1078
Author(s):  
Christof Vulsteke ◽  
Alena Pfeil ◽  
Barbara Brouwers ◽  
Matthias Schwenkglenks ◽  
Robert Paridaens ◽  
...  

1078 Background: Recently we described the impact of genetic variability on severe toxicity in breast cancer patients receiving (neo-) adjuvant FEC chemotherapy (Annals of Oncology 2013, In Press). We now further assessed the impact of a wide range of patient-related factors on FEC toxicity in routine clinical setting. Methods: Patients with early breast cancer receiving (neo-)adjuvant 6 cycles FEC or sequential 3 cycles of FEC and 3 cycles D were retrospectively evaluated through electronic chart review for febrile neutropenia (primary endpoint; CTC 3.0). Age at diagnosis, body mass index, body surface area, number of cycles received, germline genetic polymorphisms, and baseline biochemical variables (white blood cell count, absolute neutrophil count, platelets, aspartate aminotransferase, alanine aminotransferase, total bilirubin and creatinine) were available for most patients (missing data <10%). All patients had follow up for progression free survival (PFS) and overall survival (OS). Multivariate logistic regression analysis was performed including univariate associates of outcome with a p-value <0.25. Results: We identified 1,031 patients treated between 2000-2010 with 6x FEC (n=488) or 3x FEC followed by 3x D (n=543). 174 (16.9%) patients developed febrile neutropenia during FEC. After logistic regression analysis febrile neutropenia was found to be significantly associated with carriers of the rs45511401 variant T-allele in the MRP1 gene found in 12% of patients (p= 0.03, OR1.99, CI 1.07-3.71) and with increasing serum creatinine values (p=0.05 OR 4.58/CI 0.99-20.98); all other investigated patient-related parameters were not retained by the model. At a mean follow up of 5.2 years, the occurrence of febrile neutropenia was not correlated with PFS and OS. Conclusions: In this study, only the baseline level of serum creatinine and germline genetic polymorphisms in the MRP-1 gene were predictive for the occurrence of febrile neutropenia in patients receiving FEC chemotherapy. The occurrence of febrile neutropenia did not seem to impact on outcome.


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