Histological Confirmed Breast Cancer Research Articles

Somatic Mutations in KEAP1-NRF2 Complex in Breast Cancer.

Breast cancer remains the leading cause of cancer deaths for women. Long-term estrogen exposure is considered carcinogenic due to semiquinone production and to compromised detoxification. Metabolic regulator polymorphisms, such as KEAP1 (rs1048290) and NRF2 (rs35652124, rs6721961, rs6706649), can be valuable in understanding the individual cytoprotection profile. Thus, we aim to genotype these polymorphisms in blood, tumours and surrounding tissue, to identify somatic mutations and correlate it to prognoses. A total of 23 controls and 69 women with histological confirmed breast cancer were recruited, and DNA from blood/surrounding/tumour tissue was genotyped. Genotyping and clinicopathological data were correlated. We verified that rs35652124 presents different genotype distribution between the blood/surrounding tissue (p-value = 0.023) and tumour/surrounding tissues (p-value = 0.041). Apart from rs35652124 and considering the histological grade, the other four polymorphisms have different distributions among different tissues. There is a tendency towards the loss of heterozygosity in the surrounding tissue when compared to blood and tumour tissues, and higher genotype variability in histologic grade 2. These somatic mutations and different distribution patterns may indicate a heterogeneous and active microenvironment, influencing breast cancer outcome. Additionally, it would be pertinent to evaluate the predictive value of the histologic grade 2 considering somatic mutation profiles and distributions.

Experiences and desired nursing assistance of women on out-patient breast cancer chemotherapy in Southeastern Nigeria.

This study explored the experiences and nursing support needs of women undergoing out-patient breast cancer chemotherapy in two teaching hospitals in Southeastern Nigeria. Using a qualitative descriptive design, based on grounded theory approach and focus group discussion (FGD) methodology, 20 histological confirmed breast cancer patients at different stages of combination chemotherapy (cyclophosphamide, doxorubicin, and fluorouracil ) were purposively selected and engaged in FGDs at two surgical oncology clinics. Data saturation was reached at the fourth FGD. The audio-taped and transcribed data were content analyzed using thematic approach. Participants were all christians of the Igbo-speaking ethnic group, and aged between 36 and 66years. Most were married and had at least primary education. Five themes emerged from the FGDs: inadequate preparation for chemotherapy; chemotherapy scary, distressful, and financially demanding; hope, faith and courage sustained treatment; self-care actions initiated to 'weather the storm'; and nursing assistance desired to foster hope and enhance patients' acceptance of, adjustment and adherence to breast cancer chemotherapy in Nigeria. Culture influenced their chemotherapy perspectives and coping. Women with breast cancer in southeastern Nigeria desired but were inadequately prepared to cope with chemotherapy distress they experienced. Nurses could help patients to accept and navigate through chemotherapy by initiating and supporting effective and efficient self-care actions that are culturally congruent.Copyright © 2015 John Wiley & Sons, Ltd.

Who may benefit from preoperative breast MRI? A single-center analysis of 1102 consecutive patients with primary breast cancer.

Several authors question the potential benefit of preoperative magnetic resonance imaging (MRI) against the background of possible overdiagnosis, false-positive findings, and unnecessary resections in patients with newly diagnosed breast cancer. In order to reveal a better selection of patients who should undergo preoperative MRI after histological confirmed breast cancer, the present analysis was implemented. We aimed to evaluate the influence of preoperative breast MRI in patients with newly diagnosed breast cancer to find subgroups of patients that are most likely to benefit from preoperative MRI by the detection of occult malignant foci. A total of 1102 consecutive patients who underwent treatment for primary breast cancer between 2002 and 2013 were retrospectively analyzed. All patients underwent triple assessment by breast ultrasound, mammography, and bilateral breast MRI. MRI findings not seen on conventional imaging that suggested additional malignant disease was found in 344 cases (31.2 %). Histological confirmed malignant foci were found in 223 patients (20.2 %) within the index breast and in 28 patients (2.5 %) in the contralateral breast. The rate of false-negative biopsies was 31 (2.8 %) and 62 (5.6 %), respectively. Premenopausal women (p = 0.024), lobular invasive breast cancer (p = 0.02) as well as patients with high breast density [American College of Radiology (ACR) 3 + 4; p = 0.01] were significantly associated with additional malignant foci in the index breast. Multivariate analysis confirmed lobular histology (p = 0.041) as well as the co-factors "premenopausal stage" and "high breast density (ACR 3+4)" (p = 0.044) to be independently significant. Previous studies revealed that breast MRI is a reliable tool for predicting tumor extension as well as for the detection of additional ipsilateral and contralateral tumor foci in histological confirmed breast cancer. In the present study, we demonstrate that especially premenopausal patients with high breast density as well as patients with lobular histology seem to profit from preoperative MRI.

Association between vegetable, fruit and carbohydrate intake and breast cancer risk in relation to physical activity.

Although the nutritional may exert effect on the breast cancer risk, it is not clear whether the role diet is the same in sedentary and physically active women. The aim of this study was to evaluate the association between fruit, vegetable and carbohydrate intake and the risk of breast cancer among Polish women considering their physical activity level. A case-control study was conducted that included 858 women with histological confirmed breast cancer and 1,085 controls, free of any cancer diagnosis, aged 28-78 years. The study was based on a self-administered questionnaire to ascertain physical activity, dietary intake, sociodemographic characteristics, reproductive factors, family history of breast cancer, current weight and high, and other lifestyle factors. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated in unconditional logistic regression analyses including a broad range of potential confounders. With comparison of the highest vs lowest quartile of intake, strong significant associations were observed for total vegetables (OR=0.37, 95%CI=0.20-0.69 P for trend <0.01 and OR=0.53, 95%CI=0.29-0.96, P for trend <0.02), and total fruits (OR=0.47, 95%CI=0.25-0.87, P for trend <0.05 and OR=0.47, 95%CI=0.24-0.90, P for trend <0.02) among women characterized by the lowest and the highest quartile of physical activity. No associations were observed for total carbohydrate intake. Additional analysis showed a positive association for sweets and desert intake among women in the lowest quartile of physical activity (OR=3.49, 95%CI=1.67-7.30, P for trend <0.009) for extreme quartiles of intake comparing to the referent group. The results suggest that a higher consumption of vegetable and fruit may be associated with a decreased risk of breast cancer, especially among women who were low or most physically active throughout their lifetimes. These findings do not support an association between diet high in carbohydrate and breast cancer. However, a higher intake of sweets and deserts may by associated with an increased risk of breast cancer among women who were less physically active.

Dietary Fat and Physical Activity in Relation to Breast Cancer among Polish Women

Dietary fat has been inconsistently associated with the risk of breast cancer. The purpose of this study was to examine the relationship between meat and animal and plant fat intake and breast cancer risk in subgroups by total lifetime physical activity, using data from a case-control study conducted in the Region of Western Pomerania, Poland. The study included 858 women with histological confirmed breast cancer and 1,085 controls, free of any cancer diagnosis. The study was based on a self-administered questionnaire including questions about socio-demographic characteristics, current weight and height, reproductive factors, family history of breast cancer and lifestyle habits. Unconditional logistic regression was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs). High animal fat intake significantly increased OR from 1.7 times (OR=1.66, 95%CI=1.07-3.59) to 2.9 times (OR=2.9, 95%CI=1.37- 6.14) independent of physical activity level, comparing the third versus the lowest quartile. Women with a high intake of red meat or processed meat and low physical activity showed increased risk of breast cancer: OR=2.70, 95%CI=1.21-6.03 and 1.78, 95%CI=1.04-3.59, respectively. The plant fat dietary pattern was negatively associated with breast cancer in sedentary women (OR=0.57, 95%CI=0.32-0.99). These results indicated that a diet characterized by a high consumption of animal fat is associated with a higher breast cancer risk in sedentary women, while consumption of plant fat products may reduce risk in the same group.

Impact of menstrual and reproductive factors on breast cancer risk in Tunisia: a case–control study

This report examined the relationship between menstrual and reproductive factors and breast cancer risk. The case-control study was conducted on 400 women with histological confirmed breast cancer operated during the 2006-2009 period at Farhat Hached University Hospital, Sousse, Tunisia, and 400 cancer-free controls, aged 25-75 years. The menstrual and reproductive history was assessed using a structured questionnaire. Odds ratios (ORs), 95 % confidence intervals (CI) and a full confounding assessment, included in this analysis, were derived using logistic regression. A positive family history of breast cancer was associated with a significantly increased risk of breast cancer (OR = 5.15, 95 % CI 1.48-17.94). Significant risk reduction was found with later age at menarche (P = 0.02). There was an insignificant increase in risk with later age at menopause (≥ 51 years; OR = 1.87), later age at first live birth (≥ 26 years; OR = 1.76) and nulliparous women compared to parous women (OR = 2.35). An insignificant decrease in risk was observed with increasing parity number (≥ 3 delivery; OR = 0.86). A significantly reduced risk of breast cancer was found for those women whose lifetime duration of breastfeeding was 73-108 months and for those who breastfed for ≥ 109 months (P = 0.00). Our findings suggest that age at menarche and breastfeeding history have great effects on breast cancer risk among Tunisian women.

Physical activity reduces breast cancer risk: A case–control study in Tunisia

Purpose: This study examined the relationship between lifetime history of physical activity and breast cancer risk. Methods: The case–control study was conducted on 400 women with histological confirmed breast cancer operated during the 2006–2009 period at Farhat Hached University Hospital, Sousse, Tunisia, and 400 cancer-free controls, aged 25–75 years. The physical activity was assessed using a structured questionnaire on each activity: type, duration, frequency, and intensity. Odds ratios (ORs), 95% confidence intervals (CI) and a full confounding assessment, included in this analysis, were derived using logistic regression. Results: These cases had lower lifetime averages for total physical activity for both forms of activity measurements (hours/week/year and MET-hours/week/year) and (Ptrend<0.001 and Ptrend=0.002, respectively). Significant risk reductions were found in total physical activity for both forms of activity measurements (OR=0.27, 95% CI: 0.18–0.52, OR=0.42, 95% CI: 0.26–0.73, respectively) for the highest versus the lowest level of activity (Ptrend=0.001 and 0.004, respectively). The stratification by menopausal status showed a significant 56% reduction in breast cancer risk for post-menopausal women (Ptrend=0.001, adjusted for age). The risk was further reduced to 68% (Ptrend=0.002, multivariate adjusted). Among pre-menopausal women, the total physical activity was not significantly associated with reduced risk, ORs were 0.88 (95% CI: 0.40–1.99, age adjusted) and 0.43 (95% CI: 0.12–1.38, multivariate adjusted). Conclusion: These data are in concordance with the majority of previous reports which involved physical inactivity as an important risk factor for breast cancer.

Body mass index and waist circumference are predictor biomarkers of breast cancer risk in Iranian women

Both obesity and breast cancer incidence increased dramatically during two recent decades in a rapidly changing society in northern Iran. In this study, we examined the ability of body mass index (BMI) and waist circumference (WC) as predictor biomarkers of breast cancer risk in Iranian women. In a case-control study of 100 new cases of histological confirmed breast cancer and 200 age-matched controls, in Babol, we measured weight, height, waist and hip circumference at time of diagnosis with standard methods. The data of demographic, characteristics, reproductive and lifestyle factors were collected by interview. We used both regression and receiver operator characteristics (ROC) analysis to estimate the predictive ability of BMI and WC for breast cancer as estimated by area under the curve (AUC). The results showed a significant difference in the mean of weight, BMI and WC between patients and controls in pre- and postmenopausal women (P<0.001). While after adjusting for BMI, no longer an association between WC and breast cancer was found. The overall accuracy of observed BMI and WC were 0.79 (95% CI: 0.74-0.84) and 0.68 (95% CI: 0.61-0.74), respectively. The accuracy of BMI and WC were 0.82 (95% CI: 0.76-0.89), 0.75(0.67-0.83) for premenopausal and 0.77(0.68-0.85), 0.60 (0.50-0.71) for postmenopausal women, respectively. BMI and WC are predictor biomarkers of breast cancer risk in both pre- and postmenopausal Iranian women while after adjusting for BMI, no longer an association between WC and breast cancer was observed. These findings imply to perform breast cancer screening program in women with a higher BMI and WC.

Breast cancer risk and common single nucleotide polymorphisms in homologous recombination DNA repair pathway genes XRCC2, XRCC3, NBS1 and RAD51

The possible role for DNA repair deficiencies in cancer development, namely in breast cancer has been the subject of increasing interest since it has been reported that breast cancer patients might be deficient in the repair of DNA damage. Exposure to ionizing radiation has been pointed out as a risk factor for breast cancer, and the type of DNA lesions induced by this carcinogen can be repaired by homologous recombination DNA repair (HRR) pathway. To evaluate the potential modifying role of some single nucleotide polymorphisms (SNP) in HRR involved genes on the individual susceptibility to breast cancer we carried out a hospital based case–control study in a Caucasian Portuguese population (289 histological confirmed breast cancer patients and 548 control individuals). We genotyped 4 SNPs in 4 different HRR pathway genes, XRCC2 (Ex3+442G>A, R188H, rs3218536), XRCC3 (Ex8-5C>T, T241M, rs861539), NBS1 (Ex5-32C>G, E185Q, rs1805794) and RAD51 5′UTR (Ex1-59G>T, rs1801321), tagging 41 SNPs in these genes. The frequency of the different polymorphisms in the Portuguese control population is similar to the ones reported for other Caucasian populations, and the deviation of the Hardy–Weinberg equilibrium was only observed for the XRCC2 (Ex3+442G>A, R188H, rs3218536) polymorphism in the control population. The results obtained, after logistic regression analysis, did not reveal a major role of these polymorphisms on breast cancer susceptibility. However, when the population was stratified according to breast feeding (women that breast fed and women that never breast fed) it is observed, in women that never breast fed, that the heterozygous individuals for the XRCC2 (Ex3+442G>A, R188H, rs3218536) polymorphism have a decreased risk for breast cancer [adjusted OR=0.45; 95% CI=0.22–0.92] (P=0.03). Additionally, after stratification according to menopausal status, our results suggest that post-menopausal women carrying at least one variant allele for the XRCC3 (Ex8-5C>T, T241M, rs861539) polymorphism have a lower risk for breast cancer [adjusted OR=0.67; 95% CI, 0.47–0.94] (P=0.03). Most of the studies suggest that breastfeeding may be responsible for 2/3 of the estimate reduction of breast cancer. The longer the duration of breastfeeding the lower the potential risk associated with breast cancer. Therefore, in our study the potential protective role of the variant allele of XRCC2 (Ex3+442G>A, R188H, rs3218536), in never breast fed women, might be related with a more efficient DNA repair activity.

Lifetime physical activity and the risk of breast cancer: A case–control study

Background: The association between breast cancer and lifetime histories of physical activity was studied to determine whether exercise may reduce development of this cancer. Methods: The case–control study was based on 250 women living in the Region of Western Pomerania with histological confirmed breast cancer operated during 1999–2003 in the Szczecin hospitals, and 301 controls, free of any cancer diagnosis, aged 35–75 years. Physical activity was assessed using a self-administered questionnaire with questions on type of activity, duration, frequency, and intensity for each type of activity. Data on physical activity from exercise/sports, household and outdoor chores, and occupational activity separately throughout a woman's lifetime were collected. Recreational physical activity was examined for the four age periods (14–20, 21–34, 35–50, and after the age of 50 years). Logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CI) and a full assessment of confounding was included in analysis. Results: Lifetime total physical activity among all women was associated with a reduced breast cancer risk; after controlling for potential confounders the multivariate ORs associated with <110, 110–150, and >150 metabolic equivalent (MET)-hours/week/year were 1.00 (referent), 0.60 (95% CI: 0.60–1.06), and 0.43 (95% CI: 0.25–0.75), respectively ( P trend = 0.004). Analyses by type of lifetime activity for household and recreational activities revealed significant risk reductions: 1.00 (referent); 0.51, 95% CI: 0.29–0.87; 0.54, 95% CI: 0.31–0.94 ( P trend = 0.002), and 1.00 (referent); 0.54, 95% CI: 0.31–0.94; 0.40, 95% CI: 0.22–0.70 ( P trend < 0.001), respectively. For lifetime occupational activity a modest association could not be ruled out when measured the activity by average annual hours/week; the ORs were 0.51, 95% CI: 0.29–0.91, and 0.58, 95% CI: 0.33–1.00, the inverse trend in risk was not significant ( P trend = 0.51). Women who started recreational activity after age of 20 years had much more higher breast cancer risk than either those who were active between ages 14 and 20 years and were inactive after age 20 years or continued their activity throughout adult life. Conclusions: These data are in concordance with the hypothesis that lifetime total physical activity is associated with decreased breast cancer risk. They also suggest that recreational physical activity at ages 14–20 years is the most beneficial. In addition, these findings confirm the majority of previous reports which implicated physical inactivity as important risk factor for breast cancer.

Sentinel node biopsy in breast cancer after neoadjuvant therapy

691 Background: Sentinel lymph node biopsy (SNL) for breast cancer is becoming clinical standard. However there is a discussion on the accuracy of SNL after neoadjuvant chemotherapy. The question is whether SNL biopsy is reliable or the false negative rate is too high? Methods: Twenty-nine patients were treated with neoadjuvant chemotherapy in a period of six months. We included patients with histological confirmed breast cancer stage II or III. Following they underwent SLN biopsy and the complete axillary lymph node dissection. At the same operation each patient received a breast conserving surgery or a mastectomy. Lymph node mapping was performed with Technetium99 Nanocolloid. Results: The mean age was 52 years (41–63yrs.). The clinical examination showed in 90% none palpable lymph nodes. The axillary ultrasonography indicated positive lymph node in 45% (13/29). The SNL identification rate was 100% (29/29). In 27/29 patients (93%) SLNs accurately predicted the axillary status. Eight patients of the 29 had positive SNLs (28%), and in 6 of those 8 patients, the SNL was the only positive node (75%). Two patients had false-negative SLN biopsy (7). SNL biopsy had a sensitivity of 80% and a specificity of 87,5%. Compared with the 45% positive nodes by ultrasound before chemotherapy, only 31% (4/13) showed furthermore positive SNLs after neoadjuvant chemotherapy. Conclusions: According to the prior studies SNL biopsy was possible after neoadjuvant chemotherapy. But there was a false negative rate of 7%. It is questionable if SLN biopsy is an option for patients who received neodadjuvant chemotherapy. No significant financial relationships to disclose.