Knowledge, Attitude, and Practice (KAP) toward Cervical Cancer Screening among Adama Science and Technology University Female Students, Ethiopia

Background. Cervical cancer is a complication of Human Papillomavirus (HPV) infection is the second most common cancer in women worldwide. Eighty percent of the cases occur in low-resource countries. According to the 2009 World Health Organization report, the age-adjusted incidence rate of cervical cancer in Ethiopia was 35.9 per 100,000 patients with 7619 annual number of new cases and 60-81 deaths every year. The study is aimed at assessing the level of knowledge, attitude, and practice concerning cervical cancer among female students at Adama Science and Technology University. Methodology. An institutional based cross-sectional study was conducted among 667Adama Science and Technology University female students. A simple random sampling method was used to select the respondents. Structured self-administered questionnaire was used for data collection. Results. About 404 (60.6%) of the participants heard about cervical cancer, 478 (71.7%) had positive attitude towards cervical cancer screening, and only 15 (2.2%) participants were screened for cervical cancer. Lack of information about cervical cancer was the most reported reason for not attending to cervical cancer screening. Conclusion and Recommendation. The study showed that there was low knowledge on cervical cancer and screening for premalignant lesion among women. There is a need to promote and encourage women to early cervical cancer screening at precancerous stage by informing their susceptibility to cervical cancer.

Indeterminate (B3) Breast Lesions and the Ongoing Role of Diagnostic Open Biopsy

Introduction. Due to their uncertain malignant potential, indeterminate breast lesions on core needle biopsy (CNB) require diagnostic open biopsy (DOB). This study evaluated DOB results given largely benign pathology. Lesions included are atypical papilloma, atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), and radial scar/complex sclerosing lesions (RS/CSL). Methodology. A retrospective audit from 2010 to 2017 analysed patients with a screen-detected suspicious lesion and indeterminate (B3) CNB diagnosis. Primary outcome was the malignancy upgrade rate, with secondary evaluation of patient factors predictive of malignancy including age, symptoms, mammogram characteristics, lesion size, biopsy method, and past and family history. Results. 152 patients (median age 57 years) were included, with atypical papillomas being the largest subgroup (44.7%). On DOB histology, 99.34% were benign, resulting in a 0.66% malignancy upgrade rate. Patient characteristic analysis identified 86.84% of B3 lesions were in patients greater than 50 years old. 90.13% were asymptomatic, whilst 98.68% and 72.37% had a negative past and family history. Majority 46.71% of lesions had the mammogram characteristic of being a mass. However, with 57.89% of the lesion imaging size less than 4 mm, a corresponding 60.5% of core needle biopsies were performed stereotactically. The small malignant subgroup limited predictive factor evaluation. Conclusion. Albeit a low 0.66% malignancy upgrade rate in B3 lesions, no statistically significant patient predictive factors were identified. Until predictive factors and further assessment of vacuum-assisted excision (VAE) techniques evolve, DOB remains the standard of care.

Survival Outcomes among Human Epidermal Growth Factor Receptor 2- (HER2-) Positive Breast Cancer Patients at Kenyatta National Hospital

Introduction. HER2-positive breast cancer is associated with poor outcomes and higher mortality rates than other breast cancer subtypes. The advent of trastuzumab has significantly changed the natural history of HER2-positive breast cancer. However, it is not an affordable treatment option in sub-Saharan African countries. Because of the expense, most patients in our setting do not receive trastuzumab for the optimal control of their disease. Additionally, there is a lack of comprehensive data about the survival outcomes of HER2-positive breast cancer patients in our setting. The present study was aimed at determining the survival outcomes among HER2-positive breast cancer patients at the Oncology Department of Kenyatta National Hospital. Methods. A hospital-based retrospective cohort design was used to evaluate the survival outcomes among patients with HER2-positive breast cancer treated from 1st January 2015 to 31st December 2019 at Kenyatta National Hospital. A total of 50 eligible HER2-positive breast cancer patients were included in the study. In the predesigned data abstraction tool, data were collected by reviewing the medical records of the patients. The data were entered and analyzed using the Statistical Package for the Social Sciences version 27 software. The mean survival time was estimated using Kaplan-Meier survival analysis. Results. The mean age was 45.44 ± 12.218 years, with a majority (80%) of the patients being below 60 years. Most patients (64%) had advanced-stage disease. The median follow-up time for patients with curative stages of breast cancer was 41 months, while the median follow-up time for those with the advanced incurable disease was 8.5 months. The 4-year survival rate was 62.5% for those curable-stage HER2-positive breast cancer compared to 5.6% for those with metastatic disease at presentation. Conclusion. The 4-year survival rate for both early-stage and advanced-stage HER2-positive breast cancer in our setting is suboptimal when compared to existing outcome data from health care systems where trastuzumab is more widely available.

CD44 Variant Exon 6 Isoform Expression as a Potential Predictor of Lymph Node Metastasis in Invasive Breast Carcinoma of No Special Type

Background. Invasive breast carcinoma of no special type (IBC-NST) is the most widespread invasive carcinoma subtype causing primarily regional metastases of the lymphatic node (LNM). The capacity of CD44 variant exon 6 (CD44v6) expression as an LNM predictor biomarker in IBC-NST was explored. Methods. We conducted a cross-sectional research with 48 paraffin blocks containing IBC-NST primary tumors that were divided into two groups by LNM. The assessment has been carried out in terms of age, tumor size, tumor grade, lymphovascular invasion (LVI), and CD44v6 expression. The expression of CD44v6 was analyzed on the grounds of immunohistochemical (IHC) staining, while other data were taken from archives. Statistical analysis is carried out by univariate, multivariate, and AUROC. Results. CD44v6 exhibits a dominant expression in IBC-NST tumor cells. Univariate analysis revealed a significant association between CD44v6 and LNM status ( p = 0.001 ). Multiple logistic regression results showed that CD44v6 expression and LVI were significantly associated with LNM with OR 10.7 (95% CI: 2.43 to 47.08) and 6.22 (95% CI: 1.4 to 27.88), respectively. CD44v6 expression was able to discriminate against LNM with AUROC 0.863 ± 0.053 (95% CI: 0.759 to 0.967) at the H-score cut-off 133.889 (75% sensitivity and 83.3% specificity). Conclusion. CD44v6 expression and LVI are potential predictors of LNM in IBC-NST. The H-score cut-off of the CD44v6 expression can also be used as a threshold for classification in further investigation.

Truncated WT1 Protein Isoform Expression Is Increased in MCF-7 Cells with Long-Term Estrogen Depletion

Background. The wt1 gene codes for a transcription factor that presents several protein isoforms with diverse biological properties, capable of positively and negatively regulating genes involved in proliferation, differentiation, and apoptosis. WT1 protein is overexpressed in more than 90% of breast cancer; however, its role during tumor progression is still unknown. Methodology. In this work, we analyzed the expression of WT1 isoforms in several breast cancer cells with different tumor marker statuses and an in vitro assay using MCF-7 cells cultured with long-term estrogen depletion (MCF-7 LTED cells) with the finality to mimic the process of switching from hormone-dependent to hormone-independent. Moreover, growth kinetics, sensitivity to tamoxifen, and relative expression analysis of ER and Her2/neu were performed. Results. Initially, the expression of 52-54 kDa protein isoform of WT1 in the breast cancer cell line ER (+) was detected by western blot and was absent in ER (-), and the 36-38 kDa protein isoform of WT1 was detected in all cell lines analyzed. The analysis of alternative splicing by RT-PCR shows that the 17AA (+)/KTS (-) isoform of WT1 was the most frequent in the four cell lines analyzed. In vitro, the MCF-7 cells in the estrogen depletion assay show an increase in the expression of the 52-54 kDa isoform of WT1 in the first 48 hours, and this was maintained until week 13, and later, this expression was decreased, and the 36-38 kDa isoform of WT1 did not show change during the first 48 hours but from week 1 showed an increase of expression, and this remained until week 27. Growth kinetic analysis showed that MCF-7 LTED cells presented a 1.4-fold decrease in cellular proliferation compared to MCF-7 cells cultured under normal conditions. In addition, MCF-7 LTED cells showed a decrease in sensitivity to the antiproliferative effect of tamoxifen ( p ≤ 0.05 ). Samples collected until week 57 analyzed by qRT-PCR showed an increase in the relative expression of the Her2/neu and ER. Conclusions. Modulation of protein isoforms showed differential expression of WT1 isoforms dependent on estrogen receptor. The absence of 52-54 kDa and the presence of the 36-38 kDa protein isoform of WT1 were detected in ER-negative breast cancer cell lines classified as advanced stage cells. Long-term estrogen depletion assay in MCF-7 cells increased the expression of the 36-38 kDa isoform and reduced the 52-54 kDa isoform, and these cells show an increase in the expression of tumor markers of ER and Her2/neu. MCF-7 LTED cells showed low proliferation and insensitivity to tamoxifen compared to MCF-7 cells in normal conditions. These results support the theory about the relationship of the 36-38 kDa isoform of WT1 and the absence of ER function in advanced breast cancer.

Signs of Central Hypersensitivity, Stress, and Anxiety following Treatment for Breast Cancer: A Case Control Study

Background. With treatment for breast cancer, women treated may present significant sensory abnormalities in the upper extremity. However, there are no conclusive studies that have evaluated pressure pain thresholds (PPT) in the shoulder of postoperated women for breast cancer. The aim of this study was to compare PPT in the shoulder, stress, anxiety, depression symptoms, and quality of sleep among postoperated women for breast cancer (PO group) and asymptomatic women of shoulder pain (control group). Methods. 40 women participated ( n = 20 , PO group, age: average ± standard deviation , 49.2 ± 8.3 years; body mass index (BMI): 27.5 ± 3.0 kg/cm2; surgery time: 22.2 ± 34.4 months; n = 20 , control group, 46.9 ± 8.1 years; BMI: 26.8 ± 3.5 kg/cm2). The PPT was evaluated with a digital algometer at 32 points in the shoulder region and one control point in the tibialis anterior. Stress, anxiety, and depression were evaluated with the Depression, Anxiety and Stress Scale 21 (DASS-21) and the quality of sleep by the Pittsburgh Sleep Quality Index. Results. Significant differences were observed over 1.5 kgf/cm2 in 33 points evaluated ( p < 0.01 ) with a small to high effect size (Cliff’s delta range = 0.16 ; 0.92) and higher levels of anxiety and stress in the PO group (anxiety: median [first; third quartile], 5[3; 12.5]; stress: 9.7 ± 4.7 (7.8; 11.8)) in comparison with the control group (anxiety: 2.5[1; 4.8]; stress: 6.7 ± 3.31 (5.2; 8.3), ( p < 0.05 )). No significant differences were found between the groups in depression and sleep quality ( p > 0.05 ). Conclusion. Postoperated women for breast cancer present hyperalgesia in the shoulder anterior and posterior region, low PPT in the tibialis anterior, and higher levels of stress and anxiety compared to the control group.

Detection of High- and Low-Risk HPV DNA in Archived Breast Carcinoma Tissues from Ethiopian Women

Background. Human papilloma virus (HPV) is involved in the development of cancer of the cervix, mouth and throat, anus, penis, vulva, or vagina, but it has not been much considered as a cause of breast cancer. Recently, a number of investigations have linked breast cancer to viral infections. High-risk HPV types, predominantly HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59, are established as carcinogens in humans. In this study we aimed to detect 19 high-risk and 9 low-risk HPVs from archived breast tumor tissue among Ethiopian women. Methods. In this study, 75 breast cancer patients from Tikur Anbassa Specialized Hospital in Addis Ababa (Ethiopia) were included. HPV detection and genotyping were done using the novel Anyplex™ II HPV28 Detection Assay at the Orebro University Hospital, Sweden. The Anyplex™ II PCR System detects 19 high-risk HPV types (16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 69, 73, and 82) and 9 low-risk HPV types (6, 11, 40, 42, 43, 44, 54, 61, and 70). IHC for p16 was done using an automated system, the Dako Autostainer Link. Results. Out of the 75 valid tests, two were found to be positive (2.7%) for HPV. One of the cases was positive for the high-risk HPV16 genotype while the other was positive both for the high-risk HPV39 and the low-risk HPV6. The cell cycle protein p16 was highly expressed in the case positive for the high-risk HPV16, but it was not expressed in the case positive for HPV39. Conclusion. The prevalence of HPV is low in Ethiopian breast cancer patients, but the role played by HPV in breast carcinogenesis among Ethiopian breast cancer patients cannot be commented based on these observations.

Premenopausal Breast Cancer Risk Factors and Associations with Molecular Subtypes: A Case-Control Study

Background. Breast cancer (BC) is the most prevalent cancer in women and the leading cause of women’s cancer-related deaths and morbidity worldwide. In Rwanda, BC incidence is increasing with an unacceptably high mortality rate in premenopausal women. Objectives. The purpose was to identify modifiable BC risk factors and assess associations between common breast cancer risks factors and molecular subtypes in premenopausal women in Rwanda. Methods. This was a case-control study. Premenopausal women with histological confirmation of BC and frequency-matched for age controls were recruited. A preestablished questionnaire was administered to both cases and controls for sociodemographics, BC probable risk factors, and clinical and pathological characteristics. BC was classified into luminal A, luminal B, HER2-type, basal-like (triple negative), and unclassified molecular subtypes by immunohistochemistry (IHC). Odds ratio (OR) and 95% confidence interval (CI) were estimated using multivariate logistic regression analysis. Results. 340 participants were recruited into the study (170 cases vs. 170 controls). The median age was 39 years. The majority of cases presented at advanced stages of the disease (51.2% in stages III and IV) and had invasive ductal carcinoma (98.2%). 60.6% had subtypes of poor prognosis (HER2 enriched 14.7%, triple negative 12.9%, and unclassified 32.9%). Alcohol intake AOR = 3.73 , 95 % C I 2.19 − 6.32 , p < 0.001 , obesity/overweight in adolescence or early adulthood AOR = 10.86 , 95 % C I 4.82 − 24.4 , p < 0.001 , history of primary infertility AOR = 33.8 , 95 % C I 3.5 − 321.5 , p = 0.002 , nulliparity AOR = 3.75 , 95 % C I 1.61 − 8.75 , p = 0.002 , and a history of benign breast disease AOR = 6.06 , 95 % C I 1.19 − 30.73 , p = 0.03 were associated with the occurrence of premenopausal breast cancer. There was no significant difference between risk factor stratification per molecular subtype. Conclusion. Several reproductive, environmental, and lifestyle risk factors have been identified to be associated with premenopausal BC. Among them, alcohol intake and obesity/overweight during adolescence/early adulthood can be modified. Interventions targeting alcohol consumption and obesity/overweight in adolescents and young adults may decrease the incidence of premenopausal breast cancer.

Knowledge and Practice of Breast Cancer Screening Methods among Female Community Pharmacists in Jordan: A Cross-Sectional Study

Objectives. Our study is aimed at exploring the knowledge and personal practice of breast cancer screening among female community pharmacists in Jordan. Methods. A cross-sectional survey was carried out using a nonrandom sample selection method for pharmacists in community pharmacies. Results. A total of 551 female pharmacists completed the questionnaire. The mean age of pharmacists was 29.1 ± 7.3 years (range 21–67), and most have bachelor degrees in pharmacy (89.1%). The mean score of knowledge of breast cancer signs and symptoms was 4.2 ± 1.5 out of 6 points (range 0–6). The mean score of knowledge of risk factors was 7.6 ± 1.9 out of 12 points (ranging from 2–12). The mean score for knowledge of screening guidelines was 2.8 ± 0.9 out of 4 points (range 0–4). Overall, 452 pharmacists (85.8%) had acceptable knowledge while 75 pharmacists (14.2%) had poor knowledge of breast cancer. Pharmacists surveyed were aware of the different screening methods of breast cancer. The percentage of pharmacists who has performed breast self-examination (BSE), clinical breast examination (CBE), and mammography was 46.6%, 16.5%, and 5.4%, respectively. The most common reason for the lack of BSE and CBE performance was the absence of breast symptoms. Not being at the age recommended for mammography was the most common reason for not undergoing this screening method. Knowledge and practice of screening methods were influenced by age, years of experience, geographic region, personal history of breast cancer, and educational level among community pharmacists. Conclusions. This study revealed some gaps in the knowledge of breast cancer among female community pharmacists. The practice of the different screening methods was suboptimal, and variable reasons were indicated for the low uptake of these screening methods. Community pharmacists need to practice preventive behaviors to a satisfactory level to encourage women in the community to adopt similar behavior.

Dose-Dense Docetaxel versus Weekly Paclitaxel following Dose-Dense Epirubicin and Cyclophosphamide as Adjuvant Chemotherapy in Node-Positive Breast Cancer Patients: A Retrospective Cohort Analysis

Background/Aims. The anthracycline and taxane-based chemotherapy regimens are the standard adjuvant treatment of node-positive breast cancer patients. Although it was believed that docetaxel and paclitaxel are similarly effective as adjuvant treatment in node-positive breast cancer, recent studies report that weekly paclitaxel is superior to weekly and triweekly docetaxel schedules in terms of overall survival (OS) and disease-free survival (DFS). However, to the best of our knowledge, no study has compared weekly paclitaxel with a dose-dense regimen of docetaxel. The current study is aimed at evaluating the outcome of women with node-positive breast cancer who had received weekly paclitaxel compared with those treated with dose-dense docetaxel. Methods. This study included patients from two prospective studies conducted in our institute from April 2007 to March 2009. Ninety-one women with axillary lymph node-positive breast cancer who had received four cycles of dose-dense epirubicin and cyclophosphamide were treated with either weekly paclitaxel (80 mg/m2) for 12 doses or biweekly docetaxel (75 mg/m2) for four cycles. Results. After a median follow-up of 88 and 109 months, 11 (23.4%) and 10 (22.7%) patients had experienced disease recurrence ( p = 0.16 ), while 10 (21.3%) and 5 (11.4%) patients had died in the paclitaxel and docetaxel arm, respectively ( p = 0.56 ). No significant difference could be seen in 5-year DFS or OS among groups (HR: 0.58; 95% CI: 0.19–1.81, p = 0.35 ; HR: 0.58; 95% CI: 0.19–1.81, p = 0.35 , respectively). Conclusion. In conclusion, both evaluated adjuvant chemotherapy regimens have comparable effectiveness regarding DFS and OS.