Introduction: Breast cancer is considered nowadays the most prevalent cancer worldwide. The molecular era has successfully divided breast cancer into subtypes based on the various hormonal receptors. These molecular subtypes play a major role in determining the neoadjuvant chemotherapy to be administered. It was noted that the use of neoadjuvant chemotherapy was associated with higher achievement of pathological complete response. The aim of the study was to determine the predictive role of breast cancer subtypes in the efficacy and prognosis of neoadjuvant chemotherapy regimens.
Methods: Combining dose dense anthracycline-based, regular dose anthracycline-based, and nonanthracycline-based chemotherapy, we observed data from 87 patients with breast cancer who received surgery after administration of neoadjuvant chemotherapy at our institution between January 2015 and July 2018. The patients were classified into luminal A, luminal B, HER2 overexpression, and triple negative breast cancer as well as low Ki67 (≤14%) and high Ki67 (>14%) expression groups using immunohistochemistry. Pathologic complete response was the only neoadjuvant chemotherapy outcome parameter. To evaluate variables associated with pathologic complete response, we used univariate analyses followed by multivariate logistic regression.
Results: 87 patients with breast cancer were classified into different subtypes according to the 12th St. Gallen International Breast Cancer Conference. The response rate to neoadjuvant chemotherapy was significantly different (p = 0.046) between the subgroups. There were significant correlations between pathological complete response (pCR) and ER status (p < 0.0001), HER2 (p = 0.013), molecular subtypes (p = 0.018), T stage (p = 0.024), N stage before chemotherapy (p = 0.04), and type of chemotherapy (p = 0.029). Luminal B type patients had the lowest pCR, followed by luminal A type patients.
Conclusion: Evaluating molecular subtype's significance in breast cancer prognosis warrants additional studies in our region with extensive data about patient-specific neoadjuvant chemotherapy regimens. Our study was able to reproduce results complementary to those present in the literature in other outcomes.
Background: Triple negative breast cancer (TNBC) is a biologically separate entity of breast cancer that cannot get benefits from targeted or endocrine therapy.
Objective: To assess the expression of MALAT1 and BACH1, as well as monocyte-myeloid-derived suppressor cell (Mo-MDSC) levels and circulating tumor cell (CTC) count in TNBC to correlate these markers with the clinic-pathological criteria of TNCB patients and to evaluate their roles as predictive markers for selection of the patients that can be operated by oncoplastic conserving breast surgery.
Methods: Eighty-eight TNBC were managed by modified doughnut breast oncoplastic surgery in early stages and by modified radical mastectomy for patients with late stages unsuitable for breast-conserving. All were examined for MALAT1 and BACH1 expression by immunohistochemistry and RT-PCR as well as Mo-MDSC levels and CTCs.
Results: MALAT1 and BACH1 expressions are correlated with the larger size, lymph node, distance metastasis, and TNM staging (p < 0.05). CTCs ≥ 5 and high MO-MDSCs were significantly more in TNBC with MALAT1 and BACH1 overexpression. The survival study proved that DFS for patients with both positive expression of MALAT1 and BACH1 was shorter than that of one positive expression, and both negative expression p ≤ 0.001, CTCs ≥ 5, and high Mo-MDSCs are associated with poor outcomes. No significant difference between modified round block and modified radical mastectomy techniques as regards recurrence. However, all postoperative management outcomes were significantly better in patients operated by oncoplastic conserving breast surgery.
Conclusion: BACH1 and MALAT1 expressions are significantly upregulated in TNBC. They are correlated with CTCs and Mo-MDCs, and all are associated with poor outcomes. Not all TNBC patients have a bad prognosis, patients negative for one of MALAT1 and BACH1 or both, have a slightly good prognosis, and so can be managed by breast oncoplastic conserving surgery.
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.
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.
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.
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.
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.
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.
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.
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