International Journal of Breast Cancer最新文献

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.

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%CI 2.19 - 6.32, p < 0.001), obesity/overweight in adolescence or early adulthood (AOR = 10.86, 95%CI 4.82 - 24.4, p < 0.001), history of primary infertility (AOR = 33.8, 95%CI 3.5 - 321.5, p = 0.002), nulliparity (AOR = 3.75, 95%CI 1.61 - 8.75, p = 0.002), and a history of benign breast disease (AOR = 6.06, 95%CI 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.

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.

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.

Background: This study was performed in knowledge of the increasing gap between breast disease treatment in countries with restricted resources and developed countries with increasingly sophisticated examination methods.

Methods: The authors present the analysis of a breast disease register consisting of diagnostic cases from Mazar e Sharif and Herat in 2018 and 2019. The study comprises a total of 567 cases, which were presented to experts via telemedicine for final diagnosis. 62 cases (10.9%) were excluded due to inacceptable data or insufficient image quality. These data provided by daily diagnostic classification were used for the built-up of a profile for each frequent breast disease and a breast cancer register. All images and cases were seen by at least 3 independent experts. The diagnoses were made in 60% of cases by cytology of fine needle aspiration and in 40% by histological images.

Results: For each entity of breast diseases (e.g., fibroadenoma), a profile of context variables was constructed allowing to assist medical decisions, as "wait and see," elective surgery or immediate surgical intervention with R0 (complete) resection. These "profiles" could be described for fibroadenoma, mastitis, galactocele, fibrous-cystic disease, and invasive breast cancer.

Conclusions: The presented preliminary data set could serve as a cost-effective basis for a North Afghan breast cancer registry, with option to extent to a national model. These preliminary data are transformed in profiles of breast diseases, which are used by the local physicians in charge of breast disease patients. Each new case can be compared by the local treating physician with the profile of all preceded cases with the same diagnosis.

Breast cancer has become a real public health problem in Cameroon, particularly in rural areas due to late diagnosis, resulting partly from the absence of national screening programs. This work is aimed at assessing breast cancer awareness in the North Region of Cameroon. Participants were selected in six health centers surrounding the rural area of Garoua, North Region, Cameroon, and administered a questionnaire aimed at assessing their awareness about breast cancer risk factors and screening. Out of the 475 women (including 37 medical personnel) interviewed, 45.5% attended at least secondary school; 91.3% were aware of the disease with the main sources of information from those around them (64.8%), media (46.5%), and health professionals in health facilities (42.7%). 23.3% had misconceptions and myth-based ideas on the origin of the disease. Ignorance was the main reason preventing the performance of breast self-examination, and the high cost prevents individuals from going for mammography. The highest awareness rate was observed in employed women with higher level of education. Our study highlights the need to raise awareness among the populations in North Region, Cameroon, about the risk factors and clinical signs of breast cancer and the importance of screening practice for early diagnosis of breast cancer.

Breast diseases have been one of the major battles the world has been fighting. In winning this fight, the role of medical imaging cannot be overlooked. Breast imaging reveals hidden lesions which aid physicians to give the appropriate diagnosis and definitive treatment, hence this study, to determine the clinical and imaging findings of breast examinations to document the radiologic features in our setting. This cross-sectional retrospective study reviewed the sociodemographics, imaging reports (mammography and ultrasonography with BI-RADS scores and their features), and the clinical data of 425 patients from September 2017 to September 2020 in the Cape Coast Teaching Hospital. 72 solid lesions with their histology reports were also reviewed. Data obtained were organized, coded, and analyzed using Statistical Package for Social Sciences (SPSS Inc., Chicago, IL, USA) version 20.0. The results obtained were presented in appropriate tables and charts. A chi-squared test was employed for associations and statistical significance was specified at p ≤ 0.05. 63.29% of the patients were married, but only 18.59% had a positive family history of breast cancer. BI-RADS scores 1(57.46%) and 2(27.99%) were the most recurrent findings. The most common BI-RADS 2, 3, 4, and 5 imaging features were benign-looking axillary lymph nodes (66.33%), well-defined solid masses (61.54%), ill-defined solid masses (42.86%), and ill-defined solid masses with suspicious-looking axillary lymph nodes (100.00%), respectively. The most frequent indications were routine screening (49.18%), mastalgia (26.59%), and painless breast masses (19.77%). There was significant association between duration of symptoms and breast cancer (p value = 0.007). In conclusion, routine breast screening and mastalgia were the topmost indications for breast imaging. BI-RADS 1 and 2 were the commonest BI-RADS scores, and benign-looking axillary lymph nodes and simple cysts were the most frequent imaging features for BI-RADS 2 and ill-defined solid masses and suspicious-looking axillary lymph nodes for BI-RADS 4 and 5.

Objectives: The response to HER2-targeted neoadjuvant chemotherapy (NAC) in HER2-positive (+) breast cancer can be quantified using residual cancer burden (RCB) pathologic evaluation to predict relapse free/overall survival. However, more information is needed to characterize the relationship between patterns of HER2 testing results and response to NAC. We evaluated clinicopathologic characteristics associated with RCB categories in HER2+ patients who underwent HER2-directed NAC.

Methods: A retrospective chart review was conducted with Stage I-III HER2+ breast cancer cases following NAC and surgical resection. HER2 immunohistochemistry (IHC) staining and fluorescence in situ hybridization (FISH), histologic/clinical characteristics, hormone receptor status, and RCB scores (RCB-0, RCB-I, RCB-II, and RCB-III) were evaluated.

Results: 64/151 (42.4%) patients with HER2+ disease had pathologic complete response (pCR). Tumors with suboptimal response (RCB-II and RCB-III) were more likely to demonstrate less than 100% HER2 IHC 3+ staining (p < 0.0001), lower HER2 FISH copies (p < 0.0001), and lower HER2/CEP17 ratios (p = 0.0015) compared to RCB-I and RCB-II responses. Estrogen receptor classification using ≥10% versus ≥1% staining showed greater association with higher RCB categories.

Conclusions: HER2+ characteristics show differing response to therapy despite all being categorized as positive; tumors with less than 100% IHC 3+ staining, lower HER2 FISH copies, and lower HER2/CEP17 ratios resulted in higher RCB scores.