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Challenges and Opportunities in Breast Cancer Screening

Challenges and Opportunities in Breast Cancer Screening

Ayugi, J., Ndagijimana, G., Luyima, S., & Kitara, D. L. (2022). 

Abstract

Background: Breast Cancer is one of the most common cancers that occur universally among women. The disability-adjusted life years lost by women to breast cancer globally are more than any other cancer. Breast cancer occurs in women worldwide after puberty with increasing rates in later life. Improvements in breast cancer survival began in the 1980s in countries where early detection programs combined with different modes of treatment to eradicate the invasive form of the disease are practiced. Recent data show a higher prevalence of breast cancer among women in Northern Uganda compared to the rest of the country.

This study aimed to determine factors associated with breast cancer awareness, breast self-examination, clinical breast examination, and other modalities for screening and early breast cancer detection among adult women in Gulu Main Market.

Methods: We conducted a cross-sectional study in Gulu’s Main Market in 2020. We recruited Ninety-eight adult women for the study using a random sampling method. The questionnaire had an internal validity of Cronbach’s α=0.72, and a local IRB approved the study. We used SPSS version 26.0 for data analysis, and a p-value less than 0.05 was considered significant.

Results: Most participants were 20-29 years 41(41.8%), married 44(44.9%), monthly incomes of more than one million shillings 51(52.2%), Acholi 81(82.7%), Catholics 46(46.9%), vendors 75(76.5%), work duration in the Market (1-10 years) 64(65.4%), primary level of education 39(39.8%), and had 1-2 pregnancies 37(37.8%). The independent factors associated with breast cancer awareness, breast self-examination, and clinical breast examination were vendor (primary occupation) (β=-0.130, t=-2.979, p=0.004), work duration in the Main Market (1-10 years) (β=-0.186, t=-2.452, p=0.016), and the highest level of education (β=-0.091, t=-2.506, p=0.014).

Conclusions: Breast cancer awareness and downstaging practices among adult women in Gulu’s Main Market are thought-provoking. Women with better socioeconomic status (higher education level, moderate work duration in the Market, and vendors) in Gulu Main Market were more likely aware and practiced breast cancer downstaging activities. There is a need to strengthen publicity on breast cancer-related knowledge for lower-income occupational groups and those with lower educational levels to understand better the importance of conducting early breast cancer detection activities.

Püschel, K., Paz, S., Fowler, M. D., Vescovic, Z., Fuentes, I., Sánchez, C., & Acevedo, F. (2023). 

Abstract

Background: Breast cancer is the leading cause of death from cancer among women in Latin America. Most Latin American countries started national mammogram screening programs a decade ago. The implementation level and effects of screening programs in Latin America have not been evaluated.

Aim: To evaluate the association between screening programs implementation and breast cancer mortality in selected North American and European countries compared to a group of Latin American countries with national screening programs.

MethodsThe study applied an ecological design with secondary data from official national and international sources. Join point regression analysis was conducted to describe the trends in mortality rates in a group of five Latin American countries (Brazil, Chile, Colombia, Costa Rica and Mexico) with five Non-Latin American countries (Canada, Spain, Sweden, United Kingdom and the United States of America). The association between screening and mortality rates was explored using correlation and linear regression. National cancer plans were assessed to describe screening strategies among selected countries.

ResultsA significant reduction in standardized breast cancer mortality rates was observed in all Non-Latin American countries with an Average Annual Percent Change (AAPC) of -2.00 (p<.05, 95%CI [-3.33, -0.70]) for the period 2010-2020. In contrast, Latin American countries reported a significant increase in the AAPC of +1.38 (p<.05, 95%CI [0.86,1.76]) in breast cancer mortality rates for the period 2010-2020. For Latin American countries, with screening rates below 50%, there was no correlation between screening and mortality rates for the period 1985-2020 (r = -0.17, p = .78). For non-Latin American countries, with screening rates over 70%, the linear regression model explained significantly 55% of the variance in mortality rates (R2aj =.55, F (5,14) = 5.69, p = .005), with a negative and significant effect of mammogram screening on mortality rates (β = -0.14, p = .01). The National Plans analysis revealed an opportunistic screening model for Latin American countries and an organized-systematic model in Non-Latin American countries.

ConclusionThere is an association between the level of implementation of screening programs and mortality rates from breast cancer. Latin American countries should transform their opportunistic strategy into an organized-systematic model.

Jones, T., Wisdom-Chambers, K., Freeman, K., & Edwards, K. (2023). 

Abstract

Background: In the United States (US), Black/African American women suffer disproportionately from breast cancer health disparities with a 40% higher death rate compared to White women. Mammography screening is considered a critical tool in mitigating disparities, yet Black women experience barriers to screening and are more likely to be diagnosed with advanced-stage breast cancer. The purpose of this study was to assess the relative frequency of mammography screening and to examine perceived and actual barriers to screening among women who receive care in our nurse-led community health center.

Methods: We conducted a survey examining frequency of mammography screening and beliefs about breast cancer including perceived susceptibility, perceived benefits, and perceived barriers to mammography screening, guided by the Champion Health Belief Model.

Results: A total of 30 Black/African American women completed the survey. The mean age of the participants was 54.3 years ± 9.17 (SD); 43.3% had a high school education or less; 50% had incomes below $60,000 per year; 26.7% were uninsured; 10% were on Medicaid; and only 50% were working full-time. We found that only half of the participants reported having annual mammograms 16 (53.3%), 1 (3.3%) every 6 months, 8 (26.6%) every 2-3 years, and 5 (16.7%) never had a mammogram in their lifetime. Frequently cited barriers included: ‘getting a mammogram would be inconvenient for me’; ‘getting a mammogram could cause breast cancer’; ‘the treatment I would get for breast cancer would be worse than the cancer itself’; ‘being treated for breast cancer would cause me a lot of problems’; ‘other health problems would keep me from having a mammogram’; concern about pain with having a mammogram would keep me from having one; and not being able to afford a mammogram would keep me from having one’. Having no health insurance was also a barrier.

Conclusion:  This study found suboptimal utilization of annual screening mammograms among low-income Black women at a community health center in Florida and women reported several barriers. Given the high mortality rate of breast cancer among Black/African American women, we have integrated a Patient Navigator in our health system to reduce barriers to breast cancer screening, follow-up care, and to facilitate timely access to treatment, thus ultimately reducing breast cancer health disparities and promoting health equity.

Singh, M., Prakash, S., Kaur, S., Sharma, N., Jha, D., Pandav, C., & Hoffman, F. (2023). 

Abstract

Introduction: Breast cancer is the most common cancer in women around the world, including India. The peak incidence in India is occurring between the ages of 45 -49 years. The solution to problem lies in early detection. The two important methodologies are tactile examination and radiological assessment in form of Mammography. This study explores the concept of enabling and training visually impaired women known as Medical Tactile Examiners with enhanced tactile sense to perform Tactile Breast Examination (TBE) for early detection of Breast Cancer.

Material & Method: A total 1338 women were enrolled. Tactile Breast Examination included intensive and meticulous examination of every cm of breast by three different touch pressures using specialized strips to guide the visually impaired. It was preceded by recording information around lifestyle habits, pregnancy, lactation, menstruation, family history, etc. The radiological assessment included Ultrasound for women less than 40 years and Mammogram for 40 years and above. Data generated was statistically analyzed.

Results: 2.6% of 1338 women were doing routine breast screening; 16% had Body Mass Index > 30; 3% were into substance abuse; 7% experienced menstrual irregularities; 16% were nulliparous; 15% of the parous women had insufficient lactation. 5% had family history of Hereditary Breast and Ovarian Cancer and 4% had previous history     of Breast Cancer. Tactile Breast Examination findings were normal in 756/1338 (56.5%), amongst which 8/756 (1%) had radiology reports with BIRADS 4 (suspicious for malignancy) findings. Medical Tactile Examiners during the process of TBE identified palpable breast alterations in 582/1338 (43.5%) of the cases, amongst which 29/582 (5%) were identified as BIRADS 4. The statistical analysis suggests Tactile Breast Examination having a high sensitivity (78.3%) and a very high negative predictive value (98.9%)

Conclusion: The process of Tactile Breast Examination by visually impaired appears apt for breast screening as it detects almost any aberration both benign and malignant in breast which is amenable to human touch and misses out in just 1% changes which can be malignant. It has the potential to become vocational avenue for visually impaired women.

Ramathebane, M., Maja, L., Sooro, M. A., Sello, M., Mokhethi, M. C., & Mputsoe, K. A. (2023). 

Abstract

Background: It has been estimated that, more than 60% of the new breast cancer cases and 70% of related deaths will be seen in Low-Middle Income Countries in the coming 20 years. In Lesotho, out of 228 women, 177 had heard about breast cancer while 72.9% had heard of breast cancer screening. Given limited treatment facilities and options in Lesotho, many patients die soon after diagnosis, before they are able to access treatment; to date this cannot be quantified. Another challenge that affects breast cancer management is treatment and travel-related costs, particularly for those not living close to the medical centre. Most patients are coming with advanced disease stage and are sent home for home-based care, some of which could have been prevented with early screening.

Aim: The aim of study is to determine challenges faced by breast cancer patients, the cost to the health system and the opportunities this may bring to the country.

Methods: A quantitative cross-sectional, prospective and retrospective study was conducted on 45 breast cancer patients who were initiated chemotherapy at the only cancer treatment centre in Lesotho; Senkatana oncology clinic located at the Botshabelo complex in Maseru.

Results: The majority of patients were facing challenges of arranging transport to the doctor (83.3%, n=15), of being far from the healthcare facilities even if transportation was available (77.8%, n=14), paying for healthcare (83.3%, n=15), paying for transport (77.8%, n=14) and paying for diagnostic test (88.9%, n=16) in all ages. Majority of patients who presented for care and treatment late faced challenges more than those who presented earlier. Diagnostic and monitoring laboratory test constituted 64.5% of total direct medical costs followed by 24.7 % from chemotherapy.

Conclusion: The challenges faced by breast cancer patients are of financial and practical nature and they get higher for patients who presented at advanced stage for care and treatment. In order to improve breast cancer care and treatment outcome at lower costs efforts for breast cancer awareness need to be intensified so that patients presented early at the health centers. In term of direct medical cost, the largest cost came from the diagnostic and monitoring laboratory tests.

Burton, R. C. (2022). 

Abstract

In Australia and many other high and middle-income countries diagnosis of the most curable stages of breast cancer, early breast cancer (EBC), in women by population based mammographic screening began after 1990. In many of these same and other high and middle-income countries administering adjuvant endocrine and chemotherapy after surgical complete resection of EBC (adjuvant therapy) also began in the 1990s. Some populations then underwent declines in breast cancer mortality that were recorded in population-based Cancer Registries that were attributed to either mammographic screening and/or adjuvant therapy. In only a few populations, for example, in the State of Victoria Australia from 1986-2019 long term trends in the incidence of breast cancer stages at diagnosis have been recorded by the population-based Victorian Cancer registry (VCR). These long-term stage trends have shown that advanced stages of breast cancer have increased or remained stable in those populations, so mammographic screening could not have directly caused the recorded declines in breast cancer mortality in their population-based Cancer Registries. In contrast in Victoria Australia adjuvant therapy use can explain all the recorded mortality decline.

Mehdipour, P. (2023b).

Abstract

Successful cancer evolution (CE) relies on the sequential molecular and functional events including 1) telomere; 2) sub-telomere; 3) epigenetic; 4-6) hit-episodes; 7) an innovative cell cycle machinery, as the multi-phase, and 8) chromosomal abnormalities. In this regard, eight available, fundamental/evolutionary and strategic key information (Evolutionary- ID) presented.

Telomere length (TL), has the fundamental role in cancer development, with serious challenges in the clinical managements. Breast cancer and brain tumor are an unresolved problem in Science and Medicine. Besides, an early and translatable diagnostic- prognostic-predictive platform, by considering the targets-ID, is required. Diverse TL in two cases affected with astrocytoma with grade IV, revealed to be 12500 and 15000 bp in tumor, and 10000 and 9000 bp at genomic level. Interestingly, TL is declined in the lymph node, i.e., occurrence of evolution.

Sub-telomeres (STs) through the cellular journey, are the neighboring destination at genomic and somatic level. The evolutionary pattern of STs has not been, routinely, decoded to the personalized clinical managements. The STsequences, are diversely predisposed to variety of environmental factors and play influential role in healthy individuals and the patients. An early detection is available by analysis of the ST- hybridized signals in the biopsy of auxiliary lymph nodes (ALN), and/or by circulating tumor cells (CTCs) into the blood stream. Diverse pattern of signal frequency and intensity in individual chromosomes at both somatic (ALN) and genomic (lymphocytes) levels were remarkable. The most common involved targets included chromosomes 5 and 9, 16 and 19; with diverse intensity at p and q chromosomal arms respectively. These findings have the predisposing, and an initial influence through the patients’ course of disease.

ST- signals, by providing the STs-ID, offer periodical and predictive, indices in cancer screening and therapy.

Furthermore, the complementary, cell cycle protein expression (PE) including Ki67, cyclin D1, and cyclin E, accelerates an early clinical management through the period of disease based on the CTCs.

Epigenetics is the next molecular destination by focusing on the genomic/somatic index, as an evolutionary Epigenetics-ID with its impact on the cancer management. The target panel is Ataxia Telangiectasia mutated gene (ATM) as the molecular marker and an initiator of different cancers.

ATM has remarkable roles, including: 1) in DNA double strand break (DSB), 2) to initiate different types of neoplastic disorders, including cancer, and 3), polymorphism, D1853N as a peridisposing marker by initiating the hit process. The influential characteristics include: family history of neoplastic disorders through the pedigree, the key role of ATM promoter methylation, cooperation of ATM/Rb protein expression, D1853N- marker, telomere length (TL) and the clinico-pathological characteristics in different types of brain tumors, and the environmental factors. Interestingly, TL has an independent influence on the progressive cancer evolution. An early detection by CTCs based on the D1853N/Sub-TL/Cell cycle checkpoints based on the PE assay and molecular test facilitate an early detection and therapy, based on the personalized approach.

By highlighting the preventive insight in Medicine, a brief record on the “Methylation in Chorionic villus samples (CVS)” with aim of an early detective strategy is provided. All nine CVS samples were methylated for the MCPH1 gene. An early detection is possible either through CV sampling or by the circulating CV cells in the maternal blood.

Evolutionary Hit includes: presence of D1853N polymorphism of ATM, as the hit-initiator through an evolutionary and progressive molecular based sequential alterations led to discovery of three-hit hypothesis in a patient affected with astrocytoma. More hits include five, and eight- hit hypotheses in primary breast cancer patients. Such platforms are considered as the individualized model in cancer. The pedigrees and details at the molecular follow-up studies and functional alteration at protein level are available in the provided sections.

Novel strategy of Cell cycle phases in breast cancer is the major intersection for cancer therapy.

The novel cell cycle hypothesis (CCH) highlights the mosaic based of dual and/or multi-phases, as minor clones at single cell level in the breast cancer (BC) -patients, escorted by the normal cell population. Such mosaicism provided an archetypal, unique diagnostic and therapeutic model, by applying different mosaic patterns (MPs) as well as “G1/S, S/G2 and G1/S/G2, and accompanied by normal phases, as a sole including G1, S, and G2 at the single cells level.  

Diagnosis is based on the mode of signal copy numbers (SCN) and the related PE. Interestingly MPs were also unmasked in patients with chronic myelogeneous leukemia and other solid tumors.

Finally, the predisposing/predictive/prognostic/preventive square provides an innovate CDKs inhibitor-based therapy in BC and other cancers.

Personalized base cancer therapy is the confusing procedure and requires the pedigree-based data, personalized, evolutionary based information including molecular and functional at both genomic and somatic, at single cell levelThe target territories comprise cell cycle phases, proteins, Telomere length, telomerase, sub-telomere, and Epigenetics. The aim is directing the cell cycle fundamental forces back to normal, by performing:

1) Applying personalized, single cell-based approach, at molecular, functional level, pedigree analysis, and balancing the micro-/macro-environmental factors, including nutrition.

2) Satisfactory high single cell enumeration based on the FISH and protein expression assays;

3) Decoding the required dosage and combined therapeutic regimens accordingly,

4) Unmasking the cell cycle combined (mosaic) phases including different Cyclins; and

5) Bilateral cooperation between Pharmacology, Medicine, and Cancer Genetics/cell biology.


 Let’s combine the evolutionary based strategy by translating the personalized data at molecular/ Functional/ Informative, and pedigree-based level to the personalized therapy.

Wu, D., & Kim, S. (2022).

Abstract

Aims: Accurate estimation of the three key parameters (sensitivity, time duration in disease-free state and sojourn time in preclinical state) in cancer screening are critical. Likelihood method with a new link function was applied to the Health Insurance Plan of Greater New York (HIP) breast cancer screening data, to estimate the onset age of preclinical state and the sojourn time in the preclinical state for breast cancer.

Materials and Methods: A new link function to model sensitivity as a function of time in the preclinical state and the sojourn time was adopted. Markov Chain Monte Carlo simulations were used to obtain posterior samples and make inference on the three key parameters. Maximum likelihood estimate was also used for comparison.

Results: The onset age of the preclinical state has a wide range for breast cancer; the peak onset age was 65.07 years (95% credible interval [C.I.], 55.76 to 73.02). The mean sojourn time was 2.00 years (95% C.I., 0.85 to 2.95). The 95 % C.I. for the sojourn time was 0.16 to 5.53 years. Sensitivity at onset of the preclinical state was 0.75 (95% C.I., 0.54 to 0.88); and sensitivity at the end of the preclinical state was 0.84 (95% C.I., 0.67 to 0.88).   

Conclusion: The HIP study was the oldest breast cancer mass screening. The estimates reflect key parameters in those days with lower screening sensitivity. However, it is helpful to know other parameters in the planning for future breast cancer screening.

Mbaye, F., Agendey, N., & Sembene, M. (2023). 

Abstract

Breast tumors are a frequent cause of medical consultations. Although these tumors are mainly benign, they can become malignant or cancerous. This study aimed to elucidate the involvement of genetic alterations in the C-MYC oncogene in breast tumorigenesis in Senegalese females. After PCR, the epidemiological and molecular profiles of 45 samples, including 19 controls (C) from healthy individuals and 11 benign (BT) and 15 cancerous (MT) samples from patients with tumors, were determined. Mutations were determined using Mutation Surveyor software, and their pathogenicity was assessed using SIFT, Polyphen-2, Mutpred2, SNAP2, PANTER-PSEP, PROVEAN, PhD-SNP, SNP&GO, MUpro, and I-mutant prediction tools. At the epidemiological level, the average ages of the BT and MT groups were 21 and 49.76 years, respectively, and the average ages at menarche were 14.14 and 14.58 years, respectively, with a high frequency of adenofibromas (53.85%) in the BT group and only infiltrating ductal carcinomas (100%) found in the MT group. The stages (III and IV) and grade of SBR were specific to the MT group 76.47% and 58.82%, respectively. At the molecular level, four mutations were identified, all of which were heterozygous and novel, and three of which were non-synonymous. One of the mutations (c.115 T > TC; p.Tyr39His) was recurrent (frequency = 26.67%, 4/15 in the MT group; and 10.53%, 2/19 in the C group) and the other two (c.113 T > TC; p.Phe38Ser and c.117 C > CT) were exclusive to the C group, with the same frequency of 5.26% (1/19). No mutations were found in the BT group. The p.Phe38Ser and p.Tyr39His mutations were described as deleterious and can cause cancer according to the prediction tools. Overall, these mutations can be considered as variants of interest and are the subject of PCR screening for breast cancer prevention.