Optimizing breast cancer diagnosis: combining hybrid architectures through Apache Spark

Background Earlier detection of breast cancer through mammography screening has reduced disease-specific mortality; however, confounding issues such as technical challenges, breast density, and tumor size can result in false negatives and ultimately later stage diagnosis. Next generation liquid biopsy has the potential to complement mammography and enable earlier detection for more women. We have previously demonstrated high sensitivity and specificity for early detection of invasive breast cancer (IBC) by utilizing a novel category of cancer-associated small RNAs, termed orphan noncoding RNAs (oncRNAs), through a liquid biopsy platform. Here, we further improve the ability to detect breast cancer in a larger, multi-source cohort through an AI-driven approach and demonstrate potential for detection of ductal carcinoma in-situ (DCIS). Methods We utilized The Cancer Genome Atlas (TCGA) small RNA-seq database to discover a library of 20,538 oncRNAs, through a female-specific analysis, that were significantly enriched among 1,103 breast tumors compared to 349 normal tissue samples spanning multiple tissue sites. The diagnostic performance of these oncRNAs were assessed in an independent cohort of archived serum samples from 663 female individuals, sourced from Indivumed (Hamburg, Germany), Proteogenex (Inglewood, CA), and MT Group (Los Angeles, CA), including 279 breast cancer patients of various stages (221 IBC and 58 DCIS; mean age: 57.0 ± 13.8 years; ever-smoker: 25.8%) and 304 age-matched controls (mean age: 58.5 ± 13.9 years; ever-smoker: 23.4%) without breast cancer. All samples were collected between 2010–2022 at time of diagnosis for breast cancer patients. We sequenced the small RNA content of these samples at an average depth of 25.28 ± 9.37 million 50-bp single-end reads. We detected 18,025 (87.8%) unique breast cancer-specific oncRNA species within at least one sample from the study cohort. We then trained a generative AI model using 5-fold cross-validation to predict cancer status for all samples. Results Our oncRNA-based model achieved an overall AUC of 0.95 (95% CI, 0.93–0.97) for prediction of IBC versus cancer-free controls with a sensitivity of 0.87 (0.82–0.91) at 90% specificity. We observed high sensitivities, also at 90% specificity, across all tumor stages and tumor sizes (Table 1). Sensitivities for the earliest stage and smallest tumor size were 0.87 (0.78–0.93) and 0.81 (0.61–0.93) for Stage I (n=83) and T1a–b ( >1mm to ≤10mm; n=26), respectively. Additionally, in a small single-source cohort, we also saw high model accuracy and sensitivity for DCIS, which we aim to confirm in additional cohorts. While our overall cancer cohort primarily consisted of individuals with luminal breast cancer, our model had high sensitivities across all breast cancer subtypes at 0.90 (0.84–0.94), 0.73 (0.59–0.85), and 0.86 (0.42–1.0) for luminal (n=181), HER2 positive (n=49), and triple negative (n=7), respectively. Conclusions We further demonstrate the potential utility of oncRNAs as a blood-based biomarker using an AI algorithm for sensitive and accurate early detection of breast cancer in a large cohort. Additionally, we have shown that this oncRNA-based assay performs well in detecting small, early-stage invasive breast tumors, with potential to detect precursors of breast cancer. Table 1: Model sensitivity in breast cancer by tumor stage and size For each tumor stage and size, as defined by the AJCC 7th Edition breast cancer staging system, sensitivity and 95% Pearson-Clopper confidence intervals (CI) are reported at 90% specificity for the number of samples (N). Citation Format: Noura Tbeileh, Taylor Cavazos, Mehran Karimzadeh, Jeffrey Wang, Alice Huang, Dung Ngoc Lam, Seda Kilinc, Jieyang Wang, Xuan Zhao, Andy Pohl, Helen Li, Lisa Fish, Kimberly Chau, Marra Francis, Lee Schwartzberg, Patrick Arensdorf, Hani Goodarzi, Fereydoun Hormozdiari, Babak Alipanahi. Cell-free orphan noncoding RNAs and AI enable early detection of invasive breast cancer and ductal carcinoma in-situ [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-13-08.

Tumor antigens, expressed early in disease, which can induce specific antibody response could serve as biomarkers for early detection of human breast cancer. However, the ability to obtain sera from women prior to the development of breast cancer is limited, which makes it difficult to identify early antigens directly from breast cancer patients. Transgenic mouse models have been proved to demonstrate similar antigen repertoire to breast cancer patients. Therefore, we propose to identify early tumor antigens in neu transgenic mice and use them as diagnostic targets for early detection of human breast cancer. We have collected serial sera from neu transgenic mice, sera collected before the animals develop palpable tumor “pre-diagnostic sera”. With serological analysis of recombinant cDNA expression libraries (SEREX) approach, we were able to identify nine tumor antigens from pre-diagnostic sera, Rpl5, TNFaip3/A20, Pdhx, Otud6b, Stk39, Zfp238, Dnajc10, Lgals8 and Vps35. These antigens demonstrated detectable IgG antibody response prior to tumor development in neu transgenic mice. IgM is the first antibody to be produced during a humoral immune response, so we questioned whether including antigen specific IgM with IgG responses could achieve a better diagnostic performance. Firstly, we analyzed receiver-operating-characteristic (ROC) curves of these antigens by IgG and IgM ELISA analysis in neu transgenic mice and 26 FVB control mice. By combining IgG and IgM ELISA, we were able to achieve a higher AUC: Otud6b and Stk39 show an AUC of 0.882, and adding Lgals8 IgG ELISA to this panel can achieve an AUC of 0.924 in discriminating cases from control mice. We documented that these autoantibodies are also detectable in the serum of women with breast cancer and then screened a panel of sera derived from the Women's Health Initiative cohort (samples obtained 6-18 months prior to the development of breast cancer) and case matched controls. We evaluated serum for the presence of IgG and IgM specific autoantibodies to Pdhx, Otud6b, and Stk39. With both IgG and IgM ELISA analysis, a panel combining the three antigens demonstrates an AUC of 0.633 in patients diagnosed within 5 month and an AUC of 0.688 in patients diagnosed within 5-18 month of the blood draw. In summary, we conclude that tumor antigens identified in neu transgenic mouse model can be used for early detection and diagnosis of breast cancer in women. The combination of antigen specific IgG and IgM antibodies may enhance the sensitivity of the assay for early detection. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2683. doi:10.1158/1538-7445.AM2011-2683

Simple SummaryEarly diagnosis of breast cancer greatly increases the chance of cure and survival from the disease. The mammogram is widely used for early detection of breast cancer, but its effectiveness and accuracy have been a concern for a long time as well as its inability in detecting small cancers, especially in women with dense breast tissues. Therefore, it is an unmet clinical need to develop a simple, convenient test to overcome the shortcomings of mammography. Liquid biopsy, which is based on the analysis of body fluids, has attracted much attention in the search for cancer biomarkers. Recent advances in analytical techniques have gradually made it possible to detect breast cancer early through a biomarker analysis of blood, nipple aspirate fluid, sweat, urine, tears, or the breath. We envision that a simple blood or breath test holds great promise as a biomarker for early detection of breast cancer in the near future.Breast cancer is the most common cancer in women worldwide. Accurate early diagnosis of breast cancer is critical in the management of the disease. Although mammogram screening has been widely used for breast cancer screening, high false-positive and false-negative rates and radiation from mammography have always been a concern. Over the last 20 years, the emergence of “omics” strategies has resulted in significant advances in the search for non-invasive biomarkers for breast cancer diagnosis at an early stage. Circulating carcinoma antigens, circulating tumor cells, circulating cell-free tumor nucleic acids (DNA or RNA), circulating microRNAs, and circulating extracellular vesicles in the peripheral blood, nipple aspirate fluid, sweat, urine, and tears, as well as volatile organic compounds in the breath, have emerged as potential non-invasive diagnostic biomarkers to supplement current clinical approaches to earlier detection of breast cancer. In this review, we summarize the current progress of research in these areas.

The present study was conducted to assess the awareness and practice regarding early detection and prevention of breast and cervical cancers among women of kudumbashree units. A quantitative approach and non experimental descriptive design was used for the study. The study was theoretically supported by Nola J Pender's revised health promotion model. A total of 504 women of kudumbashree units were selected using multistage sampling technique. The data was collected using socio personal data sheet, structured questionnaire to measure the awareness and a rating scale to rate the practice regarding early detection and prevention of breast and cervical cancers, all developed by the researcher. The data was analysed using descriptive and inferential statistics. The findings of the study revealed that 81.9% of women of kudumbashree units had average awareness and 59.5% of women of kudumbashree units had good practice. There was no significant correlation between awareness and practice among women of kudumbashree units regarding early detection and prevention of breast and cervical cancers. The selected variables namely education of women of kudumbashree units, occupation of women of kudumbashree units and previous exposure to information regarding breast or cervical cancers had association with awareness regarding early detection and prevention of breast and cervical cancers. Also, there is no association between practice regarding early detection and prevention of breast and cervical cancers and any of the selected variables. An information booklet was prepared on early detection and prevention of breast and cervical cancers and distributed to all study participants.

Introduction: The use of social media by healthcare professionals to create disease awareness has been increased worldwide. It is easily available and accessible to the larger number of populations and hence helps in bridging the gap between doctor and patient. Breast cancer is the leading cause of cancer among women in India and the main reason for higher mortality among them is the late presentation to the surgeons, owing to various myths and social and physical taboos. We conducted a study to assess the awareness of breast cancer among the women in general population and also to check the effectiveness of WhatsApp in improving women's knowledge regarding the risk reduction, myths, early detection and treatment of breast cancer. The study was a pre-post health educational study including 146 wom Methods: en. Multiple WhatsApp groups were created to share information regarding breast cancer awareness, early detection, risk factors, common myths, self-breast examination and treatment of breast cancer in the form of audio, video, text and images. The group was active for 4-5 days as an interactive session. Data were collected through google forms. We noticed a signicant improvement in the knowledge of women regard Results: ing the common myths regarding breast cancer and the symptoms of breast cancer. There was signicant increase in performance of self-breast examination from 14.4% to 84.6% (p- <0.001). Most of the women found the video of self-breast examination useful. The commonly Conclusion: used social networking site like WhatsApp can be used as a tool to assess the awareness of breast cancer among women. This also helped in exchange of the knowledge among women, which in turn helped in the risk reduction and early detection of breast cancer. This app is a useful tool that can be incorporated into health education strategies that focus on breast cancer.

Reproductive health for housewives in the work area of the Passo Health Center is carried out based on problems from the partner group, namely low knowledge and minimal information about women's reproductive health, especially cervical cancer and breast cancer as well as skills in practicing or performing the BSE method resulting in low awareness of the importance women's reproductive health, this is shown through the low behavior of early detection carried out by housewives both the IVA test for early detection of cervical cancer and the application of the BSE method for early detection of breast cancer. With the aim of increasing the knowledge, skills and health of housewives in the target group regarding reproductive health, especially cervical cancer and breast cancer as a prevention effort. As well as increasing the knowledge of mothers about basic clinical information on cervical cancer and breast cancer, methods of detection as prevention and treatment methods, the number of mothers who are detected and can be treated. The solutions applied to the above problems are (1). Counseling to increase the knowledge of housewives about women's reproductive health (cervical Ca and breast Ca); (2). perform early detection of cervical cancer and early detection (screening) of breast cancer. The method used for the implementation of the solution is (1). Lectures, questions and answers and discussions both audio (sound) and visual (pictures and video) to increase mothers' knowledge about women's reproductive health; (2). Visual inspection method with acetic acid, also known as visual inspection with acetic acid (IVA test) for early detection of cervical cancer in housewives of the target group; Evaluation is carried out for each implementation of activities to encourage understanding of housewives to behave healthily towards reproductive health.

Breast cancer and prostate cancer, the most common cancers in American women and men, respectively, are major public health concerns. Investigations into the prevention and early detection of breast and prostate cancer include research on the potential impact of diet, particularly dietary fat, on breast cancer risk; the chemoprevention of breast cancer using tamoxifen and N-(4-hydroxyphenyl)retinamide(4-HPR); the importance of mammography in early detection of breast cancer; the potential of finasteride in preventing or retarding the progression of early-stage prostate cancer; and improved detection of prostate cancer by combining various screening modalities. The importance of transferring information gained though such research to the health care community cannot be overemphasized. Further, it is critical that cancer prevention and detection education be built into the curricula of leading medical and biomedical institutions. Education is key to developing a strong and vigorous cancer prevention and early detection research program.

Background: Breast cancer is a major public health problem, with a high incidence among females worldwide, increasing with age and environmental conditions. Hormonal biomarkers have gained attention for their potential utility in the early detection of breast cancer. The study aimed to investigate the effect of biomarkers of different hormone levels, including prolactin, Testosterone, Cortisol, and Human Chorionic Gonadotropin (HCG) in the diagnosis and early detection of breast cancer risk. Methodology: Blood and saliva samples were collected from volunteer females, including 50 healthy females (NB), 111 benign breasts (BB), and 20 malignant breasts (MB) samples to determine hormone level biomarkers using enzyme-linked immunosorbent assay (ELISA). Results: The results showed that hormonal biomarkers, particularly prolactin, testosterone, and HCG, can serve as indicators for the early detection of breast cancer in both serum and saliva. In contrast, cortisol hormonal biomarkers did not have an effective association with early breast cancer detection. Conclusion: The results of this study showed that the present association between hormonal biomarkers, including prolactin, testosterone, and HCG, could serve as biomarkers for the early detection of breast cancer. In contrast, cortisol did not have an effective association with early breast cancer detection.

Background: Our 2004 survey of breast cancer survivors in the Katowice region (Poland) showed that the detection of the disease was triggered by self-examination in 58.9%, mammography in 19.2%, and clinical examination in 19.7% of cases. The purpose of the current study (2019/2020) was to determine if the implementation of national screening (mammography) in 2007 resulted in an increase of the relative contribution of mammography to detection of cancer. Methods: Subjects were 215 breast cancer patients, members of self-support groups in Katowice region. The questionnaire included questions on early detection of breast cancer, participation in screening, and socio-economic status. Results: Early detection of cancer was initiated by self-examination in 63.7%, mammography in 22.8%, clinical examination in 13.5% of subjects. Age at detection depended on the method (p < 0.001): 54.1 ± 10.8 years for self-examination, 60.0 ± 7.6 years for mammography, and 58.7 ± 10.8 years for clinical examination. Conclusions: Both in 2004 and 2020 self-examination is the most frequent method of early detection of breast cancer in the study area. The contribution of mammography remains on a low level (23%). This finding could be explained by a low participation in screening and by age of 50 years used as the entry criterion to national screening of breast cancer in Poland.

Breast cancer remains one of the major global health challenges, the Human Epidermal Receptor-2 (HER-2) subtype is characterized by aggressive tumor growth due to overexpression of the HER2-positive. Early detection of HER2-positive breast cancer is crucial for improving patient’s outcomes and reducing the risk of metastatic disease. Circulating Tumor DNA is DNA fragments which are released by cancer cells into the bloodstream, and has emerged as a promising non-invasive biomarker for early cancer detection. This review will explore the role of ctDNA in the early detection of HER2-positive breast cancer and its role in prognosis. Studies have shown the high relevance of ctDNA as a diagnostic biomarker, particularly in early-stage disease. Multiple studies have evaluated the role of ctDNA in breast cancer patients, which results consistently showed a strong relation between ctDNA detection and early-stage disease. Additionally, research has indicated that high ctDNA levels are related with a higher risk of recurrence and poorer survival outcomes. The non-invasive nature of ctDNA testing offers several advantages compared to traditional methods, including the ability of monitoring disease progression and treatment response without any need for invasive procedures. Early detection of HER2-positive breast cancer through ctDNA analysis can potentially improve patient outcomes by enabling timely intervention and targeted therapies. By identifying patients with high risk and monitoring disease status, ctDNA testing may contribute to more effective management of HER2-positive breast cancer. While ctDNA analysis shows great promise, it is also important to acknowledge the current limitations and challenges associated with its clinical application. Issues such as standardization of detection methods, sensitivity, and specificity need to be addressed to ensure the widespread adoption of ctDNA testing in routine clinical practice. In conclusion, ctDNA represents a promising biomarker for the early detection and management of HER2-positive breast cancer. Further research and advancements in ctDNA analysis are essential to completely realize its potential and improve patient outcomes.

Studies of the etiology, early detection, and prevention of breast cancer reported in the past year are reviewed in this paper. Studies of the etiology of breast cancer include reports on genetic and environmental factors. A major advance in the study of inherited forms of breast and ovarian cancer occurred with the identification of the BRCA1 gene. A second breast cancer susceptibility gene, the BRCA2 gene, was localized to chromosome 13q12-13. Multiple mutations in the BRCA1 gene have been identified, presenting a challenge for the development of predictive testing. Controversy continues over the association between hormone replacement therapy and the development of breast cancer. A study of exercise suggests a strong protective effect against the development of early onset breast cancer. Recent studies have failed to find a strong link between dietary fat intake and the development of breast cancer. A meta-analysis of studies of the efficacy of screening for the prevention of breast cancer mortality demonstrates a significant reduction in mortality among women 50 years of age and older. A lowering of breast cancer mortality for women aged 40 to 49 was only demonstrated after 10 to 12 years of follow-up. The risks and benefits of tamoxifen therapy, a potential breast cancer chemoprevention agent, continue to be clarified. Adverse effects on the endometrium, including an increased risk of endometrial cancer, have been reported. Beneficial effects include an improved cardiovascular risk profile and preservation of bone mineral density among postmenopausal women.

Optimization and normalization strategies for long term untargeted HILIC-LC-qTOF-MS based metabolomics analysis: Early diagnosis of breast cancer

Background: The existence of Higher Education has three main tasks, namely carrying out education and teaching, research, and community service. These three things constitute the Tridharma of Higher Education. In Indonesia, breast cancer is the second most common cancer suffered by women after oral/cervical cancer. Breast cancer generally attacks women who are over 40 years old. However, young women can get this cancer. To find early symptoms of breast cancer can be detected early by women themselves. Women can routinely perform the Breast Self-Examination (BSE) method by massaging and feeling around their breasts to find out whether or not there are lumps around the breasts. BSE is an effective way to detect breast cancer as early as possible.&#x0D; Objective: Carry out community service by conducting activities to teach breast self-examination (BSE) to young women.&#x0D; Method: This community service activity consists of counseling related to information on early detection of breast cancer and followed by a demonstration of breast self-examination (BSE) using the Breast Phantom tool.&#x0D; Result: Counseling and early detection of breast cancer was attended by 45 students of Madrasah Aliyah. Most students do not know about early detection of breast cancer and how to check BSE. After being given information about BSE, adolescents felt satisfied and committed to be able to carry out early detection of breast cancer.&#x0D; Conclusion: Community service activities have been carried out regarding information on early detection of breast cancer in young women.

Stereoscopic digital mammography holds the promise of improving the early detection and diagnosis of breast cancer compared to standard planar views. A stereo mammogram provides the radiologist with an in depth view of the breast, in which a subtle lesion is directly seen volumetrically. The increased detection sensitivity from stereo seems to arise from the separation of overlying and underlying normal tissue from the lesion, and also from capabilities provided to the reader to manipulate characteristics of the displayed stereo image. In a recently completed project, stereo mammography was shown to significantly improve diagnostic accuracy and led to detection of a significant number of new lesions in the stereo mammograms that were not detected in the films.

Early detection of breast cancer is carried out by using mammographic images. Due to low contrast nature of these images, it is difficult to detect signs such as micro calcifications and masses. This paper describes novel algorithms for early detection of breast cancer using image processing techniques. Novel algorithms are implemented for 1) Mass region extraction to get exact shape of the mass 2) Superposition of boundary of mass on mammogram helps doctors to view the boundary easily as mass region overlaps with breast parenchyma 3) Extraction of texture features like mean, standard deviation, entropy, kurtosis etc, geometric features like area perimeter L:S, ENC, (Elliptical normalized circumference) wavelet based features, so that signatures can be assigned for identification and classification of benign and malignant masses. Fourteen patients' mammograms have been processed. Features of six patients have been extracted that have masses.