Poly (adenosine diphosphate-ribose) polymerase inhibitors in the treatment of triple-negative breast cancer with homologous repair deficiency.

Breast cancer (BC) is a highly heterogeneous disease, and the presence of germline breast cancer gene mutation (gBRCAm) is associated with a poor prognosis. Triple-negative breast cancer (TNBC) is a BC subtype, characterized by the absence of hormone and growth factor receptor expression, making therapeutic decisions difficult. Defects in the DNA damage response pathway due to mutation in breast cancer genes (BRCA 1/2) lead to homologous recombination deficiency (HRD). However, in HRD conditions, poly (adenosine diphosphate-ribose) polymerase (PARP) proteins repair DNA damage and lead to tumor cell survival. Biological understanding of HRD leads to the development of PARP inhibitors (PARPi), which trap PARP proteins and cause genomic instability and tumor cell lysis. HRD assessment can be an important biomarker in identifying gBRCAm patients with BC who could benefit from PARPi therapy. HRD can be identified by homologous recombination repair (HRR) gene-based assays, genomic-scarring assays and mutational signatures, transcription and protein expression profiles, and functional assays. However, gold standard methodologies that are robust and reliable to assess HRD are not available currently. Hence, there is a pressing need to develop accurate biomarkers identifying HRD tumors to guide targeted therapies such as PARPi in patients with BC. HRD assessment has shown fruitful outcomes in chemotherapy studies and preliminary evidence on PARPi intervention as monotherapy and combination therapy in HRD-stratified patients. Furthermore, ongoing trials are exploring the potential of PARPi in BC and clinically complex TNBC settings, where HRD testing is used as an adjunct to stratify patients based on BRCA mutations.

Does structural racism impact receipt of NCCN guideline-concordant breast cancer treatment?

PURPOSE: Disparities in breast cancer survival remain a challenge. We aimed to analyze the effect of structural racism, as measured by the Index of Concentration at the Extremes (ICE), on receipt of National Cancer Center Network (NCCN) guideline-concordant breast cancer treatment. METHODS: We identified patients treated at two institutions from 2005 to 2017 with stage I-IV breast cancer. Census tracts served as neighborhood proxies. Using 5-year estimates from the American Community Survey, 5 ICE variables were computed to create 5 models, controlling for economic segregation, non-Hispanic Black (NHB) segregation, NHB/economic segregation, Hispanic segregation, and Hispanic/economic segregation. Multi-level logistic regression models were used to determine the association between individual and neighborhood-level characteristics on receipt of NCCN guideline-concordant breast cancer treatment. RESULTS: 5173 patients were included: 55.2% were Hispanic, 27.5% were NHW, and 17.3% were NHB. Regardless of economic or residential segregation, a NHB patient was less likely to receive appropriate treatment [(OR)Model1 0.58 (0.45-0.74); ORModel2 0.59 (0.46-0.78); ORModel3 0.62 (0.47-0.81); ORModel4 0.53 (0.40-0.69); ORModel5 0.59(0.46-0.76); p < 0.05]. CONCLUSION: To our knowledge, this is the first analysis assessing receipt of NCCN guideline-concordant treatment by ICE, a validated measure for structural racism. While much literature emphasizes neighborhood-level barriers to treatment, our results demonstrate that compared to NHW patients, NHB patients are less likely to receive NCCN guideline-concordant breast cancer treatment, independent of economic or residential segregation. Our study suggests that there are potential unaccounted individual or neighborhood barriers to receipt of appropriate care that go beyond economic or residential segregation.

Patient-reported observations on medical procedure timeliness (PROMPT) in breast cancer: a qualitative study.

PURPOSE: Timeliness of care is an important healthcare outcome measure. The objective of this study was to explore patient perspectives on the timeliness of breast cancer diagnosis and treatment at accredited breast cancer centers. METHODS: In this qualitative study, 1 hour virtual interviews were conducted with participants 18-75 years old who were diagnosed and treated for stage 0-III breast cancer at a National Accreditation Program for Breast Centers facility from 2018 to 2022. Thematic analysis was used to identify key themes of participant experiences. RESULTS: Twenty-eight participants were interviewed. Two thematic domains were identified: etiologies of expedited or delayed care and the impact of delayed or expedited care on patients. Within these domains, multiple themes emerged. For etiologies of expedited or delayed care, participants discussed (1) the effect of scheduling appointments, (2) the COVID-19 pandemic, (3) dissatisfaction with the timeline for various parts of the diagnostic workup, and (4) delays related to patient factors, including socioeconomic status. For the impact of expedited or delayed care, patients discussed (1) the emotional and mental impact of waiting, (2) the importance of communication and clear expectations, and (3) the impact of electronic health portals. Patients desired each care interval (e.g., the time from mammogram to breast biopsy) to be approximately 7 days, with longer intervals sometimes preferred prior to surgery. CONCLUSION: These patient interviews identify areas of delay and provide patient-centered, actionable items to improve the timeliness of breast cancer care.

Persistent Pain After Breast Cancer Treatment, an Underreported Burden for Breast Cancer Survivors.

BACKGROUND: Many patients who have undergone surgery experience persistent pain after breast cancer treatment (PPBCT). These symptoms often remain unnoticed by treating physician(s), and the pathophysiology of PPBCT remains poorly understood. The purpose of this study was to determine prevalence of PPBCT and examine the association between PPBCT and various patient, tumor, and treatment characteristics. PATIENTS AND METHODS: We conducted a questionnaire-based cross-sectional study enrolling patients with breast cancer treated at Máxima Medical Center between 2005 and 2016. PPBCT was defined as pain in the breast, anterior thorax, axilla, and/or medial upper arm that persists for at least 3 months after surgery. Tumor and treatment characteristics were derived from the Dutch Cancer Registry and electronic patient files. RESULTS: Between February and March 2019, a questionnaire was sent to 2022 women, of whom 56.5% responded. Prevalence of PPBCT among the responders was 37.9%, with 50.8% reporting moderate to severe pain. Multivariable analyses showed that women with signs of anxiety, depression or a history of smoking had a higher risk of experiencing PPBCT. Women aged 70 years or older at diagnosis were significantly less likely to report PPBCT compared with younger women. No significant association was found between PPBCT and treatment characteristics, including type of axillary surgery and radiotherapy. CONCLUSIONS: A considerable percentage of patients with breast cancer experience PPBCT. Women with signs of anxiety or depression and women with a history of smoking are more likely to report PPBCT. Further research is required to understand the underlying etiology and to improve prevention and treatment strategies for PPBCT.

Investigating the effects of artificial intelligence on the personalization of breast cancer management: a systematic study.

BACKGROUND: Providing appropriate specialized treatment to the right patient at the right time is considered necessary in cancer management. Targeted therapy tailored to the genetic changes of each breast cancer patient is a desirable feature of precision oncology, which can not only reduce disease progression but also potentially increase patient survival. The use of artificial intelligence alongside precision oncology can help physicians by identifying and selecting more effective treatment factors for patients. METHOD: A systematic review was conducted using the PubMed, Embase, Scopus, and Web of Science databases in September 2023. We performed the search strategy with keywords, namely: Breast Cancer, Artificial intelligence, and precision Oncology along with their synonyms in the article titles. Descriptive, qualitative, review, and non-English studies were excluded. The quality assessment of the articles and evaluation of bias were determined based on the SJR journal and JBI indices, as well as the PRISMA2020 guideline. RESULTS: Forty-six studies were selected that focused on personalized breast cancer management using artificial intelligence models. Seventeen studies using various deep learning methods achieved a satisfactory outcome in predicting treatment response and prognosis, contributing to personalized breast cancer management. Two studies utilizing neural networks and clustering provided acceptable indicators for predicting patient survival and categorizing breast tumors. One study employed transfer learning to predict treatment response. Twenty-six studies utilizing machine-learning methods demonstrated that these techniques can improve breast cancer classification, screening, diagnosis, and prognosis. The most frequent modeling techniques used were NB, SVM, RF, XGBoost, and Reinforcement Learning. The average area under the curve (AUC) for the models was 0.91. Moreover, the average values for accuracy, sensitivity, specificity, and precision were reported to be in the range of 90-96% for the models. CONCLUSION: Artificial intelligence has proven to be effective in assisting physicians and researchers in managing breast cancer treatment by uncovering hidden patterns in complex omics and genetic data. Intelligent processing of omics data through protein and gene pattern classification and the utilization of deep neural patterns has the potential to significantly transform the field of complex disease management.

Lost in Translation: Multilingual Analysis of Online Breast Cancer Information.

INTRODUCTION: Patients use the internet to learn more about health conditions. Non-English-speaking patients may face additional challenges. The quality of online breast cancer information, the most common cancer in women, is uncertain. This study aims to examine the quality of online breast cancer information for English and non-English-speaking patients. METHODS: Three search engines were queried using the terms: "how to do a breast examination," "when do I need a mammogram," and "what are the treatment options for breast cancer" in English, Spanish, and Chinese. For each language, 60 unique websites were included and classified by type and information source. Two language-fluent reviewers evaluated website quality using the Journal of American Medical Association benchmark criteria (0-4) and the DISCERN tool (1-5), with higher scores representing higher quality. Scores were averaged for each language. Health On the Net code presence was noted. Inter-rater reliability between reviewers was assessed. RESULTS: English and Spanish websites most commonly originated from US sources (92% and 80%, respectively) compared to Chinese websites (33%, P < 0.001). The most common website type was hospital-affiliated for English (43%) and foundation/advocacy for Spanish and Chinese (43% and 45%, respectively). English websites had the highest and Chinese websites the lowest mean the Journal of American Medical Association (2.2 ± 1.4 versus 1.0 ± 0.8, P = 0.002) and DISCERN scores (3.5 ± 0.9 versus 2.3 ± 0.6, P < 0.001). Health On the Net code was present on 16 (8.9%) websites. Inter-rater reliability ranged from moderate to substantial agreement. CONCLUSIONS: The quality of online information on breast cancer across all three languages is poor. Information quality was poorest for Chinese websites. Improvements to enhance the reliability of breast cancer information across languages are needed.

Novel naphthoquinone-1H-1,2,3-triazole hybrids: Design, synthesis and evaluation as inductors of ROS-mediated apoptosis in the MCF-7 cells.

The search for novel anticancer drugs is essential to expand treatment options, overcome drug resistance, reduce toxicity, promote innovation, and tackle the economic impact. The importance of these studies lies in their contribution to advancing cancer research and enhancing patient outcomes in the battle against cancer. Here, we developed new asymmetric hybrids containing two different naphthoquinones linked by a 1,2,3-1H-triazole nucleus, which are potential new drugs for cancer treatment. The antitumor activity of the novel compounds was tested using the breast cancer cell lines MCF-7 and MDA-MB-231, using the non-cancer cell line MCF10A as control. Our results showed that two out of twenty-two substances tested presented potential antitumor activity against the breast cancer cell lines. These potential drugs, named here 12g and 12h were effective in reducing cell viability and promoting cell death of the tumor cell lines, exhibiting minimal effects on the control cell line. The mechanism of action of the novel drugs was assessed revealing that both drugs increased reactive oxygen species production with consequent activation of the AMPK pathway. Therefore, we concluded that 12g and 12h are novel AMPK activators presenting selective antitumor effects.

Male Breast Cancer: a Review on Diagnosis, Treatment, and Survivorship.

PURPOSE OF REVIEW: Male breast cancer is a relatively uncommon and rare disease that is often managed based on evidence adopted from trials pertaining to female breast cancer due to low accrual rates or exclusion of males. This is despite the known differences in the biology and epidemiology of this condition. This review provides an update regarding the management and surveillance of male breast cancer. RECENT FINDINGS: Men with breast cancer tend to undergo more extensive surgery in the breast and axilla. The outcomes of male breast cancer compared to a similar subtype of female breast cancer appear worse when matched for stage. Systemic therapies remain predominantly based on recommendations for female breast cancer, although tamoxifen is the more optimal endocrine therapy for men than women. Surveillance with mammograms is recommended for patients harboring a breast cancer susceptibility gene but is otherwise not advised for men who have undergone a mastectomy. Notably, the role of other imaging modalities, including ultrasound and magnetic resonance imaging, is minimal. Although the focus on survivorship care among men is low, it is abundantly clear that this is a stigmatizing diagnosis for men, and they suffer from long-term physical and psychological sequelae following a diagnosis and treatment of breast cancer. In summary, providing more gender-inclusive care and advocating for increased representation of men in prospective breast cancer studies and clinical trials may help improve outcomes and provide enhanced support for this population.

Magnetically modified-mitoxantrone mesoporous organosilica drugs: an emergent multimodal nanochemotherapy for breast cancer.

BACKGROUND: Chemotherapy, the mainstay treatment for metastatic cancer, presents serious side effects due to off-target exposure. In addition to the negative impact on patients' quality of life, side effects limit the dose that can be administered and thus the efficacy of the drug. Encapsulation of chemotherapeutic drugs in nanocarriers is a promising strategy to mitigate these issues. However, avoiding premature drug release from the nanocarriers and selectively targeting the tumour remains a challenge. RESULTS: In this study, we present a pioneering method for drug integration into nanoparticles known as mesoporous organosilica drugs (MODs), a distinctive variant of periodic mesoporous organosilica nanoparticles (PMOs) in which the drug is an inherent component of the silica nanoparticle structure. This groundbreaking approach involves the chemical modification of drugs to produce bis-organosilane prodrugs, which act as silica precursors for MOD synthesis. Mitoxantrone (MTO), a drug used to treat metastatic breast cancer, was selected for the development of MTO@MOD nanomedicines, which demonstrated a significant reduction in breast cancer cell viability. Several MODs with different amounts of MTO were synthesised and found to be efficient nanoplatforms for the sustained delivery of MTO after biodegradation. In addition, Fe3O4 NPs were incorporated into the MODs to generate magnetic MODs to actively target the tumour and further enhance drug efficacy. Importantly, magnetic MTO@MODs underwent a Fenton reaction, which increased cancer cell death twofold compared to non-magnetic MODs. CONCLUSIONS: A new PMO-based material, MOD nanomedicines, was synthesised using the chemotherapeutic drug MTO as a silica precursor. MTO@MOD nanomedicines demonstrated their efficacy in significantly reducing the viability of breast cancer cells. In addition, we incorporated Fe3O4 into MODs to generate magnetic MODs for active tumour targeting and enhanced drug efficacy by ROS generation. These findings pave the way for the designing of silica-based multitherapeutic nanomedicines for cancer treatment with improved drug delivery, reduced side effects and enhanced efficacy.

Apigenin's Modulation of Doxorubicin Efficacy in Breast Cancer.

Apigenin, a naturally derived flavonoid, is increasingly being acknowledged for its potential therapeutic applications, especially in oncology. This research explores apigenin's capacity to modulate cancer cell viability, emphasizing its roles beyond its minimal antioxidant activity attributed to its basic molecular structure devoid of hydroxyl groups. We investigated apigenin's effects on two breast cancer cell lines, estrogen-dependent MCF-7 and non-estrogen-dependent MDA-MB-231 cells. Our findings reveal that apigenin exerts a dose-dependent cytotoxic and anti-migratory impact on these cells. Interestingly, both apigenin and doxorubicin-a standard chemotherapeutic agent-induced lipid droplet accumulation in a dose-dependent manner in MDA-MB-231 cells. This phenomenon was absent in MCF-7 cells and not evident when doxorubicin and apigenin were used concurrently, suggesting distinct cellular responses to these treatments that imply that their synergistic effects might be mediated through mechanisms unrelated to lipid metabolism. A further chemoinformatics analysis indicated that apigenin and doxorubicin might interact primarily at the level of ATP-binding cassette (ABC) transporter proteins, with potential indirect influences from the AKT and MYC signaling pathways. These results highlight the importance of understanding the nuanced interactions between apigenin and conventional chemotherapeutic drugs, as they could lead to more effective strategies for cancer treatment. This study underscores apigenin's potential as a modulator of cancer cell dynamics through mechanisms independent of its direct antioxidant effects, thereby contributing to the development of flavonoid-based adjunct therapies in cancer management.

'I presumed the pain would eventually get better by itself'; challenges with access to rehabilitation for upper limb dysfunction after breast cancer treatment - Descriptive and qualitative findings from a cross-sectional survey.

PURPOSE: Sixty percent of breast cancer patients develop persistent upper limb pain and dysfunction, but only limited knowledge exists about how these symptoms relate to rehabilitation access. METHODS: A postal survey was sent to patients treated at a London University Teaching Hospital (2018-2020). Data were collected on pain (Pain Detect), shoulder function (Disability of Shoulder Arm and Hand (DASH)), quality-of-life (QoL) (EQ-5D-5L), and clinical characteristics, including treatment and access to rehabilitation. The free-text section invited patients' comments on upper limb symptoms and management strategies, which were analysed thematically. Quantitative data were analysed descriptively, and the medians were examined with Mann-Whitley U-Tests or Kruskal-Wallis Test. RESULTS: Of 511 patients surveyed, 162 (32 %) questionnaires were returned and analysed. Respondents' mean age was 62 years (SD 11.3). The majority had Sentinel Node Biopsy 71 % (116/162) and mastectomy 61 % (99/162). 73 % (119/162) reported pain. Mean (SD) Pain Detect and DASH Score were respectively 11.07 (7) and 21.7 (21.5), with 51 % recording significant shoulder dysfunction, and only 28 % reporting access to rehabilitation. Individuals with neuropathic pain had significantly higher median (range) DASH score 60.8 (35.8, 75.0) p = 0.000. Median DASH score for sedentary individuals was significantly higher 22.9 (7.9, 31.8) p = 0.0009. Free-text analysis revealed persistent, progressive symptoms, mixed attitudes towards exercise and variations in access to rehabilitation and support. CONCLUSION: Two years following surgery many patients reported significant upper limb symptoms which adversely impact on QoL. However, approximately two thirds did not access potentially beneficial rehabilitation treatments. There is a need to improve pathways of care.

Sensitivity of automated and manual treatment planning approaches to contouring variation in early-breast cancer treatment.

PURPOSE: One of the advantages of integrating automated processes in treatment planning is the reduction of manual planning variability. This study aims to assess whether a deep-learning-based auto-planning solution can also reduce the contouring variation-related impact on the planned dose for early-breast cancer treatment. METHODS: Auto- and manual plans were optimized for 20 patients using both auto- and manual OARs, including both lungs, right breast, heart, and left-anterior-descending (LAD) artery. Differences in terms of recalculated dose (ΔDrcM,ΔDrcA) and reoptimized dose (ΔDroM,ΔDroA) for manual (M) and auto (A)-plans, were evaluated on manual structures. The correlation between several geometric similarities and dose differences was also explored (Spearman's test). RESULTS: Auto-contours were found slightly smaller in size than manual contours for right breast and heart and more than twice larger for LAD. Recalculated dose differences were found negligible for both planning approaches except for heart (ΔDrcM=-0.4 Gy, ΔDrcA=-0.3 Gy) and right breast (ΔDrcM=-1.2 Gy, ΔDrcA=-1.3 Gy) maximum dose. Re-optimized dose differences were considered equivalent to recalculated ones for both lungs and LAD, while they were significantly smaller for heart (ΔDroM=-0.2 Gy, ΔDroA=-0.2 Gy) and right breast (ΔDroM =-0.3 Gy, ΔDroA=-0.9 Gy) maximum dose. Twenty-one correlations were found for ΔDrcM,A (M=8,A=13) that reduced to four for ΔDroM,A (M=3,A=1). CONCLUSIONS: The sensitivity of auto-planning to contouring variation was found not relevant when compared to manual planning, regardless of the method used to calculate the dose differences. Nonetheless, the method employed to define the dose differences strongly affected the correlation analysis resulting highly reduced when dose was reoptimized, regardless of the planning approach.

Recent advances in breast cancer metastasis with special emphasis on metastasis to the brain.

Understanding the underlying mechanisms of breast cancer metastasis is of vital importance for developing treatment approaches. This review emphasizes contemporary breakthrough studies with special focus on breast cancer brain metastasis. Acquired mutational changes in metastatic lesions are often distinct from the primary tumor, suggesting altered mutagenesis pathways. The concept of micrometastases and heterogeneity within the tumors unravels novel therapeutic targets at genomic and molecular levels through epigenetic and proteomic profiling. Several pre-clinical studies have identified mechanisms involving the immune system, where tumor associated macrophages are key players. Expression of cell proteins like Syndecan1, fatty acid-binding protein 7 and tropomyosin kinase receptor B have been implicated in aiding the transmigration of breast cancer cells to the brain. Changes in the proteomic landscape of the blood-brain-barrier show altered permeability characteristics, supporting entry of cancer cells. Findings from laboratory studies pave the path for the emergence of new biomarkers, especially blood-based miRNA and circulating tumor cell markers for prognostic staging. The constantly evolving therapeutics call for clinical trials backing supportive evidence of efficacies of both novel and existing approaches. The challenge lying ahead is discovering innovative techniques to replace use of human samples and optimize small-scale patient recruitment in trials.

Antiprogestins for breast cancer treatment: We are almost ready.

The development of antiprogestins was initially a gynecological purpose. However, since mifepristone was developed, its application for breast cancer treatment was immediately proposed. Later, new compounds with lower antiglucocorticoid and antiandrogenic effects were developed to be applied to different pathologies, including breast cancer. We describe herein the studies performed in the breast cancer field with special focus on those reported in recent years, ranging from preclinical biological models to those carried out in patients. We highlight the potential use of antiprogestins in breast cancer prevention in women with BRCA1 mutations, and their use for breast cancer treatment, emphasizing the need to elucidate which patients will respond. In this sense, the PR isoform ratio has emerged as a possible tool to predict antiprogestin responsiveness. The effects of combined treatments of antiprogestins together with other drugs currently used in the clinic, such as tamoxifen, CDK4/CDK6 inhibitors or pembrolizumab in preclinical models is discussed since it is in this scenario that antiprogestins will be probably introduced. Finally, we explain how transcriptomic or proteomic studies, that were carried out in different luminal breast cancer models and in breast cancer samples that responded or were predicted to respond to the antiprogestin therapy, show a decrease in proliferative pathways. Deregulated pathways intrinsic of each model are discussed, as well as how these analyses may contribute to a better understanding of the mechanisms involved.

Real-World Study of Adjuvant Biosimilar Trastuzumab-dkst for HER2-Positive Breast Cancer Treatment in a Brazilian Population.

INTRODUCTION: Biological monoclonal antibodies play a pivotal role in cancer treatment, with biosimilars significantly enhancing their accessibility. In Brazil's ethnically diverse setting, real-world evidence is crucial for assessing the effectiveness and applicability of these therapies in routine clinical practice. METHODS: We performed a multicentric, observational, prospective real-world study on biosimilar trastuzumab-dkst for adjuvant treatment of early HER2-positive breast cancer in Brazilian patients. Data were collected using a case-report form. RESULTS: Of the 176 recruited, we present data from the first 59 patients (mean age 51.7 ± 12.9 years) who had completed treatment with trastuzumab-dkst. The mean time from diagnosis to the first adjuvant treatment with trastuzumab-dkst was 5.5 ± 2.7 months. Of the patients, 59% of patients achieved at least a 30-month follow-up. The 31.7-month invasive disease-free survival rate (IDFS) was 94.5% (95% CI 83.9-98.2%) and median IDFS was not achieved, since only three patients had invasive disease recurrence. The overall survival rate was 100% until the last assessment. The observed adverse events were similar to those presented by other studies using biosimilar or reference trastuzumab. Four serious adverse events (8.5%) were observed. A reduction in left ventricular ejection fraction of at least 10% was observed in 16.9% of participants. There was no treatment interruption, and three participants (5.1%) had their trastuzumab-dkst dose reduced. CONCLUSION: Our study reinforces the existing pivotal data, underscoring the real-world efficacy and safety of biosimilar trastuzumab-dkst in the adjuvant treatment for early HER2-positive breast cancer. The preliminary long-term effectiveness and safety data we present further validate trastuzumab-dkst's role as a cost-saving alternative in oncological care. These findings have important implications for improving patient access to crucial treatments and for the more efficient use of healthcare resources. GOV REGISTRATION: NCT03892655.

Steroid profile in patients with breast cancer and in mice treated with mifepristone.

Progesterone receptors (PRs) are biomarkers used as prognostic and predictive factors in breast cancer, but they are still not used as therapeutic targets. We have proposed that the ratio between PR isoforms A and B (PRA and PRB) predicts antiprogestin responsiveness. The MIPRA trial confirmed the benefit of 200 mg mifepristone, administered to patients with tumors with a high PRA/PRB ratio, but dose-ranging has not been conducted. The aim of this study was to establish the plasma mifepristone levels of patients from the MIPRA trial, along with the resultant steroid profiles, and compare these with those observed in mifepristone-treated mice using therapeutic schemes able to induce the regression of experimental mammary carcinomas with high PRA/PRB ratios: 6 mg pellets implanted subcutaneously, or daily doses of 12 mg/kg body weight. The plasma levels of mifepristone and other 19 plasma steroids were measured by liquid chromatography-tandem mass spectometry. In mifepristone-treated mice, plasma levels were lower than those registered in mifepristone-treated patients (i.e. day 7 after treatment initiation, pellet-treated mice: 8.4 ± 3.9 ng/mL; mifepristone-treated patients: 300.3 ± 31.7 ng/mL (mean ± s.d.; P < 0.001)). The increase in corticoid related steroids observed in patients was not observed in mifepristone-treated mice. The increase in progesterone levels was the most significant side effect detected in mifepristone-treated mice after 14 or 21 days of treatment, probably due to an ovarian compensatory effect not observed in postmenopausal patients. We conclude that in future clinical trials using mifepristone, the possibility of lowering the standard daily dose of 200 mg should be considered.

Towards Agility in Breast Cancer Treatment Principles as Adopted from Agile Software Engineering.

Purpose: The complex nature of breast cancer demands flexible and adaptable principles that can account for the diverse characteristics and evolving conditions of each patient. However, there are no common breast cancer treatment agility principles that can influence policies and direct breast cancer professionals and healthcare providers into enhancing the delivery of health outcomes to patients under these conditions along with continuous rapid improvements in breast cancer treatment plan design. The incorporation of agile principles from software engineering offers a promising avenue for enhancing patient care. This research is conducted to identify breast cancer treatment agility principles adopted from the software engineering field and to validate their conformance to agility through work reported from literature in breast cancer treatment context. Material and Methods: The authors applied a structured research methodology that involved interviews for eliciting and validating twelve agility principles from oncologists. Discussion of each principle is reflected using work reported from literature as a form of validation. Finally, a domain expert reviewed the literature-driven validation for each of the twelve identified breast cancer treatment agile principle to finally validate their conformance to agility and provide results. Results: This work resulted twelve validated agility principles for breast cancer treatment and classified whether they are meeting, partially-(hybrid), or not meeting agility. Seven out of the twelve agile principles resulted as meeting agility, where the remaining five principles resulted as partially meeting agility. None of them is recorded as not meeting agility. Conclusion: The work contributes to forming an agile mindset that can empower breast cancer professionals to optimize treatment plans, enhance patient experiences, and continuously improve the quality of care. The twelve identified agile principles are anticipated to contribute to driving more efficient oncology practices, policies, and protocols. It is concluded that the breast cancer treatment agility principles are not limited to twelve.

Enhancing breast cancer treatment selection through 2TLIVq-ROFS-based multi-attribute group decision making.

Introduction: Breast cancer is an extremely common and potentially fatal illness that impacts millions of women worldwide. Multiple criteria and inclinations must be taken into account when selecting the optimal treatment option for each patient. Methods: The selection of breast cancer treatments can be modeled as a multi-attribute group decision-making (MAGDM) problem, in which a group of experts evaluate and rank alternative treatments based on multiple attributes. MAGDM methods can aid in enhancing the quality and efficacy of breast cancer treatment selection decisions. For this purpose, we introduce the concept of a 2-tuple linguistic interval-valued q-rung orthopair fuzzy set (2TLIVq-ROFS), a new development in fuzzy set theory that incorporates the characteristics of interval-valued q-rung orthopair fuzzy set (IVq-ROFS) and 2-tuple linguistic terms. It can express the quantitative and qualitative aspects of uncertain information, as well as the decision-makers' level of satisfaction and dissatisfaction. Results: Then, the 2TLIVq-ROF weighted average (2TLIVq-ROFWA) operator and the 2TLIVq-ROF weighted geometric (2TLIVq-ROFWJ) operator are introduced as two new aggregation operators. In addition, the multi-attribute border approximation area comparison (MABAC) method is extended to solve the MAGDM problem with 2TLIVq-ROF information. Discussion: To demonstrate the efficacy and applicability of the suggested model, a case study of selecting the optimal breast cancer treatment is presented. The results of the computations show that the suggested MAGDM model is able to handle imprecision and subjectivity in complicated decision-making scenarios and opens new research scenarios for scholars.

Menopausal Symptoms and Utian Quality of Life Scale Following a Breast Cancer Diagnosis and Its Impact on Endocrine Adherence.

Introduction Standard treatment for oestrogen-positive breast cancers involves a minimum of five years of adjuvant endocrine treatment with a significant improvement in survival. However, the side effects of endocrine treatments are often underestimated. We aimed to identify the frequency of side effects, adherence to treatment, and impact on the quality of life of breast cancer survivors. Methods All patients attending holistic needs assessment and health and wellbeing events with a clinical nurse specialist between March and October 2023 were given a menopause symptom proforma and Utian menopausal quality of life scale questionnaire. Results A total of 99/150 (66%) patients attending a health needs assessment with a clinical nurse specialist following a diagnosis of breast cancer returned forms. The mean age of respondents was 56.7 years, with a mean 2.5-year duration since diagnosis. Thirty-seven percent of respondents were premenopausal at diagnosis, and 63% were postmenopausal. Five percent stopped treatment early due to menopausal symptoms, and 2.2% changed endocrine treatment. Overall, the mean menopausal quality of life score was -0.454 (p=0.0052). Within the premenopausal cohort, 84% reported hot flushes, 81% a low-sex drive, 73% night sweats, 89% memory problems, 89% fatigue, and 76% joint aches. This group scored -0.20 SD on the quality of life scale. The postmenopausal group reported a 71% incidence of hot flushes, 79% both poor sleep and joint pain, 60% breast pain, and 86% fatigue. They demonstrated a mean of -0.58 SD on the quality of life scale. The failure to adhere to endocrine treatment was reported by 6% of respondents, who cited side effects as the reason for non-compliance. Conclusion In conclusion, there is a significant increase in menopausal symptoms following treatment for breast cancer, which is negatively impacting well-being, quality of life, and endocrine adherence.