Breast Cancer Research and Treatment最新文献

Background: Managing cardiovascular risk is key for breast cancer survivors, many of whom have pre-existing conditions like hypertension and hyperlipidaemia. Research suggests compliance with cardiovascular medication declines after a breast cancer diagnosis. However, these studies rely on population-level averages, which mask patient heterogeneity and longitudinal variations in compliance. This study aimed to identify compliance trajectories with cardiovascular medication around a breast cancer diagnosis and describe associated characteristics.

Methods: Using the French National Health Data System, we constructed a cohort of women diagnosed with incident breast cancer (2016-2020) who received at least 2 cardiovascular drug classes before diagnosis for primary prevention, defined as treatment of cardiovascular risk factors in the absence of established cardiovascular disease. Compliance trajectories were analysed over 3 years using group-based trajectory modelling.

Results: Among 35,399 women, 6 trajectories were identified: stable high compliance (49.9%), moderate stable (21.2%), low stable (12.8%), sharp decline post-diagnosis (9.8%), treatment discontinuation post-diagnosis (3.4%), and very low and declining (2.9%). Declining trajectories were associated with higher rates of metastases and chemotherapy.

Conclusion: This study revealed substantial heterogeneity in compliance responses post-diagnosis. While most women maintained stable compliance, a significant subset experienced sharp declines, likely linked to cancer severity. Early interventions post-diagnosis could reduce cardiovascular risk and improve outcomes.

Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by high rates of tumor protein 53 (TP53) mutation and with limited targeted therapies. Despite being clinically advantageous, direct targeting of mutant TP53 has been challenging. Therefore, we hypothesized that p53-mutant TNBC cells rely upon other potentially targetable survival pathways.

Methods: In vitro and in silico screens were used to identify drugs that induced preferential death in TP53-mutant cells. The effect of the ferroptosis inducer ML-162 was tested both in vitro and in vivo and the mechanism of cell death following ML-162 treatment or GPX4 knockout was determined.

Results: High-throughput drug screening demonstrated that TP53-mutant TNBCs are highly sensitive to peroxidase, cell cycle, cell division, and proteasome inhibitors. We further characterized the effect of the ferroptosis inducer ML-162 and demonstrated that ML-162 induces preferential ferroptosis in TP53-mutant TNBC cells. Treatment of TP53-mutant xenografts with ML-162 suppressed tumor growth and increased lipid peroxidation in vivo. Testing ferroptosis inducers demonstrated TP53-missense mutant, and not TP53-null or wild-type cells, were more sensitive to ferroptosis, and expression of mutant TP53 genes in p53-null cells sensitized cells to ML-162 treatment.

Conclusions: This study demonstrates that TP53-mutant TNBC cells have unique survival pathways that can be effectively targeted. Our results illustrate the intrinsic vulnerability of TP53-mutant TNBCs to ferroptosis and highlight GPX4 as a potential target for the precision treatment of TP53-mutant TNBC.

RISE UP (Revolutionizing Investigations to StEp Up Prevention) for breast cancer brought together leading cancer specialists, women's health providers, basic and population scientists, regulators, politicians, industry leaders, patient advocates, and more from around the world to discuss and chart a radical rethinking of breast cancer prevention and risk reduction through a lens of hormonal management across a woman's life course. The presentations at RISE UP were organized to outline a path forward by leveraging what we know about breast cancer biology, early detection, treatment, and endocrine therapy toward a better and sustainable approach for breast cancer prevention. Important conference considerations were to expand our thinking about prevention by broadly considering how the hormonal environment during different life phases or common benign conditions could be better managed to minimize breast cancer risk. This set the stage for transitioning to advances in risk prediction, promising risk-reducing agents, and biomarker-driven trials to test them. Biomarker-based trials discussed focused on 1) lower or intermittent doses of standard prevention agents, 2) drugs already approved for other health purposes, and 3) maximizing benefits from lifestyle interventions alone or in combination. Throughout RISE UP, there was a strong focus on promoting health equity, including comprehensive reproductive health access, equitable representation in clinical trials, and strategies to educate women, providers, and advocates about disparities in care and how to successfully reduce them. The meeting concluded with a competition for innovative approaches to breast cancer prevention that could be integrated into hormonal and women's health interventions. RISE UP was an innovative conference that provided a forum for cross-cutting topics in women's health that do not currently exist. The insights shared at RISE UP will be paradigm shifting in breast cancer prevention and women's health space in the years to come.

Purpose: The risk of second non-breast primary cancer in Chinese women with breast cancer who carry germline BRCA1/2 pathogenic variants (PVs) is largely unknown.

Methods: From October 2003 to February 2023, 11,212 women with breast cancer were recruited. BRCA1/2 mutation status of these patients was determined; the age-specific cumulative risk of second non-breast primary cancer was estimated.

Results: Of the 11,212 breast cancer patients, 284 carried BRCA1 PVs, 433 carried BRCA2 PVs, and 10,495 were non-carriers. After a median follow-up of 8.4 years, 10.9% of BRCA1 carriers, 7.2% of BRCA2 carriers, and 3.6% of non-carriers developed second non-breast primary cancers; and 6.7% of BRCA1 carriers, 1.4% of BRCA2 carriers, and 0.1% of non-carriers developed ovarian cancer. Cumulative risks of second primary cancer to age 70 years were 28.4% for BRCA1 carriers, 17.3% for BRCA2 carriers, and 6.2% for non-carriers. Cumulative risks of ovarian cancer to age 70 years were 19.8% for BRCA1 carriers, 3.9% for BRCA2 carriers, and 0.4% for non-carriers. No BRCA1 and BRCA2 carriers developed ovarian cancer before the ages of 40 and 45 years, respectively. BRCA2 carriers had higher risks of thyroid cancer (relative risk [RR] 2.16; 95% CI, 1.04-4.51; P = 0.039) and endometrial adenocarcinoma (RR 3.90; 95% CI, 1.47-10.32; P = 0.006) than non-carriers.

Conclusions: BRCA1/2 carriers exhibit a 2- to 3-fold higher risk of second primary cancer than non-carriers. Ovarian cancer represents the majority of second primary cancers in BRCA1 carriers, while BRCA2 carriers have a wider spectrum of second primary cancers.

Purpose: Genomic testing informs treatment decisions for estrogen receptor-positive, progesterone receptor-positive, and HER2-negative early-stage breast cancer, yet uptake remains disproportionately low among racially and ethnically minoritized and low-income populations. Understanding the multilevel barriers driving these disparities is essential for equitable delivery of personalized cancer care. This study explores barriers to and potential solutions for equitable access to genomic testing, incorporating perspectives from patients, caregivers, clinicians, navigators, payers, and policymakers.

Methods: We conducted a qualitative study using community-based participatory research principles in partnership with five community-based organizations. Semi-structured interviews were completed with 32 participants: patients (n = 20), caregivers (n = 2), clinicians (n = 4), navigators (n = 2), payers (n = 2), and policymakers (n = 2). Transcripts were analyzed using constructivist grounded theory and interpretive description.

Results: Three major themes emerged: (1) Limited awareness and information across interested groups, including confusion between genomic and genetic testing, particularly among patients, caregivers, and some healthcare staff; (2) Modifiable challenges in accessing genomic testing, such as administrative complexity, insurance barriers, and financial toxicity; and (3) Racial, ethnic, and socioeconomic factors, including language barriers and lack of culturally appropriate materials, that impede equitable access to testing.

Conclusions: Equitable delivery of genomic testing in breast cancer requires multilevel interventions targeting structural barriers, administrative complexity, and culturally tailored education. Addressing these barriers is likely to reduce disparities and further improve health equity in cancer care.

Background: People receiving treatment for breast cancer often report sleep disturbance. This systematic review explored the prevalence and impact of breast cancer treatment on sleep disturbance.

Methods: The Medline, Embase, CINAHL Plus with full text, Psych INFO, Cochrane Library/Central Register of Controlled Trials, and Scopus databases were searched up to December 2024. Eligible studies recruited people undergoing breast cancer treatment and reported the impact of treatment on their sleep. Two authors reviewed full-text publications for eligibility, data extraction, and quality appraisal. Demographics and sleep outcomes were summarised via descriptive statistics.

Results: Among the 32,119 studies identified, 80 met the eligibility criteria. Studies have used a variety of sleep assessment measures and thresholds to define sleep disturbance. The Pittsburgh Sleep Quality Index (PSQI) and actigraphy were the most frequently used, 63% and 24%, respectively. The mean prevalence of poor sleep quality (as per the PSQI) for each treatment was as follows: surgery, 63%; chemotherapy, 62%; radiation therapy, 64%; and endocrine therapy, 57%; and clinically significant insomnia (as per the Insomnia Severity Index) for surgery, 20%; chemotherapy, 24%; radiation therapy, 23%; and endocrine therapy, 35%. A significant increase in sleep disturbance related to cancer treatment was reported in 62% of the studies assessing chemotherapy, 39% assessing radiation therapy, 20% assessing endocrine therapy, and 17% assessing breast surgery.

Conclusion: Sleep disturbance is reported in approximately 60% of people receiving treatment for breast cancer, with chemotherapy being the most studied treatment. The prevalence and severity of sleep disturbance vary across studies due to the heterogeneity of assessment tools used, and thresholds to define poor sleep. This highlights the need for a consistent method of assessing sleep disturbance and the need for effective strategies to improve sleep.

Purpose: To understand how access to care influences metastatic breast cancer burden (MBC) while accounting for molecular tumor characteristics, and identify interventions to reduce metastatic disease burden.

Methods: The Carolina Breast Cancer Study is a population-based cohort with invasive breast cancer (diagnosed 2008-2013). Both de novo metastasis (stage IV at diagnosis) and distant recurrence were evaluated (12 years of follow-up. Tumor data were from medical records, pathology reports, and RNA expression data. Social variables and access to care were from participant surveys. Generalized linear models were used to estimate associations of biological and access characteristics with MBC; Cox models were used to estimate recurrence hazards.

Results: 464/2998 patients (15.5%) had MBC (n = 109 de novo; n = 355 recurrent). MBC was associated with grade 3 vs 1 (odds ratio (OR) = 4.15, 95% CI: 2.60, 6.99), LumB vs LumA (OR = 2.08, 95% CI: 1.48, 2.90), and high vs low PAM50 risk of recurrence score (OR = 4.45, 95% CI: 2.93, 6.99) vs. non-MBC. MBC was associated with Black race (Hazard ratio (HR) = 1.66, 95% CI: 1.32, 2.11), poverty (HR = 1.47; 95% CI: 1.09, 1.99), and low education (HR = 1.48, 95% CI: 1.03, 2.13). Controlling for healthcare access (screening, regular care, delayed treatment, and community healthcare) attenuated associations with metastasis for poverty and education, but had lesser effects on race associations.

Conclusions: Disparities in MBC burden persist after adjustment for individual- and community-level healthcare access. Reducing burden of MBC in Black women necessitates simultaneous targeting of biological and access to care factors.

Introduction: Black women in the United States have higher breast cancer mortality rates compared to women of other races/ethnicities. Heterogeneity in body composition between Black and non-Black women may contribute to differences in relative drug dosing and chemotherapy toxicities, leading to treatment delays and lower treatment completion rates. This study evaluated the extent to which drug dose/kilogram (kg) fat free mass (FFM) differs by race, and whether measures of FFM or adipose tissue (AT) are independently and/or jointly associated with hematologic toxicity, treatment delays, treatment discontinuation, and relative dose intensity (RDI).

Methods: Women who were treated with neo/adjuvant anthracycline- and/or taxane-containing regimens for breast cancer between 2012-2019 and had an abdominal CT scan within 12 weeks of chemotherapy initiation were included in this retrospective study. Visceral and subcutaneous AT area and FFM were measured using CT scan slices at the L3 vertebra level.

Results: A total of 230 women met the inclusion criteria. On average, Black women were older and had higher weight, FFM and AT compared to non-Black women; however, Black women had lower percent FFM. No statistically significant differences in initial or cumulative drug dose/kg FFM were observed between Black vs non-Black women for any individual drug. Similarly, neither FFM or AT were independently or jointly associated with incidence of hematologic toxicity, treatment delays or discontinuation for any individual chemotherapy drug.

Conclusion: Current BSA-based chemotherapy dosing regimens do not appear to contribute to disparities in treatment-associated toxicity or chemotherapy completion.

Purpose: This study assessed the accuracy of self-reported inflammatory breast cancer (IBC) diagnoses within the Count Me In (CMI) Metastatic Breast Cancer Project. Given IBC's aggressive nature and diagnostic complexity, we aimed to evaluate the reliability of patient-reported data by quantifying concordance rates between self-reported and clinically confirmed diagnoses.

Methods: Medical records from 79 patients who self-identified as having IBC were reviewed to confirm the diagnosis through provider documentation. When explicit confirmation was absent, a recently validated quantitative IBC scoring system was applied. Each patient's diagnosis was adjudicated by an expert physician, with cases classified as concordant or discordant based on predefined criteria. A concordance threshold of 90% was established to consider patient-reported diagnoses as sufficiently reliable.

Results: Among the 79 patients, 57/79 (72.2%) had concordant diagnoses based on either explicit documentation or scoring system verification. Specifically, 51/79 (64.6%) had explicit documentation, while an additional 6/79 (7.6%) met scoring system criteria. However, 22/79 (27.8%) were discordant, either lacking evidence or unable to be confirmed due to incomplete medical records, falling below the 90% concordance threshold required for reliability.

Conclusion: Although patient self-reporting via the CMI initiative allows rapid data collection, reliance solely on self-identification for diagnosing IBC may lead to misclassification. Future strategies should incorporate refined symptom-specific screening and prioritize enrolling patients with stage III IBC. Advanced technologies such as AI-assisted medical record analysis could further enhance diagnostic accuracy and facilitate high-quality data collection for improved diagnosis and outcomes.

Purpose: Systemic therapy is standard for metastatic inflammatory breast cancer (MIBC), but the role of locoregional therapy in survival remains unclear. The objective of this study was to compare overall survival (OS) between patients with MIBC who received trimodal therapy vs chemotherapy alone.

Methods: Patients diagnosed with MIBC between 2004 and 2021 were identified in the NCDB. The cohort was divided into those who received trimodal therapy vs chemotherapy only. Trimodal therapy included receipt of chemotherapy, surgery (modified radical or radical mastectomy), and radiation therapy. Overlap Propensity Score Weighted Cox proportional hazard models examined the association between treatment (chemotherapy versus trimodal therapy) and OS.

Results: A total of 2872 patients with MIBC were included, of whom 403 (14.0%) underwent trimodal therapy and 2469 (86.0%) received chemotherapy alone. Median OS was longer with trimodality therapy than with chemotherapy alone (47.0 months vs 34.4 months, p < 0.001). Receiving trimodal therapy was associated with a 28% lower hazard of mortality compared to chemotherapy only (aHR: 0.72, 95% CI 0.62-0.84).

Conclusions: In this NCDB cohort of patients with MIBC, receipt of trimodal therapy improved OS compared with chemotherapy only.