Treatment Of Breast Cancer Patients Research Articles

Palbociclib Is Safe for Breast Cancer Patients With Mild Hepatic Impairment: A Multicenter Retrospective Study Using Real-World Data.

The liver is crucial for metabolizing the anticancer drug palbociclib, but limited information is available on the impact of hepatic impairment on its toxicity and efficacy, with no real-world data available. This study aims to evaluate how hepatic impairment affects hematological toxicity and progression-free survival (PFS) of palbociclib in advanced hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer, using the National Cancer Institute scoring system, in a large real-world dataset. This multicenter retrospective observational study included female patients treated with palbociclib between August 2017 and February 2024. Regression analysis was used to compare the risk of developing grade 3/4 hematological toxicity and PFS between patients with normal and mild impaired liver function. In total, 478 female patients were included. Patients with mild hepatic impairment (n = 205) did not have an increased risk of developing grade 3/4 neutropenia compared with patients with normal hepatic function (n = 273) (hazard ratio (HR) = 1.11; 95% CI 0.83-1.47). In addition, the PFS was not significantly different between both groups (HR = 1.15; 95% CI 0.93-1.42). In real-world settings, patients with mild hepatic impairment do not have a higher risk of developing palbociclib-induced neutropenia or disease progression than patients with normal hepatic function. These findings can guide clinicians when treating breast cancer patients with mild hepatic impairment.

Therapeutic alliance in a stepped digital psychosocial intervention for breast cancer patients: findings from a multicentre randomised controlled trial.

Action mechanisms of therapeutic alliance in stepped and digital interventions remain unclear. (a) To compare the development of therapeutic alliance between psychosocial treatment as usual (PTAU) and a stepped digital intervention designed to prevent distress in cancer patients; (b) to analyse the level of agreement between patients' and therapists' therapeutic alliance ratings; and (c) to explore variables associated with therapeutic alliance in the digital intervention. A multicentre randomised controlled trial with 184 newly diagnosed breast cancer women was conducted. Patients were assigned to digital intervention or PTAU. Therapeutic alliance was assessed at 3, 6 and 12 months after inclusion using the working alliance inventory for patients and therapists. Age, usability (system usability scale), satisfaction (visual analogue scale), type and amount of patient-therapist communication were analysed as associated variables. Patients and therapists established high therapeutic alliance in the digital intervention, although significantly lower compared with PTAU. The development of patients' therapeutic alliance did not differ between interventions, unlike that of the therapists. No agreement was found between patients' and therapists' therapeutic alliance ratings. Patients' therapeutic alliance was associated with usability and satisfaction with app, whereas therapists' therapeutic alliance was associated with satisfaction with monitoring platform. A stepped digital intervention for cancer patients could develop and maintain strong therapeutic alliance. Neither the type nor amount of communication affected patients' therapeutic alliance, suggesting that flexible and available digital communication fosters a sense of care and connection. The association between usability and satisfaction with digital tools highlights their importance as key therapeutic alliance components in digital settings.

BRCA Mutation Negatively Impacts TPT1/TCTP-Regulated Autophagic Response in Breast Cancer

Autophagy plays a crucial role in both cancer prevention and cancer progression. The multi-faceted process allows for the degradation of cellular components as well as their recycling for energy. TPT1 (tumor protein, translationally controlled 1) overexpression is associated with cancer progression in several tumor types, and it has been identified as a regulator of autophagic expression through its control of various upstream pathways, including mTOR and p53. Through the inhibition of p53 and the indirect promotion of mTOR, TPT1 effectively impedes the autophagic response. Commonly mutated in breast cancer tumor cells, BRCA is a tumor suppressor protein in which a mutation may lead to tumorigenesis. A search in the TCGA database revealed that TPT1 overexpression is associated with increased survivability in breast cancer patients with BRCA mutations; however, previous studies iterated the opposite, indicating TPT1 overexpression led to poor prognosis in breast cancer. In this study, we describe the influence of BRCA mutations on TPT1-mediated autophagic pathways. In breast cancer wild-type cells, TPT1 knockdown leads to increased autophagic expression and autophagosome formation while in BRCA mutant cells, the effect is negated. Furthermore, we demonstrate that BRCA mutations block TPT1-mediated upregulation of mTOR and its downstream signaling molecules. We further demonstrate that BRCA mutations do not impact AMPK phosphorylation by p53 or the repression of p53 through TPT1. Overall, these findings suggest that BRCA mutations can antagonize TPT1-mediated autophagy via the regulation of p53-independent mTOR signaling. Further understanding of the interaction between these pathways may contribute to new therapeutic approaches to treating breast cancer patients.

Recent advances of antibody-drug conjugates in treating breast cancer with different HER2 status.

Despite the availability of multiple treatment options for breast cancer, challenges such as adverse events, drug resistance, and disease progression persist for patients. The identification of human epidermal growth factor receptor 2 (HER2) as an oncogenic driver in a subset of breast cancers, alongside the development of HER2-targeted therapies, has significantly improved the prognosis of HER2-amplified breast cancers. However, therapeutic options remain limited for HER2-overexpressing or HER2-negative breast cancers. In response to this gap, antibody-drug conjugates (ADCs) have emerged as a promising approach. ADCs combine the specificity of monoclonal antibodies with the cytotoxic effects of chemotherapy, which allows for the targeted delivery of a cytotoxic payload to cancer cells. ADCs have been used as adjuvant chemotherapeutic treatments and salvage therapies across various breast cancer subtypes, which have greatly improved the prognosis of breast cancer patients. Numerous ongoing clinical trials seek to optimize dosing strategies and identify patient populations that would benefit most from ADCs. This review presents an updated and comprehensive overview of emerging investigational ADCs for treating breast cancer patients with various HER2 subtypes. These ADCs are spearheading a new era in targeted cancer therapy, promising to innovate treatment paradigms for both HER2-positive and HER2-low breast cancers.

Characteristics of positive and negative effects on the quality of life of breast cancer patients

BackgroundPostoperative and ongoing treatment of breast cancer is traumatic to women with breast cancer and may lead to positive and negative psychological diseases, which can affect the prognosis of patients with breast cancer. Positive affect (PA) and negative affect (NA) significantly impact the prognosis of postoperative breast cancer patients. However, the effects of specific emotions on patient prognosis and the relationships between them are still unclear.MethodsA case–control study was conducted to investigate the characteristics of PA and NA and their effects on Quality of Life (QoL) in breast cancer patients. 442 postoperative breast cancer patients and 444 healthy women were recruited from November to December 2021. For the observation group, participants were eligible if they (1) were aged between 16 and 80 years and (2) had a confirmed pathological diagnosis of breast cancer and (3) possessed the ability to read text, voluntarily agreed to participate, provided informed consent, and cooperated with the study procedures. The control group consisted of individuals without breast cancer who met all other criteria, as stated above. Patients were excluded from the study if they (1) had severe comorbid conditions causing functional impairment or life-threatening risks or (2) suffered from mental disorders or were unconscious at the time of the study. For the control group, individuals with a pathological diagnosis of breast cancer were also excluded. All other exclusion criteria were consistent with those for the observation group. The demographic information and clinicopathological information of the participants were collected. The Positive Affect and Negative Affect Scale (PANAS) is a scale containing 20 emotional scores related to emotion and is used to assess the level of positive and negative affect. The Quality of Life Questionnaire Core 30 (QLQ-C30) was used to assess the quality of life of cancer patients in 15 domains. SPSS 24.0 was used to analyze and process the data. Independent-sample t-tests, one-way ANOVA and Pearson correlation analysis, were used to analyze PA and NA in different treatment phases. Polynomial regression and response surface analysis were conducted to assess the relationships among PA, NA, and QoL. The results were considered statistically significant at P < 0.05.ResultsCompared with healthy women, breast cancer patients had lower scores on "alert" and "distressed" but higher scores on "inspired," "scared," and "afraid." There were no significant differences in the relationships between PA and NA between patients and healthy women (P > 0.05). During the initial treatment phase, the highest proportion of patients had an NA greater than the PA (PA < NA). In the rehabilitation phase, the highest proportion of patients had PA greater than or equal to the NA (PA ≥ NA). The relationship between PA and QoL was an inverted U-shaped curve (P < 0.05), whereas the relationship between NA and QoL was a positive U-shaped curve (P < 0.05). There was an interaction effect between PA and NA (P < 0.001). The relationships among PA, NA, and QoL varied across treatment phases. In the initial treatment phase, the presence of both positive and negative affect improved QoL. In the endocrine therapy phase, excessive positive effects decrease QoL. During the rehabilitation phase, QoL improved as positive affect increased relative to negative affect.ConclusionThere are significant differences in the distributions of positive and negative effects in breast cancer patients at different treatment phases. The impact of PA and NA on QoL varies by treatment phase. Our findings have important implications for tailoring emotional interventions for breast cancer patients at different stages of treatment.

Relationship between perceived social support, mental adjustment to cancer, and depression among patients with breast cancer.

Psychological morbidity is common among patients with breast cancer. The present study aimed to find the relationship between modifiable determinants, that is, perceived social support (PSS) and mental adjustment to cancer (reflecting coping) with depression in patients with breast cancer. A total of 76 adult patients with breast cancer undergoing treatment at a tertiary care hospital were recruited in this cross-sectional study. Patients were diagnosed for depression as per ICD-10 criteria. Hamilton Depression Rating Scale was used for assessing the severity of depression. PSS and coping style were assessed using the Multidimensional Scale for Perceived Social Support and Mini-Mental Adjustment to Cancer scale. We analyzed the data using Fisher exact test, Mann-Whitney U test, Spearman's correlation, logistic regression, and mediation analysis. 26.3% patients had depression. The logistic regression showed that PSS is a significant predictor of the occurrence of depression in patients with breast cancer (OR = 0.793, 95% CI: 0.634-0.992). The mediation analysis showed that hopelessness-helplessness (a maladaptive subscale) mediates the effects of PSS on depression. The effect of PSS on the occurrence of depression is mediated through maladaptive coping (hopelessness-helplessness). Accessing these factors can provide an important avenue for psychological intervention in breast cancer patients.

Breast cancer patients with a pre-existing mental illness are less likely to receive guideline-recommended cancer treatment: A systematic review and meta-analysis.

Breast cancer is the most commonly diagnosed cancer worldwide, with early detection and advanced treatments contributing to declining mortality rates. However, managing comorbid conditions, particularly mental illness, presents significant challenges for cancer treatment. This study systematically reviews and meta-analyses the impact of having a pre-existing mental illness on breast cancer treatment utilisation, focusing on specific treatments and comparing different mental illnesses. MEDLINE, EMBASE, CINAHL, and APA PsycInfo databases were searched. After screening, fifteen studies were identified as meeting the inclusion criteria. The included studies were predominantly from high-income countries, and compared breast cancer treatment in patients with and without pre-existing mental illnesses including anxiety, mood disorders, schizophrenia and psychotic disorders, and neurodevelopmental disorders. Meta-analysis revealed that patients with mental illnesses were significantly less likely to receive guideline-recommended treatments (OR=0.78, 95% CI 0.72-0.83, N=5), chemotherapy (OR=0.56, 95% CI 0.34-0.78, N=6), or radiotherapy (OR=0.79, 95% CI 0.66-0.93, N=5). They were also significantly more likely to undergo mastectomy instead of breast-conserving surgery (OR=1.38, 95% CI 1.24-1.52, N=4). Findings were consistent across different mental illnesses. This review highlights the need for targeted interventions to improve healthcare access and address provider biases, promoting better integration of mental health and oncology care.

Exploring Aerobic Energy Metabolism in Breast Cancer: A Mutational Profile of Glycolysis and Oxidative Phosphorylation.

Energy metabolism is a fundamental aspect of the aggressiveness and invasiveness of breast cancer (BC), the neoplasm that most affects women worldwide. Nonetheless, the impact of genetic somatic mutations on glycolysis and oxidative phosphorylation (OXPHOS) genes in BC remains unclear. To fill these gaps, the mutational profiles of 205 screened genes related to glycolysis and OXPHOS in 968 individuals with BC from The Cancer Genome Atlas (TCGA) project were performed. We carried out analyses to characterize the mutational profile of BC, assess the clonality of tumors, identify somatic mutation co-occurrence, and predict the pathogenicity of these alterations. In total, 408 mutations in 132 genes related to the glycolysis and OXPHOS pathways were detected. The PGK1, PC, PCK1, HK1, DONSON, GPD1, NDUFS1, and FOXRED1 genes are also associated with the tumorigenesis process in other types of cancer, as are the genes BRCA1, BRCA2, and HMCN1, which had been previously described as oncogenes in BC, with whom the target genes of this work were associated. Seven mutations were identified and highlighted due to the high pathogenicity, which are present in more than one of our results and are documented in the literature as being correlated with other diseases. These mutations are rs267606829 (FOXRED1), COSV53860306 (HK1), rs201634181 (NDUFS1), rs774052186 (DONSON), rs119103242 (PC), rs1436643226 (PC), and rs104894677 (ETFB). They could be further investigated as potential biomarkers for diagnosis, prognosis, and treatment of BC patients.

074. Pulmonary Lacunae Due to Chemotherapy-Induced Pneumothorax in Metastatic Breast Cancer: A Rare Case Report and Review of Literature

Background: Chemotherapy plays a major role in treating breast cancer patients who develop hematogenous spread or disseminated metastase. Spontaneous pneumothorax is a rare complication of chemotherapy and is commonly associated with chemosensitive tumours such as germ-cell tumours, lymphomas, and sarcomas and rarely with lung and gynaecological malignant disease. Pneumothorax seems to occur 2–7 days after chemotherapy treatment and can be unilateral or bilateral. To present the rare case of a A 56-year-old woman with breast cancer on chemoterapy who had secondary pneumothorax after undergo chemotherapy and treated with chest tube insertion. Methods: Clinical and imagery review of a secondary pnuemothorax after several chemoterapy outlined in case report also review of literature. Results: The patient underwent a chest tube insertion and hospitalized 10 days. She was discharged and responds well to therapy. Conclusion: This is the case of secondary penumothorax due to chemoterapy in breast cancer patient. The mechanisms involved in chemotherapy-related pneumothorax have been proposed because of tumor necrosis inducing the formation of a fistula. Our patient underwent chest tube insertion and other pharmacology therapy to decreased patient her complaint.

Cardiovascular disease risk after breast cancer treatment in patients with a BRCA1/2 pathogenic variant.

Breast cancer (BC) treatment can induce adverse events, such as cardiovascular disease (CVD). Defective DNA repair, as in carriers of BRCA1/2 pathogenic variants (BRCA1/2pv), may contribute to CVD risk. We aimed to study if female BRCA1/2pv carriers are more sensitive to develop CVD after BC treatment than BC patients without a known BRCA1/2pv. In a hospital-based cohort of 17,300 female BC patients, we identified 509 BRCA1/2pv carriers. Cardiovascular morbidity and mortality were assessed through hospital charts and general practitioner questionnaires. We performed Cox regression analyses comparing BRCA1/2pv carriers with all other BC patients, adjusting for age, radiotherapy regimen, chemotherapy regimen, and smoking status. Median follow-up time since BC treatment was 14years. In total, 1108 women experienced ischemic heart disease (IHD), of whom 20 (1.8%) were BRCA1/2pv carriers. Heart failure (HF) was diagnosed in 638 women, of whom 10 (1.6%) were BRCA1/2pv carriers. BRCA1/2pv carriership was associated with a slight not statistically significant increase of IHD (adjHR 1.51, 95%CI 0.93; 2.42), but not with risk of HF (adjHR 0.86, 95%CI 0.44; 1.69). The association between radiotherapy and IHD risk was not significantly different between BRCA1/2pv carriers [HR 2.30 (95%CI 0.79; 6.66)] and other BC patients (HR 1.50, 95%CI 1.30; 1.73). Associations between anthracycline-based chemotherapy and HF risk also did not differ between carriers and other BC patients (HRs of 4.02 (95%CI 1.02; 15.77) and 2.31 (95%CI 1.77; 3.01), respectively). In BRCA1/2pv BC patients, we found no evidence for a higher risk of BC treatment-related CVD than in other BC patients.

Relationship Between Anxiety and Events Chemotherapy-Induced Nausea Vomiting (CINV) Breast Cancer Patients with Chemotherapy in Jember, East Java, Indonesia

In Indonesia and worldwide, breast cancer accounts for the greatest number of cancer patients. Chemotherapy is the treatment used to treat breast cancer patients; however, it might cause One of the psychological adverse effects that chemotherapy usually causes for individuals with breast cancer is anxiety. Chemotherapy-Induced Nausea Vomiting (CINV) is the most common physical adverse effect experienced by breast cancer patients receiving chemotherapy. This cross-sectional study employs certain research approaches. Patients receiving chemotherapy for breast cancer at the RSD Dr. Soebandi Jember and Baladhika Husada Jember Hospital made up the study's population. This research was conducted for one month, and the number of samples used in this research was 120. Anxiety measurement uses a questionnaire Hamilton Anxiety Rating Scale (HAM-A) to measure levels of anxiety, and the Multinational Association of Supportive Care in Cancer (MASCC) Antiemesis Tool (MAT) to measure Chemotherapy Induces Nausea and Vomiting (CINV). Data analysis with a paired sample t test using the IBM SPSS v.25 for Windows programme. The results of the Pearson correlation test between anxiety and CINV in breast cancer patients undergoing chemotherapy showed a significance value of 0.00 or &lt;0.05, which means there is a correlation between anxiety and CINV experienced by respondents. The higher the level of anxiety, the more CINV complaints the patient will experience. Vice versa, the lower the level of anxiety, the CINV experienced by the patient will be minimal. Keyword: anxiety, CINV, Breast Cancer, Chemotherapy

The effects of Tai Chi and Baduanjin on breast cancer patients: systematic review and meta-analysis of randomized controlled trials.

Tai Chi and Baduanjin are nonpharmacological interventions that are widely applied among cancer patients. This meta-analysis aimed to assess the effect of Tai Chi and Baduanjin on breast cancer patients by summarizing and pooling the results of previous studies. The PubMed, Embase, Web of Science, Scopus and Cochrane Library and several databases were searched up to December 1, 2023, to identify high-quality RCTs. Relevant terms such as Tai Chi and Baduanjin were used as keywords. Stata 15.0 software and Review Manager (version 5.3; Cochrane Training) were used to screen the studies, extract the data, code the data, and perform the meta-analysis. The mean differences (MDs) and standardized mean differences (SMDs) with 95% CIs were used to calculate continuous variables. The Cochrane risk of bias assessment tool was used to evaluate the risk of bias. The PICOS framework was used to develop the following eligibility criteria: (i) population - breast cancer patients; (ii) intervention - Tai Chi and Baduanjin intervention; (iii) comparison - Tai Chi and Baduanjin group and different intervention (e.g., regular intervention, routine rehabilitation training, waiting list, sham Qigong, usual care, no intervention); (iv) outcomes - cognitive ability, shoulder joint function, anxiety, depression, fatigue, sleep quality, quality of life; and (v) study design - randomized controlled trial. From January 2013 to December 2023, we included a total of 16 RCTs involving 1247 patients. A total of 647 patients were in the experimental group and were treated with Tai Chi and Baduanjin, while 600 patients were in the control group and were treated with traditional methods. The results of our meta-analysis indicate that Tai Chi and Baduanjin yield outcomes that are comparable to those of traditional treatment methods. Specifically, Tai Chi and Baduanjin significantly increased cognitive function, increased shoulder joint function, improved sleep quality indicators and improved quality of life indicators. Furthermore, Tai Chi and Baduanjin significantly reduced anxiety symptoms, depression symptoms, and fatigue symptoms among breast cancer patients. Sensitivity analysis was performed, a funnel plot was constructed. No publication bias was indicated by Egger's or Begg's test. Overall, Tai Chi and Baduanjin are viable and effective nonpharmacological approaches for treating breast cancer patients, as they yield better results than traditional treatment methods. However, these findings should be interpreted with caution due to the limited number of controlled trials, small sample sizes, and low quality of the evidence. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023469301.

Prevalence and mechanisms of subacromial impingement in breast cancer patients after breast-conserving surgery and radiation therapy: a case-cohort study.

Subacromial impingement is a painful shoulder disorder, which may be common after breast cancer treatment. A previous study showed a high prevalence after mastectomy but prevalence after conservatively treated patients is unknown. Impingement mechanisms in breast cancer survivors have not been studied. Twenty-four breast cancer survivors who had undergone breast-conserving surgery without axillary lymph node dissection followed by radiation therapy, and 12 cancer-free controls were included. Breast cancer survivors were grouped by the presence of subacromial impingement pain. The subacromial space and the supraspinatus tendon were imaged using ultrasound on the treated side in the breast cancer survivors and a randomly chosen side in controls. In these images, the width of the subacromial space, thickness of the supraspinatus tendon and combined thickness of the supraspinatus tendon and surrounding soft tissues were measured. Subacromial impingement prevalence among breast cancer survivors was 54%. The width of the subacromial space and the thickness of the supraspinatus tendon were not different in breast cancer survivors with subacromial impingement compared to breast cancer survivors without subacromial impingement and controls. Combined thickness of the supraspinatus tendon and surrounding soft tissues was grater in breast cancer survivors with subacromial impingement. Prevalence of subacromial impingement is high, even in the most conservatively treated breast cancer patients. The presence of subacromial impingement pain is unrelated to width of the subacromial space, but greater thickness of the supraspinatus tendon and surrounding soft tissue may be part of the impingement mechanism.

Acupressure On Chemotherapy-Induced Nausea and Vomiting among Breast Cancer Patients: A Systematic Review and Meta-analysis.

Nausea and vomiting are one of the common and distressing side effects of chemotherapy in breast cancer patients often impacting their quality of life and treatment adherence. The purpose of this systematic review and meta-analysis was to determine whether acupressure is effective in treating breast cancer patients' acute nausea and vomiting brought on by chemotherapy as well as delayed nausea and vomiting. We systematically searched for Randomized controlled trials and quasi-experimental studies in PubMed, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Clinical Key, Web of Science, EMBASE, and Scopus. Based on the inclusion criteria two reviewers independently identified the articles using key thesaurus and free text terms. The review was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement. According to the pooled findings, acupressure combined with antiemetics greatly lessens the severity of acute nausea [SMD, (95% CI)] [-0.35(-0.62,-0.08), P=0.01, I2=0%], delayed nausea [SMD, (95% CI)] [-0.52(-0.78,-0.26), P<0.001, I2=16%], and delayed vomiting [SMD, (95% CI)] [-0.46(- 0.83,-0.08), P=0.02, I2=43%] brought on by chemotherapy. For chemotherapy-treated breast cancer patients, acupressure is a helpful complementary therapy for easing nausea and vomiting.

Breast-cancer specific comprehensive archive of Patient-Reported Outcome Measures (PROMs) for clinical research and clinical practice in oncology: Results from the PRO4All project

BackgroundInclusion of patient-reported outcomes (PROs) in oncology clinical trials is strongly recommended. However, selecting the most appropriate patient-reported outcome measures (PROMs) is not easy. This study aimed to develop a breast cancer (BC) specific comprehensive archive of PROMs. MethodsAs part of the PRO4All project, we identified available PROMs in oncology by searching facit.org, eortc.org, eprovide.mapi-trust.org, PubMed, ema.europa.eu (European Public Assessment Reports) and published reviews. For this analysis, only BC tools were extracted. We described information about PROM name, type of questionnaire, questionnaire variant(s), recall period, number of items, and presence of minimum clinically important difference (MCID) reference in literature. Then, we assigned each item to a specific domain according to a predefined taxonomy of 38 items for outcome classification. ResultsWe identified and analyzed 383 PROMs. Of these, 29 were BC specific, but 2 were excluded because the questionnaires description was not available. 6 (22.2 %) were variants of another questionnaire. All questionnaires were self-reported. In 6 cases (22.2 %) the recall period to consider was the “last week”. The mean number of items per questionnaire was 25.81 (range 6–71). 602 items were assigned to an outcome domain: emotional functioning/wellbeing in 26.6 % of cases, physical functioning in 14.1 %, delivery of care in 10.8 %, and general outcomes in 10.5 %. MCID reference was found only in 4 (14.8 %) cases. ConclusionsThe newly developed archive represents a useful tool to optimize the use of PROMs in the evaluation of treatments in BC patients, promoting a patient-centered approach both in clinical research and practice.

Melatonin increases Olaparib sensitivity and suppresses cancer-associated fibroblast infiltration via suppressing the LAMB3-CXCL2 axis in TNBC

Triple-negative breast cancer (TNBC) is the most malignant breast cancer subtype, characterized with high aggressiveness and a high recurrence rate. Olaparib is the first US Food and Drug Administration-approved poly(ADP ribose) polymerase (PARP) inhibitor (PARPi) to treat breast cancer patients with a germline BRCA1 or BRCA2 mutation. However, resistance to Olaparib treatment restricts the therapeutic effects, and thus novel therapeutics are urgently required. In the present study, we identified that the combination of melatonin and Olaparib synergistically enhanced the sensitivity of TNBC cells. Moreover, melatonin exerted promising antitumor activities in Olaparib-resistant cells, implying the potential for its clinical application. An RNA-sequencing analysis revealed that melatonin treatment downregulated laminin subunit beta 3 (LAMB3) expression. Genetic ablation of LAMB3 significantly increased Olaparib sensitivity, and subsequently suppressed proliferation, epithelial-to-mesenchymal transition (EMT)-related gene expressions, and aggressiveness of breast cancer cells. Accordingly, LAMB3 expression was positively correlated with C-X-C motif chemokine ligand 2 (CXCL2), and they collaboratively promoted cancer-associated fibroblast (CAF) infiltration. An in vivo study demonstrated that combined treatment with melatonin and Olaparib showed enhanced inhibitory efficacy against tumor growth, LAMB3 expression, CXCL2 levels, and CAF infiltration compared to single treatment groups, and combined treatment with melatonin and Olaparib significantly ameliorated the immunosuppressive tumor microenvironment. These findings illustrate a promising therapeutic strategy using melatonin to overcome Olaparib resistance and activate antitumor immunity via attenuating the LAMB3-CXCL2 axis in breast cancer patients.

Cancer cell stiffening via CoQ10 and UBIAD1 regulates ECM signaling and ferroptosis in breast cancer

CoQ10 (Coenzyme Q10) is an essential fat-soluble metabolite that plays a key role in cellular metabolism. A less-known function of CoQ10 is whether it may act as a plasma membrane-stabilizing agent and whether this property can affect cancer development and progression. Here, we show that CoQ10 and its biosynthetic enzyme UBIAD1 play a critical role in plasmamembrane mechanical properties that are of interest for breast cancer (BC) progression and treatment. CoQ10 and UBIAD1 increase membrane fluidity leading to increased cell stiffness in BC. Furthermore, CoQ10 and UBIAD1 states impair ECM (extracellular matrix)-mediated oncogenic signaling and reduce ferroptosis resistance in BC settings. Analyses on human patients and mouse models reveal that UBIAD1 loss is associated with BC development and progression and UBIAD1 expression in BC limits CTCs (circulating tumor cells) survival and lung metastasis formation. Overall, this study reveals that CoQ10 and UBIAD1 can be further investigated to develop therapeutic interventions to treat BC patients with poor prognosis.

High-dose chemotherapy for patients with stage III breast cancer with homologous recombination deficiency: a discrete choice experiment among healthcare providers.

High-dose chemotherapy with autologous stem cell rescue (HDCT) is currently under investigation as a potential therapy for patients with stage III HER2-negative breast cancer with homologous recombination deficiency (HRD). In addition to survival, the impact on short- and long-term side effects might influence the uptake of HDCT by healthcare professionals. As part of the SUBITO trial, we investigated healthcare professionals' treatment (outcome) preferences for patients with HRD stage III HER2-negative breast cancer and established how healthcare professionals make trade-offs between these treatment outcomes. We conducted a discrete choice experiment in which healthcare professionals were asked to choose repeatedly between scenarios with two treatment options (HDCT or standard of care (SOC)) that varied in outcome with respect to 10-year overall survival (OS), short-term toxicity, long-term cognitive impairment, and premature menopause. We analysed treatment preferences, relative importance, and trade-offs using a multinomial logistic model. Thirty-five of the 151 dedicated breast cancer professionals with extensive experience in treating breast cancer patients completed the survey. The 10-year OS and long-term cognitive impairment were the most important attributes. The results indicate a requirement of 10.4% and 25.1% absolute additional improvement in the 10-year survival rate to justify accepting moderate or severe long-term cognitive impairment as a trade-off, respectively. Therefore, we found in our dataset that healthcare professionals expected a large improvement in 10-year OS to accept moderate to severe cognitive impairment. This information calls for further research into chemotherapy-related cognitive impairment, shared decision-making, and treatment preferences for patients with stage III breast cancer.

ASO Visual Abstract: Surgery Plays a Leading Role in Breast Cancer Treatment for Patients Aged ≥90 Years: A Large Retrospective Cohort Study.

ASO Visual Abstract: Surgery Plays a Leading Role in Breast Cancer Treatment for Patients Aged ≥90 Years: A Large Retrospective Cohort Study.

PTCOG international survey of practice patterns and trends in utilization of proton therapy for breast cancer

Purpose/objectivesThe indications, techniques, and extent to which proton beam therapy (PBT) is employed for breast cancer are unknown. We seek to determine PBT utilization for breast cancer. Materials/methodsThe Particle Therapy Co-Operative Group (PTCOG) Breast Subcommittee developed an IRB-approved 29-question survey and sent it to breast cancer radiation oncologists at all active PBT centers worldwide in June 2023. Descriptive statistics were used to summarize responses, and comparisons by continent were performed using Fisher’s exact tests. ResultsOf 79 surveys distributed, 28 recipients submitted responses (35 % response rate) representing fifteen U.S., 8 European, and 5 Asian centers (continent response rate 50 %, 38 %, and 18 %, respectively). Overall, 93 % reported treating breast cancer patients with PBT; 13 (50 %) have treated ≥100 breast cancer patients at their center since opening. Most (89 %) have pencil beam scanning technology. Nearly half (46 %) use moderate hypofractionation (15–20 fractions) for regional nodal irradiation and 42 % conventional fractionation (25–30 fractions). More European centers prefer hypofractionation (88 %) vs. Asian (50 %) and U.S. (21 %) centers (p = 0.003). Common patient selection methods were practitioner determination/patient preference (n = 16) and comparative plan evaluation (n = 15). U.S. centers reported the most experience with breast PBT, with 71 % having treated ≥100 breast cancer patients vs. 38 % in Europe and none in Asia (p = 0.001). Of respondent centers, 39 % enrolled ≥75 % of breast PBT patients on a research study. ConclusionUtilization, patient selection methods, and dose-fractionation approaches for breast cancer PBT vary worldwide. These survey data serve as a benchmark from which successor surveys can provide insight on practice pattern evolution.