Treatment Options For Breast Cancer Research Articles

Physician and Patient-Reported Outcomes of a Phase III Trial of Ultra-Hypofractionated vs. Moderate Hypofractionated Radiotherapy to the Whole Breast after Breast-Conserving Surgery

To report a final analysis evaluating physician and patient-reported outcomes of early breast cancer patients receiving moderate hypofractionation or ultra-hypofractionated whole breast radiotherapy (RT). Between April 4, 2018, and February 11, 2020, patients with localized breast cancer (T1-T3, N0-N1, and M0) managed with breast-conserving surgery (BCS) were enrolled. Patients were randomized to receive whole breast RT with moderate hypofractionation to 40 Gy in 15 fractions (Arm A) or ultra-hypofractionation to 25 Gy in 5 fractions (Arm B). An optional concurrent integrated boost to 48 Gy on Arm A or 30 Gy on Arm B was allowed. Early toxicity (<3 months), late toxicity (> 3 months), quality of life (QOL), cosmesis, Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), and deterioration of cosmesis were analyzed. One hundred and seven patients were randomized to moderate hypofractionation (n = 54) or ultra-hypofractionation (n = 53). With a median follow-up of 36 months, no significant differences in patient characteristics were noted between the two arms. There were no patients with a grade ≥3 or higher toxicity. Grade 2 toxicities were 7.4% in Arm A and 7.5% in Arm B, and primarily consisted of radiation dermatitis (6 patients), fibrosis (1 patient) and lymphedema (1 patient). The average Harvard Cosmesis score and overall QoL were similar between arms at all time points, with no patients developing cosmetic deterioration. Patient-reported moderate to severe radiation skin burns were more commonly reported in Arm A (21.05%) vs. Arm B (6.25%) at the end of treatment (EOT) (p = 0.078). At EOT, patients receiving moderate hypofractionation had higher mean toxicity scores in breast tenderness (2.66 vs. 1.5, p = 0.018), skin flaking or peeling (0.63 vs. 0.06, p = 0.035), blistering (0.74 vs. 0.06, p = 0.028), pruritis (2.53 vs. 0.87, p < 0.001), erythema (4.24 vs. 2.0, p <0.001), telangiectasias (1.0 vs. 0.28, p = 0.021). Additionally, patients receiving moderate hypofractionation reported significantly worse changes from baseline at EOT in breast tenderness (-2.25 vs. -.86, p = 0.02), telangiectasia (-0.81 vs. 0.18, p = 0.012), skin discoloration (-4.31 vs. -1.04, p < 0.001), skin flaking or peeling (-.55 vs. 0.04, p = 0.053), blistering (-0.82 vs. -0.07, p = 0.033), and pruritus (-2.27 vs. -.67, p = 0.002). There was a return to baseline in all patient-reported breast domains by 3 months (p >0.05) in both arms. Ultra-hypofractionated whole breast irradiation, consisting of 25 Gy in 5 fractions, provided comparable provider assessed toxicity and cosmetic outcomes to 40 Gy in 15 fractions. At the EOT assessment, ultra-hypofractionation had a better patient reported toxicity profile. Our findings provide further evidence to support daily ultra-hypofractionated whole breast radiotherapy as an appropriate treatment option for early-stage breast cancer.

Nomogram for Predicting Risk of Cancer Therapy-Related Cardiac Dysfunction in Patients With Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer.

Cancer therapy-related cardiac dysfunction (CTRCD) is an important treatment-limiting toxicity for patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer that adversely affects cancer and cardiovascular outcomes. Easy-to-use tools that incorporate readily accessible clinical variables for individual estimation of CTRCD risk are needed. From 2004 to 2013, 1440 patients with stage I to III HER2-positive breast cancer treated with trastuzumab-based therapy were identified. A multivariable Cox proportional hazards model was constructed to identify risk factors for CTRCD and included the 1377 patients in whom data were complete. Nine clinical variables, including age, race, body mass index, left ventricular ejection fraction, systolic blood pressure, coronary artery disease, diabetes, arrhythmia, and anthracycline exposure were built into a nomogram estimating risk of CTRCD at 1 year. The nomogram was validated for calibration and discrimination using bootstrap resampling. A total of 177 CTRCD events occurred within 1 year of HER2-targeted treatment. The nomogram for prediction of 1-year CTRCD probability demonstrated good discrimination, with a concordance index of 0.687. The predicted and observed probabilities of CTRCD were similar, demonstrating good model calibration. A nomogram composed of 9 readily accessible clinical variables provides an individualized 1-year risk estimate of CTRCD among women with HER2-positive breast cancer receiving HER2-targeted therapy. This nomogram represents a simple-to-use tool for clinicians and patients that can inform clinical decision-making on breast cancer treatment options, optimal frequency of cardiac surveillance, and role of cardioprotective strategies.

In vitro anti-cancer and antimicrobial effects of manganese oxide nanoparticles synthesized using the Glycyrrhiza uralensis leaf extract on breast cancer cell lines

Abstract In this study, we evaluated the antiproliferative and apoptotic properties of Pluronic-F127-containing manganese oxide nanoparticles (PF-127-coated Mn2O3 NPs) derived from the leaf extract of Glycyrrhiza uralensis (GU) on breast adenocarcinoma, MCF7, and MDA-MB-231 cell lines. The leaf extract of GU contains bioactive molecules that act as a reducing or capping agent to form Mn2O3 NPs. Various analytical techniques were used to characterize the physiochemical properties of PF-127-coated Mn2O3 NPs, including spectroscopy (ultralight-Vis, Fourier transform infrared, photoluminescence), electron microscopy (field emission scanning electron microscopy and transmission electron microscopy), X-ray diffraction (XRD), electron diffracted X-ray spectroscopy (EDAX), and dynamic light scattering. The average crystallite size of Mn2O3 NPs was estimated to be 80 nm, and the NPs had a cubic crystalline structure. PF127-encapsulated Mn2O3 NPs significantly reduce MDA-MB-231 and MCF-7 cell proliferation, while increasing endogenous ROS and lowering mitochondrial matrix protein levels. DAPI, EtBr/AO dual staining, and Annexin-V-FITC-based flow cytometry analysis revealed that PF127-coated Mn2O3 NP-treated breast cancer cells exhibit nuclear damage and apoptotic cell death, resulting in cell cycle arrest in the S phase. Furthermore, PF127-encapsulated Mn2O3 NPs show strong antimicrobial efficacy against various strains. As a result, we can conclude that PF127-coated Mn2O3 NPs may be effective as future anticancer agents and treatment options for breast cancer.

Chitosan/Alginate Polymeric Nanoparticle-Loaded α-Mangostin: Characterization, Cytotoxicity, and In Vivo Evaluation against Breast Cancer Cells.

α-mangostin (Amg), a compound isolated from the mangosteen rind (Garcinia mangostana, L.), has demonstrated promising anticancer activity. However, its low solubility and selectivity against cancer cells limit its efficacy. To address this issue, researchers have developed chitosan/alginate polymeric nanoparticles (NANO-AMCAL) to enhance the effectiveness of Amg. In vitro studies have demonstrated that NANO-AMCAL is highly active against breast cancer cells. Therefore, an in vivo study was conducted to evaluate the efficacy of NANO-AMCAL in treating breast cancer in Wistar rats (Rattus norvegicus) and determine the effective dose. The rats were divided into seven treatment groups, including positive control, negative control, pure Amg, and NANO-AMCAL 5 mg, 10 mg, and 20 mg. The rats were injected subcutaneously with a carcinogenic agent, 7,12-dimethylbenz(a)anthracene (DMBA) and were evaluated for weight and tumor volume every three days during treatment. Surgery was performed on day 14, and histopathological studies were carried out on breast and lung cancer tissues. The results showed that NANO-AMCAL significantly enhanced the anticancer activity of Amg in treating breast cancer in Wistar rats. NANO-AMCAL containing 0.33 mg of Amg had a healing effect three times better than 20 mg pure Amg and was comparable to tamoxifen. The effective dose of NANO-AMCAL for anti-breast cancer treatment in Wistar rats was found to be 20 mg, which exhibited a good healing response, and the tumor volume continued to decrease up to 17.43% on the 14th day. Furthermore, histopathological tests showed tissue repair and no metastases. These findings suggest that NANO-AMCAL may be a promising therapeutic option for breast cancer treatment.

Experimental Investigation for Detecting Mitotic Cells in Medical Image using an Automated Algorithm

Cancer of the breast is a malignant tumour that originates in the cells of the breast tissue. It is by far the most common kind of cancer found in females around the world, with a projected 2.3 million new cases will be discovered in the year 2020 alone. It is projected that one in eight women will be diagnosed with breast cancer at some point in their life, despite the fact that breast cancer can also occur in men. Breast cancer is a complex condition that can arise from a diverse set of factors, express itself in a variety of ways, and can be treated in a variety of ways. Ductal carcinoma in situ, invasive ductal carcinoma, and invasive lobular carcinoma are all different subtypes. Both the available treatment options and the expected outcome of breast cancer are very variable depending on the particular subtype of the illness. Breast cancer risk factors include drinking alcohol and not getting enough exercise, as well as getting older, having a family history of the disease, having genetic mutations, being exposed to estrogens, and having a family history of the disease. There is not always a connection between having risk factors and developing breast cancer, despite the fact that there can be a link between the two. The prognosis and treatment options for breast cancer are highly dependent on the stage of the disease at the time of diagnosis. During staging, the extent to which the cancer has spread throughout the body and how far it has progressed are both measured. The TNM system, the IAFCM system, the ACM system, and the MPIG system are just few of the staging systems that are used to classify breast cancer. These staging systems consider not only the size of the tumor but also whether or not lymph nodes are involved and whether or not distant metastases are present. The severity of breast cancer symptoms can vary widely, depending not only on the subtype of the disease but also on how far along it has progressed. Alterations in the size or shape of the breast, discharge from the nipple, and alterations in the skin of the breast (such as redness or dimpling) are all common indications. On the other hand, not all cases of breast cancer present themselves in a visible manner, and mammography and other forms of routine screening may be able to detect some of these cases. Options for treating breast cancer vary depending on the patient's condition and the stage of the disease, as well as the patient's overall health and their preferences towards therapy. Common examples of medical interventions include surgery, radiotherapy, chemotherapy, hormone therapy, and targeted therapy. Other examples include. In certain cases, it may be appropriate to participate in more than one form of treatment.

The anti-breast cancer potential of indole/isatin hybrids.

Breast cancer (BC) is one of the most prevalent malignancies and the major contributor to cancer mortality in women globally, with a high degree of heterogeneity and a dismal prognosis. As drug resistance is responsible for most BC fatalities and advanced BC is currently considered incurable, finding innovative anti-BC chemotherapeutics is urgently required. Indole and its analog isatin (indole-1H-2,3-dione) are prominent pharmacophores in the development of novel medications, and their derivatives exhibit strong anticancer activities, also against BC. In particular, indole/isatin hybrids exhibit significant potency against BC including multidrug-resistant forms and excellent selectivity by influencing a variety of biological targets associated with the disease, supplying helpful building blocks for the identification of potential new BC treatment options. This review includes articles from 2020 to the present and provides insights into the in vitro and in vivo anti-BCpotential, molecular mechanisms, and structure-activity relationships (SARs) of indole/isatin hybrids that may be helpful in the development of innovative anti-BC chemotherapeutics.

Chitosan-dibenzylideneacetone based Schiff base: Evaluation of antimicrobial activity and in-vitro cytotoxicity on MCF-7 and L-132

This study holds significant importance as it explores the synthesis and characterization of two chitosan dibenzylideneacetone Schiff bases. Various analytical techniques, such as UV–visible spectroscopy, FTIR, XRD, TGA, DSC, SEM, and elemental analysis, were employed to thoroughly examine these derivatives. The antimicrobial activity of the chitosan derivatives was evaluated against a range of bacterial and fungal strains, while cytotoxicity tests were conducted on MCF-7, L-132, and VERO cell lines. In the antimicrobial tests, the chitosan derivatives exhibited remarkable antibacterial properties against S. aureus, E. coli, and Pseudomonas aeruginosa, as well as potent antifungal properties against Candida albicans and Aspergillus fumigatus. The cytotoxicity assessment revealed that the dibenzylideneacetone chitosan Schiff base (CHDBA) showed significant effectiveness against the L-132 cell line, surpassing the efficacy of doxorubicin by 2.44 times. Moreover, it exhibited substantial activity against the L-132 and MCF-7 cell lines, with IC50 values of 55.29 μg/mL and 185.8 μg/mL, respectively. Notably, none of the chitosan derivatives demonstrated cytotoxicity towards the normal cell line, indicating their non-toxic nature and safe usability. Based on these findings, it is evident that CHDBA holds promise for further development as a potential treatment option for breast cancer and lung cancer.

Site-selective superassembly of biomimetic nanorobots enabling deep penetration into tumor with stiff stroma

Chemotherapy remains as the first-choice treatment option for triple-negative breast cancer (TNBC). However, the limited tumor penetration and low cellular internalization efficiency of current nanocarrier-based systems impede the access of anticancer drugs to TNBC with dense stroma and thereby greatly restricts clinical therapeutic efficacy, especially for TNBC bone metastasis. In this work, biomimetic head/hollow tail nanorobots were designed through a site-selective superassembly strategy. We show that nanorobots enable efficient remodeling of the dense tumor stromal microenvironments (TSM) for deep tumor penetration. Furthermore, the self-movement ability and spiky head markedly promote interfacial cellular uptake efficacy, transvascular extravasation, and intratumoral penetration. These nanorobots, which integrate deep tumor penetration, active cellular internalization, near-infrared (NIR) light-responsive release, and photothermal therapy capacities into a single nanodevice efficiently suppress tumor growth in a bone metastasis female mouse model of TNBC and also demonstrate potent antitumor efficacy in three different subcutaneous tumor models.

Spectrum of ultrasound findings in patients with history of breast conservative treatment.

Breast conservative treatment (BCT) is currently accepted as the standard treatment option for breast cancer. Targeted ultrasound helps detect recurrent lesions, postoperative changes, and scarring tissue. In this pictorial essay, we review the ultrasound features of benign (seroma, hematoma, fat necrosis, traumatic neuroma, fibrosis/scarring) and malignant (recurrence, new primary cancer) causes of palpable lumps after BCT and provide images from our patients to illustrate some typical findings of common pathologies. Ultrasound, especially as an adjunct to mammography, can make a specific diagnosis in most cases.

Coq10 for preventing cardiotoxicity in breast cancer patients treated with trastuzumab.

Trastuzumab is a successful treatment option for HER2-positive breast cancer, but a decline in left ventricular ejection fraction (LVEF) and an increase in inflammatory and cardiac enzyme biomarkers can lead to cessation and termination of therapy. This study aimed to investigate the ability of Coenzyme Q10 (Coq10) to avoid these adverse effects. The study included 100 female patients with HER2+ (HER2+3 or amplified gene) breast cancer. All patients underwent standard adjuvant chemotherapy regimens, which involved a four-cycle treatment of Adriamycin, Cyclophosphamide, Docetaxel, and an initial 8 mg/kg loading dose of trastuzumab, followed by a year of 6 mg/kg maintenance doses every three weeks. One group of 50 patients received trastuzumab and a placebo, while the other 50 were given trastuzumab and CoQ10 for a full year. The CoQ10-treated group exhibited a statistically significant decrease in levels of monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL6), soluble toll-like receptor 4 (sTLR4), and cardiac troponin I (cTnI) compared to the control group (p<0.05). However, there was no significant difference in the mean F2-isoprostane levels between the treated and the control groups at any data collection point. Furthermore, the CoQ10-treated group experienced a significant reduction in the decline of EF levels compared to the control group at all stages except for baseline. According to our findings, Coenzyme Q10 protected patients with HER2+3 breast cancer from the cardiotoxicity of trastuzumab by increasing ejection fraction and decreasing inflammatory biomarkers and cardiac enzyme levels.

Retrospective observational study of outcomes in HER2-positive metastatic breast cancer patients treated with trastuzumab emtansine in single center.

15 Background: Trastuzumab emtansine (T-DM1) was established as a standard second line treatment option for metastatic HER2 positive breast cancer (mBC). However, the EMILIA study did not include disease progression patients who received pertuzumab plus trastuzumab previously. After CLEOPATRA study, the dual blockade treatment was indicated for advanced breast cancer as first line treatment. In this study, we attempted to build the T-DM1 predictive model and to evaluate the association between dual blockade and T-DM1 for metastatic HER2-positive breast cancer. Methods: This retrospective cohort study was conducted in Taiwan. Consecutive patients with metastatic HER2-positive breast cancer who had received T-DM1 between January 2013 and December 2022 were enrolled. Those patients were divided to two groups based on strategy of trastuzumab only or dual-blockade as prior therapy. Demographic, clinical, and pre- and post-T-DM1 treatment characteristics were described. The swimmer plots were used to estimate time to treatment discontinuation (TTD) and overall survival (OS). Results: Of 32 patients treated with T-DM1, 12 (38%) had prior treatment with pertuzumab plus trastuzumab. The median age was 60 years. Most patients had visceral disease and 59% had two or more prior treatments for mBC before T-DM1 (range 1–8 lines). Most patients (63%) stopped T-DM1 due to disease progressed and followed by financial problem (22%). In dual-blockade group, median TTD with T-DM1 was 4.5 months; median OS from diagnosis day was 68.2 months (8 patients still alive in the end of study). In trastuzumab only group, median TTD with T-DM1 was 3.8 months; median OS from diagnosis day was 73.2 months (5 patients still alive in the end of study). In our swimmer plots we found a trend that the shorter interval between trastuzumab +/- pertuzumab and T-DM1 the longer TTD with T-DM1. Conclusions: Patients treated with T-DM1 in this study appeared to have more advanced disease than patients in clinical trials and were treated in later lines of therapy. We should prescribe T-DM1 once trastuzumab with or without pertuzumab failure for the longer TTD. The small patient number was a major limitation in our study. A multi-center analysis is needed and it will help us for treatment suggestion under the Taiwan’s National Health Insurance clinical practice.

Accelerated Atherosclerosis and Cardiovascular Toxicity Induced by Radiotherapy in Breast Cancer.

The number of patients diagnosed with breast cancer and cardiovascular disease is continuously rising. Treatment options for breast cancer have greatly evolved, but radiotherapy (RT) still has a key role in it. Despite many advances in RT techniques, cardiotoxicity is one of the most important side effects. The new cardio-oncology guidelines recommend a baseline evaluation, risk stratification and follow-up of these patients. Cardiotoxicity induced by RT can be represented by almost all forms of cardiovascular disease, with atherosclerosis being the most frequent. An interdisciplinary team should manage these patients, in order to have maximum therapeutic effect and minimum cardiovascular toxicity. This review will summarize the current incidence, risk factors, mechanisms and follow-up of RT-induced cardiovascular toxicity.

Construction and validation of a cuproptosis-related five-lncRNA signature for predicting prognosis, immune response and drug sensitivity in breast cancer

BackgroundDespite advances in treatment, recurrence and mortality rates from breast cancer (BrCa) continue to rise, clinical effectiveness is limited, and prognosis remains disappointing, especially for patients with HER2-positive, triple-negative, or advanced breast cancer. Based on cuproptosis-related long noncoding RNAs (CRLs), this study aims to create a predictive signature to assess the prognosis in patients with BrCa.MethodsThe related CRLs RNA-seq data clinicopathological data were collected from The Cancer Genome Atlas (TCGA) database, and the predictive model was constructed after correlation analysis. Subsequently, we examined and validated connections and changes in the CRLs model with prognostic features (including risk curves, ROC curves and nomograms), pathway and functional enrichment, tumor mutation (TMB), tumor immune dysfunction and exclusion (TIDE) and treatment sensitivity.ResultsA prediction model formula composed of 5 CRLs was obtained, and divided breast cancer patients into high and low risk subgroups according to the obtained risk scores. The results showed that the overall survival (OS) of patients in the high-risk group was lower than that in the low-risk group, and the AUC of all samples at 1, 3 and 5 years were 0.704, 0.668 and 0.647, respectively. It was indicated that CRLs prognostic model could independently predict prognostic indicators of BrCa patients. In addition, analysis of gene set enrichment, immune function, TMB, and TIDE showed that these differentially expressed CRLs had a wealth of related pathways and functions, and might be closely related to immune response and immune microenvironment. Additionally, TP53 was found to have the highest mutation frequency in high-risk group (40%), while PIK3CA was found to have the highest mutation frequency in low-risk group (42%), which might become new targets for targeted therapy. Finally, we compared susceptibility to anticancer agents to identify potential treatment options for breast cancer. Lapatinib, Sunitinib, Phenformin, Idelalisib, Ruxolitinib, Cabozantinib were more sensitive to patients in the low-risk group, while Sorafenib, Vinorelbine, Pyrimethamine were more sensitive to patients in high-risk group, namely, these drugs could potentially be used in the future to treat breast cancer patients grouped according to the risk model.ConclusionThis study identified CRLs associated with breast cancer and provided a tailored tool for predicting prognosis, immune response, and drug sensitivity in patients with BrCa.

Impact of AKT1 on cell invasion and radiosensitivity in a triple negative breast cancer cell line developing brain metastasis.

The PI3K/AKT pathway is activated in 43-70% of breast cancer (BC)-patients and promotes the metastatic potential of BC cells by increasing cell proliferation, invasion and radioresistance. Therefore, AKT1-inhibition in combination with radiotherapy might be an effective treatment option for triple-negative breast cancer (TNBC)-patients with brain metastases. The impact of AKT1-knockout (AKT1_KO) and AKT-inhibition using Ipatasertib on MDA-MB-231 BR cells was assessed using in vitro cell proliferation and migration assays. AKT1-knockout in MDA-MB-231BR cells was performed using CRISPR/Cas9. The effect of AKT1-knockout on radiosensitivity of MDA-MB-231BR cell lines was determined via colony formation assays after cell irradiation. To detect genomic variants in AKT1_KO MDA-MB-231BR cells, whole-genome sequencing (WGS) was performed. Pharmacological inhibition of AKT with the pan-AKT inhibitor Ipatasertib led to a significant reduction of cell viability but did not impact cell migration. Moreover, only MDA-MB-231BR cells were sensitized following Ipatasertib-treatment. Furthermore, specific AKT1-knockout in MDA-MB-231BR showed reduced cell viability in comparison to control cells, with significant effect in one of two analyzed clones. Unexpectedly, AKT1 knockout led to increased cell migration and clonogenic potential in both AKT1_KO clones. RNAseq-analysis revealed the deregulation of CTSO, CYBB, GPR68, CEBPA, ID1, ID4, METTL15, PBX1 and PTGFRN leading to the increased cell migration, higher clonogenic survival and decreased radiosensitivity as a consequence of the AKT1 knockout in MDA-MB-231BR. Collectively, our results demonstrate that Ipatasertib leads to radiosensitization and reduced cell proliferation of MDA-MB-231BR. AKT1-inhibition showed altered gene expression profile leading to modified cell migration, clonogenic survival and radioresistance in MDA-MB-231BR. We conclude, that AKT1-inhibition in combination with radiotherapy contribute to novel treatment strategies for breast cancer brain metastases.

Polymeric graphene oxide nanoparticles loaded with doxorubicin for combined photothermal and chemotherapy in triple negative breast cancer

Combining photothermal and chemotherapy is an emerging strategy for tumor irradiation in a minimally invasive manner, utilizing photothermal transduction agents and anticancer drugs. The present work developed a 2D carbon nanomaterial graphene oxide (GO)-based nanoplatform that converted to 3D colloidal spherical structures upon functionalization with an amphiphilic polymer mPEG-PLA (1, 0.5/1/2) and entrapped doxorubicin (Dox) physically. The Dox@GO(mPP) (1/0.5) NPs displayed the least particle size (161 nm), the highest stability with no aggregation, the highest Dox loading (6.3 %) and encapsulation efficiency (70 %). The therapeutic efficacy was determined in vitro and in vivo using murine (4 T1) and human triple-negative breast cancer cells (MDA-MB-231), and 4 T1-Luc-tumor bearing mouse models. The results demonstrated that the Dox@GO(mPP) (1/0.5) NPs treatment with laser (+L) (808 nm) was highly efficient in inducing apoptosis, cell cycle arrest (G2/M) phase, significant cytotoxicity, mitochondrial membrane depolarization, ROS generation, and photothermal effect leading to a higher proportion of cell death than free Dox, and Dox@GO(mPP) (1/0.5) NPs (−L). The anticancer studies in mice harboring the 4 T1-Luc tumor showed that combination of Dox@GO(mPP) (1/0.5) NPs (+L) effectively reduced tumor development and decreased lung metastasis. The developed nanoplatform could be a promising combination chemo-photothermal treatment option for triple-negative breast cancer.

Cost-effectiveness analysis of trastuzumab deruxtecan in patients with HER2-low advanced breast cancer based on DESTINY-Breast04.

Breast cancer is a rapidly raising healthcare problem worldwide. DESTINY-Breast04 demonstrated that trastuzumab deruxtecan (T-Dxd) had a survival advantage comparing to the physician's choice of chemotherapy for patients with HER2-low metastatic breast cancer. But at the same time, this expensive novel treatment also brought an economic burden. This study assessed the cost-effectiveness of T-Dxd based on results of DESTINY-Breast04 from the perspective of Chinese healthcare system. A three-state partitioned-survival model [progression-free survival (PFS), progressive disease (PD) and death] based on data from DESTINY-Breast04 and Chinese healthcare system was used to estimate the incremental cost-effectiveness ratio (ICER) of T-Dxd vs. the physician's choice of chemotherapy for HER2-low metastatic breast cancer. Costs, quality-adjusted life-years (QALYs) and the ICER in terms of 2022 US$ per QALY gained were calculated for both hormone receptor-positive cohort and all patients. One-way and probabilistic sensitivity analyses were performed to assess the model robustness. Compared with the physician's choice of chemotherapy, T-Dxd increased costs by $104,168.30, while gaining 0.31 QALYs, resulting in an ICER of $336,026.77 per QALY in all patients. The costs of T-Dxd and the utility of PFS were the crucial factors in determining the ICER. In the hormone receptor-positive cohort, the ICER was lower than that in all patients, with the ICER of $274,905.72 per QALY. The ICER was much higher than the commonly accepted willingness-to-pay threshold ($357,96.83 per QALY). T-Dxd as second- or subsequent-line treatment is not a cost-effective treatment option for HER2-low metastatic breast cancer from the perspective of the Chinese healthcare system.

Triple Negative Breast Cancer Treatment Options and Limitations: Future Outlook.

Triple negative breast cancer (TNBC) has a negative expression of estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptors (HER2). The survival rate for TNBC is generally worse than other breast cancer subtypes. TNBC treatment has made significant advances, but certain limitations remain. Treatment for TNBC can be challenging since the disease has various molecular subtypes. A variety of treatment options are available, such as chemotherapy, immunotherapy, radiotherapy, and surgery. Chemotherapy is the most common of these options. TNBC is generally treated with systemic chemotherapy using drugs such as anthracyclines and taxanes in neoadjuvant or adjuvant settings. Developing resistance to anticancer drugs and off-target toxicity are the primary hindrances to chemotherapeutic solutions for cancer. It is imperative that researchers, clinicians, and pharmaceutical companies work together to develop effective treatment options for TNBC. Several studies have suggested nanotechnology as a potential solution to the problem of suboptimal TNBC treatment. In this review, we summarized possible treatment options for TNBC, including chemotherapy, immunotherapy, targeted therapy, combination therapy, and nanoparticle-based therapy, and some solutions for the treatment of TNBC in the future. Moreover, we gave general information about TNBC in terms of its characteristics and aggressiveness.

A review of treatment options in HER2-low breast cancer and proposed treatment sequencing algorithm.

The expansion of the spectrum of human epidermal growth factor receptor 2 (HER2)-status to HER2-low, defined as HER2 expression of 1+ by immunohistochemistry (IHC) or 2+ by IHC without gene amplification, has made a major impact in the field of oncology. The HER2-low expression has emerged as a targetable biomarker, and anti-HER2 antibody-drug conjugate trastuzumab deruxtecan has shown significant survival benefit in pretreated metastatic HER2-low breast cancer (BC). With these recent data, the treatment algorithm for hormone receptor-positive and triple-negative BC needs to be reconsidered, as approximately half of these BCs are HER2-low. Although there are different therapeutic agents for hormone receptor-positive and hormone receptor-negative HER2-low BCs, there is no consensus regarding the sequencing of these agents. In this article, the treatment options for HER2-low BC are enumerated and a treatment sequencing algorithm based on the current clinical evidence proposed.

Mastectomy with Reconstruction Including Robotic Endoscopic Surgery (MARRES): a prospective cohort study of the Korea Robot-Endoscopy Minimal Access Breast Surgery Study Group (KoREa-BSG) and Korean Breast Cancer Study Group (KBCSG)

BackgroundRobotic nipple-sparing mastectomy (RNSM) has emerged as a new treatment option for breast cancer and risk-reducing mastectomy (RRM) for women who have a high risk of pathogenic variants. Even though several studies have reported that RNSM is a feasible procedure, some argue that it should only be performed by specialized surgeons, and data on oncologic outcomes and patient-reported outcomes (PROs) are limited. Recently, the United States Food and Drug Administration and several surgeons warned that robotic breast surgery should be performed only by specialized surgeons and recommended that the benefits, risks, and alternatives of all available treatment options be discussed with patients so they can make informed treatment decisions. The Korea Robot-Endoscopy Minimal Access Breast Surgery Study Group (KoREa-BSG) has been established to evaluate, standardize, and teach this state-of-the-art procedure. We have designed a multicenter prospective cohort study entitled Mastectomy with Reconstruction Including Robot Endoscopic Surgery (MARRES) to report surgical, PRO, and oncologic outcomes.MethodsMARRES is a multi-institution cohort study prospectively collecting data from patients undergoing mastectomy and reconstruction. The patient inclusion criteria are adult women older than 19 with breast cancer or a high risk of breast cancer (patients with BRCA1/2, TP53, PALB2 mutations, etc.), who have scheduled therapeutic or RRM and want immediate reconstruction. Surgical outcomes, including pre- and postoperative photos, oncologic outcomes, cost-effectiveness, and PRO, are collected. The primary endpoints are postoperative complication rates within 30 postoperative days and the Clavien-Dindo grade of postoperative complications within 180 postoperative days. The secondary endpoints are 5-year postoperative recurrence-free survival and cancer incidence rate (for those who underwent RRM), patient satisfaction with reconstruction expectations preoperative (baseline) and results within 6 to 12 postoperative months, surgeon satisfaction with postoperative results in 6 postoperative months, and cost-effectiveness of the definitive surgery. Patient recruitment will be completed in April 2025, and the target number of enrolled patients is 2000.DiscussionThis study will provide evidence about the surgical outcomes, oncologic outcomes, and patient satisfaction with RNSM and endoscopic nipple-sparing mastectomy (NSM), compared with conventional NSM.Trial registrationClinicalTrials.gov Identifier NCT04585074. Registered April 8, 2020.

Thymoquinone Inhibition of Chemokines in TNF-α-Induced Inflammatory and Metastatic Effects in Triple-Negative Breast Cancer Cells.

The lack of identifiable molecular targets or biomarkers hinders the development of treatment options in triple-negative breast cancer (TNBC). However, natural products offer a promising alternative by targeting inflammatory chemokines in the tumor microenvironment (TME). Chemokines are crucial in promoting breast cancer growth and metastasis and correlate to the altered inflammatory process. In the present study, we evaluated the anti-inflammatory and antimetastatic effects of the natural product thymoquinone (TQ) on TNF-α-stimulated TNBC cells (MDA-MB-231 and MDA-MB-468) to study the cytotoxic, antiproliferative, anticolony, antimigratory, and antichemokine effects using enzyme-linked immunosorbent assays, quantitative real-time reverse transcription-polymerase chain reactions, and Western blots were used in sequence to validate the microarray results further. Four downregulated inflammatory cytokines were identified, CCL2 and CCL20 in MDA-MB-468 cells and CCL3 and CCL4 in MDA-MB-231 cells. Furthermore, when TNF-α-stimulated MDA-MB-231 cells were compared with MDA-MB-468 cells, the two cells were sensitive to TQ's antichemokine and antimetastatic effect in preventing cell migration. It was concluded from this investigation that genetically different cell lines may respond to TQ differently, as TQ targets CCL3 and CCL4 in MDA-MB-231 cells and CCL2 and CCL20 in MDA-MB-468 cells. Therefore, the results indicate that TQ may be recommended as a component of the therapeutic strategy for TNBC treatment. These outcomes stem from the compound's capacity to suppress the chemokine. Even though these findings support the usage of TQ as part of a therapy strategy for TNBC associated with the identified chemokine dysregulations, additional in vivo studies are needed to confirm these in vitro results.