Treatment Of Breast Cancer Research Articles

Tamoxifen Retinopathy. An Uncommon but Serious Complication: Case Report

Tamoxifen is a selective estrogen receptor modulator most widely used in the treatment of hormone-dependent breast cancer. We describe a case of a 51-year-old woman treated with tamoxifen for 4 years who had gradual diminution of vision in both eyes of three months duration. On examination, visual acuity was 20/40 in the right eye and 20/50 in the left eye. A fundus examination revealed bilateral symmetric crystalline deposits in the macula. There were characteristic structural changes on spectral domain-optical coherence tomography, including abnormalities of the ellipsoid zone and outer nuclear layer. Subsequently, tamoxifen was switched to anastrozole. Despite cessation of tamoxifen, her vision did not improve. The clinical presentation of tamoxifen retinopathy is discussed, along with the importance of regular ophthalmic examination for individuals receiving tamoxifen, even in low doses.

Advances in antibody-drug conjugates in the treatment of advanced triple-negative breast cancer: a narrative review

Advances in antibody-drug conjugates in the treatment of advanced triple-negative breast cancer: a narrative review

Discovery of novel JQ1 derivatives as dual ferroptosis and apoptosis inducers for the treatment of triple-negative breast cancer.

The activation of ferroptosis in refractory cancers may enhances their sensitivity to apoptosis-based chemotherapy, resulting in a synergistic effect via combination therapy. To enhance the anticancer effect of JQ1, a known BRD4 inhibitor with a significant antiproliferative effect on triple-negative breast cancer (TNBC), various new JQ1 derivatives as dual ferroptosis and apoptosis inducers were designed and synthesized. Among them, compound BG11 revealed a remarkable inhibitory activity against TNBC cells and obviously suppressed BRD4 and GPX4 expression and activities. Further studies suggested that BG11 induced cell ferroptosis through promoting Fe2+ and intracellular lipid peroxide deposition. In addition, BG11 could induce apoptosis through increasing Bax (apoptotic protein) expression and decreasing Bcl-2 (anti-apoptotic protein) expression within MDA-MB-231cells. Surprisingly, BG11 significantly inhibited tumor proliferation in the MDA-MB-231 xenograft model without obvious toxicity. Based on the above findings, BG11 may be the candidate dual ferroptosis and apoptosis inducers for treating TNBC.

Long-term outcome for neoadjuvant versus adjuvant chemotherapy in early breast cancer and the prognostic impact of nodal therapy response: A population-based study.

Although neoadjuvant systemic treatment for non-metastatic breast cancer has gained ground during the past decade, there is no compelling evidence that it improves overall survival compared to primary tumor resection and adjuvant treatment. At the same time, the approach to responders to neoadjuvant treatment in the axilla is evolving. This is a retrospective analysis of a prospectively collected population-based registry. Patients that received neoadjuvant (n=2126) or adjuvant chemotherapy (n=4754) for non-metastatic breast cancer during 2007-2020 in the Stockholm-Gotland region, which comprises 25% of the entire Swedish population, were included. Overall survival of patients treated preoperatively and postoperatively was compared using inverse probability treatment weighting and landmark analysis. The prognostic impact of change between prechemotherapy clinical to postchemotherapy pathologic nodal stage (cN/pN) in women receiving neoadjuvant treatment was investigated. Median follow-up was 4.93 years. There was no difference in adjusted overall survival between adjuvant (reference) and neoadjuvant treatment in the entire population (HR=1.38, 95% CI 0.98-1.93, p=0.062) or in breast cancer subtypes. Patients converting from positive clinical to negative pathologic nodal stage (cN+/pN0) had improved outcomes compared to cN0/pN0 or patients with pN0 following primary surgery. These patients had a particular disease trajectory, with early peak in risk of death followed by quick and sustained decrease. There was no difference in survival of patients treated with neoadjuvant versus adjuvant systemic therapy for non-metastatic breast cancer. Patients with cN+/pN0 have excellent prognosis and represent potential candidates for de-escalation of local and systemic treatment.

The recent advance and prospect of poly(ADP-ribose) polymerase inhibitors for the treatment of cancer.

Chemotherapies are commonly used in cancer therapy, their applications are limited to low specificity, severe adverse reactions, and long-term medication-induced drug resistance. Poly(ADP-ribose)polymerase (PARP)inhibitors are a novel class of antitumor drugs developed to solve these intractable problems based on the mechanism of DNA damage repair, which have been widely applied in the treatment of ovarian cancer, breast cancer, and other cancers through inducing synthetic lethal effect and trapping PARP-DNAcomplex in BRCA gene mutated cancer cells. In recent years, PARP inhibitors have been widely used in combination with various first-line chemotherapy drugs, targeted drugs and immune checkpoint inhibitors to expand the scope of clinical application. However, the intricate mechanisms underlying the drug resistance to PARP inhibitors, including the restoration of homologous recombination, stabilization of DNA replication forks, overexpression of drug efflux protein, and epigenetic modifications pose great challenges and desirability in the development of novel PARP inhibitors. In this review, we will focus on the mechanism, structure-activity relationship, and multidrug resistance associated with the representative PARP inhibitors. Furthermore, we aim to provide insights into the development prospects and emerging trends to offer guidance for the clinical application and inspiration for the development of novel PARP inhibitors and degraders.

Complication Rates After Mastectomy and Reconstruction in Breast Cancer Patients Treated with Hypofractionated Radiation Therapy Compared to Conventional Fractionation: A Single Institutional Analysis.

Radiation therapy plays an important role in the treatment of localized breast cancer. Hypofractionated (HF) radiation therapy has emerged as a promising alternative to conventional fractionation (CF) schedules, offering comparable efficacy with reduced treatment duration and costs. However, concerns remain regarding its safety and rate of toxicity, particularly in patients undergoing mastectomy with breast reconstruction. This study aimed to assess the implant-related complications in breast cancer patients receiving HF post-mastectomy radiation therapy (PMRT) and reconstruction compared to CF PMRT. A retrospective study was conducted on 59 breast cancer patients who underwent mastectomy and breast reconstruction between 2013 and 2021 and received adjuvant PMRT. Patient demographics, treatment characteristics, and implant-related complications were analyzed. Statistical tests including chi-square, Fischer's exact test, and multivariable Cox regression were employed for analysis. Of the 59 patients, 29 received HF PMRT and 30 received CF PMRT. At a median follow-up of 23.4 months, there was no significant difference in major implant-related complications between the two groups (24.1% in HF vs. 33.3% in CF, p = 0.436). Most complications in the HF group occurred within the first two years post-radiation. Age over 40 was identified as a significant predictor for higher implant-related complications (p = 0.029). Our findings indicate that HF PMRT and reconstruction does not increase the risk of major implant-related complications compared to CF PMRT. These results align with the existing literature, supporting the safety of HF radiation in breast cancer patients who underwent mastectomy with reconstruction.

Integrated multiple interventional radiologic procedures for diagnosis and treatment of unresectable breast cancer: a case description.

Integrated multiple interventional radiologic procedures for diagnosis and treatment of unresectable breast cancer: a case description.

De-escalation of axillary treatment in early breast cancer—a narrative review of current trials

De-escalation of axillary treatment in early breast cancer—a narrative review of current trials

Fabrication and characterization of teriflunomide-loaded chondroitin sulfate hybridized zein nanoparticles for the management of triple negative breast cancer.

The objective of this work was to explore the Teriflunomide (TFM) -loaded chondroitin sulfate hybridized zein nanoparticles (TZCNPs) for the treatment of triple-negative breast cancer (TNBC). The particle size, PDI and %EE of optimized TZCNPs was found 208.7 ± 7.26 nm,0.173 ± 0.004, and 80.18 ± 1.03 %, respectively. TZCNPs demonstrate a 7-10 folds increase in cytotoxicity against free TFM in MDA-MB-231 cells and a 4-6 folds increase in MCF-7 cells, respectively. CD44 receptor blocking resulted in a 3.4-fold reduction in anti-cancer efficacy and a 1.7-fold decrease in cellular uptake of TZCNPs in MDA-MB-231 cells, significantly/strongly indicating the critical role of the CD44-mediated uptake mechanism. TZCNPs displayed enhanced apoptosis, mitochondrial depolarization, ROS generation, cell invasion inhibition, and inhibited colony formation compared to free TFM in MDA-MB-231 cells. TZCNPs exhibited approximately 6.8-fold enhanced cytotoxicity and a 1.66-fold decrease in spheroid volume in a multicellular tumor spheroid model of MDA-MB-231 cells compared to free TFM. TZCNPs also exhibited greater disintegration of spheroids and more dead cells (live/dead staining). In pharmacokinetic studies, TZCNPs displayed reduced CL and enhanced the AUC, MRT, and t ½ by 3.64-fold, 2.17-fold, 1.83-fold, and 1.73-fold than the free TFM suspension. An acute toxicity study revealed a good safety profile of TZCNPs, which could be a potential treatment option for TNBC.

Synthesis, Anti-proliferation, Apoptosis Induction in Breast Cancer Cells, and Aromatase Inhibition of Coumarin-Triazole Hybrids: In Vitro and In Silico Studies.

Breast cancer is one of the most common cancers found in women worldwide. Besides the availability of clinical drugs, drug resistance and considerable side effects are concerning issues driven the needs for the discovery of novel anticancer agents. Aromatase inhibition is one of the effective strategies for management of hormone-dependent breast cancer. Triazole, coumarin, and isatin are heterocyclic scaffolds holding great attention in the field of drug design. Molecular hybridization is a well-known strategy to achieve new molecules with improved potency and properties. Herein, a set of 27 triazole-based hybrids (i.e., coumarin-triazoles series 5-6 and isatin-triazoles series 7) were synthesized and investigated for their anti-proliferation, apoptosis induction, and aromatase inhibitory potentials. Anti-proliferative study against the hormone-dependent breast cancer (T47D) cell line indicated that coumarin-triazole 5h (R = NO2) and 6i (R = SO2NH2) were the two most potent antiproliferative agents. Particularly, compound 5h showed comparable potency and superior selectivity index than that of the reference drug, doxorubicin. Moreover, the coumarin-triazole 5h induced cellular apoptosis of the estrogen-dependent breast cancer (MCF-7) cells. Additionally, findings from the aromatase inhibitory assay suggested four compounds as potential aromatase inhibitors (i.e., 5i, 6f, 6g and 6i, IC50 = 1.4-2.4 μM). Two QSAR models with preferable predictive performances were constructed to reveal key properties influencing antiproliferative and aromatase inhibitory effects. Molecular docking was conducted to elucidate the possible binding modalities against the target aromatase enzyme. Key structural features essential for the binding were highlighted. Moreover, the drug-like properties of top-ranking compounds were assessed to ensure their possibilities for successful development.

Lateral transpositional flaps (LTF) in management of outer quadrant breast cancer: An assessment of the oncological safety and cosmetic outcome

Lateral transpositional flaps (LTF) in management of outer quadrant breast cancer: An assessment of the oncological safety and cosmetic outcome

Targeted NIR-triggered doxorubicin release using carbon dots-poly(ethylene glycol)-folate conjugates for breast cancer treatment.

Carbon dot (CD)-based theranostics offers a promising approach for breast cancer (BC) treatment, integrating ultra-localized chemo-photothermal effects to address chemoresistance and enhance therapeutic control. Herein, the development of a targeted theranostic nanosystem for the chemo-phototherapy of breast cancer is described. Fluorescent and biocompatible CDs were passivated with 1,2-bis(3-aminopropylamino)ethane (bAPAE) and decorated with the targeting agent folic acid (FA) through conjugation with a PEG spacer. This yielded CDs-bAPAE-PEG-FA, hydrophilic nanocarriers (12 nm) with a high drug interaction surface. Fluorescence analysis confirmed their utility as bioimaging probes, while NIR light stimulation demonstrated good photothermal conversion. Doxorubicin-loaded CDs (CDs-bAPAE-PEG-FA/Dox) showed an on-demand NIR-boosted drug release, increased by 50% after localized NIR exposure, while in vitro studies on BC cells MCF-7 and MDA-MB-231 demonstrated NIR-enhanced antitumor efficacy, providing the opportunity to realize selective and remote-controlled synergistic therapy. Furthermore, uptake investigations highlighted the imaging potential of CDs and efficient internalization of doxorubicin, emphasizing FA's role in receptor-mediated specific targeting. Data suggest that CDs-bAPAE-PEG-FA/Dox could perform efficient image-guided and selective BC therapy, enhancing the therapeutic outcomes.

Facile integration of a binary nano-prodrug with αPD-L1 as a translatable technology for potent immunotherapy of TNBC.

Immune checkpoint blockers (ICBs)-based immunotherapy is a favorable approach for efficient triple-negative breast cancer (TNBC) treatment. However, the therapeutic efficacy of ICBs is greatly compromised by immunosuppressive tumor microenvironments (TMEs) and low expression levels of programmed cell death ligand-1 (PD-L1). Herein, we constructed an amphiphilic prodrug by linking a hydrophobic STING agonist, MSA-2 and a hydrophilic chemotherapeutic drug, gemcitabine (GEM) via an ester bond, which can self-assemble into GEM-MSA-2 (G-M) nanoparticles (NPs) with a tumor growth inhibition (TGI) value of 87.1% in a murine 4T1 transplantation tumor model. Notably, the immunogenic cell death (ICD)-triggering effect of GEM together with the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway activation properties of MSA-2 enables efficient infiltration of non-exhausting T cells and repolarization of macrophages from M2 to M1 types in the tumor microenvironment for transforming a cold tumor to a hot one. Most importantly, G-M NPs treatment increases the PD-L1 expression levels, thus providing a unique opportunity for further integration with anti-PD-L1 monoclonal antibody (αPD-L1) for eliciting stronger immunity that ultimately leads to a TGI value of 98.0% in the primary tumor and significantly protects against distal and disseminated tumor rechallenge. Overall, this study presents a minimalist nano-prodrug combined with αPD-L1 as a simple yet robust translatable nanotechnology for potent chemo-immunotherapy of TNBC. STATEMENT OF SIGNIFICANCE: Enhancing the therapeutic efficacy of αPD-L1 for tumor immunotherapy via a translatable technology remains a challenge. We report herein facile integration of a binary nano-prodrug with αPD-L1 for potent immunotherapy of TNBC. An amphiphilic prodrug is constructed by linking a hydrophobic STING agonist, MSA-2 and a hydrophilic chemotherapeutic drug, gemcitabine (GEM) via an ester bond. The resulting self-assembled GEM-MSA-2 (G-M) nanoparticles (NPs) show a tumor growth inhibition (TGI) value of 87.1% in a murine 4T1 transplantation tumor model. Besides the induced immunogenic cell death (ICD) and activated cGAS-STING pathway, G-M NPs increase the PD-L1 expression levels, providing a unique opportunity for further integration with αPD-L1 to elicit stronger immunity that ultimately leads to a TGI value of 98.0% in the primary tumor and significantly protects against distal and disseminated tumor rechallenge.

The impact of COVID-19 on breast cancer mortality trends in Brazil: A time-series study.

There is a lack of research on whether COVID-19 disruptions in breast cancer screening, diagnosis, and treatment affected mortality rates over time. This ecological time series study, covering the period between 2013 and 2023, utilizes the inflection point regression model and calculates the Annual Percentage Change (APC). The study used open-access data from the Brazilian Mortality Information System. The dependent variables measured were mortality rates due to breast cancer as an underlying cause and contributing cause in women aged 20 and over. The double exponential smoothing method was applied to predict mortality rates for 2020-2023. During the study period, the mortality rate due to breast cancer as a contributing cause increased approximately tenfold compared to mortality as an underlying cause (APC 6.9% vs. 0.7%). On average, 12% of breast cancer-related deaths were attributed to the disease as a contributing cause. Breast cancer deaths as an underlying cause declined in 2020 and 2021, remaining below the 95% predicted interval (95% PI), but showed recovery until 2023. Mortality due to breast cancer as a contributing cause increased early in the pandemic, with deaths related to COVID-19 as an underlying cause comprising 39.6% of cases in 2021. Breast cancer-related deaths, both as an underlying and contributing cause, showed an upward trend until 2021 and remained within the 95% PI until 2023. During the pandemic, deaths due to breast cancer as an underlying cause decreased while contributing deaths increased, with total mortality remaining within the predicted range.

MicroRNAs and their role in breast cancer metabolism (Review).

Breast cancer (BC) continues to be the leading cause of cancer‑related mortality among women, placing a substantial disease burden on the global female population. MicroRNAs (miRNAs) are members of a large class of non‑coding RNAs capable of regulating gene expression at the post‑transcriptional level. With cases of early‑onset BC on the rise, miRNAs are promising biomarkers and therapeutic targets for early BC detection and treatment. Dysregulated miRNA expression is known to be closely linked to BC development and metastasis in cancer cells via metabolic reprogramming. Normal cellular metabolism is tightly regulated by various complex signaling pathways. Therefore, dysregulation of metabolism due to metabolic reprogramming is considered a hallmark of cancer. The present review delves into the crucial roles that miRNAs serve in disordered cellular metabolism of BC by targeting gene transcripts, key metabolic enzymes and transporter proteins responsible for regulating major cellular metabolism pathways. The future outlook and clinical implications of miRNAs as potential diagnostic, prognostic and therapeutic markers in BC metabolism are also discussed.

Glow in the dark tumor: Enhanced near-IR visualization and destruction of cancer with a self-quenched theranostic.

Late diagnosis is one of the major obstacles for the treatment of breast cancer which can be overcome with a system offering sensitive imaging and selective therapeutic effect. In this study, we developed a "dark-bright" multifunctional drug delivery system bringing real-time imaging and non-invasive therapy together. Theranostic ability of the system was delivered by Verteporfin (VP), serving as a fluorescence probe and a photosensitizer. To create a "dark state" system via self-quenching ability of VP, it was immobilized onto the superparamagnetic iron oxide nanoparticle (SPION) surface. Upon cellular uptake of the "dark state" system, release of VP led to fluorescence regain, switching the system to "bright state" after which photodynamic therapy (PDT) was initiated to lead to cell death. Theranostic feature of the system was evaluated in MCF-7 and MDA-MB-231 cell lines. Following internalization, fluorescence signal was increased up to ∼56-fold in MCF-7 cells. The IC50 value decreased ∼20-fold and ∼117-fold in MCF-7 and MDA-MB-231 cell lines, respectively. Moreover, the system significantly inhibited migration in the highly aggressive MDA-MB-231 cell line and induced apoptosis by caspase-3 activation. The developed "dark-bright" system is a promising multifunctional drug delivery vehicle with extraordinary theranostic features for the detection and destruction of micro tumors.

MicroRNA-mediated regulation of BCL-2 in breast cancer

<p>Breast cancer, a prominent form of cancer in women, arises from the inner lining of mammary glands, ducts, and lobules. With an approximate prevalence rate of 1 in 8 women, the standard treatment methods for this condition include the surgical excision of afflicted tissues, chemotherapy, radiation, and hormone therapy. The BCL-2 gene, also known as the B cell lymphoma gene, prevents apoptosis in eukaryotic cells. It is commonly found to be excessively active in many types of malignancies, such as leukemia, carcinomas, and breast cancer. The excessive expression of this gene has a role in the advancement of cancer by inhibiting apoptosis. Recent research emphasizes the function of microRNAs (miRs) in regulating the expression of BCL-2. These miRs can either decrease or increase the activity of specific genes involved in programmed cell death, thus making them potential targets for therapeutic interventions. This review explicitly examines the regulatory impacts of several miRs on BCL-2, thereby investigating their ability to trigger apoptosis and function as targeted treatments for breast cancer. By comprehending the complex interplay between miRs and BCL-2, it is possible to devise novel therapeutic approaches that can augment the efficacy of breast cancer treatments, thus eventually enhancing patient outcomes.</p>

PH-sensitive phthalocyanine-loaded polymeric nanoparticles as a novel treatment strategy for breast cancer.

Novel pH-sensitive polymeric photosensitizer carriers from the phthalocyanine (Pc) group were investigated as potential photodynamic therapy drugs for the treatment of breast cancer. Their high antiproliferative activity was confirmed by photocytotoxicity studies, which indicated their high efficacy and specificity toward the SK-BR-3 cell line. Importantly, the Pcs encapsulated in the polymeric nanoparticle (NP) carrier exhibited a much better penetration into the acidic environment of tumor cells than their free form. The investigated Pc4-NPs and TT1-NPs exhibited a high selectivity to healthy fibroblasts as well as non-toxicity without irradiation. This paper describes the detailed mechanism of action of the evaluated compounds by measuring reactive oxygen species (ROS), including singlet oxygen; imaging cellular localization; and analyzing key signaling pathway proteins. An additional advantage of the evaluated compounds is their ability to inhibit the Akt protein expression, including its phosphorylation, which the Western blot test confirmed. This is particularly important because breast cancers often overexpress the HER-2 receptor-related signaling proteins. Moreover, an analysis of proteins such as GLUT-1, HO-1, phospho-p42/44, and BID revealed the significant involvement of ROS in disrupting cellular homeostasis, thereby leading to the induction of oxidative stress and resulting in apoptotic cell death.

Hsa-miR-214-3p inhibits breast cancer cell growth and improves the tumor immune microenvironment by downregulating B7H3.

Immune checkpoint inhibitors play an important role in the treatment of solid tumors, but the currently used immune checkpoint inhibitors targeting programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), and cytotoxic T-lymphocyte antigen-4 (CTLA-4) show limited clinical efficacy in many breast cancers. B7H3 has been widely reported as an immunosuppressive molecule, but its immunological function in breast cancer patients remains unclear. We analyzed the expression of B7H3 in breast cancer samples using data from the Cancer Genome Atlas Program (TCGA) and the Gene Expression Omnibus (GEO) databases. MicroRNAs were selected using the TarBase, miRTarBase, and miRBase databases. The regulatory role of the microRNA hsa-miR-214-3p on B7H3 was investigated through dual-luciferase reporter assays, which identified the specific action sites of interaction. The expression levels of B7H3 and hsa-miR-214-3p in human breast cancer tissues and adjacent normal tissues were quantified using Western blotting and quantitative PCR (qPCR). In vitro experiments were performed to observe the effects of modulating the expression of B7H3 or hsa-miR-214-3p on breast cancer cell proliferation and apoptosis. Additionally, the regulatory impact of hsa-miR-214-3p on B7H3 was examined. Enzyme-linked immunosorbent assays (ELISA) and flow cytometry were employed to assess the effects of co-cultured breast cancer cells and normal human peripheral blood mononuclear cells (PBMCs) on immune cells and associated cytokines. In breast cancer tissues, the expression level of B7H3 is inversely correlated with that of hsa-miR-214-3p, as well as with the regulatory effects on breast cancercell behavior. Hsa-miR-214-3p was found to inhibit breast cancer cell growth by downregulating B7H3. Importantly, our research identified, for the first time, two binding sites for hsa-miR-214-3p on the 3' UTR of B7H3, both of which exert similar effects independently. Co-culture experiments revealed that hsa-miR-214-3p obstructs the suppressive function of B7H3 on CD8+ T cells and natural killer cells. This study confirms the existence of two hsa-miR-214-3p binding sites on the 3' UTR of B7H3, reinforcing the role of hsa-miR-214-3p as a regulatory factor for B7H3. In breast cancer, hsa-miR-214-3p reduces tumor cell proliferation and enhances the tumor immune microenvironment by downregulating B7H3. These findings suggest new potential targets for the clinical treatment of breast cancer.

Corrigendum to “Palbociclib-letrozole loaded solid self-nano emulsifying drug delivery system for oral treatment of breast cancer: In-vitro and In-vivo characterization” [J. Drug Deliv. Sci. Technol. 104 (2025) 106469

Corrigendum to “Palbociclib-letrozole loaded solid self-nano emulsifying drug delivery system for oral treatment of breast cancer: In-vitro and In-vivo characterization” [J. Drug Deliv. Sci. Technol. 104 (2025) 106469