BACKGROUND

The survival advantage of HER2-positive breast cancer from targeted treatment is commonly undermined by catastrophic health expenditure (CHE), particularly in resource-limited areas. Recognizing that financial catastrophe leads to non-adherence to treatment and dissaving practices, we examined the out-of-pocket (OOP) expenses of patients with HER2-positive breast cancer.

The study aimed to estimate the median total per-cycle out-of-pocket expenditure of HER2-positive breast cancer treatment from the patient perspective, in public and private clinics, evaluate the association of catastrophic health expenditure with non-adherence to treatment, and describe dissaving practices.

This was a cross-sectional micro-costing analysis of the treatment of HER2-positive breast cancer from the patient perspective from a tertiary cancer center and select private clinics in the Philippines. Random sampling of patients with HER2-positive breast cancer was done. Using a validated questionnaire, a guided interview was administered. Catastrophic health expenditure was estimated as having OOP of >20% of the household income. OOP costs were assessed retrospectively from the time of confirmed HER2 diagnosis up to the date of survey, while household income referred to the corresponding period. The proportion of patients experiencing catastrophic health expenditure was computed. Fisher's exact was used to assess for any association between CHE and non-adherence to treatment. Descriptive statistics were used to report dissaving practices. All statistical analyses were performed using Stata analytical software version 12.

A total of 101 patients participated in the study. The mean age of participants from the tertiary cancer center and private clinics were 52 and 58 years old respectively. Patients from the private clinics had a median total OOP expenditure of PhP 54,737.06 (IQR = PhP 102,670.00), compared with patients from tertiary cancer center who had a median total OOP expenditure of PhP 13,920.66 (IQR = PhP 20,830.00). The overall prevalence of CHE (90.9%, 95% CI 0.81, 0.95) and nonadherence to treatment with trastuzumab (79%, 95% CI 0.70, 0.87) were high, and similar in both groups. A number of dissaving practices such as resignation from work, borrowing money from friends, selling assets were observed.

The high rate of CHE and treatment delay among patients with HER2-positive breast cancer were not addressed by the existing cancer programs. Most OOP expenditure was for trastuzumab. Current cancer support programs have potential to address the financial impact of their treatment.

Adenoid cystic carcinoma (ACC) is a rare subtype of invasive breast cancer, occurring in <0.1% of all malignant breast tumors. Though majority are triple-negative, ACC of the breast has good prognosis with a low incidence of regional and distant metastases.

A 45-year-old premenopausal female presented with a 5-month history of a gradually enlarging mass on her left breast. After core needle biopsy and subsequent metastatic work-up, she underwent total mastectomy with sentinel lymph node biopsy. Final histopathology showed adenoid cystic carcinoma, 2.1 cm in size and no lymph nodes positive for tumor. She has completed adjuvant radiotherapy of 50 Gy to the chestwall, and is currently well after 6 years of follow-up.

Surgery with either lumpectomy or mastectomy has been established as the mainstay of treatment of adenoid cystic carcinoma of the breast, but the use of adjuvant radiotherapy (RT) and chemotherapy has not been established. While adjuvant RT has been shown to improve cause-specific and overall survival following breast-conserving surgery, its indications after a mastectomy are not as well-defined. The decision to administer adjuvant RT was based on the current evidence indicating the advantages of adjuvant treatment for breast carcinomas, lack of survival difference between invasive ductal carcinomas and adenoid cystic carcinomas, indications for post-mastectomy RT in a retrospective Rare Cancer Network study, and reported incidences of local recurrences following mastectomy alone: 21.4% and 22.2%.

Our patient with adenoid cystic carcinoma of the breast, treated with surgery and adjuvant radiation therapy, showed favorable outcomes after 6 years.

BACKGROUND

Breast cancer remains a leading malignancy among women globally. In addition to established factors like histopathology, hormone receptor status, and lymph node involvement, tools such as immunohistochemistry and molecular tests have been developed to assess tumor behavior and recurrence risk.

This study investigates the concordance between the Ki-67 proliferation index measured by immunohistochemistry and the recurrence risk scores obtained from molecular genomic testing in patients with invasive breast cancer.

This cross-sectional study included patients with invasive breast carcinoma at St. Luke’s Medical Center from 2019 to 2024, who underwent biopsy or mastectomy, with hormone status and Ki-67 index assessed by immunohistochemistry. All patients also had molecular genomic testing using either MammaPrint or OncotypeDX. Concordance between Ki-67 and the genomic recurrence risk score was evaluated using Kappa statistics, and results were further analyzed according to clinical risk and hormone receptor status.

Fifty-eight (58) patients met the study criteria. Most had grade 2, hormone receptor-positive, HER2-negative, and node-negative tumors, with high clinical risk based on Adjuvant! Online criteria (adapted from the MINDACT trial). The agreement between categorical Ki-67 and molecular recurrence risk was only fair: 66.7% for MammaPrint (kappa=0.35) and 60% for OncotypeDX (kappa = 0.29) using a 30% Ki-67 cutoff.

There is a fair agreement between Ki-67 and the molecular genomic tests. These findings are consistent with prior studies reporting weak to moderate association. Despite the limited sample size, Ki-67 remains a practical and accessible risk stratification tool, particularly where genomic assays are unavailable. The study supports integrating Ki-67 with clinicopathologic and genomic data to guide therapy, reflecting current best-practice recommendations.

Breast

Introduction: Hypocalcemia in patients with advanced malignancy is usually attributed to bone metastases, vitamin D deficiency, renal impairment, or antiresorptive therapy. Paclitaxel, a taxane-based chemotherapy agent widely used for breast cancer, is not commonly associated with calcium disturbances. Proposed mechanism includes renal tubular dysfunction, renal salt wasting, and disruptions in bone metabolism. In patients with underlying disorders of calcium homeostasis such as hypoparathyroidism, taxanebased chemotherapy such as Docetaxel and Paclitaxel may exacerbate calcium imbalance. We reported a case of recurrent hypocalcemia associated with paclitaxel therapy in a patient with metastatic breast cancer. Case: A 42-year-old female with metastatic breast cancer, involving the liver and bones, had previously undergone neoadjuvant chemotherapy, mastectomy, and adjuvant radiotherapy. Following the disease progression, she was commenced on weekly intravenous paclitaxel at a 20% dose reduction due to prior complications and underlying metabolic risk. She had a history of post-thyroidectomy hypoparathyroidism and had previously been intolerant to docetaxel during the neoadjuvant chemotherapy, which was complicated by hypocalcemia, likely secondary to renal salt wasting. During paclitaxel treatment, she developed recurrent symptomatic hypocalcemia, requiring multiple hospital admissions and repeated intravenous calcium gluconate infusions despite ongoing oral calcium and calcitriol supplementation, which were temporarily increased during the chemotherapy. These episodes occurred intermittently in temporal association with paclitaxel administration, with other causes of hypocalcemia were considered less likely. Conclusion Hypocalcemia associated with paclitaxel is rarely described in literature. This case highlights the importance of monitoring calcium level in patients receiving paclitaxel, particularly in those with pre-existing hypoparathyroidism.
Hypocalcemia ; Hypoparathyroidism ; Breast Diseases ; Paclitaxel

OBJECTIVES: To investigate the role of circular RNA circ_0000437 in regulating biological behaviors of breast cancer cells and the molecular mechanism. METHODS: Breast cancer MCF-7 and MDA-MB-231 cells were transfected with sh-circ_0000437, mimics, inhibitor, si-CTPS1, or their respective negative controls. qRT-PCR was used to detect the expression levels of circ_0000437, let-7b-5p, CTPS1, Notch1, Hes1, and Numb in breast cancer cell lines and tissues. RNase R digestion was used to confirm the circular structure of circ_0000437 and its subcellular localization in the breast cancer cells was determined by cellular distribution analysis. The changes in proliferation, invasion and migration of the transfected cells were assessed using CCK-8 assay, Transwell assay and scratch assay. Dual-luciferase reporter gene and RNA immunoprecipitation assays were employed to validate binding interactions among circ_0000437, let-7b-5p, and CTPS1. The cellular expressions of CTPS1, E-cadherin, N-cadherin, and vimentin proteins were detected with Western blotting. A tumor-bearing mouse model was used to verify the oncogenic mechanism of circ_0000437 and CTPS1. RESULTS: Circ_0000437 and CTPS1 were upregulated while let-7b-5p was downregulated in breast cancer tissues and cell lines. Circ_0000437 or CTPS1 knockdown obviously suppressed breast cancer cell proliferation, invasion, migration and epithelial-mesenchymal transition (EMT). Overexpression of let-7b-5p produced similar inhibitory effects, whereas inhibition of let-7b-5p significantly enhanced malignant behaviors of the cells. In the tumor-bearing mouse models, circ_0000437 knockdown significantly suppressed tumor growth, but co-transfection of the cells with pcDNA-CTPS1 accelerated tumor growth. Binding sites were identified between circ_0000437 and let-7b-5p and between let-7b-5p and CTPS1, and circ_0000437, let-7b-5p, and CTPS1 showed functional interactions in breast cancer cells. CONCLUSIONS Circ_0000437 is upregulated in breast cancer tissues and cells, and its high expression promotes proliferation, invasion, migration and EMT of breast cancer cells through the let-7b-5p/CTPS1 axis.
Humans ; Epithelial-Mesenchymal Transition ; Cell Proliferation ; MicroRNAs/metabolism* ; RNA, Circular ; Breast Neoplasms/metabolism* ; Cell Movement ; Female ; Neoplasm Invasiveness ; Cell Line, Tumor ; MCF-7 Cells ; Animals ; Mice

OBJECTIVES: To study the molecular mechanisms of LDH-loaded si-NEAT1 for regulating paclitaxel resistance and tumor-associated macrophage (TAM) polarization in breast cancer. METHODS: qRT-PCR and Western blotting were used to detect the expression of lncRNA NEAT1, miR-133b, and PD-L1 in breast cancer SKBR3 cells and paclitaxel-resistant SKBR3 cells (SKBR3-PR). The effects of transfection with si-NEAT1 and miR-133b mimics on MRP, MCRP and PD-L1 expressions and cell proliferation, migration and apoptosis were investigated using qRT-PCR, Western blotting, scratch and Transwell assays, and flow cytometry. Rescue experiments were conducted using si-NEAT1 and miR-133b inhibitor. Human THP-1 macrophages were cultured in the presence of conditioned media (CM) derived from SKBR3 and SKBR3-PR cells with or with si-NEAT1 transfection for comparison of IL-4-induced macrophage polarization by detecting the surface markers. LDH@si-NEAT1 nanocarriers were constructed, and their effects on MRP, MCRP and PD-L1 expressions and cell behaviors of the tumor cells were examined. THP-1 cells were treated with the CM from LDH@si-NEAT1-treated tumor cells, and the changes in their polarization were assessed. RESULTS: SKBR3-PR cells showered significantly upregulated NEAT1 and PD-L1 expressions and lowered miR-133b expression as compared with their parental cells. Transfection with si-NEAT1 and miR-133b mimics inhibited viability, promoted apoptosis and enhanced MRP and BCRP expressions in SKBR3-PR cells. NEAT1 knockdown obvious upregulated miR-133b and downregulated PD-L1, MRP and BCRP expressions. The CM from SKBR3-PR cells obviously promoted M2 polarization of THP-1 macrophages, which was significantly inhibited by CM from si-NEAT1-transfected cells. Treatment with LDH@si-NEAT1 effectively inhibited migration and invasion, promoted apoptosis, and reduced MRP, BCRP and PD-L1 expressions in the tumor cells. The CM from LDH@si-NEAT1-treated SKBR3-PR cells significantly downregulated Arg-1, CD163, IL-10, and PD-L1 and upregulated miR-133b expression in THP-1 macrophages. CONCLUSIONS LDH@si-NEAT1 reduces paclitaxel resistance of breast cancer cells and inhibits TAM polarization by targeting the miR-133b/PD-L1 axis.
Humans ; MicroRNAs/genetics* ; RNA, Long Noncoding/genetics* ; Paclitaxel/pharmacology* ; Breast Neoplasms/metabolism* ; Drug Resistance, Neoplasm ; B7-H1 Antigen/metabolism* ; Cell Line, Tumor ; Female ; Tumor-Associated Macrophages ; Apoptosis ; Cell Proliferation ; Macrophages ; Cell Movement

OBJECTIVES: To qualitatively assess the diagnostic performance of dynamic contrast enhancement (DCE), diffusion-weighted imaging (DWI), and T2-weighted imaging (T2WI), alone or in combination, in the evaluation of breast cancer. METHODS: We retrospectively reviewed the records of 394 consecutive patients with pathologically confirmed breast lesions who had undergone 3-T magnetic resonance imaging (MRI). The morphological characteristics of breast lesions were evaluated using DCE, DWI, and T2WI based on BI-RADS lexicon descriptors by trained radiologists. Patients were categorized into mass and non-mass groups based on MRI characteristics of the lesions, and the differences between benign and malignant lesions in each group were compared. Clinical prediction models for breast cancer diagnosis were constructed using logistic regression analysis. Diagnostic efficacies were compared using the area under the receiver operating characteristic curve (AUC) and DeLong test. RESULTS: For mass-like lesions, all the morphological parameters significantly differentiated benign and malignant lesions on consensus DCE, DWI, and T2WI (P<0.05). The combined method (DCE+DWI+T2WI) had a higher AUC (0.865) than any of the individual modality (DCE: 0.786; DWI: 0.793; T2WI: 0.809) (P<0.05). For non-mass-like lesions, DWI signal intensity was a significant predictor of malignancy (P=0.036), but the model using DWI alone had a low AUC (0.669). CONCLUSIONS Morphological assessment using the combination of DCE, DWI, and T2WI provides better diagnostic value in differentiating benign and malignant breast mass-like lesions than assessment with only one of the modalities.
Humans ; Female ; Breast Neoplasms/pathology* ; Retrospective Studies ; Middle Aged ; Adult ; Diffusion Magnetic Resonance Imaging/methods* ; Aged ; Magnetic Resonance Imaging/methods* ; Young Adult ; Aged, 80 and over

OBJECTIVES: To investigate the association of HOTAIR gene rs920778 single nucleotide polymorphism (SNP) with breast cancer susceptibility and response to HER2-targeted therapy in a Chinese population. METHODS: TaqMan probe-based real-time quantitative PCR was used for genotyping of the rs920778 locus (chr12:54,376,218) in peripheral blood genomic DNA from 287 breast cancer patients and 260 healthy individuals from northern Anhui Province. The genotype (GG, GT and TT) and allele (G/T) distribution frequencies were compared between the two groups to evaluate their association with breast cancer risk. Multivariate logistic regression analysis was conducted to assess the relationship between SNP at this locus and aggressive clinicopathological features (including tumor size, lymph node metastasis, ER/PR/HER2 status, and molecular subtypes) of breast cancer. For the HER2-positive subgroup, the association between rs920778 genotype and responses to dual-targeted therapy (trastuzumab [6 mg/kg q3w]+pertuzumab [420 mg q3w] + docetaxel [75 mg/m²]) was analyzed. The primary endpoints included pathological complete response rate (pCR), objective response rate (ORR), and progression-free survival (PFS). RESULTS: The TT genotype of rs920778 was associated with a significantly increased breast cancer susceptibility (OR=1.54, 95% CI: 1.09-2.19; P=0.017), an advanced tumor stage (P<0.001), lymph node metastasis (P<0.001), and the triple-negative subtype (P<0.001). In HER2-positive patients, TT genotype carriers had a markedly reduced objective response rate to dual HER2-targeted therapy (33.3% vs 89.3%, P=0.001) and a lower pathological complete response rate after neoadjuvant therapy (P=0.018). CONCLUSIONS The TT genotype of HOTAIR rs920778 serves as an independent risk factor for breast cancer susceptibility and aggressive progression in Chinese population and may predict the resistance to HER2-targeted therapies, suggesting its potential as a prognostic biomarker for precision oncology.
Adult ; Aged ; Female ; Humans ; Middle Aged ; Breast Neoplasms/drug therapy* ; Case-Control Studies ; China ; Drug Resistance, Neoplasm/genetics* ; Genetic Predisposition to Disease ; Genotype ; Polymorphism, Single Nucleotide ; Receptor, ErbB-2 ; RNA, Long Noncoding/genetics* ; East Asian People/genetics*

Amino acid metabolism plays a critical role in the progression and development of breast cancer. Cancer cells, including those in breast cancer, reprogram amino acid metabolism to meet the demands of rapid proliferation, survival, and immune evasion. This includes alterations in the uptake and utilization of amino acids, such as glutamine, serine, glycine, and arginine, which provide essential building blocks for biosynthesis, energy production, and redox homeostasis. Notably, the metabolic phenotypes of breast cancer cells vary across molecular subtypes and disease stages, emphasizing the need for patient stratification and personalized therapeutic strategies. Advances in multi-level diagnostics, including phenotyping and predictive tools, such as AI-based analysis and body fluid profiling, have highlighted the potential for tailoring treatments to individual metabolic profiles. Enzymes, such as glutaminase and serine hydroxymethyltransferase, often upregulated in breast cancer, represent promising therapeutic targets. Understanding the interplay between amino acid metabolism and breast cancer biology, alongside the integration of personalized medicine approaches, can uncover novel insights into tumor progression and guide the development of precision therapies. This review explores the metabolic pathways of amino acids in breast cancer, with a focus on their implications for personalized treatment strategies.
Humans ; Breast Neoplasms/therapy* ; Female ; Amino Acids/metabolism*