Triple-negative breast cancer (TNBC) represents an aggressive breast cancer subtype with poor prognosis and limited targeted treatment options. This investigation examined the anti-cancer potential of Caerulomycin A (Cae A), a natural compound derived from marine actinomycetes, against TNBC. Cae A demonstrated selective inhibition of viability and proliferation in TNBC cell lines, including 4T1, MDA-MB-231, and MDA-MB-468, through apoptosis induction. Mechanistic analyses revealed that the compound induced sustained endoplasmic reticulum (ER) stress and subsequent upregulation of C/EBP homologous protein (CHOP) expression, resulting in mitochondrial damage-mediated apoptosis. Inhibition of ER stress or CHOP expression knockdown reversed mitochondrial damage and apoptosis, highlighting the essential role of ER stress and CHOP in Cae A's anti-tumor mechanism. Both oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) decreased in TNBC cells following Cae A treatment, indicating reduced mitochondrial respiratory and glycolytic capacities. This diminished energy metabolism potentially triggers ER stress and subsequent apoptosis. Furthermore, Cae A exhibited significant anti-tumor effects in the 4T1 tumor model in vivo without apparent toxicity. The compound also effectively inhibited human TNBC organoid growth. These results indicate that Cae A may serve as a potential therapeutic agent for TNBC, with its efficacy likely mediated through the disruption of glucose metabolism and the induction of ER stress-associated apoptosis.
Humans ; Endoplasmic Reticulum Stress/drug effects* ; Triple Negative Breast Neoplasms/genetics* ; Apoptosis/drug effects* ; Cell Line, Tumor ; Female ; Animals ; Glucose/metabolism* ; Mice ; Cell Proliferation/drug effects* ; Transcription Factor CHOP/genetics* ; Antineoplastic Agents/pharmacology* ; Mitochondria/metabolism* ; Mice, Inbred BALB C

Objective To investigate the value of ultrasonographic features combined with immunohistochemistry in predicting axillary lymph node metastasis in middle-aged women with breast cancer.Methods A retrospective analysis was conducted on 827 middle-aged female breast cancer patients who underwent surgical treatment at the Affiliated Hospital of Chengde Medical University from June 2017 to June 2023.Ultrasonographic and immunohistochemical information was collected,and the patients were randomly allocated into a training set(579 patients)and a validation set(248 patients).Univariate and multivariate Logistic regression analyses were performed to identify ultrasonographic and immunohistochemical risk factors associated with axillary lymph node metastasis in these patients,and a nomogram model was developed.Receiver operating characteristic curves and calibration curves were established to evaluate the performance of the nomogram model,and clinical decision curves were built to assess the clinical value of the model.Results The maximum diameter,morphology,boundary,calcification,and expression of human epidermal growth facor receptor 2 and Ki-67 in breast cancer lesions were identified as risk factors for predicting axillary lymph node metastasis in middle-aged women.The areas under the curve of the nomogram model on the training and validation sets were 0.747(0.707-0.787)and 0.714(0.647-0.780),respectively.Calibration curves and clinical decision curves indicated good consistency and performance of the model.Conclusion The nomogram model constructed based on ultrasonographic features and immunohistochemistry of the primary breast cancer lesion demonstrates high value in predicting axillary lymph node metastasis in middle-aged women with breast cancer.
Humans ; Female ; Breast Neoplasms/diagnostic imaging* ; Middle Aged ; Lymphatic Metastasis/diagnostic imaging* ; Axilla ; Retrospective Studies ; Nomograms ; Ultrasonography ; Immunohistochemistry ; Lymph Nodes/diagnostic imaging* ; Risk Factors ; Ki-67 Antigen

A 32-year-old woman presented with a progressively enlarging left breast mass for about one year. Breast magnetic resonance imaging (MRI) revealed a mass at the 9 o'clock position in the left breast, classified as BI-RADS category 6. The patient underwent endoscopic left breast-conserving surgery and sentinel lymph node biopsy. Histological examination (HE staining) revealed a tumor composed of sheets of epithelioid cells and fascicles of spindle cells, with areas of transition between the two components. Epithelioid cells were small, round to short-spindled, with scant cytoplasm, crowded arrangement, and coarse chromatin. Spindle cells were loosely arranged with indistinct borders, mildly eosinophilic cytoplasm, inconspicuous nucleoli, and intervening pale pink matrix. Immunohistochemistry demonstrated: epithelioid cells were diffusely positive for CK8/18, CAM5.2 and E-cadherin; partially positive for pan-CK and CK7; focally positive for CK5/6, CK14, high molecular weight cytokeratin and P63; and negative for vimentin. Spindle cells were positive for synaptophysin, CD56 and vimentin, and for glial fibrillary acidic protein, but negative for epithelial markers (pan-CK, CK7, CK8/18, CAM5.2, E-cadherin). The diagnosis was metaplastic carcinoma with heterologous mesenchymal (neuroectodermal) differentiation. Postoperatively, the patient received 8 cycles of EC-T systemic chemotherapy. Follow-up with breast MRI and chest CT every 3 months for 23 months showed no evidence of tumor recurrence or metastasis.
Humans ; Female ; Adult ; Breast Neoplasms/pathology*

OBJECTIVES

The aim of the study is to estimate the cost of breast cancer diagnosis, treatment, and management in the Philippines. Specifically, it aims to identify the resource requirements and interventions related to breast cancer diagnosis, treatment, and management, measure resource volumes (number of units), learn to value resource items (unit costs), and determine the total cost of treatment per disease stage.

The study covered nine tertiary hospitals, seven of which were government hospitals and two were private hospitals, with all tertiary hospitals providing breast cancer services and accredited by Philippine Health Insurance Corporation (PHIC or PhilHealth) for the Z-Benefit Package. Interventions and services related to breast cancer included radiographic procedures, laboratory and imaging tests, chemotherapy drugs and medications, medical and surgical supplies, surgical rates (for breast surgery), accommodation, staff time and salary/professional fees, and other procedure fees. The study conducted in 2022, examined cost prices of breast cancer interventions and services from stage 1–3B.

Purposive and convenience sampling were used based on PhilHealth accreditation and willingness of hospitals to participate in the study. The study conducted a focus group discussion with oncologists, radiologists, anesthesiologists, and other health care providers to validate the clinical guideline used and to solicit inputs to the costing design, analysis framework, and tools for data collection. Data collection of financial cost information (charge price) was conducted using a set of costing matrices filled out by the various departments of the hospitals. Costs and median rates were calculated across hospitals on diagnostics and imaging tests, surgery costs of both public and private facilities, medical treatment, and radiotherapy.

Breast MRI, Breast Panel, and Chest CT Scan are the top 3 most expensive diagnostic procedures ranging from PhP 8,102.00 to PhP 9,800.00 per procedure. Surgical procedures for breast cancer at private hospitals and public hospitals showed huge differences in costs. The cost of a cycle of chemotherapy ranges from PhP 596.70 to PhP 3,700.00 per session, while the cost of targeted therapy can cost up to PhP 46,394.21 per session. A year of hormone therapy ranges from PhP 3,276.00 with the use of Tamoxifen, and up to PhP 68,284.00 with Goserelin. Aromatase inhibitors such as Anastrozole and Letrozole cost from PhP 18,000 to PhP 36,000, respectively. Multiple cycles depending on the diagnosis are prescribed per patient and used in combination with other chemotherapy medications or other therapies such as targeted therapy and hormone therapy are usually taken daily up to 5 to 10 years. Conventional radiotherapy can cost up to PhP 88,150.00 covering 28 sessions, CT simulation, and CT planning.

This cost study provides relevant information and better perspective on benefit development for the PHIC, policy development for Department of Health on where and how to focus their support for the patient’s financial preparedness to address medical and f inancial catastrophes.

PhilHealth needs to guide the health care providers of their costing method and to develop their own integrated, interoperable, and comprehensive cost data library.

It recommends that the government allocate budget and cover for screening and assessment for earlier stage diagnosis of patients and lower health expenditure costs on cancer treatment.

BACKGROUND AND OBJECTIVE

The burden of treatment delay in breast cancer is high, especially among developing countries. Despite adversely affecting morbidity and mortality, treatment delay remains unexplored in the Philippines. This study aimed to determine treatment delays among breast cancer patients in a tertiary hospital during surgery, neoadjuvant chemotherapy, and adjuvant chemotherapy, and to identify predictors of delay.

A cross-sectional study was conducted among breast cancer patients seen between January 1, 2012 to December 31, 2018. The following outcomes were investigated: ≥90 days from initial diagnosis to surgery, ≥8 weeks from diagnosis to initiation of neoadjuvant chemotherapy, and >120 days from diagnosis to initiation of adjuvant chemotherapy. Summary statistics were reported as percent for categorical data and as mean for continuous data. The individual correlations were performed using Chi-square for qualitative data and t-test for quantitative data while predictors were determined through logistic regression.

A total of 324 patients were included in this study. The majority of the patients were less than 65 years old living in urban areas. More than half of the patients were overweight or obese, hypertensive, and diabetic. The following delays were observed: 61.1% (n = 198) with any type of delay, 23.8% (n = 53) with delay in surgery, 53.8% (n = 120) with delay in adjuvant chemotherapy, and 74.3% (n = 75) with delay in neoadjuvant chemotherapy. The patients noted to have any type of delay were more likely to be hypertensive (p = 0.046) and residing in urban areas (p = 0.041). There were no differences in the distribution of age, body mass index, and presence of co-morbid conditions such as hypertension, diabetes mellitus, coronary artery disease, and heart failure among those with any form of delay compared with no delay.

The present study shows the presence of treatment delay among breast cancer patients and may be used to enact policy changes to optimize breast cancer care delivery. Further studies may be done to identify other factors affecting these delays and policy changes are recommended to address these gaps in surgery and chemotherapy administration among breast cancer patients.

OBJECTIVES

The influence of weight change on the response to neoadjuvant chemotherapy (NAC) among adult Filipino patients with breast cancer remains unclear. Currently, there has been increasing evidence that weight gain during NAC is associated with increased recurrence risk and decreased survival. This study aimed to investigate this relationship and identify significant predictors of pathologic complete response (pCR), overall survival (OS) and disease-free survival (DFS).

This is a retrospective study using data from 52 female patients who received NAC for stage II or III breast cancer and had complete records of weight before and after NAC. Significant predictors of pCR such as host factors and tumor characteristics and associations between weight change and pCR, OS and DFS were examined using univariate and multivariable logistic regression analyses.

The average weight of all patients before NAC was 57.0 kg while the average weight of all patients after NAC was 59.5 kg. The average BMI of all patients before NAC was 25.8 kg/m2. In total, 29 patients (55.8%) were classified in the overweight/obese (OW/OB) group, and the rest were classified in the normal weight/underweight (NW/UW) group. The pCR rate was 51.3% in the OW/OB group versus 48.7% in the NW/UW group (p = 0.11). Initial BMI was a significant factor for achieving pCR (hazard ratio, 3.85; 95% confidence interval [CI], 1.72-8.60, p = 0.001), suggesting that a higher initial BMI was associated with an increased likelihood of achieving pCR. Initial BMI was also an independent prognostic factor for OS (p = 0.0006) and DFS (p = 0.0005). On the other hand, no significant correlation was seen between pCR rates as well as OFS and DFS (p = 0.0551) among patients whose weight changed during the course of treatment.

These findings suggest that while initial weight may significantly predict pCR rates and affect DFS and OS, weight change during treatment may not be as influential. Further research is needed to validate these findings in more diverse and larger patient populations.

OBJECTIVES

The aim of the study is to estimate the cost of breast cancer diagnosis, treatment, and management in the Philippines. Specifically, it aims to identify the resource requirements and interventions related to breast cancer diagnosis, treatment, and management, measure resource volumes (number of units), learn to value resource items (unit costs), and determine the total cost of treatment per disease stage.

The study covered nine tertiary hospitals, seven of which were government hospitals and two were private hospitals, with all tertiary hospitals providing breast cancer services and accredited by Philippine Health Insurance Corporation (PHIC or PhilHealth) for the Z-Benefit Package. Interventions and services related to breast cancer included radiographic procedures, laboratory and imaging tests, chemotherapy drugs and medications, medical and surgical supplies, surgical rates (for breast surgery), accommodation, staff time and salary/professional fees, and other procedure fees. The study conducted in 2022, examined cost prices of breast cancer interventions and services from stage 1–3B.

Purposive and convenience sampling were used based on PhilHealth accreditation and willingness of hospitals to participate in the study. The study conducted a focus group discussion with oncologists, radiologists, anesthesiologists, and other health care providers to validate the clinical guideline used and to solicit inputs to the costing design, analysis framework, and tools for data collection. Data collection of financial cost information (charge price) was conducted using a set of costing matrices filled out by the various departments of the hospitals. Costs and median rates were calculated across hospitals on diagnostics and imaging tests, surgery costs of both public and private facilities, medical treatment, and radiotherapy.

Breast MRI, Breast Panel, and Chest CT Scan are the top 3 most expensive diagnostic procedures ranging from PhP 8,102.00 to PhP 9,800.00 per procedure. Surgical procedures for breast cancer at private hospitals and public hospitals showed huge differences in costs. The cost of a cycle of chemotherapy ranges from PhP 596.70 to PhP 3,700.00 per session, while the cost of targeted therapy can cost up to PhP 46,394.21 per session. A year of hormone therapy ranges from PhP 3,276.00 with the use of Tamoxifen, and up to PhP 68,284.00 with Goserelin. Aromatase inhibitors such as Anastrozole and Letrozole cost from PhP 18,000 to PhP 36,000, respectively. Multiple cycles depending on the diagnosis are prescribed per patient and used in combination with other chemotherapy medications or other therapies such as targeted therapy and hormone therapy are usually taken daily up to 5 to 10 years. Conventional radiotherapy can cost up to PhP 88,150.00 covering 28 sessions, CT simulation, and CT planning.

This cost study provides relevant information and better perspective on benefit development for the PHIC, policy development for Department of Health on where and how to focus their support for the patient’s financial preparedness to address medical and f inancial catastrophes.

PhilHealth needs to guide the health care providers of their costing method and to develop their own integrated, interoperable, and comprehensive cost data library.

It recommends that the government allocate budget and cover for screening and assessment for earlier stage diagnosis of patients and lower health expenditure costs on cancer treatment.

OBJECTIVE: To observe the effect of transcutaneous electrical acupoint stimulation (TEAS) on postoperative pain in patients undergoing modified radical mastectomy for breast cancer. METHODS: A total of 140 female patients scheduled for unilateral modified radical mastectomy for breast cancer undergoing general anesthesia were randomized into a TEAS group (70 cases) and a sham TEAS group (70 cases, 2 cases dropped out). Patients in both groups received TEAS or sham TEAS at bilateral Neiguan (PC6), Zusanli (ST36), and Danzhong (CV17), respectively, from 30 min before anesthesia induction until the end of surgery, and on 1st, 2nd, and 3rd days after surgery for 30 min a time, once a day. On 1st, 2nd, and 3rd days after surgery, the pain visual analogue scale (VAS) score was observed; on 3, 6, 12 months after surgery, the incidence rate of chronic pain was observed; before surgery, and on 1st, 3rd, and 7th days after surgery, the serum levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-10 were detected; the number of analgesia pump press, rescue analgesia, and the occurrence of adverse reaction after surgery were recorded in the two groups. RESULTS: In the TEAS group, the VAS scores on 1st and 2nd days after surgery, and the incidence rates of chronic pain on 3 and 6 months after surgery were lower than those in the sham TEAS group (P<0.05). On 1st, 3rd, and 7th days after surgery, the serum levels of TNF-α, IL-6, and IL-10 were increased compared with those before surgery in both groups (P<0.05, P<0.01); the above indexes in the TEAS group were lower than those in the sham TEAS group (P<0.05). The number of analgesia pump press and the incidence rate of rescue analgesia after surgery in the TEAS group were lower than those in the sham TEAS group (P<0.05). There was no statistically significant difference in the incidence of adverse reactions after surgery between the two groups (P>0.05). CONCLUSION TEAS can effectively improve both the postoperative acute pain and chronic pain in patients undergoing modified radical mastectomy for breast cancer, the mechanism may relate to inhibiting the inflammatory reaction.
Humans ; Female ; Acupuncture Points ; Pain, Postoperative/blood* ; Middle Aged ; Breast Neoplasms/surgery* ; Adult ; Transcutaneous Electric Nerve Stimulation ; Mastectomy, Modified Radical/adverse effects* ; Interleukin-6/blood* ; Tumor Necrosis Factor-alpha/blood* ; Interleukin-10/blood* ; Aged

INTRODUCTION: Pregnancy-associated breast cancer (PABC) is described as breast cancer diagnosed within pregnancy or within 1 year postpartum. PABC is becoming more common due to delayed childbearing, with older maternal age increasing the likelihood of tumorigenesis coinciding with pregnancy. Our review aims to outline the important principles of managing PABC, and discusses future fertility implications, genetic testing and postnatal considera-tions that are not often considered in other existing reviews. METHOD: A literature search was conducted using PubMed, Cochrane and Google Scholar databases. RESULTS: A persistent breast mass in pregnant women should be evaluated with a breast ultrasound. Total mastectomy is the standard treatment in the first trimester. Chemotherapy is contraindicated in the first trimesters, but can be given in the second and third trimester, and stopped before 35 weeks. Radiotherapy should be delayed until delivery, and hormone receptor therapy is contraindicated in pregnancy. A multidisciplinary team involving an obstetrician, medical oncologist and other allied health professionals is crucial. Delivery should be planned as close to 37 weeks as possible, and at least 3 weeks after the last chemotherapy cycle. Vaginal delivery is preferred, and breastfeeding can resume 14 days after the last chemotherapy regime. CONCLUSION A breast mass in a pregnant woman should not be dismissed. PABC must be managed by multidisciplinary teams at tertiary medical centres with access to surgery and chemoradiation therapies. Management strategies must include safe manage-ment and delivery of the fetus, contraception and future fertility planning.
Humans ; Female ; Pregnancy ; Breast Neoplasms/diagnosis* ; Pregnancy Complications, Neoplastic/diagnosis* ; Mastectomy ; Delivery, Obstetric

INTRODUCTION: Trastuzumab deruxtecan (T-DXd) has revolutionised treatment for metastatic breast cancer (MBC). While effective, its high cost and toxicities, such as fatigue and nausea, pose challenges. METHOD: Medical records from the Joint Breast Cancer Registry in Singapore were used to study MBC patients treated with T-DXd (February 2021-June 2024). This study was conducted to address whether reducing dose intensity and density may have an adverse effect on treatment outcomes. RESULTS: Eighty-seven MBC patients were treated with T-DXd, with a median age of 59 years. At the time of data cutoff, 32.1% of patients were still receiving T-DXd. Over half (54%) of the patients received treatment with an initial relative dose intensity (RDI) of <;85%. Overall median real-world progression-free survival (rwPFS) was 8.1 months. rwPFS was similar between RDI groups (<85%: 8.7 months, <85%: 8.1 months, P=0.62). However, human epidermal growth receptor 2 (HER2)-positive patients showed significantly better rwPFS outcomes compared to HER2-low patients (8.8 versus 2.5 months, P<0.001). Only 16% with central nervous system (CNS) involvement had CNS progressive disease on treatment. No significant progression-free survival (PFS) differences were found between patients with or without CNS disease, regardless of RDI groups. Five patients (5.7%) developed interstitial lung disease (ILD), with 3 (3.4%) having grade 3 events. Two required high-dose steroids and none were rechallenged after ILD. There were no fatalities. CONCLUSION Our study demonstrated that reduced dose intensity and density had no significant impact on rwPFS or treatment-related toxicities. Furthermore, only 5.7% of patients developed ILD. T-Dxd provided good control of CNS disease, with 82% of patients achieving CNS disease control.
Humans ; Female ; Breast Neoplasms/mortality* ; Middle Aged ; Trastuzumab/adverse effects* ; Aged ; Adult ; Singapore/epidemiology* ; Antineoplastic Agents, Immunological/adverse effects* ; Camptothecin/adverse effects* ; Immunoconjugates/adverse effects* ; Retrospective Studies ; Progression-Free Survival ; Receptor, ErbB-2/metabolism* ; Neoplasm Metastasis ; Dose-Response Relationship, Drug ; Treatment Outcome ; Registries