Chemotherapy In Treatment Of Breast Cancer Research Articles

Theranostics Using MCM-41-Based Mesoporous Silica Nanoparticles: Integrating Magnetic Resonance Imaging and Novel Chemotherapy for Breast Cancer Treatment

Theranostics Using MCM-41-Based Mesoporous Silica Nanoparticles: Integrating Magnetic Resonance Imaging and Novel Chemotherapy for Breast Cancer Treatment

Abstract PO2-16-12: Real world evidence of neoadjuvant chemotherapy for breast cancer treatment in a Brazilian multicenter cohort: correlation of pathological complete response and overall survival

Abstract Introduction: Breast cancer is the most common malignancy among women in Brazil and worldwide. Neoadjuvant chemotherapy (NAC) has been increasingly used for the treatment of breast cancer conditions ranging from locally advanced tumors to early-stage triple-negative and HER-2 positive tumors. Nowadays only 5% of breast cancer patients are enrolled in clinical trials. Real-world data is important to evaluate how clinical trial treatments behave in the real world with all the heterogeneous patient characteristics of those treated differently from the homogeneity of clinical trials. Objectives: To evaluate the rates of pathological complete response (pCR) in patients undergoing neoadjuvant chemotherapy (NAC) for the treatment of breast cancer (BC) To examine the differences in pathological complete response (pCR) rates between HER-2 positive breast cancer patients with and without trastuzumab treatment, and between triple-negative breast cancer (TNBC) patients with and without platinum-based treatment, Additionally, we aim to assess the impact of pCR on overall survival (OS) and disease-free survival (DFS) using real-world data (RWD). Methods: This was a retrospective, multicentric cohort study, that included female patients over 18 years of age, with a diagnosis of non-metastatic breast cancer undergoing NAC. As an exploratory real-world data study, no confirmatory hypothesis was established, so no corrections for multiple comparisons were necessary. Overall survival (OS) and disease-free survival (DFS) were estimated by the Kaplan-Meier method calculated at five years. Additionally, we conducted a multivariate analysis to identify significant associations with pathologic complete response (pCR) and overall survival (OS). We employed a forest plot to visually represent these associations Results: From 2011 to 2020, 1,891 patients were included in the study, and 421 (22,3%) achieved pCR (ypT0 ypN0) and considering the presence of residual in situ carcinoma (DCIS) the pCR was seen in 467 patients (23,5) without significant difference (p=0,567) . The pCR rate varied between the subtypes: luminal A 17,0%, luminal B 21,3%, luminal HER2 23,0%, TNBC 22,5% and HER2 28,5% (p = 0,057). The type of neoadjuvant chemotherapy (NAC) regimen was correlated with pathological complete response (pCR). Among HER2-positive patients, those who received Trastuzumab had a significantly higher rate of pCR compared to those who did not receive it (p < 0.0001). Similarly, in patients with TNBC, those who underwent treatment with platinum-based regimens also showed higher rates of pCR (p < 0.0001). There were 694 deaths, and the 5-year OS rate was 62.9%. OS was also grouped according to pCR status, and pCR OS rate was 88,3% and non-pCR 58.1% significant difference observed (p < 0.0001). Five-year DFS of pCR was 92.2% and non-pCR 64.3% (p < 0.0001). Conclusion: this real-world data study evaluated the rates of pathological complete response (pCR) in breast cancer patients undergoing neoadjuvant chemotherapy (NAC). The results revealed varying pCR rates among different breast cancer subtypes, with HER2-positive and triple-negative subtypes showing higher rates. The use of Trastuzumab in HER2-positive patients and platinum-based regimens in triple-negative patients correlated with significantly higher pCR rates. Furthermore, achieving pCR was associated with improved overall survival (OS) and disease-free survival (DFS). These findings emphasize the importance of considering individual tumor characteristics and tailoring treatment strategies for breast cancer patients to optimize outcomes. Clinicopathological characteristics of patients AJCC, American Joint Committee on Cancer; IDC, invasive ductal carcinoma; ILC, invasive lobular carcinoma; TNBC triple negative breast cancer. NAC schemas and correlation with pCR. AC-T, doxorubicin + cyclophosphamide – taxane; AC-TPlatinum, doxorubicin + cyclophosphamide – taxane+carboplatin; AC-TH, doxorubicin + cyclophosphamide – taxane+herceptin. Citation Format: Marcelo Antonini, Andre Mattar, Fernanda Grace Bauk Richter, Gabriel Pannain, Andressa Amorim, Marina Diogenes, Odair Ferraro, Luiz Gebrim, Reginaldo Coelho Lopes, Juliana Real. Real world evidence of neoadjuvant chemotherapy for breast cancer treatment in a Brazilian multicenter cohort: correlation of pathological complete response and overall survival [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-16-12.

Abstract PO2-23-04: Magnetic Seeds, used to Locate the Metastatic Axillary Lymph Node placed before Neoadjuvant Chemotherapy for Breast Cancer Treatment, do not interfere the pre-surgical MRI Breast response assessment

Abstract Background: Axillary management in clinically node-positive patients who converted to ycN0 after neoadjuvant chemotherapy (NAC) for breast cancer (BC) remains under research with the aim of de-escalation of axillary lymph node dissection (ALND). A magnetic seed is one of the several positive lymph nodes marking techniques used in targeted axillary dissection (TAD) for patients with cN1 breast cancer undergoing neoadjuvant systemic therapy. It has been criticized for its potential masking effect due to the artefact it produces in the MRI sequences used to assess a proper breast response. This study evaluates if the magnetic seeds placed before NAC for guided TAD have influenced in the breast MRI response assessments. Methods: From October 2021 to June 2023, patients with cT0-4 cN1 breast cancer who were candidates for primary systemic treatment were prospectively recruited. Once a breast lesion and axillary node positivity were confirmed, a based hydrogel marker and a magnetic seed, respectively, were placed prior NAC. Once systemic treatment was completed, imaging techniques were used to assess the response, with MRI being the imaging technique of choice to assess breast response and axillary ultrasound the imaging technique of choice to assess axillary response. Surgical pathological confirmation of response in the axilla was by TAD, including sentinel lymph node and magnetic clipped node resection. Results: A total of 43 patients were included and their characteristics are shown in Table 1. In 16 patients (37%) the tumour was located in the upper outer quadrant (UOQ). In this group, the susceptibility artefact produced by the magnetic seed in the MRI created a black hole obscuring the axilla with a mean diameter of 69 mm (range: 57-76 mm). In no case did the halo interfere with the correct MRI visualisation of the breast marker. By MRI, the mean distance of the artifact halo from the breast marker or residual breast lesion was 40 mm (range: 13-79 mm). Overall, complete radiological response (ycCR) was reported in 20 patients (46%), breast only in 21 (49%) and axilla only in 38 (88%) patients. In 5 patients, preoperative axillary ultrasound revealed residual axillary disease, confirmed by FNA, lead to direct ALND. In the remaining 38 patients the axillary TAD assessment was completed. In all cases, the magnetic clipped node was successfully surgically removed. Pathological complete response (pCR) was confirmed in 9 (21%), breast only in 11 (26%) and axilla only in 13 (30%) patients. MRI diagnostic performance in detecting residual breast disease after NAC was not altered by the magnetic clipped node artifact when comparing the tumour location in the UOQ to the other quadrants (AUC 0.764 vs. 0.702; p=0.698). Conclusions: Surgical axillary staging remains the most reliable method for assessing the axillary response after NAC. Target axillary dissection guided by magnetic seed placed before NAC is an effective and accurate technique. The artifact generated in the MRI does not interfere with the pre-surgical breast response assessment after neoadjuvant systemic treatment. Table 1: Patients and tumor characteristics Citation Format: Martin Espinosa-Bravo, Joaquin Rivero Deniz, Clara Morales Comas, Javier de la Torre Fernandez de Vega, Irene Vives Rosello, Enrica Esposito, Vicente Peg Camara, María De Les Neus Rus Calafell, Ignacio Miranda Gomez, Christian Siso Raber. Magnetic Seeds, used to Locate the Metastatic Axillary Lymph Node placed before Neoadjuvant Chemotherapy for Breast Cancer Treatment, do not interfere the pre-surgical MRI Breast response assessment [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-23-04.

11 year tertiary centre experience of neoadjuvant chemotherapy treatment for breast cancer

11 year tertiary centre experience of neoadjuvant chemotherapy treatment for breast cancer

GAIT PARAMETERS IN OLDER BREAST CANCER SURVIVORS WITH PERSISTENT CHEMOTHERAPY-INDUCED PERIPHERAL NEUROPATHY

Abstract Chemotherapy-induced peripheral neuropathy (CIPN) results from chemotherapy for breast cancer treatment. CIPN symptoms persist causing significant loss of functional abilities and increased risk of falls. This study aimed to assess the spatiotemporal gait parameters in breast cancer survivors with CIPIN using an IMU system. We hypothesized that spatiotemporal gait parameters will differ between patients with persistent CIPN as compared to normative values. Thirty-two women who completed taxane-based chemotherapy for breast cancer and who have symptomatic neuropathy >6 months following completion of chemotherapy. Gait was assessed using seven Inertial Measurement Unit (IMU) sensors positioned at the sacrum, upper and lower leg, and foot. Participants completed a 2-minute walk at a comfortable walking pace. The outcome variables assessed included gait speed, single limb support, stride length, gait cycle time, stance percent, swing percent, double support percent, and cadence. Mean age 65(10) years, gait speed was 0.95(0.2) meters/second, single limb support 37.9(2.2) % of gait cycle, stride length 1.1(0.2) meters, gait cycle time 1.2(0.1) seconds, stance percent 62.1(2.2)% GC, swing percent 37.9(2.2)% GC, double support percent 23.9(4.3)% GC, and cadence 104.6(12.3) steps/min. Gait parameters assessed in this study showed an excellent test-retest reliability (r >0.86; ICC > 0.90). This is the first study to assess gait parameters in older breast cancer survivors with CIPN. Breast cancer survivors with CIPN showed reductions in all gait parameters. Reduced gait speed and stride length are critical indicators of fall risk for women with CIPN. Our study confirmed differences in spatiotemporal parameters between patients with persistent CIPN.

Pentagamavunone-1 inhibits aggressive breast cancer cell proliferation through mitotic catastrophe and ROS-mediated activities: in vitro and in vivo studies

Pentagamavunone-1 (PGV-1), an analog of curcumin, has been studied for its cytotoxic effects in 4T1, MCF7, MCF7/HER2, and T47D breast cancer cells. Its antiproliferative effect is partly mediated through G2/M arrest; however, its molecular mechanism during cell cycle progression remains unknown. In this study, we aimed to determine whether PGV-1 has any anticancer effects on highly aggressive breast cancer cells, with a focus on cell cycle regulatory activity, reactive oxygen species (ROS) generation, and their mediated effects on cancer cells. MDA-MB-231 (triple-negative) and HCC1954 (overexpressed HER2) immortalized human breast cancer cells were used in the study. PGV-1 exhibited cytotoxic activity with an irreversible antiproliferative impact on treated cells and had good selectivity when tested in fibroblast cells. Oral PGV-1 administration suppressed tumor growth in a cell-derived xenograft mouse model. PGV-1 induced the phosphorylation of Aurora A kinase and PLK1 in MDA-MB-231 cells, while PLK1 and cyclin B1 phosphorylation were enhanced in the PGV-1-treated HCC1954 cells during prometaphase arrest. Intracellular ROS production was substantially higher upon PGV-1 treatment following mitotic arrest, and this activity caused impairment of mitochondrial respiration, induced senescence, and subsequently triggered early-to-late apoptosis. Collectively, these results suggest that the molecular mechanism of PGV-1 involves the regulation of mitotic kinases to cause cell cycle arrest and the enhancement of ROS production to impair mitochondrial activity and induce cellular senescence. The therapeutic activities demonstrated by PGV-1 in this study show its potential as an appealing candidate for chemotherapy in breast cancer treatment.

Real-world evidence of neoadjuvant chemotherapy for breast cancer treatment in a Brazilian multicenter cohort: Correlation of pathological complete response with overall survival

ObjectivesWe aimed to evaluate the pCR rate in patients receiving NAC for the treatment of breast cancer (BC) in a multicenter cohort in Brazil. Additionally, we aimed to use RWD to assess the impact of pCR on OS and DFS. MethodsThis was a retrospective, multicenter cohort study that included female patients over 18 years of age who were diagnosed with nonmetastatic breast cancer and received NAC. OS and DFS at five years were estimated by the Kaplan‒Meier method. Additionally, we conducted a multivariate analysis to identify factors that were significantly associated with pCR and OS. ResultsFrom 2011 to 2020, 1891 patients were included in the study, and 421 (22,3%) achieved pCR (ypT0 ypN0). Considering the presence of residual DCIS, pCR was achieved in 467 patients (23,5%). The pCR rate varied between the subtypes: HER-2+ (p = 0,016) and clinical stage IIIA and IIIB (p < 0,001). Among HER-2+ patients, those who received trastuzumab had a significantly higher pCR rate than those who did not receive trastuzumab (p < 0.0001). Similarly, patients with TNBC who received treatment with platinum-based regimens also showed higher pCR rates (p < 0.0001). OS was grouped according to pCR status, and the OS rate was 88,3% in the pCR group and 58.1% in the non-pCR group (p < 0.0001). The five-year DFS was 92.2% in the pCR group and 64.3% in the non-pCR group (p < 0.0001). ConclusionThe pCR rate and its prognostic value varied across BC subtypes. In our study, pCR could be used as a surrogate of favorable clinical outcome, as it was associated with higher OS and DFS rates.

Developing targeted drug delivery carriers for breast cancer using glutathione-sensitive doxorubicin-coupled glycated bovine serum albumin nanoparticles

Incorporation of the nano-based carriers into drug delivery provides a promising alternative to overcome the limitations of the conventional chemotherapy. Doxorubicin (DOXO) is an effective chemotherapeutic drug widely used in chemotherapy for breast cancer treatment. A globular protein bovine serum albumin (BSA) holds great potential as carriers in pharmaceutical applications. This work is aimed at developing the DOXO-coupled glycated BSA nanoparticles via desolvation method for improving the capability of targeting the GLUT5 transporters over-expressed on breast cancer cells. Fructosamine assay and Fourier transform infrared spectroscopy were employed to determine the content of fructosamine structure and structural changes on the surfaces of nanoparticles, respectively. Additionally, the synthesized BSA nanoparticles were further characterized by electron microscopy and dynamic light scattering. Results revealed that the DOXO-coupled glycated BSA nanoparticles were spherically shaped with a hydrodynamic diameter of ~60.74 nm and a ζ-potential of ~ − 42.20 mV. Moreover, the DOXO release behavior of as-synthesized DOXO-coupled glycated BSA nanoparticles was examined under different conditions. Finally, the DOXO-coupled glycated BSA nanoparticles were found to exhibit cytotoxicity toward both MCF-7 and MDA-MB-231 cells. Our findings evidently suggested that the drug-coupled glycated BSA nanoparticles serve as the potential candidates for targeted drug delivery platform used in breast cancer therapy.

Preparation, Characterization and Cytotoxic Studies of Cisplatin-containing Nanoliposomes on Breast Cancer Cell Lines

Objective: Today, cancer is one the most important challenges in modern medicine. Breast carcinoma is one type of cancer that is treated with cisplatin, a chemotherapy drug. By using liposomal nanocarriers, this study seeks to increase the therapeutic efficiency of cisplatin. Method: The zeta potential, particle size, and drug-release characteristics of nanoliposomal cisplatin were evaluated after it had been synthesized using the reverse phase evaporation technique. The cytotoxicity rate of nanoliposomal cisplatin was then assessed using the T-47D breast cancer cell line. Results: This study’s liposomal nanoparticles (NPs) had a zeta potential of -24.9 mV and a particle size of 342.3 nm. 3.51% and 79.6%, respectively, were found to be the drug loading level and amount of encapsulated drug. A significant improvement over the free drug was seen in this nanoliposome’s cytotoxic effect on the T-47D breast cancer cell line (P&lt;0.05). Conclusion: According to what we have discovered, cisplatin liposomal nanocarriers may prove to be a cutting-edge chemotherapy treatment for breast cancer.

Predicting Chemotherapy Benefit across Different Races in Early-Stage Breast Cancer Patients Using the Oncotype DX Score.

Oncotype DX assay, a multigene molecular test, has been widely used to stratify relapse risk and guide chemotherapy treatment in breast cancer. However, the optimal threshold of the Oncotype DX score in predicting chemotherapy benefit and its racial variation has not been investigated. In this study, we apply a random forest survival model to the SEER-Oncotype cohort data (Surveillance, Epidemiology, and End Results with Oncotype DX test information for breast cancer patients) and determine chemotherapy benefit thresholds in early-stage, estrogen-receptor-positive (ER+), and HER2-negative (HER2-) patients of different races. Our results indicate that early-stage ER+, HER2-, and LN-/LN+ patients may benefit from receiving chemotherapy at a lower Oncotype DX score than current guidelines (Recurrence Score, RS > 25 or RS > 30) suggest. According to the estimated chemotherapy sensitivity thresholds from our models, 2.05-2.72-fold more lymph-node-negative (LN-) and 2.08-5.02-fold more lymph-node-positive (LN+) patients who may not currently be recommended for chemotherapy by their Oncotype DX test result may actually have the potential to benefit from chemotherapy. Furthermore, our models indicate a racial difference in chemotherapy benefit: white, black, and Asian women with early-stage ER+/LN- tumors benefit from chemotherapy when their Oncotype DX scores are greater than 19.9, 37.2, and 18.0, respectively. Our study provides a method for calibrating multigene molecular tests to help guide treatment decisions in racially and ethnically diverse patients with cancer. Specifically, we identify key chemotherapy sensitivity thresholds for the Oncotype DX recurrence score test in breast cancer patients and provide evidence that certain patients may benefit from receiving chemotherapy at a lower threshold than the current clinical guidelines suggest.

Effects of Adriamycin-Cytoxan chemotherapy on hematological and electrolyte parameters among breast cancer patients.

Adriamycin-Cytoxan (AC) is a common chemotherapy treatment for breast cancer (BC) patients. Its electrolyte and hematological adverse effects have not been addressed adequately. This study aimed to assess the effect of AC on hematological and electrolyte parameters among BC patients. A hospital-based comparative cross-sectional study design was conducted from March to November 2022. Randomly selected AC-treated (n=100) and untreated (n=100) patients were included. Structured questionnaire and medical records were used to collect sociodemographic data. Anthropometric parameters, hematological indices, and serum electrolytes were measured. Cobas Integra 400+and SYSMEX-XT-4000i were used to analyze serum electrolytes and hematological indices respectively. The data were analyzed using SPSS version 25. Independent t-test and chi-square test were used. p-value <0.05 was considered statistically significant. AC-treated patients' mean total white blood cell (TWBC), neutrophil (NE), lymphocyte (LY), red blood cell (RBC), hemoglobin (Hgb), hematocrit (HCT), and sodium(Na+) values were significantly reduced (p<0.05) than patients with no treatment. However, mean eosinophils (EO), platelet (PLT) counts, red cell distribution-width (RDW), potassium (K+), and plateletcrit (PCT values were significantly increased (p<0.05). The majority of blood cells and serum sodium were affected by AC treatment. Incorporating these parameters in the routine analysis and further studies on the detailed mechanism of action of this drug is required.

Ex Vivo treatment of coronary artery endothelial cells with serum post-exercise training offers limited protection against in vitro exposure to FEC-T chemotherapy.

Background: Chemotherapy treatment for breast cancer associates with well-documented cardiovascular detriments. Exercise has shown promise as a potentially protective intervention against cardiac toxicity. However, there is a paucity of evidence for the benefits of exercise on the vasculature. Objectives: This study aimed to determine the effects of chemotherapy on the vascular endothelium; and if there are protective effects of serological alterations elicited by an exercise training intervention. Methods and Results: 15 women participated in a 12-week home-based exercise intervention consisting of three high-intensity interval sessions per week. Human coronary artery endothelial cells (HCAEC) were exposed to physiological concentrations of 5-fluorouracil, epirubicin, cyclophosphamide (FEC) and docetaxel to determine a dose-response. Twenty-4hours prior to FEC and docetaxel exposure, HCAECs were preconditioned with serum collected pre- and post-training. Annexin V binding and cleaved caspase-3 were assessed using flow cytometry and wound repair by scratch assays. Chemotherapy exposure increased HCAEC Annexin V binding, cleaved caspase-3 expression in a dose-dependent manner; and inhibited wound repair. Compared to pre-training serum, conditioning HCAECs with post-training serum, reduced Annexin V binding (42% vs. 30%, p = 0.01) when exposed to FEC. For docetaxel, there were no within-group differences (pre-vs post-exercise) for Annexin V binding or cleaved caspase-3 expression. There was a protective effect of post-training serum on wound repair for 5-flurouracil (p = 0.03) only. Conclusion: FEC-T chemotherapy drugs cause significant damage and dysfunction of endothelial cells. Preconditioning with serum collected after an exercise training intervention, elicited some protection against the usual toxicity of FEC-T, when compared to control serum.

Hyperthermia-sensitive Liposomes Containing Brucea Javanica Oil for Synergistic Photothermal-/Chemo-Therapy in Breast Cancer Treatment.

High mortality and limited therapeutic efficacy of clinical treatment make breast cancer a stubborn disease in women. The hypovascular issue is the main challenge needed to be overcome in breast cancer treatment. For this purpose, hyperthermia-sensitive liposomes containing indocyanine green (ICG) and brucea javanica oil (BJO) (LP(BJO/ICG)) were constructed for near-infrared (NIR) laser-induced photothermal- /chemo-antitumor therapy. ICG, an FDA-approved photothermal agent, was employed in this study to perform photothermal therapy (PTT) effect as well as relieve hypovascular conditions in breast cancer tissue. BJO triggered release from the hyperthermia-sensitive LP (BJO/ICG) due to disassembly of liposomes under the PTT effect caused by ICG under NIR laser irradiation. It was found that mice in LP (BJO/ICG) group showed the slowest tumor growth under NIR laser irradiation, illustrating the strongest antitumor effect among all groups. This responsive-release drug delivery platform can be a promising candidate for the treatment of breast cancer.

Antibody–drug conjugates: the evolving field of targeted chemotherapy for breast cancer treatment

Antibody–drug conjugates (ADCs) are a class of antineoplastic agents whose structure is composed of three main components: a monoclonal antibody (mAB) targeting a specific target antigen, a cytotoxic payload, and a linker binding the antibody to the payload. By combining the specificity of mABs with the high potency of the payloads, ADCs constitute a smart drug delivery system with improved therapeutic index. After recognition and binding of the mAB to its target surface antigen, ADCs are internalized by endocytosis by the tumor cell, releasing the payloads into the cytoplasm, where they exert their cytotoxic activity, eventually leading to cell death. The composition of some of the new ADCs confers additional functional properties that allow expanding their activity to neighboring cells not expressing the target antigen, constituting a valuable strategy to overcome tumor heterogeneity. Some of these ‘off-target effects’, such as the bystander effect, are possibly the mechanism underlying the antitumor activity demonstrated in patients with low expression of the target antigens, which represents an important paradigm shift in anticancer targeted therapy. Three ADCs are currently approved for the treatment of breast cancer (BC); two anti-HER2 (human epidermal growth factor receptor 2) ADCs (trastuzumab emtansine and trastuzumab deruxtecan); and one Trop-2-targeted ADC (sacituzumab govitecan). Based on the unprecedented efficacy data demonstrated by these agents, ADCs have been incorporated as part of standard regimens for all subtypes of advanced BC, as well as for high-risk early HER2-positive BC. Despite the remarkable advances, several hurdles still remain to overcome, including the development of reliable biomarkers for patient selection, prevention, and management of potentially severe toxicities, ADC resistance mechanisms, post-ADC resistance patterns, and optimal treatment sequencing and combinations. In this review, we will summarize the currently available evidence related to the use of these agents, as well as explore the current landscape of ADC development for BC treatment.

The trend and direct costs of screening and chemotherapy treatment of breast cancer in the new coronavirus pandemic: total and interrupted time series study

BackgroundThe COVID-19 pandemic has overloaded the healthcare systems of many countries and reduced the population’s access to treatment and prevention of other diseases. This study aims to assess whether the COVID-19 pandemic has negatively interfered with the trend and the direct costs of screening and chemotherapy treatment of breast cancer in a public and universal healthcare system.MethodThis was an ecological time series study using an open database of a public and universal health system from 2017 to 2021.ResultsIn 2020, there was a 41% reduction in the coverage rate of breast cancer screening in women aged 50 to 69 years (about 1 million mammograms missed). The total direct cost of breast cancer screening reduced proportionally to the number of tests (BRL 67 million). On the other hand, the cost of chemotherapy treatment was higher in 2020, both in advanced (BRL 465 million) and localized (BRL 113 million) diseases. In the time series, mammograms’ trend and direct costs changed from stationary to decreasing after the COVID-19 pandemic. The trend of direct costs with chemotherapy treatment for the advanced disease has been increasing and has not changed after the COVID-19 pandemic. On the other hand, in the case of localized disease, there was a trend toward reducing direct costs after the pandemic.ConclusionAfter COVID-19, there was a downward trend in breast cancer screening and its direct costs, an upward trend in chemotherapy costs for advanced disease, and a downward trend in chemotherapy costs for localized disease.

Early-stage breast cancer menopausal symptom experience and management: exploring medical oncology clinic visit conversations through qualitative analysis.

Women being treated with chemotherapy for breast cancer experience menopausal symptoms that vary in presentation and impact on quality of life. The clinical visit before each chemotherapy cycle provides an important opportunity to allow patients to dialogue with their medical oncology healthcare providers about these symptoms and identify strategies for self-management. The objective of this study was to characterize patient and provider interactions regarding the menopausal symptom experience and management in the context of breast cancer treatment. Thematic analysis was employed to analyze 61 transcripts from clinical encounters of women receiving chemotherapy treatment for breast cancer. Transcripts were chosen based on their inclusion of menopausal symptom discussion. Themes were separated into three distinct categories: patient, clinician, and dyadic themes. The overarching theme was goal discordance in the clinical visit, which was reflected in the following themes: unexpected and unprepared; distressed, disrupted and disturbed; clinical insensitivity; missed opportunity for management and empathy; and use of humor and colloquial language. Overall, women were unprepared for the menopausal symptom experience, and clinicians did not often provide management, interventions, or empathetic responses. There is a need to develop more astute assessment and communication regarding menopausal symptoms during the clinical visit. Possible interventions include a more holistic assessment, algorithms to facilitate the clinician's attention and response to menopausal symptoms, and treatment of symptoms.

Impacts of breast cancer and chemotherapy on gut microbiome, cognitive functioning, and mood relative to healthy controls

Women diagnosed with breast cancer undergoing chemotherapy experience cognitive impairment, symptoms of anxiety and depression, and physical side effects including disruption in the diversity and community composition of the gut microbiome. To date, there is limited research exploring the associations among these specific challenges. The present cross-sectional study explored the associations of self-reported cognitive functioning, depression, and anxiety symptoms, and gut microbiome diversity and community composition in women who were diagnosed with and undergoing chemotherapy treatment for breast cancer (BC) compared to cancer-free healthy controls (HC). The BC group displayed higher rates of cognitive dysfunction (p < 0.001) and depressive symptoms (p < 0.05) relative to HC. There was a significant difference in microbiome community composition between BC and HC, particularly characterized by a decreased relative abundance of the mucin-degrading genus Akkermansia in BC compared to HC (p < 0.05). Association models identified significant associations among group, cognitive, depression, and microbiome variables (p < 0.001). Overall, the study identified that BC participants experienced significant differences in self-reported cognitive functioning, self-reported depression symptoms, microbiome community composition, and mucin-degrading bacteria of the gut-mucosal barrier, relative to HC. The present study is consistent with the hypothesis that gut microbiome community composition impacts a woman’s experience with breast cancer and treatment suggesting that microbiome-based interventions have potential for improving quality of life outcomes in individuals with breast cancer.

ODP560 Thyroid Hormones membrane receptor, Integrin αvβ3, as a potential prognostic marker of chemotherapy response in breast cancer

Abstract Despite the development of novel therapies, breast cancer (BC) tumors are treated with conventional therapy eventually. Due to tumor heterogeneity, it is necessary to define new biomarkers to identify groups with different molecular characteristic and on this basis improve the treatment decision. The impact of thyroid status in BC growth has previously been studied. In particular, alterations of thyroid function during chemotherapy for BC treatment have been found and it has been demonstrated that T3 induces chemosensitization of BC cells. However, the relationship between thyroid hormones (THs) membrane receptor, integrin αvβ3, and BC response to chemotherapy remains unclear. The aim of this study is to evaluate the relationship between THs and integrin αvβ3 expression as prognostic value in BC patients. The mRNA expression of ITGB3 in the TCGA-PanCancer Atlas BC dataset (1084 patients) was associated with worse overall survival. Moreover, ITGB3 mRNA expression was significantly correlated with genes encoding multidrug resistance transporter proteins MDR1 and BCRP, (Pearson, R score &amp;gt;0.3 and p&amp;lt;0,05). The diagnostic role of ITGB3 in BC was assessed by receptor operating characteristic (ROC) curve analysis. ITGB3 mRNA levels were higher in non-responder patients treated with anthracycline (AUC=0,673, p=1.8e-10) and taxanes (AUC=0.675, p=1.9e-07). To confirm the association between the integrinαvβ3-mediated effects and multidrug resistance protein transporters, we conducted in vitro assays ofMDA-MB-231 cells treated with physiological concentrations of THs and evaluated their action on MDR1 protein levels and Rhodamine efflux as an indicator of the transporter activity. We found that THs induce MDR1 protein expression and transporter activation and this effect is blocked by the presence of the integrin selective inhibitor cilengitide. Furthermore, in MDA-MB-231 doxorubicin-resistant cells THs induce MDR1 and BCRP greater protein expression than in MDA-MB-231 parental cells and this effect is abrogated by cilengitide. Therefore, we found that integrin β3 is correlated with worse overall survival and response to anthracyclines and taxanes pointing out its role as acancer biomarker with potential clinical utility. In patients with high integrin β3 mRNA expression, we found a significant correlation with proteins involved in drug transport such as MDR1 and BCRP. We also demonstrated that THs through integrin αvβ3 modulate the expression and activity of drug transporters. These results pointout the role of THs, and their membrane receptor, in BC response to treatments and introduce a new biomarker with potential clinical significance. Presentation: No date and time listed

Breast cancer chemotherapy treatment monitoring based on serum sample Raman spectroscopy.

In this paper, breast cancer patients were monitored throughout their chemotherapy treatments (CHT), with blood serum sample Raman spectroscopy and multivariate analysis, approximately for a year. First of all, we discriminate between healthy and clinically diagnosed breast cancer patients. Breast cancer detection in terms of sensitivity and specificity were 87.14% and 90.55% respectively. Although no shifts of peaks in mean spectrum of samples from breast cancer patients were found with respect to the mean spectrum from control patients, some peaks did show clear differences in intensity, the greatest disparities found at 509, 545, 1063, 1103, 1338, 1556, 1083 and 1449 cm− 1 are associated with amino acids and phospholipid, 1246 and 1654 cm− 1, corresponding to amide III and I, respectively. Other peaks of interest encountered at 450, 661, 890, 917 and 1405 cm− 1 are associated to glutathione. Then, 6 breast cancer patients were monitored during their chemotherapy treatments, the results were in complete correspondence with their medical records, enabling a detailed study of the evolution of each patient’s cancer. A special interest arose in the possible correlation between the intensity of Raman peak, 450 cm− 1, corresponding to glutathione and evolution of cancer throughout CHT, i.e., glutathione appears to be a good candidate as breast cancer biomarker. The results confirmed that Raman spectroscopy and PCA are, not only a good support to current breast cancer detection techniques, but could also be excellent techniques to monitor more efficiently breast cancer patients undergoing CHT, using blood serum samples which are a lot less invasive than other methods.

Antiproliferative Effect of Plant-Derived Bioactive Compounds Endowed with Antioxidant Activity on Breast Cancer Cells

Several lines of evidence indicate that plant-derived antioxidant compounds can be used as anticancer agents to support conventional pharmacological therapy. In this context, heme-oxygenase-1 (HO-1) modulation has been proven to represent a valid approach for reducing cancer cells’ proliferation through the activation of apoptosis and ferroptosis. This study focused on three little studied HO-1 inducers (paeonol, rosolic acid and dimethoxy resveratrol) in order to evaluate their efficacy as antiproliferative compounds on breast cancer cells (MCF-7 and MDA-MB 231). Cell viability data showed an interesting selectivity of dimethoxy resveratrol (DMR) for MDA-MB 231 cells. The ineffectiveness of Ferrostatin-1 and Trolox treatment led to the exclusion of ferroptosis involvement; meanwhile, cell viability reduction was associated with caspase 3/7 activation and apoptosis. Taken together, our results suggest a potential role of DMR as an adjuvant in conventional chemotherapy for breast cancer treatment.