Chemotherapy In Breast Cancer Patients Research Articles

Accuracy of MRI Versus PET/CT in the Prediction of Treatment Response to Neoadjuvant Chemotherapy in Breast Cancer.

Background Breast-conserving surgeries have significantly advanced breast cancer treatment, offering favorable oncological outcomes, enhanced cosmetic results, reduced postoperative morbidity, and better psychological acceptance compared to mastectomy. The introduction of neoadjuvant therapy has expanded the applicability of breast conservation surgery to include locally advanced tumors. Tumor response to neoadjuvant chemotherapy is evaluated using imaging modalities such as breast ultrasound, breast magnetic resonance imaging (MRI), and positron emission tomography/computed tomography (PET/CT). Accurate prediction of therapeutic response facilitates the planning of surgical and adjuvant treatments. This study aims to compare the diagnostic accuracy of MRI and PET/CT in predicting treatment response to neoadjuvant chemotherapy in breast cancer patients. Methods This retrospective study was conducted at a tertiary care center in Bahrain. A total of 138 patients with locally advanced breast cancer or human epidermal growth factor receptor-2 (HER2) positive, hormone receptor-negative cancers who underwent breast-conserving surgeries between June 2018 and December 2022 were included. The inclusion criteria focused on patients achieving a complete pathological responsefollowing neoadjuvant systemic therapy, ensuring a homogenous study population. Patients with hormone receptor-positive early breast cancers or metastatic tumors, ineligible for neoadjuvant chemotherapy, were excluded. Non-responders and partial responders were also excluded from the study. Statistical analysis was performed using IBM SPSS v26.0 (IBM Corp., Armonk, US). Response rates for the imaging modalities and histopathology results were assessed. Agreement between histology and imaging modalities was computed using kappa statistics. Diagnostic performance for predicting "no residual" disease was evaluated using the McNemar Test. All tests were two-tailed, with a p-value <0.05 considered statistically significant. Results The study included 138 patients, of whom 73 (52.9%) had an incomplete response or residual disease, while 65 (47.1%) had a complete response or no residual disease according to histology reports. There was slight agreement between post-neoadjuvant MRI and histology results (Cohen's kappa 0.172, p=0.010), while substantial agreement was observed between post-neoadjuvant PET/CT and histology results (Cohen's kappa 0.614, p=0.000). PET/CT demonstrated a higher sensitivity of 93.8% (p<0.001) and a specificity of 68.5%. Although MRI was more specific, the positive predictive value was comparable for both PET/CT and MRI. Conclusion PET/CT shows higher sensitivity and can serve as an early marker for predicting complete pathological response in post-neoadjuvant breast cancer patients. However, the prediction of residual disease is optimized by combining both MRI and PET/CT as diagnostic modalities.

Predicting efficacy of neoadjuvant chemotherapy in breast cancer patients with synthetic magnetic resonance imaging method MAGiC: An observational cohort study

ObjectiveMAGnetic resonance Imaging Compilation (MAGiC) is typical method of synthetic magnetic resonance imaging (MRI). The present aimed to investigate the role of MAGiC parameters of relaxation time (T1), transverse relaxation time (T2) and proton density (PD) to predict the treatment efficacy of breast cancer patients after neoadjuvant chemotherapy (NAC). MethodsThe present prospective cohort study enrolled 120 breast cancer patients who received NAC during 2021 to 2023. Demographic data and clinical characteristics including tumor node metastasis (TNM) stage, pathological type, molecular classification and lymph node metastasis were collected. The levels of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) were measured. Patients were divided by treatment efficacy using the Miller-Payne grading as partial pathological response (pPR) group and pathological complete response (pCR). The values of MAGiC parameters of longitudinal T1, T2, and PD values were recorded. ResultsIn all 120 patients, 73 (60.83%) cases were with pPR and 47 (39.17%) cases were with pCR after treatment. T2 values were markedly lower in pPR patients compared with pCR patients. However, no significant difference was found for T1 and PD values. No significant correlation was observed between any of MAGiC parameters and HER-2, ER or PR. ROC curve showed T2 could be used for prediction of pPR with AUC 0.780. Lymph node metastasis and low levels of T2 were found as independent risk factors for pPR after treatment. ConclusionThe T2 value parameter from MAGiC is an independent risk factor for pPR following NAC in breast cancer patients, suggesting its potential as a biomarker for predicting treatment efficacy.

Toward better understanding and management of chemobrain: the potential utilities of the MemTrax memory test

ObjectiveTo study the effects of chemotherapy on cognitive function in breast cancer patients, and to investigate the relationship of MemTrax test of memory and related functions to the FACT-Cog functional self-assessment for the evaluation and management of chemobrain.MethodsIn this prospective cohort study, clinical information of pathologically confirmed female breast cancer patients who decided to receive chemotherapy were collected in a questionnaire which was developed for this study and provided as a supplementary file. The FACT-Cog self-assessment and MemTrax test were administered before and after the chemotherapy treatments. Patients with chemobrain were identified using published criteria based on FACT-Cog scores, and MemTrax scores from chemobrain patients were analyzed.ResultsFifty-six patients participated in this study, of which 41 participants completed 4 or more cycles of chemotherapy and were included in the final analyses here. Using the reported high end of minimal clinical differences (10.6 points) of FACT-Cog before and after chemotherapy, 18 patients suffered from chemobrain in this study. In these 18 chemobrain patients, no cognitive impairments were detected by MemTrax, which paradoxically demonstrated an improvement in the normal cognitive range.ConclusionThe cognitive impairment induced by chemotherapy in breast cancer patients is detectable by the FACT-Cog in a Chinese cohort but is not detected by the MemTrax memory test. The fact that the more objective MemTrax could not detect the impairment could alleviate patients’ concerns which in turn would be beneficial for patients’ mental health.

Impact of ALDH1A1 and NQO1 gene polymorphisms on the response and toxicity of chemotherapy in Bangladeshi breast cancer patients.

Cyclophosphamide, Epirubicin/Doxorubicin, 5-fluorouracil (CEF or CAF) chemotherapy has long been a standard first-line treatment for breast cancer. The genetic variations of enzymes that are responsible for the metabolism of these drugs have been linked to altered treatment response and toxicity. Two drug-metabolizing enzymes ALDH1A1 and NQO1 are critically involved in the pathways of CEF/CAF metabolism. This study aimed to evaluate the effect of ALDH1A1 (rs13959) and NQO1 (rs1800566) polymorphisms on treatment response and toxicities caused by adjuvant (ACT) and neoadjuvant chemotherapy (NACT) where CEF/CAF combination was used to treat Bangladeshi breast cancer patients. A total of 330 patients were recruited from various hospitals, with 150 receiving neoadjuvant chemotherapy and 180 receiving adjuvant chemotherapy. To extract genomic DNA, a non-enzymatic simple salting out approach was adopted. The polymerase chain reaction-restriction fragment length polymorphism method was used to detect genetic polymorphisms. Unconditional logistic regression was used to derive odds ratios (ORs) with 95% confidence intervals (CIs) to study the association between genetic polymorphisms and clinical outcome and toxicity. A statistically significant association was observed between ALDH1A1 (rs13959) polymorphism and treatment response (TT vs. CC: aOR = 6.40, p = 0.007; recessive model: aOR = 6.38, p = 0.002; allele model: p = 0.032). Patients with the genotypes TT and CT + TT of the NQO1 (rs1800566) polymorphism had a significantly higher risk of toxicities such as anemia (aOR = 0.34, p = 0.006 and aOR = 0.58, p = 0.021), neutropenia (aOR = 0.42, p = 0.044 and aOR = 0.57, p = 0.027), leukopenia (aOR = 0.33, p = 0.010 and aOR = 0.46, p = 0.005), and gastrointestinal toxicity (aOR = 0.30, p = 0.02 and aOR = 0.38, p = 0.006) when compared to the wild CC genotype, while patients with the genotype CT had a significant association with gastrointestinal toxicity (aOR = 0.42, p = 0.02) and leukopenia (aOR = 0.52, p = 0.010). The TT and CT + TT genotypes of rs13959 had a significantly higher risk of anemia (aOR = 2.00, p = 0.037 and aOR = 1.68, p = 0.029). There was no significant association between rs1800566 polymorphism and treatment response. Polymorphisms in ALDH1A1 (rs13959) and NQO1 (rs1800566) may be useful in predicting the probability of treatment response and adverse effects from CEF or CAF-based chemotherapy in breast cancer patients.

Promoter profiles in plasma CfDNA exhibits a potential utility of predicting the efficacy of neoadjuvant chemotherapy in breast cancer patients

BackgroundGene expression profiles in breast tissue biopsies contain information related to chemotherapy efficacy. The promoter profiles in cell-free DNA (cfDNA) carrying gene expression information of the original tissues may be used to predict the response to neoadjuvant chemotherapy in breast cancer as a non-invasive biomarker. In this study, the feasibility of the promoter profiles in plasma cfDNA was evaluated as a novel clinical model for noninvasively predicting the efficacy of neoadjuvant chemotherapy in breast cancer.MethodFirst of all, global chromatin (5 Mb windows), sub-compartments and promoter profiles in plasma cfDNA samples from 94 patients with breast cancer before neoadjuvant chemotherapy (pCR = 31 vs. non-pCR = 63) were analyzed, and then classifiers were developed for predicting the efficacy of neoadjuvant chemotherapy in breast cancer. Further, the promoter profile changes in sequential cfDNA samples from 30 patients (pCR = 8 vs. non-pCR = 22) during neoadjuvant chemotherapy were analyzed to explore the potential benefits of cfDNA promoter profile changes as a novel potential biomarker for predicting the treatment efficacy.ResultsThe results showed significantly distinct promoter profile in plasma cfDNA of pCR patients compared with non-pCR patients before neoadjuvant chemotherapy. The classifier based on promoter profiles in a Random Forest model produced the largest area under the curve of 0.980 (95% CI: 0.978–0.983). After neoadjuvant chemotherapy, 332 genes with significantly differential promoter profile changes in sequential cfDNA samples of pCR patients was observed, compared with non-pCR patients, and their functions were closely related to treatment response.ConclusionThese results suggest that promoter profiles in plasma cfDNA may be a powerful, non-invasive tool for predicting the efficacy of neoadjuvant chemotherapy breast cancer patients before treatment, and the on-treatment cfDNA promoter profiles have potential benefits for predicting the treatment efficacy.

Genetic Polymorphisms in Glutathione S-Transferase (GST) Gene and Their Correlation with Toxicity of Chemotherapy in Breast Cancer Patients.

Glutathione S-Transferase (GST) is a family of phase II metabolizing enzymes contribute to detoxification and elimination of variety of endogenous as well as exogenous xenobiotics including chemotherapeutic agents. The comprehensive knowledge on the impact of genetic polymorphisms in GST) enzyme coding gene will help to understand the clinical outcomes in breast cancer patients treated with either Adriamycin or paclitaxel or combination of both. In this study we attempted to assess the genetic polymorphisms in GSTM1, GSTT1, GSTP1 and their association with Adriamycin and Paclitaxel induced toxicity reactions in breast cancer patients. Two hundred BC patients receiving Adriamycin and Paclitaxel chemotherapy were enrolled in this study and chemotherapy induced hematological and non-hematological toxicity reactions were noted. The polymorphisms in GSTM1, GSTP1 and GSTT1 gene were studied by PCR and RFLP analysis. After the univariate analysis of the genetic polymorphisms of GSTM1, GSTP1 and GSTT1 showed that GSTT1 null genotype showed significant association with neutropenia (OR=2.84, 95% CI: 1.06-7.56; p=0.036) in breast cancer patients treated with Adriamycin and GSTT1 null genotype in patients with >1 CINV toxicity confirmed significant correlation (OR=3.75, 95% CI: 1.46-9.59; p=0.005). The genetic polymorphisms of GSTP1 (exon 5) A/G heterozygous genotype was significant in grade >1 toxicity reactions of mucositis (OR=3.22, 95% CI: 1.06-9.71; p=0.037) in breast cancer patients administered with Paclitaxel chemotherapy. The findings obtained from this study proposed significant involvement of GSTT1-null genotype in hematological neutropenia toxicity in response to Adriamycin and GSTM1-null genotype showed negative association with non-hematological toxicity (bodyache) in response to Paclitaxel.

Neoadjuvant endocrine treatment: Precious but insufficiently discovered issue

We would like to emphazise the importance of neoadjuvant endocrine treatment which is overshadowed by neoadjuvant chemotherapy for breast cancer patients. Missing knowledge is evaluation in terms of conventional notion of neoadjuvant chemotherapy that is it better to complete before surgery at least for some selected patients? Another point is, since it is a long term treatment, may be it will be a way give patients the chance to follow up without surgery. So this correspondence tries to ask two questions; shall we think about lengthening the duration of neoadjuvant endocrine treatment in selected patients and who are these patients?

Relationship between Tumor Infiltrating Lymphocytes and Neoadjuvant Chemoterapy Responsiveness: A Cross-Sectional Study on Breast Cancer Patients

Breast cancer is still a significant health problem in the world, with chemotherapy as an essential component in its management. Limited research on tumor- infiltrating lymphocytes (TIL) as a biomarker for the effectiveness of breast cancer treatment was conducted and is still contradictory. This study aims to investigate the relationship between TILs and the clinical response to neoadjuvant chemotherapy in breast cancer. The research used a cross-sectional study on eligible breast cancer patients in Wahidin Sudirohusodo Hospital in Makassar. TIL levels were grouped based on the histopathological examination results of breast tissue samples into three categories: low (0% to 10%), medium 15% to 50% and high (55% to 100%). Responsiveness was assessed based on changes in tumor size after neoadjuvant chemotherapy. The Chi-Square test is the primary analysis in this study. Results of 40 participants, the sample had a median age of 40 (27-73 years), mainly in the clinical stage III (40.0%), had moderate TIL concentration (47.5%), and was responsive to the neoadjuvant chemotherapy (87.5%). There was no significant association between TIL concentration and chemotherapy responsiveness (p &gt; 0.05). However, in post-chemotherapy conditions, the median value of tumor size in the group with the high TIL category was significantly lower than in the low and medium TIL groups (p=0.034). There was no association between TIL levels and the clinical response to neoadjuvant chemotherapy in breast cancer patients. Further research is needed to confirm these findings.

The Relationship Between Body Composition and Pathological Response to Neoadjuvant Chemotherapy in Breast Cancer Patients.

Background The pathological response rate in operable breast cancer (BC) patients receiving neoadjuvant chemotherapy (NAC) is postulated to be related to body composition. The success of complete pathological response (pCR) is a known prognostic factor in BC patients treated with NAC. We aimed to accurately measure body composition through BMI and skeletal muscle mass and observe their effects on pCR. Materials and methods Patients diagnosed with operable BC who had a positron emission tomography-computed tomography (PET-CT) or chest/abdominal CTtaken at the time of diagnosis were retrospectively screened and enrolled in this study. Muscle mass was defined by third lumbar vertebra (L3) level transverse CT images, and data, including weight and height, were collected from the chemotherapy records. All these data were evaluated together with the postoperative pathological results. Results Sixty-nine operable BC patients with a median age of 46 (range: 29-72) years were included in the study. In all patients, regardless of sarcopenia, 23% (n = 16) achieved pCR to NAC. The pCR rate was 37.5% (n=6) in sarcopenic patients and 62.5% (n=10) in non-sarcopenic patients (p = 0.530). Overweight (n=4; 25%) and obese (n=2; 12.5%) patients also had a lower pathological response than normal-weight (n=10; 62.5%) BC patients (p=0.261). Conclusion Both sarcopenia and obesity independently and synergistically contribute to poorer pathological responses after NAC. Addressing these conditions through tailored interventions, such as nutritional support, exercise programs, and careful monitoring of body composition, could improve treatment outcomes. Further research with larger patient populations and comprehensive body measurements is essential to fully understand these relationships and develop effective strategies to mitigate their impact.

Predictive analysis of breast cancer response to neoadjuvant chemotherapy through plasma metabolomics.

Preoperative chemotherapy is a critical component of breast cancer management, yet its effectiveness is not uniform. Moreover, the adverse effects associated with chemotherapy necessitate the identification of a patient subgroup that would derive the maximum benefit from this treatment. This study aimed to establish a method for predicting the response to neoadjuvant chemotherapy in breast cancer patients utilizing a metabolomic approach. Plasma samples were obtained from 87 breast cancer patients undergoing neoadjuvant chemotherapy at our facility, collected both before the commencement of the treatment and before the second treatment cycle. Metabolite analysis was conducted using capillary electrophoresis-mass spectrometry (CE-MS) and liquid chromatography-mass spectrometry (LC-MS). We performed comparative profiling of metabolite concentrations by assessing the metabolite profiles of patients who achieved a pathological complete response (pCR) against those who did not, both in initial and subsequent treatment cycles. Significant variances were observed in the metabolite profiles between pCR and non-pCR cases, both at the onset of preoperative chemotherapy and before the second cycle. Noteworthy distinctions were also evident between the metabolite profiles from the initial and the second neoadjuvant chemotherapy courses. Furthermore, metabolite profiles exhibited variations associated with intrinsic subtypes at all assessed time points. The application of plasma metabolomics, utilizing CE-MS and LC-MS, may serve as a tool for predicting the efficacy of neoadjuvant chemotherapy in breast cancer in the future after all necessary validations have been completed.

A nomogram for predicting pathologic node negativity after neoadjuvant chemotherapy in breast cancer patients: a nationwide, multicenter retrospective cohort study (CSBrS-012).

This study aimed to investigate the factors associated with pathologic node-negativity (ypN0) in patients who received neoadjuvant chemotherapy (NAC) to develop and validate an accurate prediction nomogram. The CSBrS-012 study (2010-2020) included female patients with primary breast cancer treated with NAC followed by breast and axillary surgery in 20 hospitals across China. In the present study, 7,711 eligible patients were included, comprising 6,428 patients in the primary cohort from 15 hospitals and 1,283 patients in the external validation cohort from five hospitals. The hospitals were randomly assigned. The primary cohort was randomized at a 3:1 ratio and divided into a training set and an internal validation set. Univariate and multivariate logistic regression analyses were performed on the training set, after which a nomogram was constructed and validated both internally and externally. In total, 3,560 patients (46.2%) achieved ypN0, and 1,558 patients (20.3%) achieved pathologic complete response in the breast (bpCR). A nomogram was constructed based on the clinical nodal stage before NAC (cN), ER, PR, HER2, Ki67, NAC treatment cycle, and bpCR, which were independently associated with ypN0. The area under the receiver operating characteristic curve (AUC) for the training set was 0.80. The internal and external validation demonstrated good discrimination, with AUCs of 0.79 and 0.76, respectively. We present a real-world study based on nationwide large-sample data that can be used to effectively screen for ypN0 to provide better advice for the management of residual axillary disease in breast cancer patients undergoing NAC.

De-Escalation of Surgical Treatment after Neoadjuvant Chemotherapy in Breast Cancer Patients

De-Escalation of Surgical Treatment after Neoadjuvant Chemotherapy in Breast Cancer Patients

Effect of Macronutrient Intake on Tolerance to Chemotherapy in Breast Cancer Patients

Effect of Macronutrient Intake on Tolerance to Chemotherapy in Breast Cancer Patients

Symptom cluster study undergoing chemotherapy in breast cancer patients: Latent class analysis and contemporaneous network analysis

ObjectiveThis study aims to explore the subgroups and networks of symptom clusters in breast cancer patients undergoing chemotherapy, and to provide effective interventions for the core symptoms. MethodsA cross-sectional survey was conducted at four comprehensive hospitals in Foshan City, China, from August to November 2023. A total of 292 participants completed the social determinants of health questionnaire, the numerical rating scale (NRS), the Pittsburgh sleep quality index (PSQI), the Chinese version of the cancer fatigue scale (CFS), and the hospital anxiety and depression Scale (HADS). Latent class analysis (LCA) was utilized to distinguish subgroups, and network analysis was utilized to identify core symptoms among different subgroups. ResultsBreast cancer patients undergoing chemotherapy exhibit symptoms were divided into two subgroups: the high burden group of symptoms (72.3%, Class 1) and the low burden group of symptoms (27.7%, Class 2). Education attainment, work status, family monthly income per capita, and daily sleep duration (hours) were associated with subgroup membership. “Panic feelings” (# HADS-A11) were the core symptom in both the full sample and Class 2, while “tension or pain” (# HADS-A1) was the core symptom in Class 1. ConclusionsThe core symptoms of fear, enjoyment, nervousness, and pain varied across subgroups of patients and could inform the current strategies for symptom management in breast cancer chemotherapy patients.

Abstract PO3-16-01: Personalized circulating tumor DNA assay precisely predicts the response of neoadjuvant chemotherapy in breast cancer patients

Abstract Introduction Circulating tumor DNA (ctDNA), which is detected in the blood as cell free DNA fragment from tumor cells, could indicates genomic landscape, tumor burden and treatment response during chemotherapy as a non-invasive method. Especially, personized ctDNA assay by next-generation sequencing(NGS) is able to detect a trace amount of ctDNA and precisely figure out the change of the amount of ctDNA during NAC and follow up period after curative surgery. Here, we performed serial ctDNA evaluations in EBC patients who diagnosed as TNBC or HER2-positive BC and received NAC followed by curative surgery. We aimed to predict NAC response and detect minimal residual disease (MRD) using personalized ctDNA assay. Methods CtDNA was detected by AlphaLiquid®Detect, a tumor-informed personalized MRD detection assay exploring most of the mutations in tumor. Whole exome sequencing (WES) of tumor tissue and peripheral blood mononuclear cells (PBMCs) was performed. Patient-specific somatic mutations were selected using a proprietary algorithm. In brief, clonal variants were prioritized using integrated information including variant allele frequency, population allele frequency databases, somatic variant databases, variant pathogenicity, and genomic context. Up to 100 variants were selected for patient monitoring. A hybridization capture panel consisting of a pool of 4 patients’ selected variants was synthesized. These bespoke panels (BSPs) were used for ctDNA detection. Patients with more than 2 tumor-derived mutations detected in plasma were considered as ctDNA positive. Inclusion criteria included patient who diagnosed as stage IIA-IIIC BC planned to NAC followed by curative surgery. Among BC subtypes, TNBC and HER2-positive BC were allowed. Collection of specimens and associated clinical data used in this study was approved by the Institutional Review Board of Samsung Medical Center (IRB File No.2021-02-033), and we received informed consents for this study. Results From May 2021 to Sep 2022, 158 patients has been enrolled. Archival tissues were not available in 47 patients and tissue WES had failed in six patients. Therefore, 105 patients were enrolled and analyzed their ctDNA at diagnosis based on tissue WES data. Of 105 patients, Median age of BC patients was 49.3 years of age (range: 26.1, 67.8). Thirty-six patients (34.3%) were post-menopausal status and others (65.7%) were pre-menopausal status. In BC pathology at diagnosis, 56 (53.3%) were TNBC and other 49 (46.7%) were HER2-positive BC. Among HER2-positive BC, hormone receptor (HR)-positive were in 21 (20.0%). In clinical stage at diagnosis, stage II were 46 (43.8%) and stage III in 59 (56.2%). In 105 patients, median number of somatic mutations was 60 (interquartile range [IQR]: 38.5, 91). CtDNA detection rate at BC diagnosis was 90.5% and all of BC which not be detected ctDNA was HER2-positive BC with clinical stage II. Median amount of ctDNA at diagnosis was 20 (IQR: 6, 44). In the number of somatic mutations, there was no difference according to BC subtypes (P=0.121) and clinical stage (P=0.700) but the amounts of ctDNA at diagnosis was different. CtDNA was much more detected in TNBC compared to HER2-positive BC (Median: 34.5 vs. 15.9; P&amp;lt; 0.001) and clinical stage III compared to clinical stage II (Median 33.2 vs. 19.5; P=0.002). After NAC, ctDNA at curative surgery was tested in 70 patients. In 70 patients, pathologic complete response(pCR) was observed in 44 patients. CtDNA was detected in ten patients (14.3%) and eight did not achieve pCR and two with pCR (Specificity of assay: 95.5%, positive predictive value: 0.80, P=0.032). Conclusions Personalized ctDNA assay can precisely detected ctDNA at diagnosis and their detection rate was associated with BC subtypes and clinical stage. In addition, ctDNA at curative surgery also can predict NAC response in EBC patients. Long term ctDNA follow up of MRD would be warranted. Citation Format: Ji-Yeon Kim, Hae Hyun Jung, Jeong Eon Lee, Seok Won Kim, Hwang-Phill Kim, Sunghoon Heo, Jongseong Ahn, Tae-You Kim, Young-Hyuck Im. Personalized circulating tumor DNA assay precisely predicts the response of neoadjuvant chemotherapy in breast cancer patients [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 PO3-16-01.

Abstract PO5-23-11: Elevated linoleic acid levels in red blood cells membrane predicts response to neoadjuvant chemotherapy in breast cancer patients

Abstract Introduction: Fatty acids (FA) consumed in the diet have been implicated in increasing the risk of breast cancer (BC). Humans have a wide variety of FAs, including saturated (SFA), monounsaturated (MUFA), and polyunsaturated (PUFA) FAs. PUFAs can be further classified into omega-3 (n-3) and omega-6 (n-6) PUFAs. While n-3 has been associated with reducing inflammation and promoting apoptosis in BC cells, n-6 has been linked to increased inflammation, oxidative stress, and the promotion of BC cell proliferation and treatment resistance. In healthy women, the n-3 content in mammary tissue correlates with n-3 content in red blood cells (RBCs). The FA profile of the RBC membrane provides an unbiased option to assess lipid intake and composition, reflecting long-term FA intake and providing an objective and sensitive measure of lipid intake and body fat deposits. Notably, BC patients have been found to display a high n-6:n-3 ratio in RBCs, which is associated with inflammatory and oxidative stress biomarkers. The neoadjuvant chemotherapy treatment (NACT) model presents a unique opportunity to study resistance mechanisms in non-metastatic BC patients. In this approach, the absence of tumor (pathologic complete response: pCR, or Residual Cancer Burden (RCB) = 0) after NACT indicates treatment sensitivity and better overall survival (OS). Objective: The objective of this study is to determine whether differences in FA profiles determined in the RBC membrane and plasma are associated with the response to NACT in non-metastatic BC patients. Methods: A prospective study was conducted, including non-metastatic BC patients scheduled to receive NACT. Blood samples were collected before the first cycle of NACT to measure plasma and RBC FA derivatives, SFAs, MUFAs, and PUFAs. The pathological complete response (pCR) and residual cancer burden (RCB) were assessed. Results: A total of twenty-eight BC patients were included in the study. When comparing pCR vs. no-pCR using total SFA, MUFA, and PUFA plasma samples, no significant differences were observed. However, in RBC, an increase in PUFA was associated with a higher rate of no-pCR (**p&amp;lt; 0.01). Furthermore, comparing omega-6 and omega-3 (both PUFA) levels, an increase in omega-6 was associated with no-pCR (**p&amp;lt; 0.01), while no significant differences were observed with omega-3. No differences were obtained in plasma samples for either omega-6 and omega-3. To determine which specific omega-6 PUFAs were responsible for the association with no-pCR, elevated levels of linoleic acid (LA) in RBC were found to be associated with no-pCR (**p&amp;lt; 0.01). Other omega-6 PUFAs, including gamma-linolenic acid (GLA), eicosadienoic acid (EDA), dihomo-gamma linolenic acid (DGLA), and arachidonic acid (ARA), showed no significant associations. Multivariate and regression analysis confirmed LA (C18:2 n-6, LA) as the most relevant FA when assessing RCB (0-1 vs. 2-3) in RBC membranes, but not in plasma. The receiver operating characteristic (ROC) curve analyzing LA levels in RBC showed an area under the curve (AUC) of 0.855 for RCB (sensitivity: 76.9%, specificity: 92.3%). Conclusions: To the best of our knowledge, this is the first study demonstrating a clear connection between RBC membrane FA composition, specifically LA concentration, and the pathological response in BC patients after NACT. The measurements taken in plasma did not show significant associations, suggesting that RBC membrane FA profile of could serve as a relevant prognostic biomarker for studying resistance mechanisms to NACT in early BC patients Table. Measured FAs in RBC membrane and plasma by pathologic complete response *Indicates p&amp;lt;0.05; abbreviations: pCR: pathological complete response; SD: standard deviation; yr: years; BMI: body mass index; HR: hormone receptor; HER2: human epidermal growth factor receptor type-2; NLR: neutrophil to lymphocyte ratio; HG: histological grade; RCB: residual cancer burden; NA: not applicable Citation Format: Benjamin Walbaum, César Sánchez, Francisco Acevedo. Elevated linoleic acid levels in red blood cells membrane predicts response to neoadjuvant chemotherapy in breast cancer patients [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 PO5-23-11.

Analysis of cost of illness and diagnosis-related group payment system in breast cancer patients with chemotherapy in Indonesia

Background: Often, breast cancer patients undergoing chemotherapy sacrifice their finances, and the financial costs also affect the government. Objective: This study aims to analyse the cost of illness and the application of an insurance payment system among breast cancer patients receiving various chemotherapy regimens. Method: This study was retrospective and used a bottom-up prevalence approach. Data were collected from a secondary hospital between 2020 and 2021. The inclusion criteria were breast cancer patients undergoing chemotherapy. Patients with incomplete detailed cost data were excluded. The cost of illness was calculated from direct medical costs and the estimated non-medical and indirect costs. Results: The cost of illness for a chemotherapy visit for a breast cancer patient spanned from USD 130.37 to USD 932.05. However, these values did not include healthcare service costs and laboratory tests. The highest regimentation chemotherapy cost is for the combination of docetaxel–cyclophosphamide–trastuzumab. There was a significant margin between insurance claims and variable medical costs (p &lt; 0,05), ranging between USD 24.21 and 104.83. Conclusion: The cost of illness for chemotherapy for breast cancer patients is high, and the coverage of the diagnosis-related payment system is limited. Therefore, the government should accelerate prevention programmes to reduce the incidence of cancer.

Influence of (C1236T and C3435T) Polymorphisms of ABCB1 Gene on Chemotherapy Treatment Outcome and Toxicity in Breast Cancer Patients.

ATP Binding Cassette Transporters (ABCB1) gene plays an important role in transport of different metabolites and anticancer drugs across the cell membrane. There is lack of knowledge on ABCB1 gene polymorphism and its correlation with Adriamycin or paclitaxel based chemotherapy induced toxicity in breast cancer patients. Therefore in this study, we explored the correlation of ABCB1 polymorphisms gene on response and toxicity in adriamycin and paclitaxel based chemotherapy in breast cancer patients from Indian population. Two hundred BC patients receiving Adriamycin and paclitaxel chemotherapy were enrolled in this study and chemotherapy induced hematological and non-hematological toxicity reactions were noted. The polymorphisms in ABCB1 gene (C1236T, C3435T) were studied by PCR and RFLP analysis. The univariate logistic regression analysis showed statistically significant negative association with protective effects of ABCB1 (C3435T) polymorphism with heterozygous genotype (OR=0.34, 95% CI: 0.13-0.89; p=0.027), homozygous variant genotype (OR=0.31, 95% CI: 0.10-0.99; p=0.049) and combined C/T+T/T genotypes (OR=0.33, 95% CI: 0.13-0.79; p=0.013) in relation with severe toxicity of chemotherapy induced nausea and vomiting in breast cancer patients treated with Adriamycin chemotherapy. The 3435 C>T polymorphism of ABCB1 gene with heterozygous C/T genotype showed significantly negative association (OR=0.37, 95% CI: 0.14-0.96; p=0.042) with peripheral neuropathy in patients treated primarily with paclitaxel thereafter Adriamycin. The findings obtained from this study revealed significant association of ABCB1 3435 C>T polymorphisms with non-hematological toxicity in response to adriamycin and paclitaxel based chemotherapy.

Implementation of personalized multidisciplinary neuropathy management program for chemotherapy-induced peripheral neuropathy symptoms in breast cancer patients

Objective To construct a personalized multidisciplinary neurotoxicity management program for chemotherapy-induced peripheral neuropathy (CIPN) symptoms in breast cancer patients and evaluate its application effects. Methods A retrospective analysis was conducted on clinical data of 133 breast cancer chemotherapy patients admitted to our hospital from January 2022 to January 2024. Based on the nursing protocols received, patients were divided into a control group (n = 66) and an intervention group (n = 67). The control group received conventional nursing interventions, while the intervention group received personalized nursing interventions in addition to the control group interventions. The nursing programs were carried out during chemotherapy. A comparison was made between the two groups before chemotherapy and 3 months after chemotherapy in terms of the degree of neuropathy, cancer-related fatigue, negative emotional status, and symptom management knowledge, attitudes, and practices (KAP). Results The intervention group showed significantly lower neuropathy severity (FACT/GOG-Ntx), cancer-related fatigue (CFS), and negative emotions (PHQ-9, GAD-7) scores after chemotherapy compared to the control group (p < 0.05). Additionally, the intervention group exhibited higher scores for symptom management knowledge, beliefs, and behaviors (p < 0.05). Conclusion Personalized multidisciplinary neurotoxicity management program significantly improved neuropathy severity, reduced cancer-related fatigue and negative emotions, and enhanced symptom management knowledge, attitudes, and practices among breast cancer patients undergoing chemotherapy.

Sentinel Lymph Node Biopsy after Neoadjuvant Chemotherapy in Breast Cancer Patients with Positive Nodes Using Low-Cost Dual Dye Technique: Identifying Factors Associated with Adequate False Negative Rate Threshold

Background: In this study, we evaluated the feasibility of the sentinel lymph node (SLN) identification rate (SLN-IR) of fluorescein-guided sentinel lymph node biopsy (SLNB) in combination with methylene blue dye (MBD) and factors which can lead to a false negative rate (FNR) threshold of 10%. Methods: This was a prospective cross-sectional non-randomized validation study in patients with post-neoadjuvant chemotherapy (NACT) clinically node negative axilla who were node positive prior to start of NACT. Patients underwent validation of SLNB using fluorescein (and blue LED light) and MBD. Axillary dissection was performed irrespective of SLNB histology. SLIN-IR and FNR were assessed and compared with various molecular subtypes. Results: The SLNs were identified in 102 out of 120 (85%) post-NACT patients. The median number of sentinel lymph nodes identified was 2 (range 1–3). The SLN-IR using MBD was 85%, FD was 82.5%, and combined MBD FD was 85%. Two or more SLNs were removed in 72 patients and 11 patients had tumor in the rest of the axilla, resulting in an FNR of 17.4%. An FNR was 25% in case only one SLN was found, and it was 11.42% if two or more than two SLNs were excised. Conclusions: This cohort study found that use of low-cost dual dyes in patients with positive axillary disease, rendered cN0 with NACT, with 2 or more negative SLNs with SLNB alone, results in an FNR of 11.4%. Her 2 positive and TNBC with 2 or more negative SLNs are associated with an FNR of <10%. However, the number of such patients was small and further studies with larger sample size are warranted to confirm these findings.