Chemotherapy For Breast Cancer Research Articles

The expression of Plakoglobin in residual cancer after neoadjuvant chemotherapy for breast cancer and its prognostic impact on patients

Objective: To investigate the relationship between the expression levels of Plakoglobin protein in residual lesions after neoadjuvant chemotherapy (NAC) and the prognosis of breast cancer patients. Methods: Clinical and pathological data from 174 breast cancer patients who underwent surgery after receiving NAC at the Cancer Hospital of Chinese Academy of Medical Sciences from January 2009 to December 2017 were collected. The expression level of Plakoglobin in residual cancer lesions was evaluated by immunohistochemistry. The correlation between Plakoglobin expression level and clinicopathological features was analyzed. Survival analysis was performed using the Kaplan-Meier method, and Cox proportional hazard regression models were used for factor analysis. Results: Among the 174 patients, 140 had low expression of Plakoglobin, and 34 had high expression. The median disease-free survival (DFS) and overall survival (OS) in the Plakoglobin low expression group were 59.46 and 71.68 months, respectively, both of which were higher than those in the high expression group (36.58 and 47.26 months, respectively, both P<0.05). Univariate analysis showed that Plakoglobin expression, pathological N stage, lymphovascular invasion status, histological grade, Ki-67, and molecular subtypes were associated with OS (all P<0.05), while pathological N stage, histological grade, and Ki-67 were associated with DFS (all P<0.05). Multivariate analysis revealed that Plakoglobin expression (HR=2.438, 95% CI: 1.256-4.735, P=0.008) was an independent predictor for OS, and Ki-67 (HR=2.228, 95% CI: 1.316-3.773, P=0.003) was an independent predictor for DFS. Conclusion: In breast cancer patients with residual lesions after NAC, those with low Plakoglobin expression have relatively longer OS and Plakoglobin is an independent prognostic factor for OS.

Prognostic effect of nodal status before and after neoadjuvant chemotherapy in breast cancer: a Dutch population-based study.

In breast cancer, neoadjuvant chemotherapy (NAC) can downstage the nodal status, and can even result in a pathological complete response, which is associated with improved prognosis. This study aimed to determine the prognostic effect of nodal status before and after NAC. Women with breast cancer treated with NAC were selected from the Netherlands Cancer Registry if diagnosed between 2005 and 2019, and classified based on nodal status before NAC: node-negative (cN0), or node-positive based on fine needle aspiration cytology or core needle biopsy (cN+). Subgroups were based on nodal status after NAC: absence (ypN0) or presence (ypN+) of nodal disease. Five-year overall survival (OS) was assessed with Kaplan-Meier survival analyses, also per breast cancer molecular subtype. To adjust for potential confounders, multivariable analyses were performed. A total of 6,580 patients were included in the cN0 group, and 11,878 in the cN+ group. The 5-year OS of the cN0ypN0-subgroup was statistically significant better than that of the cN+ypN0-subgroup (94.4% versus 90.1%, p < 0.0001). In cN0 as well as cN+ disease, ypN+ had a statistically significant worse 5-year OS compared to ypN0. For hormone receptor (HR)+ human epidermal growth factor receptor 2 (HER2)-, HR+ HER2+, HR-HER2+, and triple negative disease, respectively, 5-year OS in the cN0ypN+-subgroup was 89.7%, 90.4%, 73.7%, and 53.6%, and in the cN+ypN+-subgroup 84.7%, 83.2%, 61.4%, and 48.8%. In multivariable analyses, cN+ and ypN+ disease were both associated with worse OS. This study suggests that both cN-status and ypN-status, and molecular subtype should be considered to further improve prognostication.

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 &amp;gt;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 &amp;gt;0.86; ICC &amp;gt; 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.

Evaluation of Conservative Breast Surgery After Neoadjuvant Chemotherapy in Early Breast Cancer

Background: The breast cancer is a frequent type of cancers. It is associated with high mortality related to cancer in women. The treatment options transferred from radical surgery to less invasive operations. This was attributed to surgical advance and available neoadjuvant chemotherapy. Objective: This work aimed to evaluate the conservative breast surgery feasibility and outcome for early breast cancer received neoadjuvant chemotherapy (NACT) for downstaging. Patients and Methods: Thirty women (30) with early breast cancer were included between November 2022 and May 2023. All women were assessed in systematic manner by history, clinical, laboratory and radiological investigations before chemotherapy, before and after surgery. A true cut biopsy was drawn to estimate the histopathological nature. All surgeries were performed one and half months after the last session of NACT. A regular postoperative follow up was carried out up to six months. Any complications were recorded. Effect of NACT on the tumor grading was the primary outcome, while cosmetic results and patient satisfaction were the secondary outcomes. Results: Complications were in the form of wound infection, seroma and hematoma in 6.7%, 13.3% and 3.3% respectively. These were mild and treated conservatively. The excellent cosmetic result was achieved for 80.0% and excellent patient satisfaction was recorded for 60.0%. The effect of chemotherapy showed significant improvement of clinical and pathological post chemotherapy tumor size values when compared to clinical tumor size values before chemotherapy, the T1 grade (≤2cm) increased from 50% to 66.7%, while the T2 grade (&gt; 2cm &lt;5 cm) decreased from 50% to33.3%. Conclusion: NACT was associated with excellent response regarding tumor size reduction, negativity of lymph nodes as well as pathological response of early breast cancer, before breast conservation surgery (BCS). The BCS after NACT could be considered as a safe option with acceptable aesthetic outcome.

Co-assembly of polymeric conjugates sensitizes neoadjuvant chemotherapy of triple-negative breast cancer with reduced systemic toxicity

Rational design of polymeric conjugates could greatly potentiate the combination therapy of solid tumors. In this study, we designed and prepared two polymeric conjugates (HT-DTX and PEG-YC-1), whereas the drugs were attached to the PEG via a linker sensitive to cathepsin B, over-expressed in TNBC. Stable nanostructures were formed by these two polymer prodrug conjugates co-assembly (PPCC). The stimuli-responsiveness of PPCC was confirmed, and the size shrinkage under tumor microenvironment would facilitate the penetration of PPCC into tumor tissue. In vitro experiments revealed the molecular mechanism for the synergistic effect of the combination of DTX and YC-1. Moreover, the systemic side effects were significantly diminished since the biodistribution of PPCC was improved after i.v. administration in vivo. In this context, the co-assembled nano-structural approach could be employed for delivering therapeutic drugs with different mechanisms of action to exert a synergistic anti-tumor effect against solid tumors, including triple-negative breast cancer. Statement of significance•Co-assembly of polymeric prodrug conjugates could form stable and homogeneous nanostructures, improving cellular uptake by cancer cells and in vivo tumor penetration and retention.•Co-delivery of neoadjuvant therapeutic drug (DTX) and HIF-1α inhibitor (YC-1) synergizes the anti-tumor effect by affecting HIF-1α expression and G2/M phase arrest.•Polymer prodrug conjugates co-assembly (PPCC) could reverse tumor resistance to neoadjuvant therapy, retard tumor progression, and prevent lung metastasis with reduced systemic toxicity in a murine triple-negative breast cancer model.

Neoadjuvant pyrotinib plus trastuzumab and chemotherapy for HER2-positive breast cancer: a prospective cohort study

BackgroundThis prospective study aims to investigate the efficacy and safety of pyrotinib (P) combined with 4 cycles of epirubicin and cyclophosphamide followed by 4 cycles of taxane and trastuzumab (P + EC-TH) regimen as neoadjuvant therapy for human epidermal growth factor receptor 2 (HER2) positive breast cancer and to investigate the predictive value of p53, p63, and epidermal growth factor receptor (EGFR) status for neoadjuvant efficacy.MethodsA total of 138 HER2-positive breast cancer patients who received neoadjuvant therapy and underwent surgery were included. Case group: 55 patients received P + EC-TH regimen. Control group: 83 patients received EC-TH regimen. The chi-square test, Fisher’s exact test, and logistic regression analysis were applied. The primary endpoint was total pathologic complete response (tpCR), and the secondary endpoints were breast pathologic complete response (bpCR), overall response rate (ORR), and adverse events (AEs).ResultsIn the case group, the tpCR rate was 63.64% (35/55), the bpCR rate was 69.09% (38/55), and the ORR was 100.00% (55/55). In the control group, the tpCR rate was 39.76% (33/83), the bpCR rate was 44.58% (37/83), and the ORR was 95.18% (79/83). The case group had significantly higher tpCR and bpCR rates than those of the control group (P < 0.05), but there was no significant difference in ORR (P > 0.05). The tpCR was associated with the status of estrogen receptor (ER), progesterone receptor (PR), and androgen receptor (AR), and the patients with any negative ER, PR, AR, or combined, were more likely to achieve tpCR than those with positive results (P < 0.05). The p53-positive patients were more likely to achieve tpCR and bpCR than p53-negative patients (P < 0.05). The incidence of hypokalemia and diarrhea in the case group was higher than that in the control group (P < 0.05). The AEs developed were all manageable, and no treatment-related death occurred.ConclusionThe efficacy and safety of the P + EC-TH regimen were verified by this study. The HER2-positive breast cancer patients treated with the EC-TH neoadjuvant regimen were more likely to achieve tpCR or bpCR if pyrotinib was administered simultaneously.

Assessment of Predictive Factors for Response to Neoadjuvant Chemotherapy in Breast Cancer

Objectives The early identification of breast cancer patients who will not respond to neoadjuvant chemotherapy is valuable for timely change in management strategies. Reliable clinical and pathological markers predictive of response to treatment have considerable potential for practical clinical use. Our longitudinal study aimed to assess clinical, pathological, and immunohistological factors predictive of chemotherapy response. Material and Methods Thirty Five patients of breast cancer underwent six cycles of Taxotere, Adriamycin, and Cyclophosphamide (TAC) based neoadjuvant chemotherapy (Docetaxel 75 mg/m2, Doxorubicin 50 mg/m2 or Epirubicin 100 mg/m2 and Cyclophosphamide 500 mg/m2) every three weeks followed by surgery. Histopathological response was assessed after surgery. At a follow up of 12 months, association between factors was tested with Fisher exact test, survival analysis was done with Kaplan Meier analysis and significance was tested by log rank test. Results Five patients out of 35 had pathological complete response (pCR). 14.8% of all T4 disease (P = 0.043) and 22.7% of all Estrogen receptor (ER) negative patients had pCR (P = 0.025). Among all patients showing pCR, four patients (80%) had Grade III tumors (P = 0.018) while all five patients had high Ki67 index (P = 0.032). At 12 months, the mean estimated overall survival came out to be 11.6 months. Mean estimated disease free survival was less for patients with pCR (7.2 months) vs. partial response (10.1 months) (P = 0.44). Conclusion Our study concluded that tumors with larger size, higher stage, higher grade, ER negativity and higher proliferation index had better response to chemotherapy but these tumors also had a trend towards early relapse.

New Cardiovascular Biomarkers in Breast Cancer Patients Undergoing Doxorubicin-Based Chemotherapy.

Central Illustration : New Cardiovascular Biomarkers in Breast Cancer Patients Undergoing Doxorubicin-Based Chemotherapy. Cardiovascular diseases (CVDs) are relevant to the management of breast cancer treatment since a substantial number of patients develop these complications after chemotherapy. This study aims to evaluate new cardiovascular biomarkers, namely CXCL-16 (C-X-C motif ligand 16), FABP3 (fatty acid binding protein 3), FABP4 (fatty acid binding protein 4), LIGHT (tumor necrosis factor superfamily member 14/TNFS14), GDF-15 (Growth/differentiation factor 15), sCD4 (soluble form of CD14), and ucMGP (uncarboxylated Matrix Gla-Protein) in breast cancer patients treated with doxorubicin (DOXO). This case-control study was conducted in an oncology clinic that included 34 women diagnosed with breast cancer and chemotherapy with DOXO and 34 control women without cancer and CVD. The markers were determined immediately after the last cycle of chemotherapy. The statistical significance level adopted was 5%. The breast cancer group presented higher levels of GDF-15 (p<0.001), while control subjects had higher levels of FABP3 (p=0.038), FABP4 (p=0003), sCD14, and ucMGP (p<0.001 for both). Positive correlations were observed between FABPs and BMI in the cancer group. GDF15 is an emerging biomarker with potential clinical applicability in this scenario. FABPs are proteins related to adiposity, which are potentially involved in breast cancer biology. sCD14 and ucMGP engage in inflammatory and vascular calcification. The evaluation of these novel cardiovascular biomarkers could be useful in the management of breast cancer chemotherapy with DOXO.

Construction of a risk stratification model integrating ctDNA to predict response and survival in neoadjuvant-treated breast cancer

BackgroundThe pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) of breast cancer is closely related to a better prognosis. However, there are no reliable indicators to accurately identify which patients will achieve pCR before surgery, and a model for predicting pCR to NAC is required.MethodsA total of 269 breast cancer patients in Shandong Cancer Hospital and Liaocheng People’s Hospital receiving anthracycline and taxane-based NAC were prospectively enrolled. Expression profiling using a 457 cancer-related gene sequencing panel (DNA sequencing) covering genes recurrently mutated in breast cancer was carried out on 243 formalin-fixed paraffin-embedded tumor biopsies samples before NAC from 243 patients. The unique personalized panel of nine individual somatic mutation genes from the constructed model was used to detect and analyze ctDNA on 216 blood samples. Blood samples were collected at indicated time points including before chemotherapy initiation, after the 1st NAC and before the 2nd NAC cycle, during intermediate evaluation, and prior to surgery. In this study, we characterized the value of gene profile mutation and circulating tumor DNA (ctDNA) in combination with clinical characteristics in the prediction of pCR before surgery and investigated the prognostic prediction. The median follow-up time for survival analysis was 898 days.ResultsFirstly, we constructed a predictive NAC response model including five single nucleotide variant (SNV) mutations (TP53, SETBP1, PIK3CA, NOTCH4 and MSH2) and four copy number variation (CNV) mutations (FOXP1-gain, EGFR-gain, IL7R-gain, and NFKB1A-gain) in the breast tumor, combined with three clinical factors (luminal A, Her2 and Ki67 status). The tumor prediction model showed good discrimination of chemotherapy sensitivity for pCR and non-pCR with an AUC of 0.871 (95% CI, 0.797–0.927) in the training set, 0.771 (95% CI, 0.649–0.883) in the test set, and 0.726 (95% CI, 0.556–0.865) in an extra test set. This tumor prediction model can also effectively predict the prognosis of disease-free survival (DFS) with an AUC of 0.749 at 1 year and 0.830 at 3 years. We further screened the genes from the tumor prediction model to establish a unique personalized panel consisting of 9 individual somatic mutation genes to detect and analyze ctDNA. It was found that ctDNA positivity decreased with the passage of time during NAC, and ctDNA status can predict NAC response and metastasis recurrence. Finally, we constructed the chemotherapy prediction model combined with the tumor prediction model and pretreatment ctDNA levels, which has a better prediction effect of pCR with the AUC value of 0.961.ConclusionsIn this study, we established a chemotherapy predictive model with a non-invasive tool that is built based on genomic features, ctDNA status, as well as clinical characteristics for predicting pCR to recognize the responders and non-responders to NAC, and also predicting prognosis for DFS in breast cancer. Adding pretreatment ctDNA levels to a model containing gene profile mutation and clinical characteristics significantly improves stratification over the clinical variables alone.

Interpreting the Significance of Changes in Health-Related Quality-of-Life Scores.

To determine the significance to patients of changes in health-related quality-of-life (HLQ) scores assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30). A subjective significance questionnaire (SSQ), which asks patients about perceived changes in physical, emotional, and social functioning and in global quality of life (global QL) and the QLQ-C30 were completed by patients who received chemotherapy for either breast cancer or small-cell lung cancer (SCLC). In the SSQ, patients rated their perception of change since the last time they completed the QLQ-C30 using a 7-category scale that ranged from "much worse" through "no change" to "much better." For each category of change in the SSQ, the corresponding differences were calculated in QLQ-C30 mean scores and effect sizes were determined. For patients who indicated "no change" in the SSQ, the mean change in scores in the corresponding QLQ-C30 domains was not significantly different from 0. For patients who indicated "a little" change either for better or for worse, the mean change in scores was about 5 to 10; for "moderate" change, about 10 to 20; and for "very much" change, greater than 20. Effect sizes increased in concordance with increasing changes in SSQ ratings and QLQ-C30 scores. The significance of changes in QLQ-C30 scores can be interpreted in terms of small, moderate, or large changes in quality of life as reported by patients in the SSQ. The magnitude of these changes also can be used to calculate the sample sizes required to detect a specified change in clinical trials.

Health-related quality of life with pembrolizumab plus chemotherapy vs placebo plus chemotherapy for advanced triple-negative breast cancer: KEYNOTE-355.

In KEYNOTE-355 (NCT02819518), the addition of pembrolizumab to chemotherapy led to statistically significant improvements in progression-free survival and overall survival in patients with advanced triple-negative breast cancer with tumor programmed cell death ligand 1 (PD-L1) combined positive score of at least 10. We report patient-reported outcomes from KEYNOTE-355. Patients were randomly assigned 2:1 to pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles plus investigator's choice chemotherapy (nab-paclitaxel, paclitaxel, or gemcitabine plus carboplatin). The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30), Breast Cancer-Specific Quality of Life Questionnaire, and EuroQol 5-Dimension questionnaire visual analog scale were prespecified. Patient-reported outcomes were analyzed for patients who received at least 1 dose of study treatment and completed at least 1 patient-reported outcome assessment. Changes in patient-reported outcome scores from baseline were assessed at week 15 (latest time point at which completion and compliance rates were at least 60% and at least 80%, respectively). Time to deterioration in patient-reported outcomes was defined as time to first onset of at least a 10-point worsening in score from baseline. Patient-reported outcome analyses included 317 patients with tumor PD-L1 combined positive score of at least 10 (pembrolizumab plus chemotherapy: n = 217; placebo plus chemotherapy: n = 100). There were no between-group differences in change from baseline to week 15 in QLQ-C30 global health status/quality of life (QOL; least-squares mean difference = -1.81, 95% confidence interval [CI] = -6.92 to 3.30), emotional functioning (least-squares mean difference = -1.43, 95% CI = -7.03 to 4.16), physical functioning (least-squares mean difference = -1.05, 95% CI = -6.59 to 4.50), or EuroQol 5-Dimension questionnaire visual analog scale (least-squares mean difference = 0.18, 95% CI = -5.04 to 5.39) and no between-group difference in time to deterioration in QLQ-C30 global health status/QOL, emotional functioning, or physical functioning. Together with the efficacy and safety findings, patient-reported outcome results from KEYNOTE-355 support pembrolizumab plus chemotherapy as a standard of care for patients with advanced triple-negative breast cancer with tumor PD-L1 expression (combined positive score ≥10).

Patterns of chemotherapy receipt among patients with hormone receptor-positive, HER2-negative breast cancer.

Breast cancer chemotherapy utilization not only may differ by race and age, but also varies by genomic risk, tumor characteristics, and patient characteristics. Studies in demographically diverse populations with both clinical and genomic data are necessary to understand potential disparities by race and age. In the Carolina Breast Cancer Study Phase 3 (2008-2013), chemotherapy receipt (yes/no) and regimen type were assessed in association with age and race among hormone receptor (HR) positive and HER2-negative tumors (n = 1862). Odds ratios were estimated for the association between demographic factors and chemotherapy receipt. Monotonic decreases in frequency of adjuvant chemotherapy receipt were observed over time during the study period, while neoadjuvant chemotherapy was stable. Younger age was associated with chemotherapy receipt (OR [95% CI]: 2.9 [2.4, 3.6]) and with anthracycline-based regimens (OR [95% CI]: 1.7 [1.3, 2.4]). Participants who had Medicaid (OR [95% CI]: 1.8 [1.3, 2.5]), lived in rural settings (OR [95% CI]: 1.4 [1.0, 2.0]), or were Black (OR [95% CI]: 1.5 [1.2, 1.8]) had slightly higher odds of chemotherapy, but these associations were non-significant with adjustment for stage and grade. Associations between younger age and chemotherapy receipt were strongest among women who did not receive genomic testing. While race was not strongly associated with chemotherapy receipt, younger age remains a strong predictor of chemotherapy receipt, even with adjustment for clinical factors and among women who receive genomic testing.

Dual‑directional effect of vinorelbine combined with cisplatin or fluorouracil on tumor growth and metastasis in metronomic chemotherapy in breast cancer

Dual‑directional effect of vinorelbine combined with cisplatin or fluorouracil on tumor growth and metastasis in metronomic chemotherapy in breast cancer

18F-FDG PET/CT-based deep learning radiomics predicts 5-years disease-free survival after failure to achieve pathologic complete response to neoadjuvant chemotherapy in breast cancer

BackgroundThis study aimed to assess whether a combined model incorporating radiomic and depth features extracted from PET/CT can predict disease-free survival (DFS) in patients who failed to achieve pathologic complete response (pCR) after neoadjuvant chemotherapy.ResultsThis study retrospectively included one hundred and five non-pCR patients. After a median follow-up of 71 months, 15 and 7 patients experienced recurrence and death, respectively. The primary tumor volume underwent feature extraction, yielding a total of 3644 radiomic features and 4096 depth features. The modeling procedure employed Cox regression for feature selection and utilized Cox proportional-hazards models to make predictions on DFS. Time-dependent receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were utilized to evaluate and compare the predictive performance of different models. 2 clinical features (RCB, cT), 4 radiomic features, and 7 depth features were significant predictors of DFS and were included to develop models. The integrated model incorporating RCB, cT, and radiomic and depth features extracted from PET/CT images exhibited the highest accuracy for predicting 5-year DFS in the training (AUC 0.943) and the validation cohort (AUC 0.938).ConclusionThe integrated model combining radiomic and depth features extracted from PET/CT images can accurately predict 5-year DFS in non-pCR patients. It can help identify patients with a high risk of recurrence and strengthen adjuvant therapy to improve survival.

Trastuzumab deruxtecan versus chemotherapy treated in patients with HER2-positive metastatic breast cancer: a cost-effectiveness analysis based on the DESTINY-Breast02 trial

ABSTRACT Objectives This study aims to conduct a cost-effectiveness analysis of trastuzumab deruxtecan versus chemotherapy for HER2-positive metastatic breast cancer from the perspective of the Chinese healthcare system. Methods A three-state partitioned survival model was constructed to simulate the treatment. The analysis yielded information on the costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). Sensitivity analyses have been carried out to scrutinize the model’s uncertainties Results The total cost for the trastuzumab deruxtecan group was found to be $228601.57, while the chemotherapy group incurred a total cost of $84901.38. It was found that the trastuzumab deruxtecan group exhibited an incremental gain of 2.95 QALYs in comparison to the chemotherapy group. However, this additional benefit came at an additional cost of $143700.19 for the trastuzumab deruxtecan treatment, calculated in the ICER at $48711.93/QALY, which surpasses the willingness-to-pay threshold of $37304.34/QALY in China. Sensitivity analyses indicated that the results were robust to variations in key parameters and assumptions. Conclusion Trastuzumab deruxtecan was not a cost-effective treatment option for patients with HER2-positive metastatic breast cancer in China. However, the use of trastuzumab deruxtecan may offer a cost-effective treatment alternative provided that its price is diminished.

Efficacy of dose-dense versus standard neoadjuvant chemotherapy regimensin luminal HER2-negative breast cancer: Interim results of single-centre study

Introduction. The efficacy of dose-dense AC in adjuvant chemotherapy of luminal breast cancer (ER+ BC) compared with the standard dosing regimen followed by switching to taxanes has been proven in numerous clinical trials and in a large meta-analysis of the EBCTCG group. However, no study about efficiency of this regimen in neoadjuvant setting has been published.The aim of the study. To assess the effectiveness of dose-dense regimens of neoadjuvant chemotherapy (NAC) of ER + HER2-BC (4 AC once every 2 weeks (dose dense, ddAC), then 4 courses of Docetaxel once every 3 weeks or 12 weekly injections of Paclitaxel [4D/12P]) and their comparison with the standard ones (AC once every 3 weeks [ACq3w], hereinafter 4D/12P). Primary end points are complete response rate (pCR) and RCB0–I.Methods. This retrospective study included patients with resectable or locally advanced luminal HER2-negative breast cancer who received NAC from Janu 2017 to Aug 2022. Statistical hypothesis – the dose-dense regimen AC increases the frequency of RCB0–I from 22 to 32% compared to the standard dosing regimen with subsequent switching to taxanes, with a study power of 80%, ά = 0.05, 138 patients should be included in the study. A total of 315 patients were included in the study, of which 147 and 168 patients received dose-dense (ddAC) and standard chemotherapy (ACq3w), respectively. After propensity matching analysis 138 patients in each group were included in the final analysis.Results. The pCR rate was 18.84% in the ddAC group versus 14.49% in the AC q3w group, the differences were not statistically significant (p = 0.379). The frequency of RCB0–I was higher in the ddAC – group 33.33% versus 21.74% in the AC q3w (p = 0.040). According to the subgroup analysis, rate of RCB0–I was significantly higher in patients younger 50 years, cN0, with the expression of progesterone receptors in ≥ 20%.Conclusions. This is the first study to compare the efficacy of a ddAC NAC with a standard regimen for ER + HER2-BC. NAC with ddAC is associated with an increase in RCB0–I rate.

HTRA1 expression is associated with immune-cell infiltration and survival in breast cancer.

High temperature requirement A1 (HTRA1), a member of the HTRA family, is a serine peptidase involved in many crucial bioprocesses such as proliferation, mitochondrial homeostasis, apoptosis, and protein quality control. It also plays an important role in the development of various tumors. However, the potential role and mechanisms of action of HTRA1 in breast cancer (BRCA) remain unclear. We conducted a bioinformatics-based study to investigate HTRA1 expression in BRCA alongside its associations with immune-cell infiltrates and survival outcomes. The expression of HTRA1 in BRCA samples was analyzed using RNAseq datasets from The Cancer Genome Atlas and Gene Expression Omnibus. R software was employed to assess the relationship between HTRA1 expression and clinicopathological characteristics, tumor-infiltrating immune cells, and immunity-associated biomarkers in BRCA. MethSurv and cBioPortal database were utilized to evaluate DNA methylation and genovariation within the HTRA1 DNA. Receiver operating characteristic curves, Kaplan-Meier analysis, and Cox regression were performed to estimate the impact of HTRA1 on diagnosis, prognosis, and response to chemotherapy in BRCA. HTRA1 expression was significantly downregulated in BRCA tissues compared to adjacent normal breast tissue controls. Differentially expressed genes associated with HTRA1 expression primarily enriched in cell proliferation pathways. Furthermore, altered HTRA1 expression significantly correlated with patient age, tumor histological type, T stage, progesterone receptor/estrogen receptor status, and PAM50 subtype of BRCA. Both positive and negative associations were observed between HTRA1 levels and the abundance of different types of immune cells, as well as immune biomarkers, including resting mast cells, follicular helper T cells, PD-L1, p53, and Ki67. Low HTRA1 expression was related with pathological complete response in luminal B BRCA patients undergoing chemotherapy. Additionally, lower HTRA1 expression in BRCA was associated with inferior overall survival and relapse-free survival. HTRA1 expression is associated with immune-cell infiltration, response to chemotherapy, and survival outcomes in BRCA. HTRA1 has the potential to serve as a promising biomarker and therapeutic target moving forward.

Fabrication of self-assembly iguratimod prodrug into polymeric nanoparticles delivery for the care of breast cancer therapy

Based on occurrence, death and prevalence in 2019, GLOBOCAN reports 36 forms of cancer in 185 countries. At the moment, chemotherapy is the furthermost commonly utilized cancer management by resistant systems, gene and hormone therapeutics. Herein, we define a precise straightforward and cost-effective method that therapeutically incorporates drug reconstruction, macromolecular nano-assembled and specific tumor targeting to overcome the various experiments modelled via the distribution of the potential anticancer Iguratimod (IGU) drug. The IGU drugs were empowered to instinctually assembly into admirable, stable nanoparticles on the conjugations covalent interactions of hydrophobic linoleic acid bonded with an amide group of ∼100 nm. Various microscopic methods have proven synthesized IGU-NP morphology. Following effective fabrication, the IGU and IGU-NP anti-cancer properties of MCF-7 (breast carcinoma) and 4T1 (breast carcinoma) cell lines were assessed. Additional studies include AO-EB (acridine bromide orange ethidium), nuclear staining. In contrast with IGU, the IGU-NPs showed excellent cytocompatibility, this investigation explained that IGU-NPs are a healthy and encouraging solution in breast cancer chemotherapy and are worthy of further clinical assessment.

Abstract LB_A02: Predicting breast cancer patients’ response to neoadjuvant chemotherapy from the deconvolved transcriptome of different cell types in the tumor microenvironment

Abstract Introduction: The tumor microenvironment (TME) constitutes a multifaceted ecosystem that influences tumor growth and clinical response via dynamic interactions between diverse cell types. Considerable attention has been devoted in recent years in exploring the TME’s impact on clinical response following immunotherapy, warranting further investigation into its impact in the context of chemotherapy. To address this, we present a novel computational framework called DECODEM (DEcoupling Cell-type-specific Outcomes using DEconvolution and Machine learning). Through DECODEM, we investigate the association of cell-type-specific transcriptomic profiles within the TME with response to neoadjuvant chemotherapy (NAC) in breast cancer (BC). Methods: DECODEM leverages cellular deconvolution of bulk transcriptomics data to extract cell-type-specific transcriptomics profiles for different cell types present in the TME, and further utilizes machine learning to build cell-type-specific predictors of clinical response. Using DECODEM, we analyzed the bulk transcriptomics data across three publicly available cohorts of HER2-negative BC patients who underwent NAC. We compared the predictive powers of these cell types, both individually and in concert with each other, against a state-of-the-art predictor employing clinical and transcriptomic features. We then validated our findings in a single-cell chemotherapy cohort of triple-negative breast cancer. Furthermore, we extended DECODEM to DECODEMi that can incorporate the cell-cell interactions (CCIs) among the prominent cell types to predict clinical response, hinting at the underlying mechanism at play. Results: Our analysis revealed that the diverse cell types within the TME significantly contribute to the prediction of chemotherapy response in HER2-negative BC, thus extending beyond the impact of malignant tumor cells alone. Notably, our key findings are: 1. We demonstrated the superior predictive powers of immune cells (myeloid, plasmablasts, B-cells) and stromal cells (endothelial, normal epithelial, cancer-associated fibroblasts), as compared to the bulk mixture and the state-of-the-art predictor. 2. We illustrated the complementary impacts of the prominent cell types via building highly accurate multi-cell-ensembles, where, remarkably, a three-cell-ensemble of endothelial, myeloid, and plasmablasts displayed the best predictive capability across cohorts. 3. We displayed that DECODEMi can capture the regulatory roles of CCIs and identified new CCIs likely to mediate chemotherapy response in HER2-negative BC. Conclusion: We provide an unprecedented computational approach to objectively delineate the cell-type-specific impacts of the TME in clinical response. Our analysis provides comprehensive insights into the intricate interplay of the cells in TME and their associations with chemotherapy response in HER2-negative BC, contributing to a deeper understanding of BC treatment efficacy. Citation Format: Saugato Rahman Dhruba, Sahil Sahni, Binbin Wang, Di Wu, Yael Schmidt, Eldad Shulman, Sanju Sinha, Stephen-John Sammut, Carlos Caldas, Kun Wang, Eytan Ruppin. Predicting breast cancer patients’ response to neoadjuvant chemotherapy from the deconvolved transcriptome of different cell types in the tumor microenvironment [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr LB_A02.

Abstract C031: ABCD3 expression is upregulated Caucasian and Asian breast cancer patients and is associated with non-responsiveness to endocrine therapy in luminal breast cancers

Abstract The ABC transporters represent the largest family of transmembrane proteins. They also serve in protective roles whereby many transporters act as efflux pumps for xenobiotics. And subsequently, several members; most notably of the A, B and C subfamilies, have been implicated in cancer chemoresistance; however, D family members have not been extensively studies with regards to cancer biology and treatment. Here we report that ABCD3 transporter expression is upregulated in breast cancer (p&amp;lt;0.001). The gene was also upregulated across cancer stages (p&amp;lt;0.05). Analysis of histological subtypes revealed that ABCD3 was expressed infiltrating ductal carcinoma (IDC). Immunohistochemistry (IHC) analysis confirmed that ABCD3 protein is expressed IDC (p&amp;lt;0.001). Moreover, ABCD3 expression was elevated in White (p&amp;lt;0.001) and Asian (p&amp;lt;0.05) breast cancer patients but not in African-American patients. Analysis of molecular subtypes revealed that ABCD3 expression was significantly higher in the Luminal breast cancer subtype (p&amp;lt;0.001). Furthermore, ROC analysis of gene expression in relationship in response to treatment revealed that ABCD3 is a moderate predictor (AUC=0.644, p=0.003) of response to endocrine therapy (tamoxifen and aromatase inhibitors) and a strong predictor (AUC=08, p=0.026) to chemotherapy in luminal breast cancers. Taken collectively, ABCD3 represents a biomarker which may be important for determining therapeutic response. Citation Format: Romonia Renee Reams, Simone Heyliger, Marilyn Saulsbury. ABCD3 expression is upregulated Caucasian and Asian breast cancer patients and is associated with non-responsiveness to endocrine therapy in luminal breast cancers [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C031.