Chemotherapy For Breast Cancer Research Articles

Benefit from dose-dense adjuvant chemotherapy for breast cancer: subgroup analyses from the randomised phase 3 PANTHER trial

It is unclear whether some patients with high-risk breast cancer do not warrant adjuvant dose-dense chemotherapy due to small expected absolute benefit. The phase 3 PANTHER trial (NCT00798070) compared adjuvant sequential epirubicin/cyclophosphamide (EC) and docetaxel (D) administered in either tailored dose-dense (tDD EC/D) or standard interval schedule (FEC/D) to patients with high-risk resected early breast cancer (n=2003). We compared outcomes across key subgroups of interest, evaluated the performance of the online prognostication and treatment benefit estimation tool PREDICT and conducted a subpopulation treatment effect pattern plot (STEPP) analysis. Primary endpoint was breast cancer recurrence free survival (BCRFS). Median follow-up was 10.3 years. Treatment with tDD EC/D improved 10-year BCRFS across all subgroups including according to menopausal status, with an absolute benefit of 2% or more, as well as in luminal (Hazard Ratio [HR]=0.83, 95% Confidence Interval [CI] 0.65-1.05) and Human Epidermal Growth Factor Receptor 2 (HER2) positive (HR=0.53, 95% CI 0.30-0.93), but not triple negative breast cancer patients (HR=1.02, 95% CI 0.66-1.57). PREDICT underestimated overall survival in the entire population and across all subgroups. In STEPP analysis, absolute benefit from tDD EC/D in BCRFS was stable across risk-defined subpopulations, from 3.8% in the lowest risk patients to 3.6% in the highest risk ones. There was no differential treatment effect over time. We could not reliably identify any subgroup not benefiting from dose-dense treatment, which should be considered for patients with primary resected high-risk breast cancer. Cancerfonden, Bröstcancerförbundet, Radiumhemmets Forskningsfonder, Amgen, Roche, sanofi-aventis.

18F-FDG PET/CT radiomic analysis and artificial intelligence to predict pathological complete response after neoadjuvant chemotherapy in breast cancer patients.

Build machine learning (ML) models able to predict pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer (BC) patients based on conventional and radiomic signatures extracted from baseline [18F]FDG PET/CT. Primary tumor and the most significant lymph node metastasis were manually segmented in baseline [18F]FDG PET/CT of 52 newly diagnosed BC patients. Clinical parameters, NAC and conventional semiquantitative PET parameters were collected. The standard of reference considered was surgical pCR after NAC (ypT0;ypN0). Eight-hundred-fifty-four radiomic features (RFts) were extracted from both PET and CT datasets, according to IBSI; robust RFTs were selected. The cohort was split in training (70%) and validation (30%) sets. Four ML Models (Clinical Model, CT Model, PET Model_T and PET Model_T + N) each one with 3 learners (Random Forest (RF), Neural Network and Stochastic Gradient Descendent) were trained and tested using RFts and clinical signatures. PET Models were built considering robust RFTs extracted from either primary tumor alone (PET Model_T) or also including the reference lymph node (PET Model_T + N). 72 pathological uptakes (52 primary BC and 20 lymph node metastasis) at [18F]FDG PET/CT were segmented. pCR occurred in 44.2% cases. Twelve, 46 and 141 robust RFts were selected from CT Model, PET Model_T and PET Model_T + N, respectively. PET Models showed better performance than CT and Clinical Models. The best performances were obtained by the RF algorithm of the PET Model_T + N (AUC = 0.83;CA = 0.74;TP = 78%;TN = 72%). ML models trained on PET/CT radiomic features extracted from primary BC and lymph node metastasis could concur in the prediction of pCR after NAC and improve BC management.

An Investigation of Travel Distance and Timeliness of Breast Cancer Treatment Among a Diverse Cohort in the United States

Travel to and from distant cancer treatment facilities can place a significant burden on cancer patients, particularly rural and minority survivors. Thus, the purpose of our investigation was to examine the association between patient travel distance and delays in types of treatment for breast cancer (surgery, radiation, chemotherapy, and hormonal therapy) and treatment delays. Using a novel linkage between the state cancer registry and administrative data from Medicaid and a private insurance plan, 2155 BC patients were successfully linked to create the cohort. ArcGIS was used to geocode all case residences and treatment facility addresses and calculate network distance between the residence and each facility. Logistic regression models were used to calculate the adjusted odds of being delayed versus timely by street distance. Odds of late surgery were increased by 1% (95% CI: 1.00, 1.01) for each one-mile increase from the patient’s residence to the treatment facility. In race-stratified models, the odds of late treatment for Black patients increased by 3% per mile (95% CI 1.01, 1.06) for radiation. Increased travel distance appears to significantly increase treatment delays for surgical, radiation, and chemotherapeutic treatments for women with BC, especially among Black women.

Proteomic profiling identifies upregulation of aurora kinases causing resistance to taxane-type chemotherapy in triple negative breast cancer

Nowadays, chemotherapy and immunotherapy remain the major treatment strategies for Triple-Negative Breast Cancer (TNBC). Identifying biomarkers to pre-select and subclassify TNBC patients with distinct chemotherapy responses is essential. In the current study, we performed an unbiased Reverse Phase Protein Array (RPPA) on TNBC cells treated with chemotherapy compounds and found a leading significant increase of phosphor-AURKA/B/C, AURKA, AURKB, and PLK1, which fall into the mitotic kinase group. The increase of AURKA and AURKB protein was majorly due to a post-transcription level regulation, and Paclitaxel treatment induced Aurora Kinases protein phosphorylation on AURKA(T288)/AURKB(T232) sites and their protein stability. In our UAB TNBC cohort, the expression of AURKA and AURKB was significantly higher in TNBC tumors compared to normal adjacent tissues, and AURKB was found to be highly expressed in African American TNBC patients compared to European Americans. Moreover, Aurora Kinases overexpression in TNBC cells renders resistance to Paclitaxel treatment and attenuates the apoptosis effect triggered by chemotherapy treatment, suggesting Aurora Kinases could mediate the chemo-resistance in TNBC. Hence, a combination of Aurora kinase inhibitors or PROTAC degrader and taxane-type chemotherapy significantly enhanced the chemotherapy effect. In summary, we revealed that Aurora Kinases upregulation after treatment with chemotherapy could confer chemotherapy resistance to TNBC cells, and AURKB could serve as preselection markers for stratifying patients’ response to neoadjuvant chemotherapy.

The importance of the Autostrain RV technique in the treatment of right ventricular myocardial alterations in patients with breast cancer receiving chemotherapy

To research the value of Autostrain right ventricular (RV) technology in detecting and preventing right ventricular myocardial injury in patients undergoing breast cancer chemotherapy by providing an imaging basis for early identification. To examine the changes in various cardiac function parameters before and after chemotherapy, two-dimensional echocardiography was employed 48 h before chemotherapy, 48 h after the fourth cycle of chemotherapy, and 48 h after the eighth cycle of chemotherapy, respectively. The patients included those with breast cancer who underwent surgery and were primarily administered anthracycline-based chemotherapeutic drugs. (1) Compared with the pre-chemotherapy period, the absolute values of the right ventricular global longitudinal strain (RV4CSL) and right ventricular free-wall longitudinal strain (RVFWSL) decreased after the fourth chemotherapy cycle, and no significant differences were observed in tricuspidannular plane systolic excursion (TAPSE), right ventricular Tei index, and right ventricular fractional area change (FAC); (2) Compared with the pre-chemotherapy period, the absolute values of RV4CSL and RVFWSL decreased after the eighth chemotherapy cycle. TAPSE and FAC decreased, the right ventricular Tei index increased; (3) Compared with the end of the fourth chemotherapy cycle, the absolute values of RV4CSL and RVFWSL decreased at the end of the eighth chemotherapy cycle. TAPSE, right ventricular Tei index and FAC were not significantly different. (4) Pearson correlation analysis revealed a correlation between the absolute value of RV4CSL, the absolute value of RVFWSL, right ventricular Tei index, TAPSE and FAC. The absolute values of RV4CSL and RVFWSL are sensitive indices that reflect changes in the right ventricular myocardium in the early stages of chemotherapy. They can reflect the effects of anthracycline on the right ventricular myocardium of patients with breast cancer earlier than the TAPSE, FAC and right ventricular Tei indices. A relationship exists between the absolute value of RVFWSL, the absolute value of RV4CSL, right ventricular Tei index, TAPSE, FAC and anthracycline-induced alterations in the right ventricular myocardium. This study is helpful for early detection of right ventricular myocardial function injury caused by anthracyclines in breast cancer patients, and provides imaging basis for early clinical detection and prevention of right ventricular myocardial injury.

Possibility of breast-conserving surgery after neoadjuvant chemotherapy in patients with hormone-positive, HER2-negative breast cancer

The aim of the study was to search for data on the effectiveness of neoadjuvant therapy hormone-positive HER2-negative breast cancer.Material and methods. The literature search was conducted in PubMed and RISC databases. Publications from 2012 to 2024 were found. The keywords used were: “breast cancer”, “bneoadjuvant chemotherapy”, “bsurgery”, “bluminal tumors”, “bhormone-dependent tumors”, “bbreast-conserving surgery”.Results. The indications for neoadjuvant chemotherapy in patients with hormone-positive HER2-negative breast cancer are discussed, considering the possibility of achieving clinical and pathological response with the assessment of the number of performed breast-conserving surgeries as the main task when prescribing preoperative treatment in this group of patients, as well as the influence of pathological response on survival rates.Conclusion. Data on the effectiveness of neoadjuvant chemotherapy for hormone-positive HER2-negative breast cancer are contradictory. The rate of complete pathological response is 2.0–16.2%, with its prognostic role being ambiguous. However, most studies have shown no correlation of pCR with overall and disease-free survival. The execution of breast-conserving surgery after neoadjuvant chemotherapy is possible in 50% of cases, if other contraindications are excluded.

Neoadjuvant nivolumab and chemotherapy in early estrogen receptor-positive breast cancer: a randomized phase 3 trial.

Patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) primary breast cancer (BC) have low pathological complete response (pCR) rates with neoadjuvant chemotherapy. A subset of ER+/HER2- BC contains dense lymphocytic infiltration. We hypothesized that addition of an anti-programmed death 1 agent may increase pCR rates in this BC subtype. We conducted a randomized, multicenter, double-blind phase 3 trial to investigate the benefit of adding nivolumab to neoadjuvant chemotherapy in patients with newly diagnosed, high-risk, grade 3 or 2 (ER 1 to ≤10%) ER+/HER2- primary BC. In total, 510 patients were randomized to receive anthracycline and taxane-based chemotherapy with either intravenous nivolumab or placebo. The primary endpoint of pCR was significantly higher in the nivolumab arm compared with placebo (24.5% versus 13.8%; P = 0.0021), with greater benefit observed in patients with programmed death ligand 1-positive tumors (VENTANA SP142 ≥1%: 44.3% versus 20.2% respectively). There were no new safety signals identified. Of the five deaths that occurred in the nivolumab arm, two were related to study drug toxicity; no deaths occurred in the placebo arm. Adding nivolumab to neoadjuvant chemotherapy significantly increased pCR rates in high-risk, early-stage ER+/HER2- BC, particularly among patients with higher stromal tumor-infiltrating lymphocyte levels or programmed death ligand 1 expression, suggesting a new treatment paradigm that emphasizes the role of immunotherapy and T cell immunosurveillance in luminal disease. Clinical trials.gov identifier: NCT04109066.

A randomized controlled trial: Effects of compression therapy combined with exercise on chemotherapy-induced peripheral neuropathy in patients with breast cancer.

To investigate the effects of compression therapy combined with exercise for cancer patients (EXCAP) in patients with peripheral neuropathy caused by breast cancer chemotherapy. Overall, 108 patients with peripheral neuropathy after chemotherapy for breast cancer were randomly divided into the control group (routine nursing), experimental group 1 (compression therapy), and experimental group 2 (compression therapy and EXCAP). The National Institute of Cancer Drug Toxicity Rating Scale and the Chemotherapy-Induced Peripheral Neuropathy Assessment Tool were assessed and compared between groups. The incidence of grade 0 peripheral neuropathy in both experimental groups was higher than that in controls (P < 0.001), and the incidence in group 2 was higher than that in group 1 (P < 0.001). The incidence of grade 2 disease in both experimental groups was lower than that in controls (P < 0.001). The rate of symptoms in both experimental groups after the intervention were lower than that in the control group (P < 0.001), and those in experimental group 2 were lower than those in experimental group 1 (P < 0.001). Scores regarding activities of daily living in the experimental groups were lower than those of the control group (P < 0.001), and lower in group 2 than in group 1 (P < 0.001). Compression therapy and EXCAP can effectively reduce the incidence of chemotherapy-induced peripheral neuropathy in patients undergoing breast cancer chemotherapy. They can both positively impact patients' daily lives and symptom experiences; however, they are more effective when combined.

Prognostic value of adjuvant chemotherapy for hormone receptor-negative T1a and T1bN0M0 breast cancer patients

The benefit of adjuvant chemotherapy (CT) for hormone receptor-negative T1a and T1bN0M0 breast cancer remains uncertain. Our study was to explore prognostic value and identify candidates of adjuvant CT for these patients. The data of hormone receptor-negative T1a and T1bN0M0 breast cancer patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2015. All patients were divided into two groups according to the history of adjuvant CT namely the CT group and the no CT (No CT) group. Univariate and multivariate Cox regression analysis were utilized to identify factors linked with cancer specific survival (CSS) and overall survival (OS) for the patients. Kaplan-Meier method was employed to determine survival benefit of adjuvant CT. A total of 3889 patients were included. After propensity score-matching, 1217 patients were assigned to the CT group and 1217 patients were assigned to the No CT group respectively. Based on multivariate Cox regression analysis of OS, older age, single, T1b stage, triple-negative tumor and absence of adjuvant CT were identified as risk factors related to OS. Besides, multivariable Cox regression analysis of CSS showed significant association between grade III+IV, T1b stage, triple-negative tumor and absence of adjuvant CT and CSS. The results from Kaplan-Meier curves revealed that adjuvant CT could bring OS benefit for these patients with more than two risk factors and could improve CSS for the patients with more than one risk factor. Our study supports the implementation of individualized strategies for hormone receptor-negative T1a and T1bN0M0 breast cancer patients. Adjuvant CT was recommended for potential beneficial patients after undertaking a risk-benefit discussion.

Comparison of patient-reported symptoms with multi-item patient-reported outcome measures of fatigue, anxiety, and depression in the clinical care of women undergoing chemotherapy for early breast cancer.

As patient-reported symptoms are increasingly incorporated into routine clinical practice and captured in electronic medical records these data can be used to conduct health-related quality of life research studies. This study compares symptom reports from the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) and its precursor patient reported symptom monitoring (PRSM) (hereafter PRSM/PRO-CTCAE) with multi-item patient-reported outcome (PRO) scales for fatigue (Functional Assessment of Chronic Illness Therapy/FACIT-Fatigue) and depression and anxiety (Mental Health Index/MHI). This is a secondary analysis of data collected from women with early breast cancer (Stage I-III) scheduled for chemotherapy who completed PRSM/PRO-CTCAE, FACIT-Fatigue, and MHI scales pre- and post-chemotherapy. Spearman correlation coefficients estimated the magnitude and direction of correlations between measures (convergent validity). For each symptom, patients were then categorized based on who improved, stayed the same, or worsened on the composite PRSM/PRO-CTCAE score, and changes in scores on the PRO scales were compared. In a sample of 374 women, mean age was 57years (SD 12.6) with 76% White. PRSM/PRO-CTCAE fatigue measures were strongly correlated with FACIT-Fatigue total scale and had mixed moderate to strong correlation for individual items within the FACIT-Fatigue scale. PRSM/PRO-CTCAE Sad and Anxiety measures were strongly correlated with MHI-Depression and MHI-Anxiety total scales, respectively, and had mixed moderate to strong correlation with individual items within the MHI subscales. PRSM/PRO-CTCAE pre-post changes in symptom scores mirrored pre-post changes in FACIT-Fatigue and MHI subscales.

Neoadjuvant chemotherapy and pathological complete response in hormone-positive HER2-negative breast cancer: influence of progesterone receptor expression, tumor grade and Ki-67

Aim. To study the role of progesterone receptor expression, tumor grade and Ki-67 level as possible predictors of pathological complete response (pCR) to neoadjuvant chemotherapy in patients with stage IIA–IIB (cT1–2N1, cT2–3N0M0) breast cancer of hormone-positive HER2-negative subtype.Materials and methods. We retrospectively analysed the efficacy of neoadjuvant chemotherapy (4AC+12P/4T) in 100 patients with cancer stages IIA–IIB (cT1–2N1, cT2–3N0M0) of hormone-positive HER2-negative subtype treated at the P.A. Hertsen Moscow Oncology Research Institute from 2013 to 2022. The pathological response to neoadjuvant chemotherapy depending on the level of progesterone receptor expression, tumour grade (G) and tumour proliferation index (Ki-67) were evaluated.Results. Pathological complete response was achieved in 12 of 100 patients. The progesterone receptor expression ≤3 Allred pCR scores were found in 16.1 % (5/31) of patients, whereas with progesterone receptor &gt;3 scores in 10.1 % (7/69) (odds ratio 1.703; 95 % confidence interval (CI) 0.495–5.860; p = 0.507). Patients with high tumour grade (G3) achieved pCR in 12.1 % (4/33) cases and with G2 – in 11.9 % (8/67) (odds ratio 1.017; 95 % CI 0.283–3.658; p = 1.000). With the Ki-67 levels ≥50 % pCR was achieved in 14.6 % (7/48) cases compared to 9.6 % (5/52) with Ki-67 levels &lt;50 %(odds ratio 1.605; 95 % CI 0.473–5.445; p = 0.544). The Ki-67 threshold for achieving pCR was 70 % (area under the ROC curve 0.663 ± 0.090; 95 % CI 0.486–0.840; p = 0.068) and for progesterone receptors was 3 points (area under the ROC curve 0.625 ± 0.080; 95 % CI 0.467–0.782; p = 0.156).Conclusion. This analysis highlights the importance of considering all clinical and morphological characteristics of the tumour when planning the scope of treatment for hormone-positive HER2-negative breast cancer. The results obtained may serve as a basis for a more personalised therapeutic approach.

The prognostic value of changes in Ki67 following neoadjuvant chemotherapy in residual triple-negative breast cancer: a Swedish nationwide registry-based study.

To evaluate the prognostic significance of changes in pre- and post-neoadjuvant chemotherapy (NACT) Ki67 in patients with primary invasive triple-negative breast cancer (TNBC). Population-based registry data were retrieved for patients diagnosed with TNBC between 2007 and 2021 (n = 9262). Multivariable Cox regression analysis was performed for disease-specific survival (DSS) and overall survival (OS) adjusted for age and residual disease in the breast and nodes (RDBN). Of the 1777 TNBC patients receiving NACT, 54 achieved pathologic complete response (pCR)and 755 had residual disease. Most patients were overweight with stage II disease (78%), grade 3 tumors (53%), and RDBN score 3 (42%). Compared to baseline, tumor size (30 vs. 15mm; P < 0.0001) and Ki67 levels (63% vs. 48%; P < 2.2e - 16) generally decreased after NACT. Although only 5% of samples increased in size, Ki67 levels often remained unchanged (75%) or increased (0.9%) after treatment, respectively. However, 34% of patients discontinued treatment. Patients showing no changes in Ki67% had more unfavorable OS (P < 0.0001) and DSS (P = 0.00032), with significantly lower 5-year survival probabilities (OS: 66%; DSS: 78%) than those with decreased Ki67% (OS: 87%; DSS: 89%). All patients reaching pCR were alive 5years after diagnosis. However, only the RDBN score was an independent predictor of survival in the multivariable analyses. Ki67 often remained unchanged in TNBC patients treated with neoadjuvant chemotherapy, resulting in adverse clinical outcomes. These findings highlight the need for individualized treatment regimens and dynamic monitoring of TNBC patients with high Ki67 post-NACT.

Development and validation of a metabolic syndrome and its components to predict the efficacy of neoadjuvant chemotherapy in breast cancer: An observational, single-center, cohort study.

To assess whether metabolic syndrome can be used as a reference index to evaluate the efficacy of neoadjuvant chemotherapy treatment for breast cancer (BC). Seventy cases of female BC patients who received neoadjuvant chemotherapy treatment and surgical treatment at the Glandular Surgery Department of Hebei Provincial People's Hospital from January 2021 to December 2023 were retrospectively collected, and clinical data such as puncture pathology were recorded. The clinical data were analyzed by 1-way analysis using the χ2 test, and further multifactorial logistic regression analysis was performed for statistically significant differences. The independent risk factor metabolic syndrome (MetS) and its components were plotted in the receiver operating characteristic curve (ROC) curve and baseline graph by R Studio 4.41 software, and the meaningful components were plotted in the column graph by lasso regression analysis for internal validation, and the quality of the model was evaluated by the ROC curve and calibration graph, and then the clinical decision curve analysis was used to evaluate the clinical effectiveness of the model. The neoadjuvant efficacy was statistically associated with whether the patient was first diagnosed between 45 and 55 years of age, estrogen receptors (ER), progesterone receptors (PR) expression status, Her-2 expression status, and whether the patient had MetS, as determined by univariate analysis through χ2 (P < .05). On multifactorial binary logistic regression analysis, ER, PR status, Her-2 status, and the presence of MetS were statistically significant (P < .05) for the efficacy of neoadjuvant chemotherapy. Patients with MetS were less likely to achieve complete pathological remission than those without MetS. MetS and its components were analyzed by lasso regression analysis with RStudio 4.41 software to conclude that hypertension, hyperglycemia, and high-density lipoprotein were all correlates affecting the pathologic complete response (pCR), and a column-line graph was plotted, with a C-index of 0.76, indicating a good predictive efficacy. ER, PR status, Her-2 status and the presence of MetS are independent predictors for assessing the efficacy of neoadjuvant chemotherapy in BC, and MetS can be used as a predictor of the efficacy of neoadjuvant chemotherapy. Clinical references are provided.

A Comprehensive Analysis of Neoadjuvant Chemotherapy in Breast Cancer: Adverse Events, Clinical Response Rates, and Surgical and Pathological Outcomes-Bozyaka Experience.

Objectives: To evaluate the neoadjuvant chemotherapy (NACTx) process in breast cancer (BC), its significant treatment-related adverse events (trAEs), tumor clinical response rates, and surgical and pathological outcomes, and to analyze factors influencing cavity shaving and axillary lymph node dissection (ALND) following sentinel lymph node biopsy (SLNB). Methods: A comprehensive retrospective study was conducted at a single center on patients who received NACTx for BC between 2015 and 2021. Results: Medical records of 242 patients were reviewed. Approximately one-fifth encountered grade ≥ 3 trAEs (21.5%), leading 3.3% to discontinue chemotherapy. Anthracycline cardiotoxicity (2.2%) caused one death (mortality rate = 0.4%). For clinical response and surgical and pathological outcomes, 229 patients were eligible. Clinical progression occurred in 3.9% of the patients (14% in triple-negative BC, p = 0.004). Breast-conserving surgery (BCS) was performed in 55% of the patients. There was no significant difference between the type of breast surgery (BCS vs. mastectomy) and molecular subtype, histology, tumor size, or tumor's pathological response degree. Cavity shaving was required in one-fifth of the patients who underwent BCS (n = 134) due to an invasive tumor at the surgical margin (SM). Tumor histology (invasive ductal vs. invasive lobular carcinoma; OR: 4.962, 95% CI 1.007-24.441, p = 0.049) and tumor SUVMax value (OR: 0.866, 95% CI 0.755-0.993, p = 0.039) had significant independent efficacy on SM positivity. Initially, 75% underwent SLNB, but nearly half of them needed ALND. ALND rates were significantly higher in the luminal A and LB-HER2(-) groups (87% vs. 69%) than in the HER2(+) and TN groups (43% to 50%) (p = 0.001). All luminal A patients and those with lobular histology required ALND after SLNB, but no patients in the HER2-enriched group required ALND. ER positivity and higher PR expression levels were associated with an increased need for ALND after SLNB, whereas HER2 positivity and higher SUVMax values of LN(s) were associated with a significantly reduced need for ALND. About 27% of the patients achieved overall pCR. No pCR was achieved in the LA group. Conclusions: The BC NACTx process requires close monitoring due to severe AEs and disease progression. NACTx decisions must be made on experienced multidisciplinary tumor boards, considering tumor characteristics and expected targets.

Adjuvant Dose-Dense Chemotherapy in Hormone Receptor-Positive Breast Cancer.

In light of evolving evidence that some patients with node-positive estrogen receptor-positive (ER+) disease may receive less benefit from chemotherapy, this study reports 12-year outcomes of the C9741 trial overall, and by the sensitivity to endocrine therapy (SET2,3) test index, a biomarker measuring endocrine transcriptional activity, to identify patients most likely to benefit from dose-dense chemotherapy. In all, 1,973 patients were randomly assigned to dose-dense versus conventional chemotherapy. Hazard ratios (HRs) for prognosis and for predictive interaction with chemotherapy schedule were estimated from Cox models of long-term disease-free survival (DFS) and overall survival (OS). SET2,3 was tested on the 682 banked RNA samples from ER+ cancers. Dose-dense chemotherapy improved DFS in the overall study population by 23% (HR, 0.77 [95% CI, 0.66 to 0.90]) and OS by 20% (HR, 0.80 [95% CI, 0.67 to 0.95]); the benefits of dose-dense therapy were seen for ER+ and ER-negative subsets, without significant interaction between treatment arm and ER status. Low SET2,3 status was highly prognostic, but also predicted improved outcomes from dose-dense chemotherapy (interaction P = .0998 for DFS; 0.027 for OS), independent of menopausal status. Specifically, low endocrine transcriptional activity predicted benefit from dose-dense chemotherapy, whereas tumor burden and proliferation-driven signatures for molecular subtype classification did not. At 12-year follow-up, C9741 confirmed the sustained long-term benefit of adjuvant dose-dense chemotherapy for node-positive breast cancer. SET2,3 identified patients with ER+ breast cancer who benefited from dose-dense chemotherapy, and specifically, this benefit was predicted by low endocrine activity in the cancer, rather than tumor burden, molecular subtype, or menopausal status.

Clinical, Analytical, and Echocardiographic Associations of Impaired Cardiorespiratory Fitness After Anthracycline Chemotherapy in Breast Cancer: EPIC Fitness Study.

This study explores the effects of anthracycline chemotherapy (AC) on breast cancer patients, focusing on changes in body composition, advanced echocardiographic parameters at rest and during exercise, and biomarkers; and subsequently assesses whether these parameters are associated with impaired cardiorespiratory fitness (CRF). In this prospective study, we evaluated women with early-stage breast cancer undergoing AC at three visits: before AC, 1 month after, and 6 months post-AC. The study included 32 women with breast cancer, with functional disability increasing from 9.0% pre-AC to 43.8% at 1 month and 53.1% at 6 months post-AC. At 1 month, patients with functional disability exhibited higher rates of cancer therapy-related cardiac dysfunction (CTRCD) (85.7%vs. 55.5%) and, during exercise, showed lowerleft ventricular ejection fraction (LVEF), reduced contractile reserve and stroke volume (SV); along with elevated IL-6, PlGF, and MPO levels. By 6 months, these patients maintained higher CTRCD rates (35.3%vs. 0%), lower SV and cardiac output (CO), reduced global longitudinal strain (GLS), and decreased global work index (GWI). During exercise, they had lower SV; additionally, they exhibited higher MPO levels and increased body and visceral fat. In our multivariable model: age, body fat, resting GWI, exercise LVEF, and CO were independently associated with VO2peak. Significant and persistent CRF reductions are common in breast cancer patients post-AC. While resting LVEF and GLS were not linked to VO2peak, resting MWI and exercise LVEF and CO were, potentially identifying patients at increased long-term heart failure risk who would benefit from cardioprotective strategies like cardio-oncology rehabilitation. It is important to recognize that impaired CRF is multifactorial, as demonstrated by age and body fat being independently associated with VO2peak, and the impact of non-cardiac factors should be better studied. Our findings highlight the need for further research on CTRCD definition, suggesting that CPET and advanced exercise echocardiography could enhance risk stratification.

Time-Series MR Images Identifying Complete Response to Neoadjuvant Chemotherapy in Breast Cancer Using a Deep Learning Approach.

Pathological complete response (pCR) is an essential criterion for adjusting follow-up treatment plans for patients with breast cancer (BC). The value of the visual geometry group and long short-term memory (VGG-LSTM) network using time-series dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for pCR identification in BC is unclear. To identify pCR to neoadjuvant chemotherapy (NAC) using deep learning (DL) models based on the VGG-LSTM network. Retrospective. Center A: 235 patients (47.7 ± 10.0 years) were divided 7:3 into training (n = 164) and validation set (n = 71). Center B: 150 patients (48.5 ± 10.4 years) were used as test set. 3-T, T2-weighted spin-echo sequence imaging, and gradient echo DCE sequence imaging. Patients underwent MRI examinations at three sequential time points: pretreatment, after three cycles of treatment, and prior to surgery, with tumor regions of interest manually delineated. Histopathology was the gold standard. We used VGG-LSTM network to establish seven DL models using time-series DCE-MR images: pre-NAC images (t0 model), early NAC images (t1 model), post-NAC images (t2 model), pre-NAC and early NAC images (t0 + t1 model), pre-NAC and post-NAC images (t0 + t2 model), pre-NAC, early NAC and post-NAC images (t0 + t1 + t2 model), and the optimal model combined with the clinical features and imaging features (combined model). The models were trained and optimized on the training and validation set, and tested on the test set. The DeLong, Student's t-test, Mann-Whitney U, Chi-squared, Fisher's exact, Hosmer-Lemeshow tests, decision curve analysis, and receiver operating characteristics analysis were performed. P < 0.05 was considered significant. Compared with the other six models, the combined model achieved the best performance in the test set yielding an AUC of 0.927. The combined model that used time-series DCE-MR images, clinical features and imaging features shows promise for identifying pCR in BC. Stage 4.

Severe Deficiency of Vitamin D and Anthracycline-Taxane Regimen are associated with Cachexia Following Breast Cancer Chemotherapy: A Single Center Assessment Using Two Consensus-Based Criteria.

Cancer cachexia in breast cancer (BC) patients is not commonly reported, particularly in Indonesia. This study assessed the prevalence of cachexia in local patients with BC receiving chemotherapy, and the associated factors. This cross-sectional study included 160 BC patients who started chemotherapy between July 2018 and June 2022. We collected data including age, body mass index, comorbidity, stage, surgery type, chemotherapy information, neutrophil-to-lymphocyte ratio, albumin, vitamin D, C-reactive protein, and the presence of chemotherapy-induced nausea and vomiting. We used the Fearon and Evans criteria to define the outcomes of cachexia. A multivariate logistic regression test was used to determine the factors related to the cachexia status following chemotherapy. During and after chemotherapy, 61 participants (38.1%) and 32 participants (20%) experienced cachexia based on Fearon and Evans criteria, respectively. All the patients had a deficient vitamin D concentration at baseline and vitamin D below median value (8.94 ng/mL) was classified as severe deficiency. Vitamin D severe deficiency was associated with an increased risk of cachexia (OR 2.47, 95%CI 1.19-5.11, p=0.014 for Fearon; and OR 2.47, 95%CI 1.03-5.92, p=0.043 for Evans), as well as anthracycline-taxane regimen based on Fearon criteria only (OR 4.35, 95%CI 1.39-13.53, p=0.011). Our findings demonstrated that vitamin D severe deficiency and anthracycline-taxane regimen were associated with cachexia occurrence among BC patients following chemotherapy. Strategies and further investigation are warranted to reduce cachexia occurrence, along with nutritional support during chemotherapy.

Long-term outcome for neoadjuvant versus adjuvant chemotherapy in early breast cancer and the prognostic impact of nodal therapy response: A population-based study.

Although neoadjuvant systemic treatment for non-metastatic breast cancer has gained ground during the past decade, there is no compelling evidence that it improves overall survival compared to primary tumor resection and adjuvant treatment. At the same time, the approach to responders to neoadjuvant treatment in the axilla is evolving. This is a retrospective analysis of a prospectively collected population-based registry. Patients that received neoadjuvant (n=2126) or adjuvant chemotherapy (n=4754) for non-metastatic breast cancer during 2007-2020 in the Stockholm-Gotland region, which comprises 25% of the entire Swedish population, were included. Overall survival of patients treated preoperatively and postoperatively was compared using inverse probability treatment weighting and landmark analysis. The prognostic impact of change between prechemotherapy clinical to postchemotherapy pathologic nodal stage (cN/pN) in women receiving neoadjuvant treatment was investigated. Median follow-up was 4.93 years. There was no difference in adjusted overall survival between adjuvant (reference) and neoadjuvant treatment in the entire population (HR=1.38, 95% CI 0.98-1.93, p=0.062) or in breast cancer subtypes. Patients converting from positive clinical to negative pathologic nodal stage (cN+/pN0) had improved outcomes compared to cN0/pN0 or patients with pN0 following primary surgery. These patients had a particular disease trajectory, with early peak in risk of death followed by quick and sustained decrease. There was no difference in survival of patients treated with neoadjuvant versus adjuvant systemic therapy for non-metastatic breast cancer. Patients with cN+/pN0 have excellent prognosis and represent potential candidates for de-escalation of local and systemic treatment.

Comparative efficacy and safety of PD‐1 versus PD‐L1 inhibitors in breast cancer treatment: A systematic review and meta analysis

AbstractThe comparative efficacy and safety of programmed death‐ligand 1 (PD‐L1) inhibitors versus programmed death protein 1 (PD‐1) inhibitors in breast cancer treatment remain inconclusive, as no head‐to‐head randomized controlled trials (RCTs) conducted. This study aims to evaluate the efficacy and safety of PD‐1/PD‐L1 inhibitors as monotherapy or in combination with chemotherapy for breast cancer. A systematic review and meta‐analysis were performed using major databases and oncology conference proceedings. The primary outcomes were overall survival (OS) for advanced breast cancer and pathological complete response (PCR) rate for early breast cancer. Secondary outcomes included progression‐free survival (PFS) for advanced breast cancer and incidence of adverse events (AEs). Seventeen studies met the inclusion criteria, consisting of seven RCTs on early‐stage and 10 on advanced breast cancer. For advanced breast cancer, PD‐1/PD‐L1 inhibitors modestly improved OS compared to chemotherapy, with no significant differences between PD‐1 and PD‐L1 inhibitors. PD‐L1 inhibitors showed greater improvement in PFS compared to PD‐1 inhibitors. The likelihood of AEs of any grade was higher with PD‐L1 inhibitor treatment than with PD‐1 inhibitor treatment. In early breast cancer, combining PD‐1/PD‐L1 inhibitors with chemotherapy inducing higher PCR rates than chemotherapy alone, with PD‐1 inhibitors achieving better outcomes than PD‐L1 inhibitors. PD‐1 inhibitors were linked to slightly higher rates of grade &gt;2 AEs compared to PD‐L1 inhibitors. The findings indicate that PD‐1 inhibitors may offer advantages for advanced breast cancer due to similar OS and a lower rate of AEs. For early breast cancer, PD‐1 inhibitors are recommended given their superior PCR rates.