Adjuvant Chemotherapy For Breast Cancer Research Articles

Long-term prospective outcome data using EndoPredict as risk stratification and chemotherapy decision biomarker in hormone receptor-positive, HER2-negative early breast cancer

Abstract Purpose To report the prospective long-term outcome data of patients whose chemotherapy decision was guided by the EndoPredict test. Methods Patients with hormone receptor-positive HER2-negative early breast cancer with 0–3 positive lymph nodes were enrolled. The EndoPredict test was carried out on all tumor samples. Treatment compliance, local recurrence, distant metastases, and survival were evaluated. Associations of EPclin risk stratification with 5-year disease-free survival and distant metastasis-free survival were evaluated by time-to-event analysis. Results 368 consecutive patients were included in the analysis. Median follow-up was 8.2 years. EndoPredict allocated 238 (65%) in the low-risk and 130 (35%) patients in the high-risk group. Risk for disease recurrence or death in EPclin high-risk patients was twofold higher than in EPclin low-risk patients (hazard ratio [HR] 2.08; 95% CI 1.26–3.44; p = 0.004). EPclin low-risk patients had a 5-year disease-free survival of 95.3% (95% CI 92.6–98.0%). EPclin high-risk patients were at higher risk of developing distant metastases or death (HR 2.21; 95% CI 1.27–3.88; p = 0.005). EPclin high-risk patients who underwent chemotherapy had a 5-year DFS of 89.1% (95% CI 82.7–96.1%) in contrast to high-risk patients without chemotherapy (68.9%; 95% CI 56.2–84.5%; HR 0.46; 95% CI 0.23–0.95; p = 0.036). EPclin high-risk patients were at higher risk of experiencing distant metastases or death than EPclin low-risk patients regardless of menopausal status (premenopausal: HR 3.55; 95% CI 1.17–12.32; p = 0.025; postmenopausal: HR 1.92; 95% CI 0.99–3.7; p = 0.054). Conclusion EndoPredict can guide decisions on adjuvant chemotherapy in early luminal breast cancer. EndoPredict risk stratification is also applicable in premenopausal women.

Abstract PO2-12-12: REaCT 5G: A randomized study comparing bone pain after 5 days of filgrastim or one day of pegfilgrastim for primary febrile neutropenia prophylaxis during neo-/adjuvant chemotherapy for early breast cancer

Abstract Background: Granulocyte colony stimulating factor (G-CSF) such as filgrastim (FIL) or pegfilgrastim (PEG) significantly reduces the risk of febrile neutropenia (FN) and treatment-related hospitalization in patients with early breast cancer receiving chemotherapy. However, patients receiving G-CSF can experience clinically significant bone pain. Previous studies examining post-GCSF bone pain were mostly based on physician pain assessment and compared mixed doses (30/60/100 μg/kg) of PEG vs. FIL (5μg/kg/day or 300 μg/day) given for 7 to 14 days. Based on a randomized non-inferiority study, 5 days of FIL is considered non-inferior to 10 days of FIL to prevent FN and hospitalizations and is frequently used in patients receiving chemotherapy for breast cancer. Patient-reported bone pain after 5 days of FIL vs. single dose of PEG has never been compared in a prospective randomized study and has important implications for patient and physician treatment preferences. Methods: In this multicenter, open-label trial, patients receiving neo-/adjuvant chemotherapy for early-stage breast cancer requiring primary FN prophylaxis with G-CSF were randomized 1:1 to either 5 days of FIL (300 μg or 480μg if ≥ 90 kg) or 1 day of PEG (6 mg) with each cycle of chemotherapy. The primary endpoint was bone pain using area under the curve (AUC) of the daily pain score from days 1-5 (AUC score 0 to 40) during cycle 1. We used linear regression adjusting for stratification factors [cancer center (2 centers) and chemotherapy regimen (taxane (TAX) or anthracycline (ANTH)-based during cycle 1] and prespecified baseline covariates: age, pain, and use of pain medications pre-chemotherapy. Supportive analysis of bone pain across cycles 1 to 4 was conducted using repeated linear regression. Key secondary endpoints included incidence of FN, hospitalizations, chemotherapy delay, dose-reduction or discontinuation, and chemotherapy-related deaths. Results: From June 2021 to March 2023, 233 patients were enrolled, with 217 patients (108 FIL/109 PEG) in the intention-to-treat analysis; 16 (7.4%) patients were excluded because of incomplete follow-up. Participants were mean age 55.6 years; almost exclusively female (99.1%), on chemotherapy regimen TAX 57% vs. ANTH 43%, had mean baseline pain score 1.12, and prevalence of pain medication use pre-chemotherapy was acetaminophen 14.7%, non-steroidal anti-inflammatory drugs (NSAIDs) 6.0% and opioids 3.2%. Characteristics were balanced between arms (Table 1). After repeated measures linear regression adjusted for age, chemotherapy regimen, baseline pain, and use of pain medications pre-chemotherapy, mean AUC for bone pain at cycle 1 was 10.94 for FIL and 10.12 for PEG (mean difference 0.82; 95% CI: -1.59, 3.23; p = 0.516). There was no significant difference between arms across treatment cycles (interaction p = 0.785; mean time-averaged difference 0.28; 95% CI: -1.75, 2.32). Across cycles 1 to 4, mean peak pain over 5 days post-GCSF was 3.27 vs. 3.41 (p=0.700); frequency of bone pain during first 8 days (pain score > 0) was 52.5% vs. 51.3%; p=0.358, and mean frequency of severe pain (pain score ≥ 5) was 17.5% vs. 15.2%; p=0.014 for FIL vs. PEG, respectively. The incidence of FN [4.6% vs. 0%, absolute difference 4.6% (95% CI: -0.3%, 9.5%; p=0.069)] and hospitalization [FN and non-FN related: 10.2% vs. 1.8%, absolute difference of 8.4% (95% CI: 1.2%, 15.5%; p=0.021)] was higher in the FIL group. There were no significant differences in chemotherapy delay (13% vs. 11%; p=0.815), dose reduction (14.8% vs. 14.7%; p=0.999), early discontinuation (8.3% vs. 5.5%; p=0.580), or chemotherapy-related death (0.9% vs. 0%; p=0.996) in the FIL vs. PEG groups, respectively. Conclusion: There was no difference in patient-reported bone pain after 5 days of FIL or PEG, even after controlling for important clinical factors. Importantly, the study observed higher rates of FN and hospitalizations in patients receiving FIL for 5 days only. Table 1 Baseline Characteristics Citation Format: Terry Ng, Yuxin Zhang, Carol Stober, Jennifer Shamess, Natalie Mills, Stuart Nicholls, Mohammed Ibrahim, Daniel Davoudpour, Christopher Armiento, Marie-France Savard, Moira Rushton, Arif Awan, Sandeep Sehdev, John Hilton, Xinni Song, Rakesh Goel, Fiona Macdonald, Kelly Daigle, Lisa Vandermeer, Monica Taljaard, Mark Clemons. REaCT 5G: A randomized study comparing bone pain after 5 days of filgrastim or one day of pegfilgrastim for primary febrile neutropenia prophylaxis during neo-/adjuvant chemotherapy for early breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-12-12.

Abstract PO5-13-01: An App-Based Approach to Monitor Chemotherapy Symptoms

Abstract Introduction Patient-Reported Outcome Measures (PROM’s) are important tools that can enhance symptom management and patient quality of life in cancer treatment. Despite well-documented benefits, they are not often employed in routine care. This study aims to investigate the feasibility and acceptance of the integration of a dedicated mobile app for real-time symptom tracking and intervention using PROM’s among patients undergoing neoadjuvant or adjuvant chemotherapy for breast cancer. Methods We developed a dedicated mobile app for tracking PROM’s utilizing the NCI PRO-CTCAE to monitor 12 common chemotherapy-related symptoms. We aimed to evaluate patient acceptance and clinical feasibility of the app. Patient responses were directed to a personalized dashboard for designed for the clinical treatment team. We determined self-reported grade 3 or 4 vomiting, diarrhea, constipation, shortness of breath, cough, or peripheral neuropathy and grade 4 mucositis, nausea, or pain as symptoms severe enough to trigger an automatic alert requiring a phone call from our nursing staff for support. Each questionnaire generated up to 1 alert regardless of the number of severe symptoms. Symptomatic patients also received personalized automated instructions and video links for symptom management regardless of the severity of their symptoms. In response to staff feedback during the study, we added an additional assessment to determine whether patients with severe symptoms were interested in direct contact from the clinical staff when alerts were triggered. At baseline patients reported if they felt they were skillful at using smartphone apps. Quality of life, psychological and emotional health measures were collected at baseline, and weeks 6, 12, and 18. Categorical variable were described using percentages and compared using the chi squared test. Statistical analyses were performed by SPSS. Results: At the time of this analysis, 58 patients were recruited and found eligible for the study. All 58 patients self-reported as skilled with the use of smartphone apps. Eighteen patients (31%) withdrew from the study after receiving at least one questionnaire and their data was included up to their point of withdrawal. The different chemotherapy regimens given in the study are shown in table 1. Out of 772 questionnaires sent, 404 were returned, resulting in a 52% completion rate. These 404 completed questionnaires generated 126 (31%) alerts. After including feedback on the interest of direct contact from our nursing staff to manage alarming symptoms, only 23/102 (22.5%) alerts required clinical contact. Twenty-one patients (36%) did not complete even a single questionnaire. For the 37 (64%) patients who completed at least 1 questionnaire the completion rate was 74%. There was no significant difference in the alert rate of completed questionnaires between patients receiving TCHP, TC-AC-Pembro, and AC-T (38%, 38%, 29% p=NS). TC triggered significantly less alerts than AC-T (11% vs 29% p=0.01). Conclusion: The interim results of our ongoing study highlight the potential of a mobile app in real-time monitoring of chemotherapy-related symptoms. Our results suggest symptom monitoring using a dedicated mobile app is both acceptable and feasible for both patients and clinical personnel. The digital approach also seems effective in triggering alerts for severe symptoms, facilitating timely intervention. However, most alerts did not necessitate direct clinical contact, underscoring the role these interventions may play in allowing for patient self-care. However, over a third of patients did not utilize the app at all, emphasizing the need for further research examining the factors influencing the utilization of this technology for symptom monitoring. As the study continues, we hope to gain insights that can simplify and improve patient and clinician interaction with this tool, potentially improving symptom management for adjuvant breast cancer. Table 1 Chemotherapy Regimens DD AC-T dose dense doxorubicin cyclophosphamide paclitaxel, TCHP docetaxel carboplatin trastuzumab pertuzumab, TC-AC-Pembro paclitaxel carboplatin doxorubicin cyclophosphamide pembrolizumab, TC docetaxel cyclophosphamide,DD AC-T weekly dose dense doxorubicin cyclophosphamide paclitaxel weekly, TH paclitaxel trastuzumab, AC-THP doxorubicin cyclophosphamide paclitaxel trastuzumab pertuzumab, AC-TC doxorubicin cyclophosphamide paclitaxel carboplatin Citation Format: Opher Globus, Tal Sella, Amit Itay, Tali Shapira, Raisa Gold, Tami Modiano, Cecilia Oedegaard, Maya Krikli, Michal Bakalenik-Gavry, Beatrice Shaham, Alex Galper, Einav Nili-Gal Yam. An App-Based Approach to Monitor Chemotherapy Symptoms [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 PO5-13-01.

The role of resilience and coping strategies as predictors of well-being in breast cancer patients

PurposeThis study investigated the role of resilience and coping strategies on breast cancer patients´ well-being using a structural equation model. To achieve this objective, a model previously developed by Mayordomo´s group was partially replicated using a longitudinal study design in an oncological sample. MethodPatients with breast cancer were recruited (N=166). Resilience was measured with the Mexican Resilience Measurement Scale, coping strategies with the Forms of Coping and Dimensions Scale and perception of the psychological well-being with a short-form of Ryff’s Scales of Psychological Well-Being at the start and end of adjuvant chemotherapy (T1 and T2 respectively). ResultsThe results showed stability in the variables over time and revealed differences with respect to Mayordomo´s model. The best predictor of well-being at T2 was well-being at T1. In addition, the model indicated that resilience had a direct impact on well-being through problem-focused coping. Indeed, resilience and problem-focused coping best explained well-being at T2. ConclusionsBoth at the start and end of adjuvant chemotherapy for breast cancer, problem-focused coping positively predicted resilience, which in turn was a positive predictor of well-being. On the other hand, emotion-focused coping showed no association with resilience or well-being. As part of the multidisciplinary cancer team, oncology nurses have a key role to play in promoting resilience and problem-focused coping as an important goal of psychosocial interventions in breast cancer patients.

Hypertension Severity and Declines in Left Ventricular Ejection Fraction Among Women Receiving Adjuvant Chemotherapy for Breast Cancer (WF-97415 UPBEAT).

Hypertension is a risk factor for experiencing left ventricular ejection fraction (LVEF) declines during receipt of potentially cardiotoxic breast cancer (BC) treatment. We sought to determine whether the hypertension stage is associated with LVEF decline during BC treatment. Across 24 centers, cardiac magnetic resonance measures of LVEF and brachial arterial blood pressure (BP) measurements were performed in women with stages I to III BC before and 3 months after initiating potentially cardiotoxic chemotherapy. Using multivariable analysis, we assessed in a blinded fashion the association between 3-month ΔLVEF and precancer treatment American Heart Association/American College of Cardiology stages of hypertension. Among 204 women, age averaged 56±1 years with 75% being White and 20% of Black race. Participants received anthracycline (45.6%), trastuzumab (22.5%), cyclophosphamide (52.9%), or paclitaxel (50%). After accounting for pretreatment LVEF, diabetes status, tobacco use, age, the number of antihypertensive medications, and body mass index, those with stage II hypertension experienced an LVEF decline of -2.89% ([95% CI, -0.69% to -5.19%]; P=0.01) relative to individuals with normal BP. Other stages saw nonsignificant declines relative to normal BP to elevated BP (-1.63% [95% CI, -0.62% to 3.88%]; P=0.16) and stage I hypertension (-0.94% [95% CI, -0.90% to 2.78%]; P=0.32). Compared with women receiving treatment for BC with normal BP, there is a stronger association of decline in LVEF in women with stage II hypertension relative to women with other hypertension stages. This raises the possibility that stage along with hypertension presence may be associated with an increased risk for the LVEF decline among women receiving potentially cardiotoxic chemotherapy for BC. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02791581 and NCT01719562.

Effects of physical exercise during adjuvant chemotherapy for breast cancer on long-term tested and perceived cognition: results of a pragmatic follow-up study

PurposeCancer-related cognitive impairment (CRCI) following chemotherapy is commonly reported in breast cancer survivors, even years after treatment. Data from preclinical studies suggest that exercise during chemotherapy may prevent or diminish cognitive problems; however, clinical data are scarce.MethodsThis is a pragmatic follow-up study of two original randomized trials, which compares breast cancer patients randomized to exercise during chemotherapy to non-exercise controls 8.5 years post-treatment. Cognitive outcomes include an online neuropsychological test battery and self-reported cognitive complaints. Cognitive performance was compared to normative data and expressed as age-adjusted z-scores.ResultsA total of 143 patients participated in the online cognitive testing. Overall, cognitive performance was mildly impaired on some, but not all, cognitive domains, with no significant differences between groups. Clinically relevant cognitive impairment was present in 25% to 40% of all participants, regardless of study group. We observed no statistically significant effect of exercise, or being physically active during chemotherapy, on long-term cognitive performance or self-reported cognition, except for the task reaction time, which favored the control group (β = -2.04, 95% confidence interval: -38.48; -2.38). We observed no significant association between self-reported higher physical activity levels during chemotherapy or at follow-up and better cognitive outcomes.ConclusionIn this pragmatic follow-up study, exercising and being overall more physically active during or after adjuvant chemotherapy for breast cancer was not associated with better tested or self-reported cognitive functioning, on average, 8.5 years after treatment. Future prospective studies are needed to document the complex relationship between exercise and CRCI in cancer survivors.

Clinical impact of delaying initiation of adjuvant chemotherapy in patients with early triple negative breast cancer

PurposeThe optimal time to initiation of adjuvant chemotherapy (TTAC) for triple negative breast cancer (TNBC) patients is unclear. This study evaluates the association between TTAC and survival in TNBC patients.MethodsWe conducted a retrospective study using data from a cohort of TNBC patients diagnosed between January 1, 2010 to December 31, 2018, registered in the Tumor Centre Regensburg was conducted. Data included demographics, pathology, treatment, recurrence and survival. TTAC was defined as days from primary surgery to first dose of adjuvant chemotherapy. The Kaplan–Meier method was used to evaluate impact of TTAC on overall survival (OS) and 5-year OS.ResultsA total of 245 TNBC patients treated with adjuvant chemotherapy and valid TTAC data were included. Median TTAC was 29 days. The group receiving systemic therapy within 22 to 28 days after surgery had the most favorable outcome, with median OS of 10.2 years. Groups receiving systemic therapy between 29–35 days, 36–42 days, and more than 6 weeks after surgery had significantly decreased median survival, with median OS of 8.3 years, 7.8 years, and 6.9 years, respectively. Patients receiving therapy between 22–28 days had significantly better survival compared to those receiving therapy between 29–35 days (p = 0.043), and patients receiving therapy after 22–28 days also demonstrated significantly better survival compared to those receiving therapy after more than 43 days (p = 0.033).ConclusionTiming of adjuvant systemic therapy can influence OS in TNBC patients. Efforts should be made to avoid unnecessary delays in administering chemotherapy to ensure timely initiation of systemic therapy and optimize patient outcomes.

Are depression and poor sleep quality a major problem in Turkish Women receiving chemotherapy for breast cancer?

The aim of this study was to evaluate depression and sleep quality in Turkish women receiving neoadjuvant or adjuvant chemotherapy for breast cancer and investigate their relationship. This cross-sectional, descriptive, and analytical study included 183 patients who received chemotherapy for non-metastatic breast cancer. Data were collected using the Beck Depression Inventory-II, the Pittsburgh Sleep Quality Index, and a disease-related/sociodemographic information form. The mean age of the participants was 50.2 years, and 50.3% were in menopause. The mean Beck Depression Inventory-II score was 19.64±10.4. Mild depression was detected in 25.7% (n=47) of the women, and moderate or severe depression in 55.2% (n=101). The mean global score of sleep quality was found to be 8.28±2.62, and the majority of the participants (79.7%, n=146) had poor sleep quality. There was a positive correlation (p<0.001, r=0.43) between depression and sleep quality scores. While a negative correlation was found between depression scores and age (p<0.001, r=0.26), the surgical procedure performed did not significantly affect depression scores (p=0.705). Additionally, depression scores were positively correlated with sleep duration (p<0.001, r=0.42) and sleep latency (p=0.01, r=0.48). Very high rates of depression and poor sleep quality were detected among Turkish women receiving neoadjuvant or adjuvant chemotherapy for breast cancer. The entire healthcare team involved in the treatment process should take this relationship into consideration and use the necessary preventive and therapeutic methods.

Curative intent chemotherapy-induced alterations in specific qEEG markers of cognition in patients with breast cancer

Objectives: Chemotherapy-induced cognitive impairment is a gruesome outcome of chemotherapy among breast cancer survivors. Electroencephalogram (EEG) power measurement is a known sensitive neurophysiologic correlate of cancer treatment-related cognitive dysfunction. The objective of this study was to assess the changes in specific quantitative EEG markers of cognition among breast cancer patients before, immediately, and three months after chemotherapy. Materials and Methods: Twenty-three women planning to undergo adjuvant chemotherapy for breast cancer underwent EEG assessment before, immediately, and three months after chemotherapy. Repeated measures analysis of variance was used to analyse the data. Post hoc pairwise comparison was done with Bonferroni correction to determine the pair in which the difference existed. Results: A significant increase in resting state EEG total power was observed (P = 0.012) after chemotherapy in the frontal area. The relative alpha power (RAP) significantly decreased with chemotherapy (P = 0.039), with post hoc pairwise comparison with Bonferroni correction revealing the significant decline to be present immediately after chemotherapy (P = 0.036) only over the posterior channels. Furthermore, the alpha-to-theta ratio (ATR) over posterior areas decreased (P = 0.012) both after completion of chemotherapy (P = 0.039) as well as three months after chemotherapy (P = 0.048). However, similar changes were not observed over frontal areas. Conclusion: Chemotherapy induces enhanced frontal power with a coincidental decline in RAP and ATR in the posterior areas.

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.

Usefulness of Indian Diabetes Risk Score in Predicting Treatment-Induced Hyperglycemia in Women Undergoing Adjuvant Chemotherapy for Breast Cancer

In the curative treatment of cancer with adjuvant chemotherapy, antineoplastic drugs, along with glucocorticoids, can induce hyperglycemia. The objective of this study was to assess the utility of the Indian Diabetes Risk Score (IDRS) in predicting treatment-induced hyperglycemia in women who were nondiabetic and normoglycemic at the start of chemotherapy. This prospective study was conducted with nondiabetic women who required adjuvant chemotherapy. Participants voluntarily completed the IDRS, providing information on age, waist circumference, family history of diabetes, and physical activity. Chemotherapy-induced hyperglycemia was defined as fasting blood glucose levels ≥100 mg/dL or random blood glucose levels ≥140 mg/dL during treatment. Data were categorized into women who developed hyperglycemia and those who remained normoglycemic during treatment and were analyzed using Fisher's exact test. A significance level of p &lt; 0.05 was applied. Receiver operating characteristic (ROC) curves were constructed to validate the IDRS for predicting hyperglycemia. A total of 208 women met the inclusion criteria and participated in the study. The results revealed that 38.93% (81/208) developed hyperglycemia by the end of chemotherapy, as observed during their first follow-up after treatment. Fisher's exact test demonstrated a significant difference in the total IDRS score and its domains, including family history, physical activity, and waist circumference (p = 0.017–&lt; 0.001), but not age. ROC analysis indicated that an IDRS score above 60 increased the likelihood of developing hyperglycemia, with a sensitivity of 81.3%, specificity of 54.7%, and an area under the curve of 0.727. These findings suggest that the IDRS is a sensitive tool for predicting adjuvant chemotherapy-induced hyperglycemia in breast cancer patients without diabetes. To the best of the authors' knowledge, this is the first study to evaluate the utility of the IDRS in predicting treatment-induced hyperglycemia in women undergoing adjuvant chemotherapy for breast cancer. Ongoing efforts are focused on understanding the underlying mechanisms and strategies for mitigation.

Benefit of adjuvant chemotherapy in lymph node-negative, T1b and T1c triple-negative breast cancer.

Current guidelines recommendations regarding chemotherapy in small (T1b and T1c), node-negative triple-negative breast cancer (TNBC) differ due to lack of high-quality data. Our study aimed to assess the benefit of adjuvant chemotherapy in patients with T1bN0M0 and T1cN0M0 TNBC. We obtained data from the Surveillance, Epidemiology, and End Results database for patients with node-negative, T1b/T1c TNBC diagnosed between 2010 and 2020. Logistic regresion models assessed variables associated with chemotherapy administration. We evaluated the effect of chemotherapy on overall survival (OS) and breast cancer specific survival (BCSS) with Kaplan-Meier methods and Cox proportional hazards methods. We included 11,510 patients: 3,388 with T1b and 8,122 with T1c TNBC. During a median follow-up of 66 months, 305 patients with T1b and 995 with T1c died. After adjusting for clinicopathological, demographic and treatment factors, adjuvant chemotherapy improved OS in T1b TNBC (HR, 0.52; 95% CI, 0.41-0.68 p < 0.001) but did not improve BCSS (HR, 0.70; 95% CI, 0.45-1.07; p = 0.10); the association between chemotherapy and BCSS was not statistically significant in any subgroup. In T1c TNBC, adjuvant chemotherapy improved OS (HR, 0.54; 95% CI, 0.47-0.62; p < 0.001) and BCSS (HR, 0.79; 95% CI, 0.63-0.99; p = 0.043); the benefit of chemotherapy in OS varied by age (Pinteraction=0.024); moreover, the benefit in BCSS was similar in all subgroups. Our study results support the use of adjuvant chemotherapy in patients with node-negative, T1c TNBC. Patients with node-negative, T1b TNBC had excellent long-term outcomes; furthermore, chemotherapy was not associated with improved BCSS in these patients.

Impact of body mass index and its change on survival outcomes in patients with early breast cancer: A pooled analysis of individual-level data from BCIRG-001 and BCIRG-005 trials.

The relationships between body mass index (BMI) and survival rates are complex, and have not been thoroughly investigated in breast cancer patients who received adjuvant chemotherapy. We collected data on 2394 patients from two randomized, phase III clinical trials that investigated adjuvant chemotherapy in breast cancer identified in Project Data Sphere. The objective was to examine the effect of baseline BMI, BMI after adjuvant chemotherapy, and BMI change from baseline to post-adjuvant chemotherapy on disease-free survival (DFS) and overall survival (OS). Restricted cubic splines were used to examine potential non-linear associations between continuous BMI value and survival. Stratified analyses involved chemotherapy regimens. Severe obesity (BMI≥40.0kg/m2) at baseline was independently associated with worse DFS (hazard ration [HR]=1.48, 95% confidence interval [CI] 1.02-2.16, P=0.04) and OS (HR=1.79, 95%CI 1.17-2.74, P=0.007) compared with underweight/normal weight (BMI≤24.9kg/m2). A BMI loss >10% was also an independent prognostic factor for adverse OS (HR=2.14, 95%CI 1.17-3.93, P=0.014). Stratified analyses revealed that severe obesity adversely affected DFS (HR=2.38, 95%CI 1.26-4.34, P=0.007) and OS (HR=2.90, 95%CI 1.46-5.76, P=0.002) in the docetaxel-based group, but not in the non-docetaxel-based group. Restricted cubic splines revealed a "J-shaped" association of baseline BMI with risk of recurrence or all-cause death, and this relationship was more pronounced in the docetaxel-based group. In early breast cancer patients treated with adjuvant chemotherapy, baseline severe obesity was significantly linked to worse DFS and OS, and a BMI loss over 10% from baseline to post-adjuvant chemotherapy also negatively affected OS. Moreover, the prognostic role of BMI might differ between docetaxel-based and non-docetaxel-based groups.

Comparative Study between Results of Neo Adjuvant Chemotherapy and Upfront Surgery in Breast Cancer in Aswan Oncology Center: Cohert Study

Comparative Study between Results of Neo Adjuvant Chemotherapy and Upfront Surgery in Breast Cancer in Aswan Oncology Center: Cohert Study

Protocol for the ASTRO study (SSOP-01): a multicentre prospective cohort study investigating adverse events based on electronic patient-reported outcomes in patients with breast cancer after adjuvant chemotherapy

IntroductionSymptom-related adverse events associated with perioperative chemotherapy in patients with breast cancer include short-term adverse events such as nausea and vomiting. However, changes in the severity and duration of prolonged...

Changes in leukoencephalopathy and serum neurofilament after (neo)adjuvant chemotherapy for breast cancer

BackgroundPrevious case studies have provided evidence for chemotherapy-induced leukoencephalopathy in patients with breast cancer. However, prospective research is lacking. Hence, we investigated leukoencephalopathy before and after chemotherapy and its association with a serum neuroaxonal damage marker. MethodsThis prospective cohort study included 40 patients receiving chemotherapy for breast cancer, and two age- and education-matched control groups, recruited between 2018 and 2021 (31–64 years of age). The latter control groups consisted of 39 chemotherapy-naïve patients and 40 healthy women. Fluid-attenuated inversion-recovery magnetic resonance imaging was used for lesion volumetry (total, juxtacortical, periventricular, infratentorial, and deep white matter) and blood serum to measure neurofilament light chain (NfL) levels. Acquisition took place pre-chemotherapy and three months and one-year post-chemotherapy, or at corresponding intervals. Within/between group differences were compared using robust mixed-effects modeling, and associations between total lesion volume and serum-NfL with linear regression. ResultsStronger increases in deep white matter lesion volumes were observed shortly post-chemotherapy, compared with healthy women (ßstandardized=0.09, pFDR<0.001). Increases in total lesion volume could mainly be attributed to enlargement of existing lesions (mean±SD, 0.12±0.16 mL), rather than development of new lesions (0.02±0.02 mL). A stronger increase in serum-NfL concentration was observed shortly post-chemotherapy compared with both control groups (ß>0.70, p<0.004), neither of which showed any changes over time, whereas a decrease was observed compared with healthy women one-year post-chemotherapy (ß=-0.54, p = 0.002). Serum-NfL concentrations were associated with lesion volume one-year post-chemotherapy (or at matched timepoint; ß=0.36, p = 0.010), whereas baseline or short-term post-therapy levels or changes were not. ConclusionThese results underscore the possibility of chemotherapy-induced leukoencephalopathy months post-treatment, as well as the added value of serum-NfL as a prognostic marker for peripheral/central neurotoxicity. Translational relevancePrevious case studies have provided evidence of chemotherapy-induced leukoencephalopathy in patients with breast cancer. However, prospective studies to estimate longitudinal changes are currently missing. In this study, we used longitudinal fluid-attenuated inversion-recovery magnetic resonance imaging to assess white matter lesion volumes in patients treated for non-metastatic breast cancer and healthy women. Our findings demonstrate that chemotherapy-treated patients exhibit stronger increases in lesion volumes compared with healthy women, specifically in deep white matter, at three months post-chemotherapy. Increases could mainly be attributed to enlargement of existing lesions, rather than development of new lesions. Last, serum concentrations of neurofilament light chain, a neuroaxonal damage marker, increased shortly after chemotherapy and long-term post-chemotherapy levels were associated with lesion volumes. These findings highlight the potential of this non-invasive serum marker as a prognostic marker for peripheral and/or central neurotoxicity. Implementation in clinical practice could aid in therapeutic decisions, assessing disease activity, or monitoring treatment response.

WTP8.13 Expression of Integrin Subunit Alpha 7 (ITGA7) predicts survival from breast cancer following adjuvant chemotherapy

Abstract Aim To investigate the relevance of ITGA7 expression with respect to clinical prognostic markers, disease-free survival (DFS) and disease-specific survival (DSS) after adjuvant chemotherapy in breast cancer. Methods Breast cancer tissue was obtained from a tissue microarray comprising all tumour subtypes in 305 women. Expression of ITGA7 was determined by immunohistochemistry. Relative expression of ITGA7 was assessed. Results Overall, it was concluded that ITGA7 levels were independent of the clinical prognostic markers, tumour grade, lymph node status, oestrogen receptor status and molecular subtype. Kaplan-Meier survival analyses showed, high ITGA7 nuclear protein expression was associated with longer DFS, mean 647 days; p=0.036 in the whole cohort. The same trend was visible for ITGA7 cytoplasmic protein expression albeit that this was not significant. Sub-analysis of ER-positive breast cancers also showed that high ITGA7 nuclear protein expression was associated with both a longer DFS and DSS, 682 days, p=0.05 and 604 days, p=0.005 respectively. Kaplan-Meier survival analysis was performed separately on the patients who received either taxanes with anthracyclines or anthracyclines without taxanes. This demonstrated a significant increase in DFS, 806 days; p=0.004 in primary breast cancers that had high ITGA7 nuclear protein expression in the group that received anthracycline-based chemotherapy alone. No statistically significant difference in DFS or DSS was noted between high and low ITGA7 expression in the group that received anthracycline and taxane based adjuvant chemotherapy. Conclusion ITGA7 has been identified as impacting upon DFS and DSS in breast cancer potentially via the modification of chemoresponse.

Screening Single Nucleotide Polymorphisms Predicting the Efficacy of Electroacupuncture for Fatigue Treatment in Patients with Breast Cancer Following Adjuvant Chemotherapy.

Chemotherapy-induced fatigue reduces not only the quality of life of patients but also effect their recurrence-free survival rate. Although electroacupuncture can relieve fatigue, it has limited affect on some patients. Therefore, appropriate biomarkers are needed to help screen patients who can benefit from electroacupuncture treatment of fatigue. We conducted this study to explore the predictive ability of SNPs on the efficacy of electroacupuncture in the treatment of fatigue in patients with breast cancer after adjuvant chemotherapy. Our study included breast cancer patients with fatigue after receiving paclitaxel and/or anthracycline based adjuvant chemotherapy. The patients were divided into the electroacupuncture group and the control group. The electroacupuncture treatment group received adjuvant chemotherapy and electroacupuncture treatment, while the control group only received adjuvant chemotherapy, and then compared the fatigue relief degree of two groups. In addition, we used NCBI dbSNP and PharmGKB databases to select fatigue related genes and their SNPs. We collected peripheral blood from the included patients for SNPs typing, and recorded the efficacy of electroacupuncture to analyzed the correlation between different SNPs and therapeutic efficacy. The side effects of electroacupuncture treatment were also recorded. 76 patients in the electroacupuncture group and 48 patients in the control group were enrolled. In the electroacupuncture group, 63 patients (82.9%) experienced moderate to severe fatigue (BFI score > 3). After electroacupuncture treatment, the number of patients with a BFI score of > 3 was 46 (60.5%). Therefore, the fatigue symptoms of 26.9% patients were significantly improved (P < 0.05). In the control group, which did not receive electroacupuncture treatment, 40 of 48 patients had a BFI score of > 3. Following the same observation time used in the electroacupuncture group, 36 patients had a BFI score of > 3 points. Thus, fatigue was not significantly relieved in the control group (83.3% vs. 75.0%, P > 0.05). We included 56 patients in our analysis of the correlation between SNPs and electroacupuncture treatment effects. We divided the patients into an effective group and ineffective group according to therapeutic effects. Our results indicated that the effective rate of electroacupuncture treatment with IL1A rs3783550 AC and CC genotypes was higher than that with other genotypes (AC: 84.6%, CC: 81.8%, AA: 33.0%, P < 0.05). Similarly, the effective rate of electroacupuncture treatment with HTR1A rs6295 GG and CC genotypes was higher than that with other genotypes (GG: 63.0%, CC: 55.6%, GC: 18.2%, P < 0.05). However, no other genotypes were related to the effect of electroacupuncture treatment on fatigue. Our result showed that electroacupuncture has therapeutic effect on fatigue after adjuvant chemotherapy for breast cancer and the side effects are tolerable. In addition, IL1A rs3763550 and HTR1A rss6295 can predict the therapeutic effect of electroacupuncture on fatigue after adjuvant chemotherapy in breast cancer, which helps to better screen patients who can benefit from electroacupuncture treatment.

Survival Benefit of Adjuvant Chemotherapy in Node-Positive Breast Cancer With a 21-Gene Recurrence Score of 14 to 25: A Real-World Study Based on the Inverse Probability of Treatment Weighting Method

IntroductionThe role of recurrence score in predicting the benefits of adjuvant chemotherapy for lymph-node-positive breast cancer remains uncertain. We studied chemotherapy usage in patients with 1 to 3 positive lymph nodes and a recurrence score (RS) of 25 or lower to assess changes in clinical practice based on the RxPONDER trial. MethodsA retrospective study using the SEER database identified female patients diagnosed with ER-positive, HER2-negative breast cancer, 1 to 3 positive lymph nodes, and an RS of 25 or lower between 2010 and 2015. Patients were divided into nonchemotherapy and chemotherapy groups, with propensity score weighting to balance clinicopathologic factors. ResultsAmong 7965 patients, 5774 (72.5%) were in the nonchemotherapy group, while 2191 (27.5%) were in the chemotherapy group. Median follow-up was 39 months. Breast cancer accounted for 67 deaths, while 128 deaths were due to other causes. The weighted 5-year overall survival (OS) rates were 95.7% for the nonchemotherapy group and 97.2% for the chemotherapy group. For high-risk patients, the weighted 5-year OS rates were 95.2% and 97.0% for the nonchemotherapy and chemotherapy groups, respectively, with a significant absolute difference of 1.8% (P = .014). Multivariate analysis showed a significant difference in weighted hazard ratios for OS between the nonchemotherapy and chemotherapy groups in high-risk patients (hazard ratio: 0.64; 95% CI: 0.48-0.86). However, there were no significant differences in weighted hazard ratios for lower-risk patients, and similar results were observed for breast cancer-specific survival (BCSS). ConclusionPatients with ER-positive, HER2-negative breast cancer and 1 to 3 positive lymph nodes, assessed by a 21-gene RS of 0 to 25, exhibited heterogeneous prognosis. Adjuvant chemotherapy provided a significant survival benefit, especially for patients with RS of 14 to 25, particularly those with invasive ductal carcinoma (IDC) and 2 to 3 positive lymph nodes.

Cost-utility analysis of genomic profiling in early breast cancer in Colombia

BackgroundIn Colombia, the best strategy to establish indication for adjuvant chemotherapy in early breast cancer (EBC) remains unknown. This study aimed to identify the cost-utility of Oncotype DX™ (ODX) or Mammaprint™ (MMP) tests to establish the necessity of adjuvant chemotherapy.MethodsThis study used an adapted decision-analytic model to compare cost and outcomes of care between ODX or MMP tests and routine care without ODX or MMP tests (adjuvant chemotherapy for all patients) over a 5-year time horizon from the perspective of the Colombian National Health System (NHS; payer). Inputs were obtained from national unit cost tariffs, published literature, and clinical trial database. The study population comprised women with hormone-receptor-positive (HR +), HER2-negative, lymph-node-negative (LN0) EBC with high-risk clinical criteria for recurrence. The outcome measures were discounted incremental cost-utility ratio (ICUR; 2021 United States dollar per quality-adjusted life-year [QALY] gained) and net monetary benefit (NMB). Probabilistic (PSA) and deterministic sensitivity analysis (DSA) were performed.ResultsODX increases QALYs by 0.05 and MMP by 0.03 with savings of $2374 and $554 compared with the standard strategy, respectively, and were cost-saving in cost-utility plane. NMB for ODX was $2203 and for MMP was $416. Both tests dominate the standard strategy. Sensitivity analysis revealed that with a threshold of 1 gross domestic product per capita, ODX will be cost-effective in 95.5% of the cases compared with 70.2% cases involving MMP.DSA showed that the variable with significant influence was the monthly cost of adjuvant chemotherapy. PSA revealed that ODX was a consistently superior strategy.ConclusionsGenomic profiling using ODX or MMP tests to define the need of adjuvant chemotherapy treatment in patients with HR + and HER2 −EBC is a cost-effective strategy that allows Colombian NHS to maintain budget.