Adjuvant Chemotherapy For Breast Cancer Research Articles

21-Gene Recurrence Score and Survival Outcomes in the Phase III Multicenter TAILORx Clinical Trial.

Recurrence score (RS) based on a 21-gene genomic assay is frequently used to estimate risk of distant recurrence for choice of adjuvant chemotherapy in breast cancer. It remains unclear whether RS is an independent prognostic factor for breast cancer-specific survival (BCSS) and overall survival (OS) in the TAILORx trial population. We evaluated the association of RS with BCSS and OS plus recurrence-free interval (RFI) and invasive disease-free survival (DFS) using multivariable Cox proportional hazards regression analysis, adjusting for clinicopathologic measures, in 8,916 patients with hormone receptor-positive, HER2-negative, node-negative breast cancer. Likelihood ratio (LR) test was used to assess the relative amount of prognostic information provided by RS to BCSS, OS, RFI, and DFS, comparatively. Event rates for BCSS, OS, RFI, and DFS were 1.7%, 5.2%, 5.6%, and 12.6%, respectively, by up to 11.6 years of follow-up. Compared with low-range RS (0-10), patients with midrange (11-25) and high-range (26-100) RS had inferior BCSS (adjusted hazard ratio [aHR], 5.12 [95% CI, 2.09-16.92] and 8.03 [95% CI, 2.91-28.47], respectively) and RFI (aHR, 1.68 [95% CI, 1.23-2.36] and 3.05 [95% CI, 2.02-4.67], respectively), independent of clinicopathologic factors. High-range score was associated with an increased risk of DFS (aHR, 1.56 [95% CI, 1.20-2.04]) but not significantly associated with OS (aHR, 1.44 [95% CI, 0.95-2.18]). Midrange score was associated with neither DFS (aHR, 1.15 [95% CI, 0.96-1.38]) nor OS (HR 1.14 [95% CI, 0.87-1.52]). LR-χ2 values were 83.0 and 65.1 for RFI and BCSS, respectively, and 17.5 and 33.6 for OS and DFS, respectively (P<.0001). RS is an independent measure for BCSS and recurrence prognoses relative to OS in early-stage breast cancer. It carries more prognostic information for breast cancer-specific outcomes.

Tailored Dose-Dense Versus Standard Adjuvant Chemotherapy for High-Risk Early Breast Cancer: End-of-Study Results of the Randomized PANTHER Trial.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Although dose-dense adjuvant chemotherapy administered once every 2 weeks leads to superior outcomes compared with standard regimens once every 3 weeks, the observed improvement is largely limited to studies using the suboptimal paclitaxel schedule once every 3 weeks as control. PANTHER is an international phase III trial which compared sequential epirubicin/cyclophosphamide and docetaxel administered either once every 2 or once every 3 weeks, with tailored dosing at the dose-dense schedule according to hematologic toxicity. In this end-of-study analysis, the median follow-up was 10.3 years. Compared with standard adjuvant chemotherapy, dose-dense treatment improved breast cancer recurrence-free survival (hazard ratio [HR], 0.80 [95% CI, 0.65 to 0.98]; P = .030), event-free survival (HR, 0.78 [95% CI, 0.65 to 0.94]; P = .009), and distant disease-free survival (HR, 0.79 [95% CI, 0.64 to 0.98]; P = .030) while the improvement in overall survival was not statistically significant (HR, 0.82 [95% CI, 0.65 to 1.04]; P = .109). To our knowledge, this is the first trial that confirms the benefit of a dose-dense regimen over a control regimen containing docetaxel once every 3 weeks.

Five-year follow-up of the OptiTrain trial on concurrent resistance and high-intensity interval training during chemotherapy for patients with breast cancer

The protocol predefined aim of this study is to assess sustained effects of the OptiTrain trial on several health outcomes, 5 years after the baseline assessment. The OptiTrain study was a prospective, randomised controlled trial with 240 patients with breast cancer undergoing adjuvant chemotherapy that compared the effects of 16 weeks of two exercise programs, RT-HIIT and AT-HIIT, with usual care (UC). After a 5-year follow-up, eligible participants were evaluated for the primary outcome of cancer-related fatigue (CRF) and secondary outcomes including quality of life, symptoms, muscle strength, cardiorespiratory fitness, body mass, physical activity, and sedentary behavior. Statistical analysis was conducted using linear mixed models adjusted for baseline values. Tumour profile and menopausal status were additionally adjusted for CRF. Mean differences (MD), 95% confidence intervals (CIs), and standardized effect sizes (ES) were reported. At the 5-year follow-up, there were no statistically significant differences in total CRF between the intervention groups and the UC group. RT-HIIT reported significantly reduced pain sensitivity at the gluteus MD = 79.00 (95% CI 10.17, 147.83, ES = 0.55) compared to UC. Clinically meaningful differences for an increase in cognitive CRF and cardiorespiratory fitness were observed for the AT-HIIT versus UC group, and for lower limb strength for the RT-HIIT versus UC group, albeit without statistical significance. Engaging in targeted exercise during adjuvant chemotherapy for breast cancer provides short-term benefits in reducing fatigue and maintaining physical function. However, our 5-year follow-up indicates that these effects are limited in the long term. This underscores the need to support breast cancer survivors maintain their PA levels throughout their survivorship journey.

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

Abstract Background Breast cancer is a global health problem, with more than 1 million cases of breast cancer diagnosed worldwide each year. Introduction of neoadjuvant chemotherapy (NACT) has dramatically changed the management of breast cancer. Aim and Objectives To compare the clinicopathological features, surgical procedures, and outcome parameters of primary and post-neoadjuvant chemotherapy breast conseravtive surgery, with the aim of comparing the outcomes in terms of ipsilateral breast tumor recurrence rates and over all free survival in the two groups. Subjects and Methods This was a Comparative study, was conducted in Aswan oncology center on (40) women diagnosed with breast cancer, divided into two groups: (Group A): 20 up front surgery patients then adjuvant chemoherapy, (Group B): 20 Neo adjuvant chemotherapy then surgery patients during 6 months. Result There was statistically significant difference between the two studied groups as regard Metastatic work up and local recurrence. Conclusion The neoadjuvant chemotherapy has a nearby significant impact on pathological complete response (PCR) in patients with breast cancer with no significant increased toxicity and has significant lower rates of metastasis compared to upfront surgery.Neoadjuvant chemotherapy followed by surgery is a safe and effective rather than conventional method (primary surgery followed by Adjuvant chemotherapy) in treatment of Breast cancer.

Adjuvant Chemotherapy for Breast Cancer in Older Adult Patients

Adjuvant Chemotherapy for Breast Cancer in Older Adult Patients

Effectiveness of increasing the scalp cooling duration to prevent alopecia during adjuvant chemotherapy for breast cancer: a randomized pilot study

PurposeAlopecia is a common side-effect of chemotherapy and can be extremely distressing to patients. Scalp cooling can be used to reduce hair loss, but the optimal duration of cooling remains unclear. Our aim was to determine whether increasing the duration of scalp cooling improves hair preservation.MethodsPatients with HER2-negative, non-metastatic, breast cancer received scalp cooling during adjuvant chemotherapy: three cycles of epirubicin/cyclophosphamide (EC) followed by three cycles of paclitaxel. The patients were randomly assigned to two groups. Group A (n=18) wore a Paxman cooling cap during each infusion and for 30 min post-infusion while Group B (n=19) wore the cap from 30 min before to 2 h after each infusion. All patients were asked to complete a questionnaire recording hair loss/regrowth, adverse events, and quality of life. Success of treatment was defined as <50% hair loss.ResultsThe success rates after each of the three cycles did not differ significantly between the two groups (EC: Group A: 40%, Group B: 44%; paclitaxel: Group A: 50%, Group B: 36%; p>0.05). Hair regrowth was significantly higher in Group B at the 8-week follow-up, but not at the 6-month follow-up. Head discomfort affected more patients in Group B than in Group A during the first session (94% vs. 62%, respectively; p=0.039).ConclusionLong duration scalp cooling during chemotherapy might increase patients’ discomfort and does not appear to improve hair preservation.

Estimating benefit from dose dense adjuvant chemotherapy for early breast cancer in the PANTHER randomized phase 3 trial.

521 Background: Adjuvant dose dense chemotherapy for early breast cancer improves patient outcomes across all subgroups compared with standard interval treatment. However, the effect of dose dense treatment based on individual patient risk and over time, and the performance of the PREDICT model at this setting are not well-studied. Methods: This is an exploratory analysis from the phase 3 PANTHER trial (NCT00798070) that compared adjuvant sequential epirubicin/cyclophosphamide (EC) and docetaxel (D) administered in either tailored dose dense (tDD EC/D, every 2 weeks) or standard interval schedule (FEC/D, every 3 weeks) to patients with high-risk resected early breast cancer. Dose tailoring in the experimental arm was performed according to a predefined algorithm based on hematologic and non-hematologic toxicity. We evaluated the performance of PREDICT in terms of calibration and discrimination in the entire cohort and subgroups of interest, conducted a subpopulation treatment effect pattern plot (STEPP) analysis and observed the relative treatment effect over time. Results: The intention-to-treat population consists of n=2003 randomized patients. Median follow-up was 10.3 years (interquartile range, 9.1 – 10.5 years). PREDICT consistently underestimated 5-year (absolute difference 1.4%) and 10-year overall survival (absolute difference 6.6%) in the entire population and across all subgroups, but mostly so in the highest risk patients where the difference between observed and predicted 10-year survival reached 20.4% for patients with tumors larger than 5 cm. Discriminatory accuracy was lower for 10-year than for 5-year survival (AUC 0.728 and 0.786, respectively), although the difference in model performance between the two treatment groups was small. In STEPP analysis, absolute benefit from tDD EC/D in the primary endpoint of breast cancer relapse free survival was stable across risk-defined overlapping subpopulations and ranged from 3.8% in the lowest risk patients to 3.6% in the highest risk ones. There was no evidence of differential treatment effect through time (pinteraction &gt;0.1 for all time-to-event endpoints). Conclusions: In this largely node-positive population, PREDICT consistently overestimated risk for death in all patient subgroups. We could not reliably identify any subgroup not benefiting from dose dense treatment, which should be the standard of care for primary resected high-risk breast cancer. Clinical trial information: NCT00798070 .

Patient factors associated with chemotherapy modifications: Results from the Optimal Breast Cancer Chemotherapy Dosing (OBCD) study.

520 Background: Understanding patient factors associated with an increased likelihood of receiving chemotherapy modifications is important for treatment planning and anticipating which patient groups might require extra support through the course of treatment. Methods: We have evaluated patient and tumor factors associated with chemotherapy modifications in a cohort of 9700 women receiving adjuvant chemotherapy for breast cancer at Kaiser Permanente Northern California (KPNC) and Kaiser Permanente Washington (KPWA) in the Optimal Breast Cancer Chemotherapy Dosing (OBCD) Study diagnosed between 2005-2019. The outcome variable, receipt of a ‘chemotherapy modification’ is defined as a composite representing any of the following deviations from the intended regimen: dose reduction &gt;10% (first cycle or overall), extensive delay (any single delay &gt;14 days), regimen change, or receipt of fewer cycles of any given drug than intended in the original chemotherapy plan. Multivariable-adjusted prevalence ratios (PR) and corresponding 95% confidence intervals (95% CI) were calculated using generalized linear models of the Poisson family with a log link-function and robust standard errors. Results: Several factors were associated with chemotherapy modifications. Notably, older age was associated with an increased likelihood of modifications (p-trend&lt;0.001), with adults aged 80+ years at diagnosis 1.93-fold more likely to experience modification than adults 18-39 years (95% CI: 1.50-2.50). Increased comorbidity and BMI were also associated with increased likelihood of modification (p-trend for both:&lt;0.001), with patients with a Charlson Comorbidity Index of 3+ (vs 0) having an PR of 1.33 (95% CI: 1.19-1.48) and those with a BMI of 35+ kg/m2 (vs &lt;25 kg/m2) having an PR of 1.53 (95% CI: 1.41-1.65). HER2+ status (PR HER2+ vs HER2-: 1.99 95% CI: 1.89-2.10) and higher stage of disease (PR IIIA vs I:1.24; 95% CI: 1.13-1.35; p-trend&lt;0.001) were associated with increased likelihood of chemotherapy modification, while hormone receptor positivity was associated with lower likelihood of modification (PR ER+ and/or PR+ vs ER-/PR-: 0.93; 95% CI: 0.88-0.99). Diagnosis in more recent years was also associated with decreased likelihood of modification (PR 2015-2019 vs 2004-2009: 0.70; 95% CI: 0.66-0.75), as was higher neighborhood income (PR Q4 vs Q1: 0.78; 95% CI: 0.72-0.84). Conclusions: Several patient-level and clinical factors were associated with chemotherapy modifications, including age, comorbidity, BMI, and ER/PR/HER2 status. Future research might focus on the groups noted to have increased risk of treatment modification to better understand the factors underlying these changes, as well as the impact on patient outcomes.

Clinical outcomes of patients with HER2-positive microinvasive breast cancer.

544 Background: Although previous studies have reported that adjuvant trastuzumab with paclitaxel resulted in excellent survival outcomes in small, node-negative HER2-positive breast cancer, the necessity of adjuvant chemotherapy in HER2-positive microinvasive breast cancer (MIBC) remains controversial. Methods: Between January 2000 and January 2020, women with curatively resected pT1mi N0 and/or N1mi in Asan Medical Center were retrospectively identified and their survival outcomes including invasive disease-free survival (IDFS, excluding second primary cancer), distant recurrence-free survival (DRFS), and overall survival (OS) and the effect of adjuvant chemotherapy were analyzed. Results: A total of 833 patients were included. The median age was 51 years, and 51% (n = 426) were premenopausal. Pathologic nodal stage was pN0 in 96% (n = 799) and pN1mi in 0.7% (n = 6), and estrogen receptor (ER) was positive in 30% (n = 247). Adjuvant chemotherapy was administered to 18% (n = 147) of patients, of which 95% were fluorouracil-based. Six patients (0.7%) received adjuvant trastuzumab. With the median follow-up of 118.7 months, the 8-year IDFS and DRFS rates were 90.6% (95% CI, 88.4-92.7), and 97.3% (95% CI, 96.1-98.4), respectively, and the 8-year OS were 98.6% (95% CI, 97.8-99.5). IDFS did not differ by adjuvant chemotherapy, as the 8-year IDFS rates for patients who did and did not receive adjuvant chemotherapy were 91.1% (95% CI, 86.6-95.8) and 90.3% (95% CI, 87.9-92.8), respectively ( p = 0.930). The lack of differences in IDFS by chemotherapy was consistent across subgroups including pre-/postmenopausal patients, grade 1-2/3 tumors, and ER-negative diseases. Conclusions: In HER2-positive MIBC, a clinically meaningful proportion of patients experience IDFS events with long-term follow-up. The role of modern adjuvant chemotherapy regimens, as well as the role of adjuvant trastuzumab, should be further explored in this early-stage patient population.

Assessing the feasibility and cost-effectiveness of all oral adjuvant chemotherapy (cyclophosphamide, methotrexate, capecitabine) in high-risk hormone receptor positive breast cancer.

TPS616 Background: Women with high-risk HR+/HER2- breast cancer (BCA) receive additional chemotherapy to reduce disease recurrence. Preferred Taxane and Anthracycline based chemotherapy regimens have debilitating side effects such as cardiotoxicity, leukemia, peripheral neuropathy, severe fatigue, alopecia, downtime which are more common in black women thereby necessitating dose reductions. Metronomic cyclophosphamide, methotrexate, 5-fluourouracil (CMF) is an option but less preferred due to frequent dosing and longer therapy duration. Head-to-head comparison of CMF to anthracycline-based chemotherapy conducted 3 decades ago in early-stage BCA showed anthracycline benefit was driven by HER2+ disease with no benefit for HR+/HER2- BCA. Head-to-head comparison trials of CMF and Taxane-based regimen have not been conducted but single institution data suggest similar disease-free and similar overall survival but different toxicity profiles favoring CMF. In our ongoing trial, we converted all three chemotherapy drugs in CMF regimen to an all-oral regimen namely oral Cyclophosphamide, oral Methotrexate, oral Capecitabine (CMC) with the potential benefit of increased patient convenience, decreased costs (oral agents are generic; no chair time; no growth factors), and improved toxicity profile (low rates of grade III neutropenia, no port complications, no alopecia). This trial in progress aims to evaluate the feasibility of oral CMC by measuring the relative dose intensity in addition to the safety and tolerability of oral CMC. We hypothesize that 80% of patients will receive &gt;85% of the intended dose of oral CMC. Methods: This is a Phase II, single arm, non-randomized study enrolling 25 patients with high-risk early-stage HR+ HER2- breast cancer to receive oral CMC regimen based on dose conversion equivalent bioavailability with conventional metronomic CMF chemotherapy. Enrolled patients will receive adjuvant therapy of oral cyclophosphamide 60 mg/m2 PO days 1-21 continuously, Methotrexate 15 mg/m2 PO Day 1, 8, and 15 and Capecitabine 650 mg/m2 PO BID Day 1- 14 to be given every 21 days for 8 cycles. The primary objective is to assess feasibility which is defined as 80% of patients (greater than 20 patients) maintaining a relative dose intensity (RDI) &gt; 85%. The RDI is calculated as the ratio of the actual dose intensity/standard dose intensity; the average RDI for oral CMC regimen is the sum of RDI for each drug divided by 3. This study will be stopped if &gt;25% of patients report Grade 4+ toxicity on oral CMC. The secondary objectives will assess quality of life as reported by the patients and report adverse effects. Clinical trial information: NCT06085742 . [Table: see text]

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. MethodsThe study was a longitudinal observational survey. Patients 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.

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

PurposeTo report the prospective long-term outcome data of patients whose chemotherapy decision was guided by the EndoPredict test.MethodsPatients 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.Results368 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).ConclusionEndoPredict 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 &amp;gt; 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 Impact of Neoadjuvant Chemotherapy on Patients With T1N0M0 Triple-Negative and HER-2 Positive Breast Cancer: A Retrospective Analysis Based on the SEER Database

BackgroundThe utilization of neoadjuvant chemotherapy (NAC) originated in the treatment of locally advanced breast cancer (BC). Our study is designed to elucidate the effects of NAC on patients with T1N0M0 triple-negative and HER-2 positive BC. MethodsThis study involved the selection of 10,614 patients diagnosed with T1N0M0 triple-negative and HER-2 positive breast cancer (BC) from the surveillance, epidemiology, and end results (SEER) database. To ascertain the impact of neoadjuvant chemotherapy (NAC) on T1a, T1b, and T1c N0M0 BC, we conducted multivariate Cox regression analyses. Similarly, we performed multivariate Cox regression analyses to compare the effects of neoadjuvant chemotherapy against adjuvant chemotherapy on T1N0M0 BC. The Kaplan-Meier method was employed to delineate survival curves for different molecular subtypes and clinical stages. ResultsThe data results from the SEER database reveal a significant enhancement of overall survival (OS) in T1c BC patients as a result of NAC. For T1b BC patients, NAC does not present any significant effect. Contrarily, NAC seems to adversely impact the OS of T1a triple-negative BC patients. However, the prognosis comparison between neoadjuvant and adjuvant chemotherapy for T1N0M0 breast cancer did not show any significant difference, with the exception of T1a triple-negative BC. ConclusionsPatients with T1cN0M0 triple-negative and HER-2 positive BC may derive OS benefits from NAC. Additionally, NAC could be detrimental to T1a triple-negative BC.

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.

Personalized chemotherapy selection for patients with triple-negative breast cancer using deep learning.

Potential uncertainties and overtreatment exist in adjuvant chemotherapy for triple-negative breast cancer (TNBC) patients. This study aims to explore the performance of deep learning (DL) models in personalized chemotherapy selection and quantify the impact of baseline characteristics on treatment efficacy. Patients who received treatment recommended by models were compared to those who did not. Overall survival for treatment according to model recommendations was the primary outcome. To mitigate bias, inverse probability treatment weighting (IPTW) was employed. A mixed-effect multivariate linear regression was employed to visualize the influence of certain baseline features of patients on chemotherapy selection. A total of 10,070 female TNBC patients met the inclusion criteria. Treatment according to Self-Normalizing Balanced (SNB) individual treatment effect for survival data model recommendations was associated with a survival benefit (IPTW-adjusted hazard ratio: 0.53, 95% CI, 0.32-8.60; IPTW-adjusted risk difference: 12.90, 95% CI, 6.99-19.01; IPTW-adjusted the difference in restricted mean survival time: 5.54, 95% CI, 1.36-8.61), which surpassed other models and the National Comprehensive Cancer Network guidelines. No survival benefit for chemotherapy was seen for patients not recommended to receive this treatment. SNB predicted older patients with larger tumors and more positive lymph nodes are the optimal candidates for chemotherapy. These findings suggest that the SNB model may identify patients with TNBC who could benefit from chemotherapy. This novel analytical approach may provide debiased individual survival information and treatment recommendations. Further research is required to validate these models in clinical settings with more features and outcome measurements.