Breast Cancer Receiving Adjuvant Therapy Research Articles

Predictors of information needs among women with breast cancer receiving adjuvant therapy at Tikur Anbessa specialized hospital, Addis Ababa Ethiopia: a cross-sectional study

BackgroundWomen undergoing adjuvant therapy for breast cancer have diverse information needs that remain unfulfilled. Extensive research has shown that access to relevant information about their condition can significantly enhance the quality of life for these women, making it an essential part of cancer care. However, various clinical and socioeconomic factors influence the information needs of these women. Hence, the primary aim of this study is to identify predictors of the information needs of women undergoing adjuvant therapy for breast cancer. In addition, this study will also describe the preferred sources of information and the optimal timing for its acquisition.MethodsA facility-based cross-sectional study was undertaken at Tikur Anbessa Specialty Hospital, enlisting a cohort comprising 121 women undergoing adjuvant therapy for breast cancer. Trained interviewers administered an Amharic-translated Toronto information needs questionnaire specifically designed for breast cancer to assess the information needs of the study participants Statistical analysis was executed using the sophisticated software SPSS (version 25). Descriptive statistics were employed to summarize the variables of the study. A linear regression analyses was then carried out to identify notable predictors that significantly influenced the information needs of the women.ResultsThe total mean score for overall information needs in the current study was 194.30 (± 28.01), with a range scale of 142–260 and a standardized mean score of 3.74 (± 0.54). The disease and treatment domains had the highest information needs, with standardized mean scores (standard deviation) of 4.00 (± 0.54) and 3.77 (± 0.59), respectively. 95% of the participants sought information from healthcare professionals, and 67.7% of the women needed the information before beginning the treatments. Predictors of information needs were following a single treatment option (β = 12.68; 95% CI (0.68, 24.68); P = 0.039) and joining higher education and above (β = 17.1; 95% CI (1.47, 34.14); P = 0.033).ConclusionThe women exhibited a substantial demand for information. Healthcare professionals need to consider the women’s educational background and treatment status while delivering the needed information.

Longitudinal Trajectories of Memory Performance in Patients with Early-Stage Breast Cancer.

Background While breast cancer and its treatments may affect cognition, the longitudinal trajectories of cognition among those receiving differing cancer treatment types remain poorly understood. Prior research suggests hippocampal-prefrontal cortex network integrity may influence cognition, although how this network predicts performance over time remains unclear. Methods We conducted a prospective trial including 69 patients with early-stage breast cancer receiving adjuvant therapy and 12 controls. Longitudinal cognitive testing was conducted at four visits: pretreatment-baseline, 6-7 months, 14-15 months, and 23-24 months. Cognitive composite scores of episodic memory, executive functioning, and processing speed were assessed at each timepoint. Baseline structural MRI was obtained in a subset of these participants, and hippocampal and prefrontal cortex regional volumes were extracted. Results Longitudinal linear mixed modeling revealed significant group by time interactions on memory performance, controlling for age and education. Post hoc analyses revealed this effect was driven by patients treated with chemotherapy or chemotherapy plus hormone therapy, who demonstrated the least improvement in memory scores over time. Treatment group did not significantly influence the relationship between time and processing speed or executive functioning. Neither pretreatment hippocampal nor prefrontal volume differed between groups, and there were no significant group by time by baseline regional volume effects on cognition. Conclusion Patients with early-stage breast cancer treated with chemotherapy or chemotherapy plus hormone therapy benefit less from practice effects seen in healthy controls on memory tests. Loss of longitudinal practice effect may be a new and clinically relevant measure for capturing patients' experience of cognitive difficulties after treatment.

Abstract P4-10-16: Reactive stroma and trastuzumab resistance in HER2-positive early breast cancer

Abstract Purpose We investigated the value of reactive stroma as a predictor for trastuzumab resistance in patients with early HER2-positive breast cancer receiving adjuvant therapy. Experimental Design The pathological reactive stroma and the mRNA gene signatures that reflect reactive stroma in 209 HER2-positive breast cancer samples from the FinHer adjuvant trial were evaluated. Levels of stromal gene signatures were determined as a continuous parameter, and pathological reactive stromal findings were defined as stromal predominant breast cancer (SPBC; ≥50% stromal) and correlated with distant disease-free survival (DDFS). Results Gene signatures associated with reactive stroma in HER2-positive early breast cancer (N=209), were significantly associated with trastuzumab resistance in estrogen receptor (ER)-negative tumors (HR=1.27 p-interaction=0.014 [DCN], HR=1.58, p-interaction=0.027 [PLAU], HR=1.71, p-interaction=0.019 [HER2STROMA, novel HER2 stromal signature]), but not in ER-positive tumors (HR=0.73 p-interaction=0.47 [DCN], HR=0.71, p-interaction=0.73 [PLAU], HR=0.84; p-interaction=0.36 [HER2STROMA]). Pathological evaluation of HER2-positive/ER-negative tumors suggested an association between SPBC and trastuzumab resistance. Reactive stroma did not correlate with tumor-infiltrating lymphocytes (TILs), and the expected benefit from trastuzumab in patients with high levels of TILs was pronounced only in tumors with low stromal reactivity (SPBC <50%). Conclusions Reactive stroma in HER2-positive/ER-negative early breast cancer tumors may predict resistance to adjuvant trastuzumab therapy. Citation Format: Amir Sonnenblick, Mali Salmon-Divon, Roberto Salgado, Noam Pondé, Sibylle Loibl, Carsten Denkert, Heikki Joensuu, Pirkko-Liisa Kellokumpu-Lehtinen, Amos Azaria, Sherene Loi, Stefan Michiels, Christos Sotiriou. Reactive stroma and trastuzumab resistance in HER2-positive early breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-10-16.

Reactive stroma and trastuzumab resistance in HER2-positive early breast cancer.

We investigated the value of reactive stroma as a predictor for trastuzumab resistance in patients with early HER2-positive breast cancer receiving adjuvant therapy. The pathological reactive stroma and the mRNA gene signatures that reflect reactive stroma in 209 HER2-positive breast cancer samples from the FinHer adjuvant trial were evaluated. Levels of stromal gene signatures were determined as a continuous parameter, and pathological reactive stromal findings were defined as stromal predominant breast cancer (SPBC; ≥50% stromal) and correlated with distant disease-free survival. Gene signatures associated with reactive stroma in HER2-positive early breast cancer (N = 209) were significantly associated with trastuzumab resistance in estrogen receptor (ER)-negative tumors (hazard ratio [HR] = 1.27 p interaction = 0.014 [DCN], HR = 1.58, p interaction = 0.027 [PLAU], HR = 1.71, p interaction = 0.019 [HER2STROMA, novel HER2 stromal signature]), but not in ER-positive tumors (HR = 0.73 p interaction = 0.47 [DCN], HR = 0.71, p interaction = 0.73 [PLAU], HR = 0.84; p interaction = 0.36 [HER2STROMA]). Pathological evaluation of HER2-positive/ER-negative tumors suggested an association between SPBC and trastuzumab resistance. Reactive stroma did not correlate with tumor-infiltrating lymphocytes (TILs), and the expected benefit from trastuzumab in patients with high levels of TILs was pronounced only in tumors with low stromal reactivity (SPBC <50%). In conclusion, reactive stroma in HER2-positive/ER-negative early breast cancer tumors may predict resistance to adjuvant trastuzumab therapy.

Short-term combined exercise training improves cardiorespiratory fitness and autonomic modulation in cancer patients receiving adjuvant therapy.

The present study aimed to investigate the impact of a short-term exercise training (ET) on the cardiorespiratory fitness and autonomic modulation of women with breast cancer who were receiving adjuvant radiotherapy, chemotherapy or hormonotherapy. Eighteen women previously diagnosed with breast cancer receiving adjuvant radiotherapy, chemotherapy or hormone therapy were randomly allocated into breast cancer nonexercise (BC) and exercise groups (BC+Ex). Moreover, nine healthy physically inactive volunteers were recruited to compose the noncancer control group (CG). The BC+Ex group was underwent to a combined ET program, which was based on resistance, aerobic and flexibility exercises. ET was performed 3 times a week, on nonconsecutive days, for 4 weeks at the hospital room under the professional supervision. In turn, BC and CG remained without be engaged in physical exercise programs. Volunteers were evaluated regarding their cardiorespiratory fitness and autonomic modulation (i.e., time, frequency domains, and nonlinear [symbolic analysis]) before and after the end of the ET program. A priori, data indicate that women patients with breast cancer showed impaired exercise tolerance, as well as autonomic dysfunction in comparison with age-matched healthy control subjects. However, a 1-month combined ET program could reverse such impairments, so that after the intervention, BC+Ex and CG showing similar results in the cardiorespiratory test and heart rate variability analysis. In conclusion, data of the current study indicate that 1 month of ET is able to reverse impaired cardiorespiratory fitness and autonomic modulation in women with breast cancer receiving adjuvant therapy.

Nonalcoholic fatty liver disease after adjuvant therapy in nonmetastatic breast cancer.

9587 Background: Nonalcholic fatty liver disease (NAFLD) is an important health problem in the general population. Also NAFLD developing after treatment is very important in cases with cancer especially having long term life expectancy like breast cancer. The aim of this this study is to explore the rate and risk factors of NAFLD in cases with breast cancer receiving adjuvant therapy. Methods: In this prospective study, 201 cases with breast cancer treated by chemo and/or anti-hormonal treatment were included between years 2010-2012. Patients who had ductal carcinoma insitu and metastatic disease and also chronic HBV and HCV infections, chronic liver diseases with other reasons and liver cirrhosis were excluded. Body mass index (BMI) was calculated based on the following formula: weight in kilograms divided by height in meters squared. Diabetes mellitus, hypetension and hyperlipidemia, if there is in past medical history, were documented. NAFLD was deteced by abdominal ultrasound imaging and there was no history of alcohol consumption. Biopsy was performed in 2 patients who had refractory high transaminasis. Results: The patients were divided into three groups. Group I: Patients without NAFLD, Group II: Patients with NAFLD before cancer treatment, Group III: Patients with NAFLD after cancer treatment. There was no difference for age and menopousal status between three groups. Diabetes mellitus, hypetension and hyperlipidemiawere not important risk factors for the development of NAFLD after cancer treatment. (p values 0,085, 0,525, 0,207, respectively). BMI was found to be higher in cases with NAFLD and the occurrence of NAFLD was detected more frequently in obese patients (BMI&gt;30 kg/m2) (p=0,001). Tamoxifen, LHRH analougs and aromatase inhibitors were not found to be asociated with NAFLD (p=0,7, 0,8, 0,5, respectively) while the combination of fluorouracil, antharcycline and cyclophospamide was found to be a risk factor in the development of NAFLD (p=0,02). Conclusions: High BMI (both before and after treatment), obesity and fluorouracil, antharcycline and cyclophospamide combinationin were found to be important risk factors for the occurrence of NAFLD.

Epiphora and Canalicular Stenosis Associated With Adjuvant Docetaxel in Early Breast Cancer: Is Excessive Tearing Clinically Important?

Docetaxel, as a single agent or in combination, is widely used in the palliative treatment of many common solid tumors, including breast, lung, and prostate cancers. Docetaxel is also used in many of the adjuvant regimens in early breast cancer, including the docetaxel, carboplatin, and trastuzumab regimen, the docetaxel and cyclophosphamide combination, and those with or without an anthracycline or trastuzumab (docetaxel/doxorubicin/cyclophosphamide, fluorouracil/epirubicin/cyclophosphamide followed by docetaxel, doxorubicin/cyclophosphamide followed by docetaxel, and doxorubicin/cyclophosphamide followed by docetaxel plus trastuzumab). Adjuvant-based docetaxel may lead to well-known acute and chronic adverse events including neutropenic fever or infection, stomatitis, hypersensitive reaction, rash, fluid retention, peripheral neuropathy, and fatigue. The safety profile of docetaxel is schedule and dose dependent. Excessive tearing (epiphora) is a common adverse event reported in patients who receive docetaxel for metastatic disease. However, there is little published information about ocular toxicity, including epiphora, in the adjuvant setting. Two large docetaxel-based adjuvant phase III studies briefly reported docetaxel-related ocular toxicity. In the Breast Cancer International Research Group (BCIRG) trial 001, lacrimal disorder was reported in 11.3% versus 7.1% of patients who received TAC versus those who received fluorouracil/doxorubicin/ cyclophosphamide, respectively. In the Eastern Cooperative Oncology Group study 1199, grade 3 and 4 lacrimation was reported in 5% of patients who received weekly adjuvant docetaxel versus less than 1% of patients who received adjuvant paclitaxel once per week, paclitaxel once every 3 weeks, or docetaxel once every 3 weeks. Other ocular symptoms such as conjunctivitis were also reported in less than 1% in patients in this trial, including those who received docetaxel once per week. In the article that accompanies this editorial, Chan et al studied the prevalence of epiphora, canalicular stenosis, and nasolacrimal duct obstruction in patients with early-stage breast carcinoma who received adjuvant docetaxel-based combination chemotherapy. This is a large prospective report evaluating ocular toxicity in patients with early breast cancer receiving adjuvant therapy, although several previous studies have reported the association between docetaxel and epiphora and its anatomic correlates, canalicular stenosis and nasolacrimal duct obstruction, in patients with metastatic breast carcinoma. Our group published several reports, some dating back to 2001, on the incidence and severity of epiphora and its anatomic correlates in patients treated with docetaxel, initially in patients treated with docetaxel once every 3 weeks, and later in patients treated with docetaxel once per week. In a prospective randomized clinical trial in patients with metastatic breast cancer, we clearly demonstrated a higher incidence of canalicular stenosis and nasolacrimal duct obstruction in patients receiving docetaxel once per week compared with those receiving docetaxel once every 3 weeks. We also showed that a delay in intervention for patients receiving docetaxel once per week leads to a need for more complicated surgery and worse outcomes. In contrast to the metastatic setting, epiphora and its anatomic correlates, canalicular stenosis and nasolacrimal duct obstruction, have not been well studied previously in patients with early breast cancer. However, it has been recognized that docetaxel given every 3 weeks (not weekly), for a short overall treatment duration (9 to 18 weeks) in patients with metastatic breast cancer is associated with only mild to occasionally moderate ocular symptoms that resolve quickly. Thus, the prospective observations reported by Chan et al using similar docetaxel dosing schedules now confirm previous results that have been observed in the metastatic setting, but in a larger number of patients with early breast cancer. Chan et al reported several important clinical observations. They described rapid onset and high incidence of epiphora (86%). Nearly 70% of patients experienced epiphora before the third cycle. However, only six patients had short-lasting grade 3 epiphora. The authors did not observe any difference between short versus long regimens. However, the majority of patient received six cycles of adjuvant therapy, and we have clearly established that it is not the patients who receive docetaxel once every 3 weeks for short periods who are the subject of greatest concern. Rather, it is the patients who receive docetaxel once per week, or once every 3 weeks for extended periods (ie, patients receiving docetaxel for metastatic disease) who are at greatest risk of canalicular stenosis. In the study by Chan et al, nearly 20% of patients had asymptomatic partial lacrimal duct obstruction at baseline according to JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 31 NUMBER 17 JUNE 1

Psychological impact of exercise in women with breast cancer receiving adjuvant therapy: What is the optimal dose needed?

9074 Background: Several meta-analyses have examined the role of exercise interventions in improving psychological outcomes in cancer survivors but most did not focus on adjuvant therapy period and did not investigate the optimal dose of exercise needed. Methods: The present meta-analysis examines the impact of exercise interventions delivered at this particular period on fatigue, anxiety, depression and quality-of-life (QoL) as well as dose-response relationships between volume of prescribed exercise and these psychological outcomes. Randomized controlled trials that proposed an exercise intervention to breast cancer patients undergoing chemotherapy and/or radiotherapy were systematically identified and coded. Standardized mean differences (SMDs) of psychological outcomes were weighted by the inverse of their variances to obtain a pooled estimate using random effects model. Linear and quadratic regressions were carried out to explore dose-response relationships. Results: In total, 17 studies involving 1380 participants and 20 exercise interventions were included. Intervention subjects significantly reduced their fatigue and depression levels showing pooled effect sizes (EF) and their associated 95% confidence interval (95%CI) of -0.28 [95%CI: -0.54; -0.03] and -0.28 [95%CI: -0.46; -0.09] respectively. Levels of anxiety also appeared to be reduced but pooled estimate did not reach significance (p=0.06). Significantly increased QoL was observed: EF=0.34 [95%CI: 0.07; 0.62] favouring intervention. Consistent and significant inverse associations of weekly and total volume of prescribed exercise were observed with fatigue (F test: p=0.04, R²=0.19 and p=0.009, R²=0.26 respectively) and QoL (F test: p=0.01, R²=0.14 and p=0.02, R²=0.29 respectively), implying that SMDs magnitude decreased as exercise dose increased. Conclusions: Exercise intervention enhanced fatigue, depression and QoL in breast cancer patients undergoing adjuvant therapy. Prescription of relatively low doses of exercise (&lt;12 MET.h per week) consisting in approximately 90-120 min of weekly moderate physical exercise seems more efficacious in improving fatigue and QoL than higher doses.

A randomized double-blind placebo-controlled study of oral coenzyme Q10 to relieve self-reported cancer-treatment-related fatigue in newly diagnosed breast cancer patients.

9006 Background: Coenzyme Q10 (CoQ) is an antioxidant supplement with known cardioprotective effects and potential anticancer benefits. We performed a randomized, double-blind, placebo-controlled study of oral CoQ in female breast cancer patients to determine CoQ's effects on self-reported fatigue, depression and quality of life (QOL). Methods: Eligible women with newly diagnosed breast cancer and planned adjuvant chemotherapy were randomized to oral supplements of 300 mg CoQ or placebo, each combined with 300 IU Vitamin E, divided into three daily doses. Treatment was continued for 24 weeks. Participants were stratified by anthracycline (yes/no) and radiation therapy (yes/no). Blood tests, QOL measures, and serum CoQ and Vitamin E levels were obtained at baseline, 8, 16 and 24 weeks. Mixed effects models were used to assess treatment differences in outcomes over time. Results: Between 8/2004 and 3/2009, 236 women were enrolled. Treatment arms were well balanced with respect to age (range 28-85), PS (0, 1, 2) (91%, 8%, 4%), ethnicity (87% White/11%Black/2%Hispanic) and planned therapy (84% anthracycline; 61% RT). No serious adverse events were noted. At 24 weeks, there were no significant differences between the CoQ and placebo arms on the POMS-Fatigue (LS means 5.88 vs. 7.24, p = .27); FACIT-Fatigue (40.2 vs. 39.7, p = .77); FACT-B subscale (25.6 vs. 25.7, p = 0.92); or CES-D (10.1 vs. 10.5, p = 0.82). In the 86 pts with complete CoQ serum samples, baseline and 24 week CoQ levels in the CoQ and placebo arms were 0.72/1.98 and 0.77/0.82 μ g/mL, respectively. In this subset, higher CoQ levels were modestly associated with less fatigue. Conclusions: Supplementation with conventional doses of CoQ led to sustained increases in serum CoQ levels, but did not result in improved self-reported fatigue or QOL after 24 weeks of treatment in women with breast cancer receiving adjuvant therapy. The modest association between higher CoQ levels and less fatigue in patients with complete assays suggests that further exploration of the relationship between CoQ dose and self-reported fatigue may be warranted. Supported by NIH/NCI/DCP grant 3 U10 CA081851. No significant financial relationships to disclose.

Clinical relevance of single item quality of life indicators in cancer clinical trials.

We investigated the hypothesis that global single-item quality-of-life indicators are less precise for specific treatment effects (discriminant validity) than multi-item scales but similarly efficient for overall treatment comparisons and changes over time (responsiveness) because they reflect the summation of the individual meaning and importance of various factors. Linear analogue self-assessment (LASA) indicators for physical well-being, mood and coping were compared with the Hospital Anxiety and Depression Scale (HAD), the Mood Adjective Check List (MACL) and the emotional behaviour and social interaction scales of the Sickness Impact Profile (SIP) in 84 patients with early breast cancer receiving adjuvant therapy. Discriminant validity was investigated by multitrait-multimethod correlation, responsiveness by standardized response mean (SRM). Discriminant validity of the indicators was present at baseline but less under treatment. Responsiveness was demonstrated by the expected pattern among treatments (P = 0.008). In patients without chemotherapy, the SRMs indicated moderate (0.5–0.8) to large (>0.8) improvements in physical well-being (0.70), coping (0.92), HAD anxiety (0.89) and depression (1.19), and MACL mental well-being (0.68). In patients with chemotherapy for the first 3 months, small but clinically significant improvements (>).2) included mood (0.38), coping (0.41), HAD axiety (0.31) and MACL mental well-being (0.35). Patients with 6 months chemotherapy showed no changes. The indicators also reflected mood disorders (HAD) and marked psychosocial dysfunction (SIP) at baseline and under treatment according to pre-defined cut-off levels. Global indicators were confirmed to be efficient for evaluating treatments overall and changes over time. The lower reliability of single as opposed to multi-item scales affects primarily their discriminant validity. This is less decisive in large sample sizes. © 2001 Cancer Research Campaign http://www.bjcancer.com

Autologous bone marrow transplantation in metastatic breast cancer.

The use of adjuvant chemotherapy following the primary treatment of breast cancer has led to an increased disease-free survival. The outlook for patients who present with metastatic disease however remains dismal, with little improvement in survival in the last decade. A recent analysis by Bonadonna and his colleagues has demonstrated a strong influence of the dose of drugs administered on relapse-free survival in patients with breast cancer receiving adjuvant therapy and those with metastatic disease. The utilization of cryopreserved autologous bone marrow permits the use of more aggressive therapy without regard to marrow toxicity, the dose-limiting feature of many antineoplastic agents. Some of the questions and potential problems with the use of autologous marrow rescue in solid tumors is discussed. Preliminary data on a protocol to evaluate the role of high-dose cyclophosphamide and total body irradiation with autologous marrow transplantation in patients with metastatic breast carcinoma are presented.