Disease-free Breast Cancer Survivors Research Articles

The relationship between morbidity after axillary surgery and long-term quality of life in breast cancer patients: The role of anxiety

Aims Although arm/shoulder morbidity after sentinel lymph node biopsy (SLNB) and/or axillary lymph node dissection (ALND) has been studied before, information is lacking concerning self-imposed restrictions in activities and long-term consequences of both surgical procedures in relationship to quality of life (QoL) and anxiety. Methods Eighty-nine disease-free breast cancer survivors completed a set of questionnaires assessing arm/shoulder symptoms, limitations in daily life, anxiety and QoL. Also, the ipsi- and contra lateral arm circumference and the range of shoulder motion were measured. Results Fifty-one women had SLNB, 25 had SLNB followed by ALND and 13 had ALND. Although ALND patients experienced more shoulder symptoms, limitations in daily life and imposed more restrictions on themselves than SLNB patients, no significant differences during physical examination were found. A decreased range of motion and a higher score on trait anxiety resulted in a lower QoL. Trait anxiety and perceived limitations in daily life predicted long-term quality of life. Conclusions There is a discrepancy between experienced and measured limitations in range of shoulder motion. Anxiety and self-imposed restrictions play an important role in predicting long-term QoL and should get the necessary attention when addressing shoulder symptoms in breast cancer patients.

Health-Related Quality of Life in Survivors With Breast Cancer 1 Year After Diagnosis Compared With the General Population

To compare the health-related quality of life (HRQOL) of disease-free breast cancer survivors at the time of diagnosis and 1 year later with that of the general population (GP) and to examine the predictors of HRQOL change. Although studies that examine the changes HRQOL in breast cancer survivors with cohort design is increasing, few studies compared the HRQOL of breast cancer survivors from baseline (immediately after diagnosis) with that of the GP. We administered European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 and Quality of Life Questionnaire BR23 HRQOL immediately after diagnosis to evaluate a population-based cohort of 286 women with breast cancer. We compared HRQOL scores of subjects internally and with reference data from the GP externally. We found no significant change in HRQOL internally except for diarrhea. In the external comparison, however, breast cancer survivors reported poorer HRQOL scores than the GP at baseline and a year later; clinically meaningful detriments were found for emotional and social functioning and for the symptoms of fatigue and insomnia, financial difficulties, and most of the breast cancer-specific domains (P < 0.01 for all). Multiple linear regression analysis revealed that menopausal status and the sociodemographic characteristics of education level, employment status, and physical activity at baseline and increased symptom problems were significantly associated with functioning changes. Immediately after the diagnosis of breast cancer, patients reported a lower HRQOL than the GP, and they continued to do so a year later. Increased levels of fatigue, pain, and insomnia were the main symptoms responsible.

Quality of life and physical performance and activity of breast cancer patients after adjuvant treatments

The study aimed at investigating the quality of life (QoL) and physical performance and activity, and their interrelations, in Finnish female breast cancer patients shortly after adjuvant treatments. A total of 537 disease-free breast cancer survivors aged 35-68 years were surveyed at the beginning of a one year randomized exercise intervention. The patients were interviewed using EORTC QLQ-C30, FACIT-F, RBDI, and WHQ (for vasomotor symptoms) questionnaires. Physical performance was tested by a 2 km walking test. Physical activity was measured by a questionnaire and a prospective two-week diary. Multivariate analysis was used to study the factors associated with QoL. About 26% of the patients were rated as depressed, 20.4% as fatigued, and 82% suffered from menopausal symptoms. The global QoL was lower than in general population (69.4 vs 74.7, p<0.001). About 62% of the walking test results were below the population average. Fatigue (p<0.001), depression (p<0.001), body mass index (p = 0.016) and comorbidity (p = 0.032) impaired, and physical activity (p = 0.003) improved QoL. Physical activity level correlated positively to physical performance (r = -0.274, p<0.0001). The QoL of the patients shortly after adjuvant treatments was impaired and the physical performance poor as compared to general population. In particular, depression and fatigue were related to impaired QoL. Physical performance and activity level were the only factors that correlated positively to QoL. Thus, physical exercise could be useful in rehabilitation of cancer survivors, especially for depressed and fatigued patients.

Corroboration of Growth Following Breast Cancer: Ten Years Later.

Disease-free breast cancer survivors (n = 180) were interviewed 10 years after diagnosis. They were asked questions about the lasting effects of cancer. The vast majority identified positive effects. The validity of growth reports was investigated by: (1) comparing survivors' to significant others' responses and (2) comparing survivors' reports to their standing on relevant dimensions. Results revealed little corroboration by significant others but some corroboration by relevant dimensions. There was greater corroboration for the costs than the benefits of breast cancer. Survivors reported more benefits than significant others. There was little evidence that corroboration was greater when the significant other was a spouse compared to someone else. Research should continue to explore the validity and meaning of growth reports.

Elevated Biomarkers of Inflammation Are Associated With Reduced Survival Among Breast Cancer Patients

PURPOSE Chronic inflammation is believed to contribute to the development and progression of breast cancer. Systemic C-reactive protein (CRP) and serum amyloid A (SAA) are measures of low-grade chronic inflammation and potential predictors of cancer survival. PATIENTS AND METHODS We evaluated the relationship between circulating markers of inflammation and breast cancer survival using data from the Health, Eating, Activity, and Lifestyle (HEAL) Study (a multiethnic prospective cohort study of women diagnosed with stage 0 to IIIA breast cancer). Circulating concentrations of CRP and SAA were measured approximately 31 months after diagnosis and tested for associations with disease-free survival (approximately 4.1 years of follow-up) and overall survival (approximately 6.9 years of follow-up) in 734 disease-free breast cancer survivors. Cox proportional hazards models were used with adjustment for potential confounding factors to generate hazard ratios (HRs) and 95% CIs. Results Elevated SAA and CRP were associated with reduced overall survival, regardless of adjustment for age, tumor stage, race, and body mass index (SAA P trend < .0001; CRP P trend = .002). The HRs for SAA and CRP tertiles suggested a threshold effect on survival, rather than a dose-response relationship (highest v lowest tertile: SAA HR = 3.15; 95% CI, 1.73 to 5.65; CRP HR = 2.27; 95% CI, 1.27 to 4.08). Associations were similar and still significant after adjusting for self-reported history of cardiovascular events and censoring cardiovascular disease deaths. Elevated CRP and SAA were also associated with reduced disease-free survival, although these associations were of borderline significance (SAA P trend = .04; CRP P trend = .07). CONCLUSION Circulating SAA and CRP may be important prognostic markers for long-term survival in breast cancer patients, independent of race, tumor stage, and body mass index.

Anxiety in patients with breast cancer undergoing treatment: A systematic review

Anxiety in patients with breast cancer undergoing treatment: A systematic review

Symptom Experience and Quality of Life in Breast Cancer Survivors

The purposes of this study were to evaluate symptom experience and quality of life (QOL) and to identify the predictors of QOL among breast cancer survivors. A cross-sectional study was conducted on 200 disease-free breast cancer survivors at two hospitals between December 2007 and July 2008. Functional Assessment of Cancer Therapy Scale-B, Memorial Symptom Assessment Scale-short Form and The Linear Analogue Self Assessment Scale were used to assess symptom experience and QOL in these patients. Data were analyzed using the Pearson correlation, t-test, ANOVA, and stepwise multiple regression with SPSS/WIN 12.0. The mean score of QOL for breast cancer survivors was 95.81 (+/-18.02). The highest scores among physical and psychological symptoms were sexual interest and anxiety. Year since treatment completion was significantly associated with QOL in sociodemographic variables. Physical and psychological symptoms have a significant negative association with QOL. The results of the regression analyses showed that physical and psychological symptoms were statistically significant in predicting patients' QOL. Symptom experience and QOL are essential variables that should be acknowledged when delivering health care to breast cancer survivors. More attention to the reduction and management of psychological distress could improve QOL among breast cancer survivors.

Received and needed social support at the workplace in Norwegian and Finnish stage 1 breast cancer survivors: A study from the Nordic Study Group of Cancer and Work (NOCWO)

Background. Cross-cultural studies of comparable patients can identify differences of health care services and point to issues of possible improvement. In this cross-sectional study we compared self-reported received and needed social support at the workplace of disease-free breast cancer survivors (BCSs) stage I from Norway and Finland. Methods. Age-matched samples of 135 BCSs from Norway and 148 from Finland were examined using a questionnaire including socio-demographic factors, employment data, measurements of social support at work from supervisors, colleagues and the occupational health service (OHS), and several other measurements. Results. Finnish BCSs had significantly higher education and a higher rate of full-time employment than Norwegian ones. With adjustment for education and work time, Finnish compared to Norwegian BCSs reported significantly less received social support from supervisors, while they received significantly more social support from OHS. No differences were observed in received support from colleagues between Finnish and Norwegian BCSs. Somatic health was most strongly associated with received and needed support from supervisors, colleagues and OHS. Conclusions. The differences in received and needed social support at work observed between Norwegian and Finnish BCSs treated for stage I disease challenge strengthening of OHS for Norwegian BCSs and increased attention by supervisors in Finnish BCSs.

A comparison of the characteristics of disease-free breast cancer survivors with or without cancer-related fatigue syndrome

PurposeTo determine the prevalence of cancer-related fatigue syndrome (CRFS) in a population of disease-free breast cancer survivors and to investigate the relationship between CRFS and clinical variables. Patients and methodsWomen (200) were recruited. All participants were between 3 months and 2 years after completion of primary therapy for breast cancer and were disease free. Subjects completed a diagnostic interview for CRFS and structured psychiatric interview. Participants also completed quality of life, mood and fatigue questionnaires, and provided a blood sample for haematological and biochemical analysis and a 24-h urine specimen for cortisol estimation. Subjects wore a wrist actigraph for 7 days to measure activity and sleep. ResultsSixty women (30% of participants) were found to fulfil the criteria for CRFS. There were statistically significant differences between fatigued and non-fatigued women with respect to fatigue severity (p<0.01), mood (p<0.01) and quality of life scores (p<0.05). There were significant differences in blood variables including raised total white cell count and lower sodium (all p<0.02). There was no difference in the 24h urinary free cortisol levels. Actigraphic data demonstrated significant differences in sleep quality and disturbance, but not in overall levels of daytime activity or circadian rhythm. ConclusionCRFS affects 30% of women after breast cancer treatment and has significant effects on quality of life and mood. There is some evidence that CRFS is related to sleep disturbance or to a persistent inflammatory or immune response.

The WHOQOL-100 has good psychometric properties in breast cancer patients

Objective This prospective follow-up study examines the psychometric properties of the World Health Organization Quality of Life assessment instrument (WHOQOL-100) for assessing quality of life in women suspected of having breast cancer and disease-free breast cancer survivors. Study Design and Setting The WHOQOL-100 was tested at five points in time in women with a palpable lump in the breast or an abnormality on a screening mammography ( N = 356) and breast cancer survivors ( N = 140). Furthermore, all participants completed measures of anxiety (State Trait Anxiety Inventory) and depression (Center for Epidemiologic Studies Depression scale). Moreover, women who were diagnosed with breast cancer also completed the EORTC-QLQ-BR-23 at time points 2–5. Reliability (internal consistency; test–retest reliability) and construct validity were tested. Results Confirmatory factor analyses on the WHOQOL-100 items showed a good fit with models reflecting six factors (physical health, psychological health, level of independence, social relationships, environment, spirituality/religion/personal beliefs) or four factors (physical health, psychological health, social relationships, environment). Internal consistency was adequate. Test–retest correlations were high. The WHOQOL-100 correlated highly with related constructs and showed low correlations with unrelated constructs. Conclusion The WHOQOL-100 is a reliable and valid instrument for measuring QOL in women suspected of having breast cancer and disease-free breast cancer survivors.

Correlates of circulating C-reactive protein and serum amyloid A concentrations in breast cancer survivors

Inflammatory status may be an important prognostic factor for breast cancer. Correlates of markers of inflammation in breast cancer survivors have not been thoroughly evaluated. Using data from, the Health, Eating, Activity, and Lifestyle (HEAL) Study (a population-based, multiethnic prospective cohort study of female breast cancer patients) we evaluated the associations between circulating markers of inflammation (C-reactive protein [CRP] and serum amyloid A [SAA], measured approximately 31 months after diagnosis) and several demographic, lifestyle, and clinical characteristics in 741 disease-free breast cancer survivors. Analysis of variance and regression methods were used for statistical analyses of log-transformed values of CRP and SAA. After adjusting for age, BMI, ethnicity, and study site, higher concentrations of CRP were associated with increasing concentration of SAA (P-trend < 0.0001), increasing age (P-trend < 0.0001), increasing BMI (P-trend < 0.0001), increasing waist circumference (P-trend < 0.0001), positive history of heart failure (P = 0.0007), decreasing physical activity (P-trend = 0.005), Hispanic ethnicity (P = 0.05 vs. non-Hispanic white), and current smoking (P = 0.03 vs. never smoking). Vitamin E supplementation (P = 0.0005), tamoxifen use (P = 0.008), and radiation treatment (compared to no chemotherapy or radiation; P = 0.04) were associated with reduced CRP. Associations of CRP with clinical characteristics were not significant in the adjusted models. In a multivariate analysis, CRP showed significant associations with waist circumference, BMI, age, history of heart failure, tamoxifen use, and vitamin E supplementation (R (2) = 0.35). Similar, yet fewer, associations were observed for SAA (R (2) = 0.19). This study highlights important correlates of inflammatory status in breast cancer patients. Our results are consistent with those from similar studies of healthy women.

Fatigue and Depression in Disease-Free Breast Cancer Survivors: Prevalence, Correlates, and Association with Quality of Life

We performed this study to examine the prevalence and correlates of fatigue and depression, and their relevance to health-related quality of life in disease-free breast cancer survivors. A total of 1,933 breast cancer survivors recruited from five large hospitals in Korea completed a mailed survey, which included the Brief Fatigue Inventory, Beck Depression Inventory, European Organization for Research and Treatment of Cancer QLQ-C30, and QLQ-BR23. With a framework that included sociodemographic, clinical, and symptom characteristics, multivariate logistic regression models were used to identify factors associated with fatigue and depression. Among breast cancer survivors, 66.1% reported moderate to severe fatigue and 24.9% reported moderate to severe depression. Risk factors common to both fatigue and depression were lower income, dyspnea, insomnia, appetite loss, constipation, and arm symptoms. Risk factors for fatigue only included younger age, employment, presence of gastrointestinal disease, and pain. Having a musculoskeletal disease was identified as a risk factor for depression only. Both fatigue and depression were influenced by sociodemographic factors, comorbidity and symptom characteristics rather than cancer or treatment-related factors. Both fatigue and depression were negatively associated with survivors' health-related quality of life. However, the patterns of differences in health-related quality of life according to severity of fatigue or depression were similar. This concurrent examination of risk factors for fatigue and depression may be helpful in the development of clinical management strategies in disease-free breast cancer survivors.

How common is fatigue in disease-free breast cancer survivors? A systematic review of the literature

There is some debate in the literature as to whether fatigue persists in the long term in women who have completed adjuvant breast cancer treatment. A systematic review was conducted in order to characterise and quantify the phenomenon of post treatment fatigue (PTF). There was a wide variation in the measures of fatigue used, duration of follow-up and type of comparison made. Overall 18 studies were identified with a follow-up period of between 4 months and 10 years. Fourteen studies demonstrated the presence of continued PTF and/or differences in fatigue levels compared to a reference population up to 5 years after treatment. One short-term study reported no increase in fatigue at 4 months. Three studies (with an average follow up period of longer than 5 years) did not identify overall quality of life differences in breast cancer survivors when compared with a reference population. However there were significant differences in measures of physical functioning and mental fatigue. The authors conclude that there is good evidence of PTF occurring up to 5 years after completion of adjuvant therapy.

Acupuncture and fatigue: Current basis for shared communication between breast cancer survivors and providers

Fatigue is the most common symptom reported by survivors of cancer. At present the medical community lacks evidence-based options for its management. This paper describes the rationale, current evidence, and research in progress as related to the use of acupuncture as a potential option. Preliminary evidence suggests that clinicians and cancer survivors may find benefit in considering acupuncture as an option for managing fatigue; this is especially appealing since acupuncture appears to be a safe medical technique. We draw upon our research and clinical experience to generate a description of considerations for patient and provider when thinking about acupuncture as an option for the management of fatigue in non-anemic, disease-free breast cancer survivors. Research examining its relative effectiveness and potential for integration with other approaches is a logical next step if the results from RCTs are positive. Acupuncture is not routinely considered in mainstream discussions of options for fatigue management. While future research will more clearly determine its relative effectiveness, given the present options available clinicians and breast cancer survivors may find benefit in considering and discussing acupuncture as an approach for managing persistent fatigue.

Fatigue in breast cancer survivors two to five years post diagnosis: a HEAL Study report

The purpose of this study was to estimate prevalence of fatigue, identify correlates of fatigue and evaluate the relationship between fatigue and health-related quality of life (HRQOL) in a large cohort of disease-free breast cancer survivors. Participants are enrolled in the HEAL Study, a multi-center prospective study of women diagnosed with in-situ to Stage IIIA breast cancer. HEAL participants (n = 1183) completed a baseline and a 24-month follow-up interview. Women in this report (n = 800) also completed a quality of life questionnaire that included the Piper Fatigue Scale and the RAND SF-36 two to five years after diagnosis. Multivariate regression methods were used to identify significant factors associated with fatigue. SF-36 scores for fatigued survivors were compared to non-fatigued survivor scores and population norms. Forty-one percent of the breast cancer survivors were fatigued. Significant correlates of fatigue included pain, cognitive problems, physical inactivity, weight gain/personal appearance and antidepressant use. Fatigue was associated with poorer HRQOL, most notably in areas of role and social functioning. This study provides further support for the conclusion that a significant proportion of breast cancer survivors experience fatigue that compromises HRQOL two to five years post-diagnosis.

Health-related quality of life in disease-free survivors of breast cancer with the general population

Although most of the literature about health-related quality of life (HRQoL) focuses on breast cancer patients, few studies compared the HRQoL in disease-free breast cancer survivors with that of the general population. We administered the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 and Quality of Life Questionnaire Breast Cancer Module, McGill Quality of Life Questionnaire, Beck Depression Inventory, and Brief Fatigue Inventory to 1933 disease-free survivors for over 1 year after being diagnosed with stage 0 to III breast cancer. We performed multivariate-adjusted analyses in all HRQoL comparisons. The scores for some health-related quality of life [corrected] HRQoL scales were comparable for both disease-free breast cancer survivors and the general female population, but [corrected] there was a [corrected] clinically significant difference between the two groups [corrected] in cognitive and social functioning, fatigue, insomnia, financial difficulties, body image, future perspective, breast symptoms, and arm symptoms. [corrected] Disease-free survivors of breast cancer had good HRQoL, which was less affected by the type of treatment than it was by demographic characteristics, time since surgery, comorbidity, fatigue, and depression.

Breast cancer survivors’ supportive care needs 2–10 years after diagnosis

A significant proportion of breast cancer patients experience psychosocial morbidity after treatment, although their longer-term outcomes and supportive care service needs have not been comprehensively documented. The aim of this study was to identify longer-term outcomes and supportive care needs in disease-free breast cancer survivors. One hundred seventeen patients who had been diagnosed with breast cancer 2-10 years earlier completed questionnaires to assess psychosocial outcomes including supportive care needs, psychological distress, and quality of life (QoL). QoL and depression scores were consistent with community rates although anxiety scores were higher. Approximately two thirds of survivors reported at least one unmet need, most frequently concerning existential survivorship issues, thereby highlighting the unique needs of survivors. Years since diagnosis was not correlated with need levels. Survivors classified as clinically anxious reported over three times as many unmet needs and survivors classified as depressed reported over two and a half times as many unmet needs. Positive outcomes were frequently reported. The findings have direct clinical relevance: irrespective of years since diagnosis, comprehensive and extended supportive care services are required to identify breast cancer survivors in need of supportive care interventions and remediate high levels of anxiety.

Prevalence and correlates of fatigue and depression in breast cancer survivors: Breast cancer quality care study

683 Background: Fatigue and depression may persist for months or even years after completion of breast cancer treatment. We investigated the prevalence and correlates of fatigue and depression in disease-free breast cancer survivors. Methods: 1,933 breast cancer survivors recruited from five large hospitals in Korea completed standardized questionnaires as part of a survey study, including the patient demographics, Brief Fatigue Inventory, Beck Depression Inventory, European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, and QLQ-BR23. Women were eligible to participate if they had a past diagnosis of breast cancer (stage 0, I, II, or III) and were currently free of the disease more than one year. Eligible patients were contacted by telephone, and those who agreed to participate were sent the questionnaire with consent forms and a postage-paid return envelope. Multivariate logistic regression models were used to identify factors associated with fatigue and depression. Results: Sixty six percent of the breast cancer survivors reported moderate to severe fatigue, which was defined as a “fatigue worst” rating of 4 or greater, 24.9% reported clinical moderate to severe depression, which was defined as a rating of 19 or greater. Fatigue and depression were highly correlated (Pearson r=.593). Fatigue was associated with significantly employment status (OR=1.58), low income (OR=1.29), having gastrointestinal disease (OR=1.94), dyspnea (OR=2.15), appetite loss (OR=3.02), insomnia (OR=2.72), breast symptoms (OR=1.82), and hair loss (OR=1.75). Depression was strongly related to low income (OR=2.50), fatigue (OR=4.52), insomnia (OR=1.98), appetite loss (OR=2.24), constipation (OR=2.12), and financial difficulties (OR=1.89), systemic therapy side effect (OR=3.12). Fatigue and depression were negatively associated to QOL. Conclusion: There were subgroups of survivors who report more severe and persistent fatigue and depression. This information may be helpful in elucidating the mechanisms underlying fatigue and depression in this population, as well as directing intervention efforts. No significant financial relationships to disclose.

Circulating apoptotic proteins are increased in long-term disease-free breast cancer survivors

Circulating apoptotic proteins are increased in patients with heart failure. We evaluated whether circulating soluble (s) apoptosis-related proteins and inflammation markers are increased in long-term disease free breast cancer survivors and associated with cardiotoxicity, and if subgroups could be identified based on the applied treatments. Circulating tumour necrosis factor (TNF) α, sTNF-receptor (sTNF-R) 1 and 2, sFas, sFas ligand, sTNF-related apoptosis inducing ligand (sTRAIL) and serum HER2 were measured with immunoassay. High-sensitivity C-reactive protein (HS-CRP), fibrinogen, plasma B-type and N-terminal atrial natriuretic peptide (NT-ANP and BNP) were also determined. Thirty-four patients with median 6.0 years follow-up and 12 healthy age-matched women were enrolled. Chemotherapy, consisting of five cycles fluorouracil, epirubicin (90 mg/m2), cyclophosphamide (FEC) (n = 14) or four cycles FEC followed by myeloablation with high-dose carboplatin, cyclophosphamide, thiotepa (n = 20), preceded irradiation and tamoxifen. Circulating apoptosis markers were higher in patients than in controls. No associations with cardiac dysfunction were observed. sFas ligand and sTRAIL were higher in the high-dose than in the standard-dose group. In conclusion, we observed increased circulating apoptotic protein levels in long-term disease-free breast cancer survivors, treated with adjuvant chemoradiotherapy, particularly after myeloablative chemotherapy. The potential relation with late cardiotoxicity of antineoplastic therapy deserves further study.

Circulating apoptosis-related proteins in long-term disease free breast cancer survivors

845 Background: Adjuvant chemotherapy may result in cardiovascular dysfunction. We evaluated whether plasma levels of apoptotic proteins are increased in patients (pts) with long-term follow-up after adjuvant therapy, as potential markers for cardiotoxicity. Methods: In 40 long-term disease free adjuvant treated breast cancer survivors (5×FEC n=15, 4×FEC + high-dose (H-D) CTC n=20, 6×CMF-doxorubicin + H-D mitoxantrone, thiotepa n=5) with median follow-up 79 mo after chemotherapy, of which 28% (n=11) had a >10% decrease of left ventricular ejection fraction (EF) or an EF <50% at median 29 mo. Plasma tumor necrosis factor(TNF)-related protein levels (soluble (s) TNF receptor TNFR2, sFas/ -ligand (L), and sTNF-related apoptosis-inducing ligand (sTRAIL) were determined (ELISA). Factor VIII (F8), plasminogen activator (PA) inhibitor (I), tissue PA (t-PA) and fibrinogen were measured as endothelial damage markers. 12 age matched healthy women served as controls (contr). Results: Plasma sTRAIL, sTNFR2, sFas, sFasL, and fibrinogen levels were increased in pts vs controls (table). Median plasma sTRAIL, sTNFR2, sFas levels were higher in the H-D pts vs. standard dose pts. PAI, t-PA and F8 were higher in pts, but not significant. Conclusions: Apoptosis markers are increased in long-term disease free adjuvant-treated breast cancer survivors, especially if they received H-D chemotherapy. The potential pathogenetic role of the apoptosis markers in the development of cardiotoxicity deserves further study. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb; Roche