The primary purpose of this study was to compare differences by treatment group in HRQL domains (physical, psychological, social, spiritual and economic) among long-term breast cancer survivors. When HRQL measures were examined by treatment arm, physical role functioning emerged as the only statistically significant outcome. Trends toward significance were seen in variables such as general health perceptions, vitality, emotional role functioning and social functioning. These results are similar to Ganz et al., who found that 6-year survivors treated with adjuvant therapy reported lower levels of physical role functioning, as well as general health, bodily pain, physical functioning, and social functioning.6,36
Ahles et al. also found significantly lower scores in social and physical domains among 10-year survivors who received chemotherapy versus local therapy.37
Others have reported poorer physical role functioning among patients 5 years post-chemotherapy compared to patients without cancer38
and to patients who received adjuvant chemotherapy.3
Unlike previous studies, where a dose-response relationship was found, the present study showed the lowest SF-36 subscale means in the standard group, followed by the low-dose and high-dose groups. Survivors in the standard arm also showed significantly higher levels of systems of belief social support in the spiritual domain. These findings may be due to survivors in the standard group having less education or perhaps being less healthy than the other groups. Future studies should examine similar dose-intensities and their effect on HRQL.
In further examining the relationship of physical role functioning by treatment arm, logistic regression analyses revealed that treatment arm was no longer significantly associated with HRQL after adjusting for factors such as age, fatigue, menopausal symptoms and comorbidities interfering with daily life. A recent prospective study found lower levels of physical role functioning among women one year after receiving high-dose chemotherapy, which remained stable over 4 years but had small effect sizes that were clinically irrelevant.39
In that study, when age and menopausal status were assessed as covariates, postmenopausal women exhibited lower physical role functioning scores. Other studies have also shown lower levels of HRQL in physical/role functioning domains in high-dose chemotherapy patients that returned to baseline 1 year post-treatment.40–42
The current results, however, provide information on who may be at risk for reduced physical role functioning following the receipt of any dose of this adjuvant therapy regimen.
Age was significantly related to physical role functioning in this study, and has typically been associated with lower HRQL in past studies. Older survivors have reported decreased physical role functioning,43, 44
more physical problems, depressed mood and days affected by fatigue.45,46
Comorbidities interfering with daily life, which were significantly related to physical role functioning in this study, have consistently been shown to affect HRQL. Depression, diabetes and circulation trouble were also evident in women with lower education levels. Past studies have shown that poorer HRQL among lower SES groups may be related to increased co-morbidities and reduced access to care. Patients with lower education level have reported more physical symptoms, such as tiredness, decreased sexual interest and painful muscles.39
Fatigue was significantly related to physical role functioning in this study. Fatigue is often reported as a long-term side effect of breast cancer treatment that persists years after active treatment.6,7,47,48
Co-morbidities, such as high blood pressure, which were prevalent in this study, have been shown to be related to fatigue in previous studies.48
The presence of joint and muscle pain have also been associated with fatigue.49,50,51
Patients who most frequently reported symptoms, such as pain and fatigue 5 years post-treatment, scored significantly lower on HRQL at baseline compared to other patients.39
Future studies should assess these domains at baseline, and possible interactions with other factors, as differences may be predictive of future outcomes.
Regarding menopausal symptoms, which showed a statistically significantly association with physical role functioning, Schultz et al. concluded that despite “complex interactions” between HRQL indicators and physiologic effects of treatment, menopausal symptoms may not be different for breast cancer survivors and should not be confused with quality of life/psychosocial issues.52
Others have demonstrated that HRQL differences could not be explained by menopausal symptoms alone and that more research is needed in this area.38
There were several strengths of this study. First, it focused on the HRQL domain of physical role functioning, and factors influencing this domain, which have not been explored in previous studies. Second, it examined survivors who were 9–16 years post-diagnosis, which few studies have included. Third, the women were diagnosed at relatively the same disease stage received one of 3 known chemotherapy regimens within the same clinical trial, thus reducing variability due to treatment and stage of diagnosis. Many previous studies have used heterogeneous populations in examining stage and treatment.
Limitations of this study include reliance on self-reported co-morbidities, such as lymphedema and osteoporosis. Information on temporal changes in HRQL was not assessed since HRQL was examined at only one time point. Also, a survival bias may have occurred, whereby patients with better HRQL were more likely to be long-term survivors, and thus, eligible to participate in the follow-up study. However, analyses showed few differences between CALGB 8541 survivors who did and did not participate in this study. These limitations emphasize the need for prospective long-term studies of HRQL in breast cancer survivors from treatment through survivorship.
While chemotherapy provides a great survival benefit for cancer patients, it provides potential long-term side effects that may greatly impact HRQL. The current study demonstrated that while adjuvant chemotherapy dose was initially related to lower HRQL in physical role functioning, this effect was actually explained by demographic and clinical factors, which can be used in targeting HRQL interventions for long-term survivors. The clinical significance of these factors and their role as potential areas for interventions in improving HRQL needs to be further explored in prospective studies of HRQL in long-term breast cancer survivors.