At the time of the 2000 National Institutes of Health Consensus Conference on Adjuvant Therapy of Breast Cancer,33
all women with a tumor greater than 1 centimeter were advised to receive adjuvant chemotherapy, even though it was known to have acute and potentially longer-term effects on QOL and symptoms.12,34
A decade later, breast cancer treatments are being tailored according to tumor-specific gene expression profiles that can more successfully assess the risk for recurrence and need for chemotherapy.35,36
Even with these tools, patient preferences may still influence decision making, and accurate information about the impact of chemotherapy treatment on physical and psychosocial functioning, as well as symptoms, may be helpful. There are limited comparative data from clinical trials on these patient-reported outcomes (PROs) from contemporary adjuvant chemotherapy trials37,38
with absence of no treatment comparison groups. As a result, observational PRO data can provide valuable information that may be of help in decision making. The purpose of reporting the observational post-treatment data from the MBC trial was to examine differences in recovery after adjuvant chemotherapy by using a contemporaneous no-chemotherapy comparison group. On the basis of prior research with long-term survivors, we predicted that chemotherapy would have a negative impact on physical functioning and symptoms.10,13
Here, we examined whether prospective longitudinal PRO data collected in the year after treatment could support a causal relationship between chemotherapy exposure and these long-term effects. The observational nature of the data collection in the MBC study required the use of propensity-score adjustment accounting for differences in who was likely to receive chemotherapy (eg, younger age, hormone receptor–negative tumors). Although the outcomes in this study were self-reported QOL and symptoms and not survival, some medical and demographic factors could affect subjective assessment of PROs. To our surprise, however, these propensity-adjusted analyses suggested few differences in PROs among women in the year post treatment, specifically in relationship to prior chemotherapy exposure ( to ).
Previous cross-sectional studies of breast cancer survivors have suggested negative effects of chemotherapy on QOL, and most specifically physical functioning and symptoms, but have not controlled for background characteristics associated with treatment exposure. Findings from a recent longitudinal study that utilized more sophisticated analytic techniques found no association between chemotherapy exposure and fatigue in the 6 months after breast cancer treatment, consistent with our results.39
It is possible that the SF-36 was not sufficiently sensitive to detect nuanced differences in psychosocial parameters as a function of chemotherapy receipt. Although we did find some significantly different symptom outcomes among chemotherapy-treated patients, they are not so severe or disparate that such therapy should be avoided; however, patients can be informed that such symptoms may be a consequence of the treatment and that they may persist beyond the end of treatment.
Although we detected few outcome differences in the SF-36 scales trajectory by chemotherapy assignment, patients receiving chemotherapy may still experience more severe symptoms,6,7,10,12,40
and these may be causing some of the lasting consequences of adjuvant therapy. We found greater severity of vaginal symptoms, musculoskeletal pain, and weight problems, which were all significantly worse in patients receiving chemotherapy and persisted throughout the 1 year of observation post treatment. Surprisingly, vasomotor symptoms were not significantly different (P
= .30) by chemotherapy exposure even after controlling for menopausal status, but they were among the most severe symptoms in the two groups of patients. This observation no doubt relates to the greater tamoxifen use in women who did not receive chemotherapy, which continues in the year after primary treatment ends. The pattern of vaginal symptoms (ie, dryness, pain with intercourse) are consistent with our earlier research, and are more bothersome in women who received chemotherapy, with no improvement in severity over time.9,10,12
Potential limitations of this research include the representativeness of the study sample,22
as well as lack of detailed information about chemotherapy regimens and stage of disease in the absence of medical chart review. The chemotherapy regimens reported by these women were representative of treatments in common use at the time. Contemporary treatments more often include taxanes, which may have a different toxicity profile.41,42
Future research should more carefully assess information about specific chemotherapy regimens with the goal of determining their effects on QOL and symptom outcomes. This may be best accomplished within randomized, clinical trials. Although MBC study eligibility was limited to women with stages I and II disease, the findings are still relevant for women with more advanced disease (eg, stage III), who are often treated in a similar manner; however, a recent study by Bardwell et al43
suggests that medical factors contribute little to the self-assessment of psychosocial outcomes in breast cancer survivors.43,44
Questions also could be raised about whether trajectories for chemotherapy and nonchemotherapy patients can be explained by a modest number of covariates in a parametric model.
In conclusion, we have shown that the multiple aspects of health-related QOL improve in the year after primary breast cancer treatment, independent of use of chemotherapy; however, moderately severe symptoms persist, and many that are more severe occur in women who received chemotherapy. Prior work suggests that uncontrolled symptoms may contribute significantly to poorer physical and psychosocial health in breast cancer survivors.20
With increasing attention to the needs of cancer survivors and the development of survivorship care plans,45,46
future research should focus on the development and testing of symptom interventions to improve the health and well-being of these women.47–49
Importantly, for patients in the immediate post-treatment phase of early breast cancer, we can now provide more specific information about the trajectory of physical and psychosocial recovery, and can estimate the differential impact of chemotherapy when it is indicated as a important component of adjuvant therapy.