Persistence of Restrictions in Quality of Life From the First to the Third Year After Diagnosis in Women With Breast Cancer
http://www.100md.com
《临床肿瘤学》
the Department of Epidemiology, German Centre for Research on Ageing, Heidelberg
Department of Epidemiology, University of Ulm, Ulm
Saarland Cancer Registry, Saarbrücken, Germany
ABSTRACT
PURPOSE: To assess whether detriments in quality of life (QOL) among women with breast cancer persist over years.
PATIENTS AND METHODS: QOL was assessed in a population-based cohort of 314 women with breast cancer from Saarland (Germany) 1 and 3 years after diagnosis and compared internally and with reference data from the general population.
RESULTS: Three years after diagnosis, deficits in QOL were still apparent for role, emotional, cognitive, and social functioning and for the symptoms of insomnia, fatigue, dyspnea, and financial difficulties. Differences between breast cancer patients and women from the general population were predominantly found in younger ages. Compared with the QOL scores measured 1 year after diagnosis, only minor functional changes were observed, but recurrence of breast cancer during the follow-up interval had a deleterious effect on QOL.
CONCLUSION: Deficits in role, emotional, cognitive, and social functioning persist over years in women with breast cancer and predominantly affect younger patients.
INTRODUCTION
Breast cancer is the most common cancer in women, accounting for approximately one third of all cancers in females.1 As a result of advances in early diagnosis and therapy, the prognosis of breast cancer has improved over the last decades. Five-year relative survival estimates of approximately 86%2 indicate that the vast majority of women with breast cancer are now becoming long-term survivors. In fact, breast cancer survivors represent the largest group of long-term cancer survivors. They comprise approximately 40% of all female cancer survivors in developed countries.3 Therefore, in addition to disease-free and overall survival issues of cancer survivorship, quality of life (QOL) is particularly relevant for this form of cancer.
It has been reported that women with breast cancer attain maximum recovery from the physical and psychological trauma of cancer treatment by 1 year after diagnosis, and a number of QOL aspects and rehabilitation problems seem to worsen after 1 year.4 In particular, a large proportion of breast cancer patients are likely to suffer from persistent arm problems, which substantially affect QOL.5-7 However, the pattern does not seem to be uniform because improvements have also been reported after 1 year for overall QOL and specific psychosocial aspects including role, emotional, and social functioning.8 So far, changes in QOL after the first year have been assessed only in a few longitudinal studies4,9-14 with conflicting results. Some of the heterogeneity may be a result of methodologic differences (eg, QOL instruments, age range, setting, and length of follow-up interval). Furthermore, previous studies rarely compared QOL in breast cancer patients with QOL of women of similar age in the general population with the same instruments.
We recently found that overall QOL and physical functioning of women with breast cancer were comparable in women from the general population 1 year after diagnosis of breast cancer, when most acute treatment-related effects are likely to have disappeared.15 However, deficits in emotional, social, role, and cognitive functioning were still apparent and affected predominantly younger women with breast cancer. Specific symptoms like insomnia, fatigue, and financial difficulties also seemed to be of particular concern for women with breast cancer, resulting in a detrimental effect on QOL. In a follow-up of this large population-based cohort, we now address the questions of whether the detriments in QOL in breast cancer patients found at 1 year after diagnosis persist over a longer period and, specifically, whether young women with breast cancer continue to suffer or start to adapt and recover.
PATIENTS AND METHODS
Study Design
In October 1996, we set up a population-based, statewide cohort study on risk factors, diagnostic procedures, and prognosis for various forms of cancer in Saarland (a state in southwest Germany with a population of 1 million inhabitants). Patients with breast, colorectal, or gastric cancer, diagnosed between October 1996 and February 1998, were recruited within days after diagnosis from all hospitals that offered in-patient cancer treatment in the study region. Permission to approach the patient was obtained by the physician after the study was explained to the patient. Study eligibility criteria for recruitment included histologically confirmed invasive cancer, age 18 to 80 years, sufficient knowledge of the German language, and resident of the state of Saarland. The protocol for this study and for the subsequent follow-up were approved by the local and regional ethics committees. Informed written consent was obtained from each patient.
In total, 387 women with breast cancer were recruited shortly after diagnosis (T0) and constituted the baseline population for the first follow-up 1 year later (T1), when we sent a QOL questionnaire to each patient (see QOL Questionnaire). Fourteen women (3.6%) died during the first year after diagnosis. These women tended to be older and to have advanced tumors. Of the 373 women who were alive, 314 (84%) participated in the first QOL survey and returned the questionnaire. Respondents and surviving nonrespondents were similar with respect to age, education, and comorbidity status. However, tumor stage was more favorable among respondents.
Two years after T1 (ie, 3 years after diagnosis), we conducted a second follow-up (T2) and sent the QOL questionnaire a second time to all respondents of the 1-year follow-up to obtain information about potential changes in QOL over time. These 314 women form the study population of the study presented in this article.
Data Collection
Baseline data (T0), including patient age, education level, and marital status and date of diagnosis and comorbidity, were obtained by structured face-to-face interviews. The interviews were conducted within a few days to weeks after diagnosis of breast cancer and, in most cases, during the first hospitalization as a result of breast cancer. Information regarding tumor stage at time of diagnosis and initial therapy was abstracted from hospital records.
One year after diagnosis of cancer (T1), all study participants were sent a letter with detailed information describing the purpose of the follow-up study together with a QOL questionnaire and a stamped addressed return envelope. The questionnaire also included questions referring to therapies during the follow-up period. Nonrespondents were mailed up to two reminders and were contacted by phone if they did not respond after three mailings. If all of these attempts did not result in any response, the vital status of nonrespondents was obtained from the residents’ registration office.
Three years after diagnosis of cancer (T2), we repeated the QOL follow-up and sent the same QOL questionnaire to all respondents of the T1 follow-up. Again, nonrespondents were mailed up to two reminders and were contacted by phone if they did not respond after three mailings. The vital status of nonrespondents was obtained from the residents’ registration office.
QOL Questionnaire
QOL was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30)16 and the breast cancer–specific module BR-23, which was also developed by the EORTC.17 The EORTC QLQ-C30 is a validated, brief, self-reporting, cancer-specific measure of QOL and is composed of five multi-item functional scales that evaluate physical, role, emotional, cognitive, and social function and one global health status/QOL scale. Three multi-item symptom scales measure fatigue, pain, and nausea/vomiting, and six single items assess further symptoms (dyspnea, insomnia, appetite loss, constipation, and diarrhea) and financial difficulties. The BR-23 module incorporates multi-item scales to assess systemic therapy side effects, arm and breast symptoms, body image, and sexual functioning and single items to assess sexual enjoyment, hair loss, and future perspective.
In both instruments, high functional scores represent better functioning and QOL, whereas a high symptom score indicates more severe symptoms. The time frame for all scales in the questionnaire was the last week, except for items related to sexual activity where a 4-week time frame was applied.
Statistical Methods
The scoring of the EORTC QLQ-C30 items was performed according to the EORTC scoring manual.18 All scores were linearly transformed to a 0 to 100 points scale. In case of missing items, multi-item scores were calculated as the mean of nonmissing items if at least half of the items from the corresponding scale had been completed.
External Comparison With Reference Data
We used the age-specific QLQ-C30 data for the German general population published by Schwarz and Hinz19 as external reference. The 1,139 women and 889 men of the reference population were selected by nationwide random-route technique and interviewed in their private homes by skilled interviewers in 1998. Only QOL data referring to women were considered for our analysis. Age-standardized reference QOL scores were calculated by weighting the age-specific mean scores from the reference population according to the age structure of the breast cancer patients 3 years after diagnosis. Age-standardized and age-specific means were compared and interpreted in a descriptive way according to the findings from Osoba et al20 and Michelson et al21 that differences of 10 points or more are clinically meaningful.
Internal Comparison
Because QOL scores usually do not follow a normal distribution, we applied the Wilcoxon matched-pairs signed rank sum test to test whether changes from T1 to T2 in QOL were statistically significant. Only women who provided information in T1 and in T2 could be included for the internal comparison. In addition, we assessed the number of clinically relevant changes in QOL (differences of 10 points or more) from T1 to T2, and a 2 goodness-of-fit test was applied to test the null hypothesis of whether the proportion indicating improvement was equal to the proportion indicating clinically significant impairment. Comparisons were performed in the total cohort and also in subgroups according to age, tumor stage, type of surgery, and recurrence of disease. No adjustments for multiple testing were applied, so P values refer to the individual tests rather than to a global test for differences.
RESULTS
Characteristics of the Study Population
Characteristics of the study population are listed in Table 1. Three quarters of all breast cancer patients were 50 years old or older. In 55% of all patients, the breast cancer was confined to the breast, whereas 45% already showed clinical evidence of tumor dissemination beyond the breast. With the exception of one woman, all other women had undergone some form of breast surgery. Breast-conserving surgery and mastectomy were performed in approximately equal numbers of women.
During the 2-year follow-up interval between year 1 and year 3 after diagnosis, 31 women (10%) died. These women more often had advanced tumors (P < .01), had more frequently undergone chemotherapy (P < .01), and had poorer overall QOL at T1 (P = .02; data not shown) than the 283 women with breast cancer who were still alive at T2. Of the 283 women who remained alive, 251 returned the questionnaire (88%). Respondents and nonrespondents were similar with respect to age (P = .22), tumor stage (P = .34), therapy (P = .22 to .99), education (P = .56), comorbidity status (P = .58), and overall QOL at T1 (P = .48; not all data are shown in Table 1).
QOL 3 Years After Diagnosis: External Comparison
Three years after diagnosis, women with breast cancer and women from the general population reported virtually identical mean scores of global health and QOL (Fig 1). Also, breast cancer patients scored their physical functioning only slightly worse than women from the general population. However, larger differences indicating clinically significant detriments were found for role, emotional, cognitive, and social functioning. These deficits were observed regardless of tumor stage (data not shown).
With respect to the symptoms, the QOL among the women with breast cancer was most severely affected by insomnia, fatigue, pain, and dyspnea. More than 80% of women with breast cancer reported problems with fatigue; and trouble with sleeping was reported by 72%, pain was reported by 58%, dyspnea was reported by 49%, and financial difficulties as a result of medical treatment and/or physical condition was reported by 32%. Other symptoms, such as nausea and vomiting, constipation, diarrhea, and appetite loss, were reported less frequently (15% to 20%). All symptoms were more prevalent among the breast cancer group than among the reference group, but the differences were most pronounced for the symptoms of insomnia, fatigue, dyspnea, and financial difficulties (Fig 2). Exclusion of women with distant disease did not alter these findings (data not shown).
Age-Specific External Comparison
The differences between breast cancer patients and women from the general population regarding functional (Fig 3) and symptom scores (data not shown) were largest for all subscales among the younger age groups and diminished with older age. Deficits among women with breast cancer were most prominent for role, emotional, social, and cognitive functioning, whereas only minor differences existed in the physical functioning and global health/QOL subscales.
Changes Between the First and Third Year After Diagnosis: Internal Comparison
Table 2 lists the changes in QOL scores between the first and third year after diagnosis with respect to the items covered by the QLQ-C30 and the breast cancer–specific module BR-23. Because only scores from women who provided information at T1 and T2 could be included in this analysis, the reported means for T2 slightly differ from the data shown in Figures 1 and 2.
For most functional and symptom scales, the mean item-specific scores measured at T2 were similar to those obtained 2 years earlier, indicating that, overall, only minor changes have occurred between T1 and T2. However, clinically meaningful changes might have occurred on an individual level, but the proportion of women who reported either improvements or impairments of 10 points or more is fairly balanced for most items. Among the breast cancer–specific items covered by the BR-23, arm symptoms seem to be particularly relevant. More than 80% of all women reported restrictions in mobility, pain, and edema, which persisted during the follow-up period. Women who underwent axilla dissection reported, on average, a higher score of arm symptoms than women with breast cancer who did not undergo axilla dissection (mean score at T1, 38 v 26; mean score at T2, 37 v 26, respectively). Improvements, if any, were seen with respect to less financial difficulties, a better future perspective, and less breast symptoms. In contrast, other more general symptoms, such as dyspnea and appetite loss, seem to have become more prevalent during the follow-up.
Changes in Specific Subgroups: Internal Comparison
Stratification by age revealed that, with the exception of an increase in sleeping disorders among the patients aged 70 years and older and a decrease in financial difficulties among the patients younger than 60 years, no age-specific pattern in the temporal development was observed (data not shown). With respect to tumor stage, women with regional or distant disease rated their QOL at T1 as less favorable than women with local disease. Three years after diagnosis, the differences between patients with local versus late-stage cancer had diminished (data not shown).
Although women 3 years after breast-conserving therapy reported, on average, higher scores with respect to body image than women after mastectomy (82 v 66, respectively), women after mastectomy, compared with women after breast-conserving therapy, reported better emotional functioning (64 v 59, respectively), fewer breast symptoms (24 v 30, respectively), and better future perspective (43 v 40, respectively). Compared with their own experience 2 years earlier, women with breast-conserving therapy showed improvements with respect to emotional functioning (from 59 to 65; P < .01), future perspective (from 40 to 52; P < .01), and breast symptoms (from 30 to 24; P < .01), whereas only modest changes were observed among women who underwent mastectomy.
Recurrence of breast cancer during the follow-up interval (n = 15) had a deleterious effect on QOL (Fig 4). Dramatic impairments were observed for all function scales and all symptoms covered by the QLQ C-30 and all breast cancer–specific items covered by the BR-23 questionnaire including body image, future perspective, arm symptoms, systemic side effects, and hair loss. However, because of the small number of patients with recurrent breast cancer, the mean scores for the breast cancer patients and their differences from the mean scores of the general population shown in Figures 1 to 3 remained essentially the same when the analyses were restricted to patients without recurrent disease.
DISCUSSION
The results of our study indicate that deficits in role, emotional, cognitive, and social functioning observed 1 year after diagnosis, when acute treatment effects are thought to have declined, persist over years in women with breast cancer. The results also show that predominantly younger women are affected. Improvements in QOL from the first to the third year after diagnosis seem to be modest and are limited to improvements with respect to financial difficulties, a better future perspective, and fewer breast symptoms. In contrast, other more general symptoms, such as dyspnea and appetite loss, seem to become slightly more common, but this increase is more likely related to changes within the context of normal ageing.
Only a few studies have investigated adjustment during the period when active treatment ends and the patient begins to resume her usual activities.22 The sparse research available suggests that long-term survivors (5 years and more past diagnosis) typically rate their overall QOL as fairly high23 but that psychological issues,24,25 disturbances in body image,26 and family functioning23 continue to be a source of great distress for women with breast cancer.
It has been reported that older patients with breast cancer adjust more easily than younger women,9,27-32 both immediately after breast cancer surgery and 1 or more years after diagnosis. Similarly, in our study, young women fared worse than older women in both physical and psychological dimensions when compared with the reference population. It has been suggested that older people adjust their perception about their health, whereas younger people may hold higher expectations concerning their physical and functional status.10 In addition, treatment-related menopause may cause greater emotional disruption and poorer health perception among younger women compared with older women.27
Improvements in our study between the first and the third year after diagnosis in emotional functioning, future perspective, and breast symptoms seem to be stronger in women after breast-conserving therapy, whereas only modest improvements were observed among women who underwent mastectomy. However, women after breast-conserving therapy scored worse than women with mastectomy 1 year after diagnosis with respect to all of these scores, and it seems that the QOL scores of women who had undergone breast-conserving therapy caught up after 3 years to the QOL scores of women with mastectomy. Similar results have been recently described by Engel et al8 (another study from Germany), but other studies10,12,33,34 found no difference between breast-conserving therapy and mastectomy patients in terms of long-term adjustment after breast surgery.
Recurrence of disease had a deleterious effect on QOL among our study population. On average, all functional scores declined to a clinically meaningful degree, and most symptoms augmented considerably. In contrast, the scores remained almost identical (on average) in those patients who remained free of disease. However, our results also indicate that women who remain cancer free continue to suffer from psychosocial deficits, and this might be related to decreases in emotional support and the size of the social networks as time after diagnosis passes.10 In addition, some physical and social problems experienced by women with breast cancer persist over years. Such problems include menopause and menstrual changes, infertility, sleep problems, fatigue, lymphedema, pain, problems with physical and recreational activities, weight gain, breast pain, and fear of disease recurrence.35-39 Specific interventions, such as patient education, coping skill management, and support groups, might be helpful to improve QOL in women after diagnosis of breast cancer, but the actual impact of these treatments seems to be limited by low rates of participation.40 With respect to fatigue, which is one of the most common symptoms reported by breast cancer patients, several interventions have been recommended including application of epoetin, transfusion of RBCs, mild physical exercise, sleep hygiene, attention-restoring activities, and psychostimulants,41 but evidence from randomized trials is limited.42
In addition, arm problems, which are reported by 80% of all women with breast cancer, are a long-lasting effect and deserve further attention. Almost all women in our study underwent some form of axilla dissection (in more than 80% of all women, 10 or more lymph nodes were examined). It has been reported that over one third of all patients with breast cancer suffer persistent arm problems that substantially affect QOL.5-7 In contrast, patients undergoing sentinel lymph node biopsy, a new minimally invasive surgical method for axillary staging, seem to recover sooner and report less arm and shoulder problems (pain, lymphedema, and numbness and tingling sensations).43-45 Sentinel lymph node biopsy is now becoming more and more a routine technique and will hopefully reduce the burden of arm-related problems in breast cancer patients in the future.
Although our study suggests that 3 years after diagnosis women with breast cancer experience reductions in multiple domains of QOL, it is possible that our results are still somewhat too optimistic because we restricted our analysis to those women who had already participated in the first follow-up, leaving out those women who died during the follow-up period and those who refused to participate in the first follow-up. However, this bias might be compensated for by women who considered the treatment of their disease as completed, who did not want to be reminded of it, and who might also be less likely to participate. Another limitation is the fact that we had to rely on data from an external comparison group as reference data because no QOL data were collected from the study participants at T0. Ideally, baseline QOL data should be obtained before diagnosis of cancer to measure the impact of the disease, but this intention is almost impossible to realize. Also, it would have been of utmost interest to consider the influence of comorbidity on QOL. However, neither pertinent data from the comparison group nor data regarding the occurrence of other chronic conditions during the follow-up period were available.
Despite these limitations, our study shows that deficits in role, emotional, cognitive, and social functioning persist over years in women with breast cancer and predominantly affect younger patients. The role of individual coping behavior and the chances for intervention have to be further explored. Because the individual’s perception of the impact of breast cancer may change over time and the number of long-term survivors of breast cancer will further increase, further studies addressing the long-term consequences of breast cancer are warranted.
Authors’ Disclosures of Potential Conflicts of Interest
The authors indicated no potential conflicts of interest.
Acknowledgment
We thank Reinhold Schwarz, MD, and Andreas Hinz, PhD, from the University of Leipzig (Leipzig, Germany) for providing additional information regarding the reference scores from the German general population.
NOTES
Supported by two grants from the German Cancer Foundation (Deutsche Krebshilfe), project No. 70-1816 and 70-2413.
Presented in part at the 26th Annual Meeting of the International Association of Cancer Registries, Beijing, China, September 14-16, 2004.
Authors’ disclosures of potential conflicts of interest are found at the end of this article.
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Department of Epidemiology, University of Ulm, Ulm
Saarland Cancer Registry, Saarbrücken, Germany
ABSTRACT
PURPOSE: To assess whether detriments in quality of life (QOL) among women with breast cancer persist over years.
PATIENTS AND METHODS: QOL was assessed in a population-based cohort of 314 women with breast cancer from Saarland (Germany) 1 and 3 years after diagnosis and compared internally and with reference data from the general population.
RESULTS: Three years after diagnosis, deficits in QOL were still apparent for role, emotional, cognitive, and social functioning and for the symptoms of insomnia, fatigue, dyspnea, and financial difficulties. Differences between breast cancer patients and women from the general population were predominantly found in younger ages. Compared with the QOL scores measured 1 year after diagnosis, only minor functional changes were observed, but recurrence of breast cancer during the follow-up interval had a deleterious effect on QOL.
CONCLUSION: Deficits in role, emotional, cognitive, and social functioning persist over years in women with breast cancer and predominantly affect younger patients.
INTRODUCTION
Breast cancer is the most common cancer in women, accounting for approximately one third of all cancers in females.1 As a result of advances in early diagnosis and therapy, the prognosis of breast cancer has improved over the last decades. Five-year relative survival estimates of approximately 86%2 indicate that the vast majority of women with breast cancer are now becoming long-term survivors. In fact, breast cancer survivors represent the largest group of long-term cancer survivors. They comprise approximately 40% of all female cancer survivors in developed countries.3 Therefore, in addition to disease-free and overall survival issues of cancer survivorship, quality of life (QOL) is particularly relevant for this form of cancer.
It has been reported that women with breast cancer attain maximum recovery from the physical and psychological trauma of cancer treatment by 1 year after diagnosis, and a number of QOL aspects and rehabilitation problems seem to worsen after 1 year.4 In particular, a large proportion of breast cancer patients are likely to suffer from persistent arm problems, which substantially affect QOL.5-7 However, the pattern does not seem to be uniform because improvements have also been reported after 1 year for overall QOL and specific psychosocial aspects including role, emotional, and social functioning.8 So far, changes in QOL after the first year have been assessed only in a few longitudinal studies4,9-14 with conflicting results. Some of the heterogeneity may be a result of methodologic differences (eg, QOL instruments, age range, setting, and length of follow-up interval). Furthermore, previous studies rarely compared QOL in breast cancer patients with QOL of women of similar age in the general population with the same instruments.
We recently found that overall QOL and physical functioning of women with breast cancer were comparable in women from the general population 1 year after diagnosis of breast cancer, when most acute treatment-related effects are likely to have disappeared.15 However, deficits in emotional, social, role, and cognitive functioning were still apparent and affected predominantly younger women with breast cancer. Specific symptoms like insomnia, fatigue, and financial difficulties also seemed to be of particular concern for women with breast cancer, resulting in a detrimental effect on QOL. In a follow-up of this large population-based cohort, we now address the questions of whether the detriments in QOL in breast cancer patients found at 1 year after diagnosis persist over a longer period and, specifically, whether young women with breast cancer continue to suffer or start to adapt and recover.
PATIENTS AND METHODS
Study Design
In October 1996, we set up a population-based, statewide cohort study on risk factors, diagnostic procedures, and prognosis for various forms of cancer in Saarland (a state in southwest Germany with a population of 1 million inhabitants). Patients with breast, colorectal, or gastric cancer, diagnosed between October 1996 and February 1998, were recruited within days after diagnosis from all hospitals that offered in-patient cancer treatment in the study region. Permission to approach the patient was obtained by the physician after the study was explained to the patient. Study eligibility criteria for recruitment included histologically confirmed invasive cancer, age 18 to 80 years, sufficient knowledge of the German language, and resident of the state of Saarland. The protocol for this study and for the subsequent follow-up were approved by the local and regional ethics committees. Informed written consent was obtained from each patient.
In total, 387 women with breast cancer were recruited shortly after diagnosis (T0) and constituted the baseline population for the first follow-up 1 year later (T1), when we sent a QOL questionnaire to each patient (see QOL Questionnaire). Fourteen women (3.6%) died during the first year after diagnosis. These women tended to be older and to have advanced tumors. Of the 373 women who were alive, 314 (84%) participated in the first QOL survey and returned the questionnaire. Respondents and surviving nonrespondents were similar with respect to age, education, and comorbidity status. However, tumor stage was more favorable among respondents.
Two years after T1 (ie, 3 years after diagnosis), we conducted a second follow-up (T2) and sent the QOL questionnaire a second time to all respondents of the 1-year follow-up to obtain information about potential changes in QOL over time. These 314 women form the study population of the study presented in this article.
Data Collection
Baseline data (T0), including patient age, education level, and marital status and date of diagnosis and comorbidity, were obtained by structured face-to-face interviews. The interviews were conducted within a few days to weeks after diagnosis of breast cancer and, in most cases, during the first hospitalization as a result of breast cancer. Information regarding tumor stage at time of diagnosis and initial therapy was abstracted from hospital records.
One year after diagnosis of cancer (T1), all study participants were sent a letter with detailed information describing the purpose of the follow-up study together with a QOL questionnaire and a stamped addressed return envelope. The questionnaire also included questions referring to therapies during the follow-up period. Nonrespondents were mailed up to two reminders and were contacted by phone if they did not respond after three mailings. If all of these attempts did not result in any response, the vital status of nonrespondents was obtained from the residents’ registration office.
Three years after diagnosis of cancer (T2), we repeated the QOL follow-up and sent the same QOL questionnaire to all respondents of the T1 follow-up. Again, nonrespondents were mailed up to two reminders and were contacted by phone if they did not respond after three mailings. The vital status of nonrespondents was obtained from the residents’ registration office.
QOL Questionnaire
QOL was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30)16 and the breast cancer–specific module BR-23, which was also developed by the EORTC.17 The EORTC QLQ-C30 is a validated, brief, self-reporting, cancer-specific measure of QOL and is composed of five multi-item functional scales that evaluate physical, role, emotional, cognitive, and social function and one global health status/QOL scale. Three multi-item symptom scales measure fatigue, pain, and nausea/vomiting, and six single items assess further symptoms (dyspnea, insomnia, appetite loss, constipation, and diarrhea) and financial difficulties. The BR-23 module incorporates multi-item scales to assess systemic therapy side effects, arm and breast symptoms, body image, and sexual functioning and single items to assess sexual enjoyment, hair loss, and future perspective.
In both instruments, high functional scores represent better functioning and QOL, whereas a high symptom score indicates more severe symptoms. The time frame for all scales in the questionnaire was the last week, except for items related to sexual activity where a 4-week time frame was applied.
Statistical Methods
The scoring of the EORTC QLQ-C30 items was performed according to the EORTC scoring manual.18 All scores were linearly transformed to a 0 to 100 points scale. In case of missing items, multi-item scores were calculated as the mean of nonmissing items if at least half of the items from the corresponding scale had been completed.
External Comparison With Reference Data
We used the age-specific QLQ-C30 data for the German general population published by Schwarz and Hinz19 as external reference. The 1,139 women and 889 men of the reference population were selected by nationwide random-route technique and interviewed in their private homes by skilled interviewers in 1998. Only QOL data referring to women were considered for our analysis. Age-standardized reference QOL scores were calculated by weighting the age-specific mean scores from the reference population according to the age structure of the breast cancer patients 3 years after diagnosis. Age-standardized and age-specific means were compared and interpreted in a descriptive way according to the findings from Osoba et al20 and Michelson et al21 that differences of 10 points or more are clinically meaningful.
Internal Comparison
Because QOL scores usually do not follow a normal distribution, we applied the Wilcoxon matched-pairs signed rank sum test to test whether changes from T1 to T2 in QOL were statistically significant. Only women who provided information in T1 and in T2 could be included for the internal comparison. In addition, we assessed the number of clinically relevant changes in QOL (differences of 10 points or more) from T1 to T2, and a 2 goodness-of-fit test was applied to test the null hypothesis of whether the proportion indicating improvement was equal to the proportion indicating clinically significant impairment. Comparisons were performed in the total cohort and also in subgroups according to age, tumor stage, type of surgery, and recurrence of disease. No adjustments for multiple testing were applied, so P values refer to the individual tests rather than to a global test for differences.
RESULTS
Characteristics of the Study Population
Characteristics of the study population are listed in Table 1. Three quarters of all breast cancer patients were 50 years old or older. In 55% of all patients, the breast cancer was confined to the breast, whereas 45% already showed clinical evidence of tumor dissemination beyond the breast. With the exception of one woman, all other women had undergone some form of breast surgery. Breast-conserving surgery and mastectomy were performed in approximately equal numbers of women.
During the 2-year follow-up interval between year 1 and year 3 after diagnosis, 31 women (10%) died. These women more often had advanced tumors (P < .01), had more frequently undergone chemotherapy (P < .01), and had poorer overall QOL at T1 (P = .02; data not shown) than the 283 women with breast cancer who were still alive at T2. Of the 283 women who remained alive, 251 returned the questionnaire (88%). Respondents and nonrespondents were similar with respect to age (P = .22), tumor stage (P = .34), therapy (P = .22 to .99), education (P = .56), comorbidity status (P = .58), and overall QOL at T1 (P = .48; not all data are shown in Table 1).
QOL 3 Years After Diagnosis: External Comparison
Three years after diagnosis, women with breast cancer and women from the general population reported virtually identical mean scores of global health and QOL (Fig 1). Also, breast cancer patients scored their physical functioning only slightly worse than women from the general population. However, larger differences indicating clinically significant detriments were found for role, emotional, cognitive, and social functioning. These deficits were observed regardless of tumor stage (data not shown).
With respect to the symptoms, the QOL among the women with breast cancer was most severely affected by insomnia, fatigue, pain, and dyspnea. More than 80% of women with breast cancer reported problems with fatigue; and trouble with sleeping was reported by 72%, pain was reported by 58%, dyspnea was reported by 49%, and financial difficulties as a result of medical treatment and/or physical condition was reported by 32%. Other symptoms, such as nausea and vomiting, constipation, diarrhea, and appetite loss, were reported less frequently (15% to 20%). All symptoms were more prevalent among the breast cancer group than among the reference group, but the differences were most pronounced for the symptoms of insomnia, fatigue, dyspnea, and financial difficulties (Fig 2). Exclusion of women with distant disease did not alter these findings (data not shown).
Age-Specific External Comparison
The differences between breast cancer patients and women from the general population regarding functional (Fig 3) and symptom scores (data not shown) were largest for all subscales among the younger age groups and diminished with older age. Deficits among women with breast cancer were most prominent for role, emotional, social, and cognitive functioning, whereas only minor differences existed in the physical functioning and global health/QOL subscales.
Changes Between the First and Third Year After Diagnosis: Internal Comparison
Table 2 lists the changes in QOL scores between the first and third year after diagnosis with respect to the items covered by the QLQ-C30 and the breast cancer–specific module BR-23. Because only scores from women who provided information at T1 and T2 could be included in this analysis, the reported means for T2 slightly differ from the data shown in Figures 1 and 2.
For most functional and symptom scales, the mean item-specific scores measured at T2 were similar to those obtained 2 years earlier, indicating that, overall, only minor changes have occurred between T1 and T2. However, clinically meaningful changes might have occurred on an individual level, but the proportion of women who reported either improvements or impairments of 10 points or more is fairly balanced for most items. Among the breast cancer–specific items covered by the BR-23, arm symptoms seem to be particularly relevant. More than 80% of all women reported restrictions in mobility, pain, and edema, which persisted during the follow-up period. Women who underwent axilla dissection reported, on average, a higher score of arm symptoms than women with breast cancer who did not undergo axilla dissection (mean score at T1, 38 v 26; mean score at T2, 37 v 26, respectively). Improvements, if any, were seen with respect to less financial difficulties, a better future perspective, and less breast symptoms. In contrast, other more general symptoms, such as dyspnea and appetite loss, seem to have become more prevalent during the follow-up.
Changes in Specific Subgroups: Internal Comparison
Stratification by age revealed that, with the exception of an increase in sleeping disorders among the patients aged 70 years and older and a decrease in financial difficulties among the patients younger than 60 years, no age-specific pattern in the temporal development was observed (data not shown). With respect to tumor stage, women with regional or distant disease rated their QOL at T1 as less favorable than women with local disease. Three years after diagnosis, the differences between patients with local versus late-stage cancer had diminished (data not shown).
Although women 3 years after breast-conserving therapy reported, on average, higher scores with respect to body image than women after mastectomy (82 v 66, respectively), women after mastectomy, compared with women after breast-conserving therapy, reported better emotional functioning (64 v 59, respectively), fewer breast symptoms (24 v 30, respectively), and better future perspective (43 v 40, respectively). Compared with their own experience 2 years earlier, women with breast-conserving therapy showed improvements with respect to emotional functioning (from 59 to 65; P < .01), future perspective (from 40 to 52; P < .01), and breast symptoms (from 30 to 24; P < .01), whereas only modest changes were observed among women who underwent mastectomy.
Recurrence of breast cancer during the follow-up interval (n = 15) had a deleterious effect on QOL (Fig 4). Dramatic impairments were observed for all function scales and all symptoms covered by the QLQ C-30 and all breast cancer–specific items covered by the BR-23 questionnaire including body image, future perspective, arm symptoms, systemic side effects, and hair loss. However, because of the small number of patients with recurrent breast cancer, the mean scores for the breast cancer patients and their differences from the mean scores of the general population shown in Figures 1 to 3 remained essentially the same when the analyses were restricted to patients without recurrent disease.
DISCUSSION
The results of our study indicate that deficits in role, emotional, cognitive, and social functioning observed 1 year after diagnosis, when acute treatment effects are thought to have declined, persist over years in women with breast cancer. The results also show that predominantly younger women are affected. Improvements in QOL from the first to the third year after diagnosis seem to be modest and are limited to improvements with respect to financial difficulties, a better future perspective, and fewer breast symptoms. In contrast, other more general symptoms, such as dyspnea and appetite loss, seem to become slightly more common, but this increase is more likely related to changes within the context of normal ageing.
Only a few studies have investigated adjustment during the period when active treatment ends and the patient begins to resume her usual activities.22 The sparse research available suggests that long-term survivors (5 years and more past diagnosis) typically rate their overall QOL as fairly high23 but that psychological issues,24,25 disturbances in body image,26 and family functioning23 continue to be a source of great distress for women with breast cancer.
It has been reported that older patients with breast cancer adjust more easily than younger women,9,27-32 both immediately after breast cancer surgery and 1 or more years after diagnosis. Similarly, in our study, young women fared worse than older women in both physical and psychological dimensions when compared with the reference population. It has been suggested that older people adjust their perception about their health, whereas younger people may hold higher expectations concerning their physical and functional status.10 In addition, treatment-related menopause may cause greater emotional disruption and poorer health perception among younger women compared with older women.27
Improvements in our study between the first and the third year after diagnosis in emotional functioning, future perspective, and breast symptoms seem to be stronger in women after breast-conserving therapy, whereas only modest improvements were observed among women who underwent mastectomy. However, women after breast-conserving therapy scored worse than women with mastectomy 1 year after diagnosis with respect to all of these scores, and it seems that the QOL scores of women who had undergone breast-conserving therapy caught up after 3 years to the QOL scores of women with mastectomy. Similar results have been recently described by Engel et al8 (another study from Germany), but other studies10,12,33,34 found no difference between breast-conserving therapy and mastectomy patients in terms of long-term adjustment after breast surgery.
Recurrence of disease had a deleterious effect on QOL among our study population. On average, all functional scores declined to a clinically meaningful degree, and most symptoms augmented considerably. In contrast, the scores remained almost identical (on average) in those patients who remained free of disease. However, our results also indicate that women who remain cancer free continue to suffer from psychosocial deficits, and this might be related to decreases in emotional support and the size of the social networks as time after diagnosis passes.10 In addition, some physical and social problems experienced by women with breast cancer persist over years. Such problems include menopause and menstrual changes, infertility, sleep problems, fatigue, lymphedema, pain, problems with physical and recreational activities, weight gain, breast pain, and fear of disease recurrence.35-39 Specific interventions, such as patient education, coping skill management, and support groups, might be helpful to improve QOL in women after diagnosis of breast cancer, but the actual impact of these treatments seems to be limited by low rates of participation.40 With respect to fatigue, which is one of the most common symptoms reported by breast cancer patients, several interventions have been recommended including application of epoetin, transfusion of RBCs, mild physical exercise, sleep hygiene, attention-restoring activities, and psychostimulants,41 but evidence from randomized trials is limited.42
In addition, arm problems, which are reported by 80% of all women with breast cancer, are a long-lasting effect and deserve further attention. Almost all women in our study underwent some form of axilla dissection (in more than 80% of all women, 10 or more lymph nodes were examined). It has been reported that over one third of all patients with breast cancer suffer persistent arm problems that substantially affect QOL.5-7 In contrast, patients undergoing sentinel lymph node biopsy, a new minimally invasive surgical method for axillary staging, seem to recover sooner and report less arm and shoulder problems (pain, lymphedema, and numbness and tingling sensations).43-45 Sentinel lymph node biopsy is now becoming more and more a routine technique and will hopefully reduce the burden of arm-related problems in breast cancer patients in the future.
Although our study suggests that 3 years after diagnosis women with breast cancer experience reductions in multiple domains of QOL, it is possible that our results are still somewhat too optimistic because we restricted our analysis to those women who had already participated in the first follow-up, leaving out those women who died during the follow-up period and those who refused to participate in the first follow-up. However, this bias might be compensated for by women who considered the treatment of their disease as completed, who did not want to be reminded of it, and who might also be less likely to participate. Another limitation is the fact that we had to rely on data from an external comparison group as reference data because no QOL data were collected from the study participants at T0. Ideally, baseline QOL data should be obtained before diagnosis of cancer to measure the impact of the disease, but this intention is almost impossible to realize. Also, it would have been of utmost interest to consider the influence of comorbidity on QOL. However, neither pertinent data from the comparison group nor data regarding the occurrence of other chronic conditions during the follow-up period were available.
Despite these limitations, our study shows that deficits in role, emotional, cognitive, and social functioning persist over years in women with breast cancer and predominantly affect younger patients. The role of individual coping behavior and the chances for intervention have to be further explored. Because the individual’s perception of the impact of breast cancer may change over time and the number of long-term survivors of breast cancer will further increase, further studies addressing the long-term consequences of breast cancer are warranted.
Authors’ Disclosures of Potential Conflicts of Interest
The authors indicated no potential conflicts of interest.
Acknowledgment
We thank Reinhold Schwarz, MD, and Andreas Hinz, PhD, from the University of Leipzig (Leipzig, Germany) for providing additional information regarding the reference scores from the German general population.
NOTES
Supported by two grants from the German Cancer Foundation (Deutsche Krebshilfe), project No. 70-1816 and 70-2413.
Presented in part at the 26th Annual Meeting of the International Association of Cancer Registries, Beijing, China, September 14-16, 2004.
Authors’ disclosures of potential conflicts of interest are found at the end of this article.
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