Fear of Cancer Recurrence and Its Negative Impact on Health-Related Quality of Life in Long-term Breast Cancer Survivors

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Cancer Res Treat. 2022;54(4):1065-1073

Publication date (electronic) : 2021 December 8

doi : https://doi.org/10.4143/crt.2021.835

Thi Xuan Mai Tran¹, So-Youn Jung², Eun-Gyeong Lee², Heeyoun Cho³, Na Yeon Kim^4,5, Sungkeun Shim⁶, Ho Young Kim⁶, Danbee Kang⁵, Juhee Cho^5,6, Eunsook Lee^2,7, Yoon Jung Chang^1,3, Hyunsoon Cho^1,8

¹Department of Cancer Control and Population Health, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea

²Center for Breast Cancer, Research Institute and Hospital, National Cancer Center, Goyang, Korea

³Division of Cancer Control and Policy, National Cancer Control Institute, National Cancer Center, Goyang, Korea

⁴Cancer Education Center, Samsung Comprehensive Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

⁵Department of Clinical Research Design & Evaluation, SAIHST, Sungkyunkwan University, Seoul, Korea

⁶Center for Clinical Epidemiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

⁷Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea

⁸Division of Cancer Registration and Surveillance, National Cancer Control Institute, National Cancer Center, Goyang, Korea

Correspondence: Hyunsoon Cho, Department of Cancer Control and Population Health, Graduate School of Cancer Science and Policy, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 10408, Korea, Tel: 82-31-920-2970 E-mail: hscho@ncc.re.kr

Co-correspondence: Yoon Jung Chang, Division of Cancer Control and Policy, National Cancer Control Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 10408, Korea, Tel: 82-31-920-2190 Fax: 82-31-920-2199 E-mail: eunicemd@ncc.re.kr

Received 2021 July 22; Accepted 2021 December 08.

Abstract

Introduction

Survival after breast cancer (BC) has improved over the past decades, thanks to advances in diagnosis and targeted treatments. Ninety percent of female BC patients in Korea survive up to 5 years, and more than 80% can survive up to 10 years. This contributed to more than two hundred thousand BC survivors living in Korea at the end of 2017 [1]. The cumulative increase in incident cases and improvement in survival outcomes have contributed to continuous growth in the number of BC survivors. Though most cancer survivors improve their health status and return to everyday life after cancer, evidence suggests that some cancer survivors experience psychological problems such as depression, distress, or anxiety attributable to their fear that cancer might come back. The ongoing fear or concern might negatively impact the patients’ overall health status and physical and social functioning.

In general, fear of cancer recurrence (FCR) is defined as worry that cancer will return or progress in the same or another part of the body [2]. It is one of the most common psychological effects in all cancers. FCR is thought to persist long after the termination of cancer treatment [3]. Also, previous studies have documented that 42%–70% of BC survivors experienced a high FCR level [4], and 21%–40% of them needed help dealing with FCR [5]. However, in most studies, participants were surveyed in the early years of survivorship, during which time the concerns of diagnosis and treatment are probably most intense. Generally, long-term survivors are defined as those who have survived more than 5 years or more since the time of diagnosis [5,6], and their experience of FCR might be differ with those whose treatment are ongoing. However, the prevalence of FCR and other mood disorders in long-term cancer survivors has been much less extensively investigated.

Research on FCR has been predominantly conducted in Western populations, with few studies that have been conducted with Korean cancer survivors [7,8]. Furthermore, Korean long-term BC survivors’ characteristics might differ from those of BC survivors from other countries due to diagnosis at an early age and peaks in the 40- and 50-year age group [9]. Therefore, this study’s findings may help enhance the knowledge of FCR and health-related quality of life (HRQoL) in long-term BC survivors diagnosed at an early age. In this study, we targeted long-term BC survivors who have survived on an average of 10 years postdiagnosis, and aimed to assess their FCR level, investigate which factors are associated with FCR, and finally, how FCR impacts other patient-reported outcomes (PROs).

Materials and Methods

Results

1. Characteristics of the study population

Of the 333 participants in this study, the mean age at diagnosis was 45.5±8.1, and the mean age at the survey was 57.2±8.4 (Table 1). Half of the participants were diagnosed with BC at age 45 or earlier, and 85% of them were age 65 or younger at the survey time. Sixty-three percent of participants had a time since diagnosis ranging from 9 to 10 years, and 37% had a time since diagnosis of more than 10 years. Ninety percent of participants were diagnosed at early stages (0 to II).

Table 1

Sociodemographic and clinical characteristics of the study population (n=333)

Among 333 long-term BC survivors, 153 women (46%) reported having FCR. Those who experienced FCR had a significantly lower age at diagnosis (47.3 vs. 43.5), a lower proportion of having menopause (79% vs. 89%), and a higher proportion having a time since diagnosis of 10 years or less (69% vs. 58%). No difference in other demographic characteristics, including household income level, employment status, education level, and marital status, was observed between the two groups. Among those who experience FCR, 21 participants (14%) had a history of recurrence, which was significantly higher than that among those without experience of FCR (6%). No difference was observed in stage at diagnosis, treatment modalities, and histological subtype between the two groups.

2. FCR scores and other outcomes

Overall, the total FCRI scores ranged from 0 to 142 (over a maximum of 168), with an average of 54.4±25.7 (S1 Table). The mean Trigger and Severity subscales were 12±7 over a maximum of 32 scores. Among the EQ-5D dimensions, 44% of participants reported having problems with pain/discomfort, and 45% reported having problems with anxiety/depression, resulting in an overall EQ-5D index score of 0.918. Regarding depression measures using PHQ-9, 17 (5%) and 53 (16%) participants reported having moderate/severe and mild depression, respectively. All functioning scales assessed by the EORTC QLQ-C30 were approximately 80 or higher.

A significantly lower EQ-5D summary index, higher depression score, and lower functioning scores were reported in those with FCR (Table 2). The overall EQ-5D index score of those with FCR was 0.887±0.088, which was lower compared with 0.945±0.074 reported by those without FCR. Furthermore, a significant difference was observed in the functioning scores between the two groups, with more inferior results in those with FCR: 14.4 scores on the emotional functioning scale, 10.3 scores on the social functioning scale, and 10.1 scores on the role functioning scale (p < 0.001).

Table 2

HRQoL and depression score by FCR status (n=333)

3. Factors associated factors with FCR

Results from both univariate (S2 Table) and multivariate logistic analysis (Table 3) showed that younger age at diagnosis (adjusted odds ratio [aOR], 2.64; 95% confidence interval [CI], 1.51 to 4.60), shorter time since diagnosis (aOR, 1.75; 95% CI, 1.08 to 2.89), and having a history of cancer recurrence (aOR, 2.56; 95% CI, 1.16 to 5.65) was significantly associated with having FCR. None of the other sociodemographic and clinical variables were associated with having FCR.

Table 3

Multivariate logistic regression on factors associated with FCR (n=333)

4. Impact of FCR on other PROs from path analysis

Both the total FCR score and the severity score were significantly correlated with the scores of other PROs (Fig. 1). The total FCRI score had significant negative correlations with overall QoL status (the EQ-5D index), all EORTC QLQ-C30 functioning subscale scores, and a significant positive correlation with depression by PHQ-9 scores.

Fig. 1

Correlations between FCRI and other factors. The brown color indicates the statistically significant negative associations. The green color indicates the statistically significant positive associations. The white color indicates non-significant associations. A darker color indicates stronger correlations. EQ-5D, EuroQol 5-Dimension Questionnaire Index; FCRI, Fear of Cancer Inventory; stage, stage at diagnosis; Time dx, time since diagnosis (in year).

The path analysis showed consistent results that younger age was associated with a higher FCR level (standardized β=−0.224, p < 0.001) (Fig. 2, S3 Table). A higher FCR level had a negative association with emotional function (β=−0.531, p < 0.001) and a positive association with depression (β=0.471, p < 0.001). Furthermore, a higher FCRI score was significantly associated with a lower EQ-5D index score (β=−0.108, p=0.021) which suggests that FCR might impair overall HRQoL in cancer survivors. Depression and emotional functioning were also significantly associated with overall HRQoL (β=−0.334, p < 0.001 and β=0.366, p < 0.001, respectively). The path analysis model had a decent fit with the following indices: Goodness of Fit Index=0.976, Adjusted Goodness of Fit Index=0.926, Normed-Fit Index=0.970, Comparative Fit Index=0.986, root mean square error of approximation=0.049, and standardized root mean square residual=0.034 (S4 Table).

Fig. 2

Path diagram of the SEM model for the associations between fear of cancer recurrence and other patient-reported outcomes. The structural model presents the effects of age at diagnosis, time since diagnosis, history of recurrence, fear of cancer recurrence, and other patient-reported outcomes. FCRI, Fear of Cancer Recurrence Inventory; QoL, quality of life; SEM, structural equation model. *p < 0.05, ***p < 0.001.

Discussion

The current study targeted long-term young BC survivors with a time since diagnosis ranging from 9 to 16 years, and the study population were those diagnosed with BC at an early age (an average of 45 years). Even though FCR persists long after treatment completion [3], most previous studies assessed FCR in the early course of treatment or survivorship [4,5], and few have focused on FCR among long-term survivors, especially those 10 years or more postdiagnosis. Cancer survivors who have survived more than 5 years or more since the time of diagnosis are considered as long-term survivors [5,6]. In this study, the mean and median survival time of the participants were 11.6 years and 10 years respectively, and thus, they can be considered long-term BC survivors. These are the unique characteristics that differentiate our findings from previous work. Given the increasing number of long-term BC survivors and the limited knowledge on psychological issues in young BC survivors, findings from the current study might help provide the information needed to develop support programs for this particular population.

A low FCR level can be considered a normal reaction of survivors to cancer progression, encouraging survivors to adopt better health behaviors. However, when fear becomes clinically significant or problematic, survivors have chronic intrusive thoughts about a possible recurrence, which might increase depression risk and deteriorate their QoL. Even though 10 years had passed since the initial diagnosis, our results prove that BC survivors still had concerns and worries about their cancer disease. Approximately half of the participants had FCR, consistent with previous studies that reported an FCR prevalence of 40% to 60% [19–21]. In addition, the FCRI subscale scores and total FCRI score reported by our participants were relatively similar to previous studies despite the difference in time since cancer diagnosis [7,14]. In this study, 10% of the participants had a history of recurrence, and these women had a 2.5-fold higher risk of experiencing FCR than those without recurrence. Thus, our findings suggest that long-term BC survivors with a history of FCR might need support to reduce their FCR, and future research on a larger sample of this particular population is needed to provide more comprehensive findings.

Consistent with our research, other studies [4,22,23] found that younger cancer survivors experienced more FCR. For example, a study reported that more than 60% of young cancer survivors had clinical FCR [24]. A more aggressive tumor subtype, and worse prognosis [25] may explain why BC patients diagnosed at a younger age had more concerns and more fears about their disease’s progress. Thus, accumulated evidence supports that early age at diagnosis is a robust predictor for higher FCR. In terms of clinical factors, previous studies found a shorter time since diagnosis [22,24] and worse disease prognosis, such as having a previous recurrence or advanced stage, were associated with higher FCR levels [24,26]. Again, these findings were consistent with our study. However, it should be noted that the time since diagnosis was longer in the present study, with a minimum of 9 years, whereas other studies were commonly conducted among survivors with less than 5 years since diagnosis.

Cancer survivors are at an elevated risk for psychological issues such as FCR, distress, anxiety, and depression that might persist years after receiving treatment. For example, according to previous studies, a higher FCR level was strongly associated with higher levels of depression [2,12,27], emotional distress [7,22,24], and anxiety [27,28]. Consequently, having FCR might worsen cancer survivors’ overall QoL [14,28], which was consistent with our findings.

When fear or concern about cancer recurrence becomes problematic, screening and management for FCR are crucial. Cancer survivors with a high FCR level might benefit from psychoeducation programs or other psychological interventions such as attention training, metacognitive therapy, acceptance, or mindfulness [29,30]. The increasing number of clinical trials to develop therapies to reduce FCR in recent years indicates that FCR is one of the common unmet needs among cancer survivors, and healthcare providers are trying to help survivors with these psychological issues. However, most of the interventions were conducted in Western countries. Thus far, no research on interventions to reduce FCR among Korean cancer survivors and especially long-term cancer survivors has been conducted.

Our study had several limitations. First, due to the nature of cross-sectional data, we could not assess variation in FCR over time and likewise cannot determine causal relationships between FCR and other PROs measured in our research. Second, our results should be interpreted with caution because 90% of the study participants were in BC stage 0 to II, with nine years as the minimum time since diagnosis. In addition, this study might have selection bias due to the fact that only participants agreed to participate were included in the analysis. Thus, they would generally have better HRQoL than advanced stage-patients or those who rejected to participate in the survey.

After 5 years of adjuvant endocrine therapy, BC survivors remain at risk for cancer recurrence. The most recent National Comprehensive Cancer Network Survivorship Guidelines recommend that psychological issues, including FCR, are among the eight most common issues that should be managed in cancer survivors [31]. Long-term BC survivors in our study, especially those diagnosed at a younger age and had recurrence history, still expressed fear or concerns about cancer, which deteriorates their overall QoL and increases depression risk. Thus, long-term BC survivors who experience these psychological issues should be identified and supported.

Though BC survivors often experience worries and uncertainties about their disease, not many directly express these feelings to healthcare providers. Therefore, doctors and other healthcare providers should identify emotional distress in BC survivors and provide appropriate intervention. We believe that our research findings are of interest to healthcare providers and BC survivors because it provides a better understanding of FCR and its impact on long-term BC survivors. Future research should focus on developing screening and psychological interventions to reduce FCR for this growing survivor population, especially in Asian BC survivors.

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