Fear of cancer recurrence trajectory during radiation treatment and follow-up into survivorship of patients with breast cancer

Breast cancer (BC) is the second most common cancer in the world and the most frequent diagnosed cancer among women [1]. The majority of patients diagnosed with the disease undergo surgery, and a proportion receive chemotherapy and radiotherapy (RT). These treatments are frequently associated with significant psychosocial difficulty across the lifespan [2]. Fear of cancer recurrence (FCR) is one of the most common and aversive psychological phenomena among breast cancer patients [3]. It can be a concern for patients immediately after diagnosis or treatment and has been shown to remain stable for years [4].

Studies have shown that cancer patients “22 % to 87 % reported moderate to high degree of FCR (on average 49 %)” [5], and 55–90% of breast cancer patients report FCR throughout survivorship [6]. Cancer patients who suffer from high FCR report negative behaviour change (e.g. excessive personal checking behaviours and avoidance behaviour) [7], increased health service use [8], inability to plan for the future including work return [9] and significant psychological distress, such as depression, anxiety and post-traumatic stress symptoms [10‐13].

A systematic review of 130 studies found that a number of factors were associated with FCR [5]. Evidence showed that those at greater risk of FCR were survivors diagnosed at a young age, female gender, and with higher education level. Women diagnosed with cancer before age 50 were more likely to suffer from FCR compared with their older counterparts [14]. Various clinical factors, such as having had a mastectomy or chemotherapy, and having more physical symptoms have also been identified as strong predictors of higher FCR. However, these findings are not always consistent [15‐19].

Radiotherapy is a treatment frequently used for cancer patients involving the use of high-energy radiation [20]. Almost a half to two-thirds of cancer patients will have radiotherapy as part of their treatment plan (adjuvant treatment), and almost 75% of patients who received radiotherapy are treated to cure the cancer, rather than to relieve symptoms such as pain [21]. Radiotherapy is delivered in two ways – external to the body by a linear accelerator (external-beam radiation treatment, RT) or within the body by judicious siting of radioactive seeds/implants (brachytherapy, BT). According to the latest data, about 88% of patients received RT while the remaining 12% of patients received BT [20, 21].

To date, although studies have reported that cancer patients may suffer from different psychological problems such as anxiety, depression as well as psychological distress, in the course of RT [22, 23], there have been few studies investigating the relationship between patient’s FCR and the receipt of RT. A previous systematic review by Simard et al. [5] revealed a weak to moderate relationship between cancer treatment type (surgery/ chemotherapy/ radiation treatment) and FCR, and a recent meta-analysis [24] by our group, confirmed a weak association between RT and FCR, however, the correlation was found nonsignificant in breast cancer patients.

One study [25] has investigated FCR development over the first 6 months from surgery but does not focus specifically on the final stage of treatment (radiotherapy) where FCR first develops in earnest according to anecdotal reports. A longitudinal study by Manne et al. [26] found that almost half of the participants diagnosed with gynaecological cancer continued to experience a high level of FCR (high-stable) 6 months after diagnosis, and about 25% of the patients reported decreasing FCR over time (high-decreasing) while the remaining 25% of the sample reported consistently low FCR (low-stable) throughout the 6-month period post diagnosis. A recent report from the Netherlands followed patients soon after primary breast cancer surgery and tracked FCR at baseline, 6 months and 18 months follow up [27]. They found that FCR levels were stable for the first 6 months but at 1.5 years increased in younger compared to older patients. These studies add important information on the pattern of FCR following diagnosis but do not concentrate, we believe, on a critical phase during the patients’ time course namely at the point when RT is provided, and subsequent in the short to medium term, after the patient is discharged, from active hospital treatment. Patients during RT typically report symptoms of pain, skin problems and fatigue [28, 29]. According to Leventhal’s self-regulation model [30] some patients may misinterpret these symptoms to indicate disease progression rather than eradication, hence reflected in FCR increase over the course of treatment. No study has concentrated explicitly on FCR assessment at the RT treatment phase and soon thereafter. Neither has attention been focused on the different levels of fractionation received by patients with breast cancer. The majority of patients at the specialist cancer unit receive ‘routine’ RT treatment of 15 sessions. Patients with tumour margins that are less distinct are treated with the addition of RT with typically 4 ‘booster’ sessions, whereas DCIS patients with non-invasive disease receive 23 sessions. The clinical implications for patients’ FCR levels is unknown. To investigate therefore this stage in the patients’ ‘journey’ may assist our understanding of the development of FCR. Therefore, longitudinal studies on samples using a validated measure of FCR with cancer patients are needed during this phase of the treatment pathway [31, 32].

This is the first study to examine in detail FCR levels over the time course of RT and use the behaviour of initial levels and its trajectory to predict follow up FCR. The results of the initial FCR ratings at the start of RT confirmed previous reports, namely that FCR was less with older compared with younger patients; that chemotherapy and Herceptin use was associated with increased FCR [5]. Most women experienced a decline in fear during and after RT. However, there was considerable variation of trajectories observed that warranted explanation. Studies reveal that RT-induced side effects, such as pain, tiredness and skin reaction, are common and contribute to the symptom burden [40]. Chronic and progressive side effects may be viewed by patients as a constant reminder of their cancer or be misinterpreted as an indicator of cancer recurrence, which leads to higher FCR scores. Besides, patients may hold doubts about the efficacy of RT and feel afraid that they would not receive the same intensive attention and care from health professionals when at home. For those patients who experience a downward (i.e. negative) fear trajectory, one possible reason is that RT is usually the final treatment they received for their disease (after a long duration of treatment - surgery, chemotherapy and RT) and patients may start to feel confident about their attempt to return to normal life.

Patients in the group who received a boost reported more fears than patients in the routine and DCIS group. One explanation is that patients with a boost may conclude that they have a more serious form of breast cancer which requires more intensive treatment. As mentioned previously this is not the case and there may be an argument in favour of sharing the issue of margins with patients in the decision to perform the additional boost fractionation. DCIS patients report lower FCR levels compared to the other two groups because their clinicians typically explain that this condition is not as serious compared to other forms of breast cancer.

The LGCM analysis showed clearly that the initial level (intercept) was the strongest predictor of follow up FCR into the first 2 months of ‘survivorship’. This finding would tend to support the view that FCR is quite stable and already present at the start of RT. Of interest was the additional explanatory value of the trajectory slope with follow up FCR, independent from baseline. Hence patients who reported increasing levels of FCR during the course of their RT would be more likely to have a higher level of follow up FCR in comparison to those with decreasing FCR, taking into account the initial level of FCR. This finding, if replicated, would be important new knowledge as it would demonstrate that for an important group of patients whose concerns about the cancer returning are already being promoted in some way. It raises a crucial question of whether there might be some intervention with these patients to interrupt such a process. Theoretically, according to Leventhal’s self-regulation model [41], we can speculate that patients may be identifying a particular side effect or symptom that they dwell upon. These illness representations potentially ‘fuel the fire’ of anxieties about cancer returning at an early stage from diagnosis while being treated. Intervention while staff are in close contact may be recommended prior to patient discharge from the service. Some initial support for this interpretation has been identified [42].

FCR at approximately 2 months from final treatment of radiotherapy can be predicted reliably from their baseline FCR rating, i.e. start of RT, and in addition from their FCR trajectory during RT.