The untold story of late effects: a qualitative analysis of breast cancer survivors’ emotional responses to late effects

Breast cancer survivors are at increased risk of adverse outcomes, called late effects, years after the completion of active treatment. Late effects can significantly impair physical functioning. The current study aimed to explore breast cancer survivors’ experiences of late effects, their emotional responses to existing or potential late effects and their perceived impact. A total of 36 women treated for breast cancer in the last 10 years participated in semi-structured telephone interviews. Participant views were sought with respect to knowledge, experience, and perceived longer-term risk. A thematic analysis was conducted. Four themes emerged from the data: (1) late effects awareness, (2) framing and coping, (3) uncertainty and (4) management. There was a range of emotional responses to late effects; however, many participants reported being unaware of their risk of late effects. Participants conceptualised late effects as any long-term effect of treatment regardless of the time of onset. Women reported living with constant uncertainty and feared cancer recurrence. Many were focused on managing long-term treatment side effects, rather than late effects. Many women undergo treatment and remain unaware of associated late effect risks. National guidelines recommend patients be informed about late effects; however, the results of this study suggest a gap between policy and practice. Evidence-based interventions are needed to equip women with strategies to physically and emotionally manage late effects.

Early detection of breast cancer through screening and increasing treatment efficacy means survival rates have increased to over 90% [1]. Breast cancer treatments can be aggressive and patients experience a number of side effects during treatment that can persist after treatment is completed as well as late effects that are further changes in functioning, which emerge months to years later [2][3][4]. The cancer rehabilitation literature does not clearly differentiate between the definition of long-term side effects and late effects, yet differentiation is vital as they have different onsets, durations and levels of severity [5,6].
The negative impacts late effects can have on physical functioning are well documented [19][20][21]. Across all cancer populations, late effects have been shown to negatively affect mental and physical quality of life, ability to work, personal relationships, self-esteem and body image satisfaction [22][23][24][25]. Survivors with late effects report significantly lower mental and physical health, greater utilisation of health services and more unmet needs than those without late effects [26,27]. Yet there remains a focus on physical, rather than psychosocial, aspects of post-treatment functioning in the literature [28]. Considering the potential for late effects to affect all aspects of one's life, it is necessary to expand the focus to include potential cognitive, social and emotional impacts [29].
Some of the most commonly reported unmet needs among breast cancer survivors are information about late effects and self-management strategies to manage the illness at home [30]. Insufficient information results in women feeling unprepared for the development of late effects [31]. From the perspective of health professionals, education about late effects is considered an important focus for follow-up posttreatment [32]. However, the emotional impact of breast cancer survivors' experiences of late effects is yet to be systematically explored.
Thus, the current study aimed to explore women's experiences of late effects, their emotional responses to existing or potential late effects and their perceived impact.

Design
This was a cross-sectional qualitative study. Women who consented to the study completed an online survey. The survey included demographic and clinical characteristics as well as questions about emotional wellbeing. At the end of the survey, women were asked to provide their contact details so the researchers could contact them to arrange a telephone interview. Semi-structured individual telephone interviews were conducted to explore women's experiences of late effects, their emotional responses to these experiences and the impact of any late effects. Human research ethics approval was obtained for the study (2019/376).

Participants
Eligibility criteria for the study included (a) being female; (b) being diagnosed with breast cancer in the last 10 years (to ensure participants would be able to give detailed accounts of their experiences yet to also ensure enough time had passed for late effects to arise); (c) being older than 18 years; (d) completion of active treatment with the exception of hormone therapy, i.e., were cancer-free; and (e) sufficient English to participate in a telephone interview. Women who did not meet these criteria were excluded from the study.
Using purposive sampling, participants were recruited through Breast Cancer Network Australia (BCNA), a national support and advocacy organisation for Australians affected by breast cancer. An e-mail invitation containing a URL link to an online survey was sent to BCNA members who had previously agreed to be contacted about research. After clicking on the link and reading the participant information, participants provided online consent. After completing the survey, participants provided contact details for the researchers to arrange a telephone interview at a mutually convenient time.

Data collection
Common demographic and clinical characteristics were collected via the online Qualtrics survey (Qualtrics, Provo, UT) to enable the researchers to describe the study participants. Data collected included demographic information (age, gender, education, employment and language) and clinical information (date and stage of diagnosis and treatment(s) received) to ensure participants met eligibility criteria and to provide context for the qualitative interview, as these variables were thought to potentially impact the experience of late effects.
Emotional wellbeing was assessed using the Depression, Anxiety and Stress Scale (DASS-21), a self-report scale with seven questions in each of the three subscales [33]. Scoring ranges on a 4-point Likert scale from 0 (not at all) to 3 (very much so) according to how often each item was experienced in the past week. High scores indicate greater morbidity. The scale has reported high internal consistency (r = 0.93) and test-retest reliability (r = 0.83) [34] and has been shown to be acceptable when measuring psychological distress in cancer patients [35].
Participants also completed the Fear of Cancer Recurrence Inventory Short-Form (FCRI-SF), a 9-item scale that measures the presence and intrusiveness of thoughts surrounding fear of cancer recurrence. This is a subscale of the original 42-item FCRI [36]. Items are scored on a Likert scale from 0 (not at all or never) to 4 (a great deal or all the time). Total scores ranged from 0 to 36 with higher scores representing greater fear of recurrence. The scale has high reported internal consistency (r = 0.89) and 1-month test-retest reliability (r = 0.80) [37].
Semi-structured telephone interviews explored women's experiences with late effects, their emotional impact, potential risk of future late effects as well as coping strategies for existing late effects. The interview schedule, provided in Online Resource 1, was developed based on a grounded theory approach. Initial questions were based on identified gaps in the literature and a constant comparative approach was employed during the interviews, with the interview schedule adjusted iteratively as new information was obtained from the interviews. Interviews were conducted between June and August 2019 by a trained qualitative researcher. Interviews were audio-recorded, saved in a de-identified format and transcribed verbatim.

Data analysis
Participants' survey data were analysed descriptively and summarised with means and overall percentages. Qualitative data were thematically analysed using a framework approach [38]. The authors familiarised themselves with the data by actively rereading transcripts multiple times. Two authors (JR and JS) double coded ten interviews to identify preliminary codes and develop a draft thematic framework. Differences were resolved through discussion and consensus. The draft thematic framework was then applied to subsequent transcripts (JR), and 20% of interviews were independently doubled coded by a second researcher (JS). Any coding differences were resolved through discussion. Codes were iteratively charted by grouping them into more meaningful subthemes based on theoretical links. Finally, each theme was named, and a thematic map was created.
Regarding trustworthiness, the methodology included verbatim transcriptions, independent coding of transcripts and constant comparative methods so that new information identified was tested in subsequent interviews to ensure accuracy. Also, methods such as purposive sampling ensured results were transferable across diverse demographics within the breast cancer population. Additionally, the consolidated criteria for reporting qualitative research (COREQ) checklist was used to increase methodological rigour (Online Resource 2) [39].

Results
A total of 54 women consented to participate and completed the online survey whilst 36 women participated in interviews. Reasons for interview non-participation included no longer wanting to participate (n = 1), not being contactable/unable to find a convenient time (n = 13) or not meeting eligibility criteria (n = 4). The mean interview length was 40 min (range 15-83 min). Table 1 summarises all interview participants' socio-demographic and clinical information. The mean age was 55.89 (SD = 9.82), and many were university educated (n = 23, 63.89%). 50% (n = 18) were diagnosed with early-stage breast cancer (stage 0-2). Average time since cancer diagnosis was 8.45 years. Overall participants were psychologically well and scored similarly on the DASS-21 severity ratings to other Australian cancer populations with approximately a quarter of participants meeting criteria for moderate to severe distress in either the depression, anxiety or stress subscales [40]. Fear of cancer recurrence was high (M = 17.89, SD = 5.58) with 27.78% of participants meeting the consensus FCR clinical cut off (> 22) [37].
Most participants did not distinguish between side effects and late effects. Participants reported on average 3.06 effects from treatment, the most prevalent being joint pain (n = 22), neuropathy (n = 14), fatigue (n = 13) and cognitive impairment (n = 12). When asked about late effects, many women reported long-term side effects such as ongoing fatigue despite each interview commencing with an explanation of the definition of late effects.
And the fatigue well… I wish I didn't have it… your whole body feels like lead. You can barely put one foot in front of the other. (P27) Based on the framework analysis, four distinct themes emerged from the interviews: (1) late effects awareness, (2) framing and coping with late effects, (3) uncertainty of late effects and (4) management of late effects. Supplementary quotes are provided in Online Resource 3. Figure 1 depicts the thematic map of relationships between themes that influence emotional responses to late effects in breast cancer survivors.

Late effect awareness
Participants' awareness of late effects influenced the meaning they assigned to them. Many women were not aware of any late effects associated with their cancer treatment and were therefore unperturbed.
So long-term effects of the particular chemotherapy I got I don't really know what they are. (P44) Some women reported anxiety upon developing late effects as they assumed symptoms signified a cancer recurrence.
The breast being you know enlarged... a little bit of pain there with it and so you worry that you've got another cancer in that breast. (P21) Some women who were well informed about late effects experienced worry and concern about their perceived severity.
The initial scan suggested that I had some possible damage to my heart … it was really quite a shock to me to think that this potential side effect from chemotherapy had taken five years to show up. (P09) Yet others reported that being informed provided them agency and reduced the uncertainty associated with their potential onset and management. If you are like okay you don't have a choice because you need this treatment but know on the other side you will have to deal with neuropathy you have already taken most of the anxiety away. (P13) Many expressed a desire for more information about when to expect late effects and how to manage them, so to avoid mistaking late effects for cancer recurrence and prevent the onset or ameliorate their severity.
Had I known more prior I possibly wouldn't have ended up with as much lymphoedema as I do. (P52) Many participants recommended patients should receive this information in a dedicated late effects consultation after completing active treatment, separate from their final treatment consultation.

Framing and coping with late effects
Surviving cancer changed each woman's attitude toward life. This influenced how they later framed and coped with late effects. Some participants reported they perceived their late effects as daily physical reminders of their cancer experience and this prevented them from moving on. For many, late effects acted as triggers for fear of cancer recurrence with women reporting they were fearful of planning for the future, had trouble sleeping and in severe cases, had 'panic attacks'. Many reported dismay or disappointment about the restrictions late effects placed on their life, precluding a return to normal.
It's still really sore and tender and I find if I dive into a pool it takes my breath away, it hurts, I can't dive…. I can't mark a football. (P23) In contrast, one participant could positively frame her late effects as confirmation that her treatment was effective.
The reason that my body aches is because I have no oestrogen and having no oestrogen is a good thing so I've managed to convince myself that having my body ache is a good thing. (P09) Some women framed their late effects through the lens of social comparison. Upon hearing of other survivors' lack of late effects (through online forums or personal relationships), many women reported concern and frustration with their own poor post-treatment recovery. In contrast, some participants reported experiencing gratitude upon observing others who were worse off but also worry that their own situation may worsen.
You will meet up with someone who is really struggling with their lymphoedema and it's pretty horrifying to think that that could happen at any time. (P51) Women who perceived their trust in their medical teams had been breached reported negative responses, as they perceived late effects to have been avoidable.
The oncologist and even the breast surgeon to a degree, they are really just interested in getting their bit done… [late effects] could probably be fixed up easily and made better but the oncologist is only looking at the big picture. (P41) However, women who trusted their medical teams perceived late effects as a necessary evil and a 'small price to pay'.
If you want to be around [in ten years] you are going to do what they say and you are going to swallow those pills. (P30) Receiving validation for their experiences with late effects, either from medical teams or online forums, also influenced women's emotional responses. Participants reported relief after learning that others experienced similar symptoms. However, others who perceived their experiences were dismissed reported frustration, worry and even anger.

Uncertainty about late effects
Emotional responses were also influenced by the uncertainty surrounding the duration, eventual severity and impact of late effects. Women were ultimately worried about losing control over their quality of life.
In a few years when hopefully I'm in my 70s, how is my bone density going to be and how is my heart going to be? So, it's more about the potential reduction in life expectancy and the quality. (P23) Participants reported they were unable to plan ahead and were fearful of being unable to fulfil their work and social roles. This in turn resulted in women experiencing anxiety, bitterness and resentment towards their late effects, making coping more difficult.
It's very disappointing… because of the stress and side effects emotionally physically and psychologically from cancer, I've had to realise that this is as far as my journey in my career will go. (P30) Despite the uncertainty, some participants reported acceptance. These participants perceived it was futile to worry about something out of their control.
It's just like you know thinking about whether a plane is going to crash when you are in a plane. There is really nothing you can do about it. (P46) Additionally, participants also used hope to assert some control over the uncertainty. Some were optimistic that a 'wonder pill' will be available by the time they develop late effects.
They might find something to fix it before I get it, so I still got a few years before we have to actually worry about it big time. (P30)

Management of late effects
Many participants reported being proactive in adapting to a 'new normal', modifying behaviour or engaging in preventative self-management to reduce the physical and emotional impact of late effects. This increased coping and reduced uncertainty and, in turn, negative responses to late effects. Some strategies were behavioural and contingent on women's knowledge about late effects such as risk minimisation behaviours (e.g. healthy diet, regular exercise) as well as various treatments (e.g. taking supplements for joint pain, seeing lymphoedema therapists). Other reported strategies were cognitive changes such as having smaller expectations for what can be achieved in one day.
The more I was able to start to make a change and see the differences and not be at the impact quite as much, the more I was kind of like now I'm okay. (P34) However, when management strategies were ineffective, many participants experienced greater worry, concern or frustration.
I think I'm good you know I am really on top of it and then out of the blue there could be problems and I feel like I am back at square one again in my resentment and pity and grief and frustration. (P51)

Discussion
This qualitative study aimed to explore breast cancer survivors' experiences of late effects, their emotional responses to existing or potential late effects and their perceived impact. The analysis gave rise to four distinct themes: (1) late effects awareness, (2) framing and coping with late effects, (3) uncertainty about late effects and (4) management of late effects. Women did not distinguish between side effects and late effects. Rather, they considered late effects as any long-term effect of treatment regardless of the time of onset. Overall women reported a range of physical and cognitive effects from treatment and a range of emotional responses to them. Most women reported limited awareness of late effects, which influenced a variety of emotional responses. The results highlighted a need for evidence-based interventions tailored towards educating women about what late effects are, which specific late effects are associated with their treatments, and equipping them with emotional and physical strategies to improve coping. Quantitative measures of the impact of late effects are required, which could be incorporated into future studies on the prevalence of clinically significant emotional morbidity in response to late effects. Improving the ability to identify those at risk of significant worry or concern would be beneficial in order to allow for early intervention.
Not surprisingly, women in our study were concerned about current late effects rather than potentially developing late effects in the future, even when future late effects were life-threatening. After having experienced the existential threat to life posed by cancer, many chose to 'live in the moment', which may reduce worry about potential late effects in the future [41]. Thus, individuals tend to overestimate the likelihood of proximal threats (e.g. joint pain) rather than distal threats (e.g. cardiovascular disease) [42].
We found that uncertainty contributed to the challenge of late effects, but some women appeared more able to accept and live with uncertainty. Greater tolerance for uncertainty has been linked to greater emotional wellbeing and less distress [43]. Given that the risk of late effects, over and above the risk of recurrence, adds another layer of uncertainty to the survivorship experience, future research should investigate tolerance of uncertainty and its potential utility in reducing negative responses to late effects.
Awareness of late effects had a varied impact on women's emotional responses; however, the current results suggest that more knowledge is better than less. Consistent with previous studies, women with more knowledge about late effects were more aware of their risk and thus better equipped to prevent and manage late effects [44]. Importantly, they could also distinguish late effects from cancer recurrence. National survivorship care guidelines recommend patients be informed and supported in regard to developing and managing late effects [45]. This information is imperative, especially for late effects like cardiovascular disease where women's risk of death begins to increase 10-years post-treatment [20]. This reveals a gap between policy and practice whereby breast cancer survivors are not given adequate information to minimise their risk of death or impairment.
Patients do not generally request information about late effects, highlighting the need for health professionals to raise the topic [6]. Survivorship care plans could provide a viable solution as they note potential late effects based on treatment and personal risk factors and address steps patients should take in the event of developing late effects [46,47]. Survivorship care plans, if implemented adequately, could satisfy participants' information needs, assist with early detection, reduce uncertainty and enhance coping with late effects [48]. However, although recommendations for cancer survivors to receive a survivorship care plan are widely supported, barriers such as limited time and no reimbursement for doctors result in them not being uniformly implemented [19,49,50]. These barriers need to be addressed if care plans are to realise their potential.
Our findings suggest that interventions to help women to cognitively reframe late effects to reduce their emotional toll [51] may be helpful, but these are currently lacking [52]. Dedicated late effects clinics incorporated into survivorship care may be helpful. As survivorship clinics have been shown to enhance knowledge and increase the quality of life and satisfaction in diverse cancer survivor populations [53][54][55], it is likely that a similar multidisciplinary approach to late effects will have similar outcomes for patients.
Further research is needed to investigate the utility of these clinics in addressing specific concerns about late effects.
The present findings need to be considered in light of a number of limitations. Firstly, all participants were self-selected and recruited through a support and advocacy organisation. Hence, the results may have been influenced by selection bias. Additionally, perceptions of male breast cancer survivors on late effects remain unknown. Also, the study only investigated the experiences of women with breast cancer and may not reflect the wider experience of late effects across other cancers populations.
The current study contributes to the limited research on late effects by highlighting the importance of awareness, framing and coping, uncertainty and management in affecting the emotional responses of breast cancer survivors. Evidence-based interventions are needed to provide women with strategies to emotionally and physically cope with late effects. This would increase the quality of life and wellbeing of breast cancer survivors, as well as reduce the survivorship burden on the healthcare system.
Acknowledgements Participants in this research were recruited from Breast Cancer Network Australia's (BCNA) Review & Survey Group, a national, online group of Australian women affected by breast cancer who are interested in receiving invitations to participate in research. We acknowledge the contribution of the women involved in the Review & Survey Group who participated in this project. We also acknowledge the contribution of Profs. Bobby Zachariae and Birgitte Offersen, Aarhus University, in discussing the need for this project at its inception.
Author contribution Dr. Shaw and Dr. Butow conceived the presented idea in collaboration with Danish colleagues. Jodie Rosenberg developed the theory, collected the data and performed the analysis under the supervision of Dr. Shaw. All authors discussed the results and contributed to the final manuscript. Consent to participate After reading the PIS, participants consented to the survey by ticking a box on the first page of the Qualtrics survey. Participants consented to participating in a telephone interview by voluntarily providing their contact details on the last page of the online survey. Participants verbally consented before the interview commenced.
Consent for publication Participants consented to publication by ticking the consent box after reading the following in the PIS, 'Study findings may be published but you will not be identifiable in these publications'.

Conflict of interest
The authors declare no competing interests.