Survivorship care plans for breast cancer patients : understanding the quality of the available evidence

Methods The psychosocial topics identified in bca survivorship care plans created by two different initiatives in our province provided the platform for our search criteria: quality of life (qol), sexual function, fatigue, and lifestyle behaviours. We conducted an umbrella review to retrieve the best possible evidence, and only reviews investigating the intended outcomes in bca survivors and having moderate-to-high methodologic quality scores were included.


INTRODUCTION
Breast cancer (bca) is the most common cancer among women in both developed and developing countries 1-3 .Advancements in screening, diagnostic techniques, and cancer treatments have increased the survival rate for women with bca 4 .Although an overwhelming menu of treatment options to fight this cancer is available, no treatment is devoid of side effects.And like other cancer survivors, bca survivors experience numerous treatment-related challenges, the frequent ones being premature menopause, infertility, impaired physical and psychosocial functioning, and fear of a recurrence or a second primary cancer 5,6 .
After the U.S. Institute of Medicine made its recommendation in 2006 7 , survivorship care plans (scps) were introduced in North America and Europe to help cancer survivors as they move from treatment into the next phase of their lives.Substantial survivorship research and knowledge implementation efforts have occurred in the United States and the United Kingdom [8][9][10] .In the United States, the American Cancer Society, the Centers for Disease Control and Prevention, the livestrong Foundation, and the National Cancer Institute have been collaborating to enhance the translation of survivorship research into evidence-based interventions 11 .Although the Canadian Partnership Against Cancer made survivorship and scps a

RESULTS
The search identified 486 citations, of which 74 scientific reviews met the inclusion criteria.Of those seventy-four reviews, twenty-three were eliminated (reasons presented in Table ii).The remaining fifty-one systematic reviews or meta-analyses  were included in the synthesis. The dtails of the search for, and inclusion or exclusion of, articles are presented in Figure 1.
Of the fifty-one included reviews, twenty-six were of high quality (scores ≥ 8, with a mean quality score of 7.24 ± 1.5).Table iii presents the general characteristics of the included studies; their overall findings; the summary risk ratio estimates, odds ratios, effect sizes or standardized mean differences (when available); and the quality scores.No reviews that investigated the cancer risk in bca patients or survivors were found.Given the diversity of the included reviews and the heterogeneity in the measured outcomes, the data were synthesized qualitatively and were summarized in categories as described in the subsections that follow.
Two streams of studies were delineated: n Cancer-or treatment-related physical and emotional challenges in bca patients or survivors, or both n Interventions used in bca patients or survivors, or both, to alleviate identified challenges and the effects of those interventions

Anxiety, Depression, and Distress
Five reviews investigated anxiety, distress, and symptoms of depression in bca patients and survivors [30][31][32][33][34] .According to those reviews, anxiety and distress are frequently observed in this population and seem to persist for a very long time, although the severity can vary from person to person and across time after the diagnosis.In one review, anxiety was investigated in 1894 bca patients receiving various types of cancer treatments.The authors reported that anxiety was a pervasive issue in bca patients who undergo any of the three most common bca treatment modalities (surgery, chemotherapy, and radiotherapy) and that it tends to persist beyond the acute stage of treatment 31 .The authors also observed higher levels of anxiety among women who underwent mastectomy than among those who underwent breast-conserving therapy.Compared with other treatments, chemotherapy was associated with higher levels of anxiety, and anxiety was highest before the first chemotherapy infusion.
According to another review that investigated depression in bca survivors, levels of depressive symptoms were higher in younger survivors (<50 years of age) than in older survivors (>50 years of age) and in age-matched cancerfree women 32 .Higher levels of anxiety and depressive symptoms were found to be associated with poor social functioning 30,33 , poor physical functioning 30,32 , premature menopause, infertility concerns 30,32 , weight gain, body image, physical inactivity 32 , fear of follow-up diagnostic tests, cancer recurrence, and sexual and relationship problems 34 .

Fatigue
Three reviews reported fatigue in bca patients and survivors 28,30,38 .According to those reviews, fatigue is one of the most frequently observed side effects during the active treatment period and beyond 28,30 .One review that investigated fatigue in 526 bca patients and survivors reported that radiation was significantly and positively associated with fatigue, indicating that patients who received radiation treatment experienced higher levels of fatigue 28 .Other factors that were associated with increased fatigue were decreased appetite, nausea, vomiting, diarrhea, decreased body mass index, and anxiety and depression.Disease staging and neoadjuvant chemotherapy were not found to be associated with the level of fatigue 28 .

Quality of Life
Seven reviews reported on the quality of life (qol) of bca patients and survivors 28,29,[32][33][34][35]37 , and according to those reviews, bca patients and survivors often experience poorer qol. Tw reviews found an association between qol and age, with considerably poorer qol being experienced by younger (≤50 years of age) than by older bca patients and survivors 32,34 .In addition, positive associations were also observed for life stage; comorbid conditions; increased physical symptoms such as breast pain and fatigue; physical, emotional, and psychological dysfunctions; sexual challenges; disease stage; relapse; and active cancer treatment.
One review investigated the types of treatment given to bca patients and their effects on qol, finding that qol was poorer in patients who received chemotherapy or who underwent mastectomy than in those who underwent breast-conserving surgeries 34 .In one review, the qol of 2447 Latina bca survivors was compared with that of non-Latina bca survivors.Latina women were found to experience poorer qol than their non-Latina counterparts 33 .Additionally, bca-related lymphedema and higher levels of fatigue were significantly associated with poorer qol 28,29 .The other factors that were associated with qol were poorer mental and physical health, poor social functioning, greater distress, and greater fear of recurrence.

Lymphedema
Two reviews reported on bca-related lymphedema 27,29 .One estimated the risk for lymphedema based on the treatment that the bca patients received, and they observed that the risk for lymphedema was higher in patients who underwent mastectomy than in those who underwent lumpectomy; higher in those who had an axillary dissection than in those who had no axillary dissection; higher in those who underwent axillary dissection than in those who had a sentinel lymph node biopsy; and higher in those who received radiation and in those who had positive axillary nodes than in those who did not.The second review reported on the effect of lymphedema on qol in bca patients and survivors, finding that lymphedema was significantly associated with poor physical, psychological, and social well-being, and with poorer qol, with the effects being more pronounced in younger survivors (<40 years of age) 29 .

Cognitive Functioning
Only one review investigated cognitive functioning in bca survivors, and it observed significant deficits in cognitive functioning and in verbal and visuospatial abilities for patients who received chemotherapy compared with those who did not, although the magnitude of the effect was small 36 .Age, education, time since treatment, and endocrine therapy did not moderate the observed deficits.

Urinary Challenges
A single review investigated "urinary challenges" in 2500 bca survivors 37 .It reported that, of their cohort, 23% experienced severe urinary dysfunctions, 12% had pain on micturition, and 58% experienced mild-to-moderate difficulties with bladder control (while laughing, crying, or performing simple tasks).

Return to Work
Return to work was investigated in one review, according to which, bca patients and survivors often face a miscellany of challenges that affect the return-to-work decision 38 .They frequently experienced extreme fatigue and fear of recurrence.Also, they were apprehensive about their physical appearance and changed body image; about disclosing the diagnosis to their employer, colleagues, and relatives; and about their ability to work, therefore fearing job loss.Some of the important observations were that the women's perception about their job or work had changed: they valued work less than before, and their motivation and priorities changed and became more goal-focused toward life.Some of the women felt discriminated against because of their cancer; some felt annoyed by questions from colleagues and heard hurtful remarks; some experienced awkward moments of social silence at workplaces; and some required changes in their work situation, such as task modifications that could marginalize them further.Also, some reported not receiving needed advice or support for returning to work, and thus found the return to work difficult, leading to job loss.

Religion and Spirituality
One review investigated the relations between religious and spiritual constructs and psychological well-being in 2582 bca survivors 40 .Although the findings suggest that religion and spirituality (religious coping, religious behaviours, God's image, faith) could play a role in improving or maintaining psychological well-being, multiple operational definitions for religion and spirituality and the challenges involved in quantifying "spirituality" meant that conclusions could not be drawn.

Physical Activity Interventions
Twenty-three reviews investigated the effects on bca patients and survivors of various physical activity interventions  . The tpes of physical activity and their effects are presented in detail in Table iv.The findings of the included reviews indicate that resistance training and aerobics provide significant benefit for physical 42,44,46,48,49,[52][53][54]56,61,63 and emotional 42,45,47,49,54,55,61,63 functioning, and that recreational physical activities or any kind of light-to-vigorous physical activity provides a survival benefit 41,51

Combined Interventions
Two reviews investigated the effects on bca patients and survivors of combinations of interventions 39,64 .The first review investigated the effects of physical activity combined with psychological counselling (individually or in group sessions) provided to bca patients and survivors for physical and social recovery from breast loss.The authors found that 75%-85% of participants returned to work by about 18 months' follow-up.However, that result might not be generalizable, because three of the four studies included in the review had been published 25 years earlier.
The second review examined the effects of combinations of interventions on bca patients and survivors without analyzing the effects separately by intervention type 64 .The interventions included combinations of inpatient rehabilitation, psychological education, psychological education and information, self-help education, information support, information support plus cognitive-behavioural techniques, and exercise together with behavioural therapy.No significant effect on anxiety, depression, distress, and sleep.Such interventions were beneficial with respect to cognition, health-related qol, and social well-being.
In addition, one review that had investigated psychosocial well-being, religion, and spirituality in eighteen observational studies had included one randomized controlled trial (181 women with bca) using meditation, affirmation, imagery, and ritual as the test intervention, comparing that group with a control group receiving cognitivebehavioural therapy 40 .The test intervention was associated with improvements in spiritual integration (p = 0.001) and higher satisfaction (p = 0.006).Yoga was significantly associated with lower levels of fatigue 67 , anxiety, and depression, and with better qol 65,66,68,69 .Mindfulness-based stress reduction was associated with significant reductions in stress, anxiety, and depression in bca patients and survivors 72 .Although polarity treatment, tai chi, and reflexology showed important benefits for cancer-related fatigue in bca survivors, those results are inconclusive because of small sample sizes and high risk for bias.

DISCUSSION
The overall goal of the present study was to contribute to a consistent, province-wide, evidence-based approach to survivorship care planning by synthesizing the published literature about care for bca survivors and by updating the evidentiary base used for the scps created in our province.
To our knowledge, this umbrella review is the first to comprehensively summarize the scientific evidence about the psychosocial aspects of bca survivorship.It is important to note that, although scps aim to support people with cancer as they complete treatment and usually provide information and recommendations to lessen subsequent cancer risk, our review did not find any systematic reviews that investigated the risk of a second primary cancer or bca recurrence.Within the limits of the study design, our findings suggest that, compared with the general population, bca patients and survivors frequently experience higher levels of anxiety and depression, poorer qol, higher levels of fatigue, poorer physical functioning, and urinary dysfunction.Interventions such as physical activity, psychoeducation, yoga, and mindfulness-based stress reduction are beneficial with respect to fatigue, anxiety, depression, stress, fatigue, qol, and physical functioning.This synthesis project, which forms a part of our quality improvement initiatives, aimed to support the production of evidence-based scps and information materials that health care providers can share with bca survivors in our province.Thus, our goal was to use a systematic review of systematic reviews to synthesize, within a short timeframe, the best available evidence to inform a more comprehensive project on scps.The findings of this umbrella review accord with the existing bca scps in our province with respect to the physical and emotional challenges of bca survivors and the dietary and physical activity recommendations (Table v).However, literature concerning the cancer risks specific to bca survivors is lacking.
Although bca is one of the well-studied cancers, the serious dearth in the systematically synthesized literature concerning cancer risk in bca patients and survivors raises a serious question about the extent to which the recommendations made by bca clinicians and scps concerning cancer prevention are evidence-based.Interestingly, Norman et al. 78 described a similar challenge when reviewing the evidence for the effect of lifestyle factors on bca recurrence in early 2007.Although the authors mentioned a number of trials focused on survivors being conducted at that time, we found no systematic reviews that reported on the risk of recurrence or a second primary cancer.
In spite of the serious knowledge gap concerning lifestyle modifications, many bca scps-including the scps from our province-continue to recommend lifestyle modifications to lower future bca risk [79][80][81] .Nevertheless, we identified eighteen reviews (not included in the present umbrella review) of mild-to-moderate quality that investigated bca risk in general populations (Table ii).According to those reviews, alcohol and caffeine intake increase the risk, and healthy diet, fish (those containing long-chain fatty acids), and vitamin D and calcium intake lower the bca risk in the general population; findings for soy intake and multivitamin supplements were inconclusive.Although those findings are important in the primary prevention of bca, can that knowledge be applied for secondary prevention in bca patients and survivors?Systematically conducted reviews have been considered the "gold standard" in knowledge synthesis 24,82,83 , but we have identified a significant gap in the scientific literature that is crucial to bca survivorship care planning.Much has to be done in the area of synthesis research on survivorship, confirming what Luctkar-Flude et al. 16 recently reported.We are therefore highlighting the urgent need for appropriate studies targeting secondary prevention of cancer for bca survivors, especially studies that explore lifestyle and behavioural factors, including diet.Campbell et al. 84 indicated that support for patient self-management and use of evidence-based health promotion interventions were areas of relative weakness when survivorship models of care were analyzed in 8 livestrong Survivorship Centers of Excellence Network sites in the United States, corroborating our statement.
Our study findings concerning fatigue, anxiety, depression, and qol in bca patients and survivors further confirm what was reported recently by Sisler et al. 19 .It is typical that, when faced with certain degrees of physical or functional challenge, a person's psychological adjustment and qol can be impaired 85,86 .
Our umbrella review included a large number of scientific reviews that investigated the effects of various types of interventions on bca patients and survivors.Of those interventions, physical activity and psychoeducation seem promising with respect to fatigue, anxiety, depression, stress, physical functioning, and qol in bca patients and survivors 42,54,61,63

Fertility and birth control options
Some cancer treatments affect a woman's reproductive capabilities.Some chemotherapies can cause early menopause resulting in infertility.
Some cancer treatments can affect the ovaries and may cause temporary or permanent failure of the ovaries (menopause).Sometimes the ovaries are removed altogether.As a result, women go through menopause and experience menopausal symptoms (hot flashes and vaginal dryness).These symptoms can be more severe than those from natural menopause

Self-image, appearance
Breast cancer surgery may be very traumatic.Reconstruction may be an option for some.Low self-esteem has a negative influence on the quality of life.Many women may gain weight.
Some common changes include weight loss or weight gain, hair loss (including pubic hair), loss of a body part, and surgery scars.

Lymphedema
Once it occurs, it rarely goes away.Avoid injections in the arm, and use compression sleeves while exercising and doing strenuous work.
Lymphedema can be temporary or a long-term condition.Avoid lifting the arm to carry heavy things on the same side as the surgery.Exercise regularly, do not overdo.

Return to work
Returning to work can help resume normal routines, focus on other challenges, and reconnect with friends and coworkers.For some, returning to work provides an opportunity to resume a normal routine, to be back in control.
Many women return to work.Plan a gradual return to work in order to ease into work, especially if your work is physical.

Spirituality
You may be looking to find meaning in your life.Some people find their religion and faith helpful.You may try meditation or express through art.
Some women find relief through prayers; others renew their faith again after being diagnosed with cancer, which helps them feel good about themselves.Faith may make them stronger and healthier, giving them strength.

Physical activity
Being physically active maintains optimal bone health and decreases the risk of a bone fracture by improving bone mass and increasing muscular strength, coordination and balance and thereby reducing falls.

Caffeine
Excess caffeine can have a negative effect on bone.Limit coffee to fewer than 4 cups daily.
For optimal bone health, limit coffee to fewer than 4 cups daily.

Alcohol
The link between alcohol consumption and breast cancer recurrence is not as strong.
(No information)

Bone health
You may be at a higher risk for bone loss whether you have treatment-induced menopause or whether you had cancer treatments such as aromatase inhibitors.Bones depend on calcium and vitamin D to stay strong and healthy.Protein, calcium, and vitamin D play important roles in maintaining bone health.
Postmenopausal women have an increased risk of osteoporosis.The risk can also be further increased by factors such as family history, smoking, diet, early menopause, chemotherapy, long-term corticosteroids, and some hormonal therapies that lower estrogen.

Diet and healthy eating
Healthy eating decreases your risk of breast cancer recurrence.A lower fat diet may also help women to achieve weight loss.Breast cancer is linked to obesity, a high-fat diet, and alcohol consumption.One third of these cancers are linked to diet.Vegetables, fruits, and whole grains are healthy foods that should be the base of a balanced diet.
When following a low-fat diet, it is important to focus on both the total amount and quality (type) of fat you eat.Choosing fats found in plant-based foods such as nuts, seeds, avocados, and vegetable oils is preferred to saturated fat from animals.When eating a low-fat diet, it is also important to focus on replacing fat with foods that are minimally processed or refined.

Natural health products
Natural health products are vitamins, minerals, herbs, and other supplements that you take on a regular basis as a natural medicine rather than using them as a food.Sometimes they are taken in higher amounts than can be obtained through your diet.
There is concern about whether vitamins, minerals, and herbal supplements may affect your treatments.These natural health products are therefore not recommended during chemotherapy or radiation treatments.

Calcium and vitamin D
Calcium and vitamin D are essential for strong bones.A daily intake of calcium is 1200 mg.A daily supplement of 1000 IU vitamin D is recommended for bone health and the prevention of cancer.
Calcium and vitamin D are essential for strong bones.A daily dose is a sum of what you consume from food sources and from supplements.
The recommended daily intake of calcium is 1200 mg.Vitamin D intake from all sources should not exceed 4000 IU daily.

Organic food
The research concerning organic food and its association with cancer risk has not been studied accurately.To reduce your risk, buy locally grown foods that are in season and be sure to peel and wash vegetables and fruits well.
(No information)

Saturated fat and cholesterol
Choose lean cuts of meat, poultry without skin, and low-fat milk products.Choose an unsaturated fat.Choose low-fat milk products and lean cuts of meat.Limit high cholesterol foods such as eggs and shellfish.
Low-fat food may reduce the risk of cancer recurrence.Choose fat from plant-based foods such as nuts, seeds, avocados, and vegetable oils rather than the saturated fat from animals.

Soy
Soy contains a form of plant estrogen.Up to 2-3 servings of soy foods daily are safe in women with a history of breast cancer whether they had estrogen receptor-positive disease or use tamoxifen hormonal therapy.
Soy may contain plant estrogen.

Hormones in food
Hormones may stimulate breast cancer growth or affect hormonal treatments such as tamoxifen.Confusion exists concerning the potential harm of hormones in foods, specifically milk and other dairy products, poultry, and beef.Hormonal growth products are not present in dairy and poultry products, including turkey, in Canada.
The potential benefits and risks of foods such as flax and soy, which contain plant estrogens, are not well known at this time.

Salt intake
Limit your salt intake.Salt can have a negative effect on bone.Limit salt intake.
Salt can have a negative effect on bones.Check the nutrition label on processed foods, and limit salt to less than 2100 mg daily.
et al. 18 .Treatments for bca-such as ovarian suppression, chemotherapy, and endocrine therapies-can lead to severe menopausal symptoms in women 87,88 , and it has been postulated that estrogen deficiency might be leading to atrophy of the urinary tract, leading to urinary symptoms and sexual dysfunctions 88,89 .Although sexual dysfunction is a frequently observed side effect of treatment in bca patients and survivors, we found only one review that investigated the effects of exercise, counselling, and information interventions on sexual functioning 90 .The review reported that counselling seemed to be beneficial, but its findings remain inconclusive because of methodology flaws and a high risk for bias found both in the review itself and in the included primary studies.
The following limitations should be kept in mind in interpreting our results.Although our umbrella review included only moderate-or high-quality systematic reviews and meta-analyses, we had no control over the studies that were included in those publications.The systematic reviews-but not the original studies included in those reviews-can be assessed using amstar.Even when quality assessments were performed in the included reviews, the tools used for those assessments varied widely.We came across many reviews that reported inconclusive findings because of the heterogeneities that they observed.And heterogeneities were not restricted to measured outcomes alone; they also pertained to the measuring tools used, to follow-up periods, to the populations studied, and to the contradictory findings observed.
While recognizing those limitations, a major strength of our study is that the umbrella review was very rigorously conducted.Decision-makers are increasingly required to make evidence-informed policy decisions and often require evidence within short timeframes.In our umbrella review, we collated and highlighted the existing scientific evidence that is of superior quality, and we present a snapshot of the events and challenges that are important in bca survivorship.The amstar tool used here to assess the quality of the included reviews is reliable for quality assessment, giving us confidence in the results we have reported.
Our umbrella review combines data from high-quality systematic reviews and summarizes the best evidence available to inform clinicians delivering scps to people affected by bca.Our findings also accord with the recently published American Cancer Society and American Society of Clinical Oncology bca survivorship guideline 10 .We postulate that, in the absence of more germane systematic reviews on cancer risk for bca patients and survivors, the information presented here is current and reliable, and can help clinicians in making recommendations to women completing treatment for bca and living with or beyond cancer, complementing those recently published bca survivorship guidelines.Furthermore, our review has generated more research questions and hypotheses, thus pointing to the need for more studies that are important in survivorship care planning for women with bca.

CONCLUSIONS
Our study findings support existing scps in our province concerning the physical and emotional challenges that bca survivors often face.However, literature concerning the cancer risks specific to bca survivors is sparse.Although systematically conducted reviews are the "gold standard" in knowledge synthesis, our findings suggest that much remains to be done in the area of synthesis research to better guide practice in cancer survivorship.

FIGURE 1
FIGURE 1The process used to search for and select the final articles.

TABLE I
The outcomes of interest with respect to breast cancer patients and survivors (breast OR mammary glands) AND (cancer, carcinoma OR neoplasms) AND (quality of life, well-being, mental health, QoL, HRQOL, life quality, life qualities, qualities of life, life satisfaction OR personal satisfaction, sexual dysfunctions, bowel dysfunctions) AND (cancer patients, OR cancer survivors ) AND (physical activity, exercise) AND (diet, fiber, meat, red meat, processed meat, nutrition supplements, dairy) AND (spirituality, physiotherapy, sex therapy, education and information, cognitive therapies, psychotherapy, meditation or relaxation therapy) e449Current Oncology, Vol. 24, No. 6, December 2017 © 2017 Multimed Inc.

TABLE II
Eliminated articles and the reason for elimination e450 Current Oncology, Vol. 24, No. 6, December 2017 © 2017 Multimed Inc.

TABLE III The general characteristics of the included reviews Reference Review characteristics Outcome measured Exposure or intervention Findings AMSTAR score Type Included studies Sample
e452Current Oncology, Vol. 24, No. 6, December 2017 © 2017 Multimed Inc.

TABLE IV
Results of the studies that investigated the effect of physical activity (PA) on breast cancer (BCa) patients and survivors SURVIVORSHIP CARE PLANS FOR PEOPLE WITH BREAST CANCER, D'Souza et al.

TABLE IV Continued Reference Type of PA Supervision Duration Frequency Intensity Effect
Current Oncology, Vol. 24, No. 6, December 2017 © 2017 Multimed Inc.
. The findings concerning physical activity are in line with a recent report published by Segal e461 Current Oncology, Vol. 24, No. 6, December 2017 © 2017 Multimed Inc.

TABLE V
Outcomes of interest retrieved from the survivorship care plans (SCPs)Anxiety, depression, stress, and quality of lifeStress can affect you physically, emotionally, and behaviourally.Ongoing physical problems can be associated with anxiety, and anxiety can lead to loss of control, feeling alone.Anxiety and depression are frequently seen, and they can reduce your quality of life.Many people will experience depression at some point in their lives.It is an illness that can affect anyone at any age.Depression is very common in cancer patients and can and should be treated.Eat well and be as physically active as possible.Exercise releases endorphins, which are natural mood-boosters Physical activity helps you to feel better and less stressed, gives you more energy for daily activities, and improves your quality of life, sleep, and appetite.It promotes self-confidence and a feeling of control over your health.It also helps you cope with discomfort and manage weight.
Physical activity that is weight-bearing is best.Examples include walking, dancing, aerobics, skating, and weightlifting.Aerobic exercise targets your cardiovascular fitness and helps to maintain health.e462 Current Oncology, Vol. 24, No. 6, December 2017 © 2017 Multimed Inc.