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Increasing numbers and longevity of cancer survivors has furthered our insight into the factors affecting their health outcomes, suggesting that multiple factors play a role (e.g., effects of cancer treatments and health behaviors). Emotional and physical symptoms may not always receive sufficient attention. In this short narrative review highlighting recent literature, we describe the most common physical and emotional symptoms of breast cancer survivors aged 50 years and older and outline a multidisciplinary symptom management approach, regardless of symptom etiology.
The National Coalition for Cancer Survivorship and the NIH define a cancer survivor as “an individual from the time of cancer diagnosis, through the balance of his or her life” [1,201,202]. Due to improvements in cancer care, including earlier detection and better treatment, the number of cancer survivors in the USA has been steadily increasing over the last 30 years (~12 million in 2007) and is expected to continue to rise [2,203]. Cancer survivors also live longer after cancer diagnosis (~5 million survive more than 10 years)  and two-thirds are aged 65 years and over . Nevertheless, increased survival brings multiple challenges that range from an increased risk for cancer recurrence and the development of second or other primary cancers, to a host of chronic conditions (e.g., osteoporosis, cardiovascular disease, thromboembolic disease and cognitive impairment), and clusters of bothersome physical and emotional symptoms , as shown on Figure 1 . Evidence that underlying pathophysiological changes in survivors’ immune, neuroendocrine, metabolic and central nervous systems, including the sleep–wake cycle [4,5], contribute to these symptoms is emerging. Successfully managing these symptoms in clinical practice is crucial for several reasons. First, breast cancer survivors utilize more care during their first 5 years after diagnosis than their age-matched controls , yet often report that their needs have not been met [7,8,204]. Second, poorly controlled symptoms may lead to decreased adherence to adjuvant endocrine therapy [9,10]. Indeed, some studies show only 50% adherence to completion of 5-year adjuvant endocrine therapy treatment regimens [9,11–15], leading to inferior survival . Third, while most breast cancer survivors report comparable quality of life (QoL) to age-matched controls [17–19] and experience post-traumatic growth after cancer , for a subset of survivors, physical and emotional symptoms can disrupt their QoL .
Breast cancer survivors’ outcomes depend not only on their prognosis, but also on a host of other factors , including adverse effects of cancer treatment , access to and availability of survivorship care, social, economic, cultural and medical care variables [17,24], QoL [25,26] and health behaviors (Figure 2) [27–29]. Although substantial numbers of breast cancer survivors do not adhere to recommended health maintenance [30,31], engaging in positive health behaviors, such as limiting alcohol intake, smoking cessation, achieving and maintaining a healthy weight and regular physical activity, can significantly reduce survivors’ risk of recurrence [22,32–35]. However, benefits may be impeded by cancer-and treatment-related morbidity, particularly if the symptoms contributing to morbidity are not well controlled [34,36–38,204].
As a consequence of these changes in cancer survivorship, organizations such as the US CDC have called for “medical and public health professionals to: a) address the potential long-term and late effects of cancer and related therapy on survivors’ physical and psychosocial well-being, b) provide survivors with coordinated care to address their multiple symptoms, and, c) promote the importance of healthy behaviors (e.g., smoking cessation and physical activity) to reduce the risk for new or recurrent cancer and early detection to increase the likelihood of survival with new or recurrent cancer” . QoL of long-term cancer survivors has been proposed to be comprised of four primary domains of well-being: psychological, social, physical and spiritual . Given a number of comprehensive overviews of the entire spectrum of breast cancer survivorship QoL [40–44], we sought to provide an update of the most recently published literature. Thus, in our brief narrative review, we will highlight critical work in the field, prioritizing the last 2 years of research, with the intention of providing clinicians with practical suggestions to inform their practices. Our focus is on the most common physical and emotional symptoms of breast cancer survivors aged 50 years and older (who represent the bulk of breast cancer survivors [2,45]), and we will outline a multidisciplinary symptom management approach, regardless of symptom etiology, to improve their physical and psychological QoL. The purpose of our article was not to compare different care models, but to stress/promote the importance of screening for symptoms and involving other disciplines early on in a proactive manner (e.g., behavioral health, physical therapy, nutritional services and complementary medicine) in the hopes of forming a supportive management strategy of symptomatic breast cancer survivors.
Due to prolonged survival and increased lifespan, there is some indication that breast cancer survivors’ physical function might decline faster than that of their peers and that these survivors might benefit from an approach that is routinely applied in the aging population . First, survivors experience multiple, clustering and chronic symptoms [7,8,47,48,204]. Second, survivors demonstrate physical, psychological and behavioral changes that may impair their functional status and lead to dependence and disability , as demonstrated by higher fall risk , decreased physical activity  and observed limitations in both basic and advanced activities of daily living [50,51]. Therefore, a subset of symptomatic breast cancer survivors stand to benefit from a management approach that is routinely applied in the geriatric medicine setting, one that is: multidisciplinary (e.g., physical and behavioral factors); multifactorial (i.e., one intervention targets multiple symptoms simultaneously); increased use of nonpharmacological treatment options; and setting therapeutic goals (i.e., recognizing that complete resolution may not be achieved, but improvement is likely) [46,51–55]. In a below section, we illustrate this concept by highlighting basic assessment and management principles that apply equally across many commonly observed physical and emotional symptoms in breast cancer survivors, such as cognitive dysfunction [5,56–59], adjustment disorder or other psychosocial distress [7,8,60–64], vasomotor symptoms [41–43,65] and insomnia and fatigue [62,66–71].
A comprehensive approach to symptom management starts with an evaluation as to whether symptoms can be exclusively attributed to cancer and related treatments and procedures (including anesthesia) or to other contributing factors that are potentially reversible. These factors are numerous and may include vitamin deficiencies, anemia, organ dysfunction and endocrine, metabolic or intracranial abnormalities. Appropriate assessments include blood work, imaging studies and/or neuropsychological testing. In addition, careful listening to survivors, education and multifactorial support (e.g., with input from other disciplines, such as behavioral medicine or physical therapy) tailored to survivors’ needs might have significant therapeutic value for survivors.
Management may include pharmacological therapy (e.g., antidepressants or stimulants) in combination with a variety of nonpharmacological interventions, such as physical therapy, psychological support, nutritional counseling and complementary medicine. Some of these treatments affect multiple symptoms, which is preferable. For example, increasing physical activity not only improves functional status, fitness and survival, but also helps improve QoL , emotional, cognitive and physical symptoms  and overall and cancer-related mortality [27–29]. An informed conversation can help outline an individualized management approach that accounts for prior treatments, patient preferences and insurance coverage . Pursuing nonpharmacological management can be challenging, as it often requires more active participation of the survivor (e.g., time and expense). For example, cancer survivors might be challenged in their pursuit to initiate, resume or increase the level of physical activity by logistical barriers, acquired physical limitations or a fear of harm [38,48]. In these instances, a certified cancer exercise trainer  or a physical therapist is a valuable resource. Cancer survivors may feel discouraged when suffering with chronic symptoms, and although most breast cancer survivors cope well, some survivors become significantly burdened by symptoms, and in this instance, a brief course of psychological therapy focused on empowerment, increased self-care and coping skills may prove helpful [72,73].
Musculoskeletal symptoms are very prevalent among breast cancer survivors, whether due to chemotherapy, menopause or aromatase inhibitor therapy. More than 50% of breast cancer survivors experience a musculoskeletal syndrome upon initiation of an aromatase inhibitor, usually as either new or worsened diffuse arthralgias and myalgias, which most often improve within 2–3 months [74–82]. Approximately 30% of breast cancer survivors need to discontinue initial adjuvant aromatase inhibitor therapy due to adverse effects (~25% because of musculoskeletal symptoms) . Although a causal relationship is likely to be due to cancer treatment or menopausal transition, new diagnoses, such as autoimmune or crystalline arthritis, should not be overlooked. Treatment approaches are similar to those of osteoarthritis and may include nonpharmacological methods such as physical therapy, local heat and/or acupuncture, in combination with pharmacological therapy, such as short-term administration of NSAIDs, either systemically or topically.
In addition to arthralgia-type symptoms, breast cancer survivors may develop fibrosis, rotator cuff pathology and altered body habitus, leading to pain, limited range of motion and impaired function in daily life, which are considered to be consequences of locoregional treatment with surgery, with or without radiation therapy. Axillary web syndrome is the most extreme presentation of these symptoms [84,85]. Physical and massage therapists are of great value as they are able to provide symptom relief by administering an intense regimen of massage, stretching and exercises that minimizes the need for surgical therapy. Additional psychological support to help patients cope with pain can also be helpful.
More than half of breast cancer survivors, and especially those on adjuvant endocrine therapy or with cancer therapy-induced premature menopause, suffer from sexual dysfunction [41–43,86–89] and urinary symptoms [49,90,91]. Sexual dysfunction may include vaginal atrophy, diminished libido or pain during intercourse. Changes in libido can be due to multiple causes, which include mood, pain, body image, fatigue, relationship issues and estrogen deprivation. Sexual complaints may be at least partially alleviated by the use of a combination of local nonhormonal applications (e.g., moisturizers, lubricants and vitamin E), a low dose of topical estrogens (usually as a last resort and only upon an informed conversation), physical therapy (e.g., pelvic floor muscles exercises), gynecologic strategies (e.g., vaginal dilatational mechanical measures) and psychological care (e.g., exploring causes of decreased libido, coping strategies and partner communication).
Urinary issues may include overactive bladder with urgency, with or without incontinence. Management options for sexual and urinary symptoms partially overlap. Urinary complaints can often be helped by pelvic floor muscle exercises, topical estrogen and, in some cases, with a referral to a urogynecologist.
It is estimated that osteoporosis affects one in every three postmenopausal women, with a 40% lifetime risk of fracture and approximately 21% risk of 1-year mortality after hip fracture . Breast cancer survivors are at an even higher risk of bone loss due to chemotoxic effects on the bone, treatment-induced hypogonadism and supportive therapies that include steroids [49,92–96]. Fracture risk is not only determined by bone mass, as measured by a dual-energy x-ray absorptiometry scan, but also by the propensity to fall, which may be negatively affected by cancer or its treatment (e.g., due to chemotherapy-induced neuropathy, deconditioning, urinary incontinence, vitamin D deficiency and cognitive impairment). Simple measures, such as weight-bearing exercises, minimal or no consumption of nicotine/alcohol and an adequate daily intake of calcium and vitamin D (600 mg/400 IU twice daily), are important in fracture risk reduction . Given the evidence of an association between calcium intake and acceleration of coronary artery disease , it might be important to tailor one’s individual pill supplementation to one’s average dietary intake with help from a dietitian . For pharmacological interventions to support bone health, selection of an agent and timing of its initiation remain challenging. Gralow et al. have created an algorithm that includes the FRAX® calculator in an effort to individualize the initiation of bone medications based on a survivor’s 10-year fracture risk [95,208]. An informed conversation regarding the pros and cons of bone medications between the survivor and the provider is essential. Survivors should be monitored with baseline and surveillance dual-energy x-ray absorptiometry scans every 2 years.
Breast cancer survivors are at increased risk of cardiovascular events. Its cumulative incidence may be as high as 33%  if the patient experienced premature, chemotherapy-induced menopause [100,101] or received aromatase inhibitor therapy [23,29,102–105] and/or left-sided chest wall radiation . Cardiac toxicity is not only limited to coronary artery disease, but may also lead to cardiomyopathy, thromboembolism, arrhythmias and valvular or pericardial disease . It is important to assess and control cardiovascular risk factors including weight, physical fitness, lipid profile and glucose tolerance. A dietitian, psychologist, personal trainer or physical therapist may help facilitate these efforts. Evidence is growing that, for a subset of breast cancer survivors, the benefits of aromatase inhibitor therapy for reducing future breast cancer risk may not outweigh the risks the therapy poses to cardiovascular health .
The number and longevity of breast cancer survivors is increasing, and their symptomatology can be burdensome, complex, chronic and is often undertreated. Growing evidence has revealed that symptom management allows for improvement of QoL , while evidence about its ability to reduce healthcare utilization is scarce. An impending shortage of cancer providers  suggests that cancer survivorship care needs to be revolutionized to allow a better and more individualized outreach to survivors (residing mostly in communities without easy access to an academic medical center)  in a cost-effective, financially sustainable and easily replicable manner.
In terms of content, Ganz has promoted the ‘three Ps’ concept; in other words:
“…palliation of ongoing symptoms; prevention of late effects of cancer treatment or second cancers; and health promotion to maximize future wellness” .
To further refine this, the LIVESTRONG convened researchers, clinicians and advocates to generate consensus on the ‘essential elements’ of survivorship care . This process resulted in the consensus that all medical settings offering survivorship care must, at a minimum, provide direct access or referral to the following: a survivorship care plan; a psychosocial care plan and treatment summary; screening for new cancers and surveillance for recurrence; a care coordination strategy that addresses care coordination with primary care physicians and primary oncologists; health promotion education; and symptom management and palliative care.
In terms of care delivery, investigators have examined different types of providers (e.g., generalist and specialist physicians, physician extenders, nurses and navigators) [110–119], as well as, to a lesser degree, different care strategies (e.g., transitional, consultative and integrative) [108,120]. Although encounters are mostly performed in the traditional ‘face-to-face’ manner, in keeping with the movement towards the Accountable Care Organization , remote or virtual options might become increasingly popular and feasible (e.g., telephone , videoconferencing or [a] synchronous messaging). Timing of encounters can also vary. Some centers perform traditional consultative visits, while others alternate or even transition breast cancer survivors from their current cancer providers into a devoted survivorship program (some upon completion of acute treatment, and others years after diagnosis) [108,114]. Very few of these combinations have been compared head-to-head in terms of acceptability, feasibility and effectiveness. Therefore, studies are needed to explore the costs, feasibility and reproducibility of these various cancer survivorship care strategies .
Tailoring assistance to the needs of individual cancer survivors will be crucial in order to prioritize limited resources. First, identification and referral of cancer survivors who are in need could be facilitated proactively by many different methods, including self-assessments administered by use of technology or navigators [114,118,122–124]. One example of a validated measure that is easy to administer in a clinical setting is the Breast Cancer Prevention Trial Scale, which assesses somatic symptoms among breast cancer survivors on hormonal therapy . The FACT-ES survey allows assessment of endocrine symptoms . A validated measure that probes emotional symptoms is the Center for Epidemiologic Studies – Depression Scale and the Hospital Anxiety and Depression Scale . Survivors can be adequately supported through low-cost educational resources (in person, by phone or online), while others may require more comprehensive, face-to-face, multidisciplinary intervention. Although a framework has yet to be established in terms of how to assess physical and emotional symptoms, impairment over time and early intervention, recent publications have increased awareness of the need to integrate physical therapy [127–129] and behavioral medicine  into a cancer survivor’s care. This stepped-care approach is currently being investigated among survivors of head and neck cancer or lung cancers .
Prescribing symptom management options can be challenging. First, having been exposed to toxic treatments, breast cancer survivors often favor nonpharmacological treatment approaches . However, their costs may accumulate due to co-pays and limited health plan coverage. The latter applies to complementary medicine approaches in particular. Second, increased insight into pathophysiological changes during survivorship by assessing cancer survivors’ concerns and their changes over time in correlation with biological samples (e.g., serum, urine and fat/muscle biopsy) would enable the development of more individualized and, thus, more effective support. Third, there is a lack of evidence concerning both general and age-specific symptom management in cancer survivors. Thus, comparative effectiveness studies of various combinations of pharmacological and nonpharmacological agents are needed. Fourth, some breast cancer survivors are unable to make long-term lifestyle changes due to deconditioning, high symptom burden or lack of motivation . Thus, it might be helpful to receive proactive guidance from an easily accessible and affordable physical therapist or (cancer certified) personal trainer who could design a regimen that adapts to and slowly builds on one’s limitations. Other possible strategies to improve and maintain healthier behaviors might include direct feedback from patients (e.g., obtained via technological devices or online [interactive] resources) [114,122,133] or utilization of community-based cancer-specific exercise programs [22,134,135,212]. Research on health behaviors in the cancer population is rapidly growing [136,137] and will contribute to cancer-specific health behavior recommendations [22,138,213]. Fifth, increased attention to and care for symptoms may also help improve suboptimal adherence rates to long-term hormonal cancer therapies . Finally, experiencing chronic symptoms without sufficient relief can result in a vicious cycle of discouragement, decreased self-help and worsening of physical and emotional symptoms [63,139]. Therefore, behavioral interventions that target self-care and empowerment – delivered face-to-face or virtually – may be required to overcome this vicious cycle, as demonstrated in prostate  and breast cancer survivors , as well as persons at high risk for depression .
There is evidence that health maintenance and cancer screening among cancer survivors can be further improved . Cancer survivors often fall between the cracks because they receive care from multiple providers . A helpful tool for cancer survivors could be a cancer survivorship care plan, as mandated by the American College of Surgeons, which helps breast cancer survivors organize and remember their appointments and testing [145,214]. Which components of the care plan are most helpful and how to deliver them without interference to the clinical flow are yet to be determined [146,147]. Ideally, a treatment summary and care plan should be part of survivors’ electronic medical record, allowing easy access to survivors (e.g., via access to a patient portal) and their providers. The pediatric field has made large strides by creating an online resource with a wealth of information for both providers and survivors that can be easily adjusted as new evidence becomes available, without needing to reach out via mail or in person (e.g., Passport for Care ). Ideally, a subspecialty medical home concept [149–151] would allow remote monitoring of the performance of health maintenance and cancer screening. Additionally, it would allow remote monitoring for more cancer-specific measures, such as cancer surveillance and healthcare utilization, and trigger supportive care services in situations of suboptimal performance.
To summarize, cancer survivorship care is a field that has gained recognition and is in need of a revolution to allow better care for a larger number of survivors in a financially sustainable manner. Therefore, it is crucial to prioritize funding for prospective observational studies (with translational components) to increase our understanding of changes of symptoms and their contributors over time, as well as studies that test the efficacy and effectiveness of supportive care strategies that address both survivor- and provider-related factors. Among the latter, there is a clear need for head-to-head comparisons of various combinations of pharmacological agents and nonpharmacological therapies, including specific health behavior-related interventions, and how these combinations would affect QoL and healthcare utilization.
The authors would like to thank Ms A Cardy for her crucial contributions towards text editing.
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Financial & competing interests disclosure
Research reported in this publication was supported in part by the National Center For Advancing Translational Sciences of the NIH under Award Number KL2TR000146, the Pittsburgh Older Americans Independence Center under Award Number P30 AG024827 09, the Hartford Foundation, Magee-Womens Research Institute & Foundation and the Pittsburgh Affiliate of Susan G Komen for the Cure. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.