Supportive Care during Treatment for Breast Cancer: Resource Allocations in Low- and Middle-Income Countries. A Breast Health Global Initiative 2013 Consensus Statement

Abstract

Breast cancer patients may have unmet supportive care needs during treatment, including symptom management of treatment-related toxicities, and educational, psychosocial, and spiritual needs. Delivery of supportive care is often a low priority in low- and middle-income settings, and is also dependent on resources available.

This consensus statement describes twelve key recommendations for supportive care during treatment in LMCIs, identified by an expert international panel as part of the 5th Breast Health Global Initiative (BHGI) Global Summit for Supportive Care, which was held in October 2012, in Vienna, Austria. Panel recommendations are presented in a 4-tier resource-stratified table to illustrate how health systems can provide supportive care services during treatment to breast cancer patients, starting at a basic level of resource allocation and incrementally adding program resources as they become available. These recommendations include: health professional and patient and family education; management of treatment related toxicities, management of treatment-related symptoms of fatigue, insomnia and non-specific pain, and management of psychosocial and spiritual issues related to breast cancer treatment.

Establishing supportive care during breast cancer treatment will help ensure that breast cancer patients receive comprehensive care that can help 1) improve adhere to treatment recommendations, 2) manage treatment-related toxicities and other treatment related symptoms, and 3) address the psychosocial and spiritual aspects of breast cancer and breast cancer treatments.

Supportive Care during Treatment for Breast Cancer

Breast cancer patients receiving therapy require supportive care for the prevention and management of physical and psychosocial adverse effects of cancer and its treatments.^1–3 Studies in high-income countries (HICs) and low- and middle-income countries (LMICs) have shown that cancer patients and their families may have unmet physical and psychosocial supportive care needs during treatment.^4–7 Supportive care is often a low priority in LMICs.³ Integrating supportive care measures into existing breast cancer treatment programs is an important part of a multidisciplinary and interdisciplinary approach to cancer care, which requires both health professional education and patient awareness of supportive care services. Breast cancer treatments have acute as well as delayed side-effects; the frequency and severity differ according to the type of therapy as well as patient characteristics such as age, performance status and comorbidities. Many treatments have shared side-effects of nausea, fatigue, insomnia, and/or pain, as well as specific toxicities that affect one or more body systems (musculoskeletal, gastrointestinal, nervous system, skin/hair/nail, or hematological toxicities). Treatments can also affect women’s health issues (eg, reproductive health, fertility and sexual health). Psychosocial complications of cancer and cancer treatment (eg, emotional distress, depression, anxiety, and/or social disruptions) can affect patient outcomes and quality of life. Failure to address supportive care during cancer treatment can lead to decreased compliance and worsened outcomes, thereby diminishing the value of therapeutic interventions.

Defining “During Treatment”

“During treatment” is defined, for the purposes of this consensus statement, as the time period from initiation of treatment to approximately 6 months following the completion of the treatment, to allow us to distinguish short-term vs. long-term treatment-related issues. The term refers to surgery and adjuvant/neoadjuvant systemic therapies and radiation therapy. Long-term treatment-related side-effects (ie, persistent and late-effects) are addressed in the BHGI companion consensus statement, Supportive Care after Curative Treatment (Survivorship).⁸ Metastatic breast cancer and palliative care are addressed in the BHGI companion consensus statement, Supportive and Palliative Care for Metastatic Breast Cancer.⁹

BHGI Global Summit and Expert Panel Consensus Process

All three Breast Health Global Initiative (BHGI) supportive care consensus statements provide recommendations for breast cancer supportive care program implementation in low- and middle-resource settings. Methods developed by the BHGI for the structured creation of evidence-based, 4-tier resource-stratified guidelines and consensus statements (see Table 1) have been previously described.^10,11 A systematic literature review was performed in preparation for the 5^th BHGI Global Summit, which was held in association with the International Atomic Energy Association (IAEA) in Vienna, Austria, on October 2, 2012. Supportive care was chosen as the theme for the global summit, as it emphasizes often-overlooked aspects of medical care that are not always considered directly related to curative intent. The Supportive Care during Treatment Consensus Panel presented on key topics and then performed consensus analysis through facilitated expert panel discussion to draft the core resource-stratified table matrices, which are the primary outcome of the panel examination and deliberation. Companion consensus statements for supportive care after curative treatment⁸, and supportive and palliative care for metastatic breast cancer⁹, were developed in parallel during this 2012 Global Summit. Supportive care is an under-researched area of medicine, especially in LMICs. Systematic reviews and meta-analyses are often not available for select topics, or include only studies from HICs. When studies from LMICs are available on a topic, they are provided as additional references.

Table 1.

Resource allocation levels: basic, limited, enhanced, and maximal

Resource Allocation Level	Description
Basic	Core resources or fundamental services absolutely necessary for any breast health care system to function; basic-level services are typically applied in a single clinical interaction.
Limited	Second-tier resources or services that are intended to produce major improvements in outcome, and are attainable with limited financial means and modest infrastructure; limited-level services may involve single or multiple clinical interactions.
Enhanced	Third-tier resources or services that are optional but important; enhanced-level resources should produce further improvements in outcome and increase the number and quality of therapeutic options and patient choice.
Maximal	High-level resources or services that may be used in some high-income countries, and/or may be recommended by breast care guidelines that do not adapt to resource constraints. They should be considered lower priority than those resources or services listed in the basic, limited, or enhanced categories on the basis of extreme cost and/or impracticality for broad use in resource-limited environments; to be useful, maximal-level resources typically depend on the existence and functionality of all lower-level resources.
Stratification scheme	The table stratification scheme implies incrementally increasing resource allocation at the basic, limited, and enhanced levels. Maximal-level resources should not be targeted for implementation in LMICs, even though they may be used in some higher-resource settings.

Key Resources Needed for Supportive Care during Treatment Programs

This section describes the twelve key resource allocation categories identified by the expert international panel for supportive care during treatment. A resource-stratified recommendation follows each description of a key resource category, and is also presented in one of three tables. The resource stratified tables illustrate how a health system can provide supportive care services during treatment to breast cancer patients, starting at a basic level of resource allocation, and incrementally adding program resources. The section, Special Concerns and Emerging Issues in LMICs, highlights key issues from the panel deliberations. If a topic is covered in more detail in another companion consensus statement, a link and reference is provided.

Health Systems (Table 3)

Table 3.

Health systems resource allocations: health education, psychosocial and spiritual patient-support during treatment

	Basic	Limited	Enhanced	Maximal
Health Professional Educationa	Appropriate use of CPG Women’s health Psychosocial considerationc Spiritual considerationc Health literacy, cultural literacy, communication skills	Sexual health Psychosocial impact of breast cancer / TX (individual and community)	Psychosocial screening methods
Patient and Family Educationb	TX-related toxicities and other TX side-effects Fatigue, insomnia Reproductive health / fertility and body image Psychosocial issues Spiritual issues	Sexual health Psychosocial impact of breast cancer / TX
Psychosocial (Treatment-related)	Patient and family educationb Psychosocial considerationc Peer support by trained volunteers	Psychosocial assessment, including depression Patient and family support groups Psychosocial support by health professionals	Screening and referrals for depression and distress by mental health specialist Psychosocial counseling by mental health specialist Prescription drugs for depression	Psychiatrist, psychologist, or social worker coordinated mental health care
Spiritual (Treatment-related)	Spiritual considerationc Spiritual support: community-based

Note: The table stratification scheme implies incrementally increasing resource allocation at the basic, limited, and enhanced levels. Maximal-level resources should not be targeted for implementation in LMICs, even though they may be used in some higher-income settings.

Abbreviations: CPG, clinical practice guidelines; TX, treatment.

^aThe term “health professional” is used to acknowledge the range in medical and other professionals who provide supportive care services in LMICs. When specialists are identified as a required resource, it is assumed that a specialist has a certification for their area of expertise.

^bPatient, family and/or partner education may be the primary intervention for some supportive care services.

^c“Consideration” is a term used in this table to refer to basic patient evaluation through patient-provider interactions, including dialogue, observations, and other appropriate means of evaluation.

Health Professional Education/Training (Table 3, Row 1)

Description: The term “health professional” was chosen by the consensus panel to acknowledge the range in medical and other professionals who provide supportive care services in LMICs. When specialists are identified as a required resource, it is assumed that a specialist has a certification for their area of expertise.

Health professionals in LIMCs should be well educated regarding clinical practice guidelines (CPG) for breast cancer, including how to manage treatment-related toxicities, and how to apply best practices based on available resources. Health system resources, including the availability of treatment resources, are one of several factors that influence the acceptance and correct use of clinical practice guidelines.¹² Guidelines are available on specific treatment-related toxicities such as pain, nausea, vomiting, and anemia; guidelines on other supportive care topics include depression, rehabilitation, nutrition, and exercise. (See Table 2 for a list of some of the available guidelines.)^{10,11,13–58}

Table 2.

Guideline reference list: supportive care for breast cancer patients during treatment

The panel referred to guidelines where available, including resource-stratified guidelines on breast cancer1,2, resource-stratified guidelines on supportive cancer care in Asia3, guidelines for breast cancer follow-up and management in the adjuvant setting4–6 and ESMO breast cancer guidelines for early7 and advanced8,9 breast cancer.

General breast cancer guidelines10,11, guidelines developed for specific regions or countries, including Middle East12, Malaysia13 Mexico14, Africa15, Europe8, and developing countries16, were considered.

Guidelines targeted to elderly patients with breast cancer include the EUSOMA guidelines17 and NCCN guidelines18, and guidelines for younger women with breast cancer provided discussions on women’s health issues such as fertility and early menopause.19,20

Other guidelines consulted covered specific issues such as pain21–23, fatigue24,25, anemia26, insomnia27, lymphedema28, nausea and vomiting29–33, mucositis34, diarrhea35, depression and distress36,37, nutrition38, rehabilitation28, exercise39, bone modifying agents40–42, granulocyte-colony stimulating growth factor43, and Genetics44.

Women’s health issues related to breast cancer treatment include early menopause, reproductive health and fertility concerns, and body image and sexual health. Psychosocial complications related to breast cancer treatment include anxiety, depression, distress, and disturbances in social roles. It is widely recognized that cancer diagnosis causes stress, which has psychological, behavioral, and physiologic aspects.^59,60 When stress or emotional distress is significant, of several weeks’ duration, and disrupts daily life and functioning, it may represent biobehavioral disruptions, such as mood and/or anxiety disorders, that can continue for upwards of 24 months if left untreated.⁶¹ Screening for distress has become a component of cancer care guidelines, both in HICs⁴⁹ and some LMICs^21,62,63. Several studies in LMICs suggest that the process of screening for and identification of depression or emotional distress can reveal associated psychosocial issues such as lowered quality of life^64,65, fatigue^66,67, sleeping problems^68,69, pain⁷⁰, and interpersonal relationship stressors^68,71. Addressing underlying factors associated with depression can make diagnosis and treatment more effective.⁷²

Spiritual well-being was identified by the expert panel as an important part of supportive care for breast cancer patients, and should be considered during treatment. Attention to spiritual well-being, which includes faith, a sense of meaning, and inner peace⁷³, should be part of routine supportive care processes.^74,75 Differences between cultures may influence how religious beliefs affect participation in breast cancer programs (diminishing or enhancing it).^76–78 The traditional role for health professionals has been to recognize the importance of religious/spiritual beliefs in seriously ill patients and to refer patients to their own religious leader or community, and as more resources become available, to refer patients to in-patient services, as appropriate.⁵⁸ Health professional training in cultural literacy and communication skills should be taught as part of supportive care programs.

#1. Panel recommendations:

At basic levels of resource allocation, health professional education should include appropriate use of clinical practice guidelines, including how to manage the side-effects of chemotherapy, endocrine therapy, surgery, and radiation therapy. It should include reproductive health and fertility issues, and awareness and management of psychosocial problems that may occur during treatment, as well as spirituality issues related to breast cancer and breast cancer treatment. Communication skills, health literacy and cultural literacy should be included. At limited levels, health professional education should include sexual health issues, and the broader psychosocial impact of breast cancer and breast cancer treatment on individuals and the community. At enhanced levels, health professional education should include psychosocial screening methods.

Patient, Family and Partner Education (Table 3, Row 2)

Description: Patient education has been shown to improve patient adherence^79–82, pain management⁸³, and patient satisfaction with cancer care.^84–86 Patient education during treatment should include recognition and management of treatment-specific organ-based toxicities and other treatment effects, including women’s health effects such as possible early menopausal symptoms, infertility, body image concerns, and sexual health issues. Breast cancer patients should be informed of potential psychosocial complications related to treatment, such as anxiety and depression, and potential disruptions to their usual social roles, including employment and motherhood.

Families and partners should be included in patient education, as appropriate. Family caregivers and partners often have their own unmet psychosocial needs. See the Special Concerns in LMICs section. In LMICs, patient and family education is an important part of patient recovery. It can be reassuring for patients and their families to know what to expect, and that the symptoms they are experiencing are normal and in most cases will resolve. Partners provided with educational information and support reported lower anxiety, depression and marital problems.^87–89

Although there are no guidelines on patient and family education for supportive breast cancer care, a number of studies provide details on educational strategies^90–94 and the importance of culturally appropriate communications^95–98. For literate women, provision of written information may be helpful. Internet-based interactive content may be an effective way to provide psychoeducational interventions, and to reach a large number of people.⁹⁹ (See the companion BHGI consensus statement, Supportive Care after Curative Treatment⁸, for a discussion on family education, and recommendations and discussion on community awareness.)

#2. Panel recommendations:

At basic levels of resource allocation, patient, family, and partner education should include the recognition and management of organ-specific treatment toxicities, hematologic complications, and fatigue, and insomnia. Symptom management education should include prevention strategies for infection and when to seek medical evaluation for treatment-related complications. Patient education should include the treatment-related women’s health issues, such as early menopause, reproductive health, fertility, and body image. Potential psychosocial complications of treatment, such as anxiety, depression, and distress, should be included, as well as potential changes to roles at home or work. Spiritual well-being should be considered. At limited levels, patient education on sexual health should include partners, as appropriate. Patient education should expand to include broader psychosocial aspects of breast cancer disease and treatments. (See the Special Concerns in LMICs section.)

Psychosocial Issues (Table 3, Row 3)

Description: It is important for health professionals in LMICs to receive training in the assessment, referral, and treatment of psychosocial complications of breast cancer. A number of guidelines for depression and distress management for cancer patients have been published. (See Table 2) Multidisciplinary and interdisciplinary approaches to breast cancer supportive care can help ensure distress-related psychosocial issues are addressed.⁴⁹ Psychological conditions are known to affect treatment adherence and recovery, and to exacerbate fears¹⁰⁰ and the subjective experiences of fatigue, insomnia, and pain.⁴⁹ Reports of significant depressive symptoms among breast cancer patients in LMICs range from 8–60% based on studies from Turkey^65,101,102, Korea¹⁰³, Portugal and Spain¹⁰⁴, Croatia¹⁰⁵, India¹⁰⁶, and the Czech Republic¹⁰⁷. Reports of anxiety disorders from LMICs range from 12–60%.^{101,102,104,106} The need for psychosocial support may be greater in LMICs, where women often have limited access to professional psychosocial resources, and where breast cancer is often diagnosed at a later stage and in younger women. Screening for depression and distress in at-risk patients can help identify treatable psychosocial conditions. Screening tools developed in HICs have been successfully translated and adapted for use in low-resource settings.^{67,102–104,108,109} Formal screening for psychological problems should be implemented when resources for formal referral and treatment are available. Treatment options for psychosocial problems can include peer support and patient and family counseling; family counseling can help patients and families adjust to the impact of the disease and treatment; and social support may assist patients as they cope with cancer.^110,111 Social service counseling for employment, financial and legal issues may help alleviate anxiety and fear regarding changing roles at work and home related to cancer and cancer treatments. (See companion BHGI consensus statement, Supportive Care after Curative Treatment (Survivorship)⁸, for a discussion on social services.)

Note: “Multidisciplinary team approach” refers to a patient care model that includes experts from different disciplines, whereas an “interdisciplinary team approach” requires a more integrated and coordinated approach to patient care, where experts from different disciplines establish shared patient care goals for a more holistic approach to patient care.

#3. Panel recommendations:

At basic levels of resource allocation, patient and family education are important and may be the primary patient intervention. Health professionals should consider (through observation, dialogue and other appropriate means) psychosocial issues of breast cancer patients during treatment, and refer patients to peer support by trained volunteers and/or community-based support. At limited levels, psychosocial assessment, including assessment of depressive symptoms should be available, along with referrals for patient and family support groups and psychosocial support from trained health professionals, as appropriate. At enhanced levels, formal psychosocial screening (ie, depression and distress) and appropriate counseling from mental health professionals should be available. Pharmacotherapy for depression and distress should be considered. At maximal levels, other psychosocial resources that require psychiatrist-, psychologist- or social-worker-coordinated care, such as formal psychosocial treatment programs, could be considered.

Spirituality (Table 3, Row 4)

Description: The role of spirituality in coping with breast cancer is being studied in HICs and LMICs, across a variety of ethnicities, races and religions, including Malaysian Muslim women⁷⁶, Iranian women^78,112, Chilean women¹¹³, Jordanian women¹¹⁴, Korean immigrants and native Korean women¹¹⁵, African American women^75,116, Latinas in the USA¹¹⁷, and Catholic Filipino immigrants in the USA⁷⁴. Although most studies on spiritual well-being use interviews and other qualitative methods, a validated spiritual assessment tool, the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp) has also been used⁷³. The latter has been adapted and translated for use in Muslim settings in LMICs^112,114 and for Asian patients^118,119. High spirituality scores are associated with higher perceived quality of life and satisfaction with doctor-patient relationships in HICs.¹¹⁷ Spirituality assessed separately from religious practice has been associated with quality of life¹²⁰, suggesting that general spiritual counseling outside of religious practice may be helpful for breast cancer patients, and should be considered part of supportive care.¹²¹ (See the companion BHGI consensus statement, Supportive and Palliative Care for Metastatic Breast Cancer⁹, for further recommendations.)

#4. Panel recommendations:

At basic levels of resource allocation, spiritual considerations should be included as part of patient monitoring, and referrals for community-based spiritual support provided as needed.

Treatment-related Toxicity (A): Organ-based Toxicity Management during Treatment (Table 4)

Table 4.

Resource allocations for treatment-related toxicity (A): organ-based toxicity management during treatment

	Basic	Limited	Enhanced	Maximal
Musculoskeletal Toxicities	Basic physical activity (eg, aerobic, ROM) Pain management, including morphinea	PT focused on early lymphedema, shoulder mobility, and pain management Other drug therapy for paina	Other non-morphine opioidsa BMD assessment for at-risk patients Bone modifying agents
Gastrointestinal Toxicities	Oral/IV hydration and electrolyte replacement Drug therapy: antiemetics, antidiarrheal medications, stool softeners, laxatives Mucositis support, eg, ice chips Anxiety symptom management Consideration of parasitic and/or bacterial infection	Drug therapy: 5HT3 blockers, H2 antagonists, anti-acids, stimulant laxatives Mucositis support: topical agents Antianxiety drugs Consultation with certified dietitian	Drug therapy: NK-1 antagonists, PPIs Mucositis support: opioid analgesics for severe mucositis Individualized education by certified dietitian
Skin Toxicities, Chemotherapy Extravasation	Patient and family educationb	Topical agents (eg, steroid- or zinc- containing skin creams) DMSO Debridement surgery Coordinated patient care	Consultation with dermatology specialist Central line access/management	Dexrazoxane
Nervous System Toxicities	Pain management, including morphinea Topical agents Patient and family educationb	PT: functional limitations Drug therapy for paina	Anesthetics for nerve blockage Consultation with neurology specialist for pain management and cognitive problems

Note: The table stratification scheme implies incrementally increasing resource allocation at the basic, limited, and enhanced levels. Maximal-level resources should not be targeted for implementation in LMICs, even though they may be used in some higher-income settings.

Abbreviations: BMD, bone mineral density; DMSO, dimethyl sulfoxide; 5HT3 blockers, 5-hydroxytryptamine blockers; NK-1, Neurokinin −1; PPIs, proton pump inhibitors; ROM, range of motion; PT, physiotherapy.

^aPain management should follow the World Health Organization pain ladder recommendations. Morphine should be available and easily accessible at a basic level of resources.

^bPatient, family and/or partner education may be the primary intervention for some supportive care services.

Musculoskeletal Toxicities (Table 4, Row 1)

Description: Musculoskeletal toxicities during treatment may differ based on the type of therapy. For example, common surgical musculoskeletal toxicities include early lymphedema and pain. Early lymphedema is related to axillary lymph node dissection¹²², and is one of the most important predictive factors for chronic lymphedema¹²³. Systemic musculoskeletal toxicities may present after treatment, and include bone loss and arthralgia, which are increased in women with chemotherapy-induced ovarian failure, and patients treated with aromatase inhibitors or glucocorticoid therapy.^124,125 Chronic pain after surgery can lead to lifestyle changes due to the inability to undertake daily activities associated with paid or unpaid work, which can lead to early withdrawal from the labor force, or inability to managing a family. The use of nonsteroidal anti-inflammatory agents (NSAIDS) for bone pain and arthralgia management is well supported.¹²⁵ Consensus guidelines and systematic reviews on the management of musculoskeletal-related treatment complications have been published^55,124–126, including guidelines on basic physical activity and weight loss for bone health, and prevention and treatment of bone loss.^55,127

#5. Panel recommendations:

At basic levels of resource allocation, aerobic and range-of-motion (ROM) exercise should be encouraged as part of regular physical activities to help prevent development of early lymphedema and shoulder mobility problems. Pain management should follow the WHO pain ladder; morphine should be available. At limited levels, physiotherapy that focuses on early lymphedema, shoulder mobility and pain management should be available. At enhanced levels, pain management strategies should follow the WHO pain ladder and include non-morphine opioids. Bone mineral density assessment for at-risk patients, and bone modifying agents should be available.

Note: Free online tools for health professionals are available for estimating risk of arm lymphedema (www.lymphedemarisk.com) and volume assessment (www.armvolume.com).¹²³ (See the companion BHGI consensus statement, Supportive Care after Curative Treatment⁸, for recommendations on long-term lymphedema care.)

Gastrointestinal (GI) Toxicities (Table 4, Row 2)

Description: Treatment guidelines on GI symptom management should be followed. (See Table 2 for a list of guidelines.) GI toxicities can be complex and include nausea and vomiting, esophagitis, diarrhea, constipation, and mucositis.⁴⁴ Anxiety often accompanies these toxicities, particularly when they are severe. There are a range of antiemetic agents available to treat GI symptoms; corticosteroids are often used as antiemetics, are available at reasonable cost, and have significant efficacy against low or moderately emetogenic chemotherapy. Newer, effective but more expensive antiemetic agents, such as NK-1 antagonists, can be considered for use with highly emetogenic chemotherapy.^44,128,129 Older antiemetic drugs are less effective. GI toxicities, such as delayed or persistent nausea and vomiting, may not be apparent unless reported; patients and families should be encouraged to report GI symptoms as soon as they occur. GI toxicities, as well as other treatment-related symptoms, may be potentiated by psychological distress.¹³⁰ Consultation with a dietitian may help patients manage some treatment-related GI side-effects. Parasitic and bacterial infections should be considered in the differential diagnosis of GI symptoms during treatment.

#6. Panel recommendations:

At basic levels of resource allocation, hydration therapy should be available (oral and IV hydration and electrolyte replacement). Available antiemetics should include corticosteroids, prokinetic, non-selective serotonin antagonists, and dopamine receptor antagonists.^{40,129,131–133} Diarrhea treatments should include loperamide.⁴⁶ Stool softeners, bulk laxatives, lubricant laxatives, and lactulose should be available to manage opioid-induced and other causes of constipation. Mucositis support should include patient education on the use of ice chips, avoidance of irritants, and appropriate use of mouth rinsing with 0.9% saline solution and sodium bicarbonate. Anxiety symptoms should be managed through patient education and support. Parasitic and or bacterial infection should be considered. At limited levels, antiemetics should include selective serotonin (5-HT3) antagonists.^128,129,133 H2 antagonists could be considered to counteract steroid side-effects.⁴⁴ Anti-acids and stimulant laxatives^44,46 should be available. Anti-anxiety drugs, such as lorazepam¹³⁰, should be considered. Consultations on diet should be available. Mucositis support includes more advanced topical agents to help alleviate pain and fungal infections. At enhanced levels, newer effective antiemetics, such as NK-1 antagonists, may be used with highly emetogenic chemotherapy.^44,128,134 Proton pump inhibitors (PPIs) may be considered to counteract steroid side-effects. Opioid analgesics may be considered for severe mucositis. Individualized education with a certified dietitian should be available.

Skin and Nail Toxicities, Chemotherapy Extravasation (Table 4, Row 4)

Description: Skin and nail toxicities can occur with breast cancer treatments. Extravasation can also occur as a serious complication of some IV chemotherapy administration. Radiation-induced skin toxicity varies in severity based on: dose, duration, and site; skin type; size of breast; menopausal status; comorbidities such as diabetes¹³⁵; and smoking¹³⁶. Skin reactions can vary from mild erythema and dry desquamation to more serious moist desquamation. Chemotherapy and other medication-related toxicities include alopecia, hand-and-foot syndrome, and nail alterations and infections. Breast cellulitis is uncommon but may occur after breast-conserving surgery and radiotherapy. Debridement surgery may be needed to treat wounds related to extravasation, breast surgery, radiotherapy, or chemotherapy skin toxicities, and should be performed by a surgical professional. Dexrazoxane may reduce the need for surgery for extravasation resulting from anthracycline chemotherapy.¹³⁷ Patient education on skin care and infection prevention is important in LMICs and should include how to protect skin from infection and injury, care of skin lesions, and timely reporting of skin complications to health professionals. (See the companion BHGI consensus statement, Supportive and Palliative Care for Metastatic Breast Cancer⁹, for details on chronic skin complications and wound management.)

#7. Panel recommendation:

At basic levels of resource allocation, patient and family education on skin care is recommended. At limited levels, topical treatments (eg, corticosteroids, zinc)¹³⁸ and DMSO should be available. Debridement surgery, performed by a surgical professional, should be available. Coordinated patient care should be available to help prevent or reduce treatment-related skin complications. At enhanced levels, consultation with a dermatology specialist, and central line access and management should be available. At maximal levels, dexrazozane could be considered.

Nervous System Toxicities (Table 4, row 5)

Description: Peripheral neuropathy is a common side-effect of chemotherapy, and is a treatment emergent issue in 30–40% of patients.¹³⁹ Neuropathic pain associated with taxane infusion usually resolves in 3–7 days, but effects may last up to 2 years following treatment¹⁴⁰, and may be related to nerve pathology.^141–143 Cognitive function alterations can occur with endocrine therapy or chemotherapy, and reduce patient quality of life.^144,145 Health professional education should include: 1) the differences between nociceptive pain and neuropathic pain¹⁴⁶; 2) how the risk of neuropathy increases with increasing doses of therapy; and 3) conditions that predispose patients to neuropathy such as diabetes, alcoholism, poor nutrition, and pre-existing peripheral neuropathy. Health professional education should include how to evaluate patients for upper and lower extremity peripheral sensory neuropathy (numbness, tingling), as well as neuropathic pain symptoms (shooting/burning pain).¹⁴⁷ Assessment tools for neuropathic pain may be helpful.¹⁴⁸ Physiotherapy is especially important for patients with pre-existing peripheral neuropathy.¹⁴⁹ Pharmacologic neuropathic pain management often requires a multimodal approach¹⁵⁰, and should follow the WHO pain ladder³³ and other pain management guidelines.¹⁵¹ Chemotherapy-induced cognitive changes include short-term memory loss, as well as attention and concentration problems. Awareness of cognitive changes should be included in patient and health professional education, although more research is needed in this area.¹⁵²

#8. Panel recommendations:

At basic levels of resource allocation, pain management should include local and systemic strategies, including morphine, and should follow the WHO pain ladder recommendations. Topical agents to consider include baclofen-amitriptyline-ketamine preparations.¹⁵³ Patient education on physical activity to improve functional limitations should be provided. At limited levels, physical therapy (PT) to improve functional limitations should be provided. Drug therapy should be available based on WHO pain ladder. At enhanced levels, patients should be referred to neurologists as needed; anesthetics for nerve blockage may be considered for severe painful neuropathy. Consultation for pain management and cognitive problems with a neurology specialist should be available.

Note: Gabapentin and pregablin are sometimes used at an enhanced level of resource allocations, but studies have shown mixed results regarding its effectiveness.¹⁵⁴

Treatment-related Toxicities (B): Hematologic Complications, Symptom Management and Monitoring during Treatment (Table 5)

Table 5.

Resource allocations for treatment-related toxicity (B): hematologic complications, symptom management, women’s health concerns, and monitoring during treatment

	Basic	Limited	Enhanced	Maximal
Hematologic Toxicity and Infection	Antibiotics: broad spectrum	Antifungals Red blood cell transfusion Infectious disease consultation for febrile neutropenia	Growth factors; granulocyte growth factors Platelet transfusion Iron therapy
Fatigue, Insomnia and Non-specific Pain	Pain management, including morphinea Patient and family educationb
Women’s Health Issues	Patient and partner education: early menopause, body image, reproductive health / fertilityc	Management of menopausal symptomsd Patient and partner education: sexual healthc		Fertility clinic (ie, assisted reproduction) Egg/embryo freezing
Monitoring	Physical exam, CBC, potassium and sodium, urea, bilirubin and transaminase, and when needed CXR, UA, microbiology Check for early lymphedema, nausea and vomiting, constipation and diarrhea, fatigue and insomnia, and pain	Other blood chemistry and liver function tests Renal function assessment Non-imaging cardiovascular assessment	Extensive lab support, bone density tests

Note: The table stratification scheme implies incrementally increasing resource allocation at the basic, limited, and enhanced levels. Maximal-level resources should not be targeted for implementation in LMICs, even though they may be used in some higher-income settings.

Abbreviations: CBC, complete blood count; CXR, chest x-ray; UA, urinalysis.

^aPain management should follow the World Health Organization pain ladder recommendations. Morphine should be available and easily accessible at a basic level of resources.

^bPatient, family and/or partner education may be the primary intervention for some supportive care services.

^cWomen’s health issues for breast cancer patients include menopause, body image, reproductive health, including fertility, and sexual health; educational efforts should include partners. See the companion BHGI consensus statement Supportive Care after Curative Treatment for recommendations for menopausal symptom management.

Hematologic Toxicities (Table 5, Row 1)

Description: Hematologic toxicity is a common side-effect of most chemotherapy regimens. Adequate monitoring and management of hematologic toxicity can prevent serious complications associated with bone marrow suppression, ie, febrile neutropenia (FN) and infections, bleeding and hypoxia, which may require hospitalization. Adequate and regular monitoring may include complete blood count (CBC), clinical status, and physical examinations. Use of preventive and supportive medications can help avoid these serious complications, including infections. Iron therapy and growth factors for low blood cell count¹⁵⁵, and granulocyte growth factors, have consistently been shown to decrease the risk of FN, and should be considered when giving chemotherapy regimens with >20% incidence of FN.¹⁵⁶

#9. Panel recommendations:

At basic levels of resource allocation, broad-spectrum antibiotics should be available. At limited levels, antifungal agents should be available. Red blood cell transfusion may be needed in case of acute anemia or bleeding, and consultation with an infectious disease specialist regarding febrile neutropenia should be considered. At enhanced levels, additional therapies for low blood cell count include iron therapy, growth factors, and granulocyte growth factors. Platelet transfusion should be available for severe thrombocytopenia or thrombocytopenic bleeding.

Fatigue, Insomnia, and Non-specific Pain (Table 5, Row 2)

Description: Fatigue is a common symptom reported by breast cancer patients and a universal symptom of patients undergoing cytotoxic chemotherapy or radiotherapy.³⁵ For many patients, fatigue is more distressing than pain or nausea and vomiting, for which there are medications.³⁵ Interventions that may be effective in reducing cancer-related fatigue include physical activity¹⁵⁷, exercise programs^158–160, nutrition, and adequate hydration and electrolyte balance.³⁵ Appropriate anemia management may be effective.¹⁵⁵ Insomnia is another common symptom reported by breast cancer patients during treatment.^155,161 Interventions include patient education on sleep problems; behavioral sleep therapy is being studied in HICs.^69,162 Assessment tools for fatigue and insomnia may provide an opportunity for improved clinician-patient communication.¹⁶³

Pain, including non-specific pain, is a symptom frequently reported by breast cancer patients. A systematic review found the prevalence of pain in breast cancer patients to be 59% during treatment, 33% after treatment, and 64% in patients with metastatic disease.¹⁶⁴ General pain management often requires a multimodal approach, and should include pain assessment tools.¹⁵⁰ In many LMICs, access to pain control medications is extremely limited, generating significant additional and preventable suffering for patients. Morphine is inexpensive and efficacious, and should be available and easily accessible in all LMICs.

#10. Panel recommendations:

At basic levels of resource allocation, patient and family education is recommended for management of fatigue and insomnia and should include strategies for appropriate periods of rest and activity. Pain management should follow the WHO pain treatment ladder. Morphine should be available and easily accessible at a basic level of resources.

Note: Late cardiotoxicity effects are addressed in the BHGI companion consensus statement Supportive Care after Curative Treatment⁸. Cardiotoxicity during treatment with anthracycline-based regimens (ie, doxorubicin or epirubicin) is dose-related; associated congestive heart failure is reported to reach up to 5% in patients treated.¹⁶⁵

Women’s Health Issues (Table 5, Row 3)

Description: Women’s health issues associated with breast cancer treatment include early menopause, reproductive health (including fertility), body image and sexual health.^166–168, Consideration of fertility and body image should be part of patient treatment planning. Early menopausal symptoms and associated sexual dysfunction can be a problem for both pre- and post-menopausal women as a result of systemic cancer treatment, such as cytotoxic chemotherapy, hormonal therapy, or manipulation (ie, ovarian suppression or ablation).^169,170 Body image problems can also occur after mastectomy or after breast-conserving therapy.^171,172 Body image and sexual health should be discussed with patients during treatment.⁸⁶ Studies on sexual health in breast cancer patients found that being more than 12 months post-treatment was a significant predictor of increased interest in a sexual health program.¹⁷³ A systematic review suggests that athough some stress about body changes can diminish with time, specific suggestions and behavioral sexual therapies may produce substantive improvements in sexuality.¹⁷⁴

For patients concerned with fertility, chemotherapy regimens that may avoid DNA damage can be considered (eg, cyclophosphamide). In HICs, fertility has been shown to be important to young breast cancer patients¹⁷⁴; with increased interest in fertility preservation^{169,175–177}. Fertility is an emerging breast cancer care issue in LMICs, due to the large number of women diagnosed at a younger age, and an increase in early-stage disease diagnosis and potential curative treatment. Options for female fertility preservation include fertility clinics (ie. assisted reproduction) and cryopreservation of embryos or eggs.¹⁷⁸

#11. Panel recommendations:

At basic levels of resource allocation, patient education (including partner education) on early menopause, body image, and reproductive health should be available. At limited levels, patient and partner education on sexual health should be available. Management of menopausal symptoms should be available, as needed. (See the BHGI companion consensus statement, Supportive Care after Curative Treatment⁸, for recommendations on menopausal symptoms.) At maximal levels, referrals for appropriate counseling and potential intervention to preserve fertility through fertility clinics (ie. assisted reproduction) or egg/embryo freezing could be considered.

Monitoring (Table 5, Row 4)

Description: Monitoring for treatment-related side-effects is considered part of routine breast cancer treatment protocol, but is also an important part of supportive care and requires an interdisciplinary and/or multidisciplinary team approach. Clinical practice guidelines are available and should be followed (See Table 2).

Note: “Multidisciplinary team approach” refers to a patient care model that includes experts from different disciplines, whereas an “interdisciplinary team approach” requires a more integrated and coordinated approach to patient care, where experts from different disciplines establish shared patient care goals.

#12. Panel recommendations:

At basic levels of resource allocation, monitoring for treatment-related toxicities includes patient history, physical examination (including throat and skin), complete blood count (CBC), basic laboratory tests such as potassium and sodium, urea, bilirubin, transaminase, and, when needed, plain chest x-ray (CXR), urinalysis (UA), and microbiology. Monitoring for early lymphedema, nausea and vomiting, constipation and diarrhea, fatigue and insomnia, and bone and neuropathic pain is also recommended. At limited levels, monitoring should include other basic blood chemistry, liver function assessments, renal assessments, and non-imaging cardiovascular assessments. At enhanced levels, extensive laboratory support and bone density testing should be available.

Special Concerns and Emerging Issues in LMICs

Matching treatment choices to available resources:

During treatment planning, the availability of resources to manage the toxic effects of chemotherapy and radiotherapy, and the complications of surgery and endocrine therapy, must be considered. When resources to manage side-effects are unavailable or limited, effective chemotherapy with limited toxicities should be the treatment recommendation. When more resources are available to manage toxicities, chemotherapy with moderate toxicities can be considered; the optimal treatment goal is to have available a full range of treatment options and supportive care interventions to manage treatment-related side-effects.

Patient and family education and support:

In LMICs, patient and family education is an important part of patient recovery. Patient education can be delivered in a variety of forms (eg, oral, written, video), depending on patient preference and feasibility in specific countries or regions.^179,180 Family caregivers often have unmet educational or psychosocial needs. A study in HICs found that the majority of relatives of breast cancer patient had higher levels of depression, anxiety or distress than their relative with breast cancer.¹⁸¹ Anxiety, depression, avoidant coping and active coping, caregiving, and out-of-pocket expenses have been associated with more reported unmet needs of relatives.¹⁸²

The majority of breast cancer patients’ partners (in a HIC study), reported a need for educational interventions.⁹⁹ Partners provided with educational information and support reported lower anxiety, depression and marital distress.⁸⁹ Partners should be included in breast cancer patient education, as culturally appropriate, and with approval of the patient. Studies (in LMICs) have reported on the difficulties of partners in coping with breast changes and sexual disruption.^87,88 Internet-based interactive content may be an effective way to provide educational interventions and to reach a large number of people.⁹⁹ Existing online educational programs can be reviewed and modified to meet LMIC social and cultural needs.

Cultural sensitivity:

Educational strategies for breast cancer patients must be culturally sensitive and appropriate^94–98,183 and tailored to a patient’s specific setting¹⁸⁴. While there are no guidelines for patient and community education on these topics, a number of studies provide details on educational strategies.^90–94 Educational programs can help to dispel social and cultural myths, assist with managing social issues, and help families understand how breast cancer diagnosis and treatment can impact and/or change roles in family life and at the workplace.¹⁷⁹ Understanding cultural and traditional family dynamics, including traditional gender roles, and the type of social support available within different cultures is part of health professional cultural competency. A patient’s preference for a gender-specific health professional should be respected and accommodated. Patients may prefer peer support from members of their own culture/ethnicity. For example, a study of South Asian breast cancer patients reported patients’ preference for peer support from their own ethnic group, to cope with the social and cultural stigma of breast cancer within the broader community.¹⁸⁵ Patient and family education can include printed materials, audiotape, peer modeling video tapes, telephone support and/or counseling²³, and should be provided by health care team members (eg, primary care physicians, oncologists, nurses) trained in culturally sensitivity, health literacy, and communication skills.¹⁷⁹

Risk assessment:

Although risk assessment of treatment-related short-term and long-term complications should occur during treatment planning, a review of a patient’s treatment regimen and their associated risk of long-term complications is an important part of supportive care services. Risk assessment for both physical complications and psychosocial issues allows a health system to identify and prioritize the resources needed for supportive care for breast cancer patients. Some treatment-related risks, such as lymphedema, are well established¹⁸⁶, and assessment tools are available¹²³. Other treatment-related risks are related to type and degree of systemic therapy, such as risk of neuropathy (as a side-effect of chemotherapy)¹⁴⁹, risk of early menopause from endocrine therapy^25,187,188, or cardiovascular disease risks.¹⁸⁹ Risk assessment tools for psychosocial complications, such as depression and emotional distress, are available in HICs and have been adapted for use in LMICs. Studies in LMICs have identified patient characteristics associated with emotional distress related to cancer care, including lower education levels¹⁹⁰, prior/concurrent psychopathology¹⁹¹, severe physical symptoms^{66,70,192,193}, and recurrent disease¹⁹⁰. In addition, higher rates of distress have been found in patients receiving treatment at public rather than private hospitals or practices.^102,192

Psychosocial screening:

Screening for distress has become a component of cancer care guidelines, both in HICs⁴⁹ and in some LMICs⁶². For example, the National Comprehensive Cancer Network (NCCN) recommends that new cancer patients be assessed in the office or waiting room for evidence of distress using a brief screening tool (the distress thermometer and problem list), and that patients with higher scores be referred to psychosocial service based on patient-reported problems.⁴⁹ The screening tool problem list includes practical social, psychological, and spiritual concerns. The screening protocol requires health professionals to be knowledgeable about available patient support services at the health institution, or within the community. Quality of life measures, such as the EORTC measure, provide an assessment of psychological, social domains, disruption of role functioning, and other relevant areas and have been used in LMICs^66,194. Specific depression screening tools developed in HICs have been translated or adapted to LMICs, and include the Hospital Anxiety and Depression Scale (HADS)^102,103,109, the Beck Depression Inventory (BDI)^65,67, and a simplified depressed mood thermometer.¹⁰⁴ Although there is not conclusive evidence for the overall effectiveness of screening for distress in improving patient outcomes, it has been shown to improve communication between patients and providers, and facilitate prompt referrals to peer support or mental health professionals.¹⁹⁵

Discussion

The panel concluded that although treatment-related toxicities are one of the more medically well-defined aspects of supportive care, with clinical best practice guidelines available, this area of breast cancer treatment may be overlooked in LMICs. The resource-stratified table matrix on treatment-related toxicities can be used as a guide to implement, review, or expand this area of breast cancer care.

Health systems that are implementing supportive care programs should devote resources to educating professionals, patients and communities about supportive care services; provide resources to support monitoring of treatment-related toxicities; and provide psychosocial support. Breast cancer and its treatment can have significant impact women’s health issues, including reproductive health and sexual health. Open patient-provider discussions on women’s health issues, in a culturally appropriate manner, as an important part of breast cancer supportive care. Many treating clinicians may be uncomfortable addressing such sensitive topics and may require additional training or access to specialists for patient referral. A fuller discussion on women’s health issues can be found in the companion BHGI consensus statement, Supportive Care after Curative Treatment.⁸

Resources for psychosocial supportive should be available soon after diagnosis and during initial treatment, as this is when the majority of disease awareness and treatment-related psychosocial issues occur, with patients experiencing the greatest impact on their roles at home, at work, and in the community at this time. After initial diagnosis and treatment planning, psychosocial support may take two paths: one for patients who are likely to be cured of their disease and have a long survivorship horizon, and one for patients with advanced disease who will need palliative support. (See the companion BHGI consensus statements: Supportive Care after Curative Treatment⁸, and Supportive and Palliative Care for Metastatic Breast Cancer.⁹)

Spiritual well-being can impact treatment adherence and patient satisfaction with care, and should be addressed early in the course of cancer care. Continued spiritual support after treatment should be provided for both survivors and patients with advanced disease, but resources for initial assessment and support should be provided early on during treatment.

A number of reports on supportive care recommend that it should begin at diagnosis.^198,199 In the majority of cases, diagnosis and treatment occur within a relatively short-time period. The BHGI 2012 Global Summit did not specifically include diagnosis of breast cancer, which was addressed in the BHGI 2008 diagnosis guideline.¹⁹⁹ Establishing supportive care during initial breast cancer treatment will help ensure that breast cancer patients receive comprehensive care that can help 1) improve adhere to treatment recommendations, 2) manage treatment-related symptoms, and 3) address the psychosocial and spiritual aspects of breast cancer and cancer treatments.