The World Health Organization (WHO)’s Global Breast Cancer Initiative Implementation Framework provides national programme managers, policymakers, and multisectoral actors the guidance needed to assess, strengthen, and scale up services for the early detection and management of breast cancer.
This specialist Guidelines summary for medical and clinical oncologists covers various aspects of breast cancer care and management, including breast cancer treatment, principles of multimodality treatment, and features of a successful systemic therapy programme.
The Framework presents key strategies using three pillars:
- Pillar 1: health promotion for early detection (prevention and pre-diagnostic interval)
- Pillar 2: timely breast diagnostics (diagnostic interval)
- Pillar 3: comprehensive breast cancer management (treatment interval).
Pillar 1: The Pre-Diagnostic Interval
- The pre-diagnostic interval (Pillar 1) represents the period before an individual presents to the healthcare system with a breast complaint, or for breast screening. This includes individuals with abnormal clinical or radiographic findings who are referred for diagnostic workup
- The key performance indicator (KPI) for Pillar 1 is at least 60% of invasive cancers to be stage I or II at diagnosis. No country has achieved a sustained decline in breast cancer mortality rates of 2% per year or more for at least 3 consecutive years without also achieving a level of early detection where 60% of patients present with stage I or II disease.
Personalised Assessment of Risk for Breast Cancer
- Known breast cancer risk factors include genetic mutations, previous exposure to thoracic radiation, older age, obesity, breast density, and a family history of breast and/or ovarian cancer
- Individuals found to be at increased risk for breast cancer (>20% overall lifetime risk) are candidates for enhanced screening in settings where screening is available and sustainable
- Two commonly used risk calculators are the Breast Cancer Risk Assessment Tool designed by National Cancer Institute (US) and the Tyrer–Cuzick Risk Model. Their usefulness to low- and middle-income countries is unknown, especially in settings where screening services are unavailable.
Early Detection: Clinical Breast Assessment Skills
Obtaining a Medical History
- Healthcare professionals should know how to take an appropriate medical history and conduct a standardised physical examination in a culturally sensitive manner.
Performing a Clinical Breast Examination
- Clinical breast examination (CBE) is a systematic and specific examination of the breasts, nipples, and areolas combined with examination of axillary, infraclavicular and supraclavicular lymph-node beds as performed by a healthcare provider. First, with the individual in an upright position, the provider visually examines the uncovered breasts to look for asymmetries, puckering, dimpling, or localised skin changes. The clinician then palpates the armpit to feel for enlarged lymph nodes or masses. The individual then lies back on the examining table with her arm above her head, which flattens the breast on the chest wall. The provider then manually examines each breast with one or two fingers of each hand to feel for masses, thickenings, other localised asymmetries, or spontaneous bloody or clear nipple discharges
- Abnormal findings on CBE generally warrant diagnostic imaging and may require tissue sampling to make a definitive diagnosis. If advanced disease is suspected, a complete physical examination should be included to check for symptoms of potential metastatic disease (for example, in the form of regional nodes and/or bony tenderness). Although live or virtual workshops (including real patients, simulation-based methodologies, or videos) do have an impact, education in examining real patients is ultimately required to ensure the quality of skills in this area.
Referral for Definitive Diagnosis
- Well-functioning referral networks and patient navigation are required so that people with breast abnormalities can receive prompt, accurate, and definitive diagnoses.
Pillar 2: The Diagnostic Interval
- The diagnostic interval (Pillar 2) represents the intermediate period between referral for a diagnostic investigation and the time that a definitive benign or malignant diagnosis is made. Those found to have cancer then need to be referred for definitive treatment
- The KPI for Pillar 2 is for breast cancers to be diagnosed within 60 days (2 months) of initial presentation to a healthcare system.
Diagnostic Imaging and Tissue Sampling
- Individuals requiring a biopsy need to be guided through the multiple steps necessary to obtain a definitive diagnosis. This patient navigation process can break down if it requires the patient to travel to another location for a biopsy procedure. Ideally, imaging and biopsy procedures are performed in the same location and during the same visit. The options for biopsy procedures include core-needle biopsy (gold standard), fine-needle aspiration, or incisional biopsy.
Pathology and Biomarker Testing
- Overall, the goal of histopathology diagnosis is for 100% of patients with breast cancer to receive a confirmed diagnosis with a standard biomarker evaluation (oestrogen receptor [ER], progesterone receptor [PR], human epidermal growth factor receptor 2/neu oncogene overexpression [HER2/neu]). This includes a report that describes the breast cancer features and subtype based on these findings, guiding treatment decisions in alignment with WHO recommendations for the selection and use of essential in vitro diagnostics.
Centralisation Versus Decentralisation of Diagnostic Services
- A balance between centralised and decentralised diagnostic services is generally required. If it is not feasible to fully decentralise the imaging and pathology services, well-organised sample transport systems and information systems can effectively decentralise sample collections, while minimising patient travel and still enabling critical results to be obtained in a reasonable timeframe.
- Once a cancer diagnosis has been confirmed, the patient should undergo staging to evaluate the extent of the disease
- The most widely used classification system for breast cancer staging is the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) tumour, node, metastasis (TNM) staging (AJCC /UICC TNM) system, which is based on anatomic features: tumour size (T), nodal status (N), and metastases (M).
Monitoring and Evaluation of the Diagnostic Interval
- Although centralising diagnostic testing at referral centres may increase quality control, it can also make it difficult for patients to access these services and increase the likelihood of them not being able to complete all the indicated testing in a timely fashion. Cross-facility coordination and patient navigation are critical to minimising delays.
Pillar 3: The Treatment Interval
- The treatment interval (Pillar 3) represents the episode where patients shown to have cancer receive definitive care. Treatment includes cancer-directed therapies (surgery, radiotherapy, and systemic ‘anticancer’ treatment, combined with supportive management in an integrated care model)
- The KPI for Pillar 3 is that at least 80% of patients receive their recommended treatment to completion without abandonment.
Principles of Multimodality Treatment
- Effective breast cancer surgical services require that:
- communities have a sufficient number of surgeons trained in cancer surgery and that anticipated future needs are incorporated in workforce planning
- policymakers ensure the availability of the necessary resources (operating rooms, anaesthesiologists) to allow patients to receive surgical treatment in a timely fashion
- cancer rehabilitation services, such as those for physical therapy, are available to reduce morbidity from breast cancer surgery, such as lymphoedema.
Features of a Successful Radiation–Oncology Programme
- A successful radiation–oncology programme encompasses:
- technical expertise, including a clinical or radiation oncologist, a physicist/dosimetrist, and radiographers/radiotherapists
- evidence-based clinical regimens on breast radiation that include dosimetric objectives and constraints for target and normal tissues
- access to regularly maintained equipment for external beam radiotherapy, with backup in case of service interruptions and breakdowns
- quality assurance programmes on radiotherapy to ensure safety and efficacy
- reimbursement schemes (in local healthcare systems or private healthcare settings where applicable) based on treatment indications, not on the number of fractions given.
Systemic Therapy for Breast Cancer
- The choice of systemic therapy for breast cancer is based on the following:
- tumour biology, mainly breast cancer subtype (ER, PR, and HER2/neu receptor status). Additional factors include histological type, tumour grade, proliferation marker, and lymphovascular invasion
- genomic scores, such as OncotypeDx, also guide systemic treatment strategies
- tumour burden, determined by the TNM stage (tumour size, axillary-lymph-node involvement, and the presence/absence of distant metastases)
- patient characteristics (including age, performance status, comorbidities, and patient preferences).
Categories of Systemic Therapy Modalities
- Endocrine (hormonal) therapy, such as oestrogen receptor modulators/degraders (tamoxifen) and aromatase inhibitors
- Cytotoxic chemotherapy, such as capecitabine or vinorelbine
- Targeted therapies, such as HER2-targeted therapy.
Successful Systemic Therapy Programmes for Breast Cancer
- The choice of systemic therapy for breast cancer is based on the following:
- medical oncologists who can prescribe systemic therapy, manage toxicity, and monitor efficacy
- trained nurses who can administer systemic therapy and help in the monitoring and evaluation of toxicity
- trained pharmacists
- access to 24-hour care in emergencies
- protocols on the preparation for, and the safe handling and administration of, chemotherapy
- annual (at a minimum) quantification of medicines and volumes
- procurement mechanisms to avoid stockouts and make full use of generic manufacturers, as appropriate, to reduce costs
- access to supportive care medicines for the prevention and management of toxicities
- tumour biology, mainly breast cancer subtype (ER, PR, and HER2-receptor status plus additional factors, such as histological type, tumour grade, proliferation marker, and lymphovascular invasion, and genomic scores to guide systemic treatment, such as OncotypeDx)
- tumour burden, determined by the TNM stage (tumour size, axillary-lymph-node involvement, the presence/absence of distant metastases)
- patient characteristics, including age, performance status, comorbidities, and patient preferences.
Factors Contributing to Patient Abandonment of Prescribed Cancer Treatment
- Patient-related factors: lack of engagement, social pressure, religious beliefs, philosophical attitudes, and stigma
- Accessibility-related factors: lack of access to services due to distance to point of treatment; component delivery; lack of transportation; no provision of lodging/accommodation in or near point of delivery
- Financial factors: unaffordable treatment costs, or costs related to being able to access treatment, such as those for transport and accommodation
- Factors related to failure of the healthcare system: lack of planning, personnel and equipment; overload; structural racism; ageism; gender discrimination; and/or other forms of discrimination.
Management of Metastatic Breast Cancer
- Access to metastatic breast cancer (MBC) treatment is fundamental to ensuring equitable healthcare and avoiding stigma and the exclusion of patients with advanced/metastatic cancers
- Treatment of MBC/advanced breast cancer (ABC) is based on multiple therapeutic modalities. Since the disease is disseminated at these stages, the main therapeutic approach is systemic therapy. However, radiotherapy and, in some circumstances, surgery are also indispensable for the adequate treatment of some types of metastases. In some situations, surgery and radiotherapy are also important in the management of de novo metastatic disease
- It is crucial that patients with MBC are discussed by a multidisciplinary tumour board and that a common strategy is defined. No treatment should be initiated without the histological confirmation of malignant disease. For de novo MBC, a biopsy of the primary tumour is needed; for recurrent MBC, a biopsy of one of the metastatic lesions is recommended for confirmation. Throughout the patient’s journey, starting as early as possible, supportive oncology (including palliative care), and psychological support are also fundamental.
Metrics Useful in the Monitoring and Evaluation of Metastatic Cancer
- Completeness of the pathology evaluation of prognostic/predictive biomarkers (ER, HER2)
- Proportion of patients receiving hormone treatment for ER-positive cancer
- Proportion of patients with metastatic cancer whose data have been collected for the last 5 years.
Management of Breast Cancer During Pregnancy
- As with any breast abnormality, the evaluation of the pregnant patient with suspected breast cancer should include a physical examination, paying particular attention to the breast and regional lymph nodes. However, the preferred biopsy technique is core-needle biopsy. This provides tissue for the histologic confirmation of invasive disease and hormone-receptor and HER2 analyses and is best for distinguishing cancer from the physiological changes of pregnancy
- Once a cancer diagnosis is confirmed, the initiation of breast cancer treatment should not be delayed because of the pregnancy. The treatment options are the same as those for a patient who is not pregnant, but the sequence of treatment may be altered to avoid radiotherapy while the patient is still pregnant. The indications for systemic chemotherapy are the same in the pregnant patient as in the non-pregnant patient; however, chemotherapy should not be administered during the first trimester. Chemotherapy can be given safely during the second and third trimesters, using agents that do not cross the placental barrier and, therefore, do not directly affect the fetus. Surgery can also be performed safely during pregnancy
- The most common surgical procedure for pregnancy-associated breast cancer is modified radical mastectomy. However, breast-conserving surgery is possible if radiotherapy can be delayed until the postpartum period.
Supportive Services in Oncology
- Supportive services are essential to patient compliance and effective care delivery during treatment, as well as to recovery following therapy.
Supportive Services During Treatment
- During treatment, breast cancer patients need supportive care, including the management of treatment-related toxicities. In addition, these patients have educational, psychosocial, and spiritual needs.
Supportive Services Following Treatment
- Breast cancer survivors may experience long-term treatment complications and must live with the risk of cancer recurrence. In addition, they often experience psychosocial complications that require supportive care services. Monitoring and support services should, therefore, be available for and accessible to these individuals. Direct management may be offered with routine follow up, usually for 5 years.
Palliative Care and End-of-Life Management
- Palliative care is an approach that improves the quality of life of patients (both adults and children) and their families who face problems associated with life-threatening illness
- The holistic palliative care approach to patient care, which incorporates all domains of the human experience of illness, is traditionally applied to help cancer patients cope with the impact of the disease and its treatment, and to manage symptoms, such as pain, nausea, fatigue, anxiety, delirium, confusion, and depression
- While the purpose of end-of-life care for breast cancer patients is to enable them to ‘live well’ and with dignity, no matter the condition of their health, the primary goal is to provide them with the assurance that the process up to their death will be compatible with their cultural needs, personal views, and preferences.