Current Approaches for Breast Cancer Management
Multidisciplinary Team-Based Care
Breast cancer management must be delivered through specialized breast units by a multidisciplinary team (MDT) consisting of medical oncologists, breast surgeons, radiation oncologists, breast radiologists, breast pathologists, and breast nurses 1, 2. This approach is non-negotiable for optimal outcomes, as MDT care has been consistently associated with improved survival and treatment patterns 3, 4.
Diagnostic and Staging Workup
Initial Assessment
- Pathological diagnosis according to WHO classification from surgical specimens 2
- Minimal staging includes complete blood count, liver enzymes, alkaline phosphatase, calcium levels, contralateral mammography, clinical examination, and chest X-ray 2
- Brain imaging should NOT be routinely performed in asymptomatic patients 1
- FDG-PET-CT scanning may replace traditional imaging for staging in high-risk patients when conventional methods are inconclusive 2
Biomarker Assessment
- Validated gene expression profiles should be used to complement pathology assessment and guide adjuvant chemotherapy decisions 2
- Patients being considered for PARP inhibitor therapy must undergo genetic testing for BRCA1/BRCA2 pathogenic variants regardless of age, family history, or breast cancer subtype 1
Treatment Strategy by Disease Stage
Early-Stage Breast Cancer (Non-Metastatic)
Surgical Management
Breast-conserving surgery (BCS) is the preferred local treatment option for most early breast cancer patients, with oncoplastic techniques used when needed to maintain cosmetic outcomes 2. The key surgical principles include:
- Sentinel lymph node biopsy (SLNB) is the standard of care for axillary staging in clinically node-negative disease 2
- Further axillary surgery following positive SLNB is NOT required when there is low axillary disease burden (micrometastases or 1-2 positive sentinel nodes) if treated with postoperative tangential breast radiotherapy 2
- When mastectomy is necessary, immediate breast reconstruction should be offered to all women except those with inflammatory cancer 2
Radiation Therapy
- Radiation therapy is essential following breast-conserving surgery 2
- Axillary radiation is a valid alternative in patients with positive sentinel lymph node biopsy, regardless of breast surgery type 2
Systemic Therapy by Subtype
Hormone Receptor-Positive/HER2-Negative (70% of patients):
- Endocrine therapy for 5-10 years is essential 5
- Validated gene expression profiles should guide decisions about adding adjuvant chemotherapy 2
- Rechallenge with drugs previously used in early breast cancer is reasonable if disease-free interval is ≥12 months after last drug administration and no remaining toxicities exist 1
HER2-Positive (15-20% of patients):
- For adjuvant treatment, trastuzumab is indicated as part of treatment regimens with doxorubicin/cyclophosphamide plus paclitaxel or docetaxel, or with docetaxel/carboplatin 6
- Neoadjuvant therapy with targeted drugs has become standard of care for most early-stage HER2-positive disease, followed by risk-adapted post-surgical strategies 5
Triple-Negative (15% of patients):
- Chemotherapy alone is the standard systemic treatment 7
- Neoadjuvant therapy including immune checkpoint inhibitors has become standard of care for most early-stage triple-negative disease 5
- Note: Triple-negative breast cancer has 85% 5-year breast cancer-specific survival for stage I tumors versus 94-99% for hormone receptor-positive and HER2-positive subtypes 7
Metastatic Breast Cancer
Metastatic breast cancer is incurable but treatable, with some patients living for extended periods (many years in some circumstances) 1. Systemic therapy is the standard of care but may be supplemented with locoregional treatments 1.
Treatment Principles
- Treatment decisions must be made independent of patient age, but comorbidities, patient characteristics, and preferences need consideration through shared decision-making 1
- Patients should be encouraged to participate in clinical trials early in their disease course, with preference for enrollment in each line of therapy 1
- Sequential monochemotherapy is preferred without rapid clinical progression or life-threatening visceral metastases 2
Systemic Therapy by Subtype
Hormone Receptor-Positive/HER2-Negative:
- Endocrine therapy is the preferred option unless rapid response is warranted or endocrine resistance is suspected 2
- CDK4/6 inhibitors combined with endocrine therapy are standard for hormone receptor-positive disease 5
- PI3K inhibitors are options for specific patient populations 5
HER2-Positive:
- HER2-directed therapy should be offered early to all patients, either as single agent, combined with chemotherapy, or with endocrine therapy 2
- For first-line treatment, trastuzumab in combination with paclitaxel is indicated 6
- As single agent for patients who have received one or more chemotherapy regimens for metastatic disease 6
- Median overall survival is approximately 5 years 7
Triple-Negative:
- PARP inhibitors (olaparib or talazoparib) should be offered to patients with germline BRCA1/2 pathogenic variants, independent of hormone receptor status, as alternative to chemotherapy 1
- Prior anthracycline/taxane treatment should NOT be required before offering PARP inhibitors 1
- Immunotherapy is currently indicated for part of triple-negative disease 5
- Median overall survival is approximately 1 year 7
Site-Specific Management
Primary Stage IV Disease:
- Locoregional treatment of the primary tumor in absence of symptomatic local disease does NOT lead to overall survival benefit and is NOT routinely recommended 1
- Surgery of primary tumor may be considered for patients with bone-only metastasis, HR-positive tumors, HER2-negative tumors, age <55 years, oligometastatic disease, and good response to initial systemic therapy 1
Oligometastatic Disease:
- Patients must be discussed in multidisciplinary context to individualize management 1
- Multimodality treatment approaches involving locoregional therapy (high conformal radiotherapy, image-guided ablation, selective internal radiotherapy, and/or surgery) combined with systemic treatments are recommended 1
- Local ablative therapy to all metastatic lesions may be offered individually after multidisciplinary discussion, though it is unknown if this improves overall survival 1
Bone Metastases:
- Bone-modifying agents (bisphosphonates or denosumab) are recommended for all patients with bone metastases, regardless of symptoms 1
- Denosumab administered every 4 weeks is more effective than zoledronate in delaying first and subsequent skeletal-related events 1
- Zoledronate can be administered every 12 weeks in patients with stable disease after 3-6 monthly treatments 1
- Before bone-modifying agent initiation, patients must have complete dental evaluation and ideally complete required dental treatment; calcium and vitamin D supplements should be prescribed 1
- It is reasonable to interrupt bone-modifying agent therapy after 2 years for patients in remission 1
- Single 8-Gy radiation therapy fraction is as effective as fractionated schemes for uncomplicated bone metastases 1
Follow-Up Care
After Curative Treatment
- History, symptom elicitation, and physical examination every 3-6 months for 3 years, then every 6-12 months thereafter 2
- Routine imaging and laboratory tests for surveillance are NOT recommended based on lack of evidence for improved early detection or survival benefit 1
Metastatic Disease
- Patients should be seen frequently enough to provide optimal palliation of symptoms and maintain quality of life 2
- Early introduction of expert palliative care may help better control symptoms 1
- Supportive care should always be part of the treatment plan 1
Critical Pitfalls to Avoid
- Do NOT use concomitant chemo-hormonal therapy in metastatic breast cancer 2
- Recognize tumor marker flare can occur in first 6 weeks of effective therapy when interpreting serial values 2
- Do NOT require complete endocrine resistance demonstration before offering PARP inhibitors to HR-positive patients with BRCA mutations 1
- Do NOT routinely perform brain imaging in asymptomatic patients 1
Special Populations
Young Premenopausal Patients
- Fertility issues and preservation techniques must be discussed before initiating systemic treatment 2