What are the treatment options for breast cancer?

Treatment of Breast Cancer

Breast cancer treatment is determined by disease stage, molecular subtype (hormone receptor status, HER2 status, and triple-negative status), and requires a combination of surgery, radiation, and systemic therapy tailored to tumor biology. 1, 2

Initial Diagnostic Workup

• Comprehensive staging must be performed before treatment initiation to determine extent of disease, including physical examination, complete blood counts, routine chemistry, and bilateral mammography with ultrasound of breasts and axillae 3, 2
• Tumor characterization is mandatory and must include histological type and grade, estrogen receptor (ER) and progesterone receptor (PR) status by immunohistochemistry, HER2 status, and proliferation markers (Ki67) 1, 3
• MRI should be performed when standard imaging is inconclusive or in special clinical situations 2
• For higher-risk disease, additional staging includes chest X-ray or CT, abdominal ultrasound or CT scan, and bone scan 3
• Genetic counseling and BRCA1/2 testing should be offered to high-risk patients 2

Treatment Approach for Early-Stage (Non-Metastatic) Breast Cancer

Surgical Management

• For tumors amenable to breast conservation: breast-conserving surgery with radiation therapy is the standard approach 1, 2
• For larger tumors or multifocal disease: modified radical mastectomy is the standard 4
• Sentinel lymph node biopsy is the preferred method for axillary staging in clinically node-negative patients 2
• For patients with 1-2 positive sentinel nodes undergoing breast conservation with whole-breast radiation, completion axillary lymph node dissection may be avoided (based on ACOSOG Z0011 criteria) 2
• Immediate breast reconstruction should not compromise delivery of appropriate locoregional or systemic treatment 4, 1

Radiation Therapy

• Whole breast radiation is mandatory after breast-conserving surgery 2
• Post-mastectomy chest wall radiotherapy is indicated when risk factors for local recurrence are present, specifically with ≥4 positive lymph nodes 4, 2
• For patients with 1-3 positive nodes, radiation to chest wall, infraclavicular region, supraclavicular area, and internal mammary nodes should be strongly considered 2
• Women aged 70+ with ER-positive, clinically node-negative early breast cancer may omit radiation after lumpectomy if receiving endocrine therapy 2

Neoadjuvant (Preoperative) Therapy

• Neoadjuvant therapy is standard for locally advanced breast cancer and allows for tumor downstaging 1
• Options include neoadjuvant chemotherapy, hormone therapy, or radiotherapy depending on tumor subtype 4
• Neoadjuvant therapy has become standard of care for most early-stage HER2-positive and triple-negative breast cancer 5

Systemic Therapy by Molecular Subtype

Hormone Receptor-Positive/HER2-Negative Disease

• Endocrine therapy is the cornerstone of treatment and must be administered for hormone receptor-positive tumors 1, 3
• Tamoxifen is indicated for ER-positive or unknown receptor status tumors, given for 5-10 years 4, 6
• Menopausal status assessment is critical for determining appropriate endocrine therapy selection 4, 1
• A minority of hormone receptor-positive patients also receive chemotherapy based on tumor characteristics and risk assessment 7

HER2-Positive Disease

• Trastuzumab is mandatory for adjuvant treatment of node-positive or high-risk node-negative HER2-positive disease 1, 8
• Trastuzumab should be combined with chemotherapy (paclitaxel, docetaxel, or carboplatin) as part of treatment regimen 8
• Critical monitoring requirement: assess left ventricular ejection fraction (LVEF) prior to initiation and at regular intervals during treatment due to risk of cardiomyopathy 8
• Discontinue trastuzumab for clinically significant decrease in left ventricular function 8

Triple-Negative Breast Cancer

• Chemotherapy is the primary and only systemic treatment option for triple-negative disease 1, 2
• Immunotherapy should be considered if PD-L1 positive 3
• Triple-negative breast cancer has the highest recurrence risk, with 85% 5-year breast cancer-specific survival for stage I disease compared to 94-99% for other subtypes 7

Treatment Approach for Metastatic Breast Cancer

General Principles

• The primary treatment goal is palliation, maintaining or improving quality of life, and possibly extending survival—cure is not currently achievable 1
• Sequential single-agent chemotherapy provides equivalent survival with better quality of life compared to combination chemotherapy for most patients 1
• Combination chemotherapy should be reserved for rapid clinical progression or life-threatening visceral metastases 2

Hormone Receptor-Positive/HER2-Negative Metastatic Disease

• Endocrine therapy partnered with targeted agents (CDK4/6 inhibitors, mTOR inhibitors, PI3K inhibitors) is preferred over chemotherapy 2
• CDK4/6 inhibitors combined with endocrine therapy have shown significant progression-free survival benefits 2

HER2-Positive Metastatic Disease

• Trastuzumab with vinorelbine or a taxane is preferred for first-line therapy 2
• Dual HER2 blockade with trastuzumab and pertuzumab can be combined with docetaxel, weekly paclitaxel, vinorelbine, or nab-paclitaxel 2
• Trastuzumab as single agent is indicated for patients who have received one or more chemotherapy regimens for metastatic disease 8

Triple-Negative Metastatic Disease

• There are no specific chemotherapy recommendations different from other HER2-negative disease 2
• For previously treated patients with anthracyclines with/without taxanes, carboplatin has shown comparable efficacy with more favorable toxicity profile compared to docetaxel 2
• Median overall survival is approximately 1 year compared to approximately 5 years for other subtypes 7

Follow-Up Protocol

• History and physical examination every 3-6 months for 3 years, then every 6-12 months thereafter 2
• Annual mammography should be performed for at least 10 years, starting 6 months after treatment 4, 1
• Routine follow-up should be continued after 10 years, with timing adjusted based on risk of local recurrence 4
• Evaluation of response to therapy should occur every 2-4 months for endocrine therapy or after 2-4 cycles of chemotherapy 2
• Tumor markers may be used to evaluate response in patients with non-measurable metastatic disease, but should not be used alone to initiate treatment changes 2

Critical Pitfalls and Caveats

• Adjuvant therapy must never replace optimal locoregional treatment—both are essential components 4, 1
• Verify pregnancy status in females of reproductive potential before initiating trastuzumab due to risk of oligohydramnios and fetal harm 8
• Monitor for trastuzumab infusion reactions and pulmonary toxicity, which usually occur during or within 24 hours of administration; discontinue for anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome 8
• Incomplete pathology reporting significantly impacts treatment decisions—standardized reporting of all molecular markers is essential 3
• For multifocal lesions, nonsurgical treatment is not indicated and mastectomy should be the local treatment 4