What are the treatment options for breast cancer?

Treatment of Breast Cancer

Breast cancer treatment is determined by disease stage and molecular subtype, with surgery plus radiation (or mastectomy) for early disease, endocrine therapy for hormone receptor-positive tumors, trastuzumab for HER2-positive disease, and chemotherapy for triple-negative breast cancer, while metastatic disease requires palliative systemic therapy prioritizing quality of life over cure. 1

Initial Diagnostic Workup and Tumor Characterization

Before initiating any treatment, comprehensive staging and tumor characterization are mandatory 1:

• Pathological assessment must include: histological type and grade, estrogen receptor (ER) and progesterone receptor (PR) status by immunohistochemistry, HER2 status, and proliferation markers (Ki67) 1
• Baseline staging includes: complete blood counts, routine chemistry (liver enzymes, alkaline phosphatase, calcium), bilateral mammography with ultrasound of breasts and axillae 2, 1
• For higher-risk disease: chest X-ray or CT, abdominal ultrasound or CT scan, and bone scan are indicated 2, 1
• Menopausal status assessment is critical as it determines appropriate endocrine therapy selection 3, 1
• Genetic counseling and BRCA1/2 testing should be offered to high-risk patients 1

Critical pitfall: Incomplete pathology reporting significantly impacts treatment decisions—standardized reporting of all molecular markers is essential 1

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

Surgical Management

The choice between breast conservation and mastectomy depends on tumor characteristics 1:

• For tumors amenable to breast conservation: breast-conserving surgery with radiation therapy is the standard approach 3, 1
• For larger tumors or multifocal disease: modified radical mastectomy is the standard 1
• Sentinel lymph node biopsy is the preferred method for axillary staging in clinically node-negative patients 3, 1
• For multifocal lesions: nonsurgical treatment is not indicated and mastectomy should be the local treatment 1

Critical pitfall: Immediate breast reconstruction should not compromise delivery of appropriate locoregional or systemic treatment 3, 1

Radiation Therapy

Radiation decisions are based on surgical approach and risk factors 1:

• Whole breast radiation is mandatory after breast-conserving surgery 1
• Post-mastectomy chest wall radiotherapy is indicated when risk factors for local recurrence are present, specifically with ≥4 positive lymph nodes 1
• Exception for elderly patients: Women aged 70+ with ER-positive, clinically node-negative early breast cancer may omit radiation after lumpectomy if receiving endocrine therapy 1

Neoadjuvant (Preoperative) Therapy

Neoadjuvant therapy serves multiple purposes 1:

• Standard for locally advanced breast cancer and allows for tumor downstaging 3, 1
• Options include: neoadjuvant chemotherapy, hormone therapy, or radiotherapy depending on tumor subtype 1
• Benefit: Allows identification of in vivo tumor sensitivity and increases possibility of breast conservation 4

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 3, 1:

• Tamoxifen is indicated for ER-positive or unknown receptor status tumors, given for 5-10 years 1, 5
• Tamoxifen doubles the risk of endometrial cancer from 1 in 1,000 to 2 in 1,000 annually and increases uterine sarcoma risk 5
• For high-risk women: Tamoxifen lowers the chance of getting breast cancer by 44%, from 7 in 1,000 to 4 in 1,000 annually 5
• For women with DCIS: Tamoxifen lowers the chance of invasive breast cancer by 43%, from 17 in 1,000 to 10 in 1,000 annually 5

Critical consideration: Verify pregnancy status before initiating tamoxifen as it causes embryo-fetal toxicity 5

HER2-Positive Disease

Trastuzumab is mandatory for adjuvant treatment of node-positive or high-risk node-negative HER2-positive disease 3, 6:

• Patient selection: Select patients based on HER2 protein overexpression or HER2 gene amplification using FDA-approved companion diagnostic tests 6
• Cardiac monitoring is essential: Evaluate left ventricular ejection fraction (LVEF) prior to and at regular intervals during treatment 6
• Discontinue trastuzumab for clinically significant decrease in left ventricular function 6
• Serious risks include: cardiomyopathy (highest with anthracycline-containing regimens), infusion reactions, pulmonary toxicity, and embryo-fetal toxicity 6

Triple-Negative Breast Cancer

Chemotherapy is the primary and only systemic treatment option for triple-negative disease 3, 1:

• Immunotherapy should be considered if PD-L1 positive 1
• Triple-negative breast cancer is responsible for 15-20% of all breast cancers and presents a therapeutic challenge due to low response to treatment and highly invasive nature 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 3, 1:

• Sequential single-agent chemotherapy provides equivalent survival with better quality of life compared to combination chemotherapy for most patients 3, 1
• Evaluation of response to therapy should occur every 2-4 months for endocrine therapy or after 2-4 cycles of chemotherapy 1

Hormone Receptor-Positive/HER2-Negative Metastatic Disease

Endocrine therapy partnered with targeted agents is preferred over chemotherapy 1:

• CDK4/6 inhibitors combined with endocrine therapy have shown significant progression-free survival benefits 1
• Other targeted agents include: mTOR inhibitors and PI3K inhibitors 3

HER2-Positive Metastatic Disease

Trastuzumab with chemotherapy is preferred for first-line therapy 1, 6:

• First-line: Trastuzumab with vinorelbine or a taxane 1
• Dual HER2 blockade: Trastuzumab and pertuzumab can be combined with docetaxel, weekly paclitaxel, vinorelbine, or nab-paclitaxel 1
• FDA indication: Trastuzumab in combination with paclitaxel for first-line treatment of HER2-overexpressing metastatic breast cancer 6

Triple-Negative Metastatic Disease

No specific chemotherapy recommendations different from other HER2-negative disease 1:

• For previously treated patients: Carboplatin has shown comparable efficacy with more favorable toxicity profile compared to docetaxel 1

Follow-Up Protocol

Structured surveillance is essential for detecting recurrence 1:

• History and physical examination: Every 3-6 months for 3 years, then every 6-12 months thereafter 2, 1
• Annual mammography should be performed for at least 10 years, starting 6 months after treatment 1
• Routine follow-up should be continued after 10 years, with timing adjusted based on risk of local recurrence 1
• Documentation of normalization of parameters adversely affected by chemotherapy at first follow-up visit 2

Critical Pitfalls to Avoid

• Adjuvant therapy must never replace optimal locoregional treatment—both are essential components 3, 1
• Improper HER2 assay performance (suboptimally fixed tissue, failure to use specified reagents, deviation from assay instructions) can lead to unreliable results and inappropriate treatment selection 6
• Approximately 30% of patients with early-stage breast cancer have recurrent disease despite appropriate treatment, emphasizing the systemic nature of breast cancer from presentation 4