What are the treatment options for someone with breast cancer?

Treatment Options for Breast Cancer

Breast cancer treatment is multimodal and depends critically on stage, molecular subtype (hormone receptor and HER2 status), and anatomic extent of disease, with the primary goal of maximizing cure while minimizing toxicity through a combination of surgery, radiation, systemic therapy (chemotherapy, endocrine therapy, and targeted agents), and in select cases, immunotherapy. 1, 2, 3

Initial Evaluation and Molecular Characterization

Before initiating any treatment, comprehensive tumor characterization is essential:

• Perform ER, PR, and HER2 testing on all newly diagnosed invasive breast cancers using immunohistochemistry in CAP-accredited laboratories, as these biomarkers fundamentally determine systemic therapy selection 1
• Tumors with ≥1% ER-positive cells should be considered ER-positive and eligible for endocrine therapy 1
• HER2 testing must use FDA-approved assays with rigorous quality control, as false-positive and false-negative results are common and can lead to inappropriate treatment decisions 1
• Assess LVEF before starting any HER2-targeted therapy (trastuzumab), as cardiotoxicity is a major risk, particularly when combined with anthracyclines 4
• Verify pregnancy status in women of reproductive potential before treatment initiation, as both chemotherapy and trastuzumab carry significant embryo-fetal toxicity risks 4

Treatment by Stage

Stage 0 (Ductal Carcinoma In Situ - DCIS)

• Treat DCIS with lumpectomy plus whole-breast radiation as the standard approach, which prevents progression to invasive cancer in the majority of patients 1, 5, 6
• Mastectomy is an alternative for patients who cannot undergo or prefer to avoid radiation therapy 1
• Add tamoxifen 20 mg daily for 5 years if ER-positive to reduce risk of invasive breast cancer by approximately 43% (from 17 per 1,000 to 10 per 1,000 annually) 7, 5
• No axillary lymph node evaluation or systemic chemotherapy is indicated for pure DCIS 6

Early-Stage Invasive Disease (Stages I, IIA, IIB)

Surgical Management

• Breast-conserving surgery (lumpectomy) plus radiation therapy is equivalent to mastectomy for survival and is preferred when complete excision with acceptable cosmetic results is achievable 1, 2, 5
• Perform sentinel lymph node biopsy for clinically node-negative disease to avoid the morbidity of full axillary dissection (arm swelling, pain) 2, 6
• Radiation therapy following breast-conserving surgery is mandatory as it significantly decreases both mortality and local recurrence 1, 6

Systemic Therapy Selection by Molecular Subtype

For Hormone Receptor-Positive/HER2-Negative (70% of cases):

• Postmenopausal women should receive aromatase inhibitor therapy either as initial treatment or following 2-3 years of tamoxifen, as this is superior to tamoxifen alone 3
• Premenopausal women should receive tamoxifen 20 mg daily for 5-10 years as the cornerstone of treatment 1, 7
• Add adjuvant chemotherapy (anthracycline and taxane-based) for node-positive disease or high-risk node-negative disease 1, 5
• The standard regimen is sequential anthracycline (AC or EC) followed by taxane (paclitaxel 175 mg/m² IV over 3 hours every 3 weeks for 4 cycles), as sequential administration is superior to concurrent and less toxic 3, 8

For HER2-Positive Disease (15-20% of cases):

• All HER2-positive invasive cancers require trastuzumab-based therapy combined with chemotherapy, which dramatically improves outcomes 1, 4, 5
• Administer trastuzumab with taxane-based chemotherapy following anthracycline completion, or use non-anthracycline regimens (docetaxel/carboplatin/trastuzumab) to minimize cardiac risk 1, 4
• Monitor LVEF before each treatment cycle and discontinue trastuzumab for clinically significant decreases in left ventricular function 4
• Premedicate all patients receiving paclitaxel with dexamethasone 20 mg PO at 12 and 6 hours before, diphenhydramine 50 mg IV, and H2-blocker 30-60 minutes prior to prevent severe hypersensitivity reactions 8

For Triple-Negative Breast Cancer (15% of cases):

• Chemotherapy is the only systemic option for triple-negative disease, as these tumors lack targets for endocrine or HER2-directed therapy 5, 9, 10
• Use anthracycline and taxane-based regimens as the standard approach 3, 5
• Consider neoadjuvant chemotherapy to downsize tumors and assess treatment response, which may guide post-surgical therapy 2, 5
• Triple-negative breast cancer has worse prognosis with 85% 5-year survival for stage I disease compared to 94-99% for other subtypes 9

Locally Advanced Disease (Stage IIIA, IIIB, IIIC)

• Neoadjuvant chemotherapy is strongly recommended as first-line treatment to downsize tumors before surgery 1, 3
• Use anthracycline and taxane-based sequential regimens (AC or EC followed by taxane), which reduce breast cancer mortality by approximately one-third 3
• Consider dose-dense schedules for aggressive presentations, particularly with skin involvement (T4B disease) 3
• After neoadjuvant therapy, perform modified radical mastectomy with axillary lymph node dissection for T4B disease with skin involvement, as breast-conserving surgery is contraindicated 3
• Post-mastectomy radiation therapy is mandatory for T4B disease and should include chest wall and regional lymph nodes (supraclavicular, internal mammary) 3
• Inflammatory breast cancer requires mastectomy rather than breast-conserving surgery despite neoadjuvant chemotherapy response, followed by chest wall radiation 6

Metastatic Disease (Stage IV)

• Metastatic breast cancer is treatable but not curable, with treatment goals focused on prolonging life and palliating symptoms 5, 9
• Median overall survival is approximately 5 years for hormone receptor-positive and HER2-positive subtypes, but only 1 year for triple-negative disease 9

Treatment by Subtype:

• Hormone receptor-positive metastatic disease: Use endocrine therapy with CDK4/6 inhibitors as first-line treatment, reserving chemotherapy for endocrine-resistant or rapidly progressive disease 11, 9
• HER2-positive metastatic disease: Combine anti-HER2 therapy with chemotherapy (paclitaxel 175 mg/m² IV over 3 hours every 3 weeks is effective) 1, 8, 11
• Triple-negative metastatic disease: Chemotherapy is the mainstay, with consideration of immunotherapy if PD-L1 positive 2, 11
• For BRCA1/2 mutation carriers: Add PARP inhibitors to the treatment armamentarium 11, 9

Special Situations

Occult Primary Breast Cancer (Axillary Metastases Without Identified Primary)

• Perform breast MRI and ultrasound to identify occult primary lesions, which are detected in 70% of cases 1
• For MRI-positive disease: Treat according to clinical stage after ultrasound or MRI-guided biopsy confirmation 1
• For MRI-negative T0,N1,M0 disease: Options include mastectomy plus axillary dissection OR axillary dissection plus whole-breast radiation with similar outcomes 1
• Give systemic therapy according to stage II or III recommendations based on nodal status and tumor biology 1

Bilateral Breast Cancer

• Each breast tumor must be assessed independently for histological type, grade, ER/PR status, HER2 status, and Ki67 2
• Stage each breast cancer separately using TNM system and perform axillary management for each breast independently 2
• Base systemic therapy decisions on the biological characteristics of each tumor, recognizing that tumor heterogeneity between breasts may complicate treatment decisions and require multidisciplinary discussion 2

Critical Pitfalls to Avoid

• Never omit radiation therapy after breast-conserving surgery, as this significantly increases local recurrence and mortality risk 1, 6
• Do not use aromatase inhibitors in premenopausal women without ovarian suppression, as they are ineffective without eliminating ovarian estrogen production 1
• Never undertreat T4B disease with skin involvement - this requires aggressive multimodality therapy including neoadjuvant chemotherapy, mastectomy, and post-mastectomy radiation regardless of other favorable factors 3
• Do not delay cardiac monitoring in patients receiving trastuzumab, particularly when combined with anthracyclines, as cardiomyopathy can be severe and fatal 4
• Avoid using non-anthracycline regimens unless cardiac contraindications exist, as anthracycline-based chemotherapy is superior for breast cancer 3
• Do not perform axillary radiation after axillary dissection, as this significantly increases risk of lymphedema and other complications 1
• Never prescribe tamoxifen to pregnant women or women planning pregnancy, as it causes oligohydramnios, skeletal abnormalities, and neonatal death 4, 7