Treatment Options for Breast Cancer
Breast cancer treatment is determined by disease stage (early vs. metastatic) and molecular subtype (hormone receptor-positive/HER2-negative, HER2-positive, or triple-negative), with a multimodal approach combining surgery, radiation, and systemic therapy tailored to these characteristics. 1
Initial Evaluation and Staging
Before initiating treatment, comprehensive staging must be performed including physical examination, complete blood counts, routine chemistry, bilateral mammography with ultrasound of breasts and axillae 1. 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. For higher-risk disease, additional staging includes chest X-ray or CT, abdominal ultrasound or CT scan, and bone scan 1.
Treatment for Early-Stage (Non-Metastatic) Breast Cancer
Surgical Management
For tumors amenable to breast conservation, breast-conserving surgery (lumpectomy) with radiation therapy is the standard approach 2, 1. For larger tumors or multifocal disease, modified radical mastectomy is the standard 2, 1. Sentinel lymph node biopsy is the preferred method for axillary staging in clinically node-negative patients 1, 3.
A critical caveat: Immediate breast reconstruction should not compromise delivery of appropriate locoregional or systemic treatment 2, 1, 3.
Radiation Therapy
After breast-conserving surgery, breast radiotherapy must always be performed, using a minimum dose of 50 Gy in 25 fractions 2. Breast irradiation after breast-conserving surgery significantly reduces the risk of local recurrence irrespective of the initial disease stage 2. In women under 50 years old, a boost should be administered routinely to the tumor bed even when the margins are clear 2.
After mastectomy, chest wall radiotherapy is indicated when risk factors for local recurrence are present, specifically with ≥4 positive lymph nodes 1. 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 is standard for locally advanced breast cancer and allows for tumor downstaging 1, 3. Induction or neoadjuvant chemotherapy is an option in operable breast cancer where first-line breast-conserving surgery is not possible, in the absence of multifocal lesions, and where the patient would prefer breast conservation 2. After neoadjuvant chemotherapy, locoregional treatment should be performed in the same manner as that used for first-line locoregional treatment 2.
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 1, 4. For postmenopausal women with node-negative disease and no risk factors for metastatic relapse, tamoxifen alone is the standard 2. For those with risk factors, tamoxifen with or without chemotherapy is recommended 2.
Anthracycline-containing polychemotherapy is currently the most commonly used regimen and is more efficacious than the CMF regimen (cyclophosphamide, methotrexate, and fluorouracil) 2. The preferred regimens are dose-dense AC (doxorubicin 60 mg/m² + cyclophosphamide 600 mg/m² every 14 days × 4 cycles) followed by paclitaxel 175 mg/m² every 14 days × 4 cycles, or AC followed by weekly paclitaxel 80 mg/m² weekly × 12 weeks 5.
HER2-Positive Disease
Trastuzumab is mandatory for adjuvant treatment of node-positive or high-risk node-negative HER2-positive disease 1, 3, 6. All patients with HER2-positive, node-positive breast cancer must receive trastuzumab incorporated into adjuvant therapy, with trastuzumab also being offered for HER2-positive, node-negative tumors >1 cm 5.
The preferred regimens are AC followed by paclitaxel + concurrent trastuzumab, or TCH (docetaxel + carboplatin + trastuzumab) 5. Evaluate left ventricular ejection fraction (LVEF) prior to initiation of trastuzumab and at regular intervals during treatment 6.
Triple-Negative Breast Cancer
Chemotherapy is the primary and only systemic treatment option for triple-negative disease 1, 3. The standard chemotherapy regimens are the same anthracycline-taxane sequential regimens used for HER2-negative disease 2, 5. Immunotherapy should be considered if PD-L1 positive 1.
Treatment for Metastatic Breast Cancer
The primary treatment goal is palliation, maintaining or improving quality of life, and possibly extending survival—cure is not currently achievable 2, 1, 3. The primary goals of treatment include maximizing quality of life, prevention and palliation of symptoms, and prolongation of survival 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 1. CDK4/6 inhibitors combined with endocrine therapy have shown significant progression-free survival benefits 1.
HER2-Positive Metastatic Disease
Trastuzumab with vinorelbine or a taxane is preferred for first-line therapy 1. Trastuzumab in combination with paclitaxel is indicated for first-line treatment of HER2-overexpressing metastatic breast cancer 6. Dual HER2 blockade with trastuzumab and pertuzumab can be combined with docetaxel, weekly paclitaxel, vinorelbine, or nab-paclitaxel 1.
Triple-Negative Metastatic Disease
For most patients with metastatic breast cancer, sequential single-agent chemotherapy provides equivalent survival with better quality of life compared to combination chemotherapy 2, 1, 3. For previously treated patients with anthracyclines with/without taxanes, carboplatin has shown comparable efficacy with more favorable toxicity profile compared to docetaxel 1.
Management of Recurrent Disease
Local recurrence should be treated with surgery, with the standard treatment being a simple total mastectomy 2. Radiotherapy should not be considered except in specific cases 2. If oestrogen receptors are present, additional hormone therapy is recommended 2.
Follow-Up Protocol
History and physical examination should be performed every 3-6 months for 3 years, then every 6-12 months thereafter 1. Annual mammography should be performed for at least 10 years, starting 6 months after treatment 1, 3. Routine follow-up should be continued after 10 years, with timing adjusted based on risk of local recurrence 1.
Critical Pitfalls to Avoid
Adjuvant therapy must never replace optimal locoregional treatment—both are essential components 1, 3. Incomplete pathology reporting significantly impacts treatment decisions—standardized reporting of all molecular markers is essential 1. For multifocal lesions, nonsurgical treatment is not indicated and mastectomy should be the local treatment 1. Hormone replacement treatment for postmenopausal symptoms should not be prescribed after treatment for breast cancer, except in specific cases 2.