Management of Early Breast Cancer
Early breast cancer requires a multimodal treatment approach combining surgery, radiation therapy, and systemic therapy based on tumor biology, with breast-conserving surgery plus radiation as the preferred local treatment for most patients, followed by risk-adapted systemic therapy determined by hormone receptor status, HER2 status, and disease burden. 1, 2
Initial Treatment Planning
Treatment decisions must be based on three key factors: tumor burden (size, lymph node involvement), tumor biology (hormone receptors, HER2, Ki67, genomic signatures), and patient characteristics (age, menopausal status, comorbidities, preferences) 1. Patients should be actively involved in all management decisions after receiving comprehensive information 1.
Fertility Preservation
In younger premenopausal patients, fertility issues and fertility-preservation techniques must be discussed before initiating any systemic treatment 1. Ovarian function suppression during chemotherapy provides some protection and has no negative oncological impact, but should not be the sole fertility preservation method if pregnancy is desired 1.
Surgical Management
Primary Surgery Selection
Breast-conserving surgery (BCS) followed by radiation therapy is the preferred treatment option, offering equivalent survival outcomes to mastectomy while preserving the breast 2. BCS is appropriate for 60-80% of newly diagnosed cancers at diagnosis or after neoadjuvant therapy 1.
Mastectomy is indicated when 1:
- Tumor size is large relative to breast size
- Tumor multicentricity exists
- Negative surgical margins cannot be achieved after multiple resections
- Prior chest wall radiation or contraindications to radiation exist
- Patient preference
Non-high-risk patients who opt for bilateral mastectomy should be counseled that survival outcomes with BCS might be even better than with mastectomy 1.
Neoadjuvant Therapy Indications
Neoadjuvant systemic therapy should be preferred for tumors >2 cm and/or positive axilla, particularly in triple-negative and HER2-positive subtypes 1. This approach allows tumor downstaging, increases breast conservation rates, and provides in vivo assessment of treatment sensitivity 1.
Axillary Management
Sentinel lymph node biopsy (SLNB) is the standard of care for axillary staging in clinically node-negative early breast cancer 2. Further axillary surgery following positive SLNB is not required with low axillary disease burden (micrometastases or 1-2 positive sentinel nodes) when postoperative tangential breast radiotherapy is planned 2.
In patients with baseline axillary involvement converting to negative after neoadjuvant therapy, SLNB may be performed in selected cases, and if negative, further axillary surgery may be avoided 1.
Radiation Therapy
Postoperative radiation therapy is strongly recommended after BCS 1, 2. Boost irradiation is recommended to reduce in-breast relapse risk in patients at higher risk of local recurrence 1, 2.
Moderate hypofractionation schedules (15-16 fractions of 2.5-2.67 Gy per fraction) are recommended for routine postoperative irradiation 1.
Post-Mastectomy Radiation
Post-mastectomy radiation therapy (PMRT) is recommended for high-risk patients, including those with involved resection margins, involved axillary lymph nodes, and T3-T4 tumors 1, 2. PMRT should also be considered in patients with 1-3 positive axillary lymph nodes 1.
Comprehensive nodal irradiation is recommended for patients with involved lymph nodes 1, 2. After axillary lymph node dissection, routine axillary irradiation should not be performed to the operated part of the axilla 1.
Systemic Therapy
Adjuvant systemic treatment should preferably start within 3-6 weeks after surgery 1, 2. Neoadjuvant systemic therapy should start as soon as diagnosis and staging is completed, ideally within 2-4 weeks 1.
Luminal A-Like (ER+/HER2-, Low Ki67)
All luminal-like cancers should be treated with endocrine therapy 1. Most luminal A-like tumors do not require chemotherapy, except those with high disease burden 1.
Luminal B-Like HER2-Negative (ER+/HER2-, High Ki67)
Chemotherapy use depends on individual risk of recurrence, presumed responsiveness to endocrine therapy, and patient preferences 1. In cases of uncertainty regarding adjuvant chemotherapy indications, gene expression assays such as MammaPrint, Oncotype DX, Prosigna, EndoPredict, or Breast Cancer Index can be used 1.
Luminal B-Like HER2-Positive (ER+/HER2+)
Luminal B-like HER2-positive tumors should be treated with chemotherapy, endocrine therapy, and anti-HER2 therapy 1. In selected low-risk patients (T1abN0), the combination of anti-HER2 therapy and endocrine therapy alone may be used 1.
HER2-Positive (Non-Luminal)
HER2-positive cancers should be treated with chemotherapy plus anti-HER2 therapy, with the possible exception of selected cases with very low risk, such as T1aN0 tumors 1.
Triple-Negative Breast Cancer
Patients with triple-negative breast cancer should receive chemotherapy, with the possible exception of low-risk special histological subtypes such as secretory or adenoid cystic carcinomas or very early (T1aN0) tumors 1.
Endocrine Therapy
Premenopausal Patients
For premenopausal women, tamoxifen for 5-10 years is standard of care 1, 3. In patients becoming postmenopausal during the first 5 years of tamoxifen, a switch to letrozole should be considered, depending on predicted risk of late recurrence 1.
In patients requiring chemotherapy who recover menses (particularly in the first year but acceptable within the first 2 years), addition of ovarian function suppression (OFS) to endocrine therapy should be strongly considered 1. The role of replacing tamoxifen with an aromatase inhibitor can be considered in high-risk patients; if used, it mandates effective OFS with regular biochemical control of estrogen levels 1.
For patients <35 years not requiring chemotherapy, inferior outcomes suggest use of the most effective endocrine therapy (combination with OFS) 1.
Postmenopausal Patients
Aromatase inhibitors are preferred over tamoxifen in postmenopausal patients with early-stage breast cancer 1.
Critical Sequencing Rules
Chemotherapy should not be used concomitantly with endocrine therapy 1, with the exception of GnRH analogues used for ovarian protection 1. If chemotherapy and radiation are to be used, chemotherapy should usually precede radiation 1.
Anti-HER2 therapy may routinely be combined with non-anthracycline-based chemotherapy, endocrine therapy, and radiation therapy 1. Radiation therapy may be delivered safely during anti-HER2 therapy, endocrine therapy, and non-anthracycline, non-taxane-based chemotherapy 1.
Bisphosphonates
Bisphosphonates are recommended in women with low-estrogen status (undergoing OFS or postmenopausal), especially if at high risk of relapse 1. Bisphosphonates are also recommended in patients with treatment-related bone loss 1.
Special Populations
Elderly Patients
Treatment should be adapted to biological (not chronological) age, with consideration of less aggressive regimens in frail patients 1. In patients suitable for standard chemotherapy, a standard multidrug regimen should be used; single-agent capecitabine or docetaxel is inferior to standard multidrug regimens (AC or CMF) 1.
A geriatric assessment should be carried out before treatment decisions; the G8 tool can be used as a screening tool to select patients needing full geriatric assessment 1.
Male Breast Cancer
Tamoxifen is the standard adjuvant endocrine therapy for male breast cancer patients 1. An aromatase inhibitor alone should not be used as adjuvant endocrine therapy in male breast cancer patients 1. Chemotherapy and anti-HER2 therapy indications and regimens should follow the same recommendations as for female patients 1.
DCIS Management
Whole breast radiotherapy is recommended for the majority of women with DCIS treated with BCS 1. In patients with low-risk DCIS, omitting radiation is an option 1.
Both tamoxifen and aromatase inhibitors may be used after conservative local treatment of DCIS to prevent local recurrence and decrease the risk of second primary breast cancer 1. Following mastectomy for DCIS, tamoxifen or aromatase inhibitors might be considered to decrease contralateral breast cancer risk in high-risk patients 1.