Patient stratification – Patients with a new diagnosis of breast cancer can be stratified as having early or locally advanced disease (see ‘Patient stratification’ above). Treatment depends on multiple factors, as summarized (table 4 and algorithm 1).
Early-stage breast cancer: Surgery
The surgical approach to the primary tumor depends on the size of the tumor and the breast, and whether multifocal disease is present. Options include breast-conserving therapy (breast-conserving surgery plus radiation therapy [RT]) or mastectomy. Both approaches result in equivalent cancer-specific outcomes The surgical approach to the regional nodes depends on whether there is clinical evidence of lymph node involvement.
Early-stage breast cancer: Adjuvant systemic treatment
Hormone receptor-positive breast cancer – Patients with hormone receptor-positive breast cancer should receive adjuvant endocrine therapy. The role of adjuvant chemotherapy in these patients requires a risk-stratified approach that takes into account patient and tumor characteristics. (See “Adjuvant endocrine and targeted therapy for postmenopausal women with hormone receptor-positive breast cancer” and “Selection and administration of adjuvant chemotherapy for HER2-negative breast cancer”, section on ‘Indications for treatment’.)
Triple-negative breast cancer – Most patients with estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2 (HER2)-negative disease (triple-negative breast cancer) receive chemotherapy, with an exception for very small tumors (≤0.5 cm).
HER2-positive breast cancer – Patients with HER2-positive breast cancer >1 cm in size should receive a combination of chemotherapy plus HER2-directed therapy. Following chemotherapy, patients with ER-positive disease should also receive adjuvant endocrine therapy.
Locally advanced breast cancer – Most patients with locally advanced breast cancer and some with earlier-stage breast cancer (particularly if HER2 positive or triple negative) are treated with neoadjuvant systemic therapy prior to surgery. Neoadjuvant treatment improves the rate of breast conservation without compromising survival outcomes.
For most patients receiving neoadjuvant treatment, we offer chemotherapy rather than endocrine therapy. A HER2-directed agent should be added to the chemotherapy regimen for tumors that are HER2 positive. For select patients with high-risk triple-negative breast cancer, we incorporate immunotherapy with neoadjuvant chemotherapy.
For patients who received neoadjuvant chemotherapy:
Patients with hormone receptor-positive breast cancer should receive adjuvant endocrine therapy.
For patients with hormone receptor-negative breast cancer with residual disease after neoadjuvant treatment, adjuvant capecitabine is offered. (See “Approach to the patient following treatment for breast cancer”, section on ‘Guidelines for post-treatment follow-up’ and “Selection and administration of adjuvant chemotherapy for HER2-negative breast cancer”, section on ‘Patients who received neoadjuvant treatment’.)
Patients with triple-negative disease who initiated pembrolizumab in the neoadjuvant setting should continue it in the adjuvant setting.
Patients with HER2-positive breast cancer and a complete response to neoadjuvant treatment receive one year of trastuzumab, with or without pertuzumab, following completion of surgery. If residual disease is present, ado-trastuzumab emtansine is offered, rather than trastuzumab.
Role of radiation therapy in early and locally advanced disease
Following surgery (with or without neoadjuvant systemic therapy), all patients who undergo breast-conserving surgery should undergo adjuvant RT.
Some patients treated with a mastectomy receive postmastectomy RT. The administration of adjuvant RT is typically based upon the original pretreatment stage, though pathologic response to neoadjuvant therapy may play a role as well.
BRCA carriers – For select patients with breast cancer susceptibility gene 1 or 2 (BRCA1/2) mutations and high-risk early, HER2-negative breast cancer, adjuvant treatment an inhibitor of poly(ADP-ribose) polymerase (PARP), improves disease-free survival outcomes.
