The vast majority of patients with newly diagnosed breast cancer in the United States and developed countries have no evidence of metastatic disease. For these patients, the treatment approach depends on the stage at presentation. For treatment purposes, breast cancer is characterized using the Tumor, Node, Metastasis system (TNM).  The AJCC recommends use of the prognostic staging system for breast cancer that incorporates biomarkers, if resources are available.

CLASSIFICATION

●Early stage – This includes patients with stage I, IIA, or a subset of stage IIB disease (T2N1).
●Locally advanced – This includes a subset of patients with stage IIB disease (T3N0) and patients with stage IIIA to IIIC disease.
Approximately 5 percent of patients will have simultaneous metastatic disease identified at the initial presentation.

EARLY-STAGE BREAST CANCER

In general, patients with early-stage breast cancer undergo primary surgery (lumpectomy or mastectomy) to the breast and regional nodes with or without radiation therapy (RT). Following definitive local treatment, adjuvant systemic therapy may be offered based on primary tumor characteristics, such as tumor size, grade, number of involved lymph nodes, the status of estrogen (ER) and progesterone (PR) receptors, and expression of the human epidermal growth factor 2 (HER2) receptor.

BREAST CONSERVING THERAPY

Breast-conserving therapy (BCT) is comprised of breast-conserving surgery (BCS, ie, lumpectomy) plus radiation therapy (RT). The goals of BCT are to provide the survival equivalent of mastectomy, a cosmetically acceptable breast, and a low rate of recurrence in the treated breast. BCT allows patients with invasive breast cancer to preserve their breast without sacrificing oncologic outcome. Successful BCT requires complete surgical removal of the tumor (with negative surgical margins) followed by moderate-dose RT to eradicate any residual disease. Contraindications to BCT include multicentric disease, large tumor size in relation to breast, presence of diffuse malignant-appearing calcifications on imaging, prior history of chest RT (eg, mantle radiation for Hodgkin disease), pregnancy and persistently positive margins despite attempts at re-excision.

EVALUATION OF AXILLARY NODES

The risk for metastases to the axillary nodes is related to tumor size and location, histologic grade, and the presence of lymphatic invasion within the primary tumor. Although internal mammary or supraclavicular nodes may be involved at the initial presentation, they rarely occur in the absence of axillary node involvement. The evaluation of the regional nodes depends on whether axillary involvement is suspected prior to surgery:

For patients presenting with clinically suspicious axillary lymph nodes, a preoperative work-up including ultrasound plus fine needle aspiration (FNA) or core biopsy can help to determine the best surgical approach.

For patients with a positive biopsy, an axillary node dissection should be performed at the time of breast surgery.
For patients presenting with a negative biopsy, no further work-up is required prior to surgery. These patients should undergo a sentinel lymph node biopsy (SLNB) at the time of surgery.
Patients with a clinically negative axillary examination should undergo a SLNB at the time of surgery. Further evaluation of the regional nodes depends on the findings at SLNB.
Patients who have one or two pathologically involved sentinel nodes may not require a complete axillary node dissection. However, whether or not patients with three or more pathologically involved sentinel nodes should undergo an axillary node dissection is best determined on an individualized basis, taking into account all other tumor risk factors and the patient’s performance status and comorbidities.
Adjuvant therapy — Systemic therapy refers to the medical treatment of breast cancer using endocrine therapy, chemotherapy, and/or biologic therapy.

TUMOR CHARACTERISTICS

Tumor characteristics predict which patients are likely to benefit from specific types of therapy. For example, hormone receptor-positive patients benefit from the use of endocrine therapy. In addition, patients with human epidermal growth factor receptor 2 (HER2)-positive cancers benefit from treatment using HER2-directed treatment.

For patients with early-stage breast cancer, treatment is based on tumor characteristics, patient status, and patient preferences:

Patients with hormone receptor-positive breast cancer should receive endocrine therapy. Whether they also should receive adjuvant chemotherapy depends on patient and tumor characteristics.
For patients with ER/PR and HER2-negative disease (triple-negative breast cancer), we prefer to administer adjuvant chemotherapy if the tumor size is ≥0.5 cm. Because these patients are not candidates for endocrine therapy or treatment with HER2-directed agents, chemotherapy is their only option for adjuvant treatment, following or before radiotherapy. Patients with a triple-negative breast cancer 1 cm should receive a combination of chemotherapy plus HER2-directed therapy. The management of small (≤1 cm) HER2-positive breast cancers is controversial.
Following chemotherapy, patients with ER-positive disease should also receive adjuvant endocrine therapy.