Breast cancer: Causes, diagnosis and staging

Breast cancer is a malignancy originating from breast tissue. Disease confined to a localized breast lesion is referred to as early, primary, localized, or curable. Disease detected clinically or radiologically in sites distant from the breast is referred to as advanced or metastatic breast cancer (MBC), which is usually incurable.

Two variables most strongly associated with occurrence of breast cancer are gender and advancing age.


Two variables most strongly associated with occurrence of breast cancer are gender and advancing age. Additional risk factors include endocrine factors (e.g., early menarche, nulliparity, late age at first birth, and hormone replacement therapy), genetic factors (e.g., personal and family history, mutations of tumor suppresser genes [BRCA1 and BRCA2]), and environmental and lifestyle factors (e.g., radiation exposure).

Breast cancer cells often spread undetected by contiguity, lymph channels, and through the blood early in the course of the disease, resulting in metastatic disease after local therapy. The most common metastatic sites are lymph nodes, skin, bone, liver, lungs, and brain.

Clinical presentation

A painless lump is the initial sign of breast cancer in most women. The typical malignant mass is solitary, unilateral, solid, hard, irregular, and non-mobile. Nipple changes are less commonly seen. More advanced cases present with prominent skin edema, redness, warmth, and induration.

Symptoms of MBC depend on the site of metastases but may include bone pain, difficulty breathing, abdominal pain or enlargement, jaundice, and mental status changes.

Many women first detect some breast abnormalities themselves, but it is increasingly common for breast cancer to be detected during routine screening mammography in asymptomatic women.


Initial workup should include a careful history, physical examination of the breast, three-dimensional mammography, and, possibly, other breast imaging techniques, such as ultrasound and magnetic resonance imaging (MRI). Breast biopsy is indicated for a mammographic abnormality that suggests malignancy or for a palpable mass on physical examination.


Stage (anatomical extent of disease) is based on primary tumor extent and size (T1–4), presence and extent of lymph node involvement (N1–3), and presence or absence of distant metastases (M0–1). The staging system determines prognosis and assists with treatment decisions. Simplistically stated, these stages may be represented as follows:

Early Breast Cancer

• Stage 0: Carcinoma in situ or disease that has not invaded the basement membrane

• Stage I: Small primary invasive tumor without lymph node involvement

• Stage II: Involvement of regional lymph nodes

Locally Advanced Breast Cancer

• Stage III: Usually a large tumor with extensive nodal involvement in which the node or tumor is fixed to the chest wall; also includes inflammatory breast cancer, which is rapidly progressive

Advanced or Metastatic Breast Cancer

• Stage IV: Metastases in organs distant from the primary tumor

Prognostic factors

The ability to predict prognosis is used to design treatment recommendations to maximize quantity and quality of life. Age at diagnosis and ethnicity are patient characteristics that may affect prognosis.

Tumor size and presence and number of involved axillary lymph nodes are primary factors in assessing the risk for breast cancer recurrence and subsequent metastatic disease. Other disease characteristics that provide prognostic information are histologic subtype, nuclear or histologic grade, lymphatic and vascular invasion, and proliferation indices.

Hormone receptors [estrogen (ER) and progesterone (PR)] are not strong prognostic markers but are used clinically to predict response to endocrine therapy.

HER2/neu (HER2) overexpression is associated with transmission of growth signals that control aspects of normal cell growth and division. Overexpression of HER2 is associated with increased tumor aggressiveness, rates of recurrence, and mortality. Genetic profiling tools provide additional prognostic information to aid in treatment decisions for subgroups of patients with otherwise favorable prognostic features.


Adjuvant therapy for early and locally advanced breast cancer is administered with curative intent. Treatment of MBC is done to improve symptoms and quality of life, and to prolong survival. Treatment is rapidly evolving. Specific information regarding the most promising interventions can be found only in the primary literature. Treatment can cause substantial toxicity, which differs depending on the individual agent, administration method, and combination regimen.


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