Breast Cancer

Yvette Payne

Invasive Breast Cancer

DEFINITION

Invasive breast cancer, also referred to as infiltrating breast cancer, has spread beyond the basement membrane of the duct or lobule of the breast and into the surrounding tissue. The diagnosis of invasive breast cancer is considered to be systemic, not localized, because of its ability to spread through the vascular system. The breast includes the following specific anatomical areas:

• Nipple

• Areola

• Ducts

• Lobules

• Adipose tissue

• Pectoralis major and minor muscles

• Associated lymph nodes

INCIDENCE

Breast cancer is the most common form of cancer among women in industrialized countries. The incidence of breast cancer increases with age, beginning slowly between the ages of 45 and 50 years and then rising steadily each year thereafter. More than 70% of breast cancers occur in women 50 years of age and older. In 2007, 178,480 new cases of breast cancer are expected to be diagnosed in women living in the United States. Breast cancer is the leading cause of cancer deaths for women between 20 and 59 years of age with a projected death rate of 40,910 in 2007. Male breast cancer accounts for less than 1% of all breast cancers, with an estimated 2,030 new cancers diagnosed and 450 breast cancer deaths in 2007.

ETIOLOGY AND RISK FACTORS

There is no single cause of breast cancer. It is a heterogeneous disease likely developing as a result of multiple factors. Broad generalizations about the risk of breast cancer are often published; however, the future for an individual woman who has breast cancer is unpredictable. The following factors are those most commonly suspected to increase the probability of a woman having breast cancer:

• Sex—>99% of cases occur in women

• Age—risk increases with age

• Personal history of breast cancer—threefold to fourfold increased risk of second primary cancer

• Family history of breast cancer—the risk is particularly great if:

˚ The affected relative is on the maternal side of the family

˚ Two first-degree relatives are affected

˚ The relative has bilateral breast cancer

˚ The relative’s breast cancer was diagnosed before the age of 50 years

• Genetic influences:

˚ BRCA1 (17q21)

˚ BRCA2 (13q14)

˚ CHEK2 thought to activate BRCA1

˚ TP53 germ line mutations

˚ EMSY thought to interact with BRCA2

• History of receiving ionizing radiation

• Hormonal factors:

˚ Postmenopausal obesity

˚ Early menarche (before age 12 years) and late menopause (after age 50 years)

˚ Nulliparity

˚ First term pregnancy after 30 or 35 years of age

˚ Use of oral contraceptives before age 20 years with use lasting 6 or more years

˚ Hormone replacement therapy with estrogen plus progestin

• Proliferative breast disease, atypical hyperplasia

• Ingestion of 15 g (two drinks) or more alcohol each day

SIGNS AND SYMPTOMS

Breast cancer in its early stages is usually asymptomatic. Later signs and symptoms include the following:

• Pain is uncommon in early disease

• Changes in the size or shape of the breast

• Pink or bloody spontaneous unilateral nipple discharge may occur

• Arm edema (lymphedema)

• Skin changes—dimpling, edema, erythema, ulceration

• Nipple changes—inversion, scaling, ulceration

• Symptoms of metastases (i.e., shortness of breath), cough. Loss of appetite, abnormal liver function tests, headaches, and many others

DIAGNOSTIC WORKUP

Diagnostic mammogram for early detection of breast lesions:

• Workup may include ultrasonography, positron emission tomographic scan, or magnetic resonance imaging of the breast.

• Clinical breast examination to include bilateral breasts, axilla, and supraclavicular and infraclavicular areas

• Biopsy for a pathological diagnosis (see table on page 36)

• Imaging studies may include bone scan, computed tomographic scan of the chest and abdomen or others depending on the presenting signs and symptoms to rule out metastases

• Laboratory tests to include hematological chemistry evaluations and tests for tumor markers CA15-3 and CA27.29

Breast Biopsy Techniques

HISTOLOGY

Breast cancer is a heterogeneous disease with 24 distinct histological subtypes. Some of the more common subtypes of breast cancer are the following:

• Invasive ductal carcinoma—70% to 80% of all breast cancers

• Invasive lobular carcinoma—10% to 15% of all breast cancers

• Medullary carcinomas—5% to 7% of malignant breast tumors

• Other less common subtypes include tubular, mucinous, sarcomas, and papillary carcinomas

Inflammatory breast cancer is not a subtype but a special manifestation typically presenting with dramatic and diffuse skin edema, erythema, hyperemia, and induration of the underlying tissue.

The identification of prognostic factors is critical in determining the appropriate treatment of an individual woman’s breast cancer:

• Axillary lymph node status—prognosis worsens with increased involvement

• Tumor size—increased risk of recurrence with increasing size

• Hormone receptor status—estrogen receptor (ER)– and progesterone receptor (PR)–negative tumors are associated with a worse prognosis

• Deoxyribonucleic acid (DNA) ploidy—aneuploid tumors, those with an abnormal amount of DNA have a poorer prognosis

• High S-phase fraction predicts poorer outcome

• Histopathological considerations take into account the nuclear pattern, morphologic features, and mitotic activity. The higher the grade the worse the prognosis

• Molecular and biological factors that may be associated with a poor prognosis include the following:

˚ Loss of functioning of tumor suppression genes, p53, nm23

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