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Breast Cancer

Breast cancer

• Breast cancer refers to cancers originating from breast tissue, most commonly from the inner lining of milk ducts or the lobules that supply the ducts with milk. Cancers originating from ducts are known as ductal carcinomas; those originating from lobules are known as lobular carcinomas. There are many different types of breast cancer, with different stages (spread), aggressiveness, and genetic makeup; survival varies greatly depending on those factors. With best treatment, 10-year disease-free survival varies from 98% to 10%. Treatment includes surgery, drugs (hormonal therapy and chemotherapy), and radiation.
• Worldwide, breast cancer comprises 10.4% of all cancer incidence among women, making it the second most common type of non-skin cancer (after lung cancer) and the fifth most common cause of cancer death. In 2004, breast cancer caused 519,000 deaths worldwide (7% of cancer deaths; almost 1% of all deaths). Breast cancer is about 100 times more common in women than in men, but survival rates are equal in both sexes.

Signs and symptoms

• The first symptom, or subjective sign, of breast cancer is typically a lump that feels different from the rest of the breast tissue. More than 80% of breast cancer cases are discovered when the woman feels a lump. The first medical sign, or objective indication of breast cancer as detected by a physician, is discovered by mammogram. Lumps found in lymph nodes located in the armpits can also indicate breast cancer.
• Indications of breast cancer other than a lump may include changes in breast size or shape, skin dimpling, nipple inversion, or spontaneous single-nipple discharge. Pain (“mastodynia”) is an unreliable tool in determining the presence or absence of breast cancer, but may be indicative of other breast health issues.

Classification

• Breast cancers can be classified by different schema. They include stage (TNM), pathology, grade, receptor status, and the presence or absence of genes as determined by DNA testing:

  > Stage. The TNM classification for breast cancer is based on the size of the tumor (T), whether or not the tumor has spread to the lymph nodes (N) in the armpits, and whether the tumor has metastasized (M) or spread to a more distant part of the body. Larger size, nodal spread, and metastasis have a worse prognosis.

  > Pathology. Most breast cancers are’ derived from the epithelium lining the ducts or lobules. (Cancers from other tissues are considered “rare” cancers.) Carcinoma in situ is proliferation of cancer cells within the epithelial tissue without invasion of the surrounding tissue. Invasive carcinoma invades the surrounding tissue. Cells that are dividing more quickly have a worse prognosis. One way to measure tumor cell growth is with the presence of protein Ki67, which indicates that the cell is in S phase, and also indicates susceptibility to certain treatments.

  > Grade (Bloom-Richardson grade). When cells become differentiated, they take different shapes and forms to function as part of an organ. Cancerous cells lose that differentiation. Cells that normally line up in an orderly way to make up the milk ducts become disorganized. Cell division becomes uncontrolled. Cell nuclei become less uniform. Pathologists describe cells as well differentiated (low grade), moderately differentiated (intermediate grade), and poorly differentiated (high grade). Poorly-differentiated cancers have a worse prognosis.

Diagnosis

• Excised human breast tissue, showing an irregular, dense, white stellate area of cancer 2 cm in diameter, within yellow fatty tissue.
  While screening techniques (which are further discussed below) are useful in determining the possibility of cancer, a further testing is necessary to confirm whether a lump detected on screening is cancer, as opposed to a benign alternative such as a simple cyst.
• In a clinical setting, breast cancer is commonly diagnosed using a “triple test” of clinical breast examination (breast examination by a trained medical practitioner), mammography, and fine needle aspiration cytology. Both mammography and clinical breast exam, also used for screening, can indicate an approximate likelihood that a lump is cancer, and may also identify any other lesions. Fine Needle Aspiration and Cytology (FNAC), which may be done in a GP’s office using local anaesthetic if required, involves attempting to extract a small portion of fluid from the lump. Clear fluid makes the lump highly unlikely to be cancerous, but bloody fluid may be sent off for inspection under a microscope for cancerous cells. Together, these three tools can be used to diagnose breast cancer with a good degree of accuracy.

Risk factors

• The primary risk factors that have been identified are sex, age, childbearing, hormones, a high-fat diet, alcohol intake, obesity, and environmental factors such as tobacco use, radiation, endocrine disruptors and shiftwork.
• Well established risk factors account for 47% of cases while 5% are attributable to hereditary syndromes. In particular, carriers of the breast cancer susceptibility genes, BRCA1 and BRCA2, are at a 30-40% increased risk for breast and ovarian cancer, depending on in which portion of the protein the mutation occurs.

  > Personal history of breast cancer: A woman who had breast cancer in one breast has an increased risk of getting cancer in her other breast.

  > Family history: A woman’s risk of breast cancer is higher if her mother, sister, or daughter had breast cancer. The risk is higher if her family member got breast cancer before age 40. Having other relatives with breast cancer (in either her mother’s or father’s family) may also increase a woman’s risk.

  > Certain breast changes: Some women have cells in the breast that look abnormal under a microscope. Having certain types of abnormal cells (atypical hyperplasia and lobular carcinoma in situ [LCIS]) increases the risk of breast cancer.

  > Race: Breast cancer is diagnosed more often in Caucasian women than Latina, Asian, or African American women.

Treatment

• Breast cancer is treated first with surgery, and then with drugs, radiation, or both. Treatments are given with increasing aggressiveness according to the prognosis and risk of recurrence. Early cancers with good prognosis (T1, N0) may be treated with lumpectomy plus radiation alone or hormone therapy alone. Later cancers with poorer prognosis and greater risk of recurrence may be treated with more aggressive chemotherapy with uncomfortable and life-threatening side effects, in order to increase the likelihood of cure and lower the risk of recurrence.

• Drugs in addition to surgery are called adjuvant therapy. Hormone therapy is one class of adjuvant therapy. Some breast cancers require estrogen to continue growing. They can be identified by the presence of estrogen receptors (ER+) and progesterone receptors (PR+) on their surface (sometimes referred to together as hormone receptors, HR+). These ER+ cancers can be treated with drugs that block the production of estrogen or block the receptors, such as tamoxifen or an aromatase inhibitor).
• Radiotherapy is given after surgery to the region of the tumor bed, to destroy microscopic tumors that may have escaped surgery. Radiation therapy can be delivered as external beam radiotherapy or as brachytherapy (internal radiotherapy). Radiation can reduce the risk of recurrence by 50-66% (1/2 – 2/3rds reduction of risk) when delivered in the correct dose.