Breast Cancer

Breast cancer (malignant breast neoplasm) is cancer 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.

The size, stage, rate of growth, and other characteristics of the tumor determine the kinds of treatment. Treatment may include surgery, drugs (hormonal therapy and chemotherapy), radiation and/or immunotherapy.  Surgical removal of the tumor provides the single largest benefit, with surgery alone being capable of producing a cure in many cases. To somewhat increase the likelihood of long-term disease-free survival, several chemotherapy regimens are commonly given in addition to surgery. Most forms of chemotherapy kill cells that are dividing rapidly anywhere in the body, and as a result cause temporary hair loss and digestive disturbances. Radiation may be added to kill any cancer cells in the breast that were missed by the surgery, which usually extends survival somewhat, although radiation exposure to the heart may cause heart failure in the future.  Some breast cancers are sensitive to hormones such as estrogen and/or progesterone, which makes it possible to treat them by blocking the effects of these hormones.

Prognosis and survival rate varies greatly depending on cancer type and staging. With best treatment and dependent on staging, 5-year relative survival varies from 98% to 23, with an overall survival rate of 85%.

Worldwide, breast cancer comprises 22.9% of all non-melanoma skin cancers in women.In 2008, breast cancer caused 458,503 deaths worldwide (13.7% of cancer deaths in women). Breast cancer is more than 100 times more common in women than breast cancer in men, although males tend to have poorer outcomes due to delays in diagnosis.[

Classification

Breast cancers can be classified by different schemata. Every aspect influences treatment response and prognosis. Description of a breast cancer would optimally include multiple classification aspects, as well as other findings, such as signs found on physical exam. Classification aspects 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) (i.e. spread to a more distant part of the body). Larger size, nodal spread, and metastasis have a larger stage number and a worse prognosis.

The main stages are:

Stage 0 is a pre-cancerous or marker condition, either ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS).

Stages 1–3 are defined as 'early' cancer with a good prognosis.

Stage 4 is defined as 'advanced' and/or 'metastatic' cancer with a poor prognosis.

Histopathology. Breast cancer is usually classified primarily by its histological appearance. Most breast cancers are derived from the epithelium lining the ducts or lobules, and these cancers are classified as ductal or lobular carcinoma. Carcinoma in situ is growth of low grade cancerous or precancerous cells in particular tissue compartment such as the mammary duct without invasion of the surrounding tissue. In contrast, invasive carcinoma does not confine itself to the initial tissue compartment and invades the surrounding tissue.

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. In cancer grading, tumor cells are generally classified as well differentiated (low grade), moderately differentiated (intermediate grade), and poorly differentiated (high grade). Poorly differentiated cancers have a worse prognosis.

Receptor status. Cells have receptors on their surface and in their cytoplasm and nucleus. Chemical messengers such as hormones bind to these receptors, and this causes changes in the cell. Breast cancer cells may or may not have three important receptors: estrogen receptor (ER), progesterone receptor (PR), and HER2/neu.

ER+ cancer cells depend on estrogen for their growth, so they can be treated with drugs to block estrogen effects (e.g. tamoxifen), and generally have a better prognosis.

HER2+ breast cancer had a worse prognosis,  but HER2+ cancer cells respond to drugs such as the monoclonal antibody, trastuzumab, (in combination with conventional chemotherapy) and this has improved the prognosis significantly.  Cells with none of these receptors are called basal-like or triple negative.

DNA assays of various types including DNA microarrays have compared normal cells to breast cancer cells. The specific changes in a particular breast cancer can be used to classify the cancer in several ways, and may assist in choosing the most effective treatment for that DNA type.

Signs and symptoms

Breast cancer showing an inverted nipple, lump, skin dimpling

The first noticeable symptom 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 earliest breast cancers are detected by a 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.

Inflammatory breast cancer is a special type of breast cancer which can pose a substantial diagnostic challenge. Symptoms may resemble a breast inflammation and may include pain, swelling, nipple inversion, warmth and redness throughout the breast, as well as an orange-peel texture to the skin referred to as peau d'orange.

Another reported symptom complex of breast cancer is Paget's disease of the breast. This syndrome presents as eczematoid skin changes such as redness and mild flaking of the nipple skin. As Paget's advances, symptoms may include tingling, itching, increased sensitivity, burning, and pain. There may also be discharge from the nipple. Approximately half of women diagnosed with Paget's also have a lump in the breast.

In rare cases, what initially appears as a fibroadenoma (hard movable lump) could in fact be a phyllodes tumor. Phyllodes tumors are formed within the stroma (connective tissue) of the breast and contain glandular as well as stromal tissue. Phyllodes tumors are not staged in the usual sense; they are classified on the basis of their appearance under the microscope as benign, borderline, or malignant.

Occasionally, breast cancer presents as metastatic disease, that is, cancer that has spread beyond the original organ. Metastatic breast cancer will cause symptoms that depend on the location of metastasis. Common sites of metastasis include bone, liver, lung and brain. Unexplained weight loss can occasionally herald an occult breast cancer, as can symptoms of fevers or chills. Bone or joint pains can sometimes be manifestations of metastatic breast cancer, as can jaundice or neurological symptoms. These symptoms are "non-specific", meaning they can also be manifestations of many other illnesses.

Most symptoms of breast disorder do not turn out to represent underlying breast cancer. Benign breast diseases such as mastitis and fibroadenoma of the breast are more common causes of breast disorder symptoms. The appearance of a new symptom should be taken seriously by both patients and their doctors, because of the possibility of an underlying breast cancer at almost any age.

Risk factors

The primary risk factors for breast cancer are sex,  age,lack of childbearing or breastfeeding, higher hormone levels,  race, economic status and dietary iodine deficiency.

Most cases of breast cancer cannot be prevented through any action on the part of the affected person. The World Cancer Research Fund estimated that 38% of breast cancer cases in the US are preventable through reducing alcohol intake, increasing physical activity levels and maintaining a healthy weight.  It also estimated that 42% of breast cancer cases in the UK could be prevented in this way, as well as 28% in Brazil and 20% in China.

Smoking tobacco also increases the risk of breast cancer with the greater the amount smoking and the earlier in life smoking begins the higher the risk.

In a study of attributable risk and epidemiological factors published in 1995, later age at first birth and not having children accounted for 29.5% of U.S. breast cancer cases, family history of breast cancer accounted for 9.1% and factors correlated with higher income contributed 18.9% of cases. Attempts to explain the increased incidence (but lower mortality) correlated with higher income include epidemiologic observations such as lower birth rates correlated with higher income and better education, possible overdiagnosis and overtreatment because of better access to breast cancer screening, and the postulation of as yet unexplained lifestyle and dietary factors correlated with higher income. One such factor may be past hormone replacement therapy, which was typically more widespread in higher income groups.

The genes associated with hereditary breast-ovarian cancer syndromes usually increase the risk slightly or moderately; the exception is women and men who are carriers of BRCA mutations. These people have a very high lifetime risk for breast and ovarian cancer, depending on the portion of the proteins where the mutation occurs. Instead of a 12 percent lifetime risk of breast cancer, women with one of these genes have a risk of approximately 60 percent.

In more recent years, research has indicated the impact of diet and other behaviors on breast cancer. These additional risk factors include a high-fat diet, alcohol intake, obesity, and environmental factors such as tobacco use, radiation, endocrine disruptors and shiftwork. Although the radiation from mammography is a low dose, the cumulative effect can cause cancer.

In addition to the risk factors specified above, demographic and medical risk factors include:

Personal history of breast cancer: A woman who had breast cancer in one breast has an increased risk of getting a second breast cancer.

Family history: A woman's risk of breast cancer is higher if her mother, sister, or daughter had breast cancer, the risk becomes significant if at least two close relatives had breast or ovarian cancer. The risk is higher if her family member got breast cancer before age 40. An Australian study found that having other relatives with breast cancer (in either her mother's or father's family) may also increase a woman's risk of breast cancer and other forms of cancer, including brain and lung cancers.

Certain breast changes: Atypical hyperplasia and lobular carcinoma in situ found in benign breast conditions such as fibrocystic breast changes are correlated with an increased breast cancer risk.

Those with a normal body mass index at age 20 who gained weight as they aged had nearly double the risk of developing breast cancer after menopause in comparison to women who maintained their weight. The average 60-year-old woman's risk of developing breast cancer by age 65 is about 2 percent; her lifetime risk is 13 percent.

Prevention

Exercise may decrease breast cancer risk. Also avoiding alcohol and obesity. Prophylactic bilateral mastectomy may be considered in patients with BRCA1 and BRCA2 mutations.A 2007 report concluded that women can somewhat reduce their risk by maintaining a healthy weight, drinking less alcohol, being physically active and breastfeeding their children.