Breast Cancer - symptoms, information, causes, diagnosis and treatment

What is Breast Cancer

A malignant (cancerous) tumor that arises in the BREAST. There are many types of breast cancers, some of which are HORMONE driven (draw sustenance from ESTROGENS or PROGESTERONE) and others that are not. Primary breast cancer originates in the breast; secondary breast cancer metastasizes (spreads) to the breast from an origin elsewhere in the body. Breast cancer may also metastasize to other sites in the body such as the LUNGS or bones.

Causes of Breast Cancer

Breast cancer is the most common cancer among American women; doctors in the United States diagnose breast cancer in about 200,000 women each year. Breast cancer is currently second to LUNG CANCER as the leading cause of deaths due to cancer among women. However, significant advances in the early 2000s in understanding the mechanisms of breast cancer cells and the resulting development of new treatments are changing the landscape of breast cancer.

Genetic factors

The genes BRCA-1/BRCA-2 were the first genes conclusively linked to cancer. Inherited mutations in these genes significantly increase a woman’s risk for breast cancer and OVARIAN CANCER. Researchers continue to study these mutations for ways to take advantage of them for preventing or treating cancers in women who have either or both mutations.

Other mutations are not hereditary but instead occur over time, the consequence of molecular damage that becomes cumulative over time. Researchers have identified nearly two dozen genes that influence cell proliferation (cell growth and division) in some way. One of the most significant is the her-2 GENE (human epidermal growth factor receptor 2, also called HER-2/neu) gene, located on CHROMOSOME 17. The her-2 gene expresses (directs the production of) certain protein receptors on the surfaces of cell membranes. The receptors allow binding with the HER-2/neu protein, a protein that instructs the cell to grow and divide. Mutations in the her-2 gene cause increased numbers of HER-2/neu receptors on cells, allowing greater HER-2/neu binding. This process, called overexpression, alters the way in which the cells grow and divide.

Hormonal factors

Breast cancer cells may have receptors on the surfaces of their cell membranes for estrogen, progesterone, or both. These are hormone-positive cancer cells—designated as estrogen positive (ER+) or progesterone positive (PR+), with an accompanying percentage or numeric value that identifies the relative proportion or number of positive hormone receptors.

Immune factors

The risk for breast cancer, like most types of cancer, increases with age. As immune function diminishes with age, so does the body’s ability to protect itself against health conditions such as cancer. Researchers are exploring the roles foods and NUTRIENTS play in supporting the IMMUNE SYSTEM’s ability to identify, contain, and eliminate cancer cells that develop. Immune dysfunction appears to play a direct role in one rare but aggressive type of breast cancer, inflammatory breast cancer (IBC). In IBC the breast cancer cells collect in the LYMPH vessels, causing INFLAMMATION within the breast rather than forming a discreet tumor.

TYPES OF BREAST CANCER
ADENOCARCINOMA infiltrating comedocarcinoma
infiltrating intraductal CARCINOMA (IDC) infiltrating lobular carcinoma
inflammatory BREAST cancer (IBC) intraductal carcinoma
lobular carcinoma in situ (LCIS) mucinous (colloid) carcinoma
noninfiltrating intraductal carcinoma noninfiltrating comedocarcinoma
PAGET’S DISEASE OF THE BREAST papillary carcinoma
tubular carcinoma  

Breast cancer in men

Though people think of breast cancer as a woman’s condition, men also can develop breast cancer. Breast cancer in men is rare, occurring in 1 man for every 100 women who develop it. Men develop fewer types of breast cancers as well, because their breasts do not have the glandular tissue prevalent in the breasts of women. The types of breast cancers that occur in men are ADENOCARCINOMA, ductal carcinoma in situ (DCIS), and infiltrating ductal carcinoma (IDC). Men can also develop PAGET’S DISEASE OF THE BREAST, a condition in which cancer cells migrate into the SKIN around the nipple, though this uncommon type of cancer is even more rare in men than in women. Symptoms of male breast cancer are the same as symptoms breast cancer in women. Many treatment options are also the same. Doctors diagnose about 1,700 men with breast cancer each year in the United States.

Symptoms of Breast Cancer and Diagnosis

In most situations the only symptom of breast cancer is a lump that the woman, her health-care provider, or a mammogram detects. Most breast cancer tumors do not hurt. Other symptoms of breast cancer may include

  • nipple discharge, typically watery or sometimes blood tinged
  • dimpling of the skin on the surface of the breast
  • changes in the appearance of, or inversion of, the nipple
  • changes in the shape or profile of the breast
  • general sense of tiredness or lack of energy

The diagnostic path may include diagnostic mammogram, breast ULTRASOUND, fine-needle aspiration biopsy of the lump to obtain cell samples for laboratory examination, or excisional biopsy to remove the lump and provide tissue for laboratory examination. Excisional biopsy provides conclusive diagnosis. The pathologist determines the hormonal sensitivity of the cancer cells (estrogen or progesterone receptor positive) and whether they are her-2 positive or negative. Many cancer centers conduct further testing to analyze the genetic composition of the cancer cells. Such testing provides insights into how the cancer cells grow and often reveals their vulnerabilities, allowing precisely targeted treatments. As well, the pathologist evaluates the size and characteristics of the tumor to determine its grade (level of abnormality in the cells) and stage (extent of the tumor). These factors in combination are crucial for determining appropriate CANCER TREATMENT OPTIONS AND DECISIONS.

Breast Cancer Treatment Options and Outlook

Primary treatment for early stage breast cancer of any type is surgery to remove the cancer, which may be lumpectomy (removal of the lump and a safe margin of normal tissue), segmental MASTECTOMY (removal of the one quarter segment of the breast that contains the tumor), simple mastectomy (removal of the breast), or modified radical mastectomy (removal of the breast and some surrounding tissue along with SENTINEL LYMPH NODE DISSECTION).

Nearly all women who have surgery for breast cancer also receive adjuvant (follow-up) therapy, which may include RADIATION THERAPY, CHEMOTHERAPY, HORMONE THERAPY, or MONOCLONAL ANTIBODIES (MABS) therapy, either singularly or in combination. These therapies also may be primary treatment for later stage and recurrent breast cancers. In the late 1990s hormone therapy and MAbs therapy (also called biological response modifier therapy or IMMUNOTHERAPY) became the frontrunners in adjuvant therapy for HORMONE-DRIVEN CANCERS—tumors sensitive to estrogen (ER+) or progesterone (PR+)—and HER-2/neu-positive tumors, respectively. In late 2005 the National Comprehensive Cancer Network (NCCN) issued revised treatment guidelines for breast cancer in which the cancer’s hormone and her-2 status are the primary factors for deciding the type and course of adjuvant therapy, with the traditional practice of evaluating tumor size and the degree of METASTASIS being a secondary step.

Hormone therapy for breast cancer

Hormone therapy targets suppression of estrogen and progesterone in the woman’s body. Among the therapies to achieve this goal are

  • selective estrogen receptor modulators (SERMs), drugs that bind with estrogen receptors to keep estrogen from doing so; SERMs have some estrogen-like qualities that help maintain BONE DENSITY and lipid METABOLISM
  • estrogen receptor downregulators (ERDs), which first bind with estrogen receptors and then destroy them
  • aromatase inhibitors, which block the action of aromatase, an enzyme that converts ANDROGENS naturally occurring in body tissues such as fat into estrogen

Hormone therapy for breast cancer is effective in women who are past MENOPAUSE or who have no ovarian function due to surgical removal of the OVARIES (OOPHORECTOMY) or chemical suppression of ovarian function (medications such as goserelin and leuprolide). Blocking estrogen production cuts off the supply of estrogen to cancer cells that require it, preventing the cells from growing. Side effects that may occur with hormone therapy include JOINT PAIN, NAUSEA, DIARRHEA, HEADACHE, and HOT FLASHES.

SERMs were the first effective hormone therapy drugs (tamoxifen came on the market in the 1980s). They generally have therapeutic value for about five years, after which their ability to bind with estrogen receptors diminishes. Oncologists may recommend taking a SERM for five years and then switching to an aromatase inhibitor, which does not appear to have time-limited usefulness. Aromatase inhibitors and ERDs are too new in clinical practice to know their long-term effectiveness.

HORMONE THERAPY DRUGS TO TREAT BREAST CANCER
Selective Estrogen Receptor Modulators (SERMs)
raloxifene (Evista)
tamoxifen (Nolvadex)
toremifene (Fareston)
Aromatase Inhibitors
anastrazole (Arimidex)
exemestane (Aromasin)
letrozole (Femara)
Estrogen Receptor Downregulators (ERDs)
fulvestrant (Faslodex)

Trastuzumab (Herceptin)

Trastuzumab, a monoclonal antibody, specifically targets her-2 receptors on breast cancer cells. First produced in the early 1970s, trastuzumab demonstrated its effectiveness against her-2 positive breast cancer in the 1980s and became the cornerstone of treatment for her-2 positive metastatic breast cancer in the 1990s. Because trastuzumab so narrowly targets breast cancer cells, it causes few side effects. However, one significant, though rare, SIDE EFFECT is HEART FAILURE. In the first decade of the 2000s, oncologists began administering trastuzumab for her-2 positive stage 2, stage 3, and stage 4/metastatic breast cancers along with combination chemotherapy.

CHEMOTHERAPY AGENTS TO TREAT BREAST CANCER
capecitabine cyclophosphamide
docetaxel doxorubicin
epirubicin 5-fluorouracil (5FU)
gemcitabine paclitaxel
vinorelbine  

Risk Factors and Preventive Measures

Age is the primary risk factor for breast cancers of all types, with the likelihood of developing breast cancer reaching one in two for women 85 and older. Hereditary factors (such as BRCA-1/BRCA-2) influence about 5 percent of breast cancers. Lifestyle factors that contribute to nonhereditary breast cancers include EATING HABITS that feature high-fat foods, lack of physical exercise, cigarette smoking, and excessive ALCOHOL consumption.

There is a strong correlation between OBESITY and breast cancer, though researchers do not know whether this is a circumstance of excess body fat or the consequence of eating habits and physical inactivity. Fat cells convert androgens to estrogen, raising the level of estrogens in the blood circulation. Continued exposure to elevated levels of estrogen is a risk factor for breast cancer as well as other hormone-driven cancers.

It is not possible at present to completely prevent breast cancer. However, lifestyle improvements can significantly reduce the risk of developing breast cancer. Regular breast examination from a health care provider, breast self-examination, and mammograms make possible early detection of breast cancer, which establishes the most ideal circumstances for successful treatment.

See also CANCER PREVENTION; DIET AND HEALTH; FIBROCYSTIC BREAST DISEASE; INTRADUCTAL PAPILLOMA; MOLECULARLY TARGETED THERAPIES; MUTATION; OBESITY AND HEALTH; ONCOGENES; SMOKING AND HEALTH; STAGING AND GRADING OF CANCER; SURGERY BENEFIT AND RISK ASSESSMENT.

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