What is breast cancer..?

Cancers are a group of diseases that cause cells to grow out of control. Breast cancer begins as a tumor (lump) in breast tissue, which is made up of glands for milk production, called lobules, and the ducts that connect lobules to the nipple.

Most breast masses are benign, (not cancerous), and do not grow uncontrollably or spread. The earliest breast cancers, called "in situ" because they are confined to the ducts ("ductal carcinoma in situ") or lobules ("lobular carcinoma in situ"), are nearly all curable. More advanced tumors are called "invasive," or "infiltrating," having broken through the duct or glandular walls to invade the surrounding tissue of the breast.

The seriousness of invasive breast cancer is strongly influenced by the stage of the disease and the extent or spread of the cancer when it is first diagnosed. There are two main staging systems for cancer. The American Joint Committee on Cancer’s classification of tumors uses information on tumor size (T), lymph node involvement (N), and the presence or absence of distant metastases(M), and is commonly used in clinical settings. Once the T, N, and M are determined, a stage of I, II, III, or IV is assigned, with stage I being an early stage and stage IV being the most advanced.

A simpler system, called the SEER Summary Stage system and is used for public health research and planning. In this system,"local-stage" tumors are confined to the breast,"regional-stage" tumors have spread to nearby tissue or lymph nodes and "distant-stage" cancers have spread ("metastasized") to distant organs.

Who gets breast cancer ..?

After cancers of the skin, breast cancer is the most common cancer among women, accounting for more than 1 in 4 cancers diagnosed. Men are generally at low risk for developing breast cancer. However, they can, in fact develop the disease and therefore should report any changes in their breasts to a physician.

Both the incidence and death rates for breast cancer increase with age. Between 2000 and 2004, 95% of new cases and 97% of breast cancer deaths occurred in women over age thirty nine. Women between the ages of 20 and 24 had the lowest breast cancer rate, (1.4 cases per 100,000 women), and women aged 75-79 years had the highest, (464.8 cases per 100,000). During the same reporting period, the median age at the time of diagnosis was 61 years, (i.e. 50% of women who developed breast cancer were aged 61 or younger.

White women have a higher incidence of breast cancer than African American women after the age of 40, while African American women have a higher incidence before age 40. Individuals from the latter group and are also more likely to die from breast cancer at every age. Incidence and death rates from breast cancer are lower among women of other racial and ethnic groups than among white and African American women.

What are the risk factors..?

Many of the known breast cancer risk factors, such as age, family history etc., are not easily modifiable. However, some factors associated with increased risk are.

Breast implants are not associated with an increased risk of breast cancer, and while there are claims that abortion may increase risk, there is a large body of evidence refuting this hypothesis.

Despite concern that rising breast cancer incidence may be caused by environmental pollutants, studies to date have not found an association. Although animal studies have demonstrated that prolonged highdose exposure to many industrial chemicals can increase
mammary tumors, epidemiological studies have not found clear relationships between environmental pollutants and breast cancer.

Among the established risk factors for breast cancer are:

Increasing Age

Besides being female, age is the most important risk factor for breast cancer. Currently, a woman living in the US has a 12.3% (1 in 8) lifetime risk of developing breast cancer. In the 1970s, the risk was thought to be 1 in 11, but the increase appears due to longer life expectancy, long-term Hormone Replacement Therapy and the rising prevalence of obesity.

Family History

Women with a family history of breast cancer, especially in a first-degree relative (mother, sister, or daughter), have an increased risk for breast cancer. Also, the risk is higher still if more than one first-degree relative has developed breast cancer, particularly if at a young age. It is estimated that 5% to 10% of breast cancer cases result from inherited mutations to breast cancer susceptibility genes known as "BRCA1" and "BRCA2." (However, these mutations are present in far less than 1% of the general population.) Women with BRCA1 mutations appear to have a 65% risk for developing breast cancer by age 70, while those with BRCA2 mutations have a 45% risk.

Molecular tests are commercially available to identify some of the BRCA mutations but the interpretation of these tests is complicated. Since it is not yet possible to predict if or when women who carry a particular mutation will develop breast cancer, it is strongly recommended that anyone considering genetic testing speak with a genetic counselor or doctor qualified to interpret the test results. Also, not all familial risk results from a BRCA1 or BRCA2 mutation, with many scientists suggesting that most familial breast cancer results from the interaction between lifestyle factors and low risk variations in susceptibility factors shared by women within a family.

Hormonal Factors

Reproductive hormones are thought to influence breast cancer risk. Early menarche (<12 years), older age at menopause (>55 years), older age at first full-term pregnancy (>30 years), and fewer number of pregnancies may increase a woman’s risk. However, breastfeeding consistently decreases a woman’s risk, with greater benefit associated with longer duration of feeding. Use of oral contraceptives may slightly increase the risk of breast cancer, but those who have stopped using them for 10 years or more have the same risk as women who have never used the pill. The recent use of combination hormone replacement therapy (HRT), (combined estrogen and progestin), has been shown to increase breast cancer risk, but estrogen alone (prescribed for women without a uterus), does not appear to increase the
risk.

Clinical Factors

High breast tissue density has been shown to be a strong independent risk factor for the development of breast cancer. Also, some types of benign breast conditions are more closely linked to breast cancer risk than others. Doctors categorize benign breast conditions into 3 groups based on the degree of risk: "Non-proliferative" lesions are not associated with any overgrowth of breast tissue and have little or no effect on risk. "Proliferative lesions without atypia" (those with excessive growth of cells in the ducts or lobules) seem to raise a woman’s risk slightly (1.5 to 2 times), while "proliferative lesions with atypia" (excessive growth of cells with the cells no longer appearing normal) raise risk by 4 to 5 times.

Can I prevent breast cancer..?

There is no absolute way to prevent breast cancer, so a woman’s best overall preventive health plan is to reduce her known risk factors.

Obesity

Obesity increases risk of postmenopausal (but not premenopausal) breast cancer. Women
who gain 55 pounds or more after age 18 have almost 1.5 times the risk of breast cancer compared with those who maintained their weight. Significant weight gain after menopause is associated with an increased risk of 18%, whereas losing weight and maintaining its loss after menopause lowers risk.

Physical Activity
Growing evidence supports a small protective effect of physical activity on breast cancer. Although most studies find reduced risk only in women who exercise vigorously, one study suggests that regular physical activity, regardless of intensity, may reduce the risk of breast cancer.

Alcohol Consumption

Alcohol consumption is consistently associated with increased breast cancer risk. Many epidemiologic studies suggests that the equivalent of 2 drinks a day may increase breast cancer risk by 21%. The increased risk is dose-dependent and does not relate to the type of alcoholic beverage consumed. A likely mechanism involves the ability of alcohol to increase estrogen and androgen levels.

Hormone Replacement Therapy (HRT)

Use of combined HRT, increases the risk of breast cancer, as well as the likelihood that cancer will be found at a more advanced stage. The US Preventive Services Task Force has recommended against the routine use of HRT for the prevention of diseases such as osteoporosis and heart disease in postmenopausal women. However, if a woman and her doctor decide that HRT is appropriate, the lowest effective dose and shortest treatment short time should be used.

Chemoprevention

The use of drugs to reduce the risk of disease is called "chemoprevention." Several clinical studies have shown that the drugs tamoxifen and raloxifene may reduce this risk in women known to be at increased risk. The reduction in risk is, however, limited to estrogen-receptor positive disease. Long-term followup results indicate that the reduction in risk persists after completion of the 5-year treatment schedule. It is important to be aware though, that administration of tamoxifen results in some increased risk of endometrial cancer.

Raloxifene has also been shown to reduce the risk of invasive breast cancer, although it does not have the same protective effect against in situ cancer (DCIS or LCIS).While it does appear to have a lower incidence of side effects such as uterine cancer and blood clots in the legs, Raloxifene has not yet been approved by the Food and Drug Administration (FDA) for chemoprevention.

Women at increased risk for breast cancer should discuss taking tamoxifen or raloxifene with their doctors.

Prophylactic Surgery

Women at very high risk of breast cancer may choose preventive (prophylactic) mastectomy, and operation that removes one or both breasts before cancer has been found. This is commonly combined with immediate breast reconstruction. One study has detailed a greater than 90% reduction in risk of breast cancer in high-risk women with family history who underwent prophylactic mastectomy. Other studies confirm the benefit of prophylactic mastectomy, particularly in genetically susceptible women. Any woman considering this sort of drastic treatment should carefully consult her doctor and always obtain a second opinion.

Can cancer be found early..?

The American Cancer Society guidelines for the early detection of breast cancer depend upon a woman’s age. They include mammography and clinical breast examination (CBE) together with magnetic resonance imaging (MRI) for women at high risk. For purposes of testing, women at high risk include those who:

• have a BRCA1 or BRCA2 gene mutation or have a first-degree relative (mother, father, brother, sister, or child) with a BRCA1 or BRCA2 gene mutation, and have not had genetic testing themselves.
• have a lifetime risk of breast cancer of 20%-25% or greater, according to risk assessment tools that are based mainly on family history
• had radiation therapy to the chest when they were between the ages of 10 and 30 years
• have Li-Fraumeni syndrome, Cowden syndrome, or Bannayan-Riley-Ruvalcaba syndrome, or have a first degree relative with one of these syndromes.

Women with moderately increased risk may wish to discuss the appropriateness of occasional MRI with their doctors. This group includes:

• those with a lifetime risk of breast cancer of 15%-20%, according to risk assessment tools based mainly on family history
• those who have a personal history of breast cancer, ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS), atypical ductal hyperplasia (ADH), or atypical lobular hyperplasia (ALH)
• those who have extremely dense breasts or unevenly dense breasts on mammogram

Mammography

Early detection of breast cancer through mammography greatly improves treatment options and the chances survival, with mammography being the single most effective method of early detection. Mammography is a low-dose x-ray procedure that allows visualization of the internal structure of the breast.It is highly accurate, but not perfect, detecting on average 80%-90% of breast cancers.

It is important that women receive regular mammograms with screening intervals based upon the duration of time a breast cancer is detectable by mammography before symptoms develop. Women should talk with their doctors about a plan for receiving regular mammograms according to recommended guidelines. As long as a woman is in good health and would be a candidate for breast cancer treatment, she should continue to be screened with mammography regardless of her age.

Magnetic Resonance Imaging (MRI)

MRI uses magnetic fields instead of x-rays to produce very detailed, cross-sectional images of the body. The most useful MRI exams for breast employ a contrast material (gadolinium DTPA) that is injected into a small vein in the arm before or during the exam. While MRI is more sensitive in detecting cancers than mammograms, it also has a higher false-positive rate (findings that turn out not to be cancer), which results in more recalls and biopsies. This is why MRI is not recommended for screening women at average risk of breast cancer.

Clinical Breast Examination (CBE)

For asymptomatic women of average-risk in their 20s and 30s, it is recommended that a breast exam be performed at least every 3 years. For women aged 40 and older, annual CBE can help complement mammography. CBE provides an opportunity for a woman and her physician to discuss changes in her breasts, early detection testing, and history factors that could make her more likely to develop breast cancer.

What is the treatment for breast cancer ..?

Treatment decisions are made after consideration of the stage and biological characteristics of the cancer, the patient’s age and preferences, and the risks and benefits associated with each treatment. Most women with breast cancer will have some type of surgery. The surgery is often combined with radiation therapy, chemotherapy, hormone therapy or biologic therapy.

Surgery

The primary goal of breast cancer surgery is to remove the cancer from the breast and to assess the stage of disease. In a "lumpectomy," only the cancerous tissue plus a rim of normal tissue is removed, while "simple" mastectomy includes removal of the entire breast."Modified radical mastectomy" includes removal of the entire breast and lymph nodes under the arm. If a woman chooses to have a mastectomy, she may want to consider having breast reconstruction. This may be done employing saline-filled or silicone-filled implants or tissue from other parts of the body.

Lumpectomy is almost always followed by about 5 to 7 weeks of radiation therapy. A woman who has lumpectomy and radiation can expect the same long-term survival as if she had chosen mastectomy. Both lumpectomy and mastectomy are often accompanied by removal of lymph nodes from the armpit to determine if the disease has spread beyond the breast. Because surgery or radiation therapy involving the lymph nodes can lead to "lymphedema," a serious, chronic swelling of the arm, newer options such as "sentinel lymph node biopsy", where fewer nodes are sampled may be preferred.

Radiation Therapy

Radiation can be used to destroy cancer cells remaining in the breast or underarm area after surgery or to reduce the size of a tumor before surgery. The two types of radiation therapy, with "external radiation" being the usual type for women with breast cancer. Such radiation is focused from a machine outside the body on the cancer-affected area. "Internal radiation" therapy, also known as "brachytherapy," employs a radioactive substance sealed in seeds, wires, or catheters that are placed directly into or near the cancer. The mode of radiation chosen will on the type and stage of the cancer. Radiation therapy is typically given for 5 to 7 weeks and is almost always recommended after a lumpectomy. In some circumstances, it may be recommended following mastectomy as well. Also, radiation of the chest wall may be recommended for a woman with 4 or more positive lymph nodes or a very large tumor, even when her breast has been removed.

Systemic Therapy

Systemic therapy includes biologic therapy, chemotherapy, and hormone therapy. When given before surgery to shrink the tumor it is called neoadjuvant therapy.This may allow some women otherwise needing mastectomy to undergo breast-conserving surgery. Neoadjuvant therapy has been found to be as effective as therapy given after surgery in terms of survival and disease progression.

Systemic therapy is also used in treating women with metastatic breast cancer.

Biologic therapy

About 15% to 30% of breast cancers overproduce a growth-promoting protein called "HER2/neu." They tend to grow faster and are more likely to recur. "Herceptin®" (tratuzumab) is a monoclonal antibody that targets the HER2 protein of breast tumors and provides a survival benefit to some women with metastatic breast cancer.It has also been shown to be effective in early-stage breast cancers that over produce HER2. Adding tratuzumab to standard chemotherapy for early-stage HER2 positive breast cancer reduces the risk of recurrence and death by significant amounts.

Chemotherapy

"Adjuvant chemotherapy" means the use of chemotherapy after the tumor has been removed for the purpose of eliminating cells that may have escaped the local treatments, thereby increasing the cure rate of the patient. Drug combinations of drugs are more effective than one drug alone and chemotherapy is most effective when the full dose and cycle of drugs are completed in a timely manner. The benefit of chemotherapy is dependent upon multiple factors including tumor size, the number of lymph nodes involved, the presence of estrogen or progesterone receptors, and the amount of HER2/neu protein made by the cancer cells. The most common drugs used in combination for early breast cancer include cyclophosphamide, methotrexate, fluorouracil, doxorubicin (adriamycin),epirubicin, paclitaxel (Taxol), and docetaxel (Taxotere). Adjuvant chemotherapy is usually given for 3 to 6 months.

Hormone Therapy

Estrogen, a hormone produced by the ovaries, promotes the growth of many breast cancers. Women whose breast cancers test positive for estrogen receptors can be given hormone therapy to block the effects of estrogen on tumor cell growth. Tamoxifen, the most common "antiestrogen drug," is effective in both postmenopausal and premenopausal "receptor positive" patients. Recurrence and survival benefits generally increase with longer use of tamoxifen use and persist for at least 10 years following treatment.

A class of drugs known as aromatase inhibitors (AIs) has been approved for use in treating both early and advanced post-menopausal breast cancer. These drugs, "letrozole," "anastrozole" and "exemestane" work by blocking an enzyme that produces small amounts of estrogen in postmenopausal women. Because they cannot stop the ovaries from producing estrogen, aromatase inhibitors are not an effective treatment in premenopausal patients. Clinical trials have shown a clear advantage to using either an AI instead of tamoxifen for a total of 5 years or switching to an AI after several years of tamoxifen treatment. Although AIs have fewer side effects than tamoxifen in the form of endometrial cancer and blood clots, they can cause osteoporosis and bone fractures.