BREAST CANCER

Breast cancer is a cancer that starts in the tissues of the breast.
There are two main types of breast cancer:
• Ductal carcinoma starts in the tubes (ducts) that move milk from the breast to the nipple. Most breast cancers are of this type.
• Lobular carcinoma starts in parts of the breast, called lobules, that produce milk.

Many breast cancers are sensitive to the hormone estrogen. This means that estrogen causes the breast cancer tumor to grow. Such cancer is called estrogen receptor positive cancer or ER positive cancer. Some women have what's called HER2-positive breast cancer. HER2 refers to a gene that helps cells grow, divide, and repair themselves. When cells have too many copies of this gene, cells including cancer cells grow faster. Experts think that women with HER2-positive breast cancer have a more aggressive disease and a higher risk of recurrence than those who dont have this type.

Breast cancer, the second leading cause of cancer deaths in American women, is the disease women fear most. Experts predict 178,000 women will develop breast cancer in the United States in 2007. Breast cancer can also occur in men, but it's far less common. For 2007, the predicted number of new breast cancers in men is 2,000. Heightened awareness of breast cancer risk in the past decades has led to an increase in the number of women undergoing mammography for screening, leading to detection of cancers in earlier stages and a resultant improvement in survival rates. Still, breast cancer is the most common cause of death in women between the ages of 45 and 55. With advances in screening, diagnosis, and treatment, the death rate for breast cancer has declined by about 20% over the past decade, and research is ongoing to develop even more effective screening and treatment programs

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Causes breast cancer :

In most cases, it isn't clear what causes normal breast cells to become cancerous only 5 percent to 10 percent of breast cancers are inherited. Families that do have genetic defects in one of two genes, breast cancer gene 1 (BRCA1) or breast cancer gene 2 (BRCA2), have a much greater risk of developing both breast and ovarian cancer. Other inherited mutations including the ataxia-telangiectasia mutation gene, the cell-cycle checkpoint kinase 2 (CHEK-2) gene and the p53 tumor suppressor gene also make it more likely that you'll develop breast cancer. If one of these genes is present in your family, you have a 50 percent chance of having the gene. The new tumor has the same kind of abnormal cells and the same name as the primary tumor. For example, if breast cancer spreads to the bones, the cancer cells in the bones are actually breast cancer cells. The disease is metastatic breast cancer, not bone cancer. For that reason, it is treated as breast cancer, not bone cancer. Doctors call the new tumor or metastatic disease. Breast implants, using antiperspirants, and wearing underwire bras do not raise your risk for breast cancer. There is no evidence of a direct link between breast cancer and induced abortion or pesticides.

1. Age and gender , Your risk of developing breast cancer increases as you get older. The majority of advanced breast cancer cases are found in women over age 50. Women are 100 times more likely to get breast cancer then men.
2. Family history of breast cancer, You may also have a higher risk for breast cancer if you have a close relative has had breast, uterine, ovarian, or colon cancer. About 20-30% of women with breast cancer have a family history of the disease.
3. Genes, Some people have genes that make them more prone to developing breast cancer. The most common gene defects are found in the BRCA1 and BRCA2 genes. These genes normally produce proteins that protect you from cancer. But if a parent passes you a defective gene, you have an increased risk for breast cancer. Other genetic defects have been linked to breast cancer, including those found in the ATM gene, the CHEK-2 gene, and the p53 tumor suppressor gene, but these are very rare.
4. Menstrual cycle, Women who get their periods early (before age 12) or went through menopause late (after age 55) have an increased risk for breast cancer.
5. Other risk factors include:
6. Alcohol use, Drinking more than 1-2 glasses of alcohol a day may increase your risk for breast cancer.
7. Childbirth,Women who have never had children or who had them only after age 30 have an increased risk for breast cancer. Being pregnant more than once or becoming pregnant at an early age reduces your risk of breast cancer.
8. DES, Women who took diethylstilbestrol (DES) to prevent miscarriage may have an increased risk of breast cancer after age 40. This drug was given to the women in the 1940s-1960s.
9. Hormone replacement therapy (HRT), You have a higher risk for breast cancer if you have received hormone replacement therapy for several years or more. Many women take HRT to reduce the symptoms of menopause.
10. Obesity, Obesity has been linked to breast cancer, although this link is controversial. The theory is that obese women produce more estrogen, which can fuel the development of breast cancer.
11. Radiation, If you received radiation therapy as a child or young adult to treat cancer of the chest area, you have a significantly higher risk for developing breast cancer. The younger you started such radiation, the higher your risk especially if the radiation was given when a female was developing breasts.

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Sign and symptoms breast cancer :

1. A spontaneous clear or bloody discharge from your nipple, often associated with a breast lump
2. Retraction or indentation of your nipple
3. A change in the size or contours of your breast
4. Any flattening or indentation of the skin over your breast
5. Redness or pitting of the skin over your breast, like the skin of an orange
6. Bone pain
7. Breast pain or discomfort
8. Swelling of one arm (next to breast with cancer)
9. Weight los
10. A nipple turned inward into the breast
11. A change in the size or shape of the breast
12. A change in how the breast or nipple looks

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Screening and diagnosis breast cancer

Breast self-examination
Breast self-examination is an option beginning at age 20. By becoming proficient at breast self-examination and familiar with the usual appearance and feel of your breasts, you may be able to detect early signs of cancer. Learn how your breasts typically look and feel and watch for changes. If you detect a change, promptly bring it to your doctor's attention. Have your doctor review your examination technique if you'd like input or you have questions.

Clinical breast exam
During a clinical breast exam, your health care provider checks your breasts. You may be asked to raise your arms over your head, let them hang by your sides, or press your hands against your hips.
Your health care provider looks for differences in size or shape between your breasts. The skin of your breasts is checked for a rash, dimpling, or other abnormal signs. Your nipples may be squeezed to check for fluid.
Using the pads of the fingers to feel for lumps, your health care provider checks your entire breast, underarm, and collarbone area. A lump is generally the size of a pea before anyone can feel it. The exam is done on one side, then the other. Your health care provider checks the lymph nodes near the breast to see if they are enlarged.

A thorough clinical breast exam may take about 10 minutes
During this exam, your doctor examines your breasts for lumps or other changes. He or she may be able to feel lumps you miss when you examine your own breasts and will also check for enlarged lymph nodes in your armpit (axilla)

Screening mammogram

• Women in their 40s and older should have mammograms every 1 to 2 years. A mammogram is a picture of the breast made with x-rays.
• Women who are younger than 40 and have risk factors for breast cancer should ask their health care provider whether to have mammograms and how often to have them.
• Two types of mammograms include:
• Screening mammograms. Screening mammograms are performed on a regular basis about once a year to check your breast tissue for any changes since your last mammogram.
• Diagnostic mammograms. Your doctor may recommend a diagnostic mammogram to evaluate a breast change detected by you or your doctor. During a diagnostic mammogram, the radiologist performing the exam can take additional views to evaluate the area of concern more closely.

Other tests breast cancer :
1. Computer-aided detection (CAD)
2. Digital mammography
3. Magnetic resonance imaging (MRI)
4. Breast ultrasound (ultrasonography)
5. ductal lavage
6. Molecular breast imaging (MBI).
7. Ultrasound
8. Biopsy
9. Estrogen and progesterone receptor tests
10. Staging tests
11. Genetic tests

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Treatment breast cancer

The main stay of breast cancer treatment is surgery when the tumor is localized, with possible adjuvant hormonal therapy (with tamoxifen or an aromatase inhibitor, chemotherapy, and/or radiotherapy. At present, the treatment recommendations after surgery (adjuvant therapy) follow a pattern.Other treatments are Hormonal therapy to block certain hormones that fuel cancer growth, Targeted therapy to interfere with cancer cell grow and function.

Surgery

• Lumpectomy. This operation saves as much of your breast as possible by removing only the lump plus a surrounding area of normal tissue. Many women can have lumpectomy often followed by radiation therapy, instead of mastectomy, and in most cases survival rates for both operations are similar
• Partial or segmental mastectomy. Another breast-sparing operation, partial mastectomy involves removing the tumor as well as some of the breast tissue around the tumor and the lining of the chest muscles that lie beneath it. In almost all cases
• Simple mastectomy. During a simple mastectomy, your surgeon removes all your breast tissue the lobules, ducts, fatty tissue and skin, including the nipple and areola
• Modified radical mastectomy. In this procedure, a surgeon removes your entire breast, including the overlying skin, and some underarm lymph nodes (axillary lymph node dissection), but leaves your chest muscles intact.

Radiationtherapy
Radiation therapy uses high-energy X-rays to kill cancer cells and shrink tumors. It's administered by a radiation oncologist at a radiation center. In general, radiation is the standard of care following a lumpectomy for both invasive and noninvasive breast cancers. Oncologists are also likely to recommend radiation following a mastectomy for a large tumor, for inflammatory breast cancer, for cancer that has invaded the chest wall or for cancer that has spread to more than four lymph nodes in your armpit.

Chemotherapy
Chemotherapy uses drugs to destroy cancer cells. The size of the tumor, characteristics of the cancer cells, and extent of spread of the cancer help determine your need for chemotherapy. Treatment often involves receiving two or more drugs in different combinations. These may be administered intravenously, in pill form or both. You may have between four and eight treatments spread over three to six months.

Hormonetherapy
Hormone therapy perhaps more properly termed hormone blocking therapy is often used to treat women whose cancers are sensitive to hormones estrogen and progesterone receptor positive cancers. Similar to chemotherapyTwo classes of medications are used in hormone therapy: selective estrogen receptor modulators (SERMs) and aromatase inhibitors.

• Selective estrogen receptor modulators (SERMs)

The most common SERM prescribed for hormone therapy is tamoxifen (Nolvadex). Tamoxifen is used as a treatment for women with hormone-sensitive metastatic breast cancer, as an adjuvant therapy for women with early-stage estrogen receptor positive breast cancer, and as a preventive agent in some high-risk women

• Aromatase inhibitors

This class of drugs, which includes anastrozole (Arimidex), letrozole (Femara) and exemestane (Aromasin), blocks the conversion of a hormonal substance (androstenedione) into estrogen. This effectively stops estrogen production in cells other than the ovaries. Fat cells, the adrenal gland and other normal cells all make small amounts of estrogen

Biological therapy
1. Trastuzumab (Herceptin).
2. Bevacizumab (Avastin)
3. Lapatinib (Tykerb)

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HERCEPTIN (TRASTUZUMAB)

Herceptin is one of a new group of cancer drugs called monoclonal antibodies.Herceptin is indicated in combination with paclitaxel for treatment of HER2-overexpressing metastatic breast cancer, as well as, a single agent for treatment of HER2-overexpressing breast cancer in patients who have received one or more chemotherapy regimens for metastatic disease
Herceptin is the only HER2-targeted therapy with approved indications in both the adjuvant and metastatic settings.
Herceptin is indicated as part of a treatment regimen containing doxorubicin, cyclophosphamide, and paclitaxel for the adjuvant treatment of HER2-overexpressing breast cancer, as well as, a single agent, for the adjuvant treatment of HER2-overexpressing node-negative (ER/PR-negative or with one high-risk feature) or node-positive breast cancer, following multi-modality anthracycline-based therapy.
Herceptin (chemical name: trastuzumab) is a very effective treatment against HER2-positive breast cancer in women with stage II, III, and IV disease (medium to large cancers or cancers with lymph nodes involved or metastatic disease). It is given intravenousy into the bloodstream once every one to three weeks.

ACTION HERCEPTIN ( TRASTUZUMAB )
Herceptin stops or slows the growth of certain breast cancer cells by blocking the chemical signals they need to grow.
Chromosomes inside every cell contain genes, which regulate the cell's growth, rest, and repair. The genes do this by ordering the production of special proteins that tell the cells what to do. Each protein sets off a step in a chain of reactions, resulting in the desired cell activity growth, rest, or repair. Herceptin is a special antibody protein medication that attaches itself to the HER2 receptors on the cancer cells and blocks them from receiving growth signals. Herceptin can also alert the immune system to destroy the cancer cells it attaches to.
Herceptin works by interfering with one of the ways in which breast cancer cells divide and grow. Some breast cancer cells divide and grow when a protein that naturally occurs in the body (known as human epidermal growth factor) attaches itself to another protein known as HER2, which is found on the surface of some breast cancer cells. Herceptin blocks this process by attaching itself to the HER2 protein so that the epidermal growth factor cannot reach the breast cancer cells. This stops the cells from dividing and growing. Herceptin also works by attracting the body’s own immune cells to help destroy the cancer cells.


HOW IS HERCEPTIN ( TRASTUZUMAB ) GIVEN :
Herceptin is given by a drip (infusion) through a fine tube (cannula) inserted into a vein. which means it is dripped into your body through a needle inserted into a vein. The first dose of Herceptin you get takes about 90 minutes. After that, it only takes about 30 minutes to get the other doses of Herceptin, which are usually given weekly. If you have earlier stage disease and take Herceptin alone or as part of a regimen containing Adriamycin (chemical name: doxorubicin), Cytoxan (chemical name: cyclophosphamide), and Taxol (chemical name: paclitaxel), you receive it for a specific amount of time and then stop taking it.

DOSAGE GUIDELINES
• The recommended dosages of Herceptin are based on patient body weight.
- Initial loading dose: 4 mg/kg body weight
- Weekly subsequent doses: 2 mg/kg body weight
• To determine the correct number of milligrams of Herceptin needed for a given patient:
- Convert patient weight into kilograms: 2.2 lb =1 kg
- Insert patient weight in kilograms into the dosage equation below, using either 4 mg (loading dose) or 2 mg (subsequent doses) as the multiplier:

SIDE EFFECTS HERCEPTIN ( TRASTUZUMAB )
Herceptin causes flu-like symptoms in about 40% of the women who take it. These symptoms may include fever, chills, muscle aches, or nausea. These side effects generally become less severe after the first treatment. Other side effects, including low white or red blood cell counts, diarrhea, and infections, are seen in some women receiving Herceptin in combination with chemotherapy, but are rarely seen in women taking Herceptin alone.

1. Allergic reactions = This is a rare side effect of Herceptin. Signs of this include skin rashes and itching, wheezing, difficulty breathing, and breathlessness. You will be closely monitored during your treatment, but let your nurse or doctor know if you have any of these symptoms. To reduce the chance of developing an allergic reaction, antihistamines can be given before the infusion. The infusion can also be slowed down or stopped until the reaction is over.
2. Flu-like symptoms = This includes a high temperature (fever) and chills, shortly after the drug is given. These symptoms can be controlled or reduced with medicines, which your doctor can prescribe for you.
3. Tumour pain = Some people may experience mild pain in parts of the body to which the breast cancer has spread. Painkillers can be given to relieve this.
4. Diarrhoea = This can usually be controlled with medicine, but let your doctor know if it is severe or if it continues. It is important to drink plenty of fluids if you have diarrhoea.
5. Headaches = Let your doctor know if you have headaches while having treatment with Herceptin.
6. Effects on the heart = Herceptin may lead to some people having heart problems. For that reason it is recommended that Herceptin is not given to people with a history of heart disease or high blood pressure.

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