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Breast Cancer

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Compiled By Dr. K.B.Mallya


“When you have cancer, support is very important. Others can listen, share  burdens, pray, act as a sounding board, boost morale, and provide emotional support. But, no matter how much they would like, they cannot do certain things for you. During one night of vomiting, my mother said she wished that she could take the treatments for me. But, the cancer cells are in me, and so I must do the treatments myself, of course. And just like no one else can take the treatments for me, others cannot be joyful for me because joy is an inside job….”


BREAST CANCER: AN OVERVIEW


WHAT IS THE BREAST?


The breast is a collection of glands and fatty tissue that lies between the  skin and the chest wall. The glands inside the breast produce milk after a woman has a baby. Each gland is also called a lobule, and many lobules make up a lobe. There are 15 to 20 lobes in each breast. The milk gets to the nipple from the glands by way of tubes called ducts. The glands and ducts get bigger when a breast is filled with milk, but the tissue that is most responsible for the size and shape the breast is the fatty tissue. There are also blood vessels and lymph vessels in the breast. Lymph is a clear liquid waste product that gets drained out of the breast into lymph nodes. Lymph nodes are small, pea-sized pieces of tissue that filter and clean the lymph. Most lymph nodes that drain the breast are under the arm in what is called the axilla.


WHAT IS BREAST CANCER?


Breast cancer happens when cells in the breast begin to grow out of control and can then invade nearby tissues or spread throughout the body. Large collections of this out of control tissue are called tumors. However, some tumors are not really cancer because they cannot spread or threaten someone’s life. These are called benign tumors. The tumors that can spread throughout the body or invade nearby tissues are considered cancer and are called malignant tumors. Theoretically, any of the types of tissue in the breast can form a cancer, but usually it comes from either the ducts or the glands. Because it may take months to years for a tumor to get large enough to feel in the breast, we screen for tumors with mammograms, which can sometimes see disease before we can feel it.


AM I AT RISK FOR BREAST CANCER?


Breast cancer is the most common malignancy affecting women in North America and Europe. Every woman is at risk for breast cancer. Close to 200,000 cases of breast cancer were diagnosed in the United States in 2001. Breast cancer is the second leading cause of cancer death in American women behind lung cancer. The lifetime risk of any particular woman getting breast cancer is about 1 in 8 although the lifetime risk of dying from breast cancer is much lower at 1 in 28.


Risk factors for breast cancer can be divided into those that you cannot change and those that you can change. Some factors that increase your risk of breast cancer that you cannot alter include being a woman, getting older, having a family history (having a mother, sister, or daughter with breast cancer doubles your risk), having a previous history of breast cancer, having had radiation therapy to the chest region, being Caucasian, getting your periods young (before 12 years old), having your menopause late (after 50 years old), never having children or having them when you are older than 30, and having a genetic mutation that increases your risk. Genetic mutations for breast cancer have become a hot topic of research lately. Between 3% to 10% of breast cancers may be related to changes in either the gene BRCA1 or the gene BRCA2. Women can inherit these mutations from their parents and it may be worth testing for either mutation if a woman has a particularly strong family history of breast cancer (meaning multiple relatives affected, especially if they are under 50 years old when they get  the disease). If a woman is found to carry either mutation, she has a 50% chance of getting breast cancer before she is 70. Family members may elect to get tested to see if they carry the mutation as well. If a woman does have the mutation, she can get more rigorous screening or even undergo preventive (prophylactic) mastectomies to decrease her chances of contracting cancer. The decision to get tested is a highly personal one that should be discussed with a doctor who is trained in counseling patients about genetic testing. For more information on genetic testing, see Let the Patient Beware: Implications of Genetic Breast-Cancer Testing, Psychological Issues in Genetic Testing for Breast Cancer, and To Test or Not to Test?  Genetic Counseling Is the Key.


Certain factors which increase a woman’s risk of breast cancer can be altered including taking hormone replacement therapy (long term use of estrogens with progesterone for menopause symptoms slightly increases your risk), taking birth control pills (a very slight increased risk that disappears in women who have stopped them for over 10 years), not breastfeeding, drinking 2 to 5 alcoholic drinks a day, being overweight (especially after menopause), and not exercising. All of these modifiable risk factors are not nearly as important as gender, age, and family history, but they are things that a woman can control that may reduce her chances of developing a breast malignancy. Remember that all risk factors are based on probabilities, and even someone without any risk factors can still get breast cancer. Proper screening and early detection are our best weapons in reducing the mortality associated with this disease. For further information about breast cancer risk factors, see Breast Cancer Risk Assessment Tool,and Risk Factors and Breast Cancer.


HOW CAN I PREVENT BREAST CANCER?


The most important risk factors for the development of breast cancer cannot be controlled by the individual. There are some risk factors that are associated with an increased risk, but there is not a clear cause and effect relationship. In no way can strong recommendations be made like the cause and effect relationship seen with tobacco and lung cancer. There are a few risk factors that may be modified by a woman that potentially could influence the development of breast cancer. If possible, a woman should avoid long-term hormone replacement therapy, have children before age 30, breastfeed, avoid weight gain through exercise and proper diet, and limit alcohol consumption to 1 drink a day or less. For women already at a high risk, their risk of developing breast cancer can be reduced by about 50% by taking a drug called Tamoxifen for five years. Tamoxifen has some common side effects (like hot flashes and vaginal discharge), which are not serious and some uncommon side effects (like blood clots, pulmonary embolus, stroke, and uterine cancer) which are life threatening. Tamoxifen isn’t widely used for prevention, but may be useful in some cases. There are limited data suggesting that vitamin A may protect against breast cancer but further research is needed before it can be recommended for prevention. Other things being investigated include phytoestrogens (naturally occurring estrogens that are in high numbers in soy), vitamin E, vitamin C, and other drugs. Further testing of these substances is also needed before they can be recommended for breast cancer prevention. Right now, the most important thing any woman can do to decrease her risk of dying from breast cancer is to have regular mammogram screening, learn how to perform breast self exams, and have a regular physical examination by their physician. For more  information on breast cancer prevention, see NCI/PDQ Physician Statement: Prevention of breast cancer.


WHAT SCREENING TESTS ARE AVAILABLE?


The earlier that a breast cancer is found, the more likely it is that treatment can be curable. For this reason, we screen for breast cancer using mammograms, clinical breast exams, and breast self-exams. Screening mammograms are simply x-rays of each breast. The breast is placed between two plates for a few seconds while the x-rays are taken. If something  appears abnormal, or better views are needed, magnified views or specially angled films are taken during the mammogram. Mammograms often detect tumors before they can be felt and they can also identify tiny specks of calcium that could be an early sign of cancer. Regular screening mammograms can decrease the mortality of breast cancer by 30%. The majority of breast cancers are associated with abnormal mammographic findings. Woman should get a yearly mammogram starting at age 40 (although some groups recommend starting at 50), and women with a genetic mutation that increases their risk or a strong family history may want to begin even earlier.


Between the ages of 20 and 39, every woman should have a clinical breast exam every 3 years; and after age 40 every woman should have a clinical breast exam done each year. A clinical breast exam is an exam done by a health professional to feel for lumps and look for changes in the size or shape of your breasts. During the clinical breast exam, you can learn how to do a breast self-exam. Every woman should do a self breast exam once a month, about a week after her period ends. If you find any changes in your breasts, you need to contact your doctor. About 15% of tumors are felt but cannot be seen by regular mammographic screening.


There are some experimental screening modalities that are currently being studied. These include MRI, ductal lavage, ultrasound, optical tomography, PET scan, and digital mammograms. For more information on these experimental techniques, see Advanced Breast Imaging, Penn Leads International Study on Breast Cancer Detection, and Komen Foundation Focuses Attention on the Need for Improved Breast Imaging and Early Detection Technologies: OncoLink Talks with President and CEO Susan Braun and Director of Grants Anice Thigpen, PhD


WHAT ARE THE SIGNS OF BREAST CANCER?


Unfortunately, the early stages of breast cancer may not have any symptoms. This is why it is important to follow screening recommendations. As a tumor grows in size, it can produce a variety of symptoms including:


lump or thickening in the breast or underarm
change in size or shape of the breast
nipple discharge or nipple turning inward
redness or scaling of the skin or nipple
ridges or pitting of the breast skin
If you experience these symptoms, it doesn’t necessarily mean you have
breast cancer, but you need to be examined by a doctor.


Breast profile:


A ducts; B lobules; C dilated section of duct to hold milk; D nipple; E fat; F pectoralis major muscle; G chest wall/rib cage


Enlargement:  A – normal duct cells; B – basement membrane; C –lumen (center of duct);


HOW IS BREAST CANCER DIAGNOSED AND STAGED?


Once a patient has symptoms suggestive of a breast cancer or an abnormal screening mammogram, they will usually be referred for a diagnostic mammogram. A diagnostic mammogram is another set of x-rays; however, it is more complete with close ups on the suspicious areas. Sometimes, particularly if your doctors think that you may have a cyst or you are young and have dense breasts, you may be referred for an ultrasound. An ultrasound uses high-frequency sound waves to outline the suspicious areas of the breast. It is painless and can often distinguish between benign and malignant lesions.


Depending on the results of the mammograms and/or ultrasounds, your doctors may recommend that you get a biopsy. A biopsy is the only way to know for sure if you have cancer, because it allows your doctors to get cells that can be examined under a microscope. There are different types of biopsies; they differ on how much tissue is removed. Some biopsies use a very fine  needle, while others use thicker needles or even require a small surgical procedure to remove more tissue. Your team of doctors will decide which type of biopsy you need depending on your particular breast mass.


Once the tissue is removed, a doctor known as a pathologist will review the specimen. The pathologist can tell if it is cancer or not; and if it is cancerous, then the pathologist will characterize it by what type of tissue it arose from, how abnormal it looks (known as the grade), whether or not it is invading surrounding tissues, and if the entire lump was excised, the pathologist can tell if there are any cancer cells left at the borders (also known as the margins). The pathologist will also test the cancer cells for the presence of estrogen and progesterone receptors as well as a receptor  known as HER-2/neu. The presence of estrogen and progesterone receptors is important because cancers that have those receptors can be treated with hormonal therapies. HER-2/neu expression may also help predict outcome. There are also some therapies directed specifically at tumors dependent on the presence of HER-2/nue.


In order to guide treatment and offer some insight into prognosis, breast cancer is staged into five different groups. This staging is done in a limited fashion before surgery taking into account the size of the tumor on mammogram and any evidence of spread to other organs that is picked up with other imaging modalities; and it is done definitively after a surgical procedure that removes lymph nodes and allows a pathologist to examine them for signs of cancer. The staging system is somewhat complex, but here is a simplified version of it:


Stage 0 (called carcinoma in situ)


Lobular carcinoma in situ (LCIS) refers to abnormal cells lining a gland in the breast. This is a risk factor for the future development of cancer, but this is not felt to represent a cancer itself.


Ductal carcinoma in situ (DCIS) refers to abnormal cells lining a duct. Women with DCIS have an increased risk of getting invasive breast cancer in that breast. Treatment options are similar to patients with Stage I breast cancers.


Stage I ? early stage breast cancer where the tumor is less that 2 cm across and hasn’t spread beyond the breast


Stage II – early stage breast cancer where the tumor is either less than 2 cm across and has spread to the lymph nodes under the arm; or the tumor is between 2 and 5 cm (with or without spread to the lymph nodes under the arm); or the tumor is greater than 5 cm and hasn’t spread outside the breast


Stage III ? locally advanced breast cancer where the tumor is greater than 5 cm across and has spread to the lymph nodes under the arm; or the cancer is extensive in the underarm lymph nodes; or the cancer has spread to lymph nodes near the breastbone or to other tissues near the breast


Stage IV ? metastatic breast cancer where the cancer has spread outside the breast to other organs in the body


Depending on the stage of your cancer, your doctor may want additional tests to see if you have metastatic disease. If you have a stage III cancer, you will probably get a chest x-ray, CT scan and bone scan to look for metastases. Each patient is an individual and your doctors will decide what is necessary to adequately stage your cancer.


WHAT ARE THE TREATMENTS FOR BREAST CANCER?


SURGERY


Almost all women with breast cancer will have some type of surgery in the course of their treatment. The purpose of surgery is to remove as much of the cancer as possible, and there are many different ways that the surgery can be carried out. Some women will be candidates for what is called breast conservation therapy (BCT). In BCT, surgeons perform a lumpectomy which means they remove the tumor with a little bit of breast tissue around it but do not remove the entire breast. BCT always needs to be combined with radiation therapy to make it an option for treating breast cancer. At the time of the surgery, the surgeon may also dissect the lymph nodes under the arm so the pathologist can review them for signs of cancer. Some patients will have a sentinel lymph node biopsy procedure first to determine if a formal lymph node dissection is required. Sometimes, the surgeon will remove a larger part (but not the whole breast), and this is called a segmental or partial mastectomy. This needs to be combined with radiation therapy as well. In early stage cancers (like stage I and II), BCT is as effective as  removal of the entire breast via mastectomy. Most patients with DCIS that have a lumpectomy are treated with radiation therapy to prevent the local recurrence of DCIS (although some of these DCIS patients may be candidates for close observation after surgery). The advantage of BCT is that the patient will not need a reconstruction or prosthesis to appear like she did  before the procedure.


More advanced breast cancers are usually treated with a modified radical mastectomy. Modified radical mastectomy means removing the entire breast and dissecting the lymph nodes under the arm. Patients with DCIS that have a mastectomy do not need to have the lymph nodes removed from under the arm. Some patients are candidates for BCT but choose modified radical mastectomy for personal reasons. Your surgeon can discuss your options and the pros and cons of either procedure. Most women who have modified radical mastectomies choose to undergo a reconstruction. There are many different procedures for creating a new breast mound, and you should talk to your plastic surgeon before your surgery to discuss your options and decide on how you would like to proceed. For more information on breast reconstruction, see Breast Reconstructive Surgery Options.


CHEMOTHERAPY


Despite the fact that the tumors are removed by surgery, there is always a risk of recurrence because there may be microscopic cancer cells that have spread to distant sites in the body. In order to decrease a patient’s risk of recurrence, many breast cancer patients are offered chemotherapy.


Chemotherapy is the use of anti-cancer drugs that go throughout the entire body. The higher the stage of cancer you have, the more important it is that you receive chemotherapy; however, even stage I patients may benefit from chemotherapy in certain cases. In early stage patients, the risk of recurrence may be small, and thus the benefits of the chemotherapy are even  smaller. However, the option to receive chemotherapy should be offered to most patients with breast cancer and they can decide if the potential benefits of chemotherapy outweigh its side effects in their own particular case.


There are many different chemotherapy drugs, and they are usually given in combinations for 3 to 6 months after you receive your surgery. Depending on the type of chemotherapy regimen you receive, you may get medication every 3 or 4 weeks; and you may have to go to a clinic to get the chemotherapy because many of the drugs have to be given through a vein. Two of the most common regimens are AC (doxorubicin and cycolphosphamide) for 3 months or CMF (cyclophosphamide, methotrexate, and fluorouracil) for 6 months. There are advantages and disadvantages to each of the different regimens that your medical oncologist will discuss with you. Based on your own health, your personal values and wishes, and side effects you may wish to avoid, you can work with your doctors to come up with the best regimen for your lifestyle.


Sometimes patients have a recurrence of their cancer, or present in stage IV with disease outside of their breast. These patients will all need chemotherapy, and a variety of different agents may be tried until a response is achieved. Sometimes we give chemotherapy before surgery, and this is called neoadjuvant chemotherapy. This is usually reserved for very  advanced cancers that need to be shrunken before they can be operated on.


RADIOTHERAPY


Breast cancer commonly receives radiation therapy. Radiation therapy uses high energy rays (similar to x-rays) to kill cancer cells. It comes from an external source, and it requires patients to come in 5 days a week for up to  6 weeks to a radiation therapy treatment center. The treatment takes just a few minutes, and it is painless. Radiation therapy is used in all patients who receive breast conservation therapy (BCT). It is also recommended for patients after a mastectomy who had large tumors, lymph node involvement, or close/positive margins after the surgery. Radiation is important in reducing the risk of local recurrence and is often offered in more advanced cases to kill tumor cells that may be living in lymph nodes. Your radiation oncologist can answer questions about the utility, process, and side effects of radiation therapy in your particular case.


HORMONAL THERAPY


When the pathologist examines your tumor specimen, he or she finds out if the tumor is expressing estrogen and progesterone receptors. Patients whose tumors express estrogen receptors are candidates for therapy with an estrogen blocking drug called Tamoxifen. Tamoxifen is taken by pill form for 5 years after your surgery. This drug has been shown to drastically reduce your risk of recurrence if your tumor expresses estrogen receptors. However, there are side effects commonly associated with Tamoxifen including weight gain, hot flashes and vaginal discharge that patients may be bothered by. There are also very uncommon side effects like blood clots, strokes, or uterine cancer that may scare patients from choosing to take it. You need to remember that your chances of having a recurrence of your cancer are usually higher than your chances of having a serious problem with Tamoxifen, but the decision to undergo hormonal therapy is a personal one that you should make with your doctor. There are also newer drugs, called aromatase inhibitors that act by decreasing your body’s supply of estrogen; these drugs are reserved for patients who have already gone through menopause. Talk to your doctors about these new therapies.


BIOLOGIC THERAPY


The pathologist also examines your tumor for the presence of HER-2/neu overexpression. HER-2/neu is a receptor that some breast cancers express. If your cancer expresses it, you usually have a higher chance of having your tumor recur after surgery. A compound called Herceptin (or Trastuzumab) is a substance that blocks this receptor and helps stop the breast cancer from growing. Some patients are candidates for this medicine. Talk to your medical oncologist to see if Herceptin is right for you.


FOLLOW-UP TESTING


Once a patient has been treated for breast cancer, they need to be closely followed for a recurrence. At first, you will have follow-up visits every 3-4 months. The longer you are free of disease, the less often you will have to go for checkups. After 5 years, you could see your doctor once a year. You should have a mammogram of the treated and untreated breasts every year.
Because having had breast cancer is a risk factor for getting it again, having your mammograms done every year is extremely important. If you are taking Tamoxifen, it is important that you get a pelvic exam each year and report any abnormal vaginal bleeding to your doctor.


Clinical trials are extremely important in furthering our knowledge of this disease. It is though clinical trials that we know what we do today, and many exciting new therapies are currently being tested. Talk to your doctor about participating in clinical trials in your area.


This article is meant to give you a better understanding of breast cancer. Use this knowledge when meeting with your physician, making treatment decisions, and continuing your search for information.


Source: Abramson Cancer Center of the University of Pennsylvania, USA

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