Breast Cancer: The Basics ™

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?
Collections of cells that are growing abnormally or without control are called tumors. Tumors that do not have the ability to spread throughout the body may be referred to as “benign” and are not thought of as cancerous. Tumors that have the ability to grow into other tissues or spread to distant parts of the body are referred to as “malignant.” Malignant tumors within the breast are called “breast cancer”. Theoretically, any of the types of tissue in the breast can form a cancer, cancer cells are most likely to develop from either the ducts or the glands. These tumors may be referred to as “invasive ductal carcinoma” (cancer cells developing from ducts), or “invasive lobular carcinoma” (cancer cells developing from lobes).

Sometimes, precancerous cells may be found within breast tissue, and are referred to as ductal carcinoma in-situ (DCIS) or lobular carcinoma in-situ (LCIS). DCIS and LCIS are diseases in which cancerous cells are present within breast tissue, but are not able to spread or invade other tissues. DCIS represents about 20% of all breast cancers. Because DCIS cells may become capable of invading breast tissue, treatment for DCIS is usually recommended. In contrast, treatment is usually not needed for LCIS.

Am I at risk for breast cancer?
Breast cancer is the most common malignancy affecting women in
North America and Europe. 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. Men are also at risk for development of breast cancer, although this risk is much lower than it is for women.

The most important risk factor for development of breast cancer is increasing age. As any woman ages, her risk of breast cancer increases. Risk is also affected by the age when a woman begins menstruating (younger age may increase risk), and her age at her first pregnancy(older age may increase risk). Use of exogenous estrogens, sometimes in the form of hormone replacement treatment (HRT) may increase breast cancer risk, but use of oral contraceptives most likely does not increase risk. Family history is very important in determining breast cancer risk. Any woman with a family history of breast cancer will be at increased risk for developing breast cancer herself. Furthermore, known genetic mutations that increase risk of breast cancer are present in some families; these include mutations in the genes BRCA1 and BRCA2. Between 3% to 10% of breast cancers may be related to changes in one of the BRCA genes. Women can inherit these mutations from their parents.. Genetic testing for mutations should be considered for any woman with a strong family history of breast cancer, especially breast cancers in family members less than 50 years, or strong family history of prostate or ovarian cancer. 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 may choose to undergo more rigorous screening or even undergo preventive (prophylactic) mastectomies to decrease her chances of contracting cancer. The decision to undergo genetic testing 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.

Some factors associated with breast cancer risk can be controlled by a woman herself. Use of hormone replacement therapy (HRT), drinking more than 5 alcoholic drinks/ week, being overweight, and being inactive may all contribute to breast cancer risk. These are called modifiable risk factors.It is important to remember that 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, such as age and family history, cannot be controlled by the individual. Some risk factors may be in a woman’s control; however. These include things like avoiding long-term hormone replacement therapy, having children before age 30, breastfeeding, avoiding weight gain through exercise and proper diet, and limiting alcohol consumption to 1 drink a day or less. For women already at very high risk due to family history, 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. Use of Tamoxifen for prophylactic reasons should be considered carefully by an individual and her doctor, as its use is very individualized. 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 detected, 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 the breasts. Each 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. Many centers are now making use of digital mammograms, which may be more sensitive than conventional mammography.

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 the 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. About 15% of tumors are felt but cannot be seen by regular mammographic screening.

In certain populations of women, MRI screening may be recommended. The American Cancer Society now recommends yearly breast MRI for breast cancer screening for women who carry a known BRCA 1 or 2 mutation, those with a very strong family history of breast or ovarian cancer, and those who have had prior radiation treatment to the chest (for example, radiation as part of treatment for Hodgkin’s Lymphoma). Other populations of women who may or may not benefit from MRI screening are those who have already had breast cancer, those with known lobular carcinoma in-situ (LCIS), and those with very dense breast which may be difficult to visualize on mammograms. Decisions regarding how to screen for breast cancer (with mammograms, MRI, or both) should be made between an individual and her physician, based on her individual breast cancer risk profile.

Other screening modalities that are currently being studied include, ductal lavage, ultrasound, optical tomography, and PET scan. 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

These symptoms do not always signify the presence of breast cancer, but they should always be evaluated immediately by a healthcare professional.

How is breast cancer diagnosed and staged ?
Once a patient has symptoms suggestive of a breast cancer or an abnormal screening mammogram, she will usually be referred for a diagnostic mammogram. A diagnostic mammogram is another set of x-rays with additional angles and close-up views. Often, and ultrasound will be performed during the same session. 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 is the cells are cancerous or not, If the tumor does represent cancer, 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 whether or not the entire lump was removed during surgery. 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. See Understanding Your Pathology Report for more information.

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, and hasn't spread beyond the breast

Stage II : early stage breast cancer in which 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 in which 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 in which 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 (limited surgery with radiation) is as effective as removal of the entire breast via mastectomy. The advantage of BCT is that the patient will not need a reconstruction or prosthesis, but will be able to keep her breast. Some patients with early-stage cancer prefer to have mastectomy, and this is an appropriate option as well..

More advanced breast cancers are usually treated with a modified radical mastectomy. Modified radical mastectomy refers to removal of the entire breast, as well as and dissection of the lymph nodes under the arm. Sometimes, patients who have modified radical mastectomy will require radiation treatment afterwards to decrease the risk of the cancer coming back.

Some patients with DCIS will be candidates for BCT, while others will require modified radical mastectomy because of the size or distribution of DCIS cells. Most patients with DCIS who 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). Patients with DCIS that have a mastectomy do not need to have the lymph nodes removed from under the arm.

Your surgeon can discuss your options and the pros and cons of your needed surgical procedures. Many women who have modified radical mastectomies choose to undergo a reconstruction. A patient who desires reconstruction should try to meet with a plastic surgeon before her mastectomy to discuss reconstruction options. For more information on breast reconstruction, see Breast Reconstructive Surgery Options.

Chemotherapy
Even when tumors are removed by surgery, microscopic cancer cells can 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 to eliminate cancer cells that have broken off from the breast tumor and spread. Many factors go into determining whether an individual patient should have chemotherapy. Generally, patients with higher stage disease need chemotherapy; however, chemotherapy can be beneficial even for patients with early-stage disease. Individual factors such as age, overall health, and biologic properties of a woman’s breast tumor may go into decisions regarding whether or not she should have chemotherapy. 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 2 to 4 weeks. Most chemotherapies used for breast cancer are given through a vein, so need to be given in an oncology clinic. Drugs that are commonly used in breast cancer treatment include adriamycin (doxorubicin), cyclophosphamide, and taxanes. 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.

Generally, chemotherapy is given after surgery for early-stage breast cancer. Sometimes, chemotherapy may be given before surgery to shrink large tumors and allow surgery to be more effective. For patients with stage IV disease, chemotherapy may be given without surgery, and a variety of different agents may be tried until a response is achieved.

Radiotherapy
Breast cancer is often treated with radiation therapy. Radiation therapy refers to use of high energy x-rays to kill cancer cells. Patients having radiation usually need to come to a radiation therapy treatment center 5 days a week for up to 6 weeks to receive treatment. 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 have 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.

Some newer techniques for radiation therapy are being used in certain centers. These are ways to reduce the treatment time needed for radiotherapy, and usually take 1 – 3 weeks instead of 6 weeks, and are called accelerated partial breast irradiation (APBI). These techniques may require a patient to have a radioactive implant placed inside the breast. These techniques are experimental, and are only indicated for early-stage breast cancer patients.

Hormonal Therapy
When the pathologist examines a tumor specimen, he or she may determine that the tumor is expressing estrogen and/ or progesterone receptors. Patients whose tumors express estrogen receptors are candidates for therapy with estrogen blocking drugs. Estrogen-blocking drugs include Tamoxifen and a family of drugs called aromatase inhibitors. These drugs are delivered in pill form for 5 - 10 years after breast cancer surgery. These drugs have been shown to drastically reduce your risk of recurrence if your tumor expresses estrogen receptors. They may be accompanied by side effects, however. When taking Tamoxifen, patients may experience weight gain, hot flashes and vaginal discharge.. Taking Tamoxifen may also increase risk of serious medical issues, such as blood clots, stroke, and uterine cancer. Patients taking aromatase inhibitors may experience bone or joint pain, and are at increased risk for thinning of the bones (osteopenia or osteoporosis). Patients taking aromatase inhibitors should have yearly bone density testing, and may require treatment for bone thinning.

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. A compound called Herceptin (or Trastuzumab) is a substance that blocks this receptor and helps stop the breast cancer from growing. Patients with tumors that express HER-2/neu may benefit from Herceptin, and this should be discussed with a medical oncologist when the treatment plan is decided upon.

Follow-up testing
Once a patient has been treated for breast cancer, she needs 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.

by Christopher Dolinsky, MD and Christine Hill-Kayser, MD
Affiliation: Abramson Cancer Center of the University of Pennsylvania

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