Breast Cancer

How common is breast cancer?

Breast cancer is the most common non-skin cancer of American women, but it can also occur in men. Every year in the US, there are over 266,000 new diagnoses of breast cancer. A woman has a risk of 1 in 8 for developing breast cancer at some point during her lifetime.

Are there early signs of breast cancer? How do I know if I have breast cancer?

• There usually are no symptoms or signs of early breast cancer, but sometimes a mass or lump in the breast will be present.
• Many early breast cancers are first identified by screening mammography.
• Breast cancer screening is important because the cancers can usually be identified at an early stage, when treatments are likely to be effective and outcomes are better.

What causes breast cancer?

• The exact cause of breast cancer is not fully understood, but we know that the risk of breast cancer increases as we age.
• Other risk factors for breast cancer include a personal or family history of breast cancer and the presence of certain benign conditions in the breast.
• People who have inherited certain genetic mutations (BRCA1, BRCA2) are also at increased risk of getting breast cancer and other cancers.

Breast cancer definition

Breast cancer is a malignant tumor (a collection of cancer cells) arising from the cells of the breast. Although breast cancer predominantly occurs in women, it can also affect men. This article deals with breast cancer in women. Breast cancer and its complications can affect nearly every part of the body.

Breast cancer is rare in men (approximately 2,400 new cases diagnosed per year in the U.S.) but typically has a significantly worse outcome. This is partially related to the often late diagnosis of male breast cancer, when the cancer has already spread.

Symptoms are similar to the symptoms in women, with the most common symptom being a lump or change in skin of the breast tissue or nipple discharge. Although it can occur at any age, male breast cancer usually occurs in men over 60 years of age.

There are many types of breast cancer. Some are more common than others, and there are also combinations of cancers. Some of the most common types of cancer are as follows:

• Ductal carcinoma in situ: The most common type of non-invasive breast cancer is ductal carcinoma in situ (DCIS). This early-stage breast cancer has not spread and therefore usually has a very high cure rate.
• Invasive ductal carcinoma: This cancer starts in the milk ducts of the breast and grows into other parts of the surrounding tissue. It is the most common form of breast cancer. About 80% of invasive breast cancers are invasive ductal carcinoma.
• Invasive lobular carcinoma: This breast cancer starts in the milk-producing glands of the breast. Approximately 10% of invasive breast cancers are invasive lobular carcinoma.
• The remainder of breast cancers are much less common and include the following:
• Mucinous carcinoma are formed from mucus-producing cancer cells. Mixed tumors contain a variety of cell types.
• Medullary carcinoma is an infiltrating breast cancer that presents with well-defined boundaries between the cancerous and noncancerous tissue.
• Inflammatory breast cancer: This cancer makes the skin of the breast appear red and feel warm (giving it the appearance of an infection). These changes are due to the blockage of lymph vessels by cancer cells.
• Triple-negative breast cancers: This is a subtype of invasive cancer with cells that lack estrogen and progesterone receptors and have no excess of a specific protein (HER2) on their surface. It tends to appear more often in younger women and African-American women.
• Paget's disease of the nipple: This cancer starts in the ducts of the breast and spreads to the nipple and the area surrounding the nipple. It usually presents with crusting and redness around the nipple.
• Adenoid cystic carcinoma: These cancers have both glandular and cystic features. They tend not to spread aggressively and have a good prognosis.
• Lobular carcinoma in situ: This is not a cancer but an area of abnormal cell growth. This pre-cancer can increase the risk of invasive breast cancer later in life.

The following are other uncommon types of breast cancer:

• Papillary carcinoma
• Phyllodes tumor
• Angiosarcoma
• Tubular carcinoma

There are many risk factors that increase the chance of developing breast cancer. Although we know some of these risk factors, we don't know the cause of breast cancer or how these factors cause the development of a cancer cell.

We know that normal breast cells become cancerous because of mutations in the DNA, and although some of these are inherited, most DNA changes related to breast cells are acquired during one's life.

Proto-oncogenes help cells grow. If these cells mutate, they can increase growth of cells without any control. Such mutations are referred to as oncogenes. Such uncontrolled cell growth can lead to cancer.

Some of the breast cancer risk factors can be modified (such as alcohol consumption) while others cannot be influenced (such as age). It is important to discuss these risks with a health care provider when starting new therapies (for example, postmenopausal hormone therapy).

Several risk factors are inconclusive (such as deodorants), while in other areas, the risk is being even more clearly defined (such as alcohol use).

The following are risk factors for breast cancer:

• Age: The chances of breast cancer increase as one gets older.
• Family history: The risk of breast cancer is higher among women who have relatives with the disease. Having a close relative with the disease (sister, mother, daughter) doubles a woman's risk.
• Personal history: Having a breast cancer diagnosis in one breast increases the risk of cancer in the other breast or the chance of an additional cancer in the original breast.
• Women diagnosed with certain benign (non-cancerous) breast conditions have an increased risk of breast cancer. These include atypical hyperplasia, a condition in which there is abnormal proliferation of breast cells but no cancer has developed.
• Menstruation: Women who started their menstrual cycle at a younger age (before 12) or went through menopause later (after 55) have a slightly increased risk.
• Breast tissue: Women with dense breast tissue (as documented by mammogram) have a higher risk of breast cancer.
• Race: White women have a higher risk of developing breast cancer, but African-American women tend to have more tumors that are aggressive when they do develop breast cancer.
• Exposure to previous chest radiation or use of diethylstilbestrol increases the risk of breast cancer.
• Having no children or the first child after age 30 increases the risk of breast cancer.
• Breastfeeding for one and a half to two years might slightly lower the risk of breast cancer.
• Being overweight or obese increases the risk of breast cancer both in pre- and postmenopausal women but at different rates.
• Use of oral contraceptives in the last 10 years increases the risk of breast cancer slightly.
• Using combined hormone therapy after menopause increases the risk of breast cancer.
• Alcohol consumption increases the risk of breast cancer, and this seems to be proportional to the amount of alcohol used. A recent meta-analysis reviewing the research on alcohol use and breast cancer concluded that all levels of alcohol use are associated with an increased risk for breast cancer. This includes even light drinking.
• Exercise seems to lower the risk of breast cancer.
• Genetic risk factors: The most common causes are mutations in the BRCA1 and BRCA2 genes (breast cancer and ovarian cancer genes). Inheriting a mutated gene from a parent means that one has a significantly higher risk of developing breast cancer.

Research has shown that parabens (a preservative used in deodorants) can build up in breast tissues. However, this study did not show that parabens cause breast cancer or find a link between parabens (which many other products contain) and deodorant use.

A 2002 study did not show any increased risk for breast cancer in women using an underarm deodorant or antiperspirant. A 2003 study showed an earlier age for breast cancer diagnosis in women who shaved their underarms more frequently and used underarm deodorants.

We need more research to give us the answer about a relationship between breast cancer and underarm deodorants and blade shaving.

Yes. There are surely other questions you will wish to ask. Do not hesitate to be very open about your concerns with your doctor. There is constantly new information and new research available about breast cancer, whether BRCA-related new treatments or drugs (for example, olaparib [Lynparza]) or new treatment regiments and recommendations. The foregoing questions and comments should demonstrate that the diagnosis and treatment of breast cancer may not be a simple process. Even when all the information is available, there may be difficulties in deciding a proper course of action. However, this decision-making process has a better chance of success when you and the doctor are well informed and communicating effectively. Although the information here cannot be all-inclusive, we hope it will help you work through this process.

Although the above signs and symptoms can diagnose breast cancer, the use of screening mammography has made it possible to detect many of the cancers early before they cause any symptoms.

The American Cancer Society (ACS) has the following recommendations for breast cancer screenings:

Women should have the choice to begin annual screening between 40-44 years of age. Women age 45 and older should have a screening mammogram every year until age 54. Women 55 years of age and older should have biennial screening or have the opportunity to continue screening annually. Women should continue screening mammography as long as their overall health is good and they have a life expectancy of 10 years or longer.

Mammograms are a very good tool for breast cancer screening. As with any test, mammograms have limitations and will miss some cancers. Patients should discuss their family history and mammogram and breast exam results with their health care provider.

The ACS does not recommend clinical screening exams in women of any age.

Women at high risk (greater than 20% lifetime risk) should get an MRI and a mammogram every year. Women at moderate risk (15%-20%) should talk to their doctor about the benefits and limitations of adding MRI screening to their yearly mammogram.

For about 20% of women with breast cancer, the cancer cells test positive for HER2. HER2 is a growth-promoting protein located on the surface of some cancer cells. HER2-positive breast cancers tend to grow more rapidly and spread more aggressively.

All patients with invasive breast cancer should have their tumor cells tested for HER2.

There are four tests for HER2. Discuss the interpretation of the tests with your health care team. Health care professionals may use either immunohistochemistry (IHC) to identify the HER2 protein or in-situ hybridization (ISH) testing to look for the gene.

IHC test: This tests shows if there is too much HER2 protein in the cancer cells and is graded 0 to 3.

FISH test: This test evaluates if there are too many copies of the HER2 gene in the cancer cells. This test is either positive or negative.

SPoT-Light HER2 CISH test: This test also evaluates if there are too many copies of the HER2 gene in the cancer cells and is reported as positive or negative.

Inform HER2 Dual ISH test: This test also evaluates if there are too many copies of the HER2 gene in the cancer cells and is reported as positive or negative.

The signs and symptoms for HER2-positive breast cancers are the same as for HER2-negative breast cancers, except for the fact that HER2-positive cancers grow faster and are more likely to spread.

Your health care team needs to evaluate all therapy and provide guidance in response to all test results available and the specific circumstances of your cancer.

There are targeted therapies for HER2-positive breast cancers; a number of drugs are available to target this protein:

• Trastuzumab (Herceptin): a monoclonal antibody given by itself or with chemotherapy to treat HER2-positive breast cancers
• Pertuzumab (Perjeta): another monoclonal antibody that targets HER2-positive cancers
• Ado-trastuzumab emtansine or TDM-1 (Kadcyla): a monoclonal antibody that is attached to a chemotherapy drug
• Lapatinib (Tykerb): a kinase inhibitor usually used in adjunct with chemotherapy or hormone therapy

Staging is the process of determining the extent of the cancer and its spread in the body. Together with the type of cancer, staging is used to determine the appropriate therapy and to predict chances for survival.

To determine if the cancer has spread, several different imaging techniques can be used.

• Chest X-ray: It looks for spread of the cancer to the lung.
• Mammograms: More detailed and additional mammograms provide more images of the breast and may locate other abnormalities.
• MRI: Health care professionals use an MRI to further evaluate the breast or examine other parts of the body.
• Computerized tomography (CT scan): These specialized X-rays look at different parts of your body to determine if the breast cancer has spread. It could include a CT of the brain, lungs, or any other area of concern.
• Bone scan: A bone scan determines if the cancer has spread (metastasized) to the bones. Low-level radioactive material is injected into the bloodstream, and over a few hours, images are taken to determine if there is uptake in certain bone areas, indicating metastasis.
• Positron emission tomography (PET scan): Medical professionals inject a radioactive material that rapidly growing cells (such as cancer cells) absorb preferentially. The PET scanner then locates these areas in your body.

Staging system

A health care team uses this system to summarize in a standard way the extent and spread of the cancer. They use this staging to determine the treatment most appropriate for the type of cancer.

The most widely used system in the U.S. is the American Joint Committee on Cancer TNM system. Medical professionals developed a new eighth edition of this staging system for 2018 that includes results of testing for certain biomarkers, including the HER2 protein and the results of gene expression assays, in addition to the factors (TNM) described below.

Besides the information gained from the imaging tests, this system also uses the results from surgical procedures. After surgery, a pathologist looks at the cells from the breast cancer as well as from the lymph nodes. This information gained is incorporated into the staging, as it tends to be more accurate than the physical exam and X-ray findings alone.

TNM staging. This system uses letters and numbers to describe certain tumor characteristics in a uniform manner. This allows health care providers to stage the cancer (which helps determine the most appropriate therapy) and aids communication among health care providers.

T: This describes the size of the tumor. A number from 0 to 4 follows. Higher numbers indicate a larger tumor or greater spread:

• TX: Primary tumor cannot be assessed
• T0: No evidence of primary tumor
• Tis: Carcinoma in situ
• T1: Tumor is 2 cm or less across
• T2: Tumor is 2 cm-5 cm
• T3: Tumor is more than 5 cm
• T4: Tumor of any size growing into the chest wall or skin

N: This describes the spread to lymph node near the breast. A number from 0 to 3 follows.

• NX: Nearby lymph nodes cannot be assessed (for example if they have previously been removed).
• N0: There has been no spread to nearby lymph nodes. In addition to the numbers, this part of the staging is modified by the designation "i+" if the cancer cells are only seen by immunohistochemistry (a special stain) and "mol+" if the cancer could only be found using PCR (special detection technique to detect cancer at the molecular level).
• N1: Cancer spreads to one to three axillary lymph nodes (underarm lymph nodes) or medical professionals find tiny amounts of cancer in internal mammary lymph nodes (lymph nodes near breastbone).
• N2: Cancer has spread to four to nine axillary lymph nodes or the cancer has enlarged the internal mammary lymph nodes.
• N3: Any of the conditions below
  • Cancer has spread to 10 or more axillary lymph nodes with at least one cancer spread larger than 2 mm.
  • Cancer has spread to lymph nodes under the clavicle with at least area of cancer spread greater than 2 mm.

M: This letter is followed by a 0 or 1, indicating whether the cancer has spread to other organs.

• MX: Medical professionals cannot assess metastasis.
• M0: Health care providers find no distant spread on imaging procedures or by physical exam.
• M1: Spread to other organs is present.

Once the T, N, and M categories have been determined, physicians combine them into staging groups. There are five major staging groups, stage 0 to stage IV, which are subdivided into A and B, or A and B and C, depending on the underlying cancer and the T, N, and M scale.

Cancers with similar stages often require similar treatments.

Patients with breast cancer have many treatment options. Doctors adjust most treatments specifically to the type of cancer and the staging group. Treatment options undergo frequent adjustments, and your health care provider will have the information on the current standard of care available. Discusss treatment options with a health care team. The following are the basic treatment modalities used in the treatment of breast cancer.

Surgery

Many women with breast cancer will require surgery. Broadly, the surgical therapies for breast cancer include breast-conserving surgery and mastectomy.

Breast-conserving surgery

This surgery will only remove part of the breast (sometimes referred to as partial mastectomy). The size and location of the tumor determine the extent of the surgery.

In a lumpectomy, surgeons only remove the breast lump and some surrounding tissue. Medical professionals inspect the surrounding tissue (surgical margins) for cancer cells. If no cancer cells are found, doctors call this "negative" or "clear margins." Frequently, patients receive radiation therapy after lumpectomies.

Mastectomy

During a mastectomy (sometimes also referred to as a simple mastectomy), all the breast tissue is removed. If immediate reconstruction is considered, surgeons sometimes perform a skin-sparing mastectomy. In this surgery, surgeons remove all the breast tissue, as well, but preserve the overlying skin. A nipple-sparing mastectomy keeps the skin of the breast, as well as the areola and nipple.

Radical mastectomy

During this surgery, the surgeon removes the axillary lymph nodes as well as the chest wall muscle in addition to the breast. Physicians perform this procedure much less frequently than in the past, as in most cases, a modified radical mastectomy is as effective.

Modified radical mastectomy

This surgery removes the axillary lymph nodes in addition to the breast tissue. Depending on the stage of the cancer, a health care team might give someone a choice between a lumpectomy and a mastectomy. Lumpectomy allows sparing of the breast but usually requires radiation therapy afterward. If lumpectomy is indicated, long-term follow-up shows no advantage of a mastectomy over the lumpectomy.

Preventive surgery

For a small group of patients who have a very high risk of breast cancer, surgery to remove the breasts may be an option. Although this reduces the risk significantly, a small chance of developing cancer remains.

Double mastectomy is a surgical option to prevent breast cancer. This prophylactic (preventive) surgery can decrease the risk of breast cancer by about 90% for women at moderate to high risk for breast cancer.

Discuss such an approach with a health care team.

The discussion about whether to undergo any preventive surgery should include

• genetic testing for BRCA1 or BRCA2 gene mutations,
• full review of risk factors,
• family history of cancer and specifically breast cancer, and
• other preventive options such as medications.

Radiation therapy

Radiation therapy destroys cancer cells with high-energy rays. There are two ways to administer radiation therapy.

External beam radiation

This is the usual way health care providers administer radiation therapy for breast cancer. An external machine beam of radiation focuses onto the affected area. A health care team determines the extent of the treatment and is based on the surgical procedure performed and whether lymph nodes were affected or not.

The local area will usually be marked after the radiation team has determined the exact location for the treatments. Usually, the patient receives the treatment five days a week for five to six weeks.

Brachytherapy

This form of delivering radiation uses radioactive seeds or pellets. Instead of a beam from the outside delivering the radiation, these seeds are implanted into the breast next to the cancer.

Chemotherapy

Chemotherapy is treatment of cancers with medications that travel through the bloodstream to the cancer cells. These medications are given either by intravenous injection or by mouth.

Chemotherapy can have different indications and may be performed in different settings as follows:

• Adjuvant chemotherapy: If surgery has removed all the visible cancer, there is still the possibility that cancer cells have broken off or stay behind. If health care providers administer chemotherapy to assure that these small amounts of cells are killed as well, it is called adjunct chemotherapy. Medical professionals don't administer chemotherapy in all cases, since some women have a very low risk of recurrence even without chemotherapy, depending upon the tumor type and characteristics.
• Neoadjuvant chemotherapy: If health care professionals administer chemotherapy before surgery, it is referred to as neoadjuvant chemotherapy. Although there seems to be no advantage to long-term survival whether the therapy is given before or after surgery, there are advantages to see if the cancer responds to the therapy and by shrinking the cancer before surgical removal.
• Chemotherapy for advanced cancer: If the cancer has metastasized to distant sites in the body, chemotherapy can be used for treatment. With cases of metastatic breast cancer, the health care team will need to determine the most appropriate length of treatment.

There are many different chemotherapeutic agents that are either given alone or in combination. Usually, these drugs are given in cycles with certain treatment intervals followed by a rest period. The cycle length and rest intervals differ from drug to drug.

Hormone therapy

This therapy is often used to help reduce the risk of cancer reoccurrence after surgery, but it can also be used as adjunct treatment.

Estrogen (a hormone produced by the ovaries) promotes the growth of a few breast cancers, specifically those containing receptors for estrogen (ER positive) or progesterone (PR positive). The following drugs are examples of those health care providers use in hormone therapy:

• Tamoxifen (Nolvadex): This drug prevents estrogen from binding to estrogen receptors on breast cells.
• Toremifene (Fareston) works similar to Tamoxifen and is only indicated in metastatic breast cancer.
• Fulvestrant (Faslodex): This drug eliminates the estrogen receptor and can be used even if tamoxifen is no longer useful.
• Aromatase inhibitors: They stop estrogen production in postmenopausal women. Examples are letrozole (Femara), anastrozole (Arimidex), and exemestane (Aromasin).

BRCA-mutated breast cancer therapy

Early in 2018, the U.S. FDA approved olaparib (Lynparza) for treatment of metastatic breast cancer for patients who carry the BRCA mutation. Olaparib has already been used in ovarian cancer. The drug acts as an inhibitor of the enzyme PARP (known as a PARP-inhibitor drug), which is involved in the repair of damaged DNA. Blocking this enzyme may make it less likely to repair cancerous cells, leading to a slowdown or even stoppage of tumor growth.

Two other PARP inhibitors are approved for treating ovarian cancer but do not currently have approval in breast cancer (rucaparib [Rubraca], niraparib [Zejula]).

Targeted therapy

As we are learning more about gene changes and their involvement in causing cancer, drugs are being developed that specifically target the cancer cells. They tend to have fewer side effects than chemotherapy (as they target only the cancer cells) but usually are still used in adjunct with chemotherapy.

Alternative treatments

Whenever a disease has the potential for much harm and death, physicians search for alternative treatments. As a patient or the loved one of a patient, there may be an inclination to try everything and leave no option unexplored. The danger in this approach is usually found in the fact that the patient might not avail themselves of existing, proven therapies. One should discuss any interest in alternative treatments with a health care team and together explore the different options.

Survival rates are a way for health care professionals to discuss the prognosis and outlook of a cancer diagnosis with their patients. The number most frequently discussed is five-year survival. It is the percentage of patients who live at least five years after they are diagnosed with cancer. Many of these patients live much longer, and some patients die earlier from causes other than breast cancer. With a constant change in therapies, these numbers also change. The current five-year survival statistic is based on patients who were diagnosed at least five years ago and may have received different therapies than are available today. As with all statistics, although the numbers define outcomes for the group, any individual's outcome has the potential for a wide range of variation.

All of this needs to be taken into consideration when interpreting these numbers for oneself.

Below are the statistics from the National Cancer Institute's SEER database.

These statistics are for all patients diagnosed and reported. Several recent studies have looked at different racial survival statistics and have found a higher mortality (death rate) in African-American women compared to white women in the same geographic area.

There is no guaranteed way to prevent breast cancer. Reviewing the risk factors and modifying the ones that can be altered (increase exercise, keep a good body weight, etc.) can help in decreasing the risk.

Following the American Cancer Society's guidelines for early detection can help early detection and treatment.

There are some subgroups of women that should consider additional preventive measures.

Women with a strong family history of breast cancer should be evaluated by genetic testing. This should be discussed with a health care provider and be preceded by a meeting with a genetic counselor who can explain what the testing can and cannot tell and then help interpret the results after testing.

Chemoprevention is the use of medications to reduce the risk of cancer. The two currently approved drugs for chemoprevention of breast cancer are tamoxifen (a medication that blocks estrogen effects on the breast tissue) and raloxifene (Evista), which also blocks the effect of estrogen on breast tissues. Their side effects and whether these medications are right for an individual need to be discussed with a health care provider.

Aromatase inhibitors are medications that block the production of small amounts of estrogen usually produced in postmenopausal women. They are being used to prevent reoccurrence of breast cancer but are not approved at this time for breast cancer chemoprevention.

For a small group of patients who have a very high risk of breast cancer, surgery to remove the breasts may be an option. Although this reduces the risk significantly, a small chance of developing cancer remains.

Without research and clinical trials, there would be no progress in our treatment of cancers.

Research can take many forms, including research directly on cancer cells or using animals.

Research that a patient can be involved in is referred to as a clinical trial. In clinical trials, different treatment regimens are compared for side effects and outcomes, including long-term survival. Clinical trials are designed to find out whether new approaches are safe and effective.

Whether one should participate in a clinical trial is a personal decision and should be based upon a full understanding of the advantages and disadvantages of the trial. One should discuss the trial with a health care team and ask how this trial might be different from the treatment one would usually receive.

Someone should never be forced to participate in a clinical trial or be involved in a trial without full understanding of the trial and a written and signed consent.

If you have received a positive or possible diagnosis of breast cancer, there are a number of questions that you can ask your doctor. The answers you receive to these questions should give you a better understanding of your specific diagnosis and the corresponding treatment. It is usually helpful to write your questions down before you meet with your health care provider. This gives you the opportunity to ask all your questions in an organized fashion.

There is much information available online about breast cancer. The reader should make sure to look at reliable and nationally known resources and verify all information with their health care team.

Each question is followed by a brief explanation as to why that particular question is important. We will not attempt to answer these questions in detail here because each individual case is just that, individual. This outline is designed to provide a framework to help you and your family make certain that most of the important questions in breast cancer diagnosis and treatment have been addressed. As cancer treatments are constantly evolving, specific recommendations and treatments might change and you should always confer with your treatment team regarding any questions. You obviously should add your own questions and concerns to these when you have a discussion with your doctor.

Certain types of cancer are relatively easy to identify by standard microscopic evaluation of the tissue. This is generally true for the most common types of breast cancer. This obviously implies that you have had a biopsy (removal of some tissue at the possible cancer site) that was then reviewed by a pathologist.

However, as the search for earlier and rarer forms of breast cancer progresses, it can be difficult to be certain that a particular group of cells is malignant (cancerous). At the same time, benign conditions may have cells that are somewhat distorted in appearance or pattern of growth (known as atypical cells or atypical hyperplasia). For this reason, it is important that the pathologist reading the slides of your breast biopsy be experienced in breast pathology. Most pathology groups have multiple pathologists review questionable or troublesome slides. In more difficult cases, the slides will often be sent to recognized specialists with considerable expertise in breast pathology.

The importance of an accurate diagnosis cannot be overstated. It is the precise diagnosis that determines the recommended treatment. Treatment must be specifically tailored to the specific type of breast cancer as well as to the individual patient.

A doctor should be able to give someone a clear description of the type of breast cancer along with the treatment options that are appropriate to one's case.

Unfortunately, there are some patients who may have more than one area of malignancy in the same breast or even an additional malignancy in the other breast. If this does occur, it can greatly change the recommendations for treatment.

Therefore, it is critically important that your doctors carefully investigate beyond the immediate site of the tumor to make certain there are no other areas with possible malignancy.

Sometimes discovering these "secondary" areas requires careful review of your mammograms. It may also require the addition of special views from different angles and specialized examination of your breasts by ultrasound, MRI, or other imaging techniques. Sometimes imaging techniques will be used to evaluate the rest of your body, as well.

A well-coordinated team, which includes input from multiple specialists, is the best way to diagnose and treat breast cancer. Oncologists are physicians who specialize in cancer care and will be involved in your care and will often coordinate your care with your primary care provider. Pathologists (physicians who diagnose tissue obtained during biopsies), radiologists, and surgeons will often be involved in the care, as well. Advice from the entire team must be available during biopsies and any tumor-clearing surgery to ensure the best chance of a favorable outcome for the patient.

How important is the role of the pathologist reading my slides?

The pathologist evaluating the slides made from fine-needle aspiration biopsies, core biopsies, and tissue slides of the breast must have a great deal of experience and special training. It is important that the pathologist reliably determine the presence or absence of cancer and distinguish cancer from other conditions such as hyperplasia with atypia (an overgrowth with unusual-looking but benign cells). The pathologist also orders and interprets special studies (see below) on your cancer tissue to determine the precise characteristics of the cancer cells, such as whether the cancer expresses hormone receptors. These results are used to further specify the type of breast cancer and optimize treatment decisions. The remainder of the treatment will be based on the pathologist's diagnosis.

Have my slides been reviewed by more than one pathologist?

A review by more than one pathologist is optimal. There are many subtleties that can be overlooked when reviewing microscope slides. These can lead to both over-reading (making a false-positive diagnosis) and under-reading (making a false-negative diagnosis). When slides are read a second time by another pathologist followed by a discussion of the conclusions, most diagnostic problems are resolved. This is not a standard procedure at all hospitals.

There are almost always several pathologists available who can review the pathology of your slides (this is termed a "double reading"). The added safeguard of double reading may not be necessary in most cases of breast cancers but can be a critical factor in some cases.

Can I have my biopsy reviewed by a pathologist at another diagnostic center?

It should always be possible to send slides from your biopsy to a pathologist at another diagnostic center. First of all, there should not be a rush to treatment; breast cancer is almost never an emergency. Developing the best treatment plan depends on a good, thorough pathologic evaluation as well as a complete workup of both breasts, as noted above. You should discuss this with your treatment team or primary-care giver as they can help you arrange for this.

Second, good pathologists are never offended by a request for an outside opinion. They also usually know the names of some of the finest breast pathologists in the country and should be willing to arrange a consultation with one of these doctors.

In most cases of breast cancer, it is not necessary to obtain this in-depth consultation. However, if there are any unusual aspects of your case, it can be important in your decision-making process. The matter of obtaining additional consults may take a week or more.

If you have a strong (positive) family history for breast cancer, ovarian cancer, or even prostate cancer, this information is relevant to your diagnosis. A strong family history in this case usually means that a mother, sibling, child, or father has had a related malignancy. Information about other family members (aunts, nieces, etc.) is also important. This is especially significant if the diagnosis of breast cancer was made at an early age or involved both breasts or a breast and an ovary in the same individual. A positive family history may necessitate a more comprehensive diagnostic workup, more involved treatment, and consideration of genetic testing, not only for you but for other family members.

Microscopic evaluation of the slides made from involved tissue provides critical information about the tumor. A reasonably accurate prediction of tumor behavior can be made based on the appearance of the cancer cells, their size and similarity to one another, and the presence or absence of these cells in the lymphatic and blood vessels immediately adjacent to the tumor. This type of evaluation is a standard part of the diagnostic process.

However, there are additional relevant data that the laboratory should obtain, and this analysis is directed by the pathologist at the time of diagnosis. This information includes, at a minimum, an assessment of the estrogen and progesterone receptors on the malignant cells and the status of at least one oncogene, called her-2-neu. An oncogene is a gene that plays a normal role in cell growth but, when altered, may contribute to abnormal cell division and tumor growth.

Currently, these tests (estrogen and progesterone receptors and her-2-neu) have an accurate enough predictive value that their status should be determined in all cases of breast cancer. Test results are available within a few days to a week after removal of the tumor tissue. The results of these tests should then be taken into account in the final decision-making about treatment. These tests are constantly evolving and changing, and your treatment team will be able to discuss the current standard and advanced testing available.

Genomic assays (tests that evaluate gene expression) in the tumor tissue are often performed on certain breast cancers to help determine the likelihood that a tumor will recur (come back) and to help determine whether chemotherapy will be beneficial.

It is extremely rare that a patient must be rushed into treatment. The biology of breast tumors is established fairly early in their development, and by the time the tumors are detectable, most have been growing undetected for considerably more than a year. This means that if you take a few weeks to complete a thorough evaluation, obtain appropriate consultations, understand the situation, discuss the alternatives, and initiate a treatment plan, it is not likely to add any significant risk. This time frame, however, should allow the facts of your case to be carefully sorted out and errors to be minimized. Your treatment team should be able to help you in this process and specifically advise you on the urgency to start certain treatments.

Are there controversies in the recommended treatments among reputable experts?

Doctors may differ in their recommendations if they weigh the risks differently. There will always be uncertainties in any given case. These issues are rarely "right versus wrong." They can be compared with decisions such as, "How do I balance my desire to have the largest and safest care with the need to have convenience and economy?" There are tradeoffs. For example, certain breast-cancer treatment options may favor cosmetic appearance but slightly increase the risk of recurrence in the affected breast. If you have concerns, a second opinion by a different treatment team can often be helpful. A good treatment team will help the patient make informed decisions.

How might my treatment affect future risks and follow-up treatment?

There are often indirect consequences of treatment decisions. For example, breast-conservation therapy achieves, as its goal, treatment of the breast cancer along with preservation of the breast. This is clearly a highly desirable objective. However, in doing so, it leaves the possibility that cancer may recur in that breast. The risk is small but is definitely there. Most of the time, the recurrence will be recognized and the new tumor treated early but not always.

These risks mean that a patient choosing breast-conservation therapy must have the treated side (and the other breast as well) carefully monitored with regular examinations and imaging tests. Occasionally, tissue abnormalities develop that may suggest a new or recurrent cancer, thereby necessitating further evaluation with more tests or even another biopsy. The majority of these abnormalities turn out to be benign, perhaps caused by benign breast disease or changes from the surgery and radiation therapy. But the psychological impact of having to repeat such an evaluation may be very upsetting to some patients. Breast conservation is not appropriate for every breast-cancer patient or breast-cancer type.

There are similar considerations in each treatment plan that have to be understood and carefully evaluated before committing to a particular method of therapy. You should discuss these issues thoroughly with your doctor.

Should genetic testing be part of the treatment decision process?

The majority of breast cancers occur as unconnected (sporadic) cases and are not caused by an inherited genetic abnormality (mutation) passed from parent to child. However, if you have close family members, such as a mother or sister, who have had the disease, especially if it occurred at a young age, then the possibility of a genetic predisposition to develop cancer cells should be investigated. In these situations, genetic testing may provide valuable information. The test results may affect not only recommendations for your therapy but may also have major implications for other family members, as well. Gene testing should only be done after careful genetic counseling so that everyone has a thorough understanding of the potential value and also the limitations of these tests.

The BRCA gene test analyses DNA to look for harmful mutations in two breast cancer genes (BRCA1 or BRCA2). This test is performed as a routine blood test. The test should only be performed on patients who have specific types of breast cancers or have a family history suggesting the possibility of having an inherited mutation. These mutations are uncommon, and inherited BRCA gene mutations are responsible for about 10% of breast cancers.

This should be discussed with your health care provider or treatment team as this information is frequently updated. Guidelines for testing may include

• a personal history of breast cancer diagnosis at a young age, bilateral breast cancer, breast and ovarian cancer diagnosis, or a personal history of ovarian cancer;
• family history of breast cancer at a young age (under 50) or ovarian cancer and a personal history of breast cancer;
• family member with bilateral breast cancer, ovarian cancer, or both breast and ovarian cancer;
• relative with a known BRCA1 or BRCA2 mutation; and
• a male relative with breast cancer.

Breast cells are programmed to respond to certain hormones as signals for growth and multiplication. The most prominent examples of these hormones are estrogens and progesterone. Many breast-cancer cells retain hormone receptors (molecular configurations on the cell surface to which the hormones bind). The hormone receptors, therefore, make the cancer cells responsive to these particular hormones.

In general, taking hormones is not recommended if a diagnosis of breast cancer is under consideration. This does not necessarily mean that you can never resume postmenopausal hormone therapy. This issue is generally reconsidered after the completion of your evaluation and treatment. You should consult with your physician before you stop or start any new medications.

Following completion of your treatment for breast cancer, whether or not tamoxifen (Nolvadex) is prescribed should at least be addressed. In many cases, the primary breast cancer for which the patient is being treated may not be hormone-receptor positive. In these cases, tamoxifen (which binds to the estrogen receptor in place of estrogen) is not generally part of the treatment protocol.

However, the Breast Cancer Prevention Trial (a study of the use of tamoxifen) demonstrated a significant reduction in the development of new cancers in the opposite breast in patients who were treated with tamoxifen. So, the possible use and benefits of tamoxifen should not be ignored. A thoughtful evaluation of all the factors in a particular case will lead to a recommendation which balances the benefits of tamoxifen against the potential risks. Your treatment team should address this issue with you.

Ductal carcinoma in situ (DCIS) sometimes presents a difficult dilemma. Most patients with DCIS can undergo successful breast-conservation therapy but not all. The diagnosis implies that this is an "early" form of cancer in the sense that the cancer cells have not acquired the ability to penetrate normal tissue barriers or spread through the vascular or lymphatic channels to other sites of the body. It is important to realize that breast cancer is a wide spectrum of diseases, and no comparisons should be made just on the basis that someone you know has "breast cancer" and shares a different treatment approach with you.

However, the millions of cells forming the DCIS have accumulated a series of errors in their DNA programs that allow them to grow out of control. There are varying degrees of disturbance, called "grades," of the normal cellular patterns. Low grades are usually more favorable, and high grades are less favorable.

The DCIS cells originate from the inside of the breast gland ducts (microscopic tubes). As they multiply, the cells fill and spread through the normal ducts of the breast glandular tissue. With many DNA errors already in place and millions of these cells exposed to the usual risks of additional DNA damage, a few cells will ultimately become invasive. This invasive change is the real risk of DCIS.

Treatment that does not physically remove all of the DCIS seems to leave some risk of recurrence and, therefore, invasive disease. In cases where the DCIS has spread extensively through the breast ducts, even though the disease is in a sense "early" because it is not yet invasive, it may still require a large surgical resection, at times even a mastectomy (removal of all or part of the breast).

Your treatment team should be able to discuss the pros and cons of the different approaches and actively include you in the decision process.

The classical concept of breast-cancer treatment has been a sequence of tumor-removing surgery followed by chemotherapy and/or radiation therapy. The goal of surgery and radiation therapy is to destroy or remove the primary cancer. Follow-up chemotherapy is designed to eliminate any cancer cells, as yet undetectable, at remote sites.

Recently, there have been new findings suggesting a potential benefit in some patients when chemotherapy is started before surgery. However, initial chemotherapy (neoadjuvant chemotherapy) should be considered primarily in patients with larger tumors and those with strong evidence of lymph-node involvement at the time of initial diagnosis.

If you are enrolled in a clinical trial, the advantages and disadvantages of all protocols should have been explained to you, giving you the opportunity to make an informed decision.

If a mastectomy is necessary, immediate reconstruction offers a great psychological benefit to most women. However, as is often the case in medicine, there are trade-off risks that must be considered. If the reconstruction is done during the same surgery as the mastectomy (immediate reconstruction), the final results of the pathology tests on the removed tumor and tissue is not yet known and will not be known for at least a day or two.

There are sometimes findings on the final pathology report that make chest-wall radiation advisable in order to reduce the risk of local recurrence. If a prosthesis for the breast has been implanted, the radiation treatment will still work, but the radiation may significantly compromise the cosmetic appearance of the prosthesis. There may also be healing problems that delay chemotherapy, potentially increasing the risk of breast-cancer recurrence. These and other factors should be discussed and carefully considered before committing to immediate breast reconstruction.

Lymph nodes are small glandular structures that filter tissue fluids. They filter out and ultimately try to provide an immune response to particles and proteins that appear foreign to them. There are thousands of these nodes scattered in groups throughout the body. Each cluster is more or less responsible for the drainage of a particular region of the body.

The lymph nodes under the arm (axillary nodes) are the dominant drainage recipients from the breast. When cancer cells break free from a breast cancer, they may travel through the lymph tubes (vessels) to the lymph nodes. There, the cancer cells may establish a secondary growth site. The presence of cancer cells in the lymph nodes proves that cancer cells have traveled away from the primary breast tumor. Therefore, the presence or absence of cancer cells in these regional nodes is an important indicator of the future risk of recurrence. This information is often important in making decisions about whether to use chemotherapy and what type of chemotherapy should be employed.

Unfortunately, removal of the lymph nodes also carries a potential risk of lymphedema, a condition that may cause the arm to swell. Lymphedema can occur early after surgery or many years later. It can be a difficult and disabling condition. Here again, there are tradeoffs in risk. When more lymph nodes are removed, more accurate information about tumor spread is obtained and the chance for tumor recurrence is less. But there is a greater incidence of lymphedema.

There are alternatives to standard lymph-node removal (called axillary node dissection). These alternatives should be considered in each patient's situation. They include

1. replacing standard axillary-node removal with sentinel node biopsy (explained below);
2. not doing lymph-node removal in patients who will receive chemotherapy anyway based on other information; and
3. not doing lymph-node removal in patients with very small or "favorable" tumors.

Again, these alternatives must be selectively applied with the benefits and risks carefully evaluated.

A sentinel node biopsy takes advantage of a peculiar physiologic and anatomical finding. Although there may be many lymph nodes in a particular drainage region, it appears that only one or two are the first recipients of the regional fluids.

This means that if any nodes will be involved by tumor spread, the sentinel node will be the first. It also means in general that if the sentinel node is not involved, then no other nodes will be affected. Therefore, only the sentinel node needs to be removed. There are techniques for removing just the sentinel nodes. A sentinel node biopsy allows the pathologist to more intensively study this node and apply specialized techniques that are capable of detecting even a few cancer cells.