Breast Cancer

Breast cancer facts
♦ Breast cancer is the most common cancer among American women.
♦ One in every eight women in the United States develops breast cancer.
♦ There are many types of breastcancer that differ in their capability of spreading (metastasize) to other body tissues.
♦ The causes of breast cancerare not yet fully known, although a number of risk factors have been identified.

 
♦ There are many different types of breast cancer.
♦ Breast cancer symptoms and signs include
-- a lump in the breast or armpit,
-- bloody nipple discharge,
-- inverted nipple,
-- orange-peel texture or dimpling of the breast's skin,
-- breast pain or sore nipple,
-- swollen lymph nodes in the neck or armpit,
-- change in the size or shape of the breast or nipple.
♦ Breast cancer is diagnosed during a physical exam, by self-examination of the breasts, mammography, ultrasound testing, and biopsy.
♦ Treatment of breast cancer depends on the type of cancer and its stage (0-IV) and may involve surgery, radiation, or chemotherapy.

According to the American Cancer society:
♦ over 200,000 new cases of invasive breast cancer are diagnosed each year in women and over 2,000 in men;
♦ approximately 40,000 women and 400 men died of breast cancer in 2011;
♦ there are over 2.5 million breast cancer survivors in the United States;
♦ although breast cancer survival and awareness has increased significantly in the United States for all races, several studies have cited a significantly worse survival rate for African-American women compared to white women;
♦ guidelines for mammography differ depending on the organization making recommendations. Currently, the American Cancer Society recommends yearly mammograms starting at age 40 for women at average risk for breast cancer.


What is breast cancer?
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.

What are the different types of breast cancer?
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 noninvasive breast cancer is ductal carcinoma in situ (DCIS). This type of cancer has not spread and therefore usually has a very high cure rate.

♦ Invasive ductal carcinoma: This cancer starts in a duct of the breast and grows into 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 glands of the breast that produce milk. 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.


The following are other uncommon types of breast cancer:
♦ Papillary carcinoma
♦ Phyllodes tumor
♦ Angiosarcoma
♦ Tubular carcinoma


What are the statistics on male breast cancer?
Breast cancer is rare in men (approximately 2,000 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.


What causes breast cancer?
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 how these factors cause the development of a cancer cell.


What are breast cancer risk factors?
Some of the breast cancer risk factors can be modified (such as alcohol use) while others cannot be influenced (such as age). It is important to discuss these risks with a health-care provider anytime new therapies are started (for example, postmenopausalhormone therapy).


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 been diagnosed with breast cancer 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 certainbenign 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 theirmenstrual cycle at a younger age (before 12) or went throughmenopause later (after 55) have a slightly increased risk.
♦ Breast tissue: Women with dense breast tissue (as documented bymammogram) 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 aggressive tumors when they do develop breast cancer.
♦ Exposure to previous chest radiationor 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.
♦ Use of oral contraceptives in the last 10 years increases the risk of breast cancer.
♦ Using combined hormone therapy after menopause increases the risk of breast cancer.
♦ Alcohol use increases the risk of breast cancer, and this seems to be proportional to the amount of alcohol used.
♦ Exercise seems to lower the risk of breast cancer.
♦ Genetic risk factors: The most common causes are mutations in theBRCA1 and BRCA2 genes (breast cancer genes). Inheriting a mutated gene from a parent means that one has a significantly higher risk of developing breast cancer.


What are breast cancer symptoms and signs?
The most common sign of breast cancer is a new lump or mass in the breast. In addition, the following are possible signs of breast cancer:

♦ Thickening or lump in the breast that feels different from the surrounding area
♦ Inverting of the nipple (as a change from previous appearance)
♦ Nipple discharge or redness (especially any bloody discharge)
♦ Breast or nipple pain
♦ Swelling of part of the breast or dimpling
♦ Changes in the skin of the breast

One should discuss these or any other concerning findings with a health-care professional.


How do physicians diagnose breast cancer?
Although breast cancer can be diagnosed by the above signs and symptoms, 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 has the following recommendations for breast cancer screenings:

Women age 40 and older should have ascreening mammogram every year and should continue to do so as long as they are in good health.

Mammograms are a very good screening tool for breast cancer. As in any test, mammograms have limitations and will miss some cancers. An individual's family history and mammogram and breast exam results should be discussed with a health-care provider.

Women in their 20s and 30s should have a clinical breast exam (CBE) as part of regular health exams by a health-care professional about every three years for women in their 20s and 30s and every year for women 40 years of age and over.

Clinical breast exams are an important tool to detect changes in the breast and also trigger a discussion with a health-care provider about early detection for cancerand risk factors.

Breast self-exam (BSE) is an option for women starting in their 20s. Women should report any breast changes to their health-care professional.

If a woman wishes to do BSE, the technique should be reviewed with her health-care provider. The goal is to feel comfortable with the way the woman's breast feels and looks and therefore detect changes.

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. 

How are breast cancer stages determined? What are breast cancer survival rates by stage?
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.

Computerized tomography (CT scan): These specialized X-rays are used to 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): A radioactive material is injected that is absorbed preferentially by rapidly growing cells (such as cancer cells). The PET scanner then locates these areas in your body.

Staging system
This system is used by a health-care team to summarize in a standard way the extent and spread of the cancer. This staging can then be used 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 CancerTNM system.

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: describes the size of the tumor. It is followed by a number from 0 to 4. 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: describes the spread to lymph node near the breast. It is followed by a number from 0 to 3.
♦ 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 has spread to one to three axillary lymph nodes (underarm lymph nodes) or tiny amounts of cancer are found 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: Metastasis cannot be assessed.
♦ M0: No distant spread is found on imaging procedures or by physical exam.
♦ M1: Spread to other organs is present.


Once the T, N, and M categories have been determined, they are combined 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.

=> Breast cancer prognosis:
Survival rates are a way for health-care professionals to discuss the prognosis and outlook of a cancer diagnosis with their patients. Patients have to determine if they want to know this number or not and should let their health-care providers know.

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.

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.


Stage               Five-year survival rate
0                              100%
I                               100%
II                               93%
III                             72%
IV                             22%

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.


=> => What is the treatment for breast cancer?
Patients with breast cancer have many treatment options. Most treatments are adjusted specifically to the type of cancer and the staging group. Treatment options should be discussed with a health-care team. The following are the basic treatment modalities used in the treatment of breast cancer.

Surgery
Most women with breast cancer will require surgery. Broadly, the surgical therapies for breast cancer can be divided into breast-conserving surgery and mastectomy.

Breast-conserving surgery
This surgery will only remove part of the breast (sometimes referred to as partial mastectomy). The extent of the surgery is determined by the size and location of the tumor.

In a lumpectomy, only the breast lumpand some surrounding tissue is removed. The surrounding tissue (margins) are inspected for cancer cells. If no cancer cells are found, this is called "negative" or "clear margins." Frequently, radiation therapy is given 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, a skin-sparing mastectomy is sometimes performed. In this surgery, all the breast tissue is removed as well but the overlying skin is preserved.

Radical mastectomy
During this surgery, the surgeon removes the axillary lymph nodes as well as the chest wall muscle in addition to the breast. This procedure is done 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.

Such an approach should be carefully discussed 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,
♦ 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 radiation therapy is given for breast cancer. A beam of radiation is focused onto the affected area by an external machine. The extent of the treatment is determined by a health-care team 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 treatment is given 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 are left behind. If chemotherapy is given to assure that these small amounts of cells are killed as well, it is called adjunct chemotherapy.

Neoadjuvant chemotherapy: If chemotherapy is given 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. In this case, 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 used 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).

=> 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 then chemotherapy (as they target only the cancer cells) but usually are still used in adjunct with chemotherapy.

=> Targeting HER2/Neu protein
Monoclonal antibody: Trastuzumab is an engineered protein that attaches to the HER2/Neu protein on breast cancer cells. It helps slow the growth of the cancer cell and may also stimulate the immune system to attack the cancer cell more effectively.

It is given IV either once a week or every three weeks. The following are other examples of drugs targeting HER2 cells.
♦ Pertuzumab (Perjeta)
♦ Lapatinib (Tykerb)
♦ Ado-trastuzumab (Kadcyla): A combination drug of a HER2 targeting drug that releases a cell-killing drug once attached to the cancer cells.

Each one of these drugs has very specific indication and uses depending on other therapies already in progress.

=> 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.

=> Is it possible to prevent breast cancer?
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) andraloxifene (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.


=> What research is being done on breast cancer? Is it worthwhile to participate in a clinical trial?

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.


=> I may have breast cancer, what questions should I ask my doctor?
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.

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.


=> Is the doctor sure I have breast cancer?
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 which 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 good 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.


=> What type of breast cancer do I have?
Breast cancer is not a single disease. There are many types of breast cancer, and they may have vastly different implications. Breast cancers range from localized cancers such as ductal carcinoma in situ (DCIS) to invasive cancers that can rapidly spread (metastasize). In the middle of the spectrum are breast cancers, such as colloid carcinomas and papillary carcinomas, which have a much more favorable outlook (prognosis) than the other more typically invasive breast cancers. Sometimes, noninvasive DCIS is found around invasive breast cancers.

The treatment team should be able to explain what type of cancer you have, how they determined this, and the treatment they recommend.


=> What difference does a precise diagnosis make?
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.


=> What has been done to exclude cancer in other areas of the same breast or in my other breast?
Unfortunately, there are some patients who may have more than one area ofmalignancy 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.


=> What type of medical team do I need for the most accurate diagnosis?
A well-coordinated team, which includes input from the pathologist, surgeon, and radiologist, is usually the best way to approach treatment decisions. 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.

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.


=> Is my family history relevant to my breast cancer diagnosis?
If you have a strong (positive) family history for breast cancer, ovarian cancer, or evenprostate 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.


=> What other studies should be done on my breast tissue biopsy?
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 which 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.


=> How urgent is it that I make decisions and begin treatment?
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.


=> 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 which 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.


=> Should I stop taking hormone replacement therapy (HRT)?
Breast cells are programmed to respond to certain hormones as signals for growth and multiplication. The most prominent examples of these hormones are estrogensand 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 hormone replacement 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.


=> Even though my breast tumor does not have hormone receptors, should I take tamoxifen to reduce the risk of a new tumor?
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 PreventionTrial (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.


=> I have a ductal carcinoma in situ (DCIS), a type of localized cancer. Why have I been advised to have a mastectomy when other women with invasive cancer have lumpectomies?
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 which 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 which does not physically remove all of the DCIS seems to leave some risk of recurrence and, therefore, invasive disease. This risk of recurrence is particularly increased in the high-grade form of DCIS. 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.


=> Should I start chemotherapy before surgery?
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 I am advised to have a mastectomy, what are the risks and benefits of immediate breast reconstruction?
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 which 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 which 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 which 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.


=> => Treatment of Breast Cancer by Stages

What is breast cancer staging?
The stage of a cancer refers to the extent to which it has spread within the body at the time of diagnosis. Staging of cancers is typically done using a variety of tests and imaging studies to look for the extent of the cancer. To accurately determine the stage of atumor, doctors look at the size of the tumor, the degree to which it has spread to nearby tissues, and the degree to which it has spread via the bloodstream to other organs or via the lymphatic vessels to the lymph nodes.


Breast cancer stages are divided into four broad groups: I, II, III, and IV. Within each of these four groups are several different subgroups. Ductalcarcinoma in situ (DCIS) is a regarded as a very early form of breast cancer in which the abnormal cells have not begun to invade outside of the breast ducts; DCIS is sometimes referred to as stage 0 cancer. This article will focus on the treatment of invasive breast cancer in stages I-IV.


=> What is the treatment for stage I breast cancer?
Stage I breast cancers are small and have not spread to the lymph nodes or have spread to the lymph nodes only in a tiny area.

Surgery is the standard treatment for early stage breast cancers. Both breast-conserving surgery (BCS; also referred to as lumpectomy or partialmastectomy) or mastectomy may be performed, depending upon many factors, including both location of the tumor and patient preference. The lymph nodes will also be evaluated to make certain there is no spread to these areas. This can be done by either a sentinel lymph node biopsy(looking at the lymph node most likely to be the site of tumor spread) or an axillary lymph node dissection. Breast reconstruction surgery can be done either at the same time as the cancer surgery or later on.

When BCS is performed, it is most commonly followed by radiation therapy to help reduce the risk of the cancer coming back (recurring). In women over 70 years of age who have small tumors that have not spread to the lymph nodes, radiation therapy may not always be given if the tumor has been shown to express hormone receptors and hormone therapy is given.

Any additional therapy depends upon the characteristics of the tumor. If the tumor expresses hormone receptors (estrogen, progesterone), it is said to be hormone-sensitive or hormone receptor-positive. This means that hormones stimulate growth of the cancer cells, and hormone therapy is recommended. The goal of hormone therapy is to block the body's ability to make hormones or to interfere with the activity of hormones.

Two different kinds of hormone therapy may be given. Tamoxifen(Nolvadex) is a commonly used drug of the selective estrogen receptor modulator (SERM) class. These drugs bind to estrogen receptors, preventing estrogen from binding. Tamoxifen is typically prescribed for premenopausal women (and men) who have estrogen receptor-positive breast cancer. Tamoxifen therapy is given for five to 10 years. Another drug class used for breast cancer hormone therapy is the aromataseinhibitors (AI). Women who are postmenopausal will usually receiveadjuvant hormone therapy with an aromatase inhibitor, likeanastrozole (Arimidex), letrozole (Femara), or exemestane (Aromasin). Women who become postmenopausal during tamoxifen treatment may be switched to an aromatase inhibitor. Because women may stop having periods on tamoxifen, blood tests to measure hormone levels are often needed to determine whether menopause has occurred. Another option for premenopausal women, instead of tamoxifen, is taking a medication to suppress activity of the ovaries along with an AI. Bisphosphonates are a drug class that can help reduce bone loss and fractures as well as improve survival in women taking AIs for breast cancer.

Hormone therapy is one type of adjuvant therapy (therapy that is given for the cancer after surgery). Chemotherapy is another type of adjuvant therapy. For early stage breast cancers, including stage I tumors,chemotherapy is sometimes recommended. Chemotherapy is usually recommended if the tumor is hormone receptor-negative or is HER2-positive (see below). Chemotherapy may also be recommended for an estrogen-receptor-positive tumor is the tumor is large or has an unfavorable result on a genomic profiling assay such as the Oncotype DX Breast Cancer Assay. Chemotherapy is usually given for a period of three to six months depending upon the exact regimen selected.

Tumors that overexpress the HER2 (human epidermal growth factor receptor 2) receptor are generally treated with adjuvant HER2-targeted therapy. HER2 is a normal protein that helps normal breast cells grow and divide. However, in certain breast cancers, there are too many copies of the HER2 gene, leading to overexpression of the protein and uncontrolled cell growth. These are called HER2-positive cancers. Trastuzumab (Herceptin) is an example of an anti-HER2 drug that binds to the HER2 receptors and blocks their reception of growth signals.


=> What is the treatment for stage II breast cancer?
Stage II breast cancer is also considered to be early stage breast cancer. Stage II cancers are larger than stage I tumors or have spread to a few nearby lymph nodes.

Surgery is also indicated to remove stage II breast cancers. Both breast-conserving surgery and mastectomy may be considered, depending on the size and location of the tumor and patient preferences. As with stage I tumors, lymph node status (whether or not the cancer has spread to lymph nodes) will be assessed. Women who received BCS or had larger tumor (over 5 cm) are typically given radiation therapyas well.

Women with larger stage II tumors may be considered for neoadjuvant therapy. Unlike adjuvant therapies, which are given after surgery, neoadjuvant therapies are given before surgery. Hormone therapy, chemotherapy, and HER2-targeted therapies can all be given as neoadjuvant therapy. Typically, the reason that neoadjuvant therapy is given is to shrink the tumor prior to surgery so that less extensive surgery can be performed. Neoadjuvant therapies can shrink tumors, but they do not improve overall survival rates when compared to giving the therapies after surgery. Hormone therapy started as neoadjuvant therapy should be continued after surgery.

Types of adjuvant therapy for stage II breast cancer include hormone therapy, chemotherapy, and HER2-targeted therapy. The same considerations apply for choosing the appropriate adjuvant therapy as outlined above under stage I tumors. Sometimes more than one adjuvant therapy is recommended, such as a combination of hormone therapy and chemotherapy, or a combination of chemotherapy and HER2-targeted therapy. Other drugs that may be used for HER2-positive breast cancers include pertuzumab (Perjeta) and lapatinib (Tykerb).


=> What is the treatment for stage III breast cancer?
Stage III breast cancers are larger (5 cm across or more), have spread into local tissues like the skin or muscle, or have spread to many nearby lymph nodes.

Often, stage III breast cancers are treated with some kind of neoadjuvant therapy to shrink the tumors prior to surgery. If the tumor size can be significantly reduced, BCS may still be an option. If neoadjuvant therapy is not given or if the tumor has spread to nearby tissues, mastectomy is typically the procedure of choice. An axillary lymph node dissection is often performed to evaluate the lymph nodes, although for some patients a sentinel lymph node biopsy may be an option. Radiation therapy is recommended after surgery for patients with stage III tumors.

Adjuvant therapy is also given. The type of adjuvant therapy depends upon the characteristics of the tumor as described previously and can includehormone therapy, chemotherapy, HER2-targeted therapy, or a combination of these.


=> What is the treatment for stage IV breast cancer?
Stage IV breast cancers have spread to other sites in the body and are referred to as metastatic breast cancers.

Common sites to which tumors may have spread include the lungs, liver, and bones. Hormone therapy, chemotherapy, and HER2-targeted therapies (depending upon the characteristics of the tumor) are the mainstay of therapy. Surgery is generally not done except in special situations, such as relieving compression on the spinal cord, treating a small number of metastases in one area, or treating brain metastases in certain situations. Radiationtherapy may also be used in certain situations for symptom relief or treating certain areas of metastatic tumor.

Hormone therapy is often the first treatment for stage IV cancers that are hormone receptor-positive, but since this may take some time to work, chemotherapy may be given first if there are severe symptoms. Switching to different types of hormone therapy or chemotherapy than originally received may be indicated. Likewise, additional HER2-targeted drugs may be given to patients with stage IV breast cancers that are HER2-positive.

Clinical trials to test new combinations of drugs or new drugs are another treatment option.


=> Male breast cancer facts
♦ Male breast cancer is rare and accounts for only about 1% of all breast cancers.
♦ Breast cancer risk in men is increased by elevated levels ofestrogen, previous radiationexposure, and a family history ofbreast cancer.
♦ Mutations in specific genes are associated with an increase in risk for breast cancer in men.
♦ Infiltrating ductal carcinoma is the most common type of male breast cancer.
♦ A lump beneath the nipple is the most common symptom of male breast cancer.
♦ Male breast cancer is staged (reflecting the extent of tumor spread) identically to breast cancer in women.
♦ Surgery is the most common initial treatment for male breast cancer. Depending on the situation, chemotherapy, radiation therapy, and hormonal therapy are also considered.
♦ The prognosis of male breast cancer, like breast cancer in women, is predominantly influenced by tumor stage.
♦ The prognosis for early-stage breast cancer in men is favorable, with 5-year survival rates of 100% for stage 0 and stage 1 tumors.


=> What is male breast cancer?
Men possess a small amount of nonfunctioning breast tissue (breast tissue that cannot produce milk) that is concentrated in the area directly behind the nipple on the chest wall. Like breast cancer in women, cancer of the male breast is the uncontrolled growth with the potential for spread of some of the cells of this breast tissue. These cells become so abnormal in appearance and behavior that they are then called cancer cells.

Breast tissue in both young boys and girls consists of tubular structures known as ducts. At puberty, a girl's ovaries produce female hormones (estrogen) that cause the ducts to grow and milk glands (lobules) to develop at the ends of the ducts. The amount of fat and connective tissue in the breast also increases as girls go through puberty. On the other hand, male hormones (such as testosterone) secreted by the testes suppress the growth of breast tissue and the development of lobules. The male breast, therefore, is made up of predominantly small, undeveloped ducts and a small amount of fat and connective tissue.


=> How common is male breast cancer?
Male breast cancer is a rare condition, accounting for only about 1% of all breast cancers. Statistics from the American Cancer Society suggest that in 2015, about 2,350 new cases of breast cancer in men would be diagnosed and that breast cancer would cause approximately 440 deaths in men (in comparison, almost 40,000 women die of breast cancer each year). Breast cancer is 100 times more common in women than in men. Most cases of male breast cancer are detected in men between the ages of 60 and 70, although the condition can develop in men of any age. A man's lifetime risk of developing breast cancer is about 1/10 of 1%, or one in 1,000. Breast cancer incidence rates in men have remained fairly stable over the past 30 years.


=> What are causes and risk factors of male breast cancer?
As with cancer of the female breast, the cause of cancer of the male breast has not been fully characterized, but both environmental influences and genetic (inherited) factors likely play a role in its development. The following risk factors for the development of male breast cancer have been identified.

Radiation exposure
Exposure to ionizing radiation has been associated with an increased risk of developing male breast cancer. Men who have previously undergone radiation therapy to treat malignancies in the chest area (for example, Hodgkin's lymphoma) have an increased risk for the development of breast cancer.

Hyperestrogenism (high levels of estrogen)
Men normally produce small amounts of the female hormone estrogen, but certain conditions result in abnormally high levels of estrogen in men. The term gynecomastia means that the male breasts are abnormally enlarged in response to elevated levels of estrogen. High levels of estrogens also can increase the risk for development of male breast cancer. The majority of breast cancers in men are estrogen receptor-positive (meaning that they have proteins on the surface of the cells that can receive and transport estrogen through the cell wall and into the interor of the cell.). Two conditions in which men have abnormally high levels of estrogen that are commonly associated with breast enlargement are Klinefelter's syndrome and cirrhosis of the liver. Obesity is also associated with elevated estrogen levels and breast enlargement in men. Certain medications can causegynecomastia as a side effect when taken for long periods. These include several types of medicine used to treat high blood pressure, medicines to reduce stomach acid, valium, finasteride, medicines to treatprostate cancer, and others. Check the side effects of the medicines you take if you think you may be developing male breast tissue enlargement (gynecomastia).

Klinefelter's syndrome
Klinefelter's syndrome is an inherited condition affecting about one in 1,000 men. A normal man has two sex chromosomes (X and Y). He inherited the female X chromosome from his mother and the male Y chromosome from his father. Men with Klinefelter's syndrome have inherited an extra female X chromosome, resulting in an abnormal sex chromosome makeup of XXY rather than the normal male XY. Affected Klinefelter's patients produce high levels of estrogen and develop enlarged breasts, sparse facial and body hair, small testes, and the inability to produce sperm. Some studies have shown an increase in the risk of developing breast cancer in men with this condition. Their risk for development of breast cancer is markedly increased, up to 50 times that of normal men.

Cirrhosis (scarring) of the liver
Cirrhosis can result from chronic alcohol abuse, chronic viral hepatitis, or rare genetic conditions that result in accumulation of toxic substances within the liver. The liver produces important binding proteins that affect the transport and delivery of male and female hormones via the bloodstream. With cirrhosis, liver function is compromised, and the levels of male and female hormones in the bloodstream are altered. Men with cirrhosis of the liver have higher blood levels of estrogen and have an increased risk of developing breast cancer.

Familial predisposition
Epidemiologic studies have shown that men who have several female relatives with breast cancer also have an increased risk for development of the disease. In particular, men who have inherited mutations in the breast cancer-associated BRCA-2 gene have an increased risk for developing breast cancer, with a lifetime risk of about 6 in 100 for development of breast cancer. BRCA-2 is a gene on chromosome 13 that normally functions in suppression of cell growth. Mutations in this gene lead to an increased risk for development of breast, ovarian, and prostate cancers. A portion of breast cancers in men are thought to be attributable to BRCA-2 mutation. Mutations in the BRCA-1 gene, which has been associated with inherited breast cancers in women, increase the risk for male breast cancer to a lesser degree than mutations in BRCA-2 (lifetime risk of 1 in 100).

Other genetic mutations have also been associated with an increase in risk for breast cancer in men, including mutations in the PTEN tumor suppressor gene (Cowden’s syndrome), TP53 mutations (Li-Fraumeni syndrome), PALB2 mutations, and mutations associated with hereditary nonpolyposiscolorectal cancer (Lynch syndrome).

Finasteride use
Finasteride (Propecia, Proscar), a drug that has been used to treatbaldness, as well as benign prostatic hyperplasia (prostate enlargement) and to prevent prostate cancer, may be associated with an increased risk for male breast cancer. During clinical trials for the drug, no increased risk was shown. However, over 50 cases of male breast cancer have been reported worldwide in men taking the drug. Further studies are needed to clarify whether a causal relationship between the drug and the disease actually exists.


=> What are the different types of male breast cancer?
The most common type of male breast cancer is infiltrating ductal carcinoma, which is also a common type of breast cancer in women. Ductal carcinoma refers to cancers with origins in the ducts (tubular structures) of the breast, and the term infiltrating means that the cancer cells have spread beyond the ducts into the surrounding tissue. On the other hand, lobular cancers (cancers of the milk glands), common in women, are extremely rare in men since male breast tissue does not normally contain lobules.

Other uncommon types of cancers of the breast that have been reported in men include ductal carcinoma in situ (cancer in the ducts that has not spread beyond the ducts themselves), cystosarcoma phylloides (a type of cancer of the connective tissue surrounding the ducts), and Paget's disease of the breast (a cancer involving the skin of the nipple). Some other types of breast cancer that occur in men are named for their growth patterns and microscopic appearance of the cancer cells, including papillary carcinoma, inflammatory carcinoma, and medullary carcinoma.

About 85% of breast cancers in men have estrogen receptors on their cell membranes. Estrogen receptors on the cell membranes allow estrogen molecules to bind to the cancer cells. Estrogen binding to the cancer cells can stimulate cell growth and multiplication.


=> What are male breast cancer symptoms and signs?
The most common sign of breast cancer in men is a firm, nonpainful mass located just under the nipple. There may not be other associated symptoms. The average size of breast cancer in men when first discovered is about 2.5 cm in diameter. The cancer may cause skin changes in the area of the nipple. These changes can include ulceration of the skin; skin puckering or dimpling; redness, scaling, or itching of the nipple; or retraction (turning inward) of the nipple. Bloody or opaque discharge from the nipple may also occur. Less than 1% of cases are bilateral (occurring on both sides).

Breast cancer that has spread (metastasized) to the bones may also produce bone pain at the sites of metastases. Advanced breast cancer can also produce symptoms typical of many cancers, including malaise,weakness, and weight loss. Breast cancer in men can spread to many other organs and cause other symptoms as well.


=> How is male breast cancer diagnosed?
Diagnosis of breast cancer requires identifying cancer cells in tissue specimens obtained by taking a sample of the growth - also called a "mass" or "tumor" - by the technique of biopsy. Since men have little breast tissue, cancers in male breasts are easily palpable (located by feel) and, therefore, are easily accessible to biopsy. Fine needle aspiration or needle biopsy of a suspicious mass can usually establish a diagnosis. A needle is inserted into the mass and tissue from the suspicious area is withdrawn. Microscopic examination of the tissue by a pathologist establishes the diagnosis.

Other techniques that may be used to diagnose breast cancer in men include incisional (removing a portion of the suspicious tissue) or excisional (removing the mass in its entirety) biopsy of a breast mass. If nipple discharge is present, microscopic examination of a smear of the discharge can sometimes establish the diagnosis.

Imaging studies such as X-rays, CAT scans (CT scans), magnetic resonance imaging (MRI), ultrasound, and bone scans may be performed to evaluate the presence and extent of metastatic disease once the initial diagnosis of breast cancer has been made.


=> What is staging of male breast cancer?
Staging is carried out to determine the extent to which a cancer has spread within the body. Staging of breast cancer in men is carried out identically to the staging of breast cancer in women. The American Joint Committee on Cancer (AJCC) TNM system takes into account the tumor size, lymph nodeinvolvement by cancer, and presence of metastasis:
♦ T: tumor size and extent of local spread
♦ N: extent of tumor involvement of lymph nodes in the axillary (underarm) region. Since the nipple area is rich in lymphatic vessels, male breast cancer commonly spreads via the lymphatic channels to the axillary lymph nodes. (When the tumor has spread to the lymph nodes, doctors sometimes use the term "lymph node-positive" cancer.)
♦ M: presence of distant metastases (spread to other parts of the body through the bloodstream or lymphatic vessels)

Stage 0
Stage 0 refers to intraductal carcinoma or ductal cancer in situ, in which the cancer cells have not spread beyond the boundaries of the ducts themselves.

Stage I
In Stage I breast cancer, the tumor is 2 cm or less in greatest diameter and has not spread to the lymph nodes or to other sites in the body.

Stage II
Stage II cancers are divided into two groups. Stage IIA cancer is either less than 2 cm in diameter with spread to the axillary lymph nodes, or the tumor is between 2 cm-5 cm but has not spread to the axillary lymph nodes. Stage IIB tumors are either larger than 5 cm without spread to the lymph nodes or are between 2 cm-5 cm in size and have spread to the axillary lymph nodes.

Stage III
Stage III is considered to be locally advanced cancer. Stage IIIA means the tumor is smaller than 5 cm but has spread to the axillary lymph nodes, and the axillary lymph nodes are attached to each other or to other structures; or the tumor is greater than 5 cm in diameter with spread to the axillary lymph nodes, which may be attached to each other or to other structures. Stage IIIB tumors have spread to surrounding tissues such as skin, chest wall, or to the lymph nodes inside the chest wall.

Stage IV
Stage IV cancer refers to metastatic cancer, meaning it has spread to other parts of the body. With breast cancer, metastases (sites of tumor elsewhere in the body) are most often found in the bones, lungs, liver, or brain. Stage IV cancer is also diagnosed when the tumor can be found in the lymph nodes of the neck.


=> What is the treatment for male breast cancer?
Like breast cancer in women, treatment depends upon the stage of the cancer and the overall physical condition of the patient. Treatments are the same as for breast cancer in women.

Most men diagnosed with breast cancer are initially treated by surgery. A modified radical mastectomy (removal of the breast, lining over the chest muscles, and portions of the underarm or axillary lymph nodes) is the most common surgical treatment of male breast cancer. Sometimes portions of the muscles of the chest wall are also removed.

After surgery, adjuvant therapies are often prescribed. These are recommended especially if the cancer has spread to the lymph nodes (node-positive cancer). Adjuvant therapies include chemotherapy, radiation therapy, targeted therapy, andhormone therapy. In cases of metastatic cancer, chemotherapy, hormone therapy, or a combination of both, are generally recommended.

Chemotherapy refers to the administration of toxic drugs that stop the growth of cancer cells, or even kill some of them. Chemotherapy may be given as pills, as an injection, or via an intravenous infusion, depending upon the types of drugs chosen. Combinations of different drugs are usually given, and treatment is administered in cycles with a recovery period following each treatment. Some of the most common chemotherapeutic agents for treating breast cancer are cyclophosphamide (Cytoxan),methotrexate (Rheumatrex, Trexall), fluorouracil, and doxorubicin (Adriamycin). Numerous other chemotherapy drugs are now available as well.In most cases, chemotherapy is administered on an outpatient basis. Chemotherapy may be associated with unpleasant side effects includingfatigue, hair loss, nausea and vomiting, and diarrhea.

Radiation therapy uses high-energy radiation to kill tumor cells. Radiation therapy may be delivered either externally (using a machine to send radiation toward the tumor) or internally (radioactive substances placed in needles or catheters and inserted into the body).

Hormonal therapy prevents hormones from stimulating growth of cancer cells and is useful when the cancer cells have binding sites (receptors) for hormones. Over 90% of male breast cancers express estrogen receptors and are most commonly treated with the drug tamoxifen (Nolvadex), which blocks the action of estrogen on the cancer cells. Side effects of tamoxifen treatment can include hot flashes, weight gain, mood changes, andimpotence.

While estrogen is the most common target of hormonal therapy, studies have also shown that treatments directed against the actions of male hormones (anti-androgens) can also reduce the size of male breast cancer metastases. The reasons why anti-androgens are effective in widespread disease are not fully understood. Orchiectomy (removal of the testes) was formerly performed to lower androgen levels, but newer nonsurgical methods are currently favored. Drugs known as luteinizing hormone-releasing hormone (LHRH) analogs affect the pituitary gland and result in lowered production of male hormones by the testes.

Targeted therapy involves agents that are designed to specifically target one of the cancer-specific changes in cells. An example of targeted therapy is trastuzumab (Herceptin), a monoclonal antibody that blocks the activity the protein known as HER-2-neu that is made by some breast cancers. This treatment is only used in breast cancers whose cells express the HER-2-neu protein and is given intravenously. Trastuzumab has been shown to be effective in women with breast cancer but has not been extensively tested in men with breast cancer. Similarly, lapatinib (Tykerb) is a drug taken in pill form that also targets the HER2/neu protein. It is used in combination with other agents to treat HER2-positive breast cancer that is no longer responsive to trastuzumab.

If a cancer that has been surgically removed regrows at the original site, this is referred to as local recurrence. Locally recurrent cancers are usually treated by surgery along with chemotherapy or radiation therapy combined with chemotherapy.


=> What is the outcome (prognosis) of male breast cancer?
The prognosis of a patient with male breast cancer is considered similarly to breast cancer in a woman. As in women, the size and extent (stage) of tumor are the most important factors in the prognosis for male breast cancer. Overall survival rates for each tumor stage are similar for men and women. Since men have less breast tissue than women, it is more common for breast cancers in men to have spread beyond the breast when they are identified, resulting in a more advanced tumor stage at diagnosis.

Disease-specific five-year survival rates (meaning the percentage of patients who do not die of the disease for at least five years following diagnosis) reported for male breast cancer by stage are as follows:
♦ Stage 0 - 100%
♦ Stage I - 100%
♦ Stage II - 91%
♦ Stage III - 72%
♦ Stage IV - 20%

These survival rates were calculated using historical data, and it is likely that current treatments will lead to even greater survival rates for those recently diagnosed.


=> Inflammatory Breast Cancer
Inflammatory breast cancer facts
Inflammatory breast cancer is breast cancer that has spread to the lymphatic system, causing symptoms of inflammation (redness, swelling, tenderness) in the breast.
Symptoms of inflammatory breast cancer include
♦ swelling,
♦ redness,
♦ skin changes,
♦ tenderness,
♦ dimpling of the skin,
♦ heaviness,
♦ possibly, a lump or mass in the breast.
♦ As with other types of breast cancer, a tissue biopsy is done to confirm the diagnosis of breast cancer.
♦ Inflammatory breast cancers are stage III or stage IV at the time of diagnosis.
♦ Treatment of inflammatory breast cancers is multimodal and involves surgery, chemotherapy, and radiation therapy.
♦ Inflammatory breast cancer is more aggressive and tends to have a worse prognosis than other types of breast cancer.
♦ Targeted therapies such as trastuzumab (Herceptin) or hormonal therapies may also be given, depending upon whether or not the tumorcells express hormone receptors or the HER2 protein.
♦ Survival rates for inflammatory breast cancer are not as favorable as those for other types of breast cancer.


=> What is inflammatory breast cancer?
Inflammatory breast cancer is a rare form of breast cancer. It is typically a very aggressive disease and is called "inflammatory" because the cancer cells block the lymphatic vessels, resulting in changes in the breast (swelling and redness) that make the breast appear to be inflamed. Over 230,000 women in the United States are diagnosed with breast cancer each year; inflammatory breast cancers make up only 1%-5% of breast cancers.


=> How is inflammatory breast cancer different from other breast cancers?
Inflammatory breast cancer is typically an aggressive form of cancer that spreads rapidly. Because it involves the lymphatic system and has invaded the lymph vessels at the time of diagnosis, it is already at a more advanced stage (see below) than many breast cancers when it is discovered. This type of breast cancer is usually found in women at a younger age than most breast cancers; the median age for diagnosis of inflammatory breast cancer is 57 years compared to 62 years for all breast cancers.

Inflammatory breast cancer is more common in African American women than in Caucasian women and is diagnosed at an earlier age. In Africa American women, the median age at diagnosis of inflammatory breast cancer is 54 years, compared with 58 years for Caucasian women. Inflammatory breast cancer is also more common inobese women than in women with normal body weight.

Inflammatory breast cancers often are hormone receptor negative, meaning that their cells do not have receptors for estrogen or progesterone on the surface. This means that therapies (such as tamoxifen [Nolvadex]) that target estrogen-driven tumor growth are unlikely to be effective.


=> What are the signs and symptoms of inflammatory breast cancer?
Unlike most breast cancers, which may or may not cause any symptoms, inflammatory breast cancer produces signs and symptoms of inflammation in the breast tissue, including
♦ swelling and redness that affect a large part (at least one-third) of the breast,
♦ pitting,
♦ dimpling,
♦ bruising,
♦ orange peel (peau d'orange) appearance due to the buildup of lymphatic fluid,
♦ nipple may be pulled inward (inverted).

Other possible symptoms and signs include
♦ a rapid increase in size of the breast,
♦ heaviness,
♦ burning,
♦ tenderness.

Sometimes, a mass or lump can be felt in the breast, but commonly no mass can be felt. Enlarged lymph nodes may be present in the underarm or near the collarbone.

While the symptoms of inflammation in the breast are characteristic of inflammatory breast cancer, they can also arise due to infections and other conditions, so any unusual symptoms or changes in the breasts should be evaluated by a medical professional.

=>=> How do health-care professionals diagnose inflammatory breast cancer?

=> Mammography and imaging tests
Screening mammography has made it possible to detect many breast cancers before they produce any signs or symptoms. However, inflammatory breast cancer produces symptoms, so in the case of this cancer, mammography may be used to evaluate the breast when symptoms are present or to determine the location for abreast biopsy. Due to the rapid spread of the cancer, this cancer is sometimes found between the routine mammogram exams. Other imaging tests, including MRI,ultrasound, PET scans, and CT scans may be used to evaluate the breast if inflammatory breast cancer is suspected. Abone scan to look for spread (metastasis) to the bones may also be performed if a diagnosis of inflammatory breast cancer is confirmed.

=> Definitive diagnosis
Even if imaging tests show an abnormality or are suspicious for breast cancer, definitive diagnosis requires a tissue sample, or biopsy. A biopsy may be taken of a small area of the abnormality (an incisional biopsy), or the entire abnormal area may be removed at the time of biopsy (excisional biopsy). Biopsy allows the pathologist (a physician with special training in the diagnosis of diseases based on tissue samples) to determine if cancer is present, and if so, what type of cancer. Biopsy also provides a tissue sample for further tests that are done (see below) to determine the best type of treatment. If a mass is not identified in the breast, a skin biopsy can sometimes be used to establish the diagnosis of inflammatory breast cancer. The diagnosis of inflammatory breast cancer can be challenging.

The diagnostic guidelines for inflammatory breast cancer require that the following factors are present:
♦ A rapid onset of erythema (redness), edema (swelling), and a peau d'orange appearance and/or abnormal breast warmth, with or without a lump that can be felt
♦ These symptoms have been present for less than six months.
♦ The redness covers at least one-third of the breast.
♦ A biopsy from the affected breast reveals invasive cancer.

=> Specialized testing on breast cancer samples
Certain laboratory tests are typically performed on all breast cancer tumor samples to help determine the optimum treatment. These include:
♦ Hormone receptor status: Breast cancer tissue is tested for the presence of receptors for the hormones estrogen (estrogen receptor or ER) and progesterone (progesterone receptor or PR). If these receptors are present, the tumor is referred to as hormone receptor-positive. This means that hormone-directed therapies may be effective in stopping tumor growth.
♦ HER2: Another test performed on breast cancer tissue measures the overexpression of a protein called HER2. If a tumor is HER2-positive (HER-2+), drugs that target this specific protein may be given. About 15% of women have so-called triple-negative breast cancers. This means that they do not express any of these tumor markers (ER, PR, or HER2). As mentioned before, inflammatory breast cancers often do not express the hormone receptors ER and PR. Newer laboratory tests may be useful for some types of tumors to help determine the prognosis and treatment plan. These include, for example, studies of gene expression in the particular tumor or tests to look for the presence of circulating tumor cells or tumor DNA.

=> What are the stages of inflammatory breast cancer?
Staging of a cancer refers to the determination of how far the tumor has spread at the time of diagnosis. Staging is determined by a variety of methods including results from surgical procedures,lymph node biopsy, and imaging tests. Staging is important because it aids in developing a treatment plan.

Cancer in situ (DCIS) is referred to as stage 0, because the tumor cells have not invaded. Invasive breast cancers are staged along a scale of I to IV, with stage I being the earliest stage and stage IV representing tumors that have metastasized to distant organs like the bones, lungs, or brain. Because inflammatory breast cancers have already spread into the lymphatic vessels and cause symptoms related to this presence in the lymphatic system, inflammatory breast cancers are stage III or stage IV at diagnosis.

=> What is the treatment for inflammatory breast cancer?
Treatment for inflammatory breast cancer typically involves chemotherapy, surgery, and radiation. In some cases, additional targeted therapies are given. The term neoadjuvant refers to therapies that are given prior to surgery, while adjuvant refers to treatments given after surgery.

Neoadjuvant chemotherapy refers to chemotherapy medications that are given prior to surgery to shrink the tumor. In patients with inflammatory breast cancer, this is often done so that the tumor is smaller and easier to remove at surgery. A typical course of neoadjuvant chemotherapy would involve at least six cycles of chemotherapy over four to six months. The chemotherapy regiment usually involves taxane and anthracycline drugs.

If the tumor cells express the HER2 protein (see above), targeted therapies such as trastuzumab (Herceptin) can also be given as a neoadjuvant (prior to surgery) therapy and continued after surgery (adjuvant therapy). Inflammatory breast cancers are often positive for the HER2 protein, so the tumors can be responsive to treatments that target this protein. In addition to trastuzumab, other drugs that target HER2 activity are available.

It is less common for inflammatory breast cancers to express hormone (ER or PR) receptors, but if the tumor is hormone receptor-positive, hormone therapies that target estrogen can be effective. Tamoxifen is a drug that interferes with the activity of estrogen in the body and is a commonhormone therapy drug. It can be given to both premenopausal andpostmenopausal women. In postmenopausal women, drugs known asaromatase inhibitors are also used as of hormone therapy. Examples of aromatase inhibitors include anastrozole (Arimidex), letrozole (Femara), and exemestane (Aromasin).

Surgery for inflammatory breast cancer usually involves a modified radicalmastectomy with removal of lymph nodes, since the tumor has spread into the lymphatic system. Following surgery, radiation therapy is typically administered to the chest wall. This treatment uses radiation to destroy remaining cancer cells. The most common type of radiation therapy is given in a clinic, usually five days a week for several weeks.

Adjuvant therapy after surgery can include hormone therapy, chemotherapy, targeted therapy, or a combination of these methods described above.

Clinical trials, in which new drugs, new therapies, or combination of drugs and therapies are tested, may be available for some patients with inflammatory breast cancer and offer an additional treatment option. Anyone interested in taking part in a clinical trial should discuss this possibility doctor. Information about clinical trials is available from the National Cancer Institute's Cancer Information Service at 1-800-4-CANCER and at http://www.cancer.gov/clinicaltrials.


=> What are the survival rates andprognosis for inflammatory breast cancer?
The prognosis, or survival rates, for breast cancer depend upon the extent to which the cancer has spread and the treatment received. Because inflammatory breast cancer is diagnosed when the cancer has already spread to the lymphatic system, survival rates for this type of breast cancer are not as favorable as for other types of breast cancer. Still, it is important to remember that statistics about breast cancer are based on studies of patients who were diagnosed years ago, and since therapies are constantly improving, current survival rates may be even higher.

In terms of inflammatory breast cancer, some factors are associated with a better prognosis (more favorable outcome):
♦ Stage: Stage III tumors have a better prognosis than stage IV tumors.
♦ Grade: Higher-grade tumors (grade refers to the extent to which the cells resemble normal breast cells under a microscope; the higher the grade, the more abnormal the cells) tend to have a worse prognosis.
♦ Studies have shown that African American women with inflammatory breast cancer have a worse prognosis than women of other racial groups.
♦ Inflammatory breast cancers that are estrogen receptor-positive tend to have a better prognosis than those that are estrogen receptor-negative.
♦ Women who undergo multimodal therapy (a combination of chemotherapy, surgery, and radiation therapy) have a better prognosis than women who do not have this type of therapy.

Statistics are often reported as five-year survival rates by stage of the tumor. According the NCI's Surveillance, Epidemiology, and End Results (SEER) program, the five-year relative survival for women with inflammatory breast cancer (from 1988 through 2001) was 34%, compared to a relative five-year survival of up to 87% among women diagnosed with other invasive breast cancers.



***Courtesy: Medicinenet