Background Information-- What Is Breast Cancer?

Any uncontrolled growth of breast tissue cells, which has the capacity to spread, is breast cancer."Early" breast cancer is confined to the breast and the tumor is not larger than 5 cm (about 2 inches) across. It may also involve the lymph glands under the armpit, called the"axillary lymph nodes". It has not spread to any distant sites in the body, as far as can be told with today's technology."Locally Advanced" Breast Cancer is noted by a tumor greater than 5 cm across, or a fixed lump in the axilla representing cancer, ulceration of the skin from cancer, or involvement of the deep chest muscles. "Inflammatory Breast Cancer" is a hot, tender breast with skin looking like an orange peel, called "peau de orange" and almost always has spread to the axilla. "Metastatic" breast cancer means the disease has spread to other areas of the body, such as the lung, liver, brain, skin or bone.

Breast cancer, like other cancers, starts in just a single cell. Normally, breast cells divide infrequently after breast growth is completed; only to replace those cells lost through old age or injury. The production of new breast cells from pre-existing ones is under tight control by the genetic code, or "genes", of each cell. When this code becomes damaged, a cell may start dividing out of control. The breast cancer cell is genetically damaged, but otherwise it looks very similar to normal body tissue. This is why our immune system may fail to detect it as abnormal. These cells can pile up to form a local "tumor". A tumor simply means a swelling; it is not necessarily cancerous. Less than 1/3 of new breast lumps and bumps are cancer. A tumor which only grows in it's place or origin, and cannot spread distantly, is called"benign" and is not cancer. However, a tumor which has the capacity to spread (whether it actually does or not) is called"malignant", this is cancer. The actual process of spread is called "metastasis". It is this ability to spread to any organ in the body which makes cancers so dangerous.

How Common is Breast Cancer?

Breast cancer is the most common cancer in women, after skin cancer, with 185,000 new cases estimated for 1997 in the U.S.A. It causes 45,000 deaths per year, which makes it second leading cause of cancer death after lung cancer in women. The number of annual deaths from breast cancer has remained about the same for the past 50 years, although the number of cases is increasing. This shows the benefits of early detection, which impacts survival. Also, effective treatment is increasing survival in all breast cancer patients. One in nine women will get breast cancer in the U.S.A. during their lifetimes. Two thirds to 75% of cases are "Early Breast Cancer", 20% are "Advanced Breast Cancer" (including Metastatic), and 5% are the"Inflammatory" subtype. Initial "Early Breast Cancer" which was thought cured may be detected as the "Advanced Metastatic" type decades after the initial diagnosis and treatment. Advanced Breast cancer can "smolder" along, slowly growing in the bone, for many years before detection.

What Causes or Increases the Risk for Breast Cancer?

Like any other cancer, the exact reason why one woman gets breast cancer and another doesn't remains unknown. However, certain "risk factors" have been identified:

1) Being female (only 1% of cases are in males).
2) Family history of breast cancer in mother and aunts; BRCA-1 gene. The BRCA-1 gene stands for breast cancer, and although the risk is increased with the gene, not all patients with it get breast cancer. Also, genes for rare diseases like ataxia-telangectasia ("A-T") (lack of repair of skin to sun damage) associated with breast CA.
3) Getting older-- average age is 60 to get breast cancer.
4) Lots of estrogens-- including start of menstrual periods at a young age completion of menstrual periods at an old age, no children or first child after age 30, being obese (fat cells produce estrogen).
5) Low dose radiation exposure-- can take 10 to 50 years afterward to develop breast cancer, among others. About 6 per 1 million women are estimated to get breast cancer from the mammogram radiation, but this is believed worthwhile owing to the many early cancers found.
6) High fat in the diet. This many also be related to obesity above.
7) Tobacco smoking, alcohol or birth control pills do NOT seem to increase risk!

Is Breast Cancer Preventable?

Most of the risk factors for getting Breast Cancer are not in a woman's control. In the past, women with a very high risk sometimes had both breasts removed as a preventative measure, called"prophylactic mastectomy". This is very infrequent today, given the earlier detection and better treatment of breast cancer. Reducing fat in the diet, getting pregnant in her early 20's, and appropriate screening and prompt treatment can reduce cancer deaths.

How is Breast Cancer Screened For?

There are two common ways of screening for breast cancer. Every woman can do a Breast Self Exam" one week after her menstrual period each month, feeling for lumps. After menopause, it can be done at any standard time each month. This should also be done if a patient with a history of breast cancer has kept a breast. The American Cancer Society recommends a"baseline" mammogram at age 35 - 40 with an "every other year" mammogram from ages 40 to 50. After age 50, women should get a mammogram every year. Women at higher risk may get this test more frequently, as should women who have had breast cancer but kept their breast. In spite of the recent controversy for how often to get mammograms, the main point is to get them on a regular basis, especially as a women gets older than age 40.

What are the Symptoms of Breast Cancer?

Early breast cancer usually has no symptoms, but is picked up with screening tests. It is important to note that most new breast lumps are not cancer, but it must be "ruled out" anyway. The first symptom is usually a new lump or bump in the breast, which is of "dominant" character. This means that it is single, hard, non-movable, non-tender, and in only one breast. Occasionally (3%) breast cancer results in a nipple discharge, while 50% of watery discharges are from cancer, only 1% of milky or pussy discharges are cancerous. In more advanced breast cancer, the breast may have a large tumor, or have a lump in the armpit. Inflammatory breast cancer looks like an infection, being red and painful, and may be confused with the much more common "mastitis", which is a simple breast infection. Breast cancer spread to bones can cause pain and fractures, and to the brain can result in symptoms of imbalance, confusion, headache and local weakness or numbness. Rarely, it spreads to the eyes to cause blindness. Most commonly, however, it stays localized in the breast for many years. If it spreads, it is most commonly to bone where it may remain unapparent for many years. About 5% of patients develop cancers in both breasts, called "bilateral" breast cancer.

How Does Breast Cancer Spread?

It generally starts inside the milk ducts of the breast, then invades through the wall of the breast. If it invades, then it grows locally to form a tumor, and the first spread is to the lymph glands in same sided armpit (called the "axilla" ). When the tumor is 1 inch across, there is a 30% chance that it has spread to the axillary lymph glands; when it is 2 inches across, the chance of the axilla being involved, or"positive" is about 60%. Once the axilla is involved, the cancer is considered"systemic", that is likely to have spread to other areas of the body through the bloodstream. The most common places for it to spread, in order, are the bones, liver, lung, skin and brain.

What are the Types of Breast Cancer?

The most common type is called "Invasive Ductal Carcinoma", that is, the cancer starts in the milk duct and invades through it. This accounts for 70% of breast cancers,and is the only type found in men. It accounts for most of the locally advanced and inflammatory cancer too. The next most common type is called "lnvasive Lobular Carcinoma", it arises from the lobules in the breast and accounts for 10% of cases. Alternatively, the either the "Ductal" or the "Lobular" type of cancers may not invade, but stay locally within the ducts or lobules and grow to a large size there. "Non-invasive" or "in Situ" disease accounts for about 10% of breast cancer, it does not spread to the axilla or elsewhere, and in general patients do better than with invasive disease. It is also important because local recurrence of breast cancer (after breast conservation therapy) may be of this "non-invasive" type and so less dangerous."Ductal Carcinoma in Situ", or "DCIS " for short, is becoming more common since it often can only be detected with a mammogram. Interestingly,"Lobular Carcinoma in Situ", or "LCIS" for short, is a "marker" for the development of later invasive ductal cancer, which happens in 30% of patients. Uncommon types of breast cancer include "medullary", "mucinous" and"tubular" forms, which all tend to occur in older women and are less aggressive, and "Paget's Disease of the Nipple", which appears as a scaly irritation but has an underlying lump in the breast 70% of the time. Rarely, cancer may arise from the sweat glands of the breast ("apocrine") from the immune cells in the breast ("lymphoma") or from the muscle ("sarcoma"). The treatment for these cancers is different that the typical ductal or lobular types, and discussed in other transcripts. There may be a mixture of types 10% of cases.

How is Breast Cancer Detected and Evaluated?

Monthly breast "self-exam" by women can pick up about 30% of breast cancers, both new ones and recurrences after breast conservation therapy. Others are too small to be felt, or "palpated", but 85% of breast cancers can be detected with a mammogram. The radiation dose from a modern mammogram is 0.2 centiGray, about the same as an ordinary chest X-ray. Worrisome findings on a mammogram include lots of little calcium deposits, called "microcalcifications", especially in irregular or "starburst" patterns. About 1/3 of these will represent cancer. Sometimes, a "dominant" mass may be felt in the breast, but the mammogram doesn't show anything. Any dominant mass must be biopsied (sampled) to rule out cancer! That's because 15% of even large cancers will remain invisible on a mammogram.

If a suspicious area is found, either on exam or mammogram, the National Cancer Institute recommends a "2 part approach". Firstly, a biopsy (sampling procedure) is done to confirm or deny cancer, then secondly, a surgery is performed to remove any cancer detected. The quickest, easiest way to sample a suspicious area is called a "fine needle aspiration" in which a thin needle is placed into the tumor using radiographic guidance. Some cells are sucked up, or "aspirated", and sent to a "pathologist", that is a doctor who specializes in making diagnoses from tissue specimens. This test is over 90% accurate at detecting cancer. If it is"positive" (that means cancer is found) then surgery is done. Either the entire breast is removed (called amastectomy ), or just the area of the tumor with a surrounding safety margin (called a lumpectomy ). The cancer removed is submitted for various tests, to classify it and see how likely it is to be aggressive.

These include the following"Prognostic Factors" :

Grading the tumor The pathologist looks at the cells in the tumor to see just how closely they resemble normal breast cells. He assigns a grade, called the "Bloom-Richardson" grade, from 1 to 3. A grade of 1 means that the tumor closely resembles normal breast, that is"well-differentiated", and probably isn't very aggressive while a grade of 3 means the tumor looks very cancerous, that is"poorly differentiated" and is likely aggressive. A grade of 2 means "moderately differentiated" so is of intermediate behavior.

Estrogen and Progesterone Receptor Studies ("ER" and"PR" for short) look to see how likely the tumor is to respond to these female hormones. The chances of them being positive increases with the age of the patient. If both"ER" and "PR" are positive, the tumor is less aggressive and has an 80% chance of responding to "anti-estrogen" drugs like tamoxifen. If both are negative, their is only a 10% chance of response Positive"PR" with Negative"ER" is better than vice-versa.

The "DNA activity measurements" of"S-phase" (which tells how quickly the cells are dividing-- higher "S-phase" is more aggressive ) and "Ploidy" which also tells how similar the cancer cells are genetically to normal breast cells. "Diploid" is normal and is better than"aneuploid" which is more cancerous.

Cathepsin D -- is a cellular "enzyme", a high level suggests positive lymph glands.

"Oncogenes" look genetically at the tumor, if the "Breast Cancer" ("BCA-1") o a gene called"HER-2/neu" are increased, these tumors are more aggressive.

The size of the tumor - If it's less than 1 cm. across, 10 year survival is over 80% while if it's more than 7 cm. across, average 10 year survival is only 40%. The larger the cancer grows locally (the higher the"tumor burden" ) , the more chance it has to spread to lymph nodes and to distant body areas. The pathologist also looks at the type of breast cells to classify the cancer as"ductal or"lobular", and to see if it invades through these ducts or lobules. If the cancer invades (90% of them do) then it becomes necessary to do a second small operation, called an "axillary lymph node sampling", which is not a therapeutic procedure, but merely diagnostic. There procedure isn't done if the cancer isn't invasive (i.e. "DCIS" or "LCIS"). If the axilla's lymph glands are "negative" (not involved) then 10 year survival is over 75%, while if more than 4 lymph nodes are"positive" (involved) 10 year average survival drops to only 25%. The main point of checking the axilla is to see if chemotherapy will be necessary, if it is involved, this suggests that the cancer cells may have spread through the body, and chemotherapy will be necessary.For any Locally Advanced or Inflammatory cancer, chemotherapy is essential.

Other Standard Tests: Include"bone-scan" where a small quantity of radioactive dye is injected into a vein, and a special X-ray is then taken to see if the cancer has gone to bone. Breast cancer has a predilection to go to bone, where it may lie dormant for many years. A "baseline" scan is obtained for any invasive cancer, to make later scans easier to compare and interpret. If "something" is seen on a bone scan, it may or may not be cancer. Old fractures, inflammation, or infections can make bone scans"light up" in those areas. The 2 ways of seeing if cancer is causing the increased "uptake" is to do a bone biopsy, or do another bone scan several months later to see if the area has"progressed". In practice, bone biopsy is difficult and may still miss an area of cancer spread, giving a false sense of security. Repeat scans, and the expertise of the radiologist in determining whether cancer is causing the abnormal bone scan are relied upon. Chest X-ray and Chest and Abdominal CT scans ("Computerized Axial Tomography"). A contrast solution may be injected into an arm vein, which helps highlight blood vessels in a CT scan. Insist upon"omnipaque" brand or equivalent contrast; it is more expensive but also more comfortable and less likely to cause allergic reactions or kidney failure. These scans are obtained to help rule out spread, or "metastasis" of cancer to the lungs and liver. CT scan of the Brain or Bone Marrow Biopsy are only done if their is suspicion that the cancer has spread to these organs, or if a bone-marrow transplant is considered. Routine blood tests of "complete blood count" (CBC ) and "chemistry panel" (SMA ) are obtained prior to any therapy.

How is the Extensiveness of Breast Cancer Gauged?

Like any cancer, the extensiveness of Breast Cancer is given by the"Stage". The American Joint Cancer Committee ("AJCC") has stages given by Roman numerals:

"Stage 0" means the cancer does not invade, such as "DCIS" or "LCIS"
"Stage I" means the cancer is less than 1 inch across, and is invasive.
"Stage II" means the cancer is between 1 and 3 inches across, or the lymph glands in the axilla are involved (or both).
"Stage III" means that the cancer is greater than 3 inches across and the lymph glands in the axilla are involved and may even be hard and "fixed".
"Stage IV" means that the cancer has spread to other organs, like bone or brain. This may be as little as a single lymph node involved above the collarbone ("supraclavicular node") or as much as massive cancer spread ("dissemination") throughout the body.

What is the Survival of Breast Cancer?

This depends upon many factors, including the cancer type, grade and stage, the general condition of the patient, and the treatment(s) selected. The textbook figures are:

It is crucial to note that many patients live many productive years with their cancer! The figures given above include death from all causes, including heart attack, accidents, or a different cancer. Many patients with breast cancer are elderly and have other serious medical problems ("comorbid conditions") leading to their demise.

What are the types of Later Breast Cancer?

There are 3 basic types:"Locally Advanced Breast Cancer" involves the local area of the breast and the axilla, and refers to a large but localized cancer. "Inflammatory Breast Cancer" means that the drainage channels in the skin, called the "dermal lymphatics", are obstructed by tumor-- this causes the breast to be hot, red and tender, and have a characteristic "peau de orange" (orange peel) texture."Metastatic Breast Cancer" means that the disease has spread to other body sites, such as the bone, liver, lung and brain.

What is the Conventional Treatment for Later Breast Cancer?

Treatment has historically consisted of surgery, radiation, chemotherapy, and hormones. The combination and sequence of these treatments has been refined over the past 2 decades. Specifics of each of them is now discussed in turn, with their historic results, followed by the latest, effective combination treatments and results.

Surgery was pioneered by Dr. Halstead in the 19th century-- At that time, before routine breast self-exam and mammograms, most cases were later breast cancer by the time they came to medical attention. Dr. Halstead felt that the more breast tissue and local muscle
that could be removed, the better chance of curing the patient. He advocated"radical mastectomy". In this operation, the entire breast is removed, along with the underlying muscles of the chest wall (called the "pectoralis muscles") and the lymph glands in the axilla. Halstead believed that these lymph glands acted as "trapping stations" for the cancer, which would only spread through the body after the axilla was involved. Thus it made sense to remove those lymph nodes before the cancer could spread from them. In the 1950's an even more radical operation, the"extended radical mastectomy" was done which was a combination of a radical mastectomy plus removing the lymph glands from under the breastbone ("internal mammary nodes"). When the more drastic operations were not shown to increase cure, breast surgeons advocated "modified radical mastectomy", where the major chest wall muscles were kept in place (which helps arm function) and the internal mammary lymph nodes were again not removed. This remains the most common operation for breast removal today. Along with breast removal surgery, a new artificial breast may be constructed by sewing a back of gel material under the skin. Even a fake nipple can be formed.

Side Effects of Surgery include a standard operative death risk of 1-2%, infection risk of 10%, and possible arm weakness and swelling (called "edema" ) with extensive surgery. The recovery period depends on the extent of surgery, it is from weeks to months. Generally, tissues are 75% back to their normal strength 3 weeks after surgery.

The Results of surgery alone depended upon the type of Later Breast Cancer. For Locally Advanced Breast Cancer, 5 year survival was about 40%, For Metastatic Breast Cancer, 5 year survival was 20%, while for Inflammatory Breast Cancer, 5 year survival was a dismal 5%. The reason for these poor survivals is that the cancer was already asystemic disease (cancer cells had spread through the body) before the surgery was performed, so the patients failed "distantly" after local surgical treatment.

Radiation Therapy is thoroughly discussed now since it is currently almost always used for later cancer. It Has been used alone for cancers that were too large to remove surgically, or for patients who couldn't tolerate surgery. It used to be given by a radiologist who did X-rays, but is now prescribed by a specialized cancer doctor called a "Radiation Oncologist". Prior to starting treatment the patient is "Simulated", which means they are placed on a fake treatment machine, the chest is exposed, and aligned with laser lights. The treatment area is marked out, first with pens and eventually with small permanent tattoos. A CT scan of the chest may be obtained, and the information from the simulation is put into a"treatment planning computer". A "plan" is generated, which tells how much radiation is going to the breast, axilla, and underlying normal tissue like lung. This plan is standardly reviewed by a "Radiation Physicist" (who has at least a Master's Degree and usually a Ph.D) to ensure it's safety. For locally advanced breast cancer it is common to use a "three-field technique", that is the breast or chest wall is treated with 2 oblique radiation beams, while a third "en-face" field is aimed directly down to cover the area over the collarbone (clavicle) and axilla. Special blocks are cut to protect sensitive normal tissues, such as the underlying lung, these are placed into the head of the treatment machine. The patient need only lie still on the hard table to receive their therapy. Treatments are given Monday through Friday, taking only about 15 minutes per day for 6 - 7 weeks. The total dose of radiation is between 50 and 75 Gray (units of radiation) with the tumor area getting more dose than the "regional lymphatics" (the axilla and area above the collarbone). X-ray "verification films" are taken each week or so, which tell only about the consistency of the patient's position; they do not tell anything about the cancer. Commonly, the last week of treatment is a"boost" to the actual tumor area, sparing the lesser involved areas. The patient does not get sick, become radioactive or lose their hair. They can maintain a normal diet and most activities, like driving or taking occasional alcoholic beverages.

Side effects of local chest radiation are divided into "acute" and"late" effects. Acute effects occur during the treatment period, while late effects may occur months to years after treatment is complete. Common acute effects include redness and tenderness in the treatment area, especially about the skin folds under the breast and in the armpit. This starts occurring after about 2 weeks of treatments, and may progress to skin peeling, called "desquamation". Special salves, like acemannan, or steroid creams may reduce the irritation. Patients are also usually mildly fatigued during the treatment period. Later effects of radiation include possible lung injury, called "radiation pneumonitis", which is usually only detectable by chest X-ray and has no symptoms. Less than 10% of these patients get symptoms of cough, shortness of breath, and fatigue-- which usually quickly respond to steroid medication. Skin reaction and heart or lung problems are greater if chemotherapy is also used. Very rarely (<1%) patients may develop a severe syndrome of lung injury leading to death. Other later effects include arm swelling (especially if radiation is given after surgery) and very rarely second cancers developing in the swollen arm("lymphangiosarcoma") or in the irradiated lung (especially in smokers). More commonly the radiation is well tolerated, the skin reaction subsides after finish of treatment, and the chest tissues become somewhat firmer and tougher ("fibrotic'). The skin may have small bluish capillary markings, and be lighter in color. Ironically, some patients actually prefer the firmness of a breast which has be treated! **Results of Radiation alone are similar to surgery, with 5 year average survival at 40% for locally advanced breast cancer, 20% for Metastatic breast cancer, and 5% for inflammatory breast cancer. This again is because radiation, like surgery, only treats the local area of disease, while the cancer cells have already spread in the body.

Chemotherapy has not been conventionally used alone for treating breast cancer, but is extensively used in combination with other treatments as will be discussed. Popular Chemotherapy drugs include Adriamycin ("A"), Cyclophosphamide ("C"), Methotrexate ("M") and 5-Fluorouracil (5-FU or "F"). Taxol is a newer drug that will be discussed later. Combinations are frequently prescribed, such as CAF or CMF, usually given for six monthly "cycles". A newer convenient regimen is"AC times 4" -- that is just 2 drugs for 4 cycles. The idea of Chemotherapy in Later Breast Cancer is two-fold-- to shrink the tumor and make it easier to remove or radiate, and to kill cancer cells which have escaped from the breast tumor, traveled through the bloodstream, and implanted elsewhere in the body. These are called"micro-metastasis", and although they cannot be detected with any current technology (since they are so small), we know that they may be present and eventually grow into large tumors. If they do, it is called"distant failure", and this may be prevented with aggressive chemotherapy. Once the "tumor burden" of metastatic cells is high (i.e. they can be seen on scans) we cannot "cure" the patient (although they may live for many productive years). Chemotherapy may kill micrometastasis and thus prevent the cancer from recurring, since it travels throughout the body ("systemically"). Chemotherapy is also useful for shrinking large local tumors and reducing the risk of local recurrence in the breast or chest after surgery. That is, it can help with "local control". Both effective local and distant control are mandatory if the patient is to be cured, utilizing multiple modalities (i.e. surgery, chemotherapy, radiation, hormones) for this purpose is called "multi-modality" therapy.

Side Effects Of The Common Chemotherapeutic Agents

1)Adriamycin can cause heart damage and the dose is limited to 500 mg/square meter of patient body surface area. It is common to get a "heart scan" called a "MUGA" test before giving Adriamycin. It also causes greater skin redness and irritation (called a "recall reaction" ) if radiation is given, even months later. It is a bright red liquid given only into the veins. Adriamycin chemotherapy is considered more radical than CMF, and is given when the tumor is aggressive.
2)Cyclophosphamide (also called"Cytoxan" ) is derived from mustard gas and causes a lowering of blood counts. Drops in red-blood cell count cause anemia, with paleness and tiredness, drops in white-blood cell count lead to "neutropenia" which shows as infections and fevers, while a drop in platelet
count leads to prolonged bleeding and easy bruising. Cyclophosphamide comes in a pill which is taken daily during each chemotherapy cycle.
3) 5-Fluorouracil (5-FU) has its side effects on rapidly dividing cells in the body such as the lining of the intestines and also the bone marrow. It can therefore lower blood counts, and cause mouth sores and diarrhea. Rarely, 5-FU can cause skin peeling and nervous system symptoms. 5-FU is given into the veins either as individual injections on the first and eight day of each cycle (called "bolus" ) or as a constant drip of the drug during each cycle through a portable dose pack (called "continuous infusion" ).
4) Methotrexate has similar side effects to 5-FU, and can also cause a lowering of liver and kidney function. It comes as an intravenous injection, and can be given into the spinal fluid for the rare meningitis caused by spread of breast cancer to the central nervous system.

The Results of chemotherapy alone shows shrinkage in over 80% of tumors when it is given in combinations like CMF and CAF. Practically speaking, however, it is difficult to completely obliterate breast cancer with chemotherapy alone, and the response may be short lived. Cancer cells can develop resistance to chemotherapy. Therefore, it is used in combination with other treatments such as surgery and radiation, to increase its effectiveness. Chemotherapy for breast cancer helps gain both "local" and "distant" control of disease-- and both are necessary for the patient to be cured.

Hormonal Therapy is extensively used in breast cancer, and is especially effective for "Estrogen Receptor Positive tumors", which is the most frequent kind in women after their menopause. It has been long noted that women who had their ovaries either removed surgically called "oophorectomy" or sterilized with radiation treatments often had a slowing of the progression of their breast cancer. Instead of removing or radiating the ovaries, drugs have been developed which counteract the female hormones which can promote breast cancer growth. The most common "anti-estrogen" drug istamoxifen (nolvadex) which is given as a 10 mg. tablet twice per day. Since it also has some estrogen-like properties, it can cause an initial increase in bone pain, called a "flare" when it's first started. It commonly causes hot flashes and fatigue. Tamoxifen also appears to increase uterine cancer in women who have kept their uterus. Breast cancer may respond to tamoxifen for many years, then become resistant to it. This usually shows up as "progression" on a bone scan indicating the cancer is growing again. Other hormonal drugs, called "progestational agents" such as medroxyprogesterone (megace) may then be effective,
it is given as a 40 mg. tab 4 times per day. The cancer cells may become resistant to progesterones also, after which male-sex hormones such ashalotestin may be tried. These cause hair growth and increased muscle mass, but may stymie the cancer for a while. For later breast cancer, hormonal treatment is continued indefinitely, as long as it seems to hold the cancer at bay. While hormones don't cure breast cancer, they can buy time; often patients with metastatic hormone responsive breast cancer live many years without evident progression.

What is the Latest, Effective Therapy for Later Breast Cancer?

In general, the latest treatments use a combination of the above conventional treatments to reduce the chance that the cancer will come back. The specific treatment depends upon the type of later breast cancer.

Locally Advanced Breast Cancer:

This is about 25% of new breast cancer cases. Newest treatment combines modified radical mastectomy, axillary lymph node dissection, External Beam Radiation Treatment to the chest wall to 60 Gray, and chemotherapy with either 6 cycles of CAF or 4 intense cycles of AC, follow by long-term tamoxifen. Giving radiation had been controversial, but it is now definitely shown to lower local failure (which, when it occurs, is a painful, ugly process leading to a miserable death), and maybe up survival. The survival benefit at 5 -10 years combining all of the above treatments was shown in the Stockholm II trial and the Helsinki trial. Basically, both chest radiation and chemotherapy each benefit a given set of patients, and combining them gives the additive advantages of both. The Joint Center (at Harvard University) has shown that in patients with 4 or more positive lymph nodes in the axilla, radiation treatment reduces the risk of the breast cancer returning locally from 20% to 6%. The bottom line of several studies is that patients with 4 or more involved lymph nodes and/or a breast tumor over 5 cm. should get Radiation Treatments after their modified radical mastectomy, in addition to chemotherapy containing Adriamycin and long-term tamoxifen. This regimen increases 10 year survival from just 30% to over 55% for locally advanced breast cancer. It is advisable to give the chemotherapy first since a decrease in tumor stage is seen in 30% of patients and at least some response is seen in 85%. This helps tell how effective the chemotherapy is, and if it produces a complete response, the patient may then get radiation to the breast and local lymph node areas without a mastectomy! This "breast conservation" for locally advanced breast cancer has been done by Dr. Hortobagyi at M.D. Anderson Cancer Center, with no compromise in survival.

Bone Marrow Transplant:

When patients have 10 or more positive lymph nodes in the axilla, autologous bone marrow transplant should be considered-- This means that the patient's own bone marrow is collected, and then very high doses of chemotherapy are used, to kill the cancer. This dose of chemotherapy is so strong that it wipes out the remaining bone marrow, as well as the cancer cells (hopefully). The patient would die of anemia and infection, except that the collected bone marrow can be re-injected into their veins ("transplanted") where it finds its way back into the bones to grow into new blood-cell producing marrow. For both autologous transplants, there are two basic ways that the blood-forming cells can be collected.The first and older technique is to "harvest" bone marrow from the iliac wing bones, that is the hip area. The patient or matched donor is taken taken to the operating room and commonly put under general anesthesia. About 50 punctures are made with a special bone-boring needle into the bone above each buttock, and the marrow from this area sucked out ("aspirated"). There is no significant danger (besides anesthesia risk) to the patient, this marrow is expendable, but some scarring is common in the harvest area. The marrow is stored in glass jars. Since breast cancer cells may have contaminated the bone marrow, it may be cleaned ("purged") of breast cancer cells by using "monoclonal antibodies" (specially engineered immune proteins) against them. Research in this area is going on at the Dana Farber Cancer center. It is possible that directly injecting these monoclonal antibodies into the patient might help cure breast cancer. New techniques have improved the success of purging, but it still remains a risk to give the patient back there their disease in the transplant. The second and newer method is less invasive and does not take actual marrow, but instead"stem cells" circulating in the bloodstream. These "stem cells" can form new marrow, all of the crucial blood cells, and"reconstitute" the blood. For stem-cell collection, the procedure is not called a "Bone-Marrow" transplant but instead a "Peripheral Stem Cell Transplant". Since currently this procedure is used with the patient's own stem-cells, the full name is "Autologous Peripheral Stem Cell Transplant". For this, the patient comes in several times and has a needle ("catheter") inserted into an arm vein. Blood is drawn out and processed through a special machine which collects stem cells, and then returns the residual blood back to the patient. The cells removed are centrifuged to remove the circulating stem cells, which are packaged and stored.

The next step for any Bone Marrow Transplant is for the patient's own marrow to be destroyed by chemotherapy ("cytotoxic marrow ablation"). This is to annihilate the patient's breast cancer, and as a consequence destroys every other blood forming cell at the same time. Sometimes, part of the "preparative regimen" for Bone Marrow Transplant is the addition of "whole body radiation". For this, the patient is sent down to the Radiation Oncology Department for initial measurements of body thickness, and to make appropriate physics calculations. During the "Marrow Ablation Phase" (and while receiving the chemotherapy) about 6 whole body radiation treatments are given over 3 days (so two treatments per day about 6 hours apart). The patient, on a cart, is usually placed against a wall in the treatment room and the Linear Accelerator is turned on for about 10 minutes per treatment. They are commonly treated from each side, with their arms at their sides to help lower the dose to the lungs. A plexiglass "scatter screen" is placed between the patient and the machine, which helps boost up the dose to the skin. This is because leukemic cells can hide in the lower skin layers. The actual radiation treatment is painless, and the patient is then returned to their room.

The side-effects of the"preparative regimen" for Bone Marrow Transplant are due to a killing of all the rapidly dividing cells in the body. The side-effects will depend on whether just chemotherapy is used, or whether whole-body radiation is added also. The chemotherapy side-effects are the same as noted above for when these drugs are used a primary treatment, but for marrow ablation higher doses are given. The dose is, in fact, "super-lethal", since the patient will die if the bone marrow is not replaced. The first cells to disappear from the bloodstream are those with the shortest normal life-- white cells often only live 10 hours! Next, the platelets, with an average life of 10 days, will disappear, and finally the red blood cells with an average life of 120 days. Thus, if not replaced, we would expect to see, in order, infection, hemorrhage, and then anemia develop from the marrow ablative therapy. In practice, the patient will not live long enough to develop anemia, first dying from infection and hemorrhage. It takes a while for the re-infused bone marrow or stem cells to"take", and start producing new blood cells. This is a critical time for supportive transfusions and preventing infections. "Epogen" (erythropoetin) can help boost the red blood cell count and "Neupogen" (GM-CSF) can boost the white cell count in this critical period.

Results: The initial "complete response" ("CR") rate is as high as 65% (no detectable tumor remaining), and over 25% of patients may be cured of an otherwise fatal disease. Anti-rejection drugs are not necessary since the patient's own bone marrow is being used, but there is still about a 10% chance of dying from complications of the procedure. If you get a transplant, go to a hospital that does at least 50 per year. It unfortunately doesn't yet cure Metastatic breast cancer, although it may achieve prolonged remissions. Locally Advanced is not a uniformly fatal disease-- aggressively treat it!

Inflammatory Breast Cancer:

Used to have just 5% survival at 5 years-- The latest effective treatment is as given by Dr. Hortobagyi at M.D. Anderson Cancer Center and Dr. Fowble at the University of Pennsylvania. It is "induction chemotherapy" with CAF and BCG (an immune stimulant). Patients who have a "complete response" (no evidence of tumor) get Radiation Therapy to the breast and local lymph nodes to 50 Gray, plus a "boost" to the actual tumor site (so the total radiation dose to the tumor is about 70 Gray). If there is a "partial" or no response to chemotherapy, a modified radical mastectomy is done with radiation therapy to 50 Gray given to the chest wall and local lymph nodes. **Results are up to 65% survival at 5 years with no sign of disease! Furthermore, up to 30% of women ( those completely responding to chamois.) keep their breast!

Metastatic Breast Cancer:

Remains one of the most difficult cancers to treat. Unfortunately, no current therapy definitely cures breast cancer which has obviously spread to the bone and other organs. Naturally, is it important to be sure that the cancer actually has spread, and that the abnormal uptake seen on a bone scan is really cancer. This is accomplished with "serial bone scans" every several months to see how the area is changing. We cannot definitely say that no one has ever been cured with metastatic breast cancer, since patients may have had unrecognized metastasis at diagnosis, gotten intensive chemotherapy or even bone marrow transplant, and been cured. The rate of "total remission" (no evident cancer remaining) in bone marrow transplant patients with metastatic breast cancer is as high as 50%, but many of these patients had not had prior therapy. Mostly, chemotherapy has been started only to treat specific symptoms. The most effective chemotherapy contains Adriamycin (Doxorubicin), it is about 15% more effective than chemotherapy without it. In fact, Adriamycin alone is as effective as other "combination" regimens of multiple drugs. Often Adriamycin is reserved until other agents fail, since there is no good "third line chemotherapy" for metastatic breast cancer. Patients with metastasis to the soft tissue (e.g. muscle or fat) are most likely to respond to chemotherapy, patients with metastasis to lung or liver least likely, and patients with bone metastasis in the middle. Giving salvage chemotherapy for patients with isolated bone metastasis has produced occasional complete remissions lasting 5 years or more. The addition of the biochemical modifier"leucovorin" along with 5-FU has shown promising results as second line therapy in breast cancer, as it has in primary colon cancer.

If a patient responds to chemotherapy, the bone metastasis will slowly disappear (recalcification will occur) and the average response lasts 18 months. The main problem with chemotherapy in metastatic breast cancer is that many patients have previously been treated, and so developed resistance to the drugs. One advantage of having a bone metastasis is having "something to follow". If no response occurs after 3 cycles of chemotherapy, other "non-cross resistant" agents should be tried. The duration of remission is increased if effective chemotherapy is given continuously, as opposed to the usual 6 cycles. However, it has not been proven that this continued "maintenance chemotherapy" improves survival; and the patient must tolerate the side effects of hair loss, nausea and decreased blood counts. Taxol has about a 30% response rate in breast cancer which has failed other therapies, but causes nausea, flu-like symptoms, and lowered blood counts. It is our most effective "third line" agent available for breast or ovarian cancer. In hormone-responsive patients, the chemotherapy can be combined with hormones. Metastatic breast cancer is thought to contain different "subgroups" or "clones" of cells; some will be responsive to chemotherapy but not hormones, and vice-versa. Thus the chance of long term remission is greater if chemotherapy is added to hormonal therapy, in both premenstrual and postmenopausal patients with "hormone receptors".

Hormone Treatment alone is aimed at slowing the cancer and improving quality of life. It is not considered curative, but some patients have had sustained complete remissions lasting many years with hormones alone. Firstly, hormones work primarily in patients with hormone responsive (ER/PR positive) tumors. If both of these receptors are absent, the chance of hormones working is only 10%. However, if both ER and PR are present, the chance increases to around 70%. The average"duration" of response with a hormone is 18 months, after which the cancer progresses. Then a second line hormone is used, and then a third line one. The chance for response will decrease with each successive hormone tried. Thus many doctors don't try "fourth line" hormones. However, if hormone receptors are present but one agent doesn't work, the chance of responding to a different one is still excellent. but in the hormone responsive patient. The first "hormonal manipulation" encouraged for hormone responsive patients with breast cancer metastasis is having their ovaries removed("oophorectomy") or radiated to destroy them. This alone has held the cancer at bay for many years in occasional patients. Giving hormones (first tamoxifen, then megace, or goseralin acetate, then halotestin) can often slow the progress of the cancer significantly. Hormones can be taken as pills, or often as "deep muscle depot" injections each month. Patients may live for many years with Metastatic breast cancer, and symptoms are treated as they arise. It may be a very indolent disease.

However, symptoms should be treated aggressively, and some are even medical emergencies. When breast cancer is the most advanced type with distant disease spread through the body, the objective is no longer cure but palliation (meaning relief of pain and other symptoms). The patient would be made as comfortable as possible, and narcotic medicines like morphine (which Sir Wm. Osler called "G-d's own medicine) should never be withheld for fear of causing "addiction". Using "Fentanyl Patches" applied to the skin helps give a continuous amount of narcotic, eliminating the problems of forgotten doses, "loss" of narcotics, and smoothing out the dosing for less disturbing "highs and lows". Importantly, Radiation Treatment can help relief local symptoms (such as skin involvement), bleeding, and bone pain in over 80% of patients. It is helpful if bones have become weakened from cancer invasion, and have fractured ("pathological fracture" ) or are in danger of doing so. Radiation Therapy centers with"hyperthermia" can use this newer technology to heat an area of skin metastasis, and then give the radiation treatment. This is very effective for reducing unsightly skin spread more quickly and effectively than standard radiation treatment. Hyperthermia is also useful for decreasing the dose needed to control massive local disease invading the chest wall, with it's attendant problems of pain, oozing fluid and infection. Radiation is utilized for reducing the symptoms, and even extending survival, in patients with spread to the brain. Sometimes radiation therapy is used as an emergency measure when the cancer spreads to the spinal column and threatens to cause paralysis by pressing upon the spinal cord. Any patient with breast cancer who experiences new weakness of the extremities, numbness, or loss of bowel or bladder function must be brought into the Emergency Room immediately to see whether the tumor is compressing the spinal cord causing these symptoms.

Up to 60% of new back pain in a cancer patient is caused by spread of cancer there. The patient is given a painless Magnetic Resonance Imaging (MRI) scan to check for "epidural spinal cord compression". If this is caught early, and treatment is given, permanent paralysis may be prevented. It is unfortunately uncommon to reverse symptoms of paralysis once they have set it, however, so quick recognition is essential. As mentioned, radiation treatment can be very helpful for metastatic breast cancer. A relatively new method of radiation for spread to the brain (one of the most common areas of spread) is "Stereotactic Radiosurgery", where multiple beams of convergent radiation are aimed onto the area(s) of spread in brain, in a single painless session of one afternoon. This is usually followed by conventional External Beam Radiation. The advantage of Stereotactic Radiosurgery is that it can give a very high dose of radiation to areas of brain metastasis, and possibly enhance survival for these patients, without the risk of an open brain surgery from a neurosurgeon. CancerAnswers has a Transcript on In-Depth Radiation Therapy available through our Web Site.

Other options for patients in severe pain for multiple areas of spread to bone include "hemi-body" radiation, and "strontium-89". Hemi-Body radiation uses a low dose (6 to 8 Gray) in a single treatment to the upper or lower body to treat multiple areas of bony involvement; some anti-nauseants are usually necessary and it lowers blood counts. It is over 90% effective for pain relief lasting an average of 6 months. Strontium-89 is an injected radioisotope that goes through the bloodstream to all bony areas, and is especially attracted to cancerous areas. It also lowers blood counts but is very effective at palliating pain. It can only be done once. If no relief is gotten from medications or radiation, neurosurgical techniques to cut sensory nerves can usually afford relief, to this small population of patients. CancerAnswers has an In-Depth Transcript on Symptom Relief available through our Web Site. Committing suicide because of unrelieved pain should never be necessary with pain science today.

The most common cause of death in breast cancer spread to bone is increased blood calcium, that is "hypercalcemia". Studies have found that injectable Gallium Nitrate is the most effective drug for combating this (better than Etidronate) and it may prolong the patient's life.

Conclusion:

The patient with newly diagnosed breast cancer should not rely upon any single therapy, such as a pill or ray, but instead should use a"combination approach" to maximize the chance for success. Specifically, besides the conventional medical therapies mentioned above, consider the use of a non-toxic, not over-expensive alternative therapy you can believe in. CancerAnswers offers an Alternative Therapies Transcript on Breast Cancer available through our Web Site. Also, a program of spiritual renewal, "mind over cancer', nutritional therapy and exercise is appropriate.

Keep the most positive attitude possible. Research has shown this to be an important factor in cancer survival. Using a true"multi-modality" approach will give the confidence that you have done everything possible for a happy outcome, and will anyway improve quality of life. If the patient is willing to subject themselves to medical research, Clinical Trials are offered at Major University Academic Centers. The National Cancer Institute keeps of list of currently Open Clinical Trials on their Website; many Institutions have their own "in-house" research. However, Clinical Trials often have specific enrollment criteria, and one cannot then select which treatment (which "arm" of the study) they will get. Thus, one loses "control" of their treatment when entering a Trial. NSABP trials are well designed and will not shirk a patient from basic established therapy; they are now to "fine-tune" the treatments. Advances in the past 2 decades make it more likely for the patient with later breast cancer to live longer and more comfortable lives than in the past, and have new cause to hope for tomorrow.