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GENERAL BACKGROUND

In the United States each year approximately 180,000 patients present with carcinoma of the breast. Of these, approximately 1 percent are men. Overall, 44,000 to 50,000 women die each year from breast cancer. Breast cancer and lung cancer are the foremost causes of cancer death in women. Up until 1990 breast cancer was the leading cause of cancer deaths among women, but at that time, cancer of the lung surpassed cancer of the breast as the leading cancer killer of women.

This is secondary to the increased incidence of cigarette smoking in women. Most breast masses that women find are benign. Only about 12 percent of breast masses are ever malignant. A woman in the United States who lives to be age 100 will have a 1/10 chance of developing breast cancer sometime during her lifetime. The risks factors for breast cancer are age of 50, a personal or family history of breast cancer, not having children, or delivering the first child after the age of 30.

The increase in the number of breast cancers has been greatest in the last 20 years in those patients who are between the age of 45 and 75 years. There has been a more marked increase in the incidence of breast cancer among black women in those age groups. Breast cancer is observed more frequently in whites than non-whites, Jewish women than non-Jewish women, and in women in the upper socioeconomic classes rather than lower socioeconomic classes. It is also more common among women who have never been married, and it is more common in women who have never been pregnant.

There is a very strong relationship of the formation of breast cancer in women with a strong family history of breast cancer in immediate relatives, for instance, mother or aunt.

Patients who have been exposed to ionizing radiation during the time of puberty or after puberty have an increased risk of developing breast cancer, also. The incidence of breast cancer after exposure to radiation decreases very rapidly with the increase in the age of the person who was exposed. For instance, teenagers would have more of a chance of developing breast cancer because they were exposed to radiation than would a patient who is 50 or 60 years old.

Higher alcohol consumption has been associated with an increase in the chances of breast cancer development. Also, the use of hormone replacement therapy (HRT) has been associated with an increase in the development of breast cancer.

The most common site within the breast for the development of a breast tumor is in the upper and outer part of the breast towards the armpit. Almost 40 percent of breast tumors occur in that area. Breast cancer develops and grows very slowly. It takes about five years for the tumor to reach the size where it can be felt. As the cancer grows it travels along the ducts within the breast, eventually breaking through the basement membrane of the duct and invading adjacent lobules and fat. It can spread through the breast lymphatic vessels and into the armpit lymph nodes.

The tumor can eventually grow through the walls of blood vessels and spread into the skin and can cause swelling of the breast. Generally, cancer of the breast presents early with a tumor less than 5 cm (2 inches) in size. It is usually found by the patient or found at the time of a screening mammogram.

Occasionally patients will have tenderness, but most times breast cancers are not painful. Late changes include skin dimpling or changes in the shape, size, or color of the breast. Occasionally patients can have a bloody nipple discharge. Sometimes patients will have nodes in their axilla which are painful and palpable.

DIAGNOSIS | Back to Top
One of the more revolutionary tests for the diagnosis of breast cancer is the mammogram. Mammograms were developed back in the early 1960s and were shown to decrease the death rates of patients who were over the age of 50 when they had their breast cancer diagnosed by a mammogram. In the mid 1970s there was a great debate among radiation physicists and clinicians regarding the effectiveness of mammography.

At that time the techniques were slightly different than those used today, and there was some concern that the dosage of radiation to perform mammography was so high that over a period of time it might be enough to cause breast cancer in women.

Over the next few years there was a marked change in the technology with the use of better x-ray films, lower energy radiation beams, different generators for the radiation, and different techniques, all of which were able to lower the dose of the mammogram to less than one rad per examination. Mammograms have definitely allowed us to diagnose breast cancer at a much earlier stage than previously. Before mammography, if one could not palpate the tumor, one didn't know it was there.

Now mammography can show small changes in the breast, including the findings of very small calcifications in the ducts in the breast which allow the radiologist to alert us that there may be a cancer within the breast. This has led to earlier biopsy and, thus, diagnosis.

When a patient comes in to the doctor with a lump in her breast which she has found, the physician generally will obtain a mammogram. If a lump is seen on the mammogram, then often an ultrasound will be done to determine if the mass is solid or whether there are cystic areas within it. Cystic masses tend to be benign. If a mass has irregular edges or extremely small calcifications, it is probably best that the lesion be biopsied.

One of the newer ways to biopsy a mass is using stereotactic guidance with an ultrasound machine. This allows the surgeon or the radiologist to place six or more needles into the breast and extract tissue, which is then sent to the department of pathology. This gives the pathologist adequate tissue to examine and determine whether the mass in question is benign or cancerous.

TREATMENT | Back to Top
Once a diagnosis of cancer is made, the treatment is determined by the size of the cancer, the size of the patient's breast, and other tests which are done on the tissue.

The history of treatment of breast cancer goes back thousands of years. However, the more modern treatment of breast cancer, a radical mastectomy, was described in the late 1800s by William Halstead. At that time, there was a considerable debate regarding the spread of breast cancer. Many surgeons felt breast cancer was a disease which would be spread throughout the body at the time it was found.

However, William Halstead, a very influential surgeon at Johns Hopkins University in 1895, presented a theory in which he described the spread of cancer from the breast to the lymph nodes. He believed the cancer could be stopped by removing all the lymph nodes in the armpit. He felt when cancer cells got to the armpit they could spread further through the blood stream into the rest of the body. Dr. Halstead's theory of the treatment and spread of breast cancer was the predominant mode and philosophy of treatment in America for 80 years. Despite radical mastectomy, 30 percent of women with early breast cancer died of their disease, mainly from spread to other parts of the body. This is called metastatic disease.

In the late 1960s chemotherapy was introduced into the treatment of some of these women who had metastatic disease. It was noted that chemotherapeutic agents could cause a regression of the cancer and, in some patients, the total remission of cancer for a period of time.

Because of that, medical oncologists began to treat patient's more aggressively when they had cancer which most likely would recur — patient's with large tumors or patients with many lymph nodes in the axilla. In the mid 1970s chemotherapy became a major assisting treatment to surgery in the treatment of patients with breast cancer.

Also, over the years radiation delivered after surgery was utilized in patient's who had large tumors of the breast (more than 5 cm in size, or about two inches in diameter) and in those patients who had four or more positive lymph nodes (lymph nodes containing cancer) removed from their armpit. The radiation treatment was able to prevent the recurrence of disease on the chest wall and in the lymph nodes in the neck and over the top of the collar bone.

Besides its use as a postoperative treatment of breast cancer, radiation has been found to be a major treatment for breast cancer when the tumor has been removed by simply locally excising it (removing the lump). The treatment of breast cancer with radiation as a primary modality goes back to the 1920s in England when Sir

Geoffery Keynes began to implant breast cancers with radium needles. His results equaled those of the University of Cambridge surgeons as far as overall survival was concerned, but because of the morbidity (the side effects and complications) of the procedure it fell into disrepute. In the mid 1960s at Columbia University in New York, Dr. Haagensen, a major breast surgeon began to note that patients who had postive lymph nodes at the highest point of the axilla, in the area under the sternum or over the collar bone, very seldom were cured of their breast cancer. Therefore, he developed a triple biopsy technique performing biopsies of lymph nodes in these areas and performing frozen section diagnosis on them.

If the patient was found to have positive lymph nodes at the time of frozen section, then the mastectomy was not done and the patients were treated with cobalt radiation by Dr. Ruth Guttman in the radiation department of Columbia Presbyterian Hospital. Dr. Gutman had excellent results with 60 percent of her patients being alive five years after the radiation, free of disease, and 30 percent alive ten years after the radiation, free of disease.

In 1979, Dr. Eleanor Montague of the M.D. Anderson Hospital in Houston, Texas, presented her data revealing 96 percent local control of disease in the breast following limited surgery and radiation treatment. These results were also found in France, where the 10-year accrued survival in patients with early stage breast cancer was approximately 70 percent and equal to that of surgery. Dr. Bonnadona in Milan, Italy, performed a randomized trial and found that conservation treatment of the breast by doing a lumpectomy and axillary operation and then treating with radiation produced results equal to results of removing the breast.

In 1978 Dr. Samuel Helman, at the Joint Center for Radiation Therapy, reported excellent local control in the breast at five and ten years with good cosmetic results. Therefore, in the early 1980s, the use of conservation surgery and radiation therapy blossomed. The patients with small tumors and regular-sized breasts were offered the option of having the tumor completely removed and having their lymph nodes explored, and then having radiation treatment rather than a mastectomy. Although this would seem appealing, only about 40 percent of women choose this as their option for the treatment of their cancer, although today more women are beginning to choose this option.

Not everyone is eligible for a lumpectomy and radiation therapy. The tumor must be removable without producing a major cosmetic deformity in the breast. There should only be one primary lesion — patients with more than one lump in their breast should not be treated in this manner. Mammographic calcifications should be located in only one quadrant of the breast. The lesion should be far enough away from the nipple and the area around the nipple so the area does not have to be removed during the surgical procedure.

There should be a complete gross, and preferably a complete microscopic excision, or removal, of the mass. As part of the patient's care, lymph nodes need to be removed from the armpit. The presence of lymph nodes containing cancer in the armpit is one of the leading factors which determines whether a patient has an opportunity to be cured of breast cancer. The more cancer containing lymph nodes in the axilla, the greater the risk of spread of cancer throughout the body.

It has been common for the past 100 years to perform axillary lymph node dissections to remove anywhere from seven to twenty lymph nodes from the armpit to determine if any positive nodes are present. Fortunately, over the past five years a procedure called sentinel node biopsy has been developed which allows the surgeon to remove one or two lymph nodes and by using those lymph nodes determine whether or not there is a greater risk of other lymph nodes being positive in the armpit. If the sentinel lymph nodes are free of cancer, the chance of other lymph nodes in the armpit being involved by cancer is only about 2 percent. If the sentinel nodes are involved, then an axillary dissection should be performed to determine the exact number of lymph nodes which are involved in the armpit.

At the Carolina Regional Cancer Center, we limit conservation surgery and radiation treatment to those patients who have a tumor less than two inches in diameter and who have had a complete excision with a free margin (a clear area of tissue) around the mass as removed by the surgeon. Those patients whose mass is 1 centimeter or greater in size (greater than a half-inch in diameter) with or without positive LNs should be evaluated by the medical oncologists to determine if systemic chemotherapy might add to the chance of cure of their disease. Those patients who are in need of systemic chemotherapy should complete their chemotherapy before the radiation to the breast is begun.

The patient who chooses conservation surgery and radiation therapy will be treated with 25 to 30 treatments. Most of those treatments will be delivered to the chest wall with a beam of radiation from a linear accelerator treating the breast and chest wall tissues. The machine is somewhat distant from the patient's body, and there is no sensation during the treatment. The patient is usually in the center for 20 minutes a day and on the treatment table for roughly eight minutes, most of which is spent positioning the patient, positioning the treatment table, and positioning the linear accelerator for the therapy session. The machine is generally on for about two minutes during the daily visit.

The patient cannot feel the treatment, cannot see anything happening, and only hears the machine turn on and off. Once the treatment is completed, the patient may dress and leave the center. The patient will not be ill from the treatment and can drive her car because there is no nausea, vomiting, diarrhea, or other major effect from the treatment on a daily basis.

The final week of treatment (treatments 25 to 30) is given only to the site of the lumpectomy. The machine comes very close to the patient during thistreatment. Particles of radiation (electrons) which penetrate only the depth of the breast and do not bother the lung are used for this phase of treatment. During the course of radiation the patient will notice at approximately day 12 or 13 that the breast may become slightly pink and the nipple may become slightly tender. Also, around that time the patient may notice some mild fatigue.

Patients may experience further reddening of the breast as the number of treatments increases. Also, sometime around treatment 23 or 24 some patients may experience a loss of skin in the fold under the breast or in the upper part of the armpit. These side effects disappear within ten days after the radiation has been completed.

SIDE EFFECTS | Back to Top
There are some long-term effects from the radiation. Some patients will have weakness of the ribs. This occurs in about 1/100 patients and is related to the fact that small blood vessels feeding the ribs are at some time affected by the radiation treatment. Rib fractures may occur more frequently in these people if there is excessive stress put on the chest wall, i.e., severe coughing with the flu or pneumonia. These ribs will heal, but they will heal a little more slowly than normal.

The patient also may experience some mild reaction in her lung about six to twelve weeks after the treatment. On rare occasions, a patient may have some cough and fever associated with an inflammatory reaction in the lung caused by the radiation. This usually disappears in about two weeks, but an occasional patient may require the use of steroids and antibiotics to help alleviate some of the symptoms. About 3 percent of patients will develop this reaction and have some very mild scaring of the lung which, in general, does not cause any long-term respiratory problems.

When the left breast is treated, the tip of the heart will be in the radiation beam. The patient will not develop any coronary disease or have a heart attack because of this treatment. One in 250 people will develop some fluid in the sac around the heart which will cause the heart to beat abnormally and lead to some shortness of breath and swelling of their legs. If this were to occur, the patient would see a cardiologist and have an ultrasound of the chest done; the cardiologist would place a catheter in the pericardial sac (the sac around the heart) and extract fluid which would relieve the patient's symptoms.

Radiation not only cures cancer; it can also cause cancer. The chances of a radiation-induced cancer in the breast are approximately 1/1000. Should that occur, a mastectomy would be performed, chemotherapy would be given, and some radiation might be used on the chest wall. These tumors, however, can be extremely lethal, and most patients who develop a sarcoma after radiation will die of their disease. However, these tumors are rare, and the benefit of radiation treatment far exceeds the chances of such a disease occurring.

Radiation has allowed patients to keep their breasts. If a patient has the removal of a lump and no radiation treatment, her chances of having a recurrence of cancer in the breast area are approximately 40 percent. When radiation is used after the removal of a lump, the chance of cancer coming back in that breast is about 5 percent.

Should the patient develop a recurrence of her cancer in her breast, a mastectomy would be necessary at that time. A recurrence of tumor in the treated breast is not an indication that the patient will die of a breast cancer. It simply means, unfortunately, that a tumor has recurred in the breast and this time a mastectomy must be done because the breast was previously treated with radiation. The patient has a 70 percent of living free of disease five years after mastectomy.

The cosmetic results after radiation are good. Eighty-five percent of patients relate their cosmetic result from this treatment as excellent or very good. Ten percent of patients will have some edema (swelling) of the breast, which may last approximately two years, but this edema will gradually disappear. Another five percent of patients will have some shrinkage of the breast.

Many patients are concerned about swelling of the arm after radiation treatment. Surgical studies have shown that approximately 40 percent of patients will have some swelling of the arm after their surgical procedure even if they don't have radiation treatment. Today, with improved techniques, the chances of having a markedly swollen arm are not very high. However, the overall incidence of lymphedema reported after surgery and radiation is approximately 10 percent.
We have a very aggressive philosophy regarding edema. When we have patients in whom we see swelling beginning, we immediately send them to a local lymphedema specialist to learn techniques of care for the arm.

Before any radiation begins, patients undergo a planning session. This procedure is called the "simulation." The procedure takes about 45 minutes; the patient is placed on a special apparatus which allows her to place her arms up over her head and grab handles to keep her arms out of the way of the radiation beam. Flouroscopic procedures are performed, and then x-ray pictures are taken to initially indicate an area of treatment. At that point, multiple lines are placed on the patient's chest and arms which allow for daily, accurate positioning for radiation treatment. Following the simulation procedure, a CT scan of the chest is performed.

This CT scan is downloaded into the treatment planning computer, and this allows us to plan the radiation beams so they treat the minimal amount of lung and heart, but give the maximum amount of treatment to the breast and chest wall.

POST OPERATIVE RADIATION | Back to Top
Some patients who have a mastectomy need to have chemotherapy and radiation after their surgery. Chemotherapy is generally delivered to patients who have any lymph nodes positive or who have tumors greater than 1 cm in size (one-half inch) or who have certain other pathologic findings, such as negative estrogen receptors, positive herceptin receptors, or high proliferation factors. (Proliferation factors are indications that the disease is growing rapidly.)

Not all patients who receive chemotherapy after their surgery need radiation. Over many years we have learned that patients who have tumors which are greater than 5 cm in size or who have four or more cancer-containing lymph nodes removed from the axilla have a higher incidence of recurrence of the cancer on the chest wall.

Those patients, therefore, receive treatment to their chest wall and their lymph nodes just above the clavicle and in the low neck once their chemotherapy has been completed. This treatment for many, many years was thought not to change the survival chances of women with breast cancer but only to change the chance of disease returning on the chest wall.

However, there have now been studies that have shown the use of radiation to the chest wall and to the lymph node bearing areas, after surgery in these women, actually increases their chances of survival by 7-10 percent. The process of radiation in these women is virtually the same as in women who have kept their breast.

THE FUTURE | Back to Top
In summary, radiation as a modality of treatment of carcinoma of the breast has taken on a new and expanded role. It is now used as a primary treatment after minor surgical removal of the breast mass. It has also been found to be a modality to increase the chances of cure after the removal of fairly large cancers. Research regarding radiation in carcinoma of the breast is continuing.

There are some institutions now performing partial breast irradiation. In these techniques, only the tissue immediately around the area of the lumpectomy is treated; the remainder of the breast is spared from radiation. This is a major departure from the standard of care over the past 110 years, which has been treatment of the complete breast in a patient with breast cancer.

Partial breast irradiation can be performed in one of three ways: an implantation of radioactive seeds within the breast; the use of three-dimensional conformal radiation therapy to deliver a high dose of radiation to the area of the lump and little dose to the area around the lump; or intensity modulated radiation therapy (IMRT), a new improved way of aiming radiation at the region of the lump only. As time goes on we will have more and more data regarding this procedure which should at this time be considered experimental.

Patients who come to Carolina Regional Cancer Center undergo an initial history taking and physical examination procedure. Following that, there will be a discussion of the proposed treatment and alternative therapies which the patient may entertain. The patient can make up her mind right then and there as to what she wants to do or consider her options and let us know later.

We are always here to answer questions for the patient. When you come, please bring your family with you so that we may discuss everything with everyone all at once, allowing everyone to get the same information. We look forward to caring for you and participating in this journey with you.

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