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BREAST CANCER

* Please note that most treatment modalities listed below are based on conventional medicine. PreventDisease.com does advocate the use of any pharmaceutical drug treatments. Long-term drug therapy is detrimental to human health. All drug information is for your reference only and readers are strongly encouraged to research healthier alternatives to any drug therapies listed.

WHAT IS BREAST CANCER?

Breast cancers are potentially life-threatening malignancies that develop in one or both breasts. The structure of the female breast is important in understanding this cancer:
  • The interior of the female breast consists mostly of fatty and fibrous connective tissues.

  • It is divided into about 20 sections called lobes.

  • Each lobe is further subdivided into a collection of lobules, which are structures that contain small milk-producing glands.

  • These glands secrete milk into a complex system of tiny ducts. The ducts carry the milk through the breast and converge in a collecting chamber located just below the nipple.

  • Breast cancer is either noninvasive (generally known as in situ, that is, confined to the site of origin) or invasive (spreading).

Noninvasive Breast Cancer

Noninvasive breast cancers include the following:
  • Ductal carcinoma in situ (also called intraductal carcinoma or DCIS). DCIS consist of cancer cells in the lining of the duct. DCIS is a non-invasive, early cancer, but if left untreated, it may sometimes progress to an invasive, infiltrating ductal breast cancer.

  • Lobular carcinoma in situ, or LCIS. Although noninvasive, lobular carcinoma in situ is a marker for an increased risk of invasive cancer in both breasts. (Some experts prefer to call this condition lobular neoplasia rather than refer to it as a cancer.) According to a 2001 report, for patients with LCIS the risk for developing invasive cancer in the same breast is about 18% and in the other breast is 14% after 20 years. These invasive cancers can either be lobular or ductal.
At the time of diagnosis of these early cancers (i.e. DCIS and LCIS), there is no evidence of invasion.

Invasive Breast Cancer

Invasive cancer occurs when cancer cells spread beyond the basement membrane, which covers the underlying connective tissue in the breast. This tissue is rich in blood vessels and lymphatic channels that are capable of carrying cancer cells beyond the breast. Invasive breast cancers include the following:
  • Infiltrating ductal carcinoma. This is invasive breast cancer that penetrates the wall of a duct. It comprises between 70% and 80% of all breast cancer cases.

  • Infiltrating lobular carcinoma. This invasive cancer has spread through the wall of a lobule. It accounts for between 10% and 15% of all breast cancers. It may sometimes appear in both breasts, sometimes in several separate locations.
There are other less common breast cancers, which are not discussed in this report.

WHAT ARE THE RISK FACTORS FOR BREAST CANCER?

Experts estimate that over 193,000 new cases of female breast cancer will be diagnosed in 2001. About 1,500 breast cancers will be diagnosed in men during the year.

Age

At this time, age is a major identifiable risk factor. More than 80% of breast cancer cases occur in women over 50. The odds by age are as follows:
  • Cancer in women younger than 30 is very rare, accounting for only 1.5% of all breast cancer cases.

  • At age 40, a woman's chances for breast cancer are one in 217.

  • At age 50, they are one in 50.

  • If a woman lives to be 85, the odds of her having breast cancer are one in eight.

Ethnicity

The mortality rate in African Americans is twice that of Caucasians. Possible reasons for this disparity include the following:
  • Social and economic factors make it less likely that African American women will be screened and so they are more likely to be diagnosed at a later stage. They also are less likely to have access to effective treatments. (It should be noted that when they do have equal treatment, outcomes are the same as in Caucasian patients.)

  • Genetic factors may cause larger and more aggressive cancers in some African American patients.
Native Americans, Hispanics, and Asians have lower rates of breast cancer than Caucasians and African Americans.

Genetic Factors and Family History

An estimated 10% of all women with breast cancer have a very strong family history of the disease, which often appears in young women under the age of 50. In such families, some members may also have developed ovarian cancer as well. Certain known genes predispose women to this cancer are as follows:

BRCA1 and 2 Genes. Inherited mutations in genes known as BRCA1 or BRCA2 are now believed to be responsible for 30% to 50% of hereditary breast cancers, ovarian cancers, or both in families with a history of these cancers. The risk each carries appears to be as follows:

About half of BRCA1 carriers will develop breast cancer by age 70.

According to one study, about 37% of BRCA2 carriers develop the disease. (These percentages are even higher in some studies.) BRCA2 genes may confer an increased risk of breast cancer in men as well as in women (which is still very low).

These mutations can be passed down to the daughter by either the mother or the father.

These mutations are present in only about 0.1 of the population overall, but are present in about 2% of all Jewish women of Eastern European descent. This prevalence in a relatively large population makes mutations to BRCA1 and BRCA2 the most common serious genetic disease known in any population group. It should be noted, however, that these mutations still account for a minority of breast cancer cases overall, only 7% of all breast cancer cases in Eastern European Jewish Women, and far fewer in the general population.

Other Genetic Factors. Researchers have also identified other defective genes that contribute to breast cancer, including BRCA3, p53, CDKN2A (a genetic factor previously identified with melanoma and pancreatic cancer), and NOEY2 (which is inherited from the father). A mutant gene for the rare disorder ataxia-telangiectasia may account for some breast cancers. (The disease itself is rare, requiring two copies of the gene, but 1% of the population carries a single copy, which is enough to increase the risk for breast cancer.) Finally, a mutation in a gene located on chromosome 10 called the PTEN gene results in a disorder called Cowden's syndrome, which is associated with a higher risk of breast cancer.

Over-Exposure to Estrogen

Because growth of breast tissue is highly sensitive to estrogens, the more a women is exposed to estrogen over her lifetime, the higher the risk for breast cancer.

Role of Estrogen Metabolism. A 2000 study suggested that the chance of estrogen increasing breast cancer risk in premenopausal women is related to how it is metabolized. In some women, very powerful estrogen products, or metabolites, are generated when metabolism takes place at a site on the estrogen molecule called C-16. These metabolites appear to pose a higher risk for breast cancer. (This metabolic effect does not appear to occur in postmenopausal women.) Fortunately, the study suggests that healthy diet and exercise may be able to alter this process.

Timing of Estrogen Exposure. Women's risk for breast cancer appears to be greater at specific times of estrogen exposure. For example, there is some evidence that starting one's period at an early age may be protective, in spite of the fact that this indicates a longer lifetime duration of estrogen exposure. Higher exposure in the womb (perhaps suggested by high birth weight), during pregnancy, or at menopause, however, does appear to increase risk.

Pregnancy and Abortion. Pregnancy plays a dual role in breast cancer:

Pregnancy appears to increase the risk for up to 15 years following the first birth, particularly in older women.

Over the longer term, however, women who have given birth even once have a lower risk than those who have not given birth. (Additional births do not seem to have any added impact.)

Of considerable concern are studies that have detected an increased risk for breast cancer in women who have had abortions. The reasons may be due to the high estrogen levels that occur in the first trimester when abortions are most often performed. (Estrogen levels tend not to be high when a natural miscarriage occurs.) The increased risk from abortion is most likely to be very small, however.

Oral Contraception. There appears to be some higher risk for breast cancer in women with a family history of the disease and who took high-dose oral contraceptives (OCs) before 1975. New low-dose OCs do not appear to pose this risk, but more research is needed.

Hormone Replacement Therapy. A number of studies (but not all) have indicated an increased risk for breast cancer in postmenopausal women taking hormone replacement therapy (HRT), particularly with agents that contain both estrogen and progestin. Prolonged use increases the risk. (It should be noted that analyses of the evidence suggest that any risk is still quite small.) There is some evidence to suggest that if breast cancer does develop in women taking HRT it tends to have a more favorable outlook, but studies are needed to confirm this. Interestingly, some studies suggest that in women with a history of breast cancer HRT does not increase the risk for recurrence, and one even reported a lower recurrence rate in breast cancer patients on HRT compared to those not taking replacement therapy. Breast tissue density does increase with HRT, making mammograms more difficult to read. [See also 's Report # 40 , Estrogen, and Other Hormone Therapies .]

Breast Abnormalities

Benign breast conditions are much more commonly seen on mammograms than cancer. And in the great majority of cases they pose no risk. Some common benign breast abnormalities that pose few or no risks include the following:
  • Cysts. These mostly occur in women in their middle to late reproductive years and can be eliminated simply by aspirating fluid from them.

  • Fibroadenoma. These are solid benign lumps that occur in women between the ages of 15 and 30.

  • Breast abscesses during breast feeding.

  • Nipple discharge. Discharge from the nipple is worrisome to patients but is unlikely to be a sign of cancer. Unexplained discharge still warrants evaluation, however.

  • Mastalgia. This is breast pain that occurs can occur in association with or independently from the menstrual cycle. About 8% to 10% of women experience moderate to severe breast pain associated with their menstrual cycle. In general, breast pain does not need assessment unless it is severe and prolonged.
Some breast formations or abnormalities, however, should be watched and include the following:
  • Dense breast tissue is associated with a higher risk for breast cancer.

  • Benign proliferative breast disease or atypical cell growth, known as atypical hyperplasia, is a significant risk factor for breast cancer.

Physical Characteristics

The following physical characteristics have been associated with greater or lesser risk:
  • Studies have reported mixed results on the association between obesity and breast cancer. A number of studies have linked obesity to breast cancer after (but not before) menopause. The risk appears to be greater in women who began to gain weight after age 18. One study, in fact, suggested that being heavier as a child conferred a lower risk for breast cancer after menopause. (Estrogen levels are lower in the presence of high fat levels in premenopausal women.)

  • Estrogen is involved in building bone mass. Therefore, women with heavy, dense bones are likely to have higher estrogen levels and so be greater risk for breast cancer.

  • There have been conflicting reports of a link between increased height and breast cancer risk. One study of almost 10,000 women found no association. Other studies, however, found that taller adult height predicted a greater risk, possibly due to the higher estrogen levels associated with greater bone growth. In one study, regardless of their actual height, women who reached their full height at 13 or younger had a higher risk than those who attained maximum height at age 18, reflecting higher estrogen levels at an earlier age.

Environmental Factors

Exposure to Estrogen-like Industrial Chemicals. Chemicals with estrogen-like effects, called xenoestrogens, have been under suspicion for years. They are found in pesticides and other common industrial products. A number of studies have found no breast cancer risk associated with two of the most common environmental estrogens, PCBs and DDT. Two others, dieldrin and beta-hexachlorocyclohexane have shown a stronger association. Still, most of these chemicals have very weak estrogenic effects.

Exposure to Diethylstilbestrol (DES). Women who took diethylstilbestrol (DES) to prevent miscarriage have a slightly increased risk for breast cancer. To date, this risk has not been seen in their daughters (commonly called "DES daughters"), who were exposed to the drug when their mothers took it during pregnancy.

Radiation Exposure. Heavy exposure to radiation is a significant risk factor for breast cancer. Children receiving high-dose radiation therapy face an increased risk for breast cancer in adulthood.

Mental Health

The effects of psychiatric factors have been questioned for years. A 2000 study suggested that women who had a history of major depression were four times as likely to develop breast cancer as those without clinical depression. One expert suggested the association may be based on common hormonal factors that affect both conditions. However, stress has been largely ruled out as a risk factor for breast cancer.

Insulin-Like Growth Factor

Insulin-like growth factor 1 is an important growth hormone during development in the womb and childhood. It has powerful properties that increase cell proliferation, and high concentrations have now been linked to cancers, including premenopausal breast cancer. In fact, it may be one of the factors that are responsible for the association between height and breast cancer. More research is needed to verify a possible role of insulin-like growth factor 1 in breast cancer development.

HOW CAN THE RISK OF BREAST CANCER BE LOWERED?

Exercise

A number of studies have suggested that regular exercise, particularly if it is vigorous, offers some modest protection against breast cancer by modulating estrogen. (Exercise may also be helpful for women with early stage breast cancer by improving physical function and blunting some of the negative effects of treatments, notably fatigue.)

Dietary Factors

Much research has targeted the role of diet in breast cancer, both as a risk factor or as a factor for patients already diagnosed with cancer.

Fats. A number of studies have been conducted on fat consumption and breast cancer risk, with various and conflicting results. Some observations are as follows:
  • Although some studies have found an association between high-fat intake and breast cancer, the most recent data suggest that fat from any source (vegetable oils or animal products) plays at most an insignificant role in increasing the risk for breast cancer. In fact, in one 2000 study of postmenopausal women, the more fat in the diet, the lower the estrogen levels.

  • It should be noted, however, that one 1999 study reported that trans-fatty acids, which are manufactured hydrogenated fats such as those found in baked products, were associated with shorter survival times, although the trend was marginally significant.

  • According to some other studies, monounsaturated fats (found in olive, peanut, and canola oils) may be protective.

  • Dairy products may actually play a protective role (possibly because of the presence of calcium.) For example, a 2001 study reported a lower incidence of breast cancer in premenopausal women who drank three glasses of milk a day as children. More work is necessary in order to confirm these results.

  • In women with existing breast cancer, low-fat diets do not appear to confer a survival advantage, although more research is needed to confirm this.
Vitamins and Chemicals in Fruits and Vegetables. Many fresh fruits and vegetables contain chemicals that may be cancer fighters. Experts are investigating whether any specific vitamins, nutrients, or teams of them may be specifically valuable. Examples include the following:
  • Isothiocyanates stimulate enzymes that convert estrogen to a more benign form and may block steroid hormones that promote breast and prostate cancers. They are found in broccoli, cabbage, Brussels sprouts, cauliflower, collards, kale, kohlrabi, mustard greens, rutabaga, turnips, and bok choy.

  • Polyphenols, found in apples, onions, and green tea, may be beneficial, although this is controversial(Chemicals in green tea in particular have been studied for cancer-fighting effects in breast cancer.)

  • Lycopene, found in tomatoes may have cancer-fighting properties.

  • There is some evidence that foods containing folate (folic acid) may be protective. It is found in avocado, bananas, orange juice, asparagus, fruits, green leafy vegetables, dried beans and peas, and yeast. It is also added to commercial grain products.

  • Low levels of vitamin D may increase breast cancer risk, especially in older women. Vitamin D is activated by sunlight and obtained from fortified milk.

  • Foods high in vitamin C have also been associated with a lower risk (although there is not evidence of protection from any vitamin supplements, including C or E).
Estrogen-like compounds (called phytoestrogens) require a special discussion. Such compounds are found in soybeans, black cohosh (an herb), whole wheat, berries, and flaxseed. Results are mixed. [ See Box Soy and Phytoestrogens.]

Protein. A 1999 study reported that women with breast cancer who had a high intake of protein from poultry and dairy products had a better outlook than those with a lower intake of these foods. In this study, consumption of red meat appeared to have no effect one way or the other, although other studies have found a higher risk of breast cancer in women who consume higher quantities of flame-broiled meats, particularly women who are sensitive to chemicals released during the process. Fish may offer some protection.

Iron. Animal studies have linked a higher incidence of breast cancer with iron-rich diets, and in humans, high iron stores have been associated with a higher risk for breast cancer. Estrogen appears to increase iron levels in cells, and iron produces oxidants (damaging particles) that are associated with cancer. More research is needed to confirm rhese findings, however.

Soy and Phytoestrogens

Phytoestrogens are found in soybeans, black cohosh (an herb), whole wheat, berries, and flaxseed. Most research has focused on soy. In general the evidence on their effects on breast cancer are unclear.

In general, Asian women have a lower incidence of reproductive and breast cancers as well as a higher intake of soy. A 2000 study of 120 Asian women reported an association between high levels of soy compounds in the urine and a lower risk for breast cancer, as much as 50% lower. And a 2001 study in China reported that high soy intake during adolescence was associated with a lower risk for breast cancer later on.

In another interesting study, women with cyclical mastalgia (menstrual related breast pain) who ate flaxseed muffins every day for three months reported less breast swelling and lumpiness.

The effects of phytoestrogens, however, in all cases are far from settled, however. One study reported that soy appeared to protect against breast and uterine cell proliferation in postmenopausal women who take high doses of estrogen replacement therapy. However, when combined with low doses of estrogen replacement therapy, soy caused breast cell proliferation. Other studies on phytoestrogens in black cohosh have observed cell proliferation in the uterus under certain circumstances.

Women on hormone replacement therapy and at risk for breast cancer, however, should avoid consuming large amounts of plant products with high levels of phytoestrogens until more is known about their effects.

Avoiding Alcohol

Moderate consumption of alcohol, equal to or less than one drink a day, may increase the risk for breast cancer. Some research indicates that alcohol in such amounts increases levels of growth factors that can stimulate breast cancer cells. Ironically, with heavy drinking, these levels decline along with the risk for breast cancer. In any case, some experts estimate that only about 2% of all breast cancer is possibly related to alcohol use. Furthermore, alcohol's hypothesized benefits for the heart outweigh cancer risk in women who are light to moderate drinkers and have no other risk factors for breast cancer or alcohol abuse. (Folic acid may help reduce the risk for breast cancer among women who regularly drink alcohol-again more research is needed.)

Breast Feeding

Evidence on protection from breast feeding is weakly positive. Several studies have reported that breast feeding is associated with a lower risk for cancer in premenopausal women, and two 1999 studies suggest that some protective effect from breast feeding may last beyond menopause. Some studies also indicate that the longer the mother breast feeds the better.

Specific Preventive Measures for High-Risk Women

Lifestyle Factors. Premenopausal women at elevated risk, usually because of family history, should take as many preventive measures as possible, starting at an early age. The following life-style choices may be beneficial (although this is an area subject to change as more information becomes available):

Exercising and eating healthily is the first essential rule.
  • High risk premenopausal women may choose alternatives to oral contraceptives and, if feasible, consider having children early intheir life.

  • High-risk postmenopausal women may want to forego hormone replacement therapy.

  • Any woman at high risk for breast cancer might consider avoiding alcohol or drinking it sparingly.
Prophylactic Mastectomies and Oophorectomies. Studies suggest that preventive breast removal (called prophylactic mastectomy) reduces the risk of breast cancer by about 90% in women who harbor the BRCA genetic mutations. In one study, only three women who chose mastectomies developed breast cancer, whereas 40 would ordinarily have been expected to develop the disease. Shutting down estrogen production with preventive oophorectomy (ovary removal)may also significantly reducing the risk of breast cancer in these women.

Still, the decision is not easy. Having the genes does not mean that cancer will always occur, meaning that mastectomy might not be necessary in all such women. Furthermore, even after mastectomy, some precancerous cells may persist that can activate the disease later on. Nevertheless, in one 2000 study, 70% of women were satisfied with their decision to have prophylactic breast removal. Women should discuss all options with their physician, including oophorectomy and close monitoring. The use of other options such as tamoxifen is described below.

Tamoxifen and Other SERMs. Tamoxifen is known as a selective estrogen-receptor modulator (SERM). In a major study, tamoxifen (a drug also used to treat breast cancer) reduced the risk for breast cancer by half in high-risk women. It was particularly protective in women over 60 (who also benefit from a lower risk for osteoporosis). It may be especially beneficial for women with lobular carcinoma-in-situ or atypical ductal or lobular hyperplasia. It also appears to reduce the risk for women with the BRCA2 genetic mutations, although possibly not BRCA1. Tamoxifen is also proving to reduce the risk for recurring cancer and improve survival rates in women who have estrogen-receptor positive breast cancer. Tamoxifen poses other health hazards, including a risk for blood clots and uterine cancer. [For more information on tamoxifen see What Is Hormone Therapy In Breast Cancer.]

Raloxifene is another SERM that is also proving to be protective against breast cancer and has a lower risk than tamoxifen of causing uterine cancer. In 2001, a major on-going study on raloxifene reported a reduced risk for breast cancer of 72% over a four-year period and an 84% reduced risk for hormone receptive-positive breast cancer. More research is warranted.

Investigative Agents.
  • Aromatase inhibitors are proving to be effective treatments for hormone-receptor positive breast cancer. Like tamoxifen, they are also being investigated for protection in high-risk women. [For more information on these agents see What Is Hormone Therapy In Breast Cancer.]

  • COX-2 inhibitors, which include celecoxib (Celebrex), rofecoxib (Vioxx), and valdecoxib (Bextra), are newer anti-inflammatory agents normally used for pain relief. They also have anti-cancer properties, and, in fact, celecoxib has been approved for preventing an inherited form of colon cancer. Researchers hope these agents may also help reduce the risk for breast cancer, although there is currently no firm evidence that these agents can do so.

  • Retinoids. Analogues of vitamin A called retinoids are being studied for protection against breast cancer. One retinoid, fenretinide, appears to offer some protection against a second breast cancer in previously diagnosed, premenopausal women (but not in postmenopausal women, who in fact may do worse).

WHAT ARE THE SYMPTOMS OF BREAST CANCER?

Breast cancers in their early stages usually are painless. Often the first symptom is the discovery of a hard lump. Fifty percent of such masses are found in the upper outer quarter of the breast. The lump may make the affected breast appear elevated or asymmetric. The nipple may be retracted or scaly. Sometimes the skin of the breast is dimpled like the skin of an orange. In some cases there is a bloody or clear discharge from the nipple. Many cancers, however, produce no symptoms and cannot be felt on examination; they can be detected only with the use of a mammogram.

HOW IS BREAST CANCER DIAGNOSED?

Breast Examinations

Early detection of breast cancer significantly reduces the risk of death. Every woman between the ages of 20 and 49 should have a physical examination by a health professional every one to two years. Those over 50 should be examined annually. A woman should perform a self-examination each month, but this should not replace the annual examination done by a health professional. A breast exam by a health professional can find 10% to 25% of breast cancers that are missed by mammograms. Between 6% to 46% of the lumps detected by examination are malignant. (The yield is lowest in younger and highest in older women.)

Monthly Self-Examination

1. Pick a time of the month that is easy to remember and perform self-examination at that time each month. The breast has normal patterns of thickness and lumpiness that change within a monthly period, and a consistently scheduled examination will help differentiate between what is normal from abnormal.

2. Stand in front of a mirror . Breasts should be basically the same size (one may be slightly larger than the other). Check for changes or redness in the nipple area. Look for changes in the appearance of the skin. With hands on the hips, push the pelvis forward and pull the shoulders back and observe the breasts for irregularities. Repeat the observation with hands behind the head. Move each arm and shoulder forward.

3. Lie down on the back with a rolled towel under one shoulder. Apply lotion or bath oil over the breast area.

The finger action should be as follows: Use the 2 nd, 3 rd, and 4 th finger pads (not tips) held together and make dime-sized circles. Press lightly first to feel the breast area, then press harder using a circular motion.

Using this motion, start from the collarbone and move downward to underneath the breast. Shift the fingers slightly over, slightly overlapping the previously checked region, and work upward back to the collarbone. Repeat this up-and-down examination until the entire breast area has been examined. Be sure to cover the entire area from the collarbone to the bottom of the breast area and from the middle of the chest to the armpits. Move the towel under the other shoulder and repeat the procedure.

Examine the nipple area, by gently lifting and squeezing it and checking for discharge.

4. Repeat step 3 in an upright position. (The shower is the best place for this, using plenty of soap.)

Note: A lump can be any size or shape and can move around or remain fixed. Of special concern are specific or unusual lumps that appear to be different from the normal varying thicknesses in the breast.

Mammograms

Mammograms are very effective low-radiation screening methods for breast cancer. They are not foolproof, however. In general, they still miss up to 25% of cancers (which can sometimes be caught on a physical examination). And, furthermore, according to one study, by the time a woman has nine mammograms, she has a 43% chance of having a false-positive mammogram (one that suggests cancer that isn't really there).

A controversial 2001 study reported that mammograms did not save lives. Follow-up analyses of the data, however, reported opposite results, suggesting that screening every 12 to 33 months significantly reduced mortality rates, at least in women over 55. Expert groups recommend regular screening for many women. [See Some Recommendations for Mammography Screening.]

There are, however, a number of issues as to who should screen and when to screen.

For Women between Ages 50 and 60. Evidence suggests that annual mammograms save lives in this age group.

For Women between Ages 40 and 49. Whether premenopausal women should have routine mammograms is controversial. The areas of debate are as follows:
  • Against Screening. Most of the arguments against mammography in this population are due its inefficiencies in this age group. First, breast tissue is dense in premenopausal women and mammography often fails to detect breast cancers. Second, breast cancers in this age group are often aggressive and two year intervals may not detect them early enough to affect survival. Third, breast cancer is uncommon in young women with most of those risk factors, so frequent screening becomes very cost-inefficient and produces many unnecessary biopsies.

  • For Screening. Breast cancer fatality rates are highest in women between ages 40 and 49. Major analyses of studies have further suggested that mammography can reduce mortality by about 16% in these women. (Specific studies report even greater reductions in mortality rates.) Furthermore, advances in imaging techniques are helping to improve accuracy. Trials further clarifying the role of screening in women aged 40 to 49 are underway in the United Kingdom, though it will be several years before any data are available from this study.
For Women Over 69. The benefits of regular screening in this age group are very small (prevention of about one death per 1,000 women screened). Elderly women are also particularly likely to have non-malignant abnormalities in their breasts and so undergo unnecessary biopsies.

Some Recommendations for Mammography Screening

  • •Women with risk factors for breast cancer, including a close family member with the disease, should consider having annual mammograms starting 10 years earlier than the age at which the relative was diagnosed.

  • It is reasonable for women over 40 years old with no special risk factors to have a baseline mammogram at age 40. US Guidelines now recommend that they should then be tested every one to two years until age 50.

  • After age 50 screening should be annual. (Women over 65 account for most new cases of breast cancer.)
Uninsured women or those who have not been referred to a mammogram center can contact their local American Cancer Society for available low-cost programs.

Other Imaging Techniques

Digital Mammography. Digital mammography has recently been approved. It converts the image of the breast so it can be viewed and manipulated on a computer screen. It is improving accuracy but may not detect all cancers. No screening technique is perfect

Scintimammography. In a test called scintimammography, a radioactive chemical is injected into the circulatory system, and then selectively taken up by the tumor and revealed on mammograms. To date, this method has been very accurate in detecting the presence or absence of breast cancer, and some experts hope that it might eventually reduce the number of unnecessary invasive biopsies.

Ultrasound. New ultrasound techniques can detect tumors smaller than 1 centimeter (less than half an inch). However, ultrasound is a time-consuming procedure, and remains less efficient than mammograms. It may prove to be useful during lumpectomy to improve the surgeon's ability to obtain optimal amounts of abnormal tissue.

Biopsy

A definitive diagnosis of breast cancer can be made only by a biopsy (a microscopic examination of a tissue sample of the suspicious area).
  • When a lump can be felt and is suspicious for cancer on mammography, an excisional biopsy may be recommended. This biopsy is a surgical procedure for removing the suspicious tissue and typically requires general anesthetic.

  • A core biopsy involves a small incision and the insertion of a spring-loaded hollow needle that removes a number of samples. The patient only requires local anesthetic.

  • A wire localization biopsy may be performed if mammography detects abnormalities but there is no lump. With this procedure, using mammography as a guide, the physician inserts a small wire hook through a hollow needle and into the suspicious tissue. The needle is withdrawn and the hook is used by the surgeon to locate the lesion and to remove it. The patient may be given local or general anesthetic.

  • A new vacuum-assisted device may be useful for some biopsies. This employs a single probe through which a vacuum is used to draw out tissue. It allows several samples to be taken without having to remove and re-insert the probe.
Final analysis of the breast tissue may take several days.

Lymphadenectomy

If breast cancer has been determined, the next diagnostic step is to find out how far it has spread. To do this, the physician performs a procedure called an axillary lymphadenectomy :
  • This procedure partially or completely removes the lymph nodes in the armpit beside the affected breast (called axillary lymph nodes).

  • It may require a hospital stay of a day or two and is performed while the patient is under general anesthesia.

  • Side effects include increased risk for infection and pain, swelling, and impaired sensation and movement in the affected arm.

  • The lymph nodes are analyzed to determine whether subsequent treatment needs to be more or less aggressive.

  • If cancer has not spread to the lymph nodes, then the cancer often is referred to as node negative.

  • If cancer cells are present in the lymph nodes, it is called node positive . This increases the chance that the cancer has spread microscopically to other areas of the body. In such cases, however, it is still not known if the cancer has metastasized beyond the lymph nodes or, if so, to what extent.

  • The physician may then perform further tests to see if the cancer has spread to the bone (bone scan), lungs (x-ray or CT scan) or brain (MRI or CT scan).

Sentinel Node Biopsy

A technique known as a sentinel node biopsy is increasingly performed by experienced surgeons in selected patients. This procedure is used to determine if cancer has spread beyond the nodes help and so possibly reduce the need for complete axillary lymphadenectomies. It involves the following:
  • The procedure uses an injection of a tiny amount of a tracer, either a radioactively-labeled substance (radioisotope) or a blue dye, into the tumor site.

  • The tracer or dye then flows via the lymphatic system into the so-called sentinel node . This is the first lymph node to which any cancer would spread.

  • The sentinel lymph node and possibly one or two others are then removed.

  • If they do not show any signs of cancer, it is highly likely that the remainder of the lymph nodes will be cancer free, and further surgery becomes unnecessary.

  • It should be noted that the long-term outlook for patients who had sentinel node biopsy compared to those who had standard procedures with lymph nodes removal is still unknown. Trials are underway.

HOW SERIOUS IS BREAST CANCER?

In the US, about 40,600 women will die from breast cancer this year. (Lung cancer is the leading cancer killer in women, however.) The good news is that major international studies are now reporting improved long-term survival and lower rates of recurrence with new treatments and approaches.

A number of factors are used to determine outlook. The include the following:
  • The location of the tumor and far it has spread

  • Whether the tumor is hormone receptor-positive or negative

  • Genetic factors

  • Tumor size and shape

  • Rate of cell division

  • Certain biologic markers

Location of the Tumor

The location of the tumor is a major factor in outlook:
  • If the cancer is ductal carcinoma in situ (DCIS) or has not spread to the lymph nodes (ie, is node-negative), the five-year survival rates with treatment are up to 98%. (It should be noted, however, that the cancer recurs in between 9% and 30% of such node-negative cancers. Recurrence is a potentially life-threatening problem,, even if the disease relapses locally in the same breast. Nevertheless, in one study, among DCIS patients with locally invasive recurrence eight-year mortality rates were still only 12%.

  • If the lymph nodes contain cancer cells (ie, are node positive ) then survival rates fall. If the tumor is larger than 5 cm or there is widespread involvement in the lymph nodes, it is sometimes referred to as locally advanced. In such cases, the survival rate drops to about 75% and below.

  • If the cancer has metastasized and spread through the blood stream to other sites (most often the lung, liver and bone), the average survival time for patients treated with chemotherapy is between one and two years (with some patients living for many years). And new combinations of drugs are improving these averages.
Of additional note, the location of the tumor within the breast is an important prognostic factor; tumors that develop toward the outside of the breast tend to be less serious than those that occur more toward the middle of the breast.

Hormone Receptor-Positive or -Negative

Breast cancer cells may contain receptors, or binding sites, for hormones like estrogen or progesterone. Cells containing these binding sites are known as hormone receptor-positive cells and if they lack them are called hormone-receptor negative cells.

Hormone-receptor positive cells grow more slowly than receptor negative cells. Women have a better prognosis if their tumors are receptor-positive because these cells grow more slowly than receptor-negative cells and they have more treatment options. (Hormone receptor-negative tumors can only be treated with chemotherapy.)

The Influence of BRCA Genes

The relevance of the BRCA1 or BRCA2 mutations to survival is controversial. Some studies have suggested that these mutations offer a survival advantage, while others suggest that they make no difference or even worsen prognosis. Women with these genetic mutations do have a greater risk for a new cancer to develop. Patients with BRCA1 mutations tend to develop tumors that are hormone receptor negative, which can behave more aggressively

Tumor Markers

Researchers are investigating a number of chemical markers, substances in the tumor cells, that will indicate whether a cancer is likely to spread or not. Many are being studied. The following are only a few of the more well-researched.

HER-2. The HER-2 protein is part of the epidermal growth factor receptor family and is becoming an important marker in breast cancer. It is involved in the growth and spread of breast cancer cells, and about 25% to 30% of breast cancer patients have high levels of this protein. The presence of HER-2 may suggest aggressive cancer. It is proving to be important in determining treatment choices. For example, women who have HER-2 positive cancers tend to benefit from anthracycline-based chemotherapy and to Herceptin.

Angiogenesis Factors. Angiogenesis is the growth of new blood vessels. High levels of angiogenesis factors indicate that the tumor is developing its own blood vessel supply. Such blood vessels enable the tumor to send small colonies of cancer cells into the blood stream and increase the risk of metastasis. One angiogenesis factor, vascular endothelial growth factor (VEGF), may turn out to be an important marker for predicting recurrence in node-negative breast cancers.

P53 Gene. P53 is a tumor suppressant gene. High levels of the normal form are positive signs in determining prognosis. High levels of the mutated form may predict more aggressive tumor behavior.

Others. Many other markers are being investigated including cathepsin-D, basic fibroblast growth factor (bFGF), protein c-erbB-2, bcl-2, Ki-67, telomerase, thymidylate synthase (TS), CA 15-3, and carcinogenic embryonic antigen (CEA). The American Society of Clinical Oncology (ASCO) cautions, however, that the value of many of these factors has not yet been confirmed.

Other Factors for Predicting Outlook

Tumor Size and Shape. Large tumors pose a higher risk than small tumors. Undifferentiated tumors, which have indistinct margins, are more dangerous than those with well-defined margins.

Rate of Cell Division. The more rapidly a tumor grows, the more dangerous it is. A number of tests measure aspects of cancer cell division and may eventually prove to predict the disease. For example, the mitotic index (MI) is a measurement of the rate at which cells divide; the higher the MI, the more aggressive the cancer. Another measures cells at a certain phase of their division.

Chances for Recurrence

Most recurrences occur within five years, but can also occur up to 10 years and after. It should be noted that one study suggested that the risk factors for a first breast cancer do not necessarily place a woman at any higher risk for recurrence. (Women with a first cancer, however, do have a higher risk for a new cancer in the opposite breast.)

Considerations for Survivors

The good news is that women are living longer with breast cancer, and at this time more than two million American are survivors. Survivors must live with the uncertainties of possible recurrent and some risk for complications from the treatment itself.

WHAT ARE THE GUIDELINES FOR TREATING BREAST CANCER BY STAGE?

General Guidelines

The three major treatments of breast cancer are surgery, radiation, and drug therapy. No one treatment fits every patient, and some combination therapy is virtually always required. The choice is determined by many factors, including the age of the patient and (among women) menopausal status, the kind of cancer (eg, ductal vs. lobular), its stage, and whether the tumor contains hormone-receptors or not.

Breast cancer treatments are defined as local or systemic:
  • Local Treatment. Surgery and radiation are considered local therapies because they directly treat the tumor, breast, lymph nodes, or other specific regions. Surgery is usually the standard initial treatment.

  • Systemic Treatment. Drug treatment is called systemic therapy, because it affects the whole body.
Any or all of these therapies may be used separately or, most often, in different combinations. For example, radiation alone or with chemotherapy or hormone therapy may be beneficial before surgery, if the tumor is large or not easily removed at prevention. The optimal sequence for these therapies is being investigated. [Specific treatments and combinations are discussed in the sections below.]

Stage 0

This stage is also called noninvasive carcinoma or carcinoma in situ.

Treatment Options for Lobular Carcinoma in Situ. These are abnormal cells that pose a long-term risk for invasive cancer. (1) Careful monitoring with or without preventive use of tamoxifen or other selective estrogen-receptor modulators (SERMs). (2) In selected cases, consideration of removal of both breasts, since if the cancer does develop, it tends to do so in both breasts or to be invasive. In one study, chance for invasive cancer over a 25-year period was 25%.

Treatment Options for Ductal Carcinoma in Situ. These are cancer cells in the lining of a duct that have not invaded the surrounding breast tissue. (1) Mastectomy previously was the commonly recommended treatment. (2) Breast-sparing surgery (typically without lymph-node removal) followed by radiation therapy is reasonable for many women. Note that the risk for recurrence sometimes with a more invasive cancer is higher in women under 45 than in older women with this approach. (3) Use of tamoxifen or other SERMs after surgery and radiation to prevent recurrence in selected patients.

Stage I and Stage II

  • Stage I. Cancer cells have not spread beyond the breast and the tumor is no more than 2 cm (about 3/4 of an inch) across.

  • Stage II. One of the following conditions apply: the tumor is less than 2 cm across, and the cancer has spread to the lymph nodes under the arm; the tumor is between 2 and 5 cm (about 3/4 inch to 2 inches) with or without spreading to the lymph nodes under the arm; the tumor is larger than 5 cm but has not spread to the lymph nodes under the arm.
Primary Treatment Options for Stage I and II Breast Cancers. Choice of (1) Breast-sparing surgery (typically lumpectomy, usually with lymph node sampling) followed by external beam radiation therapy or (2) modified or radical mastectomy with or without breast reconstruction. (3) Removal or radiation of lymph nodes. Choice between (1) and (2) depends mostly on the size and location of the tumor, the size of the breast, certain features of the cancer, and how the woman feels about preserving her breast. Considerations by tumor size are as follows:
  • Tumors under 2 cm: Women can generally choose lumpectomy followed by radiation.

  • Tumors between 2 cm and 5 cm. Even if tumors are up to 5 cm, a 2000 international study suggested that lumpectomy and mastectomy offer equivalent survival rates (about 66%) and time to metastasis at 10 years. In the study, however, local recurrence occurred in 20% of lumpectomy and 12% mastectomy patients.

  • Tumors over 5 cm: Women generally choose mastectomy.
Other considerations: If women choose breast-sparing procedures, the risk for recurrence is lower with removal of as much breast tissue as possible. In women who experience a local recurrence after treatment, those who have chosen lumpectomy and radiation tend to have a better outlook than women who chose mastectomy, since cancers in the latter case would develop in the chest wall.

Adjuvant and Neoadjuvant Treatment Options. Adjuvant therapy is administered in addition to surgery or radiation therapy to prevent recurrence. (1) Combination chemotherapy can be considered for hormone receptor-negative cancers. (2) Hormonal therapy with or without chemotherapy for hormone receptor-positive cancers. Tamoxifen is the standard agent and is administered for about five years. Aromatase inhibitors (letrozole, anostrazole, and exemestane) are proving to be at least as effective as tamoxifen, althoughthe results of these agents in the adjuvant setting are still preliminary. (3) Clinical trials: ovarian ablation with tamoxifen plus goserelin; optimal sequences of chemotherapy and radiation (before or after breast sparing surgery or mastectomy); preoperative (neoadjuvant) chemotherapy using taxanes to allow breast-conserving surgery in some women with Stage II cancer; new drug combinations.

Stage III (Locally Advanced)

In this stage, the tumor in the breast is more than 5 cm across, and
  • It has spread (sometimes extensively) to the underarm lymph nodes, or

  • It has spread to other lymph nodes or tissues near the breast.
A condition called inflammatory breast cancer is also treated as a Stage III cancer.

Treatment Options for Stage III. (1) Standard therapy is mastectomy usually with radiation therapy and systemic treatment (combination chemotherapy, hormonal therapy, or both). (In very advanced Stage III, systemic drug therapy, radiation, or both sometimes achieve a response that allows a woman to avoid mastectomy, although this approach does not increase survival rates.) (2) Radiation after surgery is now recommended for women with four or more involved lymph nodes or an extensive primary tumor. It is not yet clear if radiation would benefit women with one to three involved lymph nodes. (3) Clinical trials: high-dose chemotherapy and stem cell transplantation; new chemotherapeutic, hormonal, or biologic agents; neoadjuvant therapies using taxanes alone or concurrent taxane and radiation treatment; post surgical radiation for women with one to three involved lymph nodes.

Stage IV (Metastasized Cancer)

In stage IV the cancer has spread from the breast to other parts of the body. In about 75% of cases, the cancer has spread to the bone. The cancer at this stage is considered to be chronic and incurable and the usefulness of treatments available is limited. The goals of treatment for Stage IV can be a complete or partial response, stabilization of the disease, or slowing of its progression. Unlike many other cancers, stage IV breast cancer patients have responded to as many as five rounds of intervention drug treatments.

Treatment Options for Stage IV. (1) Surgery or radiation for any localized tumors in the breast. (2) Chemotherapy, hormonal agents, or both are appropriate for most patients (durable and complete remission possible in 10% to 20% of cases but cure is very rare). Chemotherapy in patients with hormone receptor-negative disease or who have extensive metastasis which requires rapid tumor shrinkage. Ovarian ablation (in premenopausal women) or other hormonal therapies in patients with hormone receptor-positive cancer and no or minimal organ involvement. (Aromatase inhibitors, taxanes, and other agents used in combination or in innovative schedules are improving results.) (3) Metastasis to the brain may require radiation and high-dose steroids. (4) Metastasis to the bone (which occurs in 75% of cases) may be helped with radiation and bisphosphonates. Such treatments relieve and pain and help prevent bone fractures. (5) Clinical trials: standard hormonal or chemotherapy agents used as initial treatment, newly developed chemotherapeutic or hormonal agents, monoclonal antibodies, total hormone blockade using surgery, high-dose chemotherapy with stem-cell support.

Recurrent Breast Cancer

Recurrent breast cancer is considered to be an advanced cancer. In such cases, the disease has come back in spite of the initial treatment. Most recurrences appear within the first two or three years after treatment, but breast cancer can recur many years later. Treatment options are based on the stage at which the cancer reappears, whether the tumor is hormone responsive or not, and the age of the patient. Between 10% to 20% of recurring cancers are local; most are metastatic at presentation. All patients with recurring cancer are candidates for clinical trials.

Psychological Support at Any Stage

Studies have suggested that psychotherapy, group support, or both can relieve pain and reduce stress. There is no evidence that facing the realities of the condition causes any physical deterioration. Studies are mixed on possible survival benefits from psychologic support, and more research is underway to determine its effects.

WHAT ARE THE SURGICAL PROCEDURES FOR BREAST CANCER?

General Guidelines and Breast-Conserving Treatment

Surgery forms a part of nearly every patient's treatment for breast cancer. The initial surgical intervention is often a lumpectomy, the removal of the tumor itself. In the past, mastectomy (the removal of the breast) was the standard treatment for nearly all breast cancers. Now many patients with early-stage cancers can choose breast-conserving treatment, or lumpectomy followed by radiation, with or without chemotherapy.

Note: Local control rates using lumpectomy are comparable to those of mastectomy only when radiation therapy is also used for lumpectomy patients. A patient should carefully discuss all options with the physician or physician team.

Lumpectomy

Lumpectomy is the removal of the tumor, often along with lymph nodes in the armpit. It serves as an opportunity for biopsy, a diagnostic tool, and a primary treatment for small local breast tumors. If invasive cancer is found, the physician will decide to proceed with breast radiation therapy, to remove additional tissue (should the margins of the specimen show signs of cancer), or to perform a mastectomy.

Mastectomy

Mastectomy means removal of the breast, but there are a number of variations:
  • Segmental/partial mastectomy removes the cancer and a large area of breast tissue, occasionally including some of the lining over the chest muscles.

  • A total/simple mastectomy involves removal of the whole breast and sometimes lymph nodes under the armpit.

  • A radical mastectomy removes the breast, chest muscles, all of the lymph nodes under the arm, and some additional fat and skin. This procedure is rarely used anymore except when cancer is very advanced.

  • A modified radical mastectomy is the removal of the entire breast and armpit lymph nodes, with the underlying chest wall muscle.
Modified radical mastectomy may be recommended if one of the following conditions is present:
  • Tumors exist in multiple sites in the breast.

  • The cancer is located underneath the nipple.

  • Radiation therapy is not a possibility.

  • The removed lump is large and shows cancer cells on its margins.

  • Some women choose mastectomy over breast-conserving treatment even if none of these conditions are present for security and because it allows them to avoid radiation therapy.
Some studies had suggested that timing surgery during the luteal, or premenstrual, phase of a woman's cycle (typically days 15 through 29) had a positive impact on outcome, but a 1999 study reported no such association and suggested that previous observations on beneficial timing were coincidental.

Complications and Side Effects of Surgery. Short-term pain and tenderness occur in the area of the procedure, and pain relievers may be necessary.

The most frequent complication of extensive lymph node removal is edema, or swelling, of the arm, which is usually mild and rarely painful but does increase the risk for infection. The likelihood of edema can be lessened by removing only some of the lymph nodes instead of all of them.

Infrequent complications include poor wound healing, bleeding, or a reaction to the anesthesia.

After mastectomy and lymph node removal, women may experience numbness, tingling, and difficulty in extending the arm fully; these effects can last for months or years afterward.

Breast Reconstruction

After a mastectomy, some women choose a breast prosthesis or opt for breast reconstruction, which can be performed during the mastectomy itself if desired. Several studies have indicated that women who take advantage of cosmetic surgery after breast cancer have a better sense of well-being and a higher quality of life than women who do not choose reconstructive surgery. The breast is reshaped using a saline implant or, for a more cosmetic result, a muscle flap is taken from elsewhere in the body. Muscle flap procedures are more complicated, however, and blood transfusions may be required. (It should be noted that implants, including silicone implants, do not appear to put a woman at risk for breast cancer recurrence.) If the nipple is removed, it is rebuilt from other body tissues and color is applied using tattoo techniques. It is nearly impossible to rebuild a breast that is identical to its partner, and additional operations may be necessary to achieve a desirable effect.

Follow-Up After Surgery

After breast cancer surgery, women often undergo frequent testing to ensure immediate diagnosis of any recurrence. In general, annual mammograms and physical examinations, with additional tests as necessary based on clinical signs and symptoms, are reliable approaches. Patients, however, should discuss with their physician a follow-up plan that alleviates as much anxiety as possible.

Ovariectomy

Ovariectomy, the removal of the ovaries, has modestly improved breast cancer survival rates in some premenopausal women who are hormone receptor-positive. It does not benefit women after menopause, and its advantages can be blunted in women who have received adjuvant chemotherapy. The procedure causes sterility and can have a major negative emotional impact on many younger patients.

Minimally Invasive Procedures for Early Stage Cancer

A number of studies are investigating minimally invasive techniques that employ lasers, deep-freezing of cancer cells (cryosurgery), high-intensity ultrasound, and other experimental approaches to kill cancer cells and reduce severe complications of surgery. Radiofrequency ablation, for example, is an interesting approach that may eventually have a place in local treatment of breast cancer. An electrode is inserted into the tumor and emits radio waves that produce enough heat to destroy cancer cells. Early trials are promising. None of these procedures is considered standard at the present time.

WHAT ARE RADIATION TREATMENTS FOR BREAST CANCER?

Radiation therapy uses x-rays to kill cancer cells or to shrink the size of a tumor in the breast or surrounding tissue. Radiation therapy after mastectomy can reduce local recurrences in many high-risk patients, particularly those with four or more positive lymph nodes or an advanced primary cancer. Whether it adds benefits for women post mastectomywith one to three positive nodes is uncertain. Radiation is also important in advanced stages for relief of symptoms and to slow progression.

Administration of Radiation Therapy

Radiation is generally in the following ways:

External Beam Radiation. It is usually administered four to six weeks after surgery and delivered externally by an x-ray machine that targets radiation to the whole breast. It may be delivered to the chest wall in high-risk patients (e.g. large tumors, close surgical margins, or lymph node involvement). The treatment is generally given daily (except for weekends) for about six weeks. A follow-up boost of radiation therapy in patients with lumpectomies appears to reduce the risk for recurrence.

Brachytherapy. Less commonly radiation is delivered in implants (called brachytherapy). Implants are most often used as a radiation boost rather than as primary radiation therapy. Nevertheless, some evidence suggests that implants alone can reduce treatment time and may be as effective as external beam radiation in early stage breast cancer.

Side Effects of Radiation Therapy

Side effects of radiation include the following:
  • Fatigue is very common and increases with subsequent treatments, but most women are able to continue with normal activities. Exercise may be helpful.

  • Nausea and lack of appetite may develop and worsen as treatment progresses.

  • Skin changes and burns can occur on the breast skin. Using a cream that contains a corticosteroid, such as mometasone furoate (MMF) may be helpful. After repeated sessions, the skin may become moist and "weepy." Exposing the treated skin to air as much as possible helps healing. (Washing the affected skin with soap and water does not seem to be harmful and in one study was associated with a lower risk for this side effect.)

  • Uncommonly, the breast may change color, size, or become permanently firm.

  • Rarely, the nearest arm may swell and develop impaired mobility or even paralysis.

  • There is a very small risk (less than 1%) of lung irritation and scarring.

Long-Term Complications

Future complications include the following:
  • Radiation to the left breast may increase the risk for future heart attack in younger women, but the risk is still low (only 2% over 20 years).

  • One study reported a higher risk for future cancer in the opposite breast in younger women who have been given radiation to the chest wall.

  • Radiation therapy also can increase the risk of developing other cancers, such as soft tissue malignancies known as sarcomas.
Current procedures that employ precise targeting of the radiation using advanced imaging techniques reduce exposure and are likely to reduce the risks for heart disease and other serious complications.

WHAT ARE THE GENERAL GUIDELINES FOR DRUG (SYSTEMIC) TREATMENTS FOR BREAST CANCER?

The most important advances in the cure of breast cancer have come through the use of drug therapy, also called systemic therapy. Surgery and radiation therapy are effective for treating tumors confined to the breast but not for cancer cells that have spread. In such cases, drug therapy is needed. Drugs works systemically. That is, they kill cancer cells throughout the body rather than just in the breast or nearby tissue.

Agents Used for Breast Cancer

Systemic treatments for breast cancer include the following:
  • Chemotherapy. Chemotherapy employs drugs called cytotoxic agents. They are given orally or by injection that kill cancer cells throughout the body. It plays a role in a very wide range of breast cancer cases.

  • Hormone Therapy. The goal of hormone therapy is to prevent estrogen from stimulating breast cancer cells. It is now recommended for women of any age whose breast cancers are hormone-receptor positive (either estrogen or progesterone), regardless of the size of the tumor and whether or not it has spread to the lymph nodes.

Considerations for Drug Therapies

Drug therapy, either hormonal agents or chemotherapies, may be used as follows:
  • As primary therapy for patients for whom surgery or radiation therapy is not appropriate.

  • With surgery, radiation or both (adjuvant therapy). They are particularly beneficial for women who have microscopic evidence of the spread of cancer at the time of diagnosis. The use of drug therapy is designed to kill these residual breast cancer cells before they have a chance to become clinically evident.

  • Prior to local treatments (neoadjuvant therapy). The goal in such cases is usually to shrink locally advanced tumors (Stage III) to a size small enough for surgical or radiological therapy.

  • In metastatic cancer: Drugs are used in such cases not to cure but to improve quality of life and possibly prolong survival.

WHAT ARE THE CHEMOTHERAPY TREATMENTS FOR BREAST CANCER?

Chemotherapy regimens are designed to kill cancer cells throughout the body. It has advantages for nearly every breast cancer patient regardless of whether the cancer is hormone receptor-positive or negative.

Adjuvant and Neoadjuvant Regimens

Adjuvant chemotherapy is used with surgery, radiation or both. Its goal is to eradicate microscopic disease in other parts of the body. Neoadjuvant chemotherapy, which is given before other treatments, is also proving to be useful for women with locally advanced breast cancer (Stage III). In such cases, it may reduce the tumor size so that it is operable.

Candidates for Adjuvant Chemotherapy. Adjuvant chemotherapy is an appropriate consideration for most women with invasive breast cancer, regardless of menopausal status.Chemotherapy can reduce risk of relapse and prolong survival whether the tumor is node-negative or positive, or whether it is hormone-receptor positive or negative. (Patients with very small tumors that are hormone receptor positive and do not involve lymph nodes may not require chemotherapy. Management of such cases needs to be individualized.)

Regimens and Drug Combinations. Adjuvant chemotherapy is usually administered after initial surgery in combination regimens in four to six courses of treatment over three to six months and usually before follow-up radiation therapy to the breast.

The following are some important agents used in combination treatments:

Anthracyclines. Anthracyclines include doxorubicin (Adriamycin) or epirubicin (Ellence). To date, combinations using these agents have the best survival benefits. Patients who overexpress the HER-2/neu gene and have hormone receptor-negative tumors may particularly benefit from anthracyclines. The drug may have toxic effects on the heart, however.

Cyclophosphamide, 5-fluorouracil (5-FU), and methotrexate (CMF). This was the standard regimen for years, but its use has declined with the introduction of anthracyclines.

Taxanes include paclitaxel (Taxol) and docetaxel (Taxotere). Combinations using these agents are promising, but their value is still inconclusive.

Tamoxifen. After the completion of all treatments, including adjuvant chemotherapy, women with hormone-receptor-positive cancers generally take tamoxifen, which has reduced their risk of recurrence by approximately 30%. [For more information, see What Is Hormone Therapy In Breast Cancer?]

Chemotherapy in Metastatic Cancer

Patients who develop metastatic disease (ie, who relapse at distant sites) are generally not curable. Combination therapies, however, are often effective at shrinking tumors and improving quality of life and may even be improving survival rates.

Agents Used to Treat Metastatic Cancer. Combination agents that are most effective are the following:
  • Docetaxel (Taxotere) and taxanes, paclitaxel (Taxol) and,

  • Anthracyclines, doxorubicin (Adriamycin) or epirubicin (Ellence).

  • Combinations that include both anthracyclines and taxanes are showing high response rates although it is not clear whether such combinations improve overall survival compared to these drugs used as single agents.

  • Other promising combinations or agents used alone or in combinations are the following:

  • Cyclophosphamide, 5-fluorouracil (5-FU), and methotrexate (CMF) with a corticosteroid (eg, prednisone).

  • Capecitabine (Xeloda). This is a unique oral agent that may be a good substitute for 5-FU and when used alone may an effective alternative to CMF in older patients. Studies have reported response rates of up to 26% in patients previously treated with chemotherapy and of 30% when used as the first treatment for metastatic breast cancer. Combinations are being investigated. The combination of capecitabine and docetaxel may prove to be particularly useful.

  • Trastuzumab (Herceptin). Trastuzumab (Herceptin) is a monoclonal antibody, a genetically designed agent that binds only to cells that have a specific marker on the cell surface. Trastuzumab destroys cells carrying the HER-2 protein, and so is being used in women who tests positive for the gene that regulates this protein. HER-2 plays a role in cancer cell growth in about 30% of breast cancer patients. This agent is producing longer survival rates in metastatic breast cancer patients when it is used in combination with paclitaxel. (This agent is useful only in women who test positive for HER-2 gene overexpression.) Of concern are reports of toxic effects on the heart with this combination. Other agents are also showing promise in combination with Herceptin.
Other drugs showing some pro