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Cancer of the Breast

The diagnosis and treatment of breast cancer have changed dramatically during the past two decades. Screening programs did not exist 25 years ago. The preferred treatment was radical mastectomy, and adjuvant therapy did not exist. This is in marked contrast to the current situation of well-organized screening programs, effective adjuvant therapy, and alternative treatment.

The most recent figures from the National Cancer Institute reveal that after a sharp rise in the percentage of women diagnosed with breast cancer from 1980 to 1987, there has been a decline in incidence, especially among women 50 years of age and older. The lifetime risk for developing breast cancer is one in nine. This reflects an increase in life expectancy of...

The American Cancer Society predicted 180,200 new cases of breast cancer and 43,900 deaths for 1997, representing 31% of all new cases of cancer and 17% of cancer deaths. The mortality rate for breast cancer has been unchanged since 1930, increasing on an average of 0.2% per year from 1973 to 1990, but

The most important risk factor for breast cancer is advancing age. In women older than age 45 years, breast cancer occurs more frequently in upper socioeconomic classes, and whites are affected more than

Early detection is associated with increased survival and more cosmetic local treatment. Women should undergo screening and routine surveillance at timely intervals to assess risks and aid in early diagnosis. It is


The risk factors currently identified for breast cancer do not present a significant potential for control, nor are they as distinct as risk factors for lung cancer and cervical cancer. Other malignancies are associated with breast cancer, and multiple primary tumors of the ovary and uterus may be involved. Patients with endometrial cancer should be carefully screened with annual mammography; similarly, patients with breast cancer should be carefully observed for abnormal uterine bleeding.

Primary care physicians should be aware of a patient's chances of developing breast cancer and the impact of breast cancer on the general public. Breast cancer is the most common cancer. The chance of developing breast cancer by age 25 is approximately 1 in 20,000; by the age of 60, it is 1 in 24. Another way of impressing this concept is that, in the absence of any major risk factors such as breast cancer in first-degree relatives, the chance of get~ ting breast cancer between ages 30 and 40 is 1 in 1,000; between ages 40 and 50, it is 2 in 1,000; and between ages 50 and 60, it is 3 in 1,000 breast cancer, canser, brest.

Family History

The family history is an important factor in assessing an individual's risk of a heritable predisposition to breast cancer. One should attempt to distinguish women carrying mutations in

Reproductive History

Certain reproductive characteristics--nulliparity, early age of menarche, older age at menopause, and older age at first full-term pregnancy--have been associated with increased risk of breast cancer. Oophorectomy at an early age has been considered protective in reducing the risk of breast cancer in reproductive-age women by almost 70%. It has been suggested that the period between the onset of menses and the age of first

Estrogen Replacement Therapy

Physicians should understand the rationale for estrogen replacement therapy, especially in terms of the prevention of cardiovascular disease and osteoporosis, and at the same time be aware of the lack of data to

There are a number of interesting observations that suggest a relationship between estrogen replacement therapy and breast cancer. It has been known for many years that oophorectomy before the age of 35 years reduces the risk of breast cancer by 70%. Patients with metastatic breast cancer treated with aminoglutethimide, an aromatase inhibitor, have a marked reduction in estradiol from 15-20 pg/mL to about 5 pg/mL because of the failure of conversion of hormones into estrogen. The level of estradiol is increased to 30-35 pg/mL with estrogen replacement therapy.

A number of clinical studies have reported that the risk of breast cancer is slightly elevated among users of estrogen replacement therapy. A meta-analysis concluded that women who had used estrogen in the

Use of Oral Contraceptives

Soon after the approval of oral contraceptives, a number of epidemiologic studies reported on the risk of breast cancer associated with them. Oral contraceptives are widely used, and any effect on the risk of breast cancer will have important public health implications. Studies suggest that, overall, there has been no increase in the risk of breast cancer for women who had ever used oral contraceptives; however, women who had used oral

Dietary Fat Intake

International differences in rates of breast cancer and the striking increase among populations migrating from low-to high-incidence areas has suggested that environmental factors, possibly dietary, influence the

Alcohol Consumption

A number of epidemiologic studies have shown a possible relationship between moderate drinking and breast cancer. However, the benefit of decreasing alcohol consumption, if any, needs to be evaluated by coronary heart disease.

Other Factors

Approximately 10% of patients with breast cancer have a history of trauma to the breast. This trauma probably results in increased attention to the breast and the discovery of a tumor or other changes that initiate breast self-examination.

Virus-like particles have been identified in human breast milk. There is no evidence, however, that viruses are involved in breast cancer risk.

A number of histologic changes have been noted in benign fibrocystic breasts, and some have been associated with the later development of breast cancer. The College of American Pathologists has published a consensus statement indicating that there is no increased risk for breast cancer in patients with conditions such as macrocysts or microcysts, duct ectasia, fibroadenoma, mild hyperplasia, mastitis, or squamous metaplasia. There is a slight increase in risk in patients with sclerosing adenosis; biopsy-proven hyperplasia that is moderate or florid, solid or papillary; and those who had papillomas with a fibrovascular core. Finally, risk increases substantially--fourfold to fivefold--in women with biopsy-proven atypical hyperplasia or a ductal or lobular carcinoma in situ.


The histologic patterns of breast cancers can be divided into two types: 1) carcinomas of lobular epithelial original and 2) carcinomas of ductal epithelial origin. Carcinomas of lobular epithelial origin are generally classified on the basis of invasion: lobular cancer in situ or lobular neoplasia and invasive 1obular cancer. In


Appropriate staging includes a pretreatment chest X-ray, routine blood studies, and liver function tests. For invasive lesions, a bone scan is recommended, although the yield is low for T1 lesions. It is helpful to have


American Joint Committee on Cancer TNM staging for breast cancer




TX Primary tumor not assessable

T0 No evidence of primary tumor

Tis Carcinoma in situ

T1 Tumor #2 cm in greatest dimension

T1a Tumor #0.5 cm in greatest dimension

T1b Tumor >0.5 cm but not > 1 cm

T1c Tumor >1 cm but not >2 cm

T2 Tumor >2 cm but <5 cm in greatest dimension

T3 Tumor >5 cm in greatest dimension

T4 Tumor of any size with direct extension into the chest wall or skin

T4a Extension to chest wall (ribs, intercostal muscles, or serratus anterior)

T4b Peau d'orange, ulceration, or satellite skin nodules

T4c T4a plus b

T4d Inflammatory breast cancer

Regional lymph nodes

NX Regional lymph nodes not assessable

N0 No regional lymph node involvement

N1 Metastasis to movable ipsilateral axillary lymph nodes

N2 Metastases to ipsilateral axillary lymph nodes fixed to one another or to other structures

N3 Metastases to ipsilateral internal mammary lymph nodes

Distant metastases

MX Nonaccessable presence of distant metastases

M0 No distant metastases

M1 Existent distant metastases (including ipsilateral supraclavicular nodes)



Untreated breast cancer has a surprisingly predictable 5-year survival rate. In one series, 20% of patients were still alive at 5 years and 5% survived 10 years. Thus, in discussing treatment, the surgeon should be aware of the natural history of the disease and the necessity for long-term (15-25 years) follow-up to

Even with the most extensive local treatment, surgery alone does not result in cure. This realization has resulted in using a more conservative surgical approach and the involvement of the patient in the treatment planning process. Less-invasive surgical procedures, including the modified radical mastectomy and segmental resection or wide local excision combined with axillary dissection and radiotherapy, have largely replaced the classic radical mastectomy.

Alternative treatments require the expertise of the surgeon, radiation oncologist, and medical oncologist. Because of the increase in the use of a two-stage procedure, both for diagnosis and for treatment, a number of patients are referred for a second opinion. In some states, the law mandates that the physician discuss

A number of factors influence the definitive surgical treatment of breast cancer. Important considerations include the size and histology of the lesion, the skill and experience of the multidisciplinary team, and the wishes of the patient. There have been a number of published reports, both from retrospective studies and from prospective randomized clinical trials, that have concluded that segmental mastectomy or wide local

The use of conservative surgery with axillary lymphadenectomy and radiation therapy requires consideration of four important criteria: patient selection, surgery of the primary tumor, radiotherapy of the primary tumor, and surgery of the axilla. The principal advantage of conservative treatment is cosmetic. There are no data to indicate that the conservative approach provides improved survival compared with the radical or modified

Radiotherapy is begun as soon as the wounds are healed. It is generally agreed that the breast should be treated with 180-200 cGy/d for a total of 4,500-5,000 cGy. Total doses in excess of 5,000 cGy result in

The conservative approach appeals to many patients, but statistics clearly indicate that most patients in the United States are still treated with the modified radical mastectomy. In some cases, the conservative approach is not appropriate, and some patients request removal of the breast. The modified radical mastectomy should be performed in a cosmetic manner, preferably with a transverse incision to permit later reconstruction.

There are advantages and disadvantages to the conservative and radical approaches. Obviously, the main advantage of the conservative approach is the preservation of the breast; however, the price to be paid is

Although some surgeons are performing reconstruction at the time of the modified radical mastectomy, many patients elect reconstructive procedures at a later date. The patient should see the plastic surgeon before the mastectomy. Occasionally, a support group will be available to discuss the reconstructive


Based on the survival rates of patients with the best prognosis--those with negative nodes---it can be assumed that some of these patients have systemic disease. Certain major predictors of systemic recurrence exist and are the basis for recommending systemic (adjuvant) treatment. These predictors include tumor diameter and the number of involved nodes. Several less well-defined predictors, including

Several factors define high- and low-risk groups in women with node-negative breast cancer. Those associated with low risk include ductal cancer in situ, tumor smaller than 1 cm, diploid tumor, low S-phase fraction, nuclear grade 1, and tumors 1-2 cm without high-risk features. Factors associated with high risk include aneuploid tumor, high S-phase fractions, high cathepsin D levels, absent estrogen receptors, and

Several researchers have developed treatment programs based on cyclic high-dose chemotherapy regimens. These programs may not require stem cell support but do use high doses of cytotoxic agents and usually require hospitalization of the patient. The cycles are repeated as tolerated every 4-6 weeks. Although

In most treatment centers, the currently recommended adjuvant therapy consists of a standard program of either cyclophosphamide, methotrexate, and 5-fluorouracil or cyclophosphamide, doxorubicin, and 5-fluorouracil. For post-menopausal patients, tamoxifen is the standard adjuvant therapy. Although postmenopausal patients may benefit from cytotoxic chemotherapy, the survival benefit is small and the cost is high. Using active life expectancy as the primary outcome reduces the benefit and adds to the cost. It has been suggested that if active life expectancy is a relevant outcome, withholding chemotherapy for patients older than age 70 years is a reasonable approach. Adjuvant tamoxifen is now recommended for no more than 5 years. Although there has been a tendency to give tamoxifen for more than 5 years, National Surgical Adjuvant Breast Project studies have reported no additional benefit for tamoxifen taken for more than a 5-year period. In addition, other factors should be considered in deciding for or against the use of tamoxifen in the postmenopausal patient. There is evidence, for example, that there is a reduction in the development of contralateral breast cancers and improvement of risk factors for coronary heart disease, such as reduced cholesterol and osteoporosis. These changes may depend on the continued use of tamoxifen, and further studies will be required.

An increasing body of evidence supports the belief that prolonged use of tamoxifen is associated with an increased incidence of endometrial hyperplasia and endometrial carcinoma. The actual risk, however, is very low (probably 0.5%). It is essential, therefore, that patients receiving tamoxifen have a complete pelvic examination on a yearly basis; it may include, as some researchers suggest, a yearly cytologic examination of endometrial aspirate.


With current treatment protocols, patients with metastatic disease are not curable. However, they may be managed with a variety of palliative therapies, and, in some cases, they can be treated for many years with excellent quality of life. A local recurrence in a breast treated by wide local excision and primary


Prognosis is influenced by a number of factors, including histology, growth pattern, length of disease-free interval, lymphatic or blood vessel invasion, receptor status, and, more recently, evaluation of flow cytometry and other prognostic indicators. Patients with negative nodes have an approximately 75% 10-year survival rate, and patients with positive nodes have a...