Introduction
Treatment may be curative or palliative. Curative treatment is advised for clinical stage I, II, and III disease (

Table 17-2). Patients with locally advanced (T3, T4) and even inflammatory tumors may be cured with multimodality therapy, but in most palliation is all that can be expected. Palliative treatment is appropriate for all patients with stage IV disease and for previously treated patients who develop distant metastases or who have unresectable local cancers.

The growth potential of tumors and host resistance factors vary widely from patient to patient and may be altered during the course of the disease. The doubling time of breast cancer cells ranges from several weeks in a rapidly growing lesion to a year in a slowly growing one. Assuming that the rate of doubling is constant and that the neoplasm originates in one cell, a carcinoma with a doubling time of 100 days may not reach clinically detectable size (1 cm) for about 8 years. Rapidly growing cancers have a much shorter preclinical course and a greater tendency to metastasize by the time a breast mass is discovered.

The long preclinical growth phase and the tendency of breast cancers to metastasize have led clinicians to believe that most breast cancer is a systemic disease at the time of diagnosis. Although it may be true that breast cancer cells are released from the tumor prior to diagnosis, variations in the host-tumor relationship prohibit the growth of disseminated disease in many patients. Clearly, not all breast cancer is systemic at the time of diagnosis. For this reason, a pessimistic attitude concerning the management of breast cancer is unwarranted. Most patients can be cured.

Controversy surrounds the timing of surgery with respect to the menstrual cycle. Some suggest that operation during the time of unopposed estrogen adversely affects survival, but most studies support no such effect. Several randomized trials are currently examining this question.

Choice of Primary Therapy
The extent of disease and its biologic aggressiveness are the principal determinants of the outcome of primary therapy. Clinical and pathologic staging help in assessing extent of disease (

Table 17-2), but each is to some extent imprecise. Other factors, such as DNA flow cytometry, tumor grade, hormone receptor assays, and oncogene amplification, may be of prognostic value but are not important in determining the type of local therapy.

Controversy surrounds the choice of primary therapy of stage I, II, and III breast carcinoma. A number of states require physicians to inform patients of alternative treatment methods in the management of breast cancer. Currently, the standard of care for stage I, stage II, and most stage III cancer is surgical resection.

Breast-Conserving Therapy
Many nonrandomized trials, the randomized Milan trial, and a large randomized trial conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP) in the United States show that disease-free survival rates are similar for patients treated by partial mastectomy plus axillary dissection followed by radiation therapy and for those treated by modified radical mastectomy (total mastectomy plus axillary dissection). All patients whose axillary nodes contained tumor received adjuvant chemotherapy.

In the NSABP trial, patients were randomized to three treatment types: (1) “lumpectomy” (removal of the tumor with confirmed tumor-free margins) plus whole breast irradiation, (2) lumpectomy alone, and (3) total mastectomy. All patients underwent axillary lymph node dissection, and some had tumors as large as 4 cm with (or without) palpable axillary lymph nodes. With 20 years of follow-up, the lowest local recurrence rate was among patients treated with lumpectomy and postoperative irradiation; the highest - nearly 40% at 20 years of follow-up - was among patients treated with lumpectomy alone. However, no statistically significant differences were observed in overall or disease-free survival among the three treatment groups. This study shows that lumpectomy and axillary dissection with postoperative radiation therapy are as effective as modified radical mastectomy for the management of patients with stage I and stage II breast cancer.

The results of these and other trials have demonstrated that much less aggressive surgical treatment of the primary lesion than has previously been thought necessary gives equivalent therapeutic results and may preserve an acceptable cosmetic appearance.

Tumor size is a major consideration in determining the feasibility of breast conservation. The lumpectomy trial of the NSABP randomized patients with tumors as large as 4 cm. To achieve an acceptable cosmetic result, the patient must have a breast of sufficient size to enable excision of a 4-cm tumor without considerable deformity. Therefore, large size is only a relative contraindication. Subareolar tumors, also difficult to excise without deformity, are not contraindications to breast conservation. Clinically detectable multifocality is a relative contraindication to breast-conserving surgery, as is fixation to the chest wall or skin or involvement of the nipple or overlying skin. The patient - not the surgeon - should be the judge of what is cosmetically acceptable.

Axillary dissection is valuable in preventing axillary recurrences, in staging cancer, and in planning therapy. Intraoperative lymphatic mapping and sentinel node dissection identify lymph nodes most likely to harbor metastases if present in the axillary nodes. Numerous studies have confirmed the validity of this technique. Ongoing trials are examining the replacement of formal axillary dissection with sentinel node dissection. A trial from Milan with very short follow-up showed no difference between axillary dissection and sentinel node biopsy in node-negative women. Results to date suggest that sentinel node biopsy can safely replace axillary dissection for staging and treatment in histopathologically node-negative women at experienced centers. At an international consensus conference in Philadelphia in April 2001, participants recommended sentinel node biopsy as an alternative to axillary dissection in selected patients with invasive cancer. A trial by the American College of Surgeons Oncology Group is examining the role of sentinel node dissection without axillary dissection for node-positive women. Bone marrow biopsy with examination by immunocytochemistry to detect early metastases may be as sensitive a staging procedure as axillary dissection and may identify patients at high risk for disseminating disease.