This chapter focuses on the treatment of stage II breast cancer, which encompasses primary tumors > 2 cm in greatest dimension that involve ipsilateral axillary lymph nodes as well as tumors up to 5 cm without nodal involvement.

Stage II breast cancer is further subdivided into stages IIA and IIB. Patients classified as having stage IIA breast cancer include those with T0-1, N1, and T2, N0 disease. Stage IIB breast cancer includes patients with T2, N1, and T3, N0 disease. Therefore, this patient population is more heterogeneous than the populations with stages 0 and I disease. The pretreatment evaluation and type of treatment offered to patients with stage II breast cancer are based on tumor size, nodal status, and estrogen receptor status.

Treatment

SURGICAL AND RADIATION TREATMENT

Multiple studies have demonstrated that patients with stage II breast cancer who are treated with either breast-conservation therapy (lumpectomy and radiation therapy) or modified radical mastectomy have similar disease-free and overall survival rates.

Breast-conservation therapy

The optimal extent of local surgery has yet to be determined and, in the literature, has ranged from excisional biopsy to quadrantectomy. A consensus statement issued by the National Cancer Institute (NCI) recommended that the breast cancer be completely excised with negative surgical margins and that a level I–II axillary lymph node dissection be performed. Patients should subsequently be treated with adjuvant breast irradiation.

Patients with tumors > 4 to 5 cm may not be optimal candidates for breast conservation due to the risk of significant residual tumor burden and the potential for a poor cosmetic result following lumpectomy (or partial mastectomy). Neoadjuvant chemotherapy, typically used for locally advanced breast cancer, is increasingly used in earlier stage, operable breast cancers to reduce the size of the primary tumor and allow conservative treatment.

In a study of more than 300 patients treated with neoadjuvant chemotherapy at the M. D. Anderson Cancer Center, promising results were reported. At a median follow-up of 60 months, the 5-year actuarial rates of intrabreast tumor recurrence-free and locoregional recurrence-free survival were 95% and 91%, respectively. The authors concluded that breast-conservation therapy after neoadjuvant chemotherapy results in acceptably low rates of recurrence-free survival in appropriately selected patients, even those with T3 or T4 disease. Advanced nodal involvement at diagnosis, residual tumor larger than 2 cm, multifocal residual disease, and lymphovascular space invasion predict higher rates of recurrence.

In some patients, preoperative chemotherapy results in sufficient reduction in tumor response that breast-conserving therapy becomes possible. The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18 trial showed that preoperative doxorubicin-based chemotherapy decreases tumor size by > 50% in approximately 90% of operable breast cancers, resulting in a greater frequency of lumpectomy.

In a subsequent trial, NSABP B-27, women with invasive breast cancer were randomized to receive 4 cycles of preoperative AC chemotherapy followed by surgery or 4 cycles of preoperative AC (Adriamycin [doxorubicin] and cyclophosphamide) followed by 4 cycles of docetaxel (Taxotere) followed by surgery, or 4 cycles of preoperative AC chemotherapy followed by surgery followed by 4 cycles of postoperative docetaxel. A higher rate of complete pathologic response was seen at surgery in patients treated with AC followed by docetaxel versus AC alone. There were no significant differences in disease-free and overall survival between the treatment groups. However, those who had a complete pathologic response in the breast had significant improvement in disease-free (hazard ratio [HR], 0.45; P < .0001) and overall survival (HR, 0.33; P < .0001) compared with those with residual disease after preoperative chemotherapy. Since preoperative chemotherapy does not have a negative impact on survival, the preoperative approach is a reasonable option and has gained favor among many patients.

Preoperative chemotherapy had an ability to convert patients requiring mastectomy to candidates for breast-conserving surgery. However, there was an increase in local recurrence in the “converted” group compared with those deemed eligibile initially for breast-conserving surgery.

The timing of sentinel node biopsy in patients undergoing preoperative chemotherapy is controversial. Preoperative chemotherapy can sterilize the axillary nodes and lead to errors in determination of nodal involvement. Formal studies are required to determine whether sentinel node biopsy can be safely performed after the patient has completed neoadjuvant chemotherapy.

Radiation therapy after breast-conserving surgery

For patients with stages I and II breast cancer, radiation therapy following lumpectomy remains an acceptable standard of care. Randomized trials as well as single-institution experiences have consistently demonstrated a significant reduction in local relapse rates for radiotherapy following breast-conserving surgery. Furthermore, small but significant differences in distant metastasis and disease-free survival have been observed in randomized trials comparing lumpectomy alone with lumpectomy and radiation therapy for patients with invasive breast cancer.

Based on the results of a number of retrospective single-institution experiences, as well as several prospective randomized clinical trials, breast-conserving surgery followed by radiation therapy to the intact breast is now considered standard treatment for the majority of patients with stage II inva-sive breast cancer.

Radiation dose and protocol Radiation dose to the intact breast follows the same guidelines as are used in patients with stages 0 and I disease, described in chapter 9.