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 are 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 status of receptors for estrogen and v-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian; ErbB2), also known as human epidermal growth factor receptor type 2 (HER2/neu).
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 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 ipsilateral breast 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 produces a sufficient reduction in tumor response that allows patients to receive breast-conserving therapy. The 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 (Adriamycin [doxorubicin] and cyclophosphamide) chemotherapy followed by surgery or 4 cycles of preoperative AC followed by 4 cycles of docetaxel (Taxotere) followed by surgery or 4 cycles of preoperative AC 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) when 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.
Patients undergoing sentinel lymph node biopsy
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 determining nodal involvement. Formal studies are required to determine whether sentinel node biopsy can be safely performed after the patient has completed neoadjuvant chemotherapy.
