Preoperative chemotherapy for large clinical stage IIA and IIB tumors and T3N1M0 tumors

Preoperative chemotherapy should be considered for women with large clinical stage IIA, stage IIB, and T3N1M0 tumors who meet the criteria for breast-conserving therapy except for tumor size. In the available clinical trials of preoperative chemotherapy, pretreatment biopsies have been limited to core needle biopsy or FNA cytology. Therefore, in patients anticipated to receive preoperative chemotherapy, core or FNA biopsy of the breast tumor should be performed, and core or FNA biopsy of clinically suspicious axillary lymph nodes should be considered. Preoperative chemotherapy is not indicated unless invasive breast cancer is confirmed.

The current Guideline allows the performance of pretreatment sentinel lymph node resection in those women with clinically negative axillary examinations. If the sentinel lymph node is histologically negative, omission of the axillary dissection may be considered at the time of local, surgical therapy. If the sentinel lymph node is histologically positive, then level I and II axillary dissection should be performed at the time of definitive surgical therapy. If a prechemotherapy sentinel lymph node excision is not performed, then a level I and II axillary dissection (category 2A) or sentinel lymph node excision (category 3) (with level I and II axillary dissection if sentinel lymph node is positive) should be performed at the time of definitive surgical therapy.

In some patients, preoperative chemotherapy results in sufficient tumor response that breast-conserving therapy becomes possible. Because complete or near-complete clinical responses are common, the use of percutaneously placed clips into the breast under mammographic or ultrasound guidance or other method of localizing pre-chemotherapy tumor volume aids in the post-chemotherapy resection of the original area of tumor and is encouraged. The results of the NSABP B-18 trial show that breast conservation rates are higher after preoperative chemotherapy. However, preoperative chemotherapy has no demonstrated disease specific survival advantage over postoperative adjuvant chemotherapy in patients with stage II tumors. NSABP B-27 is a 3-arm, randomized phase III trial of women with invasive breast cancer treated with preoperative doxorubicin and cyclophosphamide (AC) chemotherapy for 4 cycles followed by local therapy alone, preoperative docetaxel for 4 cycles followed by local therapy, or local therapy followed by 4 cycles of postoperative docetaxel. Early results from the 2500 women randomized in NSABP B-27 show a higher rate of complete pathologic response at surgery in patients treated with 4 cycles of AC followed by 4 cycles of docetaxel versus 4 cycles of AC alone. Disease-free survival and overall survival have not been shown to be superior following docetaxel treatment in B-27, and no difference in clinical outcome between preoperative versus postoperative docetaxel has been reported.

A number of chemotherapy regimens have been studied as preoperative chemotherapy in this setting. The panel believes that the regimens recommended in the adjuvant setting ) are appropriate to consider in the preoperative chemotherapy setting. In women treatment with neoadjuvant chemotherapy whose tumors over-express HER2/ the addition of neoadjuvant trastuzumab to paclitaxel followed by FEC chemotherapy was associated with an increase in the pathologic complete response rate from 26% to 65.2% (p=0.016). Thus, the incorporation of trastuzumab into neoadjuvant chemotherapy regimens appears important in tumors over-expressing HER2/ .

Several randomized trials have assessed the value of neoadjuvant endocrine therapy in postmenopausal women with estrogen receptor-positive breast cancer. These studies have generally compared the rates of objective response and rates of breast conserving surgery among treatment with tamoxifen, anastrozole, anastrozole plus tamoxifen, or letrozole. These studies consistently demonstrate that the use of either anastrozole or letrozole alone provides superior rates of breast conserving surgery and usually objective response. On the basis of these trials, preoperative hormonal therapy with an aromatase inhibitor is an option in the treatment of postmenopausal women with hormone receptor positive disease.