Over the past 20 years, the prognosis for women diagnosed with locally advanced breast cancer (LABC; clinical stages IIB through IIIB) has improved significantly with recognition of the efficacy of multimodal therapy for reducing both local and distant recurrences, even in patients with inflammatory breast cancer (IBC). Most patients will respond to induction, or neoadjuvant, chemotherapy (NAC) with an anthracycline-based regimen, enabling many patients with large but operable tumors to undergo breast-conserving surgery (BCS) and enabling resection in most patients with inoperable disease. However, only a small percentage of patients achieve a pathologic complete response (CR) with this approach. Long-term disease-free survival (DFS) and overall survival (OS) correlate with the extent of residual disease in the breast and axillary nodes following NAC. The addition of paclitaxel or docetaxel, either in combination with an anthracycline or as a separate regimen administered before or after anthracycline-based therapy, increases clinical and pathologic response rates and may improve DFS. With the possible exception of patients with IBC, BCS does not compromise outcome. Partial mastectomy should be accompanied by standard nodal dissection in patients with clinically or radiographically positive axillae; in patients with negative axillae, sentinel lymph node (SLN) sampling, with subsequent axillary dissection reserved for patients with involved nodes, may reduce postoperative morbidity. Patients who received only anthracycline-based NAC who are found to have significant residual disease in the breast or involved axillary nodes at surgery should receive adjuvant chemotherapy with paclitaxel. Postoperative radiation to the residual breast or chest wall and regional nodal areas reduces locoregional recurrences, but its impact on OS remains controversial. Adjuvant hormonal therapy with tamoxifen improves DFS and OS in patients with hormone receptor (HR)-positive tumors, and ovarian ablation should be considered in premenopausal patients with HR-positive tumors and multiple involved nodes or stage IIIB disease. Neoadjuvant hormonal therapy with either tamoxifen or an aromatase inhibitor may benefit frail or elderly patients with HR-positive tumors for whom chemotherapy is not an option. No advantage has been demonstrated for highdose chemotherapy requiring hematopoietic stem-cell support as either NAC or adjuvant therapy in LABC. Newer treatment approaches, including trastuzumab (Herceptin, Genentech, Inc., South San Francisco, CA), in patients with Her-2-overexpressing tumors or other biologic agents, do not have a proven role in the management of LABC at this time.
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References and Recommended Reading
- 2.Hortobagyi GN, Singletary SE, Strom EA: Treatment of locally advanced and inflammatory breast cancer. In Diseases of the Breast, edn 2. Edited by Harris JR, Lippman ME, Morrow M, Osborne CK. Philadelphia: Lippincott Williams & Wilkins; 2000:645–660. An excellent discussion of the development of current treatment approaches.Google Scholar
- 7.Thomas E, Buzdar A, Hortobagyi G, et al.: Long-term follow-up of stage III breast cancer-combined modality treatment with anthracycline containing chemotherapy: the MD Anderson experience [abstract]. Proc Am Soc Clin Oncol 1999, 18:75a. Three analyses confirming the prognostic value of response to neoadjuvant treatment.Google Scholar
- 10.Bortelink H, Rubens RD, van der Schueren E, Sylvester R: Hormonal therapy prolongs survival in irradiated locally advanced breast cancer: a European Organization for Research and Treatment of Cancer randomized phase III trial. J Clin Oncol 1997, 15:207–215.Google Scholar
- 15.Dhingra K, Esparza-Guerra L, Valero V, et al.: A phase III randomized trial of dose-intensive, neoadjuvant 5FU, doxorubicin, cyclophosphamide with G-CSF in locally advanced breast cancer: efficacy and safety data [abstract]. Proc Am Soc Clin Oncol 1999, 18:74a.Google Scholar
- 16.Henderson IC, Berry D, Demetri G, et al.: Improved disease-free and overall survival from the addition of sequential paclitaxel but not from the escalation of doxorubicin dose level in the adjuvant chemotherapy of patients with node-positive primary breast cancer [abstract]. Proc Am Soc Clin Oncol 1998, 17:101a. A pivotal study regarding the benefits of sequential, non-cross-resistant chemotherapy versus dose intensification.Google Scholar
- 18.Sikov WM, Akerley WA, Legare RD, Strenger S: Neoadjuvant high-dose weekly paclitaxel in stage IIB-IIIB breast cancer: a BrUOG study [abstract]. Breast Cancer Res Treat 1999, 57:68.Google Scholar
- 20.Eremin O, Walker LG, Smith IC, et al.: Chemotherapy in breast cancer: enhanced response with docetaxel [abstract]. Proc Am Soc Clin Oncol 1999, 18:72a.Google Scholar
- 21.Pouillart P, Fumoleau P, Romieu G, et al.: Final results of a phase II randomized, parallel study of doxorubicin/ cyclophosphamide and doxorubicin/Taxol as neoadjuvant treatment of local-regional breast cancer [abstract]. Proc Am Soc Clin Oncol 1999, 18:73a.Google Scholar
- 24.Von Minckwitz G, Costa SD, Raab G, et al.: Randomized trial on preoperative dose-intensified adriamycindocetaxel (ADOC) vs. ADOC + tamoxifen in primary operable breast cancer [abstract]. Breast Cancer Res Treat 1999, 57:67.Google Scholar
- 26.Valero V, Hoff PM, Singletary SE, et al.: Combined modality treatment of locally advanced breast cancer in elderly patients using tamoxifen as primary therapy [abstract]. Proc Am Soc Clin Oncol 1998, 17:105a.Google Scholar
- 27.Dixon JM, Love CDB, Tucker S, et al.: Letrozole as primary medical therapy for locally advanced and large operable breast cancer [abstract]. Proc Am Soc Clin Oncol 1998, 17:104a.Google Scholar
- 28.Formenti SC, Spicer D, Skinner K, et al.: Pre-operative twice weekly paclitaxel and radiation therapy in locally advanced breast cancer: molecular determinants of pathological response [abstract]. Proc Am Soc Clin Oncol 1999, 18:75a.Google Scholar