Current Treatment Options in Oncology

, Volume 1, Issue 3, pp 228–238 | Cite as

Locally advanced breast cancer

  • William M. Sikov

Opinion statement

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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Chang S, Parker SL, Pham T, et al.: Inflammatory breast carcinoma incidence and survival: the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute, 1975-1992. Cancer 1998, 82:2366–2372.PubMedCrossRefGoogle Scholar
  2. 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
  3. 3.
    Fisher B, Bryant J, Wolmark N, et al.: Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol 1998, 16:2672–2685. A pivotal study of neoadjuvant versus adjuvant chemotherapy.PubMedGoogle Scholar
  4. 4.
    Kuerer HM, Newman LA, Smith TL, et al.: Clinical course of breast cancer patients with complete pathologic response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol 1999, 17:460–469. Analysis of long-term outcome for patients who achieve a pCR.PubMedGoogle Scholar
  5. 5.
    Kuerer HM, Sahin AA, Hunt KK, et al.: Incidence and impact of documented eradication of breast cancer axillary lymph node metastases before surgery in patients treated with neoadjuvant chemotherapy. Ann Surg 1999, 230:72–78.PubMedCrossRefGoogle Scholar
  6. 6.
    Machiavelli MR, Romero AO, Perez JE, et al.: Prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy for locally advanced breast carcinoma. Cancer J Sci Am 1998, 4:125–131.PubMedGoogle Scholar
  7. 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
  8. 8.
    Olson JE, Neuberg D, Pandya K, et al.: The role of radiotherapy in the management of operable locally advanced breast carcinoma: results of a randomized trial by the Eastern Cooperative Oncology Group. Cancer 1997, 79:1138–1149.PubMedCrossRefGoogle Scholar
  9. 9.
    Abdel-Wahab M, Wolfson A, Raub W, et al.: The importance of postoperative radiation therapy in multimodality management of locally advanced breast cancer: a phase II trial of neoadjuvant MVAC, surgery, and radiation. Int J Radiat Oncol Biol Phys 1998, 40:875–880.PubMedCrossRefGoogle Scholar
  10. 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
  11. 11.
    Lopez MJ, Porter KA: Inflammatory breast cancer. Surg Clin North Am 1996, 76:411–429.PubMedCrossRefGoogle Scholar
  12. 12.
    Perez CA, Fields JN, Fracasso PM, et al.: Management of locally advanced carcinoma of the breast: II. Inflammatory carcinoma. Cancer 1994, 74:466s-476s.CrossRefGoogle Scholar
  13. 13.
    Fleming RY, Asmar L, Buzdar AU, et al.: Effectiveness of mastectomy by response to induction chemotherapy for control in inflammatory breast carcinoma. Ann Surg Oncol 1997, 4:452–461.PubMedCrossRefGoogle Scholar
  14. 14.
    Ueno NT, Buzdar AU, Singletary SE, et al.: Combinedmodality treatment of inflammatory breast carcinoma: twenty years of experience at MD Anderson Cancer Center. Cancer Chemother Pharmacol 1997, 40:321–329.PubMedCrossRefGoogle Scholar
  15. 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. 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
  17. 17.
    Buzdar AU, Singletary SE, Theriault RL, et al.: Prospective randomized trial of paclitaxel versus combination chemotherapy with fluorouracil, doxorubicin, and cyclophosphamide as neoadjuvant therapy in patients with operable breast cancer. J Clin Oncol 1999, 17:3412–3417.PubMedGoogle Scholar
  18. 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
  19. 19.
    Miller KD, McCaskill-Stevens W, Sisk J, et al.: Combination versus sequential doxorubicin and docetaxel as primary chemotherapy for breast cancer: a randomized pilot trial of the Hoosier Oncology Group. J Clin Oncol 1999, 17:3033–3037.PubMedGoogle Scholar
  20. 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. 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
  22. 22.
    Honkoop AH, Pinedo HM, De Jong JS, et al.: Effects of chemotherapy on pathologic and biologic characteristics of locally advanced breast cancer. Am J Clin Pathol 1997, 107:211–218.PubMedGoogle Scholar
  23. 23.
    Smith TJ, Hillner BE: The efficacy and cost-effectiveness of adjuvant therapy of early breast cancer in premenopausal women. J Clin Oncol 1993, 11:771–776.PubMedGoogle Scholar
  24. 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
  25. 25.
    Viens P, Palangie T, Janvier M, et al.: First-line highdose sequential chemotherapy with rG-CSF and repeated blood stem cell transplantation in untreated inflammatory breast cancer: toxicity and response (PEGASE 02 trial). Br J Cancer 1999, 81:449–456.PubMedCrossRefGoogle Scholar
  26. 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. 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. 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
  29. 29.
    Touboul E, Buffat L, Lefranc JP, et al.: Possibility of conservative local treatment after combined chemotherapy and preoperative irradiation for locally advanced noninflammatory breast cancer. Int J Radiat Oncol Biol Phys 1996, 34:1019–1028.PubMedCrossRefGoogle Scholar
  30. 30.
    Smith TJ, Davidson NE, Schapira DV, et al.: American Society of Clinical Oncology 1998 update of recommended breast cancer surveillance guidelines. J Clin Oncol 1999, 17:1080–1082.PubMedGoogle Scholar

Copyright information

© Current Science Inc 2000

Authors and Affiliations

  • William M. Sikov
    • 1
  1. 1.Department of Medicine, Room 320The Miriam HospitalProvidenceUSA

Personalised recommendations