Mayo Clin Proc. • September 2007;82(9):1131-1140 • www.mayoclinicproceedings.com 1131 THERAPEUTIC CONSIDERATIONS OF BREAST CANCER For personal use. Mass reproduce only with permission from Mayo Clinic Proce e dings. For personal use. Mass reproduce only with permission from Mayo Clinic Proce e dings. SYMPOSIUM ON SOLID TUMORS From the Breast Diagnostic Clinic, Division of General Internal Medicine (S.P.), Department of Surgery (J.C.B., A.C.D.), Department of Radiology (K.R.B.), Department of Oncology (G.K.D., M.P.G., J.N.I.), Department of Laboratory Medicine and Pathology (C.A.R.), and Department of Radiation Oncology (P.J.S.), Mayo Clinic, Rochester, Minn; and Division of Hematology/ Oncology, Mayo Clinic, Jacksonville, Fla (E.A.P.). Dr Goetz is a consultant for F. Hoffman-La Roche Ltd and DNA Direct. Dr Perez serves on an advisory board for Genentech, Inc, sanofi-aventis, GlaxoSmithKline, and Novartis and receives research support from GlaxoSmithKline. Dr Ingle receives honoraria from AstraZeneca Pharmaceu- ticals LP, Novartis, and Pfizer Inc. Address correspondence to Sandhya Pruthi, MD, Division of General Internal Medicine, Mayo Clinic, 200 First St SW, Rochester, MN 55905 (e-mail: pruthi .sandhya@ mayo.edu). Individual reprints of this article and a bound reprint of the entire Symposium on Solid Tumors will be available for purchase from our Web site www.mayoclinicproceedings.com. © 2007 Mayo Foundation for Medical Education and Research A Multidisciplinary Approach to the Management of Breast Cancer, Part 2: Therapeutic Considerations SANDHYA PRUTHI, MD; JUDY C. BOUGHEY, MD; KATHLEEN R. BRANDT, MD; AMY C. DEGNIM, MD; GRACE K. DY, MD; MATTHEW P. GOETZ, MD; EDITH A. PEREZ, MD; CAROL A. REYNOLDS, MD; PAULA J. SCHOMBERG, MD; AND JAMES N. INGLE, MD New approaches to breast cancer treatment have enhanced clini- cal outcomes and patient care. These approaches include ad- vances in breast irradiation and hormonal and systemic adjuvant therapies. In addition to the identification of new drug targets and targeted therapeutics (eg, trastuzumab), there is renewed reem- phasis in the development of biomarkers for the prediction of response to therapy. One example is the pharmacogenetics of tamoxifen metabolism and the individualization of hormonal therapy. The current treatment of breast cancer continues to evolve rapidly, with new scientific and clinical achievements con- stantly changing the standard of care and leading to substantial reductions in breast cancer mortality. The goal of this article is to provide clinicians who care for women with breast cancer a multidisciplinary, state-of-the art approach to the treatment of these patients. M ayo Clin Proc. 2007;82(9):1131-1140 AI = aromatase inhibitor; DCIS = ductal carcinoma in situ; CYP2D6 = cytochrome P450 2D6; DFS = disease-free survival; FDA = Food and Drug Administration; FEC = fluorouracil, epirubicin, and cyclophospha- mide; LHRH = luteinizing hormone-releasing hormone; NSABP = Na- tional Surgical Adjuvant Breast and Bowel Project; PBI = partial breast irradiation P art 1 of this contribution discussed the multidisci- plinary approach needed for the prevention and diag- nosis of breast cancer. This team of experts includes medi- cal oncologists, breast radiologists, breast pathologists, surgical breast specialists, radiation oncologists, geneti- cists, and primary care physicians. 1 The current contribu- tion provides clinicians who care for women with breast cancer a multidisciplinary, state-of-the art approach to the treatment of these patients. WHOLE BREAST IRRADIATION VS PARTIAL BREAST IRRADIATION: WHAT IS NEW? Breast-conserving surgery (lumpectomy) is considered standard treatment of early-stage breast cancer. Random- ized trials have shown that breast irradiation after such surgery reduces the risk of recurrence in the breast and thus improves the likelihood of breast preservation. 2 To date, no subset of patients has been identified in whom radiation can be eliminated when local control and breast preserva- tion are end points. 3 Typically, the radiation schedule used in the United States has been 45 to 50 Gy in 5 to 5 1 /2 weeks to the entire breast sometimes followed by a tumor bed boost of an additional 10 to 15 Gy in 1 to 1 1 /2 weeks. Local recurrence after such an approach ranges from 6% to 14%, and survival is equivalent to the results of patients undergo- ing mastectomy. 2,4 However, some women who are candidates for a breast- conserving approach choose mastectomy instead because of issues related to the inconvenience of such a protracted treatment regimen. 5 In the United States, only 43% of pa- tients with stage I and II disease undergo breast-conserving surgery, and of these, 14% do not receive postoperative radiotherapy. 6 To address this issue of inconvenience, many investigators have explored the use of shorter treat- ment schedules. Whelan et al 7 reported a Canadian ran- domized trial that compared 42.5 Gy in 16 fractions to 50 Gy in 25 fractions. A total of 1234 women with lymph node–negative invasive breast cancer were entered into this study. With a median follow-up of 69 months, no differ- ence in local recurrence-free survival or overall survival rates was detected between the study arms. The percentage of patients with excellent or good global cosmetic outcome at 3 and 5 years was also comparable, thus suggesting that the more convenient shorter schedule is an acceptable alter- native to the standard 5-week regimen. This Canadian hypofractionated regimen has not been widely adopted in the United States but is used for some patients. Traditionally, standard radiation after lumpectomy has targeted the entire breast to treat clinically occult disease. 8 More recently, techniques for partial breast irradiation (PBI), which limits the radiation to the lumpectomy surgi- cal bed, have been introduced. These techniques are based