Wildiers H, et al. Lancet Oncol. 2007;8:1101. Breast Cancer in Elderly (>65 Years) Recommendations of the International Society of Geriatric Oncology Surgical recommendations are similar to those in younger patients Surgical recommendations are similar to those in younger patients Radiotherapy Radiotherapy –Considered after breast conservation therapy, taking into account patient health, functional status, and local recurrence risk Unlikely to affect overall survival Unlikely to affect overall survival –Postmastectomy if 4+ lymph nodes or T3–4 May be omitted if life expectancy <5 years and low risk of locoregional recurrence May be omitted if life expectancy <5 years and low risk of locoregional recurrence Adjuvant systemic therapy Adjuvant systemic therapy –Tamoxifen and/or aromatase inhibitor (AI) appropriate for hormone-sensitive tumors Consider toxicity profiles and slightly higher efficacy of AI Consider toxicity profiles and slightly higher efficacy of AI –Chemotherapy choices should take into account absolute benefit, life expectancy, and tolerability Treatment goals for metastatic disease are similar to those in younger patients Treatment goals for metastatic disease are similar to those in younger patients

Millikan RC, et al. Breast Cancer Res Treat. Epub ahead of print. Age and Molecular Subtypes Basal-like (P <.0001) HER2 Positive/ ER Negative Luminal A Luminal B Unclass -ified Premenopause55%40%41%47%53% Postmenopause45%60%59%53%47%

Quantative ER and Age Tamoxifen-Treated Arms B-14 and B-20 Age (years) ER (fmol/mg) Median P <.0001 ≤4050–59≥60

Quantative ER and Therapeutic Efficacy NSABP Studies Placebo Tamoxifen CMFT ER (fmol/mg) Median Event-Free at 12 y Postsurgery 10–49 ≥50

Muss HB, et al. J Clin Oncol. 2007;25: patients treated in 3 chemotherapy trials CALGB 8541: CAF at varying schedules and doses CALGB 9344: AC at varying doses, with or without paclitaxel CALGB 9741: Dose-dense vs standard AC-paclitaxel Chemotherapy Toxicity by Age ≤50 Years (n = 3393) 51–64 Years (n = 2323) >65 Years (n = 458) WBC (grade 4; P <.0001)16%17% Platelets (grade 4)3%4% Hemoglobin (grade 4)1% Nausea/vomiting (grade 3–4)10%7% Diarrhea (grade 3–4)1%2%1% Stomatitis (grade 3–4)5%4%5% Neurologic (grade 3–4)8%9%

1. Li C, et al. Cancer Epidemiol Biomarkers Prev. 2006;15: Diab S, et al. J Natl Cancer Inst. 2000;92: Millikan RC, et al. Breast Cancer Res Treat. Epub ahead of print. Clinicopathologic Differences in Breast Cancer in Older Women Histology 1,2 Histology 1,2 –Increased mucinous, lobular –Decreased medullary Favorable biologic characteristics Favorable biologic characteristics –Endocrine responsive 2 –Fewer p53 mutants 2 –Lower proliferative indices 2 –Fewer basal-like and more luminal A 3

Dontu G, et al. Trends Endocrinol Metab. 2004;15:193. Carcinogenesis High ER Differentiated Luminal markers Induced by HRT Sensitive to endocrine therapy

1. Li C, et al, Cancer Epidemiol Biomarkers Prev. 2007;16: Smith-Bindman R, et al. Ann Intern Med. 2006;144: Carey LA, et al. JAMA. 2006;295: Curtis E, et al. Cancer. 2008;112: Breast Cancer in African-American Women Lower overall risk, but recent decrease in incidence not seen in African Americans Lower overall risk, but recent decrease in incidence not seen in African Americans –Annual percentage change (1999–2004) Caucasians: 2.9% Caucasians: 2.9% African Americans: 0.5% 1 African Americans: 0.5% 1 Less likely to receive adequate mammography and more likely to have higher stage at diagnosis 2 Less likely to receive adequate mammography and more likely to have higher stage at diagnosis 2 Differences in molecular subtypes Differences in molecular subtypes –Higher prevalence of basal-like –Lower prevalence of luminal A 3 Worse survival, partly due to differences in screening, tumor characteristics, and treatment 4 Worse survival, partly due to differences in screening, tumor characteristics, and treatment 4