Introduction There are several important factors that are known to be associated with an increased risk of relapse after primary surgical therapy for operable breast cancer. These include the number of axillary lymph node metastases, tumor size, histological grade, and estrogen- and progesterone-receptor expression. 1 Several reports have also suggested that young age (less than 35 or 40 years of age) is also associated with higher risk of regional metastases 2 and systemic relapse. 3,4 Although some studies have demonstrated an association between young age and adverse prognostic features, young age retained an independent adverse effect when adjusted for these factors. 5,6 The poor prognosis for young women, therefore, may be due in part to undefined biologic charac- teristics of the tumor or perhaps to hormonal, immunologi- cal, or other factors. Dozens of other biological factors have been evaluated as factors that may predict relapse (prognostic factors) or bene- fit from adjuvant therapy (predictive factors), especially in patients with axillary node–negative breast cancer. 7 The most intensively studied prognostic factors include overex- pression of the mutated tumor-suppressor gene, p53, and markers indicative of angiogenesis, such as microvessel den- sity (MVD). Overexpression of mutant p53 protein, which is indicative of a mutated p53 gene, 8 is associated with a high tumor proliferation rate 9,10 and a higher risk of local 11 and systemic relapse in patients with node-negative 12 and node- Clinical Breast Cancer April 2001 • 67 communication brief Albert Einstein Comprehensive Cancer Center, Departments of Oncology and Pathology, Montefiore Medical Center, Bronx, New York Microvessel Density and p53 Overexpression in Young Women with Breast Cancer: A Case-Control Study Barry Kalfon, Susan Fineberg, Yun Gu, Kanchana Anand, Ashish Dalal, Joan Jones, Joseph A. Sparano Submitted: Sept. 28, 2000; Revised: Nov. 17, 2000; Accepted: Dec. 5, 2000 Several reports have indicated that young women (less than 40 years of age) with breast cancer have a worse prognosis than older women. We performed a case-control study in order to confirm this observation and to determine whether this was attributable to increased microvessel density (MVD) or p53 expression. Twenty-six young women (cases) with stage I-III breast cancer that had adequate paraffin-embedded archival tissue were identified by the Montefiore Medical Center Tumor Registry over a 24-year period. For each case, two or three control subjects at least 40 years of age or older were selected from the registry and matched for nodal status and tumor size. Immunohistochemistry was performed for MVD and p53 overexpression. A Cox proportional hazard model was performed to examine the influence of age, MVD, p53 overexpression, and recognized prognostic factors on disease-free and overall survival. There were 26 cases (median age, 36 years) and 72 controls (median age, 64 years). The groups were well matched for known prognostic variables. There was no significant difference in p53 overexpression or MVD in the cases and controls. In multivariate analysis, the only features associated with an increased risk of recurrence included young age (hazard ratio [HR] = 2.49; 95% confidence interval [CI]: 1.18-5.25; P = 0.02) and positive lymph nodes (HR = 2.44; 95% CI: 1.12-5.30; P = 0.02). We have confirmed previous reports demonstrating a worse prognosis for women younger than 40 years with invasive breast cancer but found no correlation between young age and MVD or p53 over- expression when adjusted for other variables. Clinical Breast Cancer, Vol. 2, No. 1, 67-72, 2001 Key words: Young age, Microvessel density, p53 overexpression, Breast cancer Abstract Address for correspondence: Joseph A. Sparano, MD, Albert Einstein Comprehensive Cancer Center, Montefiore Medical Center, Department of Oncology-2 South, Room 47, 1825 Eastchester Road, Bronx, NY 10461-2373 Fax: 718-904-2892; e-mail: sparano@jimmy.harvard.edu