BACKGROUNDPatients diagnosed with ductal carcinoma in situ (DCIS) at a young age appear to have a different natural history and biology, including a higher local relapse rate, than patients diagnosed later in life. The current study compared various pathologic and molecular features of DCIS arising in a cohort of young women with those of DCIS arising in a cohort of older women to identify potential biologic differences between these two populations of patients.METHODSThe study population consisted of 20 patients age < 42 years and 34 patients age > 60 years who were treated at Yale University School of Medicine with breast‐conserving therapy (BCT) and whose archival paraffin blocks were available and had sufficient tumor for staining. The original slides from each case were reviewed and the most representative specimen block from each case was processed for immunohistochemical staining. Pathologic characteristics evaluated for each case included histology, grade, and presence of necrosis. Paraffin‐embedded sections were immunohistochemically evaluated for expression of HER‐2/neu, estrogen receptor (ER), progesterone receptor (PR), bcl‐2, cyclin D1, Ki‐67, and p53.RESULTSAlthough there was no difference in pathologic features of the tumors between the two groups, HER‐2/neu was found to be overexpressed in a greater percentage of the younger population (P = 0.06). There was no apparent difference in expression of the other markers. Of note, HER‐2/neu expression was correlated with high nuclear grade (P = 0.004), necrosis (P = 0.06), and ER and PR negativity (P = 0.01 and P = 0.03, respectively) in the combined population.CONCLUSIONSThe current study data suggested that HER‐2/neu overexpression in younger patients may characterize a biologic difference in their tumor and may partially contribute to their higher risk of recurrence. Further studies are needed to assess whether this difference holds independent of grade and to evaluate the prognostic significance of HER‐2/neu overexpression in DCIS. Cancer 2003;97:1393–1403. © 2003 American Cancer Society.DOI 10.1002/cncr.11204

BACKGROUND. The authors identified biochemical and pathologic factors that were associated significantly with prostate cancer‐specific mortality (PCSM) after androgen deprivation therapy (ADT) in men who had rapidly rising prostate‐specific antigen (PSA) levels after they received local treatment. METHODS. The study population consisted of 67 patients who had a PSA doubling time (DT) ≤6 months after radical prostatectomy (n = 50 patients) or external beam radiation therapy (n = 17 patients) for localized prostate cancer. Multivariate Cox proportional hazards regression analysis was used to evaluate whether the interval to PSA failure, pre‐ADT PSA DT, PSA level at the time of ADT initiation, time to PSA nadir, PSA nadir after 8 months on ADT, and Gleason score were associated significantly with the time to PCSM 8 months after the initiation of ADT. RESULTS. A PSA nadir >0.2 ng/mL (adjusted hazard ratio [HR], 8.0; 95% confidence interval [95% CI], 1.7–38.7; P = 0.009) and a Gleason score ≥8 (adjusted HR, 5.2; 95% CI, 1.3–20.6; P = 0.02) were associated significantly with a short time to PCSM. The cumulative incidence estimates of 3‐year PCSM were 5.8% versus 50.9% for patients with a PSA nadir ≤0.2 ng/mL versus >0.2 ng/mL, respectively, and 10.8% versus 35.8% for patients who had tumors with a Gleason score ≤7 versus ≥8, respectively. CONCLUSIONS. Among men with a PSA DT ≤6 months, both a PSA nadir >0.2 ng/mL after ADT and a Gleason score ≥8 cancer identified men who were at high risk for PCSM. These men would be ideal candidates for Phase III studies that evaluate the impact on survival of new systemic therapies for prostate cancer. Cancer 2006. © 2006 American Cancer Society.

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