neu/erbB-2 amplification is an independent prognostic factor for risk of recurrence in ANN breast cancer. Women with tumors without neu/erbB-2 amplification have a good prognosis; aggressive therapy in this group is therefore difficult to justify. On the other hand, even with adjuvant chemotherapeutic treatment, women whose tumors exhibit neu/erbB-2 amplification have an increased risk of recurrence. We encourage a randomized trial to compare more aggressive adjuvant chemotherapy versus standard chemotherapy for ANN women whose tumors exhibit neu/erbB-2 amplification.

Aspergillosis of the sinonasal tract has four basic clinicopathologic presentations depending on the mucosal or extramucosal involvement by the fungus. Two are saprophytic (aspergilloma and allergic Aspergillus sinusitis) and two are infectious (chronic indolent and invasive fulminant sinusitis). Tissue-invasive and angioinvasive aspergillosis can be a rapidly lethal disease, particularly in the immune-compromised host. The allergic form of paranasal sinus aspergillosis is presumed to be initiated by hyperreactivity to fungal antigens. Not all allergic fungal sinusitis is associated with Aspergillus species, and culture confirmation is necessary to distinguish the fungal agent. Surgical removal of the offending fungus is the mainstay of therapy in all forms of sinonasal aspergillosis and other fungal sinusitis. Antifungal agents and steroids complement surgical removal, depending on the form of the sinusitis.

Disruption of p53 gene function seems to have a pivotal role in carcinogenesis. p53 gene changes occur before the development of breast cancer and therefore might influence breast cancer risk. We investigated the association between p53 protein accumulation and p53 mutations detected in benign breast tissue and risk of subsequent breast cancer. We conducted a case-control study nested within the cohort of 4,888 women in the Canadian National Breast Screening Study who were diagnosed with biopsy-confirmed benign breast disease during active follow-up. Cases were women with benign breast disease who subsequently developed breast cancer; five controls were matched to each case. p53 protein accumulation was assessed immunohistochemically using sections of paraffin-embedded benign breast tissue from 104 cases and 385 controls; for 82 of these cases and 327 of the controls, DNA was successfully extracted from the breast tissue for p53 gene analysis using PCR-singlestrand conformation polymorphism/direct sequencing. p53 protein accumulation was associated with a 2-fold increase in risk of progression to breast cancer [adjusted odds ratio (OR), 2.16; 95% confidence interval (95% CI), 1.08-4.30], whereas p53 nucleotide changes overall were not associated with altered risk (adjusted OR, 1.22; 95% CI, 0.68-2.19); those with both p53 immunopositivity and a p53 nucleotide change had an OR (95% CI) of 3.20 (1.21-8.50). Nonpolymorphic intronic changes were associated with a 2.8-fold increase in risk (OR, 2.84; 95% CI, 1.09-7.41). The results of this study suggest that p53 protein accumulation and nonpolymorphic intronic changes in p53 are associated with increased risk of progression to breast cancer in women with benign breast disease. (Cancer Epidemiol Biomarkers Prev 2006;15(7):1316 -23)

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