Summary Young age at diagnosis is claimed to be a prognostic factor in the natural history of breast cancer. Of 2879 patients aged < 70 years treated for primary operable breast cancer (< 5 cm diameter) at Nottingham City Hospital between 1973 and 1993, 120 were less than 35 years of age at diagnosis. Histopathological and prognostic variables were compared between patients aged < 35, 35-50 and 51-70 years. A significant reduction in metastasis disease-free survival and actuarial survival was seen in breast cancer patients aged < 35 years compared with the two older age groups. Patients aged < 35 years at diagnosis presented more frequently with high-grade cancers and vascular invasion. No differences were seen for tumour size or lymph node stage. The Nottingham Prognostic Index (NPI) was used to stratify cancers in each age group. Because of the tendency to high grade, a greater percentage of patients aged < 35 years fell into the poorprognosis group. Within each prognostic group, no difference in actuarial survival was seen between age groups. The association of young age at diagnosis with a worse prognosis in this series is explained by a higher proportion of poorly differentiated cancers; age itself had no influence on the prognosis of the individual.

We examined c-erbB3 and c-erbB4 mRNA expression in 47 primary breast cancer samples by simultaneous RT ± PCR and have investigated correlations between these parameters and the expression of both ER and EGFR mRNA and protein as measured by RT ± PCR and ICA and with Ki67 immunostaining. A direct association was found between c-erbB3 and c-erbB4 mRNA and ER marker status measured by either RT ± PCR (c-erbB3 P=0.0003; c-erbB4 P=0.02) or ICA (c-erbB-3 P=0.002; c-erbB4 P=0.01). Inverse associations were seen between c-erbB3 and c-erbB4 mRNA marker status and EGFR membrane protein (c-erbB3: P=0.003; cerbB4: P=0.003) and mRNA (c-erbB4: P=0.009) status. These associations were reinforced by Spearman Rank Correlation Tests. A signi®cant relationship was seen between Ki67 and c-erbB4 mRNA status and level. Measurements of c-erbB3 protein levels in tumour samples removed from a further 89 patients of known response to endocrine therapy: (i) con®rmed the relationship between c-erbB3 and ER and (ii) identi®ed that patients whose ER positive tumours expressed high levels of c-erbB3 were most likely to bene®t from endocrine measures. A non-signi®cant trend was recorded between c-erbB3 levels and Ki67 immunostaining. These results clearly demonstrate that increased c-erbB3 and c-erbB4 expression appears to be associated with the prognostically-favourable ER phenotype.

MUC1 is a high molecular weight glycoprotein that is overexpressed in breast cancer. Aberrant O-linked glycosylation of MUC1 in cancer has been implicated in disease progression. We investigated the O-linked glycosylation of MUC1 purified from the serum of an advanced breast cancer patient. O-Glycans were released by hydrazinolysis and analyzed by liquid chromatography-electrospray ionization-mass spectrometry and by high performance liquid chromatography coupled with sequential exoglycosidase digestions. Core 1 type glycans (83%) dominated the profile which also confirmed high levels of sialylation: 80% of the glycans were mono-, di- or trisialylated. Core 2 type structures contributed approximately 17% of the assigned glycans and the oncofoetal Thomsen-Friedenreich (TF) antigen (Galbeta1-3GalNAc) accounted for 14% of the total glycans. Interestingly, two core 1 type glycans were identified that had sialic acid alpha2-8 linked to sialylated core 1 type structures (9% of the total glycan pool). This is the first O-glycan analysis of MUC1 from the serum of a breast cancer patient; the results suggest that amongst the cell lines commonly used to express recombinant MUC1 the T47D cell line processes glycans that are most similar to patient-derived material.

Recent publications have reported the technical and clinical validation of EarlyCDT-Lung, an autoantibody test which detected elevated autoantibodies in 40% of lung cancers at diagnosis. This manuscript reports the results of EarlyCDT-Lung run on four new (postvalidation) data sets. The following four cohorts of patients (n ¼ 574) with newly diagnosed lung cancer were identified: group 1 (n ¼ 122), 100% small cell lung cancer (SCLC); group 2 (n ¼ 249), 97% non-small cell lung cancer (NSCLC); group 3 (n ¼ 122), 100% NSCLC; group 4 (n ¼ 81), 62% NSCLC. Serum samples were obtained after diagnosis, prior to any anticancer treatment. Autoantibody levels were measured against a panel of six tumor-related antigens (p53, NY-ESO-1, CAGE, GBU4-5, Annexin 1, and SOX2) in the EarlyCDT-Lung panel and previously established cutoffs applied. In groups 2, 3, and 4, patients were individually matched by gender, age, and smoking history to a control individual with no history of malignant disease. Assay sensitivity was tested in relation to cancer type and stage, and in the matched normals to demographic variables. The autoantibody panel showed sensitivity/specificity of 57%/n.d (not done) for SCLC in group 1, 34%/87% for NSCLC in group 2, 31% and 84% for NSCLC in group 3, and 35%/89% for NSCLC and 43%/89% for SCLC in group 4. There was no significant difference in positivity of EarlyCDT-Lung and different lung cancer stages. These studies confirm the value of an autoantibody assay, EarlyCDT-Lung, as an aid to detecting lung cancer in patients at high risk of the disease. Cancer Prev Res; 4(7); 1126-34. Ó2011 AACR.