Differences between palpable and nonpalpable tumors in early-stage, hormone receptor-positive breast cancer.

BACKGROUND: We compared characteristics and outcomes of palpable versus nonpalpable, hormone-sensitive, early-stage breast cancers. METHODS: Patients from the North American Fareston vs. Tamoxifen Adjuvant (NAFTA) trial were divided into palpable (n = 513) and nonpalpable (n = 1063) tumor groups. Differences in pathological features, loco-regional therapy, disease-free survival (DFS) and overall survival (OS) were analyzed. RESULTS: Patients with palpable tumors were older, had larger tumors, and higher rates of lymph-node involvement. The tumors were more likely to be poorly differentiated, of high nuclear grade, and display lymphovascular invasion. After mean followup of 59 months, DFS and OS were significantly lower for palpable than nonpalpable tumors (DFS 93.5% vs. 98.4%, p < 0.001, OS 88.5% vs. 95.6%, p < 0.001). Controlling for age, size and nodal status, palpability was an independent factor for DFS (OR = 2.56; 95%CI, 1.37-4.79, p = 0.003) and OS (OR = 2.12; 95%CI, 1.38-3.28, p < 0.001). CONCLUSIONS: In a group of hormone-sensitive, mostly postmenopausal early-stage breast cancer patients, palpable tumors were more likely to have more aggressive features and metastatic potential, which translated in to a higher incidence of breast cancer-related events and worse overall survival.

Global gene expression analysis reveals specific and redundant roles for H1 variants, H1c and H1(0), in gene expression regulation.

In mammals, the functional significance of the presence of evolutionarily conserved, multiple non-allelic H1 variants remains unclear. We used a unique overproduction approach coupled with cell cycle synchronization and early time point assays to assess differential effects of H1 variants, H1c and H1(0), on global gene expression in the absence of compensatory events that may mask variant-specific effects. We found that H1c and H1(0) act primarily as specific rather than global regulators of gene expression. Many of the genes affected were uniquely targeted by either H1c or H1(0), affirming that H1 variants have some unique roles. We also identified genes that were affected by both variants, in which cases the expression of these genes was, for the most part, affected similarly by both the variants. This observation suggests that as well as having specific functions, the H1 variants share common roles in the organization of chromatin. We further noted that H1(0) repressed more genes than did H1c, which may underlie the prevailing notion that H1(0) is a stronger repressor of transcription.