Publications

OBJECTIVE

In the absence of consistent guidelines for the use of adjuvant hormonal therapy (HT) in treating ductal carcinoma in situ (DCIS), our purpose was to explore a variety of factors associated with discussion, use, and discontinuation of this therapy for DCIS, including patient, tumor, and treatment-related characteristics and physician-patient communication factors.

METHODS

We identified women from eight California Cancer Registry regions diagnosed with DCIS from 2002 through 2005, aged ≥18 years, of Latina or non-Latina white race/ethnicity. A total of 744 women were interviewed an average of 24 months postdiagnosis about whether they had (1) discussed with a physician, (2) used, and (3) discontinued adjuvant HT.

RESULTS

Although 83% of women discussed adjuvant HT with a physician, 47% used adjuvant HT, and 23% of users reported discontinuation by a median of 11 months. In multivariable adjusted analyses, Latina Spanish speakers were less likely than white women to discuss therapy (odds ratio [OR] 0.36, 95% confidence interval [CI] 0.18-0.69) and more likely to discontinue therapy (OR 2.67, 95% CI 1.05-6.81). Seeing an oncologist for follow-up care was associated with discussion (OR 5.10, 95% CI 3.14-8.28) and use of therapy (OR 4.20, 95% CI 2.05-8.61). Similarly, physician recommendation that treatment was necessary vs. optional was positively associated with use (OR 11.2, 95% CI 6.50-19.4) and inversely associated with discontinuation (OR 0.38, 95% CI 0.19-0.73).

CONCLUSIONS

Physician recommendation is an important factor associated with use and discontinuation of adjuvant HT for DCIS. Differences in discussion and discontinuation of therapy according to patient characteristics, particularly ethnicity/language, suggest challenges to physician-patient communication about adjuvant HT across a language barrier.

Airway epithelial cancer cells produce increased amounts of the chemokine interleukin-8 (IL-8), inducing pro-tumor responses. Multiple stimuli induce airway epithelial IL-8 production epidermal growth factor receptor (EGFR) dependently, but the mechanisms that exaggerate IL-8 production in airway cancers remain unknown. Here we show that direct activation of EGFR (EGFR-P) by its ligand transforming growth factor (TGF)-alpha induces a second EGFR-P in human airway (NCI-H292) cancer cells but not in normal human bronchial epithelial (NHBE) cells, exaggerating IL-8 production in these cancer cells. The second EGFR-P in NCI-H292 cells was caused by metalloprotease TNF-alpha-converting enzyme (TACE)-dependent cleavage of EGFR pro-ligands and was responsible for most of the total IL-8 induced by TGF-alpha. In NCI-H292 cells, TGF-alpha induced cyclooxygenase (COX)-2-dependent prostaglandin (PG)E2 production and release. PGE2 increased the second EGFR-P and IL-8 production via binding to its Gi-protein-coupled E-prostanoid (EP)3 receptor. In NHBE cells, TGF-alpha-induced EGFR-P did not lead to PGE2 production or to a second EGFR-P, and less IL-8 was produced. Thus, we conclude that a positive feedback pathway involving COX-2/PGE2/EP3 receptor-dependent EGFR reactivation exaggerates IL-8 production in NCI-H292 cancer cells but not in NHBE (normal) cells.

BACKGROUND AND AIMS

This review summarizes the scientific literature relevant to occupational risk factors for chronic obstructive pulmonary disease (COPD).

MATERIAL AND METHODS

This review emphasizes recent work in the field, while placing this in the context of two previous systematic reviews of the subject.

RESULTS

Both the earlier summaries of the literature estimated that the population attributable risk percent (PAR%) of COPD linked to occupational exposures is approximately 15%. More recent studies also strongly support the association between workplace exposures and COPD. Among never smokers, the PAR% for work-related factors may approach 40%. Emerging data also indicate that occupational exposures, at a minimum, are additive to smoking-associated risk of COPD.

CONCLUSIONS

The PAR% for work-related COPD is at least 15%. Scientific significance. The consistency, strength, and plausibility of these data support a causal relationship between occupational exposures and COPD.