Impact of the Tips From Former Smokers Anti-Smoking Media Campaign on Youth Smoking Behaviors and Anti-Tobacco Attitudes.

INTRODUCTION: Anti-tobacco media campaigns can prevent youth smoking, but there is little research on how adult-targeted campaigns affect youth. We investigated the association between the Tips From Former Smokers (Tips) campaign and youth smoking behaviors and anti-tobacco attitudes, and variation by sex, race and/or ethnicity, or socioeconomic status. AIMS AND METHODS: We used data from the monitoring of the future study, a nationally representative survey on 8th, 10th, and 12th graders, from 2013-2015. Quartiles of Tips gross rating points (GRPs) were used to estimate exposure. Youth smoking behavior outcomes included smoking prevalence, initiation, and susceptibility. The anti-tobacco attitude outcomes included the extent that anti-tobacco ads made participants (1) less favorable towards smoking or (2) less likely to smoke cigarettes. Modified Poisson regression models estimated average marginal effects; separate additive interactions between Tips GRP exposure and sex, race and/or ethnicity, parents' highest education, and college plans (12th graders only) were used to test for effect modification. RESULTS: Tips GRPs were not associated with smoking behaviors within any grade. However, 12th graders in the highest quartile of Tips had a 7.0 percentage point higher probability (95% CI = 0.023-0.116) of responding that anti-tobacco ads made them less likely to smoke. Tips GRPs were associated with a lower probability of past 30-day smoking prevalence among 10th grade females, but not males (joint P-value = .002). No additional statistically significant interactions were found for any other outcomes for any grade. CONCLUSIONS: This study revealed the potential for adult-targeted campaigns to increase youth's anti-smoking attitudes, but campaign exposure was not associated with smoking behaviors. IMPLICATIONS: Few studies have examined the potential for anti-smoking media campaigns to influence audiences outside their targeted audience. In this study, we show the potential for adult-targeted campaigns to impact youth and suggest that Tips exposure may promote anti-smoking attitudes among youth.

Collagen and PAPP-A in the Etiology of Postpartum Breast Cancer.

Pregnancy has a dual effect on the risk of breast cancer. On one hand, pregnancy at a young age is known to be protective. However, pregnancy is also associated with a transient increased risk of breast cancer. For women that have children after the age of 30, the risk remains higher than women who never had children for decades. Involution of the breast has been identified as a window of mammary development associated with the adverse effect of pregnancy. In this review, we summarize the current understanding of the role of involution and describe the role of collagen in this setting. We also discuss the role of a collagen-dependent protease, pappalysin-1, in postpartum breast cancer and its role in activating both insulin-like growth factor signaling and discoidin domain collagen receptor 2, DDR2. Together, these novel advances in our understanding of postpartum breast cancer open the way to targeted therapies against this aggressive breast cancer sub-type.

Parity predisposes breasts to the oncogenic action of PAPP-A and activation of the collagen receptor DDR2.

BACKGROUND: Women who had children at a young age (less than 25) show a reduced overall risk of breast cancer. However, epidemiological studies showed that for all other women, pregnancy increases the risk of breast cancer and the risk remains higher for decades. Further, even in women who had children at a young age, there is a transient increase risk that peaks 6 years after pregnancy. Women diagnosed with breast cancer following pregnancy show a higher rate of metastasis. Yet, the factors that increase the predisposition of post-partum breasts to more aggressive cancers remain unknown. Pregnancy-associated plasma protein A (PAPP-A) is a secreted protease that is overexpressed in more than 70% of breast cancers. However, PAPP-A is a collagen-dependent oncogene. We initiated this study to test the effect of PAPP-A on the predisposition of post-partum breasts. METHODS: We used PAPP-A mouse models for the analysis of its effect on virgin, involuting, or post-partum mammary glands. We performed second-harmonic generation microscopy for the analysis of collagen, defined tumor-associated collagen signature (TACS), the rate of mammary tumors, and the status of the collagen-DDR2-Snail axis of metastasis. We knockdown DDR2 by CRISPR and performed invasion assays. A transcriptomic approach was used to define a PAPP-A and parity-dependent genetic signature and assess its correlation with breast cancer recurrence in humans. RESULTS: We confirmed that post-partum mammary glands have a higher level of collagen than virgin glands and that this collagen is characterized by an anti-proliferative architecture. However, PAPP-A converts the anti-proliferative post-partum collagen into pro-tumorigenic collagen. We show that PAPP-A activates the collagen receptor DDR2 and metastasis. Further, deletion of DDR2 by CRISPR abolished the effect of PAPP-A on invasion. We defined a PAPP-A-driven genetic signature that identifies patients at higher risk of metastasis. CONCLUSIONS: These results support the notion that information about pregnancy may be critical in the prognosis of breast cancer as passage through a single pregnancy predisposes to the oncogenic action of PAPP-A. Our data indicate that history of pregnancy combined with the expression of PAPP-A-driven genetic signature may be useful to identify patients at higher risk of metastatic disease.