Dairy product consumption and development of cancer: an overview of reviews.

OBJECTIVES: To provide a comprehensive systematic overview of current evidence from pooled analyses/meta-analyses and systematic reviews (PMASRs) pertaining to dairy consumption and incident cancer and/or all-cause or cancer-specific mortality. DESIGN: Overview of reviews. SETTING: Community setting. PARTICIPANTS: The unit of analysis is PMASRs. A total of 42 PMASRs was included in this overview of reviews. INTERVENTIONS/EXPOSURES: Any dairy product consumption (eg, milk, yogurt, etc). PRIMARY AND SECONDARY OUTCOMES MEASURES: Primary outcome measure is development of any type of cancer. Secondary outcome measures are all-cause mortality and cancer-specific mortality. RESULTS: From 9693 citations identified, we included 42 PMASRs (52 study reports) published between 1991 and 2017. Thirty-one (74%) of these was pooled analyses/meta analyses, and only 11 (26%) were systematic reviews and meta-analyses. There was a wide variability in the type of study designs included within the other PMASRs, thus contributing to variable and, in instances, divergent estimates of cancer risk for several cancer subtypes. For example, only one systematic review and meta-analysis exclusively included prospective study designs. Most PMASRs were of low to moderate quality based on the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) scores. The median AMSTAR score was 5 (IQR 2-7). Our overview identified conflicting evidence from PMASRs on association between dairy consumption and incident cancers or mortality. Heterogeneity in summary estimates reflected the inclusion of variable study designs and overall low methodological quality of individual PMASRs. CONCLUSIONS: The association between dairy consumption and cancer risk has been explored in PMASRs with a variety of study designs and of low to moderate quality. To fully characterise valid associations between dairy consumption and risk of cancer and/or mortality rigorously conducted, PMASRs including only high-quality prospective study designs are required. TRIAL REGISTRATION NUMBER: CRD42017078463.

Androgen Receptor and Ki67 Expression and Survival Outcomes in Non-small Cell Lung Cancer.

Lung cancer is the most common cause of cancer-related deaths worldwide with non-small cell lung cancer (NSCLC) making up most of these cases. Males have poorer overall survival compared to women following a lung cancer diagnosis. Many studies have focused on the effects of estrogen to explain higher survival rates among women, but few have looked at the effects of androgens. We describe the expression of the androgen receptor (AR) and Ki67 in lung cancer specimens in the Manitoba Tumor Bank (MTB) and correlate these factors with patient outcome. Using the MTB, we performed immunohistochemistry on lung cancer tissue to determine expression of the AR and Ki67. These were then correlated with patient outcome. Of the 136 cases, 55% were female and 55% were adenocarcinoma. AR expression was not independently associated with outcome. Ki67 was associated with a significantly higher hazard ratio for death and recurrence (HR 2.19, 95% CI 1.30-3.70; HR 1.92, 95% CI 1.07-3.46, respectively). AR expression modified the effect of Ki67 on outcome, such that when both were expressed, there was no association with recurrence or survival (HR 2.39, 95% CI 1.31-4.36 for AR- Ki67+ vs HR 1.54, 95% CI 0.44-5.37 for AR+ Ki67+). Ki67 was associated with poorer outcomes alone. AR status alone was not associated with outcome. Although the mechanism remains unclear, AR status seems to negate the association of a high Ki67 and poor outcome.

The Role of Prolactin in Bone Metastasis and Breast Cancer Cell-Mediated Osteoclast Differentiation.

BACKGROUND: Metastasis to the bone is a deleterious aspect of breast cancer and is a preferred site that results in bone loss. Hormones such as prolactin (PRL) have not yet been studied for their role in modulating the secondary tumor bone microenvironment. METHODS: We used quantitative immunohistochemistry with 134 samples of human primary breast cancer and 17 matched primary breast cancers and bone metastases. A Cox proportional hazards regression model was fitted to evaluate the associations between high prolactin receptor (PRLR) expression and time to bone metastasis, adjusting for estrogen receptor status, lymph node status, and chemotherapy status. We assessed osteoclast differentiation, osteoclast size, and measured pit formation in dentine slices. Statistical tests were two-sided. RESULTS: High PRLR expression in the primary breast tumor was associated with a shorter time to metastasis that includes bone (PRLRAQUA Max-per 100 unit hazard ratio = 1.04, 95% confidence interval = 1.00 to 1.07, P = .03). We observed the PRLR in rare samples of bone metastases and matched primary breast cancer. PRL treatment of breast cancer cells induced osteoclast differentiation and bone lysis via secreted factors and was abrogated by a PRLR antagonist (delta1-9-G129R-hPRL). We demonstrated that sonic hedgehog is a PRL-regulated cytokine in breast cancer cells and part of the mechanism that induces osteoclast differentiation. CONCLUSIONS: Our evidence indicates that PRL-PRLR can escalate the impact of breast cancer on bone metastasis and that the presence of the PRLR in the tumor microenvironment of breast cancer bone metastasis has the potential to modulate the microenvironment to induce lytic osteoclast formation.