Involvement of fine particulate matter exposure with gene expression pathways in breast tumor and adjacent-normal breast tissue.

BACKGROUND: Fine particulate matter (PM2.5) has been associated with breast cancer specific mortality, particularly for women with Stage I cancer. We examined the biological pathways that are perturbed by PM2.5 exposures by analyzing gene expression measurements from breast tissue specimens. METHODS: The Nurses' Health Studies (NHS and NHSII) are prospective cohorts with archival breast tissue specimens from breast cancer cases. Global gene expression data were ascertained with the Affymetrix Glue Human Transcriptome Array 3.0. PM2.5 was estimated using spatio-temporal models linked to participants' home addresses. All analyses were performed separately in tumor (n = 591) and adjacent-normal (n = 497) samples, and stratified by estrogen receptor (ER) status and stage. We used multivariable linear regression, gene-set enrichment analyses (GSEA), and the least squares kernel machine (LSKM) to assess whether 3-year cumulative average pre-diagnosis PM2.5 exposure was associated with breast-tissue gene expression pathways among predominately Stage I and II women (90.7%) and postmenopausal (81.2%) women. Replication samples (tumor, n = 245; adjacent-normal, n = 165) were measured on Affymetrix Human Transcriptome Array (HTA 2.0). RESULTS: Overall, no pathways in the tumor area were significantly associated with PM2.5 exposure. Among 272 adjacent-normal samples from Stage I ER-positive women, PM2.5 was associated with perturbations in the oxidative phosphorylation, protein secretion, and mTORC1 signaling pathways (GSEA and LSKM p-values <0.05); however, results were not replicated in a small set of replication samples (n = 80). CONCLUSIONS: PM2.5 was generally not associated with breast tissue gene expression though was suggested to perturb oxidative phosphorylation and regulation of proteins and cellular signaling in adjacent-normal breast tissue. More research is needed on the biological role of PM2.5 that influences breast tumor progression.

Gynaecological cancer pathway for faster cancer treatment: a clinical audit.

Gynaecological cancers make up 10% of cancer cases and 10% of female cancer deaths in New Zealand. The services for investigation and treatment of these women are regionally specific rather than centrally organised; hence we need appropriate standards of service and clear pathways for communication and management of these patients to ensure consistent care that is in line with the Ministry of Health goals for faster cancer treatment. AIM: The aim of this audit is to ensure faster gynaecological cancer management pathways for Northland patients. METHODS: There were 72 gynaecological cancer cases identified from the gynaecological oncology referral data. These were the patients referred for multidisciplinary discussion of their newly diagnosed gynaecological cancer from June 2014-June 2015. Seventeen cases were excluded from this audit. The patients' information regarding their health care during the investigation and treatment of their cancer was obtained via an electronic patient record system. The time taken for each patient to complete various investigation, referrals, decisions and treatment was then compared against Ministry of Health faster cancer treatment targets and standards of service provision. RESULTS: The results showed that the overall target of patients having their first treatment within 62 days of initial referral for suspected cancer was being met only in 39% of cases. The best performing area of the pathway was the time from first referral from Northland DHB until the date of the first MDM discussion for a patient with an aim of ≤14 days with 93% of cases meeting this. The worst performing area was the time from decision to biopsy for tissue diagnosis to the time the histology report was produced, aiming for ≤14 days. We met this target in only 35% of cases. CONCLUSION: Over half of Northland patients are not receiving treatment in time that meets national targets. This delay seems to be mainly at the tissue diagnosis stage especially if operative intervention is required and while waiting on a management plan from the multidisciplinary team. Further input into appropriate tracking of cancer patients, management of prioritisation of operating lists and perhaps increased theatre time for gynaecology cancer patients should be considered. Increasing the frequency of multidisciplinary meetings for management plan decisions to be made should also be considered. The standards for service provision should also be altered to have a time course for referral, investigation and management that is in line with the Ministry faster cancer treatment targets.