Patient perceptions and expectations regarding imaging for metastatic disease in early stage breast cancer

Abstract Purpose The probability of detecting radiologically evident metastatic disease in asymptomatic women with newly diagnosed operable breast cancer is low. Despite the recommendations of most practice guidelines imaging is still frequently performed. Relatively little is known about what patients believe is important when it comes to radiologic staging. Methods Patients with early stage breast cancer who had completed their definitive breast surgery were surveyed about their personal experiences, perceptions, and expectations on the issue of perioperative imaging for distant metastatic disease. Results Over a 3 month period, 245 women with primary operable breast cancer completed the questionnaire (87.0% response rate) and 80.8% indicated having had at least one imaging test for distant metastatic disease. These were either of the thorax (72.2%), abdomen (55.9%) or skeleton (65.3%) with a total of 701 imaging tests (average of 3.5 tests per patient imaged) performed. Overall, 57.1% indicated that they would want imaging done if the chance of detecting metastases was ≤10%. Although 80.0% of patients indicated that, “doing whatever their doctor recommended” was important to them, 70.4% also noted that they would be uncomfortable if their physician did not order imaging, even if this was in keeping with practice guidelines. Conclusions Most patients with early stage breast cancer recall having imaging tests for distant metastases. Given the choice, most would prefer having imaging performed, even if this is not in line with current guidelines. If patient expectations are, in part, driving excessive imaging, new strategies addressing this are required

Studies on the mechanism of action of New Pressor Protein, bradykinin, pituitary adenylate cyclase-activating polypeptide and adrenal catecholamines as possible mediators of its cardiovascular effects

grantor: University of TorontoEnzymic "New Pressor Protein" (NPP) from human plasma shares homology with the active beta fragment of human coagulation factor XII (ßFXIIa) and raises blood pressure (BP) and heart rate in bioassay rats. Concurrently, it also triggers a substantial release of adrenal catecholamines, especially adrenaline. The cardiovascular effects of NPP are potentiated by the ACE inhibitor (ACEI) Captopril, as well as by ganglion blockade, thereby suggesting that the adrenal effects are mediated by a "peptidergic pathway", rather than by sympathetic cholinergic mechanisms. Two peptides, bradykinin and pituitary adenylate cyclase-activating polypeptide demonstrably mimicked NPP's cardiovascular actions, but administration of their antagonists only partially blocked NPP, suggesting that other mediators are also involved. Results from this project demonstrate that NPP/ßFXIIa may represent a novel axis connecting blood coagulation to endocrine pathways, adrenal medullary function and BP regulation that may interfere with and counteract the normally beneficial effects of ACEIs.M.Sc

Doxycycline-Induced Changes in Circulating MMP or TIMP2 Levels Are Not Associated with Skeletal-Related Event-Free or Overall Survival in Patients with Bone Metastases from Breast Cancer

Doxycycline is often used as a promoter of inducible gene expression in preclinical models; however, it can also have direct effects on tumor growth and survival. This is due in part to its ability to inhibit cell invasion and regulate matrix metalloproteinase (MMP) expression. Given that doxycycline is also osteotropic, a clinical study to assess its effects on modulation of tumor progression or prevention of skeletal-related events (SRE) in patients with bone metastases from breast cancer (the Achilles trial) was undertaken. Patients received 100 mg of oral doxycycline twice daily for 12 weeks, with serum obtained at baseline and 4, 8 and 12 weeks post-initiation of doxycycline treatment. Exploratory analysis of the effects of doxycycline on circulating levels of MMP or tissue inhibitor of matrix metalloproteinase 2 (TIMP2) was performed in enrolled patients. Statistically significant associations were observed between MMP2, MMP9 and TIMP2 at baseline with significant associations maintained between absolute levels and changes in levels of MMP2 and TIMP2 at weeks 4–12 post initiation of doxycycline. Treatment with doxycycline generally resulted in decreases in MMP2 and MMP9 levels with concurrent upregulation of TIMP2 at 12 weeks post-initiation of doxycycline treatment. Despite this, we observed no association with the levels of any of these factors with either SRE-free or overall survival in this patient cohort. In summary, despite observing hypothesized effects of doxycycline administration on surrogate markers of its anti-tumor activity, measures of circulating levels of these biomarkers were not prognostic in this patient population

Doxycycline-Induced Changes in Circulating MMP or TIMP2 Levels Are Not Associated with Skeletal-Related Event-Free or Overall Survival in Patients with Bone Metastases from Breast Cancer

Doxycycline is often used as a promoter of inducible gene expression in preclinical models; however, it can also have direct effects on tumor growth and survival. This is due in part to its ability to inhibit cell invasion and regulate matrix metalloproteinase (MMP) expression. Given that doxycycline is also osteotropic, a clinical study to assess its effects on modulation of tumor progression or prevention of skeletal-related events (SRE) in patients with bone metastases from breast cancer (the Achilles trial) was undertaken. Patients received 100 mg of oral doxycycline twice daily for 12 weeks, with serum obtained at baseline and 4, 8 and 12 weeks post-initiation of doxycycline treatment. Exploratory analysis of the effects of doxycycline on circulating levels of MMP or tissue inhibitor of matrix metalloproteinase 2 (TIMP2) was performed in enrolled patients. Statistically significant associations were observed between MMP2, MMP9 and TIMP2 at baseline with significant associations maintained between absolute levels and changes in levels of MMP2 and TIMP2 at weeks 4–12 post initiation of doxycycline. Treatment with doxycycline generally resulted in decreases in MMP2 and MMP9 levels with concurrent upregulation of TIMP2 at 12 weeks post-initiation of doxycycline treatment. Despite this, we observed no association with the levels of any of these factors with either SRE-free or overall survival in this patient cohort. In summary, despite observing hypothesized effects of doxycycline administration on surrogate markers of its anti-tumor activity, measures of circulating levels of these biomarkers were not prognostic in this patient population

A Randomized Trial Comparing 3- versus 4-Monthly Cardiac Monitoring in Patients Receiving Trastuzumab-Based Chemotherapy for Early Breast Cancer

Purpose: The optimal frequency for cardiac monitoring of left ventricular ejection fraction (LVEF) in patients receiving trastuzumab-based therapy for early breast cancer (EBC) is unknown. We conducted a randomized controlled trial comparing 3- versus 4-monthly cardiac monitoring. Patients and Method: Patients scheduled to receive trastuzumab-containing cancer therapy for EBC with normal (>53%) baseline LVEF were randomized to undergo LVEF assessments every 3 or 4 months. The primary outcome was the change in LVEF from baseline. Secondary outcomes included the rate of cardiac dysfunction (defined as a decrease in the LVEF of ≥10 percentage points, to a value <53%), delays in or discontinuation of trastuzumab therapy, and cardiology referral. Results: Of the 200 eligible and enrolled patients, 100 (50%) were randomized to 3-monthly and 100 (50%) to 4-monthly cardiac monitoring. Of these patients, 98 and 97 respectively underwent at least one cardiac scan. The estimated mean difference in LVEF from baseline was −0.94% (one-sided 95% lower bound: −2.14), which exceeded the pre-defined non-inferiority margin of −4%. There were also no significant differences between the two study arms for any of the secondary endpoints. The rate of detection of cardiac dysfunction was 16.3% (16/98) and 12.4% (12/97) in the 3- and 4-monthly arms, respectively (95% CI: 4.0 [−5.9, 13.8]). Conclusions: Cardiac monitoring every 4 months was deemed non-inferior to that every 3 months in patients with HER2-positive EBC being treated with trastuzumab-based therapy. Given its costs and inconvenience, cardiac monitoring every 4 months should be considered standard practice. Registration: NCT02696707, 18 February 2016