Colon and rectal cancer risk after bariatric surgery in a multicountry Nordic cohort study

Obesity is a risk factor for colorectal cancer. Yet, some research indicates that weight-reducing bariatric surgery also increases colorectal cancer risk. Our study was undertaken because current evidence examining bariatric surgery and risk of colorectal cancer is limited and inconsistent. This population-based cohort study included adults with a documented obesity diagnosis in Denmark, Finland, Iceland, Norway or Sweden in 1980–2015. The incidence of colorectal cancer in participants with obesity who had and had not undergone bariatric surgery was compared to the incidence in the corresponding background population by calculating standardized incidence ratios (SIR) with 95% confidence intervals (CI). Additionally, operated and nonoperated participants with obesity were compared using multivariable Cox regression, providing hazard ratios (HR) with 95% CIs adjusted for confounders. Among 502,772 cohort participants with an obesity diagnosis, 49,931(9.9%) underwent bariatric surgery. The overall SIR of colon cancer was increased after bariatric surgery (SIR 1.56; 95% CI 1.28–1.88), with higher SIRs ≥10 years postsurgery. The overall HR of colon cancer in operated compared to nonoperated participants was 1.13 (95% CI 0.92–1.39) and 1.55 (95% CI 1.04–2.31) 10–14 years after bariatric surgery. Bariatric surgery did not significantly increase the risk of rectal cancer (SIR 1.14, 95% CI 0.83–1.52; HR 1.08, 95% CI 0.79–1.49), but the risk estimates increased with longer follow-up periods. Our study suggests that bariatric surgery is associated with an increased risk of colon cancer, while the support for an increased risk of rectal cancer was weaker.     

Exposure to ambient air pollution and the incidence of lung cancer and breast cancer in the Ontario Population Health and Environment Cohort

Lung and female breast cancers are highly prevalent worldwide. Although the association between exposure to ambient fine particulate matter (PM_2.5) and lung cancer has been recognized, there is less evidence for associations with other common air pollutants such as nitrogen dioxide (NO₂) and ozone (O₃). Even less is known about potential associations between these pollutants and breast cancer. We conducted a population-based cohort study to investigate the associations of chronic exposure to PM_2.5, NO₂, O₃ and redox-weighted average of NO₂ and O₃ (O_x) with incident lung and breast cancer, using the Ontario Population Health and Environment Cohort (ONPHEC), which includes all long-term residents aged 35–85 years who lived in Ontario, Canada, 2001–2015. Incident lung and breast cancers were ascertained using the Ontario Cancer Registry. Annual estimates of exposures were assigned to the residential postal codes of subjects for each year during follow-up. We used Cox proportional-hazards models adjusting for personal- and neighborhood-level covariates. Our cohorts for lung and breast cancer analyses included ~4.9 million individuals and ~2.5 million women, respectively. During follow-up, 100,146 incident cases of lung cancer and 91,146 incident cases of breast cancer were diagnosed. The fully adjusted analyses showed positive associations of lung cancer incidence with PM_2.5 (hazard ratio [HR] = 1.02 [95% CI: 1.01–1.05] per 5.3 μg/m³) and NO₂ (HR = 1.05 [95% CI: 1.03–1.07] per 14 ppb). No associations with lung cancer were observed for O₃ or O_x. Relationships between PM_2.5 and NO₂ with lung cancer exhibited a sublinear shape. We did not find compelling evidence linking air pollution to breast cancer.     

Factors of the evolution of fatigue dimensions in patients with breast cancer during the 2 years after surgery

Women with breast cancer are increasingly being cured of the disease but fatigue remains the most frequently reported symptom. The aims of our study were to identify distinct trajectories in four fatigue dimensions during 2 years after breast cancer surgery and to explore the demographic, clinical and personality characteristics associated with these profiles. We included women from the prospective longitudinal multicenter FATSEIN cohort in France. They completed the Multidimensional Fatigue Inventory for nine follow-ups over 24 months after surgery. A group-based trajectory model identified distinct trajectories in each fatigue dimension. Multinomial logistic regression determined the factors associated with each profile. From the 459 women followed, 3–5 fatigue trajectories were revealed in each fatigue dimension, from its absence to its severest degree. In our multivariate analysis, the risk of severe fatigue was decreased in all dimensions by a high quality of life before surgery (measured by the European Organization for Research and Treatment of Cancer 30-item QoL questionnaire; e.g., for general and physical fatigue: OR = 0.93, 95% CI 0.91, 0.96), especially a high physical and emotional functions for general and physical fatigue, and a high cognitive function for mental fatigue. Both severe mental fatigue and severely reduced motivation worsened with low optimism before surgery (e.g., for mental fatigue: OR = 0.93, 95% CI 0.89, 0.97). Severely reduced activities increased by having chemotherapy (OR = 9.41, 95% CI 2.28, 38.79). Targeting women at risk for severe fatigue can provide early preventive and curative treatment and appropriate psychological support.     

Phase I and pharmacokinetic study of veliparib,a PARP inhibitor,and pegylated liposomal doxorubicin (PLD) in recurrent gynecologic cancer and triple negative breast cancer with long-term follow-up

Poly(ADP-ribosyl) polymerases (PARPs) are nuclear enzymes with roles in DNA damage recognition and repair. PARP1 inhibition enhances the effects of DNA-damaging agents like doxorubicin. We sought to determine the recommended phase two dose (RP2D) of veliparib with pegylated liposomal doxorubicin (PLD) in breast and recurrent gynecologic cancer patients. Veliparib and PLD were administered in a standard phase 1, 3 + 3 dose-escalation design starting at 50 mg veliparib BID on days 1–14 with PLD 40 mg/mg2 on day 1 of a 28-day cycle. Dose escalation proceeded in two strata: A (prior PLD exposure) and B (no prior PLD exposure). Patients underwent limited pharmacokinetic (PK) sampling; an expansion PK cohort was added. 44 patients with recurrent ovarian or triple negative breast cancer were enrolled. Median age 56 years; 23 patients BRCA mutation carriers; median prior regimens four. Patients received a median of four cycles of veliparib/PLD. Grade 3/4 toxicities were observed in 10% of patients. Antitumor activity was observed in both sporadic and BRCA-deficient cancers. Two BRCA mutation carriers had complete responses. Two BRCA patients developed oral squamous cell cancers after completing this regimen. PLD exposure was observed to be higher when veliparib doses were > 200 mg BID. The RP2D is 200 mg veliparib BID on days 1–14 with 40 mg/m2 PLD on day 1 of a 28-day cycle. Anti-tumor activity was seen in both strata. However, given development of long-term squamous cell cancers and the PK interaction observed, efforts should focus on other targeted combinations to improve efficacy.