Females with breast cancer and diabetes have poorer prognosis than those with breast cancer without diabetes, but why?
Females with breast cancer who have pre-existing diabetes have a higher risk for all-cause mortality that has long-lasting effects compared to females who do not have pre-existing diabetes. The link between diabetes and breast cancer is not known, however. Is all-mortality dependent on lack of chemotherapeutic treatment? Or, is it contingent upon clinical or biological interaction between the two diseases? In hopes of answering one of those questions, researchers in Canada completed a population-based study from a retrospective cohort. Iliana Lega and colleagues investigated whether diagnosis of diabetes has an impact on following guideline-based chemotherapeutic regimens or radiation therapy for treatment of breast cancer and whether those females with breast cancer and diabetes have a worse all-cause and breast cancer-specific mortality than their counterparts without diabetes.
For the completion of the retrospective cohort, investigators utilized the population-based health databases, which cover over 12 million residents from Ontario, Canada. Those females who were over the age of 20 and who had diagnosis of breast cancer stages I, II and III were included in the study, only if they underwent a lumpectomy or mastectomy within 6 months to a year following their diagnosis. Females with a history of prior cancers (not including nonmelanoma skin cancers) and individuals residing in long-term care facilities were excluded. Diabetes diagnosis was determined through health databases as well. Females who had breast cancer but not diabetes served as the controls. Researchers matched the participants of the study by age, year of breast cancer diagnosis and cancer stage. Primary outcome of the study was to evaluate the treatment of breast cancer: women without diabetes versus women with diabetes who are receiving chemotherapy regimens for stage III disease or radiotherapy regimens for stage II breast cancer. Both neoadjuvant and adjuvant therapy was recorded. Investigators sought to determine the all-cause and breast cancer-specific mortality as well.
The study enrolled 9,910 females with breast-cancer without DM and 4,955 females with breast cancer and with diabetes. Subjects with diabetes who had stage III BC were slightly less likely to receive chemotherapeutic treatment, when compared to individuals without DM, relative ratio of 0.93. Similar results were seen with radiation therapy as well: females with BC and DM were slightly less likely to undergo radiation therapy relative ratio of 0.93. With the respect to mortality, diabetic females with BC had a statistically significant risk of all-cause and cancer-specific mortality, hazard ratio of 1.42 and 1.24, respectively. Similar results were seen even after adjustment for receipt of chemotherapy or radiation therapy, HR 1.40 and 1.25, respectively. However, after adjusting for presence of cardiovascular disease, breast-cancer specific mortality was not significant any longer, HR of 1.11. Breast-cancer specific mortality was found to be increased only in those women who had diabetes for over five years and those females with pre-existing cardiovascular disease.
Lega et al. concluded that study subjects with DM and BC had a higher all-cause mortality than those without diabetes. On the other hand, breast cancer-specific mortality was not enhanced due to DM, unless the individuals had cardiovascular disease as well, or if they were diagnosed with diabetes for longer than five years. Moreover, researchers did not find a difference in chemotherapy or radiotherapy treatment between the study groups. Due to the design of the retrospective cohort, researchers report some limitations to the study conducted; primarily, lack of data regarding the metabolic markers of diabetes control, imaging results for cardiovascular disease, obesity, or use of glucose-lowering medications. Specific chemotherapeutic regimens used in individuals were not known as well. Therefore, at this time, more studies need to be conducted to discover the reason behind the increased all-cause mortality in women with diabetes that we have seen here in order to provide better treatment and outcomes of women with diabetes and breast cancer.
- After adjusting for cardiovascular disease, females with diabetes were as likely as females who do not have diabetes to receive chemotherapy or radiation therapy for treatment of their breast cancer.
- Breast cancer-specific mortality was increased only in women who had diabetes for longer than five years and those with pre-existing cardiovascular disease.
- All-cause mortality remained high for females with diabetes and breast cancer, even after adjustment for cardiovascular disease.
Iliana Lega, Peter Austin, Hadas Fischer, et al. “The Impact of Diabetes on Breast Cancer Treatments and Outcomes: A Population-Based Study.” Diabetes Care. 2018. http://care.diabetesjournals.org/content/early/2018/01/17/dc17-2012. Accessed Jan 2018.
Bethany Barone, Hsin-Chieh Yeh, Claire Snyder, et al. “Long-term All-Cause Mortality in Cancer Patients With Preexisting Diabetes Mellitus.” JAMA/ 2008. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3093051/. Accessed Jan 2018.
Lamija Zimic, PharmD(c), University of South Florida, College of Pharmacy