Diabetes is associated with more advanced stage breast cancer, according to a new study by the Institute for Clinical Evaluative Sciences (ICES) and Women’s College Hospital.
The findings, published today in the journal Breast Cancer Research and Treatment, confirm a strong link between diabetes and later stage breast cancer at diagnosis for Canadian women.
“Our findings suggest that women with diabetes may be predisposed to more advanced stage breast cancer, which may be a contributor to their higher cancer mortality,” said Dr. Lorraine Lipscombe, a scientist at ICES and Women’s College Research Institute.
In the study, Dr. Lipscombe examined stage at diagnosis among women aged 20-105 years who were newly diagnosed with invasive breast cancer between 2007 and 2012.
From an analysis of more than 38,000 women with breast cancer, 6,115 (15.9 per cent) of the women had diabetes. Breast cancer patients with diabetes were significantly more likely to present with advanced stage breast cancer than those without diabetes. Women with diabetes were 14 per cent more likely to present with Stage II breast cancer, 21 per cent more likely to present with Stage III breast cancer, and 16 per cent more likely to present with Stage IV than to present with Stage I. The results also show lower mammogram rates in women with diabetes, which could account for later stage disease. Women with diabetes also had a higher risk of lymph node metastases (spreading of the cancer) and larger tumors than women without diabetes.
Breast cancer often begins in the breast ducts as ductal carcinoma in situ (DCIS). Once out of the breast, cancer often spreads first to the axillary (underarm) lymph nodes. One or more of the lymph nodes are usually removed during breast surgery to determine whether the nodes are involved. (See the axillary node dissection and sentinel node biopsy sections for more information on how lymph nodes are removed). In some cases, breast cancer may spread to other regions of the body without involving the axillary lymph nodes. If the cancerous tumor is located in the medial portion of the breast (near the nipple), it may spread to the internal mammary nodes which are located between the ribs and beneath the sternum. In some cases, cancer may spread through the bloodstream without being detected in the lymphatic system.
In 10% of breast cancer diagnoses, the cancer has already spread to distant organs in the body. A primary diagnosis of Stage IV breast cancer may indicate a rapid progression of the disease or that the cancer was present but not detected in the breast for some time. To help detect breast cancer in its earlier stages when it is most curable, women should follow the guidelines for early detection established by the American Cancer Society which include monthly breast self-examinations, annual clinical breast exams, and annual mammography (the latter beginning at age 40).
Metastatic breast cancer may also occur from a recurrence (return) of breast cancer after initial treatment. There are three types of breast cancer recurrences: local, regional, and distant. Local and regional recurrences are usually less serious than distant recurrences and may be detected by mammogram or seen as abnormalities with breast imaging exams (such as ultrasound or T-scan).
“In addition, the risk of advanced stage breast cancer was greatest in younger women and those with longer-standing diabetes,” added Lipscombe.
Diabetes mellitus and cancer are major causes of morbidity and death worldwide. In the United States alone, by 2007 there were approximately 24 million people with diabetes (approximately 8% of the adult population) and 2.5 million survivors of breast cancer. Recent research has focused attention on the effect of comorbid conditions on all-cause mortality in women with breast cancer. Potential interactions between diabetes and breast cancer, in particular, are complex.
Survival in patients with diabetes and breast cancer may be negatively affected by less intensive diabetes and/or cancer care. Factors may include delay in diagnosis, lower use of effective adjuvant therapies, and diabetes-related comorbidities. Metformin is a commonly used oral diabetic agent that reduces hyperinsulinemia and may favorably affect some measures of outcome in patients with breast cancer. Specifically, hyperinsulinemia and insulin-like growth factors may play a role by promoting tumor growth, and preclinical data show an in vitro effect of metformin in breast cancer cells. Metformin modulates known breast cancer prognostic factors by increasing skeletal muscle glucose uptake and reducing both hyperglycemia and hyperinsulinemia, and may have insulin-independent effects through inhibition of the adenosine monophosphate - activated protein kinase/mammalian target of rapamycin/S6 kinase 1 pathway. Retrospective clinical data show higher rates of pathologic response after preoperative chemotherapy in patients with diabetes and breast cancer receiving metformin, providing a rationale to test new strategies in chemoprevention and in the adjuvant setting.
The study showed that the majority of diabetes patients presented with Stage II or III breast cancer, which translated into a 15 per cent decrease in five-year survival for diabetes patients at the time of cancer diagnosis.
The researchers suggest that breast cancer screening and detection practices may need to be modified in patients with diabetes to reduce the chances of later-stage detection.
Doctors typically categorize breast cancer by stages. According to the National Cancer Institute, those stages are defined as follows.
Stage 1: This is the earliest stage of breast cancer. The tumor is no bigger than two centimeters. Some miniscule cancer clusters may be present in the lymph nodes.
Stage 2: Though similar to stage 1, stage 2 signifies that the cancer has started to spread. Cancer may be present in some of the lymph nodes, and the breast tumor may be larger than two centimeters, but not larger than five centimeters.
Stage 3: Doctors consider this a more advanced form of breast cancer. It may have spread to the tissues in the chest and to several lymph nodes. The tumor can be of any size at this stage. Sometimes, the cancer has moved to the skin of the breast to cause inflammation and possibly ulcers.
Stage 4: The cancer has spread to other areas of the body.
The study was funded by the Canadian Institutes for Health Research and the Ontario Institute for Cancer Research.
“The association between diabetes and breast cancer stage at diagnosis: A population-based study,” was published today in Breast Cancer Research and Treatment.
Authors: Lorraine L. Lipscombe, Hadas Fischer, Peter C. Austin, Longdi Fu, R. Liisa Jaakkimainen, Ophira Ginsburg, Paula Rochon, Steven Narod, Lawrence Paszat.
Women’s College Hospital
Breast Cancer Research and Treatment