Experts explain how diabetes increases risks of triple-negative breast cancer

“Diabetes is a serious metabolic disorder characterized by sustained hyperglycemia, hyperinsulinemia, and hyperlipidemia due to insulin resistance, which potentially enhances the risk of cancer, especially triple-negative breast cancer (TNBC), the deadliest form of breast cancer. Diabetes and cancer are two major public health problems occurring mainly in the Pakistan, the causative link is yet to be proven, but the relative risks imparted by diabetes are said to be greatest (about two-fold or higher) for cancers of the liver, pancreas and endometrium, and less (about 1.2–1.5 fold) for cancers of the colon, rectum, breast and bladder.”

These views were shared by Dr Lubna Saleem, consultant medical oncologist and assistant professor at the Cancer Foundation Hospital, at a seminar titled ‘Diabetes & Cancers, A Hidden Link’.

Data on site-specific cancer were available for 50 sites. The women-to-men ratios showed statistically significant higher risks for women with diabetes for kidney (11 per cent higher), oral (13 per cent higher), stomach (14 per cent higher), and leukemia (15 per cent higher) cancers, compared to men with diabetes. For liver cancer the risk for women with diabetes was 12 per cent lower than for men with diabetes, Dr Lubna said while addressing the seminar recently held at Dr Essa Laboratory & Diagnostic Center.

Recent large-scale studies have shown that diabetic patients have 20–30 percent higher risk of developing TNBC, the advanced stage responsible for 50 percent of breast cancer mortality. At the economic level, TNBC is associated with a substantial economic burden on the healthcare system. In addition, patients who have both diabetes and TNBC result in worse patient-reported outcomes due to the high risk of distant relapse. The number of the mortality rate due to TNBC has been projected to increase in East and South Asian countries in the next ten years.

“As diabetes progresses, the body’s metabolism undergoes fundamental changes, with elevated levels of lipids (fats), insulin and glucose in the blood. These metabolic changes in turn disrupt and alter the normal functions of cells, causing damage to the DNA and the cell’s own structures, uncontrolled cell proliferation, and inhibition of a process called apoptosis, a normal form of programmed cell death that is a key part of cellular development and renewal. Inhibition of apoptosis in breast cancer cells serves to initiate or promote the growth of breast tumors” she explained.

Furthermore, insulin resistance can influence the build-up of proteins in the muscles. That is, if the body fails to respond to insulin, it will lose muscle mass and strength, and that is a huge problem for a lot of cancer patients, Dr Lubna suggests clinicians should check patients' blood sugar level even when it appears to be normal, because insulin resistance can be hard to spot as the body will simply compensate by producing more insulin.

“There is an urgent need to establish preventive medicine, precise cancer diagnosis, and a novel targeted therapeutic approach in order to improve diabetes management and to enhance cancer cell sensitivity to chemotherapy and radiotherapy to treat cancers in diabetics,” she advised.

“People with type 2 diabetes have a higher risk of 57 other health conditions, including cancer, kidney disease and neurological illnesses,” said Dr Riasat Ali Khan, consultant diabetologist & endocrinologist and president of Primary Care Diabetes Association (PCDA) Pakistan.

On average, those with the condition had these health problems as many as five years earlier than people without it. Those with type 2 diabetes had a 9 percent increased risk of cancer, those with type 2 diabetes were 5.2 times more likely to have end-stage kidney disease, 4.4 times more likely to have liver cancer and 3.2 times more likely to have macular degeneration.

Genes with diabetes association and their wide spectrum of variants have been identified. Genetic factors become more significant due to repeated marriages among close relatives; i.e., consanguinity. Due to high consanguinity in Pakistan, the probability of genetic expression increases. So, repeated marriages within the family increase the chances of diabetes.

Guest speaker Dr Abdul Qayyum, consultant oncologist and medical director at Bait-Ul-Sukoon Cancer Hospital, also presented local as well as international studies that show a direct connection between elevated insulin levels, a common occurrence in individuals with obesity and Type 2 diabetes, and pancreatic cancer.

These landmark studies offer the first comprehensive explanation for the heightened risk of pancreatic cancer among people with obesity and Type 2 diabetes.

The research reveals that excessive insulin levels can overstimulate pancreatic acinar cells responsible for producing digestive juices. This overstimulation triggers inflammation, which transforms these cells into precancerous cells.

The focus of these studies was on pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer, known for its high aggressiveness and five-year survival rate of less than 10 percent. The incidence of pancreatic cancer is on the rise, and by 2030, PDAC is expected to become one of the leading causes of cancer-related deaths. “While drugs are important, as oncologists, we need to also look at comorbidities and modifiable risk factors to improve patient survival outcomes. Therapies and lifestyle changes can go hand in hand,” Dr Abdul Qayyum emphasized.

Earlier, Dr Farhan Essa Abdullah, CEO of Dr Essa Laboratory & Diagnostic Center & an Infectious Disease Expert, inaugurate the seminar and thanked to audience. According to him diabetes is on the rampage in Pakistan. We are now a country with the third largest population of diabetic adults after China and India.

According to the International Diabetes Federation 2022, 26.7 percent of adults in Pakistan are affected by diabetes making the total number of cases approximately 33,000,000. Even more alarmingly, if we do not take remedial action in terms of prevention and treatment, by 2030 this number is projected to swell to around 43 million. Currently, 8.9 million people are also estimated to be undiagnosed and another 11 million adults have impaired glucose intolerance, i.e., prediabetes.

On current trend, one in two people will be diagnosed with cancer by age 85. To reduce this risk, he suggests we make better dietary choices, eat a little less (smoking meats or cooking them at a high temperature creates compounds called PAHs. Studies are under way to see how they affect people), move a little more as lack of fitness portends hazardous complications, don’t smoke because it impairs response to cancer treatment, curb drinking and loss some weight because obesity increases recurrence risk.

What is to be done? Prevention, early diagnosis through mass screening, and proper management are vital — which is easier said than done as it requires a comprehensive health system response. This includes integrated delivery of preventive, promotive, curative and rehabilitative health services at all levels of the healthcare system, but most importantly at primary healthcare level. Our health system is not equipped to deal with the epidemic of diabetes. It needs sustained and coordinated whole-of-government and societal efforts. The private health sector also has to be taken into the loop, advised by Dr Farhan Essa.