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High insulin levels linked to worse prognosis in advanced breast cancer

Metformin may help to extend survival, say researchers

Caroline White

Thursday, 05 November 2015

Patients with advanced breast cancer who have higher insulin levels than normal, but who are not diabetic, have a significantly worse prognosis than those with normal insulin levels, finds preliminary research* presented to the Advanced Breast Cancer Third International Consensus Conference in Lisbon, Portugal today.

The negative impact of higher insulin levels in early breast cancer patients is already known, but this is the first time that insulin resistance has been linked to worse prognosis in patients with metastatic breast cancer.

The study involved 125 women with advanced breast cancer, none of which was HER2 positive. They were all receiving first-line chemotherapy on its own as part of a clinical trial, and had an average age of 60.

The researchers assessed the relationship between insulin resistance and the length of time the patient lived without the disease worsening as well as the length of time that the patient remained alive.

The researchers measured glucose levels in the patients using the HOMA index, a mathematical formula which assesses individual levels of insulin sensitivity. A normal range is around 2; a score of 2.5 or above is likely to indicate insulin resistance.

Overall, 46.95% of the patients were classified as insulin resistant, 40.5% were overweight, and 16.37% were obese (BMI of more than 30).

After taking account of other influential factors, disease free survival was around 11.5 months in those with a HOMA score of less than 2.5 and 8.5 months in those with a score of 2.5 and over.

“We found clear evidence that insulin resistance is associated with a significantly worse prognosis for metastatic breast cancer patients, and that metabolic status influences this prognosis,” commented Dr Nicoletta Provinciali, of the EO Ospedali Galliera, Genoa, Italy. “We need to consider ways of targeting this metabolism in order to give these patients a better chance,” she added.

“We know that growth factors are critical to cancer development and progression. We know that insulin is an important growth factor for all body tissues, even if we do not know exactly how it affects the development of cancer cells,” she continued.

Possible options could include adopting simple lifestyle changes such as a better diet and more exercise, and the use of cheap and widely available drugs such as metformin, say the researchers.

More awareness of the effect of insulin resistance on cancer progression among clinicians is also needed, they suggest.

“Although we know that higher insulin levels adversely affect prognosis in cancer patients and is an independent risk factor in several types of cancer – for example specific organ sites such as pancreas, liver, and endometrium – the evidence is still quite recent and needs to be better known by clinicians and even oncologists. We also need more trials to better define effective treatment strategies for these patients,” says Provinciali.

Co-chair of the conference, Professor Fatima Cardoso, Director of the Breast Unit of the Champalimaud Cancer Centre in Lisbon, Portugal, said: “The potential use of an inexpensive and common drug such as metformin to treat and to prevent breast cancer is a very exciting finding.

“We already had data in early breast cancer regarding the impact on prognosis of insulin resistance and obesity as well as the potential preventive role of physical exercise. This study now provides some evidence of the same impact in advanced breast cancer. It will be very important to study the role of anti-diabetic drugs in association with anti-cancer agents for this incurable disease.”

* Provinciali N, et al. Insulin resistance (IR) and prognosis of metastatic breast cancer (MBC) patients. The Breast 24 S3 (2015), BP129.

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