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High Levels of Two Proteins Linked to Reduced Survival in Patients With Breast Cancer

SEATLLE, Wash -- May 25, 2009 -- A study has identified 2 proteins in the blood that could become important prognostic markers for long-term survival in patients with breast cancer. The proteins are associated with chronic inflammation, which is known to contribute to cancer development and progression. The study appears in the May 18 issue of the Journal of Clinical Oncology.

Cornelia Ulrich, PhD, Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, Washington, and colleagues measured the levels of C-reactive protein (CRP) and serum amyloid A (SAA) in 734 patients with breast cancer at 31 months after diagnosis.

They found that elevated levels of CRP and SAA are associated with reduced overall survival, regardless of patient age, tumour stage, race, and body mass index (BMI).

For example, women with breast cancer who had SAA levels that were in the highest third in amount measured in their blood were 3 times more likely to die from their disease within the following 7 years compared with patients with the lowest-third amount. Similarly, women in the highest third of CRP levels had a 2-fold increased risk of death.

"These associations are strong and they suggest that, in the long-term, elevated levels of inflammatory markers predict a woman's chances of surviving after breast cancer," said Dr. Ulrich. "It also appears that there may be a threshold effect in that only women in the highest third of inflammation markers had increased mortality."

"To our knowledge, this is the largest population-based cohort study to date that examined the relationship between systemic inflammation and breast cancer survival, and the first to evaluate SAA as a prognostic marker for breast cancer," said Dr. Ulrich.

Patient data was drawn from the Health, Eating, Activity and Lifestyle (HEAL) study, a multiethnic National Institutes of Health-funded prospective group of women diagnosed with Stage 0 to Stage IIIa breast cancer.

Clinical and experimental data suggest that chronic inflammation promotes mammary tumor development. Patients with breast cancer have elevated concentrations of CRP before surgery, more so in women with advanced disease, which suggests that CRP may be related to tumour burden or progression.
Cancer survivors with chronic inflammation may have an elevated risk of recurrence as a result of the effects of inflammatory processes on cell growth or the presence of cancer cells that induce inflammation, according to the study.

"It is interesting that markers measured in the blood nearly 3 years after diagnosis predicted prognosis," said Dr. Ulrich. "We also found these associations to hold up after adjusting for a number of factors that associate with systemic inflammation, such as obesity."

"However, more research is needed to confirm these findings and to get more precise estimates of risk. We also need to learn more about the biologic mechanisms."

SOURCE: Fred Hutchinson Cancer Research Center

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