C Reactive Protein, Serum Amyloid A and Breast Cancer Survival

Two blood proteins blood that could become important markers for long-term breast cancer survival have been identified by research out of Fred Hutchinson Cancer Research Center (FHCRC)1. The proteins, C-reactive protein (CRP) and serum amyloid A (SAA), are linked with chronic inflammation, known to contribute to cancer development and progression, according to the study in the May 18 2009 edition of the Journal of Clinical Oncology.

Levels of C-reactive protein (CRP) and serum amyloid A (SAA) were monitored in 734 breast cancer patients 31 months after diagnosis. Elevated levels of CRP and SAA were found to be associated with reduced overall survival, no matter what the patient’s age, tumor stage, race or body mass index.

“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 Cornelia Ulrich, Ph.D, and member of the FHCRC Prevention Program. “It also appears that there may be a threshold effect in that only women in the highest third of inflammation markers had increased mortality.”

For instance, breast cancer patients who had SAA blood levels in the highest third of the group were three times more likely to die from their disease in the following seven years, compared to patients with the lowest-third amount. Correspondingly, women in the highest third of CRP levels had a two-fold increased risk of death.

Serum Amyloid A as Breast Cancer Marker

“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 Ulrich.

CRP and SAA are nonspecific, acute-phase liver associated proteins, secreted into the circulating blood stream in response to cytokines including interleukin-1, interleukin-6 and tumor necrosis factor.

Acute phase serum amyloid A proteins (A-SAAs) are secreted during the acute phase of inflammation. These proteins have several roles, such as transport of cholesterol to the liver for secretion into the bile, recruitment of immune cells to inflammatory sites and induction of enzymes that degrade extracellular matrix. A-SAAs are implicated in several chronic inflammatory diseases, such as amyloidosis, atherosclerosis, and rheumatoid arthritis.(2)

The sudy’s patient data was drawn from the Health, Eating, Activity and Lifestyle (HEAL) study, a multi-ethnic NIH-funded prospective group of women diagnosed with stage 0 through Stage IIIa breast cancer.

Previous Research

In previous studies, elevated CRP was linked with poor survival in patients with metastatic prostate cancer>sup>(3) as well as those with colorectal, gastroesophogeal, inoperable small-cell lung and pancreatic cancers. Preoperative levels of SAA have been associated with survival of both patients with gastric cancer and those with renal cell carcinoma.

Experimental and clinical data suggests that chronic inflammation promotes mammary tumor development. Furthermore, breast cancer patients have elevated concentrations of CRP prior to surgery. This is even more the case in women in advanced stages, suggesting that C-Reactive protein may be related to tumor progression.

According to the FHCRC study, cancer survivors with chronic inflammation may have higher risk of recurrence, resulting from the effects on cell growth of inflammatory processes, or the presence of cancer cells that induce inflammation.

“It is interesting that markers measured in the blood nearly three years after diagnosis predicted prognosis,” Ulrich said. “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.”

References

1. Elevated Biomarkers of Inflammation Are Associated With Reduced Survival Among Breast Cancer Patients
Brandon L. Pierce, Rachel Ballard-Barbash, Leslie Bernstein, Richard N. Baumgartner, Marian L. Neuhouser, Mark H. Wener, Kathy B. Baumgartner, Frank D. Gilliland, Bess E. Sorensen, Anne McTiernan, and Cornelia M. Ulrich
JCO published online May 26, 2009, DOI:10.1200/JCO.2008.18.9068

2. Zhang N, Ahsan MH, Purchio AF, West DB (2005). “Serum amyloid A-luciferase transgenic mice: response to sepsis, acute arthritis, and contact hypersensitivity and the effects of proteasome inhibition”. J. Immunol. 174 (12): 8125–34. PMID 15944321. http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=15944321

3. American Association For Cancer Research (2006, November 14). Two Markers Strongly Linked To Prostate Cancer Incidence And Mortality Almost A Decade Prior To Diagnosis. ScienceDaily., from http://www.sciencedaily.com/releases/2006/11/061112235628.htm

Image of human C-reactive protein by T. Greenhough & A. Shrive, Wellcome Images, Creative Commons Attribution License.