CRP and prognostic marker for survival

[michka]

Inflammation-Associated Biomarkers Predict Breast Cancer Survival

Hi all. I just read this article and since I am shaking . My CRP markers are always high (12 to 15 when normal is <5). Anyone heard about this study? Do you have or did you have high CRP? My onc. looks at the marker and says it is nothing. Maybe the Faslodex. Does he say that to reassure me?

J Clin Oncol. 2009 Jul 20;27(21):3437-3444, BL Pierce, R Ballard-Barbash, L Bernstein, RN Baumgartner, ML Neuhouser, MH Wener, KB Baumgartner, FD Gilliland, BE Sorensen, A McTiernan, CM Ulrich
Biomarkers associated with inflammation, C-reactive protein and serum amyloid A, are independent prognostic markers for breast cancer survival.
STUDY IN CONTEXT


Persistent cytokine production by liver cells induces chronic inflammation, which is a known mediator of tumor development and progression. Two hepatic proteins, C-reactive protein (CRP) and serum amyloid A (SAA), are secreted in response to cytokine secretion. Both CRP and SAA are biomarkers for low-grade chronic inflammation and presumably also of cancer risk. Both CRP and SAA have been associated with poor survival in several types of cancers. In particular, chronic inflammation appears to be involved in mammary tumor development. However, the relationship between CRP and SAA and breast cancer survival has not been investigated. CRP has been studied in relationship to tumor burden and breast cancer progression, but SAA has never been evaluated in terms of breast cancer outcomes. The aim of this study by Pierce et al was to determine the prognostic significance of circulating CRP and SAA levels in breast cancer survivors at 31 months after diagnosis. The analysis involved 734 women enrolled in the Health, Eating, Activity, and Lifestyle (HEAL) Study. The HEAL study is a prospective cohort study of breast cancer survivors who were recruited through Surveillance, Epidemiology, and End Results (SEER) registries. Among the study cohort (mean age at 24 months, 57.5 years), 23.3%, 54.5%, and 22.3% of women had in situ, localized, and regional stage disease, respectively. As of September 30, 2004, after a median follow-up period of 6.9 years for overall survival (OS) and 4.1 years for disease-free survival (DFS), 88 deaths and 91 DFS events had occurred.
Higher levels of SAA were significantly associated with shorter OS (P for trend < .0001). Hazard ratios (HRs) among the SAA tertiles indicated a threshold effect rather than a dose-dependant response. In a model adjusted for age, disease stage, race/study site, and body mass index, no significant difference in SAA was observed between the lowest and middle tertiles (hazard ratio [HR], 0.98; 95% CI, 0.50-1.90). However, between the lowest and highest SAA tertiles (SAA <4.2 mg/L vs >8.1 mg/L), a significant difference in OS was observed (HR, 3.08; 95% CI, 1.73-5.47). Further adjustment for hormone receptor status resulted in no significant change in the interaction. SAA levels had borderline associations with reduced DFS (P for trend = .07).
Elevated CRP was significantly associated with shorter OS only for the highest tertile (>3.9 mg/L), and to a lesser extent than with SAA. CRP was associated with DFS in a dose-dependant manner. In a model adjusted for age, disease stage, race/study site, body-mass index, estrogen receptor/progesterone receptor status, and cardiovascular events, the HR for recurrence was 1.91 (95% CI, 1.04-3.51; P for trend = .04).
Further adjustment for cardiovascular comorbidity (which is correlated with inflammation) slightly diminished the effect for all interactions between survival and SAA or CRP, suggesting that this is a potentially confounding factor.
In conclusion, significant associations between shortened OS and elevated concentrations of SAA and CRP were observed when these inflammation biomarkers were measured at approximately 31 months after diagnosis. Elevated CRP was also associated with shortened DFS. The associations between elevated CRP and SAA levels and survival were independent of other factors. Therefore, chronic systemic inflammation may be an important prognostic indicator of long-term survival in women with breast cancer.
Michka

[AlaskaAngel]

Hi Michka,

I think the CRP is useful too in keeping an eye on inflammation.

It does take a while for things to settle down after treatment. I don't have the answer about Faslodex. Is there anything you can do in terms of the diet to help, or are you already doing that?

A.A.

[Hopeful]

Michka,

I posted this same article in the articles forum yesterday, along with the abstract and an additional editorial that puts the study in a better context, I think:
http://jco.ascopubs.org/cgi/content/full/27/21/3418

Have you asked your doctor about this study specifically? Perhaps, if you show it to him, he will have some additional thoughts.

Best of luck to you,

Hopeful

[Jackie07]

Michka,

My oncologist never believed that I was sick - no matter what my lab number was - probably because I looked fine. Because of his inactiveness, I began to go back to my family doctor for advice this year. That's how we found out about the non-cancerous liver hemangioma this spring. We just did another abdominal/pelvic CT scans Monday - a follow-up issued by my family doctor, though three month ago my oncologist did look at the films when an ultrasound was ordered after the CT scan.

I looked back at my old lab work after finding the recurrence in 2007 - the lab numbers before 2007 were off, but because it was always off (the brain tumor, the cancer...,) and the mammogram reading was inacurate, they thought I was just 'hypochondriac'. It's very hard for the doctors to admit their errors. Because even after I had caught the recurrence by myself in 2007, a year later my oncologist still acted like I was worring too much.

Since we know our body (feelings) better than anybody else, I think the best way is to carefully observe our own 'vital signs'. In my case, I know that everytime I had cancer growing, my skin would have problems. And my weight always was dropping in an unexplanable way.

Only us long-term cancer fighters know what it's like. Thank you for the article which provides excellent information.

[R.B.]

Hi Michka,

CRP is a a marker of inflammation. CRP is also considered a marker for cardiac disease.https://www.blogger.com/comment.g?blogID=1629175743855013102&postID=1112984564831125592 Omega 6 increases inflammation.

Oestrogen in women increases their ability to make the long chain omega-3 fats like DHA and EPA from the plant-based Omega three linolenic acid. Women have a very high need of long chain Omega threes. Women have smaller more neuron dense brains with more sophisticated connections. DHA is essential to brain health and the maintenance of healthy neurons. DHA is also essential to many other functions in the body including the fertility cycle. Omega six ultimately controls the ability of the body to make the hormones.

Fats have an important role to play in the risk of breast cancer. Omega six derivative has been shown to promote HER2 expression. these two trials give an indication of the importance of fats in breast cancer. The link below called the Greek diet contains many more.

http://annonc.oxfordjournals.org/cgi/content/full/15/11/1719

http://journals.lww.com/eurjcancerprev/Abstract/2005/06000/Exogenous_supplementation_with__omega__3.11.aspx


This should be an essay, but I will try and put it succinctly.

Omega three which you have probably heard of has a sibling fat called Omega six. A significant number of trials and papers suggests that Omega three reduces the risk of breast cancer and Omega six increases it.


http://her2support.org/vbulletin/showthread.php?t=24410&highlight=greek+diet


Commonly used in vegetable oils contain a very large proportion of plant-based Omega six called linoleic acid. Omega six is found in small quantities in all parts and in high quantities in plant reproductive material like seed nuts and corn.

Omega three on the other hand generally exerts anti-inflammatory influence in the body. The plant-based Omega three is found in small quantities in all plants, and in quantity in a very limited number of seats like flax.

Animals and humans take the plant-based fats and turn them into longer fats of the same of families. These longer fats are used to make families of chemicals. The Omega six chemicals are very inflammatory. The Omega three chemicals are anti-inflammatory.

Our modern diet is heavily in balanced in favour of Omega six and generally lacks Omega threes which makes the body very much more prone to inflammation.

We make things worse because we feed our animals on grains which distorts their Omega 3:6 profile as well. A factory chicken fed on grain produces eggs with 10 times as much Omega six as Omega three, whereas a true farm fed chicken will produce eggs with a balanced Omega 3:6 ratio. The distortion of these ratios goes through the food chain.

The biggest source of Omega six is vegetable oils. The common vegetable oils like sunflower grapeseed safflower soy peanut etc are all between 50 and 70% Omega six. Our intake of Omega six has increased from 1/2 to 2% of calories to 10% and higher in the modern diet. Intakes of Omega three have substantially decreased. Many women have woefully low intakes of long chain Omega three DHA.

Reducing the intake of plant-based Omega six and increasing the intakes of plant-based Omega three , and the long chain Omega three found in fish oil will help to reduce inflammation and so CRP.

There are a number of trials that suggest Omega threes reduce CRP and Omega sixes increase CRP.

The Greek diet thread above shows that Omega three and six also have big roles in determining the risk of breast cancer.

There is also evidence that drugs that block inflammation like NASIDs reduce the risk of breast cancer. The Omega three fat DHA which is found in fish has been shown to be more effective than some NASIDs.

Here are some links to some trials that suggest that Omega threes reduce CRP and Omega sixes increase CRP.

Fish oil can thin the blood and may have adverse effects for some are on medication for heart conditions, so please discuss significant dietary changes with your doctor.

Fish and shellfish are the place to start as they contain both long chain Omega threes and important minerals that are essential to body function. Seaweed is also a good source of minerals and iodine.

I have written a book on the subject. it is not very well edited, but the underlying science is generally good and it hopefully explains why the Omega 3:6 balance is so important. I have spent a year totally rewriting it and the new version is being professionally edited and hopefully a huge improvement. The title is intended to be interesting and controversial but was probably a mistake. The book contains over 700 references. The revised version will hopefully be available towards the end of this year or the beginning of the next. http://www.amazon.com/Omega-Six-Devils-Message-Dietary/dp/0955707404 http://www.amazon.co.uk/Omega-Six-Devils-Fat-infertility/dp/0955707404/ref=sr_1_1?ie=UTF8&qid=1249517186&sr=8-1


C-reactive protein, dietary n-3 fatty acids, and the extent of coronary artery disease
http://cat.inist.fr/?aModele=afficheN&cpsidt=14104433

DHA Supplementation Decreases Serum C-Reactive Protein and Other Markers of Inflammation in Hypertriglyceridemic Men1–3,
http://jn.nutrition.org/cgi/content/abstract/139/3/495
Increased alpha-linolenic acid intake lowers C-reactive protein, but has no effect on markers of atherosclerosis. http://www.ncbi.nlm.nih.gov/pubmed/15220952

N-3 Fatty Acid Enriched Egg Decreases C-Reactive Protein in Healthy Adults
http://www.fasebj.org/cgi/content/meeting_abstract/21/6/A740-b

Dietary -linolenic acid decreases C-reactive protein, serum amyloid A and interleukin-6 in dyslipidaemic patients
http://www.ingentaconnect.com/content/els/00219150/2003/00000167/00000002/art00427

Isomer-specific effect of conjugated linoleic acid on inflammatory adipokines associated with fat accumulation in 3T3-L1 adipocytes.
http://www.ncbi.nlm.nih.gov/pubmed/17004891

[R.B.]

Duplicate post my error I apologise

[Ellie F]

The message seems to be reduce vegetable fat intake and increase fish oil intake by both eating lots of fish and taking pure fish oil supplements.
In this modern day and age lots of foods contain vegetable oil, even ones you don't expect which makes life more difficult.
Certainly when I look back my own diet had virtually no omega 3 and was loaded with omega 6 for years so I am persuaded that I lived in a state of low grade chronic inflammation which I believe 'grew' the cancer.
I also wonder if chronic stress is a contributory factor and whether this also reduces omega 3 levels and'fuels' cancer growth?
Ellie

[michka]

Thank you for all these suggestions. I have to continue investigating with my doctors as Jackie suggested to be sure this high CRP is not hiding something important.
As for the diet, I have always been very careful to eat well. All my life, in fact, thanks to my mother. I do not eat fat food, eat vegetables and fruits and only use olive oil. It was not enough to protect me but I do not do a lot of sports. I now take a supplement of fish oil every day. I read on this site a few months ago that it was important(thanks to R.B!).
I must admit that this article got me real upset. I now it is stupid but it did. Just by answering my posts you make me feel better. I will have the CRP tested again in September and if it is not normal, I'll see my onc sooner than November. Michka

[R.B.]

Michka

Olive oil contains 10% plant based Omega 6 and no 3.

So you need to look at flaxseed or oil to balance the plant based Omega 6.

Many fish oil capsules do not contain much Omega 3 DHA. I would suggest at least a gram of EPA and DHA a day, but not too much more and please talk to your doctor if on heart medication of any sort or blood thinners.

Quality bottled fish oil is a cheaper way, and it does not repeat these days.

You also need to make sure you are getting adequate minerals. Some soils can be low in some minerals.


http://acb.rsmjournals.com/cgi/content/abstract/42/5/364

[R.B.]

CoQ10 may help when taken with vit E.

http://www.ajcn.org/cgi/content/abstract/80/3/649