researchers moving in on earlier detection of bone metastases in breast cancer

[Lani]

ABSTRACT: Alpha CTX as a Biomarker of Skeletal Invasion of Breast Cancer: Immunolocalization and the Load Dependency of Urinary Excretion [Cancer Epidemiology, Biomarkers and Prevention; Subscribe]
We recently showed that increased urinary excretion of the cross-linked, nonisomerized form of the C-telopeptide of collagen type I (??CTX) could be a sensitive indicator of the presence of bone metastases in breast cancer patients. The present study was sought to investigate (a) the localization of ?CTX epitopes in the proximity of a bone metastasis and (b) the relationship between number of metastases and the urinary excretion of ??CTX. Adjacent bone sections from breast cancer patients were stained for the presence of tumor cells (anti-cytokeratin antibody), osteoclasts (TRAcP activity), and CTX? (anti-?CTX antibody). The association between the extent of metastatic bone disease and urinary excretion of ??CTX measured with ELISA was assessed in 90 breast cancer patients (45 with bone metastasis and 45 without bone metastasis). Immunohistochemistry revealed accumulation of TRAcP-positive osteoclasts and intense staining for ?CTX epitopes in the proximity of cytokeratin-positive bone metastasis. Areas of ?CTX staining showed unstructured bone tissue under polarized light. In addition, there was a significant linear association between the number of bone metastases and the urinary levels of ??CTX in breast cancer patients with metastatic bone disease, independent of age and body mass index (r = 0.56, P < 0.001). The estimated relative increases in ??CTX associated with the presence of one, two, or three metastases are 38%, 57%, and 81%, respectively. Taken into account the 17% intraindividual variation of the assay, ??CTX could be a sensitive biochemical marker for the close monitoring of cancer patients aiming the facilitation of early metastasis detection.

[heblaj01]

In 2003 researchers in Taiwan published the results of their study of urine deoxypyridinoline tests for detecting & monitoring metastatic bone lesions as shown in abstract below.
In the full text of their paper where various ranges of deoxypyridinoline levels are provided with their significance, they claim that the test can detect bone metastases 3 to 6 months before any other marker (as of 2003).
If this test is not surpassed by better more recent markers it might still be an easy non invasive & relatively inexpensive diagnostic tool.

http://www.annclinlabsci.org/cgi/content/abstract/33/1/55

Diagnostic Value of Urine Deoxypyridinoline for Detecting Bone Metastases in Breast Cancer Patients

Hou MF (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Hou+MF%22%5BAuthor%5D), Lin SB (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Lin+SB%22%5BAuthor%5D), Yuan SS (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Yuan+SS%22%5BAuthor%5D), Tsai LY (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Tsai+LY%22%5BAuthor%5D), Tsai SM (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Tsai+SM%22%5BAuthor%5D), Hsieh JS (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Hsieh+JS%22%5BAuthor%5D), Huang TJ (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Search&itool=pubmed_Abstract&term=%22Huang+TJ%22%5BAuthor%5D).

Department of Surgery, Obstetrics and Gynecology, Kaohsiung Medical University, Taiwan, Republic of China.

Deoxypyridinoline (Dpd), a crosslink product of collagen molecules found in bone and excreted in urine during bone degradation, has been described as a marker of bone turnover in metastatic breast cancer. In this study, the urine deoxypyridinoline/creatinine (Dpd/Cre) ratio was determined by enzyme immunoassay in urine samples from 116 women with breast cancer. Bone metastases were confirmed by x-ray or CT scan, with follow-up > 6 mo. The urine Dpd/Cre ratio was significantly higher in patients with bone metastasis, compared to those without bone metastasis (p < 0.05). In patients with bone metastasis, ratios of urine Dpd/Cre were higher in those with multiple lesions, compared to those with a solitary lesion, and the values also reflected therapeutic response (p < 0.05). Serial monitoring of urine Dpd/Cre revealed that an elevation was correlated with disease progression. Patients with stable bone disease under effective therapy had significant diminution of the urine Dpd/Cre ratios, compared to those with progression of bone disease (p < 0.05). In conclusion, the urine Dpd/Cre ratio may be a useful marker for detecting bone metastases and evaluating their response to therapy

[Esther]

Ok, I thought the old line of thinking was that earlier detection of mets without symptoms did not translate into incrased longevity?

Does not hold true anymore? I'm not sure what the advantage of finding bone mets earlier would be.

[Barbara H.]

I don't totally believe that line of thinking, Esther. I think there are exceptions. It's hard to fix damaged bones at our age and cancer damages them. As soon as you are diagnosed you are given Zometa which offers some protection. Statistics are too complicated and each person is an individual. For example, Steph's cancer had just started to go into the bones and 4 years later she is NED.
I think it would be great to catch bone mets early and/ or to monitor them other than with a scan.
Best,
Barbara H.

[astrid]

What are the signs of bone mets? How do you know you have them??

[Lani]

If everyone fed into these old wive's tales like oncologists dogma noone would ever look into whether new treatments and new ways of detecting recurrence earlier made any difference. The dogma is that once metastasis occurs all die inon average 2 years (except her2s who dieon average in one year)no matter what you do --should we just go along with that , not try anytiing? Those on this board wouldn't have been in the position they are in if ALL the doctors and researchers went along with the dogma (thank God some don't)

Someone posted an editorial by one of the leading breast oncologists at MDAnderson a while ago, citing that he had been surprised, even pre-Herceptin, at the unusual longevity of those diagnosed early with just minimal metastatic disease ie, as if finding it when the tumor burder was not overwhelming made likelihood of getting it to a proportion where the immune system or other means could successfully compete against it were possible. He suggested a clinical trial/research into it l, but I have not heard further.

Do we wait until people have pain from fracture, or, as in Lyn's case, encroachment on the spinal cord. There must be a better way, but if people keep mouthing/believing the dogma we will never get there!

Off my soapbox for now!

Lani

PS also metastases in bone wreak their damage by activating osteoclases (bone dissolving cells) and that can be slowed/prevented by bisphosphonates. Why let someones bones dissolve and break (a process that takes many months) when the process could be VERY VERY substantially slowed down And we don't know what we could do if we detected it even earlier!!!!

[Barbara H.]

My oncologist is usually quite positive, but I think I will discuss what you stated in the above post.
Thanks,
Barbara H.

[heblaj01]

There are two possible additional arguments that militate in favour of both early detection & treatment of bone cancer:
First, there is a vicious cercle between cancer & bone degradation by cancer. They reinforce each other according to some basic research. This may mean for some patients a cancer that progresses faster.

Second, if cancer progresses faster it becomes less responsive to slow but otherwise effective non cytotoxic treatments such as antiangiogenesis agents or metronomic administration of chemo drugs .
This reduces the number of available treatment options when the worsening condition of the patient calls for more not less safe alternatives.

[Lani]

the editorial was by Gabriel Hortobagyi of MD Anderson

[Kaye]

Is this lab test available now?

[Lani]

I had saved the original article and when looking at the authors saw that one came from a company in Denmark

Here is the link to their website

http://www.nbdiagnostics.com/613/293