Normalisation of biochemical markers of bone formation correlates with clinical benefit from therapy in metastatic breast cancer.
BACKGROUND
Type I collagen is the most abundant protein of bone. We measured a panel of biochemical markers of bone metabolism including the amino-terminal propeptide (PINP) of type I collagen, the carboxy-terminal telopeptide (ICTP) of type I collagen, the urinary desoxypyridinium (DPD) crosslinks excretion, the alkaline phosphatase (AP) and serum calcium (Ca) levels as well as CA 27.29 as mass tumor marker in 73 breast cancer patients with bone metastases under specific antitumor therapy and supportive treatment with pamidronate.


METHODS
Representative longitudinal single-time-point evaluations of all markers were correlated to response assessment in UICC criteria. Restaging was done by standard procedures. PINP and ICTP were measured using standardized radioimmunoassays with cut-offs of normal of 84 micrograms/l and 5 micrograms/l, respectively. DPD was measured on a chemiluminescence basis using an upper limit of normal of 13 nmol/mmol.


RESULTS
The distributions of all pooled levels of CA 27.29 and AP were statistically significantly different (or just missed statistical significance) between patients with stabilized disease as compared to progressing patients with p = 0.012 for CA 27.29 and p = 0.053 for AP. AP was the only parameter which normalized below the cut-off of normal statistically significantly (p = 0.003) more often in the group of patients with clinical benefit as compared to progressive patients. PINP showed the second best result for normalisation with p = 0.083, though missing statistical significance.


CONCLUSIONS
Clinical benefit from systemic therapy was primarily accompanied by a normalization of biochemical markers representing bone formation. This result reflects the physiology of the "bone remodeling unit". In patients without this normalization, thorough and early restaging is warranted since the systemic therapy may be ineffective.
Lüftner
D
D
Medizinische Klinik und Poliklinik II, Universitätsklinikum Charité, Campus Mitte, Humboldt-Universität zu Berlin, Schumannstr. 20-21, 10117 Berlin, Germany. Diana.Lueftner@rz.hu-berlin.de
Richter
A
A
Geppert
R
R
Wernecke
K D
KD
Possinger
K
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000097:blood; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000032:analysis; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D002118:Calcium / Q000097:blood; D024042:Collagen Type I / Q000097:blood*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D010012:Osteogenesis; D017698:Postmenopause; D017697:Premenopause; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D013997:Time Factors
D015295:Antigens, Tumor-Associated, Carbohydrate; D000970:Antineoplastic Agents; D015415:Biomarkers; D014408:Biomarkers, Tumor; C090797:CA 27-29 antigen; D024042:Collagen Type I; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000469:Alkaline Phosphatase; D002118:Calcium