Biochemical aids to the staging of breast cancer.

Up to fifteen plasma proteins were measured before treatment in 249 women presenting with lumps in the breast. Concentrations showed considerable overlap between the various clinical stages, and were often normal even in metastatic disease. A discriminant function is proposed, based on measurement of C-reactive protein, beta 2-microglobulin, carcinoembryonic antigen and ferritin and calculation of a score for each subject. High-risk scores resulted for all 18 patients with Stage 4 (i.e., metastatic) disease, and the number of Stage 1 patients attaining high scores was consistent with the reported incidence of development of metastases in such a group. Follow-up studies are in progress.

Screening for metastases in breast cancer: an assessment of biochemical and physical methods.

Ten tumor markers were measured in serum or urine at approximately three month intervals in patients with breast cancer following mastectomy but before development of overt metastatic disease. In 23 patients who later had metastases, only three markers, alkaline phosphatase, carcinoembryonic antigen (CEA), and gamma-glutamyl transpeptidase (gamma-GT) were consistently abnormal prior to the development of detectable metastases in more than one patient. In half the patients, a "lead interval" of three months or more was obtained using these three markers and little advantage was obtained by the addition of any other biochemical marker. The value of these three measurements was then assessed in a larger group of patients and compared with other tests for metastases. Alkaline phosphatase, CEA, gamma-GT, clinical examination, and chest x-ray were the best indices of the metastatic state in breast cancer, being collectively abnormal in 98% of patients at first presentation with metastases. The authors recommend screening patients postoperatively with these five tests for metastases; more detailed tests should only be carried out if results of one or more these are abnormal.

Standardization of immunochemical determinations of serum albumin.

When we compared four commercially available preparations of human serum albumin with the human serum standard IFCC 74/1 by radial immunodiffusion, by immunoprecipitation turbidimetry, by laser nephelometry, and by "rocket" immunoelectrophoresis, three of the preparations gave almost "theoretical" results with the immunoprecipitation turbidimetric method. Results by the other three methods tended inconsistently to be low. Four pools of normal human serum were also analyzed for albumin by these four immunochemical methods, again with IFCC 74/1 as the reference standard. The results were virtually identical with those obtained by fractionation with 1.8 mol/L sodium sulfate and determination of protein nitrogen in the filtrate. We suggest that a combination of (a) fractionation of a pool of normal human serum in this way and (b) critical comparison with selected commercial preparations of human serum albumin will permit standardization of the serum albumin determination.

Serum beta2-microglobulin in controls and cancer patients.

Serum beta2-microglobulin levels have been measured in 210 cancer and control patients to assess the significance of this investigation in cancer patients. Subjects studied included patients with breast and gastrointestinal cancer, corresponding control patients in both categories, and healthy volunteers. The composition of these groups allowed an assessment of the relative importance of changes related to cancer, benign disease, age and sex. A significant rise in serum beta2-microglobulin levels with advancing age was demonstrated in the control subjects. Mean levels were also consistently higher in females than in males in each patient group. After statistical correction for these age and sex effects, mean values remained significantly higher in each of the various cancer groups than in their controls. Patients with more advanced breast cancer had higher levels than those with 'early' disease, as did patients with stomach cancer compared to those with colo-rectal cancer. One possible interpretation is that levels increase with increasing tumour bulk, and therefore the estimation of serum beta2-microglobulin may be useful as one of a battery of tests in the management of cancer patients.

Serum alpha-1-acid glycoprotein as an index of dissemination in breast cancer.

Assay of the serum alpha-1-acid glycoprotein (SAGP) produced by the liver in response to many disease states is shown to reflect prognosis and monitor progress in patients with early, recurrent and disseminated breast cancer. Eighteen of 26 patients with localized breast cancer and positive bone scans had elevated SAGP when first seen, but within 5 months of treatment 5 further patients with positive bone scans developed an elevated SAGP. Furthermore, an initially abnormal SAGP level became normal within 5 months in 5 of 6 patients with negative bone scans. While elevated SAGP in breast cancer correlates with positive bone scans, a series of normal values may indicate patients without early haematogenous dissemination of their disease.

Serum immunoglobulins after surgical operation.

We measured immunoglobulins in the sera of 33 patients on days 1, 3, 6, 10, and 17 and three to four weeks after surgical operations (mostly hysterectomy or appendectomy) or (six patients) after spinal injury. In the absence of infection or blood transfusion, IgG usually decreased slightly and transiently after hysterectomy or appendectomy, as did IgA or IgM after hysterectomy. IgD concentrations showed no consistent changes, but in one patient after hysterectomy and with minimal infection IgD concentration decreased sharply, which contrasted with significant and early increases in IgG, IgA, and IgM. IgD concentration was not correlated with type of operation, presence of infection, or changes in the other immunoglobulins. IgE concentrations either die not change or, in some patients, increased or decreased initially, after operation. We conclude that immunoglobulin concentrations in serum are subject to multiple, unpredictable influences after trauma.

Left ventricular ejection time. multiple relation to physiological and biometrical data; prediction of reference standards.

The relationship between left ventricular ejection time, and physiological or biometrical data, is submitted to multivariate statistical analysis. Methodology is intended to attain three objectives: 1) to simulate a controlled-condition experiment in clinical research, by using the statistical method of multiple regression; 2) to get a wide inference of conclusions, by selecting a sample of two hundred subjects whose biological data cover a wide field; 3) to check the really prospective value of results, by applying the formula worked out in a group of a hundred subjects to another independent group of a hundred subjects. The prediction formula of ejection time takes into account: stroke volume, cardiac cycle duration, body height, sex, age, pulse pressure, blood capacity in oxygen, presence or absence of digitalis treatment or atrial fibrillation. The first aim of the formula is to better evaluate the normal relationship between considered variables. Secondarily it leads to a proposal for estimating mechanical performance of the left ventricle.