Evaluation of MSA as a serum marker in breast cancer: a comparison with CEA

In a blind study, 518 serum samples were assayed for serum levels of mammary serum antigen (MSA) by an enzyme immunoassay (EIA) using the 3E1.2 monoclonal antibody. Using 300 IU as the arbitrary cut off to distinguish normal from abnormal individuals, 75% of patients with primary Stage I carcinoma of the breast (n = 12), 89% of those with Stage II (n = 9) and 93% of those with Stage IV (n = 57) had elevated levels of MSA. A relationship was observed between the level of MSA and stage of disease, and therefore with the extent of tumour burden. Levels of MSA were also determined in a series of 19 patients undergoing chemotherapy for breast cancer. Over a 2-24 month period, the change of MSA levels corresponded with the clinical course of the disease in 17 (89%) cases. MSA levels were also raised in some patients with ovarian, colon, lung and kidney cancer, but the average level was lower than in patients with breast cancer. A comparison of CEA and MSA levels in these patients revealed that MSA was a substantially better marker for breast cancer than CEA. The results of this study demonstrate that MSA levels are elevated in patients with breast cancer and may provide a useful means of following the clinical course of patients with this disease.     

Time to diagnosis and breast cancer stage by race/ethnicity

We examined differences in time to diagnosis by race/ethnicity, the relationship between time to diagnosis and stage, and the extent to which it explains differences in stage at diagnosis across racial/ethnic groups. Our analytic sample includes 21,427 non-Hispanic White (White), Hispanic, non-Hispanic Black (Black) and non-Hispanic Asian/Pacific Islander (Asian) women diagnosed with stage I to IV breast cancer between January 1, 2000 and December 31, 2007 at one of eight National Comprehensive Cancer Network centers. We measured time from initial abnormal mammogram or symptom to breast cancer diagnosis. Stage was classified using AJCC criteria. Initial sign of breast cancer modified the association between race/ethnicity and time to diagnosis. Among symptomatic women, median time to diagnosis ranged from 36?days among Whites to 53.6 for Blacks. Among women with abnormal mammograms, median time to diagnosis ranged from 21?days among Whites to 29 for Blacks. Blacks had the highest proportion (26?%) of Stage III or IV tumors. After accounting for time to diagnosis, the observed increased risk of stage III/IV breast cancer was reduced from 40 to 28?% among Hispanics and from 113 to 100?% among Blacks, but estimates remained statistically significant. We were unable to fully account for the higher proportion of late-stage tumors among Blacks. Blacks and Hispanics experienced longer time to diagnosis than Whites, and Blacks were more likely to be diagnosed with late-stage tumors. Longer time to diagnosis did not fully explain differences in stage between racial/ethnicity groups.     

Prognostic significance of serum c-erbB-2 protein in breast cancer patients

Summary The tissue expression of c-erbB-2 protein in breast cancer is a marker of poor prognosis in a number of studies. More recently it has also been suggested that c-erbB-2 expression may predict response to systemic therapy in patients with advanced breast cancer. The measurement of c-erbB-2 protein in the serum of breast cancer patients has now been reported, but the significance of this finding is not clear. In this study an ELISA assay was used to measure c-erbB-2 in the sera of 23 normal controls, 46 benign breast disease patients, and 119 breast cancer patients. Elevated serum c-erbB-2 protein levels were detected in 13% (3/23) of normal controls, 15% (7/46) of benign disease patients, 15% (7/46) of Stage I/II patients, 26% (9/35) of Stage III patients, and 21% (8/38) of Stage IV patients. The tissue expression of the c-erbB-2 protein showed no association with detection of the serum c-erbB-2 protein (p = 0.31). In the 67 Stage III and IV patients who had assessable disease the presence of the c-erbB-2 protein in the serum bore no relationship to response to hormonal therapy (p = 0.71). Serum detection of the c-erbB-2 protein in Stage I/II patients predicted for a worsening of both survival outcome (p = 0.002) and disease free interval (p = 0.002). A worse outcome was also seen for the Stage III patients (p = 0.04) and Stage IV patients, although the latter did not reach statistical significance (p = 0.27).This study found that the presence of c-erbB-2 in the serum of breast cancer patients was of prognostic significance for all stages of disease.     

Serum UDP-galactosyl transferase as a potential biomarker for breast carcinoma

UDP-galactose:N-acetylglucosamine galactosyltransferase (GT) is a membrane-bound enzyme active in the biosynthesis of the carbohydrate moiety of glyco-proteins and glycolipids. A soluble form of GT, present in human serum, has recently been found to be elevated in the presence of various neoplasms. In this study, GT levels were measured in randomized serum samples obtained from normal controls (group I, n = 49), patients with benign breast disease (group II, n = 46), disease controls (group III, n = 50), patients with primary breast carcinoma (group IV, n = 53), and untreated metastatic breast cancer (group V, n = 23). Although substantial serum GT elevations were observed in individual control patients with active inflammatory or metabolic diseases, the mean GT levels were signficantly higher in the groups with breast carcinoma (P < 0.001, 0.001, 0.02; P < 0.001, 0.001, 0.001 for groups IV and V vs groups, 1, II, and III, respectively). Furthermore, when serum GT levels were correlated with the preoperative clinical stage of breast cancer, significant elevations were found in 14.3% (3/21) of stage I, 66.7% (8/12) of stage II, 78.6% (11/14) of stage III, and 96.5% (28/29) of stage IV patients. These data indicate that serum GT levels are elevated in the presence of breast carcinoma and that the enzyme elevations correlate positively with the clinical stage of disease. Serum GT may be potentially useful in the detection of recurrent breast carcinoma and as a marker of tumor response to therapy for advanced disease.     

Tumour markers in breast cancer.

The clinical usefulness of 8 potential tumour markers has been evaluated in 69 patients with Stage I and II breast cancer and 57 patients with Stage III and IV. Serum CEA concentrations were raised in 13% of patients with local and 65% of those with advanced breast cancer. In patients with clinical evidence of progression or regression of tumour, serum CEA levels changed appropriately in 83% of cases. Taking 4 of the markers (carcinoembryonic antigen (CEA), lactalbumin, alpha subunit and haptoglobin) serum concentrations of one or more were raised in 33% of patients with local disease and 81% of those with advanced breast cancer. However, marker concentrations were often only marginally raised, and are unlikely to provide sensitive guide to tumour burden. CEA, lactalbumin and alpha subunit were detectable in 68%, 43% and 40% respectively of extracts of primary breast cancers.     

The use of CA15.3 as a serum tumour marker in breast carcinoma

There is, as yet, no tumour marker which is sufficiently specific and sensitive for use in the routine assessment of breast cancer patients. CA15.3 is a recently described tumour marker determined by two monoclonal antibodies. We have estimated CA15.3 by immunoradiometric assay in 187 patients attending a breast clinic. Eighty-one patients with benign disease were used as controls and 32 U/ml was taken as the upper limit of the normal range (means + 3SD = 31.7). Of 58 women with Stage I and II disease, only four had abnormal concentrations of CA15.3 and all are disease-free at a mean follow-up of 31 months. Seven women with normal CA15.3 concentrations developed recurrent disease at a mean of 18.7 months (range 10-25 months). Seven-day postoperative values were significantly lower than pre-operative values. There was no association between the CA15.3 value and the axillary nodal status. The patients with disseminated disease had a wide range of CA15.3 concentrations and there was no association between the CA15.3 concentration and the apparent tumour load.     

Sigma S, a measure of reactive sulfur groups of immunoglobulin G, is a sensitive tumor marker discriminating different stages of breast cancer

Sigma S is a measure of the disulfide bonds and free thiol groups of serum immunoglobulin (Ig) G, as determined by the reaction with dithionitrobenzoate. Significant decreases of sigma S previously were detected in malignant compared with benign diseases of various organs. This study shows the application of sigma S for the diagnosis of breast cancer. The following results were obtained. First, 132 patients with benign breast diseases showed a sigma S of 1.48 +/- 0.29 (standard deviation) per mole IgG; this was not different from 1.51 +/- 0.36 found in 182 controls. In contrast, IgG from 198 patients with primary breast carcinoma of all four stages (tumor-node-metastasis system) gave a sigma S of 1.22 +/- 0.29, a significant (P less than 0.0001) decrease of sigma S from benign to malignant breast disease. Second, sigma S values of single Stages I, II, III, and IV, were 1.27 (n = 59), 1.23 (n = 83), 1.19 (n = 35), and 1.10 (n = 21), respectively, each significantly different from sigma S in benign disease and showing a decreasing trend with increasing tumor progress. Differences were significant between Stages I and IV (P less than 0.025) and II and IV (P less than 0.05). Third, 63% of Stage I breast carcinoma patients had sigma S values below a critical threshold of 1.38. This serum positivity rose to 90% in Stage IV. These values exceeded those reported with other tumor markers. The overall power of sigma S to distinguish between benign and malignant breast disease had a specificity of 61% and a sensitivity of 78%. Early stages (I and II) of breast cancer could be distinguished from benign diseases with 64% specificity and 69% sensitivity. Advanced Stage IV could be discriminated from early Stages I and II with 55% specificity and 71% sensitivity. Thus, the analysis of sigma S may significantly contribute to the surveillance of patients with breast cancer.     

The use of skin sparing mastectomy in the treatment of breast cancer: The Emory experience

INTRODUCTION: Long-term follow-up of the use of skin sparing mastectomy (SSM) in the treatment of breast cancer is presented to determine the impact of local recurrence (LR) on survival. METHODS: 565 cases of breast cancer were treated by SSM and IBR from 1/1/1989-12/31/1998. The AJCC pathological staging was Stage 0 175 (31%), Stage I 135 (23.9%), Stage II 173 (30.6%), Stage III 54 (9.6%), Stage IV 8 (1.4%), recurrent 20 (3.5%). Forty-one patients received postoperative adjuvant radiation therapy. RESULTS: Thirty-one patients developed a LR during the follow-up including five who received adjuvant radiation. The distribution of LR stratified by cancer stage was Stage 0 1 (3.2%), Stage I 5 (16.1%), Stage II 17 (54.8%), Stage III 6 (19.4%), and recurrent 2 (6.5%). The overall LR was 5.5%. Isolated LRs were treated with surgical resection and radiation therapy if not previously administered. Twenty-four patients (77.4%) developed a systemic relapse and 7 (22.6%) patients remained free of recurrent disease at a mean follow-up of 78.1 months. The cancer stage of those remaining disease free was Stage 0 1, Stage I 4, and Stage II 2. CONCLUSIONS: LR of breast cancer after SSM is not always associated with systemic relapse.     

Patterns of local-regional recurrence and results in Stages I and II breast cancer treated by irradiation following limited surgery. An update

One hundred forty-six women with Stage I and Stage II breast cancer received radical radiotherapy after having excisional biopsy ( lumpectomy ) at Massachusetts General Hospital between 1956-1978. They were grouped according to age: those younger than 49 years and those older than 50 years. The 5-year survival rates were 93 and 73% for patients with Stage I and Stage II cancer, respectively; the corresponding 5-year relapse survival rates were 75 and 56%. The local recurrence rate was 8% in patients with Stage I disease and 17% in those with Stage II disease. Survival was not significantly affected by patients' age, by the presence or absence of blood vessel or lymphatic involvement, or by the addition of adjuvant chemotherapy. No major complications occurred. Modification in radiation dose and technique resulted in improved overall survival and local control. Limited surgery followed by radical radiation therapy offers a therapeutically effective, cosmetically acceptable alternative to radical surgery for early stage breast cancer.     

The use of oncofetal ferritin-bearing lymphocytes as a marker for the screening, diagnosis, and follow-up of patients with early breast malignancy screening of 3400 women

The potential of using a blood test enumerating oncofetal ferritin-bearing lymphocytes (FBL) as a biomarker for early breast cancer was further explored. Nine hundred women attending a high-risk breast cancer clinic and 2500 normal-risk women were physically examined and their blood drawn for FBL determination using a newly developed radioimmunoassay. The FBL test results were compared to clinically or histopathologically diagnosed breast disease and to known breast cancer risk factors. A gradual increase in the mean FBL ratio was seen from normal risk disease-free women to those with in situ or early stage breast cancer. The percentage of women with positive FBL was 13.6% for the normal risk group, 19% and 25.7% for clinically and histopathologically diagnosed benign breast disease, respectively, and 100, 77.8, and 66.7% for in situ, Stage I, and Stage II breast cancer, respectively. In locally advanced disease (Stage III) the percentage of positive women was only 17.2%. It was further found that a negative FBL result in known breast cancer patients at Stage I, II of the disease was a bad prognostic marker indicating a shorter disease-free survival. The follow-up of patients after surgery by periodical clinical examination and the FBL test revealed that the positive FBL was declining after removal of the precancerous or malignant tumor and that it was highly sensitive (100%) in predicting tumor development and recurrence. Using a logistic regression analysis, an FBL-positive test indicated a significant association with risk of early breast cancer (odds ratio = 2.9; 95% confidence interval = 1.4-5.8). Being a measure of the immune response the positive FBL was associated with early breast cancer and good prognosis. Since patients with locally advanced cancer and poor prognosis were FBL negative but such patients were shown to have increased serum ferritin levels. It is suggested to use the FBL and serum ferritin assays for screening and diagnosis of breast cancer.     

Uncontrolled local recurrence after treatment of breast cancer with breast conservation

Three hundred fifty-six patients with early (Stage I and II) breast cancer and 55 with advanced (Stage III and IV) breast cancer were treated between 1979 and 1985 with a consistent policy of breast conservation irrespective of tumor site, size, or histologic features. Only three patients underwent primary mastectomy (Stage III), and the remainder were treated either by wide local excision and postoperative radiotherapy (357 cases) or by needle biopsy and primary irradiation (51 cases). A total of seven of 356 (2%) Stage I and II patients have developed uncontrolled local or nodal recurrence at a median follow-up of 5 years, and nine of 55 (16%) of Stage III and IV patients. Of the 62 Stage I and II patients who have died, seven (11%) have died with uncontrolled locoregional disease. Of the 22 Stage III and IV patients who have died, eight (36%) have died with uncontrolled locoregional disease. Although the majority of local recurrences within the conserved breast could be salvaged by secondary surgery (37/38 Stage I and II patients), the development of chest wall or nodal recurrence was usually associated with the appearance of distant metastases and a poor prognosis. Data on uncontrolled local recurrence should be given in all studies of breast cancer treatment, since it represents an important end-point of therapy and a difficult clinical problem.     

Female patients with breast carcinoma age 30 years and younger have a poor prognosis: the M.D. Anderson Cancer Center experience.

BACKGROUND: The objective of this study was to analyze the outcome of treatment in young women with breast carcinoma who were treated at a single institution and to develop a clearer understanding of the natural history of the disease in these women. METHODS: One hundred eighty-five women age < or = 30 years in whom a diagnosis of invasive breast carcinoma was made between October 1985 and September 1995 were identified in the Tumor Registry data base. Patient data were obtained by chart review. All female patients with breast carcinoma who were age > 30 years and who were identified in the same data base and received treatment during the same period served as the control population. The stage-stratified overall survival (OS) rate for the study patients was compared with the OS rate for both the control population and patients in the National Cancer Data Base (NCDB). RESULTS: Of 185 patients, 11% presented with Stage I disease, 45% presented with Stage II disease, 38% presented with Stage III disease, and 6% presented with Stage IV disease. Twenty-nine percent of patients with Stage I disease received adjuvant therapy, and 84% of patients with Stage II disease and 96% of patients with Stage III disease received either adjuvant or neoadjuvant chemotherapy. Among patients with Stage I disease, 8 patients underwent mastectomy and 13 patients underwent breast-conserving surgery (BCS). Among patients with Stage II disease, 66 patients underwent mastectomy and 17 patients underwent BCS. Among patients with Stage III disease, 65 patients underwent mastectomy and 5 patients underwent BCS. The 5-year OS rate was 87% for patients with Stage I disease, 60% for patients with Stage II disease, 42% for patients with Stage III disease, and 16% for patients with Stage IV disease. Compared with the control patients and those in the NCDB, there was a trend toward worse OS rates in women age < or = 30 years. CONCLUSIONS: Women who are diagnosed with breast carcinoma at an age < or = 30 years appear to have a poorer prognosis compared with that for their older counterparts.     

Plasma insulin-like growth factor binding protein-3 proteolysis is increased in primary breast cancer.

Fasting blood samples were obtained before definitive surgery or biopsy in 128 patients referred to the department of surgery with suspected or manifest breast cancer. Insulin-like growth factor (IGF)-I, IGF-II and free IGF-I were measured by radioimmunoassay/immunoradiometric assay, while IGFBP-3 proteolysis was evaluated by Western immunoblot. 12 patients had ductal carcinoma in situ benign conditions, while staging revealed metastatic disease in 15 of 16 patients with invasive cancers. IGFBP-3 proteolysis above the normal range was recorded in 19 patients with invasive cancers, but in none of the patients suffering from DCIS/benign conditions. Increased IGFBP-3 proteolysis was most frequently recorded in patients harbouring large tumours and metastatic disease (Stage I: 0/19, 0%; Stage II: 3/45, 7%, Stage III: 9/37, 24%, and Stage IV: 7/15, 47%). IGFBP-3 proteolysis was significantly higher in Stage III (P =0.01) and IV (P< 0.001) patients compared to the other stage groups (P = 0.001). IGF-I and IGF-II correlated negatively to IGFBP-3 proteolysis and age. Plasma levels of IGF-I and -II were significantly lower in patients with elevated IGFBP-3 proteolysis compared to those within the normal range. Our findings reveal alterations in the IGF-system among a substantial number of patients with large primary breast cancers.     

Breast conservation therapy in the United States following the 1990 National Institutes of Health Consensus Development Conference on the treatment of patients with early stage invasive breast carcinoma.

BACKGROUND: A National Institutes of Health (NIH) Consensus Development Conference on the treatment of patients with early stage invasive breast carcinoma, held in June 1990, recommended breast conservation therapy for the majority of women with Stage I or II breast carcinoma. The authors evaluated the national use of breast conservation therapy before and after the conference to determine whether the conference had had an impact on utilization. METHODS: Women with Stage I or II breast carcinoma (n = 109,880), diagnosed during the years 1983-1995, were identified via 9 population-based cancer registries of the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute. The likelihood of breast conservation surgery versus mastectomy and, among women who underwent breast conservation surgery, the likelihood of postoperative radiation therapy versus none, were assessed for 3 time periods (January 1983 to April 1985, May 1985 to June 1990, and July 1990 to December 1995). Associations between the use of breast conservation surgery or postoperative radiotherapy according to patient stage, age, race, and region were compared among women diagnosed before and after the NIH Consensus Development Conference. RESULTS: From 1985 (the year that the U.S. randomized controlled trial demonstrating equivalent efficacy between breast conservation therapy and mastectomy was published) through 1989, approximately 35% of women with Stage I and 19% of women with Stage II breast carcinoma underwent breast conservation surgery; these percentages remained constant throughout this period. Beginning in 1990, the year of the NIH Consensus Development Conference, the use of breast conservation surgery increased in each subsequent year; by 1995, 60% of women with Stage I and 39% of women with Stage II breast carcinoma received such treatment. However, regional variation in use was observed (Stage I, range 41.4-71.4% for 1995) and no registry reported breast conservation therapy for the majority of women with Stage II disease (range, 23.8-48.0%). The use of postoperative radiotherapy for women who underwent breast conservation surgery was similar in the periods before and after the conference. CONCLUSIONS: Although breast conservation therapy was performed more frequently following the NIH Consensus Development Conference, variation in use by region of the U.S. suggests the continued presence of barriers to widespread adoption of the recommendations formulated at the conference.     

Comparison of mammary serum antigen (MSA) and CA15-3 levels in the serum of patients with breast cancer

Serum levels of mammary serum antigen (MSA) and CA15-3 were evaluated in 135 individuals in order to determine their single and combined value in the diagnosis and monitoring of breast cancer. Raised MSA levels (greater than 300 IU) were found in 68% of patients with Stage I and II breast cancer compared to only 3% having raised CA15-3 levels (greater than 40 U ml-1). Of 38 patients with Stage IV breast cancer, 95% had raised levels of MSA and CA15-3 combined with each test individually detecting 82% of those with Stage IV disease. No correlation was found between MSA and CA15-3 levels. Four patients being treated for breast cancer were followed over a 5-17 week period; MSA levels correlated with disease course in 3 and CA-15 in 2. The overall sensitivity, specificity and accuracy in detecting breast cancer were 76%, 91% and 96% for MSA; and 47%, 95% and 97% for CA15-3 respectively. When both tests were used together combined evaluation gave the highest sensitivity (84%) and specificity (100%). MSA seems to be superior to CA15-3 for early breast cancer diagnosis and a combination of the two tests gave the best results for metastatic disease.     

Prognostic importance of serum ferritin in patients with Stages III and IV neuroblastoma: the Childrens Cancer Study Group experience

Ferritin was measured in sera obtained at diagnosis from 241 patients with neuroblastoma to determine (a) the incidence of elevated ferritin and (b) the relationship between ferritin level and outcome. Ferritin was infrequently elevated in sera from patients with Stages I and II disease but was abnormally elevated in 37 and 54% of those with Stages III and IV neuroblastoma, respectively. The mean and median levels for each stage were compared and were highest for Stages III and IV disease. Analysis of progression-free survival for children with Stages III and IV disease indicated that elevated ferritin was associated with a significantly poorer prognosis than was normal ferritin and that this correlation was independent of stage and age at diagnosis. Progression-free survival at 24 months of follow-up for patients with Stage III disease with normal ferritin was 76% and with elevated ferritin was 23%. For those with Stage IV disease, progression-free survival was 27 and 3% with normal and elevated ferritin, respectively. We conclude that determination of the level of ferritin in serum at diagnosis is useful for selecting appropriate therapy for patients with Stage III neuroblastoma. Those with normal ferritin (63% of patients) have a good outcome with current therapy, but those with elevated ferritin (37%) do poorly and require more effective therapy. Although ferritin defines subgroups with Stage IV disease, the outcome of all groups must be improved.     

Gastric Cancer Treatments and Survival Trends in the United States

Gastric cancer is the third most common cause of cancer deaths worldwide. Despite evidence-based recommendation for treatment, the current treatment patterns for all stages of gastric cancer remain largely unexplored. This study investigates trends in the treatments and survival of gastric cancer. The National Cancer Database was used to identify gastric adenocarcinoma patients from 2004–2016. Chi-square tests were used to examine subgroup differences between disease stages: Stage I, II/III and IV. Multivariate analyses identified factors associated with the receipt of guideline concordant care. The Kaplan–Meier method was used to assess three-year overall survival. The final cohort included 108,150 patients: 23,584 Stage I, 40,216 Stage II/III, and 44,350 Stage IV. Stage specific guideline concordant care was received in only 73% of patients with Stage I disease and 51% of patients with Stage II/III disease. Patients who received guideline consistent care had significantly improved survival compared to those who did not. Overall, we found only moderate improvement in guideline adherence and three-year overall survival during the 13-year study time period. This study showed underutilization of stage specific guideline concordant care for stage I and II/III disease.     

Body weight, serum cholesterol, and stage of primary breast cancer

To determine if body weight and serum cholesterol are associated with advanced primary breast cancer, the authors compared levels of both by TNM stage and estrogen receptor protein (ERP) concentration in a population of 148 premenopausal and 167 postmenopausal white women with histologically confirmed Stage I, II, and IIIa breast cancer. The women were admitted to Memorial Sloan-Kettering Cancer Center (MSKCC) in New York City between 1982 and 1984. Overweight, whether measured as body weight in pounds, Quetelet index, or body surface area, was not found to be associated with TNM tumor stage, tumor size, extent of axillary node disease, or ERP concentration at mastectomy. Elevated serum cholesterol, either alone or in combination with overweight, also showed no association. When assessed in light of earlier studies, the study findings suggest that if overweight, as defined in this study, and/or elevated serum cholesterol do influence early breast cancer recurrence, they do so other than through an association with advanced primary disease. Suggestions for future research are proposed.     

The value of urinary polyamine assay in stomach cancer. Comparison with serum carcinoembryonic antigen

The authors recently established a new simple enzymatic assay method for total urinary polyamines (Cancer Res 1983; 43:2263-2367). In order to assess the clinical usefulness of measuring total urinary polyamines for the detection of cancer, this method has been applied to the assay of polyamines in the urine of 45 patients with stomach cancer who were classified as to clinical stage. In addition, the value of serum carcinoembryonic antigen (CEA) in the same individual patients was measured for comparison. Percentage of patients with elevated levels of total urinary polyamines increased with International Union Against Cancer (UICC) clinical stage, and was 40.0% (6/15), 50% (3/6), 72.7% (8/11), and 84.6% (11/13) for Stage I, II, III and IV stomach cancer patients, respectively. In 32 patients with stomach cancer of potentially operable Stage I, II, and III, elevated levels of total urinary polyamines were found in 17 patients and elevated levels of serum CEA were found in 5 patients. In 13 patients with inoperable stage IV stomach cancer, elevated levels of total urinary polyamines were found in 11 patients and elevated levels of serum CEA were found in 5 patients. Statistical differences in the detection rate were found between the two markers in these two groups of patients. The combination of these two markers did not increase the detection rate of stomach cancer significantly. The data indicate that the determination of total urinary polyamines by the new assay is clinically useful as a potential marker for the detection of advanced stages of stomach cancer and may be more useful than that of serum CEA. Furthermore, this study demonstrates the relationship between urinary polyamine levels and tumor regression and also the prognostic significance of polyamine determination in stomach cancer patients. In 6 of 13 patients who showed elevated levels of urinary polyamines before surgery, polyamine levels fell to within the normal range after successful surgical removal of tumor. In general, each polyamine level decreased significantly following surgery by paired Student's t test analysis. All of the five Stage IV patients with polyamine levels greater than 4.0 mumol/kg/24 hour died in less than 3 months whereas five of eight Stage IV patients with polyamine levels less than or equal to 4.0 mumol/kg/24 hour survived 10 to 20 months. Statistical differences in survival were observed between Stage IV patients with polyamine levels greater than 4.0 mumol/kg/24 hour and those with polyamine levels less than or equal to 4.0 mumol/kg/24 hour.(ABSTRACT TRUNCATED AT 400 WORDS)     

Double antibody radioimmunoassay for monitoring metastatic breast cancer

We previously reported the production of a panel of murine monoclonal antibodies which recognize glycoproteins abnormally expressed in human breast tumours. Using two of these antibodies, a double antibody radioimmunoassay was designed to quantify levels of these breast tumour marker glycoproteins in serum. Marker levels greater than 28 units were considered abnormal. Using this criterion, 63% and 75% of patients with breast cancer stages I and II, respectively, and 88% of those with metastatic disease were found to have elevated marker levels. Thirteen percent of patients with non-malignant breast disease also had elevated marker levels. Elevated marker levels were also detected in patients with non breast neoplasms. One hundred and eleven women with metastatic disease were followed. Eighty-two percent of those with progressive disease and 73% of those where disease regressed had 20% changes in marker levels. These changes in marker levels preceded by up to 6 months changes in disease state. From these results we conclude that this assay may be useful for monitoring the course of disease in breast cancer patients.