***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    Input: Between 1977 and 1993 , 384 breast cancer patients were followed up post-operatively every 4 or 6 months with a serum tumour marker panel ( CEA-TPA-CA15 - 3 ) and the usual imaging techniques .  Twenty-eight patients were treated 13.5 + /- 10 months ( mean + /- s.d . ) before the clinical and /or radiological occurrence of distant metastases that were suspected because of an increase in the tumour markers ( patients treated ' early ' ) . Their outcome was compared with that of 22 similar patients who were treated only after a definite radiological diagnosis was achieved ( patients treated ' not early ' ) . The median survivals from mastectomy and salvage treatment were also compared for the two groups . The groups were similar for all the major prognostic factors ( menopause , staging , hormone dependency ) . In the group treated ' early ' , the lead time from the tumour marker increase to the clinical and radiological signs of metastases was significantly longer than that of the group not treated ' early ' ( 13.5 + /- 10 vs 3.4 + /- 2.8 months respectively ; P < 0.001 by unpaired t-test ) . For patients treated ' early ' , the survival curves up to 30 months after salvage treatment and up to 72 months after mastectomy showed greater survival than those for the patients treated later ( 42.9 % vs 13.6 % and 42.9 % vs 22.7 % respectively ; P = 0.04 in both instances ) . These data suggest that treatment triggered by rising tumour markers before clinical and /or radiological appearance of distant metastases can be useful in prolonging both the asymptomatic interval and the duration of response of some relapsed patients . R and omized prospect i ve trials must be encouraged to confirm these data and to better evaluate the effect on the disease-free survival ( DFS ) and overall survival ( OS ) of ' early ' salvage treatment protocol Summary To evaluate the utility of CEA and CA 15.3 for early diagnosis of recurrence , serial serum determinations of both antigens were performed in 1023 patients ( follow-up : 1–10 years , mean 6.2 years ) with primary breast cancer ( CA 15.3 in 533 cases ) and no evidence of residual disease ( NED ) after radical treatment ( radical mastectomy or simple mastectomy and radiotherapy ) . 246 patients developed metastases during follow-up . Results : CEA and CA 15.3 were elevated ( > 10 ng/ml or > 60 U/ml , respectively ) prior to diagnosis in 40 % ( 98/246 ) and 41 % ( 37/91 ) of the patients with recurrence , with a lead time of 4.9 ± 2.2 and 4.2 ± 2.3 months , respectively . When patients with locoregional recurrences were excluded , sensitivity improved to 46 % ( CEA ) and 54 % ( CA 15.3 ) , and to 64 % with both tumor markers ( CEA and /or CA 15.3 ) . Higher levels of both CEA and CA 15.3 at diagnosis of recurrence , higher sensitivity in early diagnosis of relapse , and a higher lead time were found in ER+ ( CEA ) or PgR+ patients ( CA 15.3 ) than in those that were negative for these receptors in the primary tumor ( p < 0.001 ) . Specificity of the tumor markers was 99 % for both CEA ( 777 NED patients ) and for CA 15.3 ( 444 NED patients ) , respectively . In conclusion , CEA and CA 15.3 are useful tools for early diagnosis of metastases , mainly in those patients with ER+ or PR+ tumors OBJECTIVES R and omised trials on breast cancer showed no significant benefit from post-operative follow-up with clinical and /or conventional radiological means . We hypothesised that carcinoembryonic antigen ( CEA ) , tissue polipeptyde antigen ( TPA ) , breast cancer associated antigen 115 D8/DF3 ( CA15.3 ) tumour marker panel is sensitive enough for significantly anticipating salvage treatment and prolonging survival of relapsing breast cancer patients . METHODS From October 1981 to May 1999 , 68 ( 62 % ) of 109 patients with distant metastases were recruited . Thirty-six ( 53 % ) received salvage treatment at the time of significant increase in one or more components of CEA-TPA-CA15.3 tumour marker panel and negative instrumental examinations ( " tumour marker guided " treatment ) and 32 ( 47 % ) were treated only after radiological confirmation of metastases ( conventional treatment ) . The prognostic factors of the two groups did not show any statistically significant difference . RESULTS The time from one or more tumour marker increase to clear clinical and /or radiological signs of distant metastases ( lead time ) was significantly prolonged in the 36 patients with " tumour marker guided " treatment ( 17.3 + /- 13.1 vs. 2.9 + /- 2.9 months , P < 0.001 , Wilcoxon test ) as well as the survival curves from salvage therapy and from mastectomy ( the proportion of survivors was : at 36 months from salvage therapy 28 % vs. 9 % , P = 0.0094 ; at 84 months from mastectomy 42 % vs. 19 % , P = 0.0017 ) . The multivariate Cox analysis showed that time from mastectomy to tumour marker increase and " tumour marker guided  "  salvage treatment were the only significantly different variables ( P = 0.00001 and 0.005 , respectively ) . CONCLUSION These data point out that " tumour marker guided " salvage treatment significantly prolongs disease-free and overall survivals of relapsing responsive patients Altogether , 243 female breast cancer patients with localised disease diagnosed between 1991 and 1995 in the Tampere University Hospital area were followed prospect ively after primary treatment until the first relapse . In the follow-up period , the  serum tumour marker Ca 15 - 3  was analysed every 6 months to ascertain the validity of this marker in detecting the first relapse . The sensitivity and specificity of the test were analysed in different metastatic situations . During the 5 years of follow-up , 59 ( 24 % ) relapses were discovered . Ca 15 - 3 was elevated in 21/59 ( 36 % ) of the relapsed cases at least once . The 59 patients were subjected to 199 tests , of which 25 ( 13 % ) were positive . Among the 184 patients without recurrence , there were 6 ( 3 % ) with a positive Ca 15 - 3 level . The test failed to detect locoregional relapse or contralateral breast cancer . It was elevated in approximately half of bone-only metastases and in all of the liver-only metastases . In the pulmonary-only recurrences , the marker value was not elevated . We conclude that the  Ca 15 - 3 tumour marker test  is specific , but not sensitive enough to indicate the first relapse earlier than other methods . The positive predictive value especially remained poor in patients with a relatively good prognosis . Our results confirm that the test is not suitable alone for breast cancer follow-up BACKGROUND CA 15 - 3 is the most widely used serum marker in breast cancer . Currently , its main uses are in the surveillance of patients with diagnosed disease and monitoring the treatment of patients with advanced disease . METHODS  Preoperative CA 15 - 3 concentrations were measured prospect ively in 600 patients with histologically confirmed breast cancer . Marker concentrations were related to patient outcome by both univariate and multivariate analysis . RESULTS After a median follow-up of 6.27 years , patients with high preoperative concentrations of CA 15 - 3 ( > 30 units/L ) had a significantly shorter overall survival pattern than those with low concentrations . As a prognostic factor , CA 15 - 3 was independent of tumor size , axillary node status , and patient age . As well as being prognostic in the total population of patients , CA 15 - 3 also predicted outcome in different subgroups of patients , including those with both node-negative and node-positive disease , those who were both estrogen receptor (ER)-negative and ER-positive , and those younger and older that 50 years of age . CA 15 - 3 was also predictive of outcome irrespective of the type of adjuvant therapy administered , i.e. , whether adjuvant hormone therapy , adjuvant chemotherapy , or radiotherapy was administered . CONCLUSION Assay of CA 15 - 3 is a relatively inexpensive , convenient , and noninvasive method for evaluating prognosis in newly diagnosed breast cancer patients Increasing levels of tumor markers such as carcinoembryonic antigen , mucin-like carcinoma-associated antigen ( MCA ) , CA 15.3 , and monoclonal antibody H23 in  breast cancer patients following the treatment of the primary disease and adjuvant radiation and chemotherapy  reflect sub clinical development of metastatic disease . Overt metastatic disease is usually incurable and prolongation of life at this stage is impossible , and the treatment is only palliative . The efficacy of tamoxifen , a least-toxic agent , in the treatment of early and minimal metastatic disease detected only by increasing serum levels of MCA was studied prospect ively in a r and omized study . Our preliminary , albeit encouraging , results showed that the rate of relapse within a median follow-up period of 11 months was 24.1 % in the control arm as compared with 0 % in the tamoxifen arm ( Fisher 's exact test , P=0.012 ) . None of the patients with a relapse had positive progesterone receptors ( PR ) . We may carefully conclude that early treatment may be warranted in young patients with negative PR and continuously increasing serum levels of the marker BACKGROUND Follow-up tests for patients after diagnosis and primary treatment of breast cancer are routinely performed . However , the usefulness of these follow-up parameters remains unclear . We determined the yield of a variety of blood tests used to detect the presence of overt metastatic disease . METHODS 4105 patients enrolled in International ( Ludwig ) Breast Cancer Study Group ( IBCSG ) r and omized clinical trials from 1978 to 1985 were analyzed for abnormal or equivocal findings in six routine blood tests obtained every 3 months for the first two years , every six months for years 3 - 5 and yearly thereafter . The relationship of test results to the occurrence of overt metastatic disease was evaluated . The relapses were categorized as follows in order to estimate the yield of the different tests for relevant sites of metastases : any breast cancer relapse , bone + /- other ; liver + /- other . RESULTS Alkaline phosphatase alone was abnormal in a high proportion of patients with either bone metastases , liver metastases , or both . SGOT and gamma-GT were also sensitive for patients with liver metastases . Bilirubin , serum calcium , and serum creatinine were relatively insensitive indicators of relapse . Abnormal test results were reported sometime during a patient 's disease-free period for 3 % to 6 % of patients , depending on the test . CONCLUSIONS Alkaline phosphatase was the most effective blood test to distinguish patients with relapse from those without relapse . It is inexpensive and its yield is relatively high for predicting liver and bone metastases . The routine use of the other tests analyzed to detect metastases was not justified Objective The significance of serum tumor markers in monitoring advanced breast cancer patients is still controversial . To clarify this issue , the Tumor Marker Study Group of the Japanese Breast Cancer Society conducted a prospect i ve study . Methods Patients with advanced breast cancer who were treated with systemic therapy between January and December 2002 were recruited from five collaborative institutes in Japan . The patients were monitored every four weeks using three serum tumor markers , CEA , CA 15 - 3 and NCC-ST-439 during the therapy . Results Findings from 108 eligible patients were analyzed . The pretreatment positivity rates were 51.9 % for CEA , 50 % for CA 15 - 3 , and 34.3 % for NCC-ST-439 . The changes in each marker level at 8 and 12 weeks but not at 4 weeks after the start of therapy seemed to correlate with the response to therapy in pretreatment marker-positive patients but not in negative patients . The Cox proportional hazard model revealed a greater than 20 % reduction in CEA , CA 15 - 3 or NCC-ST-439 levels at 4 , 8 and /or 12 weeks after the start of therapy to be an independent predictive factor for longer time-to-progression ( TTP ) in pretreatment marker-positive patients . Conclusion This prospect i ve study supported the findings obtained from our previous retrospective study that in pretreatment marker-positive patients 1 ) the changes in serum tumor marker levels after the start of therapy correlate with the response to therapy ; and 2 ) a greater than 20 % reduction in the tumor marker levels was a favorable predictive factor for TTP during systemic therapy . When the pretreatment serum level of these markers is over the respective cut-off value , sequential measurement of them may be useful for evaluating the efficacy of treatment as well as monitoring the outcome of patients with advanced breast cancer The purpose of this prospect i ve study was to evaluate the usefulness of tumor marker CA 15.3 determined at the time of primary diagnosis as a prognostic factor in breast cancer . The power of CA 15.3 to predict survival was compared to established prognostic markers , namely stage , grade , receptor status , and histological subtype . CA 15.3 was abnormal ( ≥30 U 
    Output:
    
RESULTS Because of a lack of sensitivity for early disease and lack of specificity , none of the available markers is of value for the detection of early breast cancer .
Although serial determinations of tumor markers after primary treatment for breast cancer can pre clinical ly detect recurrent/metastatic disease with lead times of approximately 2 - 9 months , the clinical value of this lead time remains to be determined .
Serum markers , however , are the only vali date d approach for monitoring treatment in patients with advanced disease that can not be evaluated by use of conventional criteria .
CA 15 - 3 is one of the first circulating prognostic factors for breast cancer .