what wpuld cause my cea marker to triple in three months
J Clin Med Res. 2017 Mar; 9(3): 183–187.
Prognostic Impact of the Tumor Marker CA 15-3 in Patients With Breast Cancer and Bone Metastases Treated With Palliative Radiotherapy
Carsten Nieder
aSection of Oncology and Palliative Medicine, Nordland Hospital, 8092 Bodo, Norway
bSection of Clinical Medicine, Faculty of Health Sciences, University of Tromso, 9037 Tromso, Norway
Astrid Dalhaug
aDepartment of Oncology and Palliative Medicine, Nordland Hospital, 8092 Bodo, Kingdom of norway
bDepartment of Clinical Medicine, Faculty of Wellness Sciences, University of Tromso, 9037 Tromso, Kingdom of norway
Ellinor Haukland
aDepartment of Oncology and Palliative Medicine, Nordland Infirmary, 8092 Bodo, Norway
Bard Mannsaker
aDepartment of Oncology and Palliative Medicine, Nordland Hospital, 8092 Bodo, Norway
Adam Pawinski
aDepartment of Oncology and Palliative Medicine, Nordland Hospital, 8092 Bodo, Kingdom of norway
Abstract
Background
The aim of the study was to explore the prognostic impact of unlike abnormal claret tests and the tumor marker CA 15-3 every bit well as established parameters such equally disease extent and receptor status in patients with bone metastases from breast cancer who received palliative radiotherapy in add-on to contemporary systemic treatment.
Methods
This was a retrospective uni- and multivariate analysis of 118 female patients treated in the time menstruum from 2007 to 2014 (median follow-up 28 months).
Results
The median historic period was 61 years and the median time interval from the initial diagnosis of breast cancer was 57 months (median time interval from metastatic disease to radiotherapy was seven months). Only 16% of patients had normal serum CA 15-three. HER2 receptor status correlated with CA 15-three. The median survival was 17.6 months (everyman CA 15-3 quartile), 14.vii months (intermediate), and half-dozen.nine months (highest quartile) (P = 0.002). However, multivariate analysis showed that survival was influenced by extent of extra-skeletal metastases, pleural metastases/effusion, lung metastases, estrogen receptor status, serum C-reactive poly peptide, and anemia with demand for blood transfusion (all P < 0.05) rather than CA 15-3.
Conclusions
Survival was highly variable. The tumor marker CA 15-3 did not provide independent prognostic information. Yet, the results of simple blood tests contributed to the multivariate prognostic model.
Keywords: Biomarker, Bone metastases, Chest cancer, Prognostic factors, Radiotherapy
Introduction
Patients with metastatic breast cancer often accept widespread affliction, for example in the lungs, pleura, liver, lymph nodes and bones. Relatively few patients nowadays with oligometastatic disease [1]. Apply of palliative radiotherapy is common in patients with painful os metastases, which represent a large group [two, 3]. While the chance of long-term survival is higher in patients with limited tumor burden and less aggressive histological type, substantial individual variation exists [iv]. Performance status, organ function, biological affliction characteristics and eligibility for constructive local and systemic treatment are of import prognostic and predictive factors [five]. Prognostic models might be helpful in pre-treatment assessment [6]. In this regard, the function of the tumor marker CA 15-three has not been studied extensively. Therefore, we evaluated the survival and prognostic factors, including a console of claret tests, in patients treated with palliative radiotherapy for os metastases.
Methods
Patients and treatment
This retrospective intention-to-care for written report included 118 consecutive female patients with bone metastases from histologically confirmed chest cancer who received palliative external beam radiotherapy at Nordland Hospital Bodo. All patients were treated between 2007 and 2014. Some presented with synchronous bone metastases at get-go cancer diagnosis, others with delayed or metachronous skeletal interest. Systemic handling was given according to the guidelines of the Norwegian Breast Cancer Group (NBCG), which are stratified by biological subtype and bachelor online. Radionuclide handling was not available.
Claret tests
Lactate dehydrogenase (LDH), albumin, hemoglobin, C-reactive protein (CRP) and alkaline phosphatase (ALP) were part of routine laboratory and radiology assessment in patients with metastatic breast cancer. However, some patients had incomplete tests performed. Tumor marker analyses were performed at the discretion of the treating oncologist. The infirmary'southward electronic patient record system was used to collect all baseline information including laboratory analyses. The latter had to be no older than 2 weeks before the first fraction of radiotherapy, mirroring our previous study [half dozen]. Elevated LDH was divers as ≥ 205 U/L according to the hospitals' reference value (low albumin < 34 chiliad/Fifty; loftier ALP ≥ 105 U/L; normal CRP < 5 mg/L; low hemoglobin < xi.vii g/dL; claret transfusion was given if hemoglobin was < 10 m/dL). Normal CA 15-3 was divers as 0 - 25 kIE/L.
Statistical methods
Actuarial survival from the first day of radiotherapy was calculated with the Kaplan-Meier method. Survival curves of dissimilar groups were compared with the log-rank test. Multivariate analysis consisted of Cox regression (backward conditional method). Associations betwixt unlike variables of interest were assessed with the Chi-square or Fisher exact probability test (two-tailed). A P-value ≤ 0.05 was considered statistically pregnant. Twenty-five patients were live at last follow-up (June 15, 2015). Surviving patients had a median follow-up of 28 months. This study did non require approval from the Regional Committee for Medical and Health Research Ethics (REK Nord), because retrospective quality-of-care analyses are permitted without commission vote. All analyses were carried out according to our institutions' guidelines and with permission to access the patients' information.
Results
Patient characteristics
While 17 patients (15%) had no previous history of cancer, i.eastward. bone metastases at initial diagnosis or de novo stage IV disease, the vast bulk developed metastases at later time points. The median age of our patients was 61 years (range 33 - 87 years). The median fourth dimension interval from the initial diagnosis of breast cancer was 57 months (range 1 - 384 months) and the median time interval from metastatic affliction to radiotherapy was vii months (range 1 - 180 months). The patient characteristics are shown in Table one. The most common fractionation regimen was ten fractions of 3 Gy (55%) followed by 5 fractions of four Gy (24%). Fifty patients (42%) had spinal target volumes. 40-two patients (36%) received simultaneous radiotherapy to ii target volumes and 16 (14%) to at least iii target volumes. All simply one patient completed their prescribed class of radiotherapy.
Table one
Patient Characteristics Before Radiotherapy (RT) and Survival Outcomes (n = 118)
| Parameter | n | % | Median survival, months | P-value |
|---|---|---|---|---|
| Estrogen receptor (ER) positive | 91 | 77 | 15.6 | |
| Estrogen receptor (ER) negative | 27 | 23 | 5.8 | 0.004 |
| HER2 positivea | xx | eighteen | xiv.iv | |
| HER2 negativea | xc | 82 | 12.4 | 0.65 |
| Triple negativea | 22 | 20 | five.5 | |
| ER positive HER2 negativea | 68 | 62 | 15.5 | |
| ER negative HER2 positivea | five | five | 11.four | |
| ER and HER2 positivea | 15 | xiv | fifteen.ix | 0.007b |
| Metastases at first diagnosisa | 17 | 15 | 6.9 | |
| Metachronous metastatic diseasea | 98 | 85 | fourteen.7 | 0.13 |
| Interval from metastatic illness to RT ≤ 1 montha | 32 | 28 | 17.6 | |
| Interval from metastatic disease to RT two - 6 monthsa | 24 | 21 | xiii.9 | |
| Interval from metastatic disease to RT seven - 12 monthsa | 14 | 12 | seven.5 | |
| Interval from metastatic disease to RT xiii - 59 monthsa | 35 | 30 | nine.0 | |
| Interval from metastatic illness to RT ≥ lx monthsa | 10 | nine | 9.0 | 0.02b |
| No extra-skeletal visceral metastases | 57 | 48 | 22.nine | |
| 1 site of visceral metastases, due east.g. lung(s) | 43 | 36 | 8.2 | |
| More 1 site of visceral metastases | xviii | xv | five.ane | 0.0001b |
| Liver metastases | 36 | 31 | 7.3 | 0.0001 |
| Lung metastases | 38 | 32 | 7.iii | 0.004 |
| Pleural metastases/effusion | 19 | 16 | iii.9 | 0.0001 |
| Brain metastases | four | 3 | three.4 | 0.0001 |
| ECOG PS 0 | 32 | 27 | 27.3 | |
| ECOG PS 1 | 38 | 32 | 15.six | |
| ECOG PS two | 32 | 27 | ten.iii | |
| ECOG PS 3 - 4 | 16 | 14 | three.1 | 0.0001b |
| Received no previous RT | 26 | 22 | 14.9 | |
| One previous course | 51 | 43 | 16.ix | |
| At least two previous courses | 41 | 35 | ix.0 | 0.01b |
| Serum albumin normala | 94 | 84 | 15.5 | |
| Serum albumin lowa | eighteen | 16 | 5.1 | 0.001 |
| Serum LDH normala | 45 | 45 | 27.0 | |
| Serum LDH loftiera | 56 | 55 | 6.9 | 0.0001 |
| Serum ALP normala | 47 | 45 | 21.ane | |
| Serum ALP loftiera | 58 | 55 | 9.0 | 0.0001 |
| Serum CRP normala | 55 | 50 | 22.9 | |
| Serum CRP loftier (≤ 30)a | 29 | 26 | 12.seven | |
| Serum CRP high (31 - sixty)a | thirteen | 12 | 5.viii | |
| Serum CRP high (> 60)a | 14 | 13 | 5.0 | 0.0001b |
| Hemoglobin normala | fourscore | 71 | xv.9 | |
| Hemoglobin lowa | 33 | 29 | eight.2 | 0.004 |
| Received blood transfusion earlier RT | ix | 8 | 9.0 | 0.01 |
| CA 15-three normala | 14 | 16 | 36.2 | |
| CA fifteen-3 higha | 75 | 84 | 12.two | 0.007 |
Tumor marker analyses
CA xv-3 was analyzed in 89 patients (75%) and normal in 14 of these (16%). The median value was 61 kIE/L (range 9 - 30,000 and interquartile range (25-75%) 32.5 - 208). Patients with HER2 positive master tumors had significantly higher likelihood of normal CA xv-3 (36% vs. 13% in HER2 negatives, P = 0.049). No meaning correlation between patterns of metastatic disease, extra-skeletal disease extent or estrogen receptor status and CA fifteen-3 abnormality was observed. Effigy 1 shows the correlation between CA fifteen-3 and survival (median 17.six months, xiv.7 months, and 6.9 months, P = 0.002).
Actuarial Kaplan-Meier survival curves for 89 patients with bone metastases from breast cancer stratified by serum CA 15-3 level (median 17.6 for lowest quartile (< 32.5 kIE/L) versus xiv.7 months for intermediate levels and half dozen.ix months for highest quartile (> 208 kIE/L), P = 0.002), log-rank test.
Overall survival
Median survival was 12.7 months and 22% of the patients were live after three years. Median survival from initial diagnosis of metastatic affliction was 20 months. As shown in Table i, a large number of patient and disease characteristics were associated with survival after radiotherapy. These included for example breast cancer type, patterns of metastatic disease, CA xv-3, LDH, albumin, CRP, hemoglobin and ALP, but not historic period or radiotherapy-related factors. All parameters with significant P-value were included in a multivariate regression analysis, which confirmed six independent prognostic factors: absenteeism or limited extent of extra-skeletal metastases (P = 0.0001), no pleural metastases/effusion (P = 0.0001), CRP < five mg/L (P = 0.0001), positive estrogen receptor (P = 0.001), no lung metastases (P = 0.001), and no demand for blood transfusion (P = 0.048).
Word
Bone metastases from breast cancer are a common clinical challenge for oncologists worldwide [1, 5]. Jensen et al estimated the overall and almanac incidence of skeletal metastases and related events (SREs) in newly diagnosed chest cancer patients in Kingdom of denmark from 1999 to 2007 using the Danish National Patient Registry [7]. Of the 35,912 patients with chest cancer, 178 (0.v%) presented with skeletal involvement at the time of initial cancer diagnosis, and of these, 43% developed an SRE during follow-up. The term SRE relates to pathological fractures, orthopedic surgery, spinal cord pinch and utilization of radiotherapy. A total of 1,272 of 35,690 (3.6%) patients without distant disease at kickoff diagnosis adult skeletal metastases during a median follow-upwards time of 3.4 years. Among these patients, 46% later on developed an SRE. The 5-year survival charge per unit of patients with os metastases was 8% [eight].
Given that survival is highly variable, prognostic models are necessary to inform choice of handling and counsel patients. Every bit a upshot of previous research [6], we were interested in serum biomarkers, in particular the tumor marking CA 15-3. In previous studies that included multivariate models, elevated CA fifteen-3 earlier surgery was significantly associated with tumor size, axillary node involvement and advanced stage [9, 10]. Moreover, in phase-matched analyses prognosis of patients with elevated serum CA xv-iii was worse compared to those with normal value. Further studies demonstrated that serial postoperative surveillance of CA xv-three values during follow-up may be useful for early detection of recurrent breast cancer [xi-13].
In a retrospective report, Geng et al analyzed the clan of serum CA 15-3 levels with clinicopathological parameters in women with metastatic breast cancer and determined whether the summit of the tumor mark was correlated with metastatic sites [14]. In their study, 136 patients had only ane metastatic site and 148 patients had involvement of several sites. 60-7 pct of patients with several sites of affliction had an increased CA 15-three level. This figure was significantly college than the 47% reported in women with a single metastasis (P = 0.001). In a different study, increased CA fifteen-iii levels were found more frequently in patients with liver metastases and in those with pleural effusion [15]. Whereas Yerushalmi and coworkers did not identify significant differences in CA fifteen-3 levels betwixt different sites of metastasis [xvi], Al-Jarallah et al reported that the highest proportions of pathologically elevated CA 15-3 levels were detected in women with os metastases [17]. In our study, the simply clinicopathological parameter associated with elevated CA 15-three levels was HER2 receptor status. Our study shares limitations with previous ones, due east.chiliad. the retrospective study design. Considering merely 89 patients had their tumor mark analyzed, many subgroups were relatively small and therefore the statistical ability was not optimal.
A typical patient in our study was a postmenopausal woman with estrogen receptor positive and HER2 negative illness who developed metachronous metastases (Table 1). Co-ordinate to the national guidelines, such patients receive zoledronic acid and several lines of sequential hormonal and cytotoxic therapy, depending on visceral tumor load, response to previous therapy and other parameters. We found a large number of patient and disease characteristics to be associated with survival after radiotherapy. These included for example breast cancer type (shortest survival for triple negative status, median 5.5 months), patterns of metastatic disease (longest survival for bone only disease, median 22.9 months), CA fifteen-3, LDH, albumin, hemoglobin, CRP and ALP, but not age. However, merely six independent prognostic factors were confirmed by multivariate analysis: presence of extra-skeletal metastases together with number of involved sites, pleural metastases/effusion, lung metastases, elevated CRP, negative estrogen receptor, and anemia with need for blood transfusion. Interestingly, performance condition was less important than patterns of metastases and the other factors only mentioned. A potential explanation might exist that poor performance status resulting from bone hurting often improves rapidly after radiotherapy. The touch on of hormone receptor condition is well known from the literature [1, 4, five]. But like LDH, ALP and albumin, increased CA 15-3 was not significant in our multivariate analysis.
In contrast, Turanli et al institute CA 15-3 to be an independent cistron associated with overall survival [18]. However, their study included a dissimilar patient population with isolated os metastases treated between June 2004 and Jan 2007 (129 consecutive female patients). Serum CA 15-3 levels were elevated in 63% of patients with isolated bone metastases. In multivariate analysis, the serum CA xv-3 level influenced survival with a relative hazard of 2.five (95% confidence interval: 1.36 - 4.64, P = 0.003). In an older study of a more than diverse patient population (1997 - 2001; due north = 492), which was better comparable to ours, James et al also reported that CA 15-three was associated with survival [5]. These authors studied patients with newly diagnosed metastatic breast cancer, including those with metachronous presentation and those with metastatic disease at the time of initial diagnosis of breast cancer. Several of the factors analyzed were significantly associated with improve survival in women with bone metastases. These were estrogen receptor condition (P = 0.0003), histological class (P = 0.034), additional sites of metastatic disease (P = 0.0004), patient historic period (P = 0.0003), number of hot spots on isotope bone scan (P = 0.040) and metastasis-costless interval (P = 0.0045). In addition, the tumor markers CA 15-3 and CEA were significantly related to survival likewise (P = 0.0026 and 0.017, respectively). In multivariate assay, long metastasis-free interval, absence of metastases at sites other than os, estrogen receptor positivity, and normal CEA and CA 15-3 values at presentation contributed independently towards longer survival from time of presentation with skeletal metastases.
Bidard et al analyzed CA xv-3 levels in 1,298 patients, of whom 892 (69%) had increased values [19]. According to the univariate analysis, abnormal CA 15-3 was significantly associated with decreased overall survival (hazard ratio: 1.59, 95% conviction interval: 1.31 - 1.93, P < 0.0001). When added to their clinicopathological models, logistic regression tests showed that the dichotomized marker (< upper limit of normal vs. ≥ upper limit of normal) added some prognostic information only increases in C-indices were negligible. Their master focus was on circulating tumor cells, which contributed better prognostic information than CA xv-iii. Other innovative markers are also of considerable involvement [20-23]. Even so, none of these are function of routine clinical practise nonetheless. A drawback of most studies, resulting in difficulties with comparison of the results, is that not all potential prognostic factors were included, e.one thousand. CRP and hemoglobin.
Conclusions
Many patients survived for several years rather than a few months merely. The tumor marker CA xv-3 did non provide independent prognostic information. Nevertheless, the results of simple blood tests contributed to the multivariate model.
Disclosures
The authors declare that they have no conflicts of interest. No funding was received.
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Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5289136/
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