Skip to main content
Erschienen in: Breast Cancer 4/2020

10.02.2020 | Original Article

Tumor markers CA15-3, CA125, CEA and breast cancer survival by molecular subtype: a cohort study

verfasst von: Junxian Li, Luyang Liu, Ziwei Feng, Xin Wang, Yubei Huang, Hongji Dai, Liwen Zhang, Fangfang Song, Dezheng Wang, Pengyu Zhang, Baoshan Ma, Haixin Li, Hong Zheng, Fengju Song, Kexin Chen

Erschienen in: Breast Cancer | Ausgabe 4/2020

Einloggen, um Zugang zu erhalten

Abstract

Background

The burden of breast cancer has grown rapidly in China during recent decades. However, the association between tumor markers (CA15-3, CA125, and CEA) and breast cancer survival among certain molecular subtypes is unclear; we described this association in a large, population-based study.

Methods

We conducted a cohort study including 10,836 women according to the Tianjin Breast Cancer Cases Cohort. Demographic and epidemiologic data were collected by a structured face-to-face questionnaire. Clinico-pathological parameters were abstracted from medical records, and follow-up information was obtained once a year by telephone. The primary endpoints were breast cancer-specific survival (BCSS) and disease-free survival (DFS). We utilized the Cox proportional hazard model to calculate hazard ratios (HRs) and 95% confidence intervals (CI).

Results

Among all patients, elevated CA15-3 and CEA exhibited consistently and statistically significant reduced BCSS compared with normal ones (CA15-3: HR 1.54, 95% CI 1.01–2.34; CEA: HR 2.45, 95% CI 1.40–4.30). Similar patterns of association were observed for DFS (CA15-3: HR 2.09, 95% CI 1.44–3.02; CEA: HR 2.71, 95% CI 1.71–4.27). Moreover, in luminal A subtype, high CA15-3 and CEA levels were associated with decreased BCSS (CA15-3: HR 4.47, 95% CI 2.04–9.81; CEA: HR 3.79, 95% CI 1.68–8.55) and DFS (CA15-3: HR 4.06, 95% CI 2.29–7.18, CEA: HR 3.41, 95% CI 1.75–6.64). In basal-like subtype, elevated CEA conferred reduction for BCSS (HR 5.13, 95% CI 1.65–15.9). However, no association was observed between CA125 and breast cancer outcome.

Conclusions

Preoperative CA15-3 and CEA levels differ in breast cancer molecular subtypes and yield strong prognostic information in Chinese women with breast cancer. Measuring CA15-3 and CEA levels before surgery may have the potential in predicting breast cancer survival and offering patients’ personalized treatment strategy among luminal A and basal-like subtypes.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.
2.
Zurück zum Zitat Li H, Zheng RS, Zhang SW, Zeng HM, Sun KX, Xia CF, et al. Incidence and mortality of female breast cancer in China, 2014. Zhonghua Zhong Liu Za Zhi. 2018;40(3):166–71.PubMed Li H, Zheng RS, Zhang SW, Zeng HM, Sun KX, Xia CF, et al. Incidence and mortality of female breast cancer in China, 2014. Zhonghua Zhong Liu Za Zhi. 2018;40(3):166–71.PubMed
3.
Zurück zum Zitat Campbell HE, Gray AM, Harris AL, Briggs AH, Taylor MA. Estimation and external validation of a new prognostic model for predicting recurrence-free survival for early breast cancer patients in the UK. Br J Cancer. 2010;103(6):776–86.CrossRef Campbell HE, Gray AM, Harris AL, Briggs AH, Taylor MA. Estimation and external validation of a new prognostic model for predicting recurrence-free survival for early breast cancer patients in the UK. Br J Cancer. 2010;103(6):776–86.CrossRef
4.
Zurück zum Zitat Soerjomataram I, Louwman MW, Ribot JG, Roukema JA, Coebergh JW. An overview of prognostic factors for long-term survivors of breast cancer. Breast Cancer Res Treat. 2008;107(3):309–30.CrossRef Soerjomataram I, Louwman MW, Ribot JG, Roukema JA, Coebergh JW. An overview of prognostic factors for long-term survivors of breast cancer. Breast Cancer Res Treat. 2008;107(3):309–30.CrossRef
5.
Zurück zum Zitat Perey L, Hayes DF, Maimonis P, Abe M, O'Hara C, Kufe DW. Tumor selective reactivity of a monoclonal antibody prepared against a recombinant peptide derived from the DF3 human breast carcinoma-associated antigen. Cancer Res. 1992;52(9):2563–8.PubMed Perey L, Hayes DF, Maimonis P, Abe M, O'Hara C, Kufe DW. Tumor selective reactivity of a monoclonal antibody prepared against a recombinant peptide derived from the DF3 human breast carcinoma-associated antigen. Cancer Res. 1992;52(9):2563–8.PubMed
6.
Zurück zum Zitat Falkson HC, Watt JJ, Der V, Portugal MA, Pitout MJ, Falkson G. Carcinoembryonic antigen in patients with breast cancer: an adjunctive tool to monitor response and therapy. Cancer. 1978;42:1308–13.CrossRef Falkson HC, Watt JJ, Der V, Portugal MA, Pitout MJ, Falkson G. Carcinoembryonic antigen in patients with breast cancer: an adjunctive tool to monitor response and therapy. Cancer. 1978;42:1308–13.CrossRef
7.
Zurück zum Zitat Mughal AW, Hortobagyi GN, Fritsche HA, Buzdar AU, Yap HY. Blumenschein GR, Serial plasma carcinoembryonic antigen measurements during treatment of metastatic breast cancer. JAMA. 1983;249(14):1881.CrossRef Mughal AW, Hortobagyi GN, Fritsche HA, Buzdar AU, Yap HY. Blumenschein GR, Serial plasma carcinoembryonic antigen measurements during treatment of metastatic breast cancer. JAMA. 1983;249(14):1881.CrossRef
8.
Zurück zum Zitat Reinartz S, Failer S, Schuell T, Wagner U. CA125 (MUC16) gene silencing suppresses growth properties of ovarian and breast cancer cells. Eur J Cancer. 2012;48(10):1558–699.CrossRef Reinartz S, Failer S, Schuell T, Wagner U. CA125 (MUC16) gene silencing suppresses growth properties of ovarian and breast cancer cells. Eur J Cancer. 2012;48(10):1558–699.CrossRef
9.
Zurück zum Zitat Molina R, Barak V, Dalen AV, Duffy MJ, Einarsson R, Gion M, et al. Tumor markers in breast cancer—European group on tumor markers recommendations. Tumour Biol. 2005;26(2):281–93.CrossRef Molina R, Barak V, Dalen AV, Duffy MJ, Einarsson R, Gion M, et al. Tumor markers in breast cancer—European group on tumor markers recommendations. Tumour Biol. 2005;26(2):281–93.CrossRef
10.
Zurück zum Zitat Harris L, Fritsche H, Mennel R, Norton L, Ravdin P, Taube S, American Society of Clinical Oncology, et al. 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol. 2007;25(33):5287–312.CrossRef Harris L, Fritsche H, Mennel R, Norton L, Ravdin P, Taube S, American Society of Clinical Oncology, et al. 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol. 2007;25(33):5287–312.CrossRef
11.
Zurück zum Zitat Baskiä D, Ristiä P, Matiä S, Bankoviä D, Popoviä S, Arsenijeviä N. Clinical evaluation of the simultaneous determination of CA 15–3, CA 125 and sHER2 in breast cancer. Biomarkers. 2007;12(6):657–67.CrossRef Baskiä D, Ristiä P, Matiä S, Bankoviä D, Popoviä S, Arsenijeviä N. Clinical evaluation of the simultaneous determination of CA 15–3, CA 125 and sHER2 in breast cancer. Biomarkers. 2007;12(6):657–67.CrossRef
12.
Zurück zum Zitat Zhao S, Mei Y, Wang J, Zhang K, Ma R. Different levels of CEA, CA153 and CA125 in milk and benign and malignant nipple discharge. PLoS ONE. 2016;11(6):e0157639.CrossRef Zhao S, Mei Y, Wang J, Zhang K, Ma R. Different levels of CEA, CA153 and CA125 in milk and benign and malignant nipple discharge. PLoS ONE. 2016;11(6):e0157639.CrossRef
13.
Zurück zum Zitat Marić P, Ozretić P, Levanat S, Oresković S, Antunac K, Beketić-Oresković L. Tumor markers in breast cancer—evaluation of their clinical usefulness. Coll Antropol. 2011;35(1):241–7.PubMed Marić P, Ozretić P, Levanat S, Oresković S, Antunac K, Beketić-Oresković L. Tumor markers in breast cancer—evaluation of their clinical usefulness. Coll Antropol. 2011;35(1):241–7.PubMed
14.
Zurück zum Zitat Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thürlimann B, Senn HJ, et al. Strategies for subtypesṣ—dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol. 2011;22(8):1736–47.CrossRef Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thürlimann B, Senn HJ, et al. Strategies for subtypesṣ—dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol. 2011;22(8):1736–47.CrossRef
15.
Zurück zum Zitat Holm J, Eriksson L, Ploner A, Eriksson M, Rantalainen M, Li J, et al. Assessment of breast cancer risk factors reveals subtype heterogeneity. Cancer Res. 2017;77(13):3708–17.CrossRef Holm J, Eriksson L, Ploner A, Eriksson M, Rantalainen M, Li J, et al. Assessment of breast cancer risk factors reveals subtype heterogeneity. Cancer Res. 2017;77(13):3708–17.CrossRef
16.
Zurück zum Zitat Zhang L, Huang Y, Feng Z, Wang X, Li H, Song F, et al. Comparison of breast cancer risk factors among molecular subtypes: a case-only study. Cancer Med. 2019;20:20. Zhang L, Huang Y, Feng Z, Wang X, Li H, Song F, et al. Comparison of breast cancer risk factors among molecular subtypes: a case-only study. Cancer Med. 2019;20:20.
17.
Zurück zum Zitat Lee JS, Park S, Park JM, Cho JH, Kim SI, Park BW. Elevated levels of preoperative CA 15–3 and CEA serum levels have independently poor prognostic significance in breast cancer. Ann Oncol. 2013;24(5):1225–311.CrossRef Lee JS, Park S, Park JM, Cho JH, Kim SI, Park BW. Elevated levels of preoperative CA 15–3 and CEA serum levels have independently poor prognostic significance in breast cancer. Ann Oncol. 2013;24(5):1225–311.CrossRef
18.
Zurück zum Zitat Gion M, Boracchi P, Dittadi R, Biganzoli E, Peloso L, Mione R, et al. Prognostic role of serum CA15.3 in 362 node-negative breast cancers. An old player for a new game. Eur J Cancer. 2002;38(9):1181–8.CrossRef Gion M, Boracchi P, Dittadi R, Biganzoli E, Peloso L, Mione R, et al. Prognostic role of serum CA15.3 in 362 node-negative breast cancers. An old player for a new game. Eur J Cancer. 2002;38(9):1181–8.CrossRef
19.
Zurück zum Zitat Rafael M, Auge JM, Blanca F, Gabriel Z, Jaume P, Montserrat MO, et al. Prospective evaluation of carcinoembryonic antigen (CEA) and carbohydrate antigen 15.3 (CA 15.3) in patients with primary locoregional breast cancer. Clin Chem. 2010;56(7):1148.CrossRef Rafael M, Auge JM, Blanca F, Gabriel Z, Jaume P, Montserrat MO, et al. Prospective evaluation of carcinoembryonic antigen (CEA) and carbohydrate antigen 15.3 (CA 15.3) in patients with primary locoregional breast cancer. Clin Chem. 2010;56(7):1148.CrossRef
20.
Zurück zum Zitat Berruti A, Tampellini M, Torta M, Buniva T, Gorzegno G, Dogliotti L. Prognostic value in predicting overall survival of two mucinous markers: CA 15–3 and CA 125 in breast cancer patients at first relapse of disease. Eur J Cancer. 1994;30(14):2082–4.CrossRef Berruti A, Tampellini M, Torta M, Buniva T, Gorzegno G, Dogliotti L. Prognostic value in predicting overall survival of two mucinous markers: CA 15–3 and CA 125 in breast cancer patients at first relapse of disease. Eur J Cancer. 1994;30(14):2082–4.CrossRef
21.
Zurück zum Zitat Gasparini G, Toi M, Gion M, Verderio P, Dittadi R, Hanatani M, et al. Prognostic significance of vascular endothelial growth factor protein in node-negative breast carcinoma. J Natl Cancer Inst. 1997;89:139–47.CrossRef Gasparini G, Toi M, Gion M, Verderio P, Dittadi R, Hanatani M, et al. Prognostic significance of vascular endothelial growth factor protein in node-negative breast carcinoma. J Natl Cancer Inst. 1997;89:139–47.CrossRef
22.
Zurück zum Zitat Ebeling FG, Stieber P, Untch M, Nagel D, Konecny GE, Schmitt UM, et al. Serum CEA and CA 15–3 as prognostic factors in primary breast cancer. Br J Cancer. 2002;86(8):1217.CrossRef Ebeling FG, Stieber P, Untch M, Nagel D, Konecny GE, Schmitt UM, et al. Serum CEA and CA 15–3 as prognostic factors in primary breast cancer. Br J Cancer. 2002;86(8):1217.CrossRef
23.
Zurück zum Zitat Clinton SR, Beason KL, Bryant S, Johnson JT, Jackson M, Wilson C, et al. A comparative study of four serological tumor markers for the detection of breast cancer. Biomed Sci Instrum. 2003;39:408–14.PubMed Clinton SR, Beason KL, Bryant S, Johnson JT, Jackson M, Wilson C, et al. A comparative study of four serological tumor markers for the detection of breast cancer. Biomed Sci Instrum. 2003;39:408–14.PubMed
24.
Zurück zum Zitat Li X, Dai D, Chen B, Tang H, Xie X, Wei W. Determination of the prognostic value of preoperative CA15–3 and CEA in predicting the prognosis of young patients with breast cancer. Oncol Lett. 2018;16(4):4679–88.PubMedPubMedCentral Li X, Dai D, Chen B, Tang H, Xie X, Wei W. Determination of the prognostic value of preoperative CA15–3 and CEA in predicting the prognosis of young patients with breast cancer. Oncol Lett. 2018;16(4):4679–88.PubMedPubMedCentral
25.
Zurück zum Zitat Fang C, Cao Y, Liu X, Zeng XT, Li Y. Serum CA125 is a predictive marker for breast cancer outcomes and correlates with molecular subtypes. Oncotarget. 2017;8(38):63963.CrossRef Fang C, Cao Y, Liu X, Zeng XT, Li Y. Serum CA125 is a predictive marker for breast cancer outcomes and correlates with molecular subtypes. Oncotarget. 2017;8(38):63963.CrossRef
26.
Zurück zum Zitat San-Gang W, Zhen-Yu H, Juan Z, Jia-Yuan S, Feng-Yan L, Qin L, et al. Serum levels of CEA and CA15-3 in different molecular subtypes and prognostic value in Chinese breast cancer. Breast. 2014;23(1):88–93.CrossRef San-Gang W, Zhen-Yu H, Juan Z, Jia-Yuan S, Feng-Yan L, Qin L, et al. Serum levels of CEA and CA15-3 in different molecular subtypes and prognostic value in Chinese breast cancer. Breast. 2014;23(1):88–93.CrossRef
27.
Zurück zum Zitat Shao Y, Sun X, He Y, Liu C, Liu H. Elevated levels of serum tumor markers CEA and CA15-3 are prognostic parameters for different molecular subtypes of breast cancer. PLoS ONE. 2015;10(7):e0133830.CrossRef Shao Y, Sun X, He Y, Liu C, Liu H. Elevated levels of serum tumor markers CEA and CA15-3 are prognostic parameters for different molecular subtypes of breast cancer. PLoS ONE. 2015;10(7):e0133830.CrossRef
28.
Zurück zum Zitat Riedinger JM, Goussot V, Desmoulins I, Lorgis V, Coutant C, Beltjens F, et al. CEA and early detection of relapse in breast cancer subtypes: comparison with CA 15–3. Bull Cancer. 2016;103(5):434–43.CrossRef Riedinger JM, Goussot V, Desmoulins I, Lorgis V, Coutant C, Beltjens F, et al. CEA and early detection of relapse in breast cancer subtypes: comparison with CA 15–3. Bull Cancer. 2016;103(5):434–43.CrossRef
29.
Zurück zum Zitat Mudduwa LK, Wijayaratne GB, Peiris HH, Gunasekera SN, Abeysiriwardhana D, Liyanage N. Elevated pre-surgical CA15-3: does it predict the short-term disease-free survival of breast cancer patients without distant metastasis? Int J Womens Health. 2018;10:329–35.CrossRef Mudduwa LK, Wijayaratne GB, Peiris HH, Gunasekera SN, Abeysiriwardhana D, Liyanage N. Elevated pre-surgical CA15-3: does it predict the short-term disease-free survival of breast cancer patients without distant metastasis? Int J Womens Health. 2018;10:329–35.CrossRef
30.
Zurück zum Zitat Clarke RB. Isolation and characterization of human mammary stem cells. Cell Prolif. 2005;38(6):375–86.CrossRef Clarke RB. Isolation and characterization of human mammary stem cells. Cell Prolif. 2005;38(6):375–86.CrossRef
31.
Zurück zum Zitat Moldovan L, Mitroi A, Petrescu CM, Aschie M. Classification of breast carcinomas according to gene expression profiles. J Med Life. 2013;6(1):14–7.PubMedPubMedCentral Moldovan L, Mitroi A, Petrescu CM, Aschie M. Classification of breast carcinomas according to gene expression profiles. J Med Life. 2013;6(1):14–7.PubMedPubMedCentral
32.
Zurück zum Zitat Milioli HH, Tishchenko I, Riveros C, Berretta R, Moscato P. Basal-like breast cancer: molecular profiles, clinical features and survival outcomes. BMC Med Genom. 2017;10(1):19.CrossRef Milioli HH, Tishchenko I, Riveros C, Berretta R, Moscato P. Basal-like breast cancer: molecular profiles, clinical features and survival outcomes. BMC Med Genom. 2017;10(1):19.CrossRef
Metadaten
Titel
Tumor markers CA15-3, CA125, CEA and breast cancer survival by molecular subtype: a cohort study
verfasst von
Junxian Li
Luyang Liu
Ziwei Feng
Xin Wang
Yubei Huang
Hongji Dai
Liwen Zhang
Fangfang Song
Dezheng Wang
Pengyu Zhang
Baoshan Ma
Haixin Li
Hong Zheng
Fengju Song
Kexin Chen
Publikationsdatum
10.02.2020
Verlag
Springer Japan
Erschienen in
Breast Cancer / Ausgabe 4/2020
Print ISSN: 1340-6868
Elektronische ISSN: 1880-4233
DOI
https://doi.org/10.1007/s12282-020-01058-3

Weitere Artikel der Ausgabe 4/2020

Breast Cancer 4/2020 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.