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Breast Cancer (Carcinoma) Markers
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Breast Cancer (Carcinoma) Markers

Breast cancer is a cancer of the breast tissue. Worldwide, it is the most common form of cancer in females - affecting, at some time in their lives, approximately one out of thirty-nine to one out of three women who reach age ninety in the Western world. According to the United Nations World Health Organization, it is the leading cause of cancer deaths among women worldwide. The number of cases has significantly increased since the 1970s, a phenomenon partly blamed on modern lifestyles in the Western world. Because the breast is composed of identical tissues in males and females, breast cancer also occurs in males, though it is far less common.

6-PGDH (6-phosphogluconate dehydrogenase)

  • a better prognostic indicator in primary breast cancer than oestrogen receptor status. PMID: 3797962

17HSD1 (17beta-hydroxysteroid dehydrogenase type 1)

17HSD14

  • a prognostic marker in estrogen receptor-positive breast cancer. PMID: 17145895

44-3A6

  • may serve as an important marker in the differentiation of normal breast epithelium into an atypical or malignant lesion. PMID: 1660186

aHIF

  • In our series of breast cancer patients, aHIF, and not HIF-1alpha transcript, is a marker of poor prognosis. PMID: 14580258

Alkaline Phosphatase (ALP)

  • skeletal ALP could represent a valid marker for bone metastases in association with mucinous markers in the follow-up of patients operated for breast cancer. PMID: 7629426

Alpha-Lactalbumin

  • serum levels of alpha-lactalbumin may be useful as a marker for monitoring breast cancer. PMID: 2337516

AMAS (anti-malignin antibody in serum)

  • more sensitive (97%) in detecting breast cancer than CEA (0%), CA 15-3 (10%), CA 19-5 (5%) or CA 125 (16%) in the same patients. PMID: 10680591

Androgen Receptor (AR)

  • AR immunohistochemistry could serve as a marker to increase sensitivity for identifying breast cancer in skin metastasis of unknown primary sites. PMID: 10697267

ANX7

  • has prognostic value for predicting survival of breast cancer patients, is a bio-marker in prostate and breast cancer progression. PMID: 11673658

Bcl-2

  • an independent predictor of breast cancer outcome and seems to be useful as a prognostic adjunct to the NPI, particularly in the first 5 years after diagnosis. PMID: 16638854

Beta 1-6 branched oligosaccharides

  • a marker of tumor progression in human breast and colon neoplasia. PMID: 1985789

beta-catenin

  • can be involved in breast cancer formation and/or progression and may serve as a target for breast cancer therapy. PMID: 10759547

BNIP3

  • a progression marker in primary human breast cancer; opposing functions in in situ versus invasive cancer. PMID: 17255267

CA IX

  • a marker of poor prognosis in premenopausal breast cancer patients and it is an independent predictor of survival in patients with one to three positive lymph nodes. PMID: 17085655

Carbonic Anhydrase XII (CA-12)

  • a marker of good prognosis in invasive breast carcinoma. PMID: 12671706

CA 15.3 (CA15-3)

  • can predict survival in primary breast cancer. PMID: 12452445
  • most widely used as a serum tumor marker in follow-up and detection of breast cancer recurrence. PMID: 11192831
  • highly useful in the diagnosis, differential diagnosis, and monitoring of metastases and recurrences of breast cancer, and is superior to CEA. PMID: 10920962
  • a tumor marker associated with mammary tumors. PMID: 1563679
  • significantly better than CEA in the detection of breast cancer metastases. PMID: 2065278
  • may thus be the first independent prognostic serum marker in breast cancer. PMID: 11192829

CA27.29

  • suitable for routine use in the management of patients with breast cancer. PMID: 11239757

CA549

CaR (calcium-sensing receptor)

  • expression is common in a selected group of patients with advanced primary breast cancers. PMID: 16564154

Carcinoembryonic antigen (CEA)

  • CEA monitoring should be considered an expensive and inefficient method of follow-up evaluation for breast cancer patients, and it provides no additional value when used in combination with CA 15.3. PMID: 11489813

CD24

  • CD24 expression in primary breast cancer as detected by immunohistochemistry might be a new marker for a more aggressive breast cancer biology. PMID: 14581365
  • a useful marker for human breast carcinoma and play a role in facilitating metastasis by the interaction between tumor cells and platelets or endothelial cells. PMID: 10465342

CD44s

  • CD44s detection by immunohistochemistry is useful in distinguishing intraductal papillomas from papillary carcinomas of the breast. PMID: 10690183

C-erbB2 oncoprotein

  • prognostic marker in breast cancer. PMID: 16286993
  • overexpression of c-erbB2 in the primary tumour is an independent marker of relative resistance to first-line endocrine therapy in patients with advanced breast cancer. PMID: 10098763

CK-BB (Creatine kinase-BB)

  • CSF activity of CK-BB appears to be a contribution in the diagnosis of MC secondary to breast cancer and seems superior to protein and LDH. PMID: 2632253

Cyclin A

  • a good marker for tumour proliferation and prognosis in breast cancer. PMID: 16091759

Cyclin E

  • in breast cancer, the alterations in cyclin E expression become progressively worse with increasing stage and grade of the tumor, suggesting its potential use as a new prognostic marker. PMID: 7903908

CYFRA 21-1 (cytokeratin-19 fragments)

  • a useful tumour marker for detecting disease relapse and assessing treatment efficacy in breast cancer. PMID: 15280913  

D2-40

  • identifies lymphatic invasion in breast tumors and is a significant predictor of outcome in breast cancer. PMID: 17206106

DAP-kinase (death associated protein-kinase)

  • Loss of DAP-kinase expression negatively correlates to survival and positively correlates to the probability of recurrence in a very significant manner. DAP-kinase thus constitutes a novel and independent prognosis marker for breast cancer. PMID: 15131053

Endoglin (CD105)

  • a marker of breast carcinoma-induced neo-vascularization. PMID: 9858949

ERbeta (oestrogen receptor beta)

  • ERalpha is more dysregulated in breast cancer, and thereby ERbeta is more tightly regulated in the tumour. PMID: 16289616

ErbB-2 (C-erbB-2 oncogene protein)

  • a prognostic marker of breast carcinoma, and serum ErbB-2 is a preoperative prognostic marker and may be useful for monitoring tumor recurrence of the breast. PMID: 17044019
  • the determination of ErbB-2 in tissue extracts of breast carcinoma may be useful for assessing c-erbB-2 protein expression in the primary tissue and indicates that serum ErbB-2 may be a sensitive marker for monitoring tumor relapse. PMID: 10956406

Ets-1

  • a strong, independent predictor of poor prognosis in breast cancer. PMID: 12466970

EZH2 (enhancer of zeste homologue 2)

  • a marker of aggressive breast cancer. PMID: 16489070
  • significantly associated with increased tumor cell proliferation and is a marker of aggressive breast cancer. PMID: 16489070
  • a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. PMID: 14500907

Ferritin

  • a marker of therapeutic response in stage III and IV breast cancer. PMID: 2137790

GATA3

  • may be the basis for a new clinically applicable test to predict tumor recurrence early in the progression of breast cancer. PMID: 16357129

GCDFP-15

  • a specific marker for breast cancer and is superior to ALA in this respect. PMID: 2542151

GCDFP-24

  • could well be a good biochemical marker for monitoring the response to androgenic and antiestrogenic compounds in the therapy of advanced breast cancer. PMID: 2351114

Glut-1

  • TMA analysis for Glut-1 expression may be useful to predict disease free survival but it does not predict race specific recurrence. PMID: 16228617

GST (glutathione S-transferase)

  • measurement of GST B1 or GST B2 in lung lavage fluid could be a useful aid in the diagnosis of lung malignancy. PMID: 2302756

HER2/Neu

  • a predictor of prognosis in breast cancer and a potential marker for selecting the optimal adjuvant chemotherapy. PMID: 16137437
  • an important independent prognostic factor in early stage breast cancer. PMID: 10066073
  • coexistence of HER2 over-expression and p53 protein accumulation is a strong prognostic molecular marker in breast cancer. PMID: 14680497

HSP70

  • nuclear share of hsp70 is associated with various biological characteristics of malignant breast tumours, while the occurrence of cytoplasmatic hsp70 influences OS and SR. PMID: 12820347

Hypoxia inducible factor-1alpha (HIF-1 alpha)

  • a prognostic marker in premenopausal patients with intermediate to highly differentiated breast cancer but not a predictive marker for tamoxifen response. PMID: 16381002

Human kallikrein 10 (hK10)

IGFBP-2

  • a marker for antiestrogen resistant breast cancer cell lines, although IGFBP-2 was not a major contributor to the resistant cell growth. PMID: 16893667

KAI-1

  • in addition to its role in human prostate, pancreatic and non-small cell lung cancer, KAI1 may also be a useful marker for staging human breast disease. PMID: 9570365

Ki-67

  • a prognostic marker in early breast cancer. PMID: 17453008
  • Tumor proliferative activity as evaluated by the monoclonal antibody Ki-67 seems to be an effective indicator of prognosis in breast cancer for DFS and OS. PMID: 8508358

KL-6

  • serum KL-6 may be helpful for clinical use as a tumor marker for breast cancer, and it may play an important role, especially in the surveillance of disease relapse. PMID: 11051258

KLK15

  • an independent and favourable prognostic marker for breast cancer. PMID: 12439720

KPNA2 (karyopherin alpha2)

  • a potential novel prognostic marker in breast cancer. PMID: 16818692

Laminin

  • serum determination of laminin could be a useful diagnostic tool in breast cancer and a valuable parameter in the prediction of metastasis. PMID: 10356660

Leptin

  • a marker of breast cancer progression: possible role of obesity-related stimuli. PMID: 16533767

LY-6K

  • not only a target antigen for HNSCC but also a significant new molecular marker for diagnosis and gene therapy in patients with breast cancer. PMID: 17089039

M3/M21

  • the detection of breast cancer recurrence with CA 15-3 is improved by combination with M3/M21. PMID: 8920765

MAGE-A (Melanoma antigen gene A)

  • gene expression may be used for the surveillance of circulating breast carcinoma cells after primary therapy by RT-nested PCR using MMRPs. PMID: 15937912

MAM-6 antigen

  • a new serum marker for breast cancer monitoring. PMID: 3697998

Mammaglobin (MAM)

  • as measured by the ELISA, holds significant promise for breast cancer screening with the realistic potential to impact management of this disease. PMID: 16166429
  • hMAM mRNA detection by RT-PCR is a specific assay potentially suitable for identification of occult cancer cells in peripheral blood of BC patients. PMID: 16110760
  • MAM gene expression on leukapheresis products of high-risk breast cancer patients is an indicator of poor prognosis. PMID: 15447988
  • detection of mammaglobin protein and mRNA in clinical samples may be a useful marker for primary, metastatic, and occult breast cancer. PMID: 11193781
  • RT-PCR using mammaglobin B gene could therefore be a useful tool for detection of micrometastases of breast cancer. PMID: 10674878
  • a novel marker of minimal residual disease in early stages breast cancer. PMID: 15254674
  • one of the first relatively mammary-specific and mammary-sensitive markers. Mammaglobin and BRST-2 appear to represent useful markers for breast cancer and should be used as a component of panels evaluating tumors of unknown primary sites. PMID: 14521461

MCA (mucinous carcinoma associated antigen)

  • a promising tumor marker in breast cancer. Especially high values may have diagnostic significance. PMID: 3178156
  • the new tumour marker antigen MCA reacts with breast cancer cells in paraffin sections. It might be used in identification of cancer cells in tissue sections. MCA can also be used as a weak indicator of aggressiveness of the tumour. PMID: 1695077

Mcm-2

  • may be of utility as a prognostic marker to refine the prediction of outcome in breast cancer, for example when combined with parameters currently used in the NPI. PMID: 14645419

MDM2

MGB1

  • can serve as a differential molecular marker. In practice, prospective examination, using the nine cases with a history of breast cancer, confirmed the usefulness of MGB1 in differential diagnosis. PMID: 15096563

MIB-1

  • the growth fraction of a tumour as determined by the MIB-1 labelling index is an important prognostic factor in patients with primary breast cancer. PMID: 9716027

MMP-1

  • a candidate marker that may be useful for identification of breast lesions that can develop into cancer. PMID: 15864312

MMP-2

  • MMP-2 immunoreactive protein has been associated strongly with a shortened survival independent of major prognostic indicators in patients with primary breast carcinoma, increasing the risk of death 3.6-fold during the first 10 years of follow-up. PMID: 9740080

MMP-13

  • primarily expressed by myofibroblasts in human breast carcinoma and that expression in DCIS lesions often is associated with microinvasive events. PMID: 11585740

MSA (Mammary serum antigen)

  • serum levels do not allow to discriminate benign from malignant breast diseases and MSA is 2.5 to 3 times more sensitive for the prediction of early stages breast cancer compared to CA15-3, TPA and CEA. PMID: 9082702
  • 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. PMID: 3355770
  • MSA levels may therefore be of some use for the monitoring of breast cancer patients, and as a diagnostic aid to screen populations for breast cancer. PMID: 3609486

NCC-ST-439

  • the NCC-ST-439 level, especially in combination with the CEA level, may be useful for the early detection and the monitoring of relapses in breast cancer patients. PMID: 2232168

Nectin-4

  • a 66-kDa adhesion molecule of the Nectin family, which is a valuable new histological and serological marker for breast carcinoma. PMID: 15784625

Neu (c-erbB-2)

  • a tumor marker in carcinoma of the female breast. PMID: 1981830

NRP-1 (neuropilin-1)

  • a marker of axillary lymph node breast metastases. PMID: 10451484
  • may be a multiple function protein in human breast and may be involved in the induction of local invasiveness of neoplasia and angiogenesis and have direct relevance to the progression of breast cancer. PMID: 12216067

p53

  • Immunohistochemically detected p53 protein accumulation was an independent marker of shortened survival and was seen more often in familial than in sporadic carcinomas. PMID: 1317462
  • p53 positive Bcl-2 negative phenotype is an independent marker of prognosis in breast cancer. PMID: 17187363
  • p53 expression status was a significant molecular marker as well as the response to first-line endocrine therapy for predicting TTEF in recurrent breast cancer with hormone-sensitive disease. PMID: 17180510
  • Mutant p53 protein in serum could be used as a molecular marker in human breast cancer. PMID: 16525651
  • nuclear p53 protein expression may represent an adverse prognostic marker in inflammatory breast cancer (IBC) and may provide a valuable tool for selecting treatment for this aggressive disease. PMID: 15448010

p63

  • as part of the diagnostic workup of challenging spindle cell tumors of the breast as a highly specific marker for metaplastic carcinomas. PMID: 15489655

P120

  • a prognostic marker in node-negative breast cancer. PMID: 7940158

Pepsinogen C

  • a new prognostic factor for early recurrence and death in both node-positive and node-negative breast cancer. PMID: 7799043

PINP

  • serum marker of metastatic spread to the bone in breast cancer patients. PMID: 16033050

PKC alpha (Protein Kinase C alpha)

  • a marker for antiestrogen resistance and as a promising therapeutic target in the treatment of tamoxifen resistant breast cancer. PMID: 17061041

Plasminogen Activator

  • can be used as an effective functional marker for hormone dependence in human breast cancer. PMID: 3082829

ppGalNAc-T6

  • could be a specific marker applicable to the molecular diagnosis of breast cancer cells dissemination. PMID: 16596643
  • a new immunohistochemical breast cancer marker. PMID: 16260590

pS2 and ER

  • are useful tools for predicting tumour regression with neoadjuvant tamoxifen in post-menopausal breast carcinoma patients. PMID: 8855985

PSA

  • might be useful as a marker for a subset of breast cancers with better prognosis, which could respond to endocrine therapy, in correlation with other prognostic markers. PMID: 16575473

PSE (Prostate Specific Ets)

  • a potentially informative novel marker for detection of metastatic breast cancer in axillary lymph nodes, and should be included in any study that involves molecular profiling of breast cancer. PMID: 11953821

PTA (prothymosin alpha)

  • a potential prognostic marker for primary breast cancer. PMID: 10682670

PTEN

  • might play an important and major role in its HER2/PI3K/Akt-mediated antitumour effect, and could be a useful biomarker for predicting the efficacy of trastuzumab in the treatment of breast cancer. PMID: 16404430

PTTG (pituitary tumor-transforming gene)

  • expression in primary tumors of the breast is a powerful tool for the assessment of potential tumor aggressiveness. PMID: 14759723

RCP (riboflavin carrier protein)

  • measurement of circulatory RCP and the immunohistochemical staining pattern of RCP in biopsy specimens could be exploited as an additional marker in diagnosis/prognosis of breast cancer in women. PMID: 11494224

Sigma S

  • a measure of reactive sulfur groups of immunoglobulin G, is a sensitive tumor marker discriminating different stages of breast cancer. PMID: 1913474

SNCG

  • expected to be a useful marker for breast cancer progression and a potential target for breast cancer treatment. PMID: 16821081

S-NSE (serum neuron-specific enolase)

  • may be a useful marker for monitoring treatment and predicting relapse in patients with Small cell lung cancer (SCLC). PMID: 2155054

Spot 14 (S14)

  • a marker of aggressive breast cancer and a potential therapeutic target. PMID: 16809441
  • identifies a subset of high-risk breast cancers that is not specified by analysis of sex steroid receptors, Her2/neu, or cyclin D1, and provides a molecular correlate to histologic features that predict recurrence. PMID: 16552628

ST-439

  • a useful tumor marker not only in monitoring the recurrence, but also in the diagnosis of primary breast cancer. PMID: 2069399

STC-1 (Stanniocalcin 1)

  • is proposed as a novel, specific, and clinically useful molecular marker for detecting occult breast cancer cells in the BM and blood. PMID: 12684415

Survivin

  • might be used as a new marker to stratify breast cancer patients for more optimal treatment modalities, or it could be a promising new target for therapy. PMID: 15364883

TAG12 (Tumor associated glycoprotein 12)

TEM-8

  • a useful marker for identifying tumour associated micro-vessels and that elevated levels are associated with disease progression, which may have some bearing on the prognostic outcome in breast cancer. PMID: 17016666

Thioesterase II

  • may be a useful serum marker for mammary cancer. PMID: 3524817

Thrombomodulin (TM)

  • might play an active role in cancer invasion and metastasis, and serve as a new prognostic factor in invasive breast cancer. PMID: 9216709

TIMP-1 (tissue inhibitor of metalloproteinase-1)

  • a prognostic marker in primary breast cancer. PMID: 15073104
  • may be useful as a prognostic marker in combination with uPA/PAI-1 and adds substantial positive information on the use of TIMP-1 as a prognostic marker in breast cancer. PMID: 15073104

Tissue-type plasminogen activator

topo IIalpha

  • overexpression appears to be linked with cellular dedifferentiation and potentially aggressive tumor phenotype in invasive breast cancer. PMID: 11174071

TP53

  • TP53 mutation is a strong marker for the prediction of overall and disease-free survival in breast cancer, irrespective of nodal status. PMID: 10987229

TPpA (Tissue polypeptide antigen)

  • a marker of central nervous system metastases of breast cancer. PMID: 2041052

TPS (Serum tissue polypeptide specific antigen)

  • a complementary tumor marker to CA 15-3 in the management of breast cancer. PMID: 11678313
  • Serum TPS at admission had a significant predictive value with regard to survival up to 12 months in breast cancer patients. PMID: 8687149

TRACP

  • a useful marker of metastatic bone disease and response to treatment in breast cancer patients. PMID: 10650803

TRACP 5b

  • Tartrate-resistant acid phosphatase 5b activity is a useful bone marker for monitoring bone metastases in breast cancer patients after treatment. PMID: 16537696PMID: 15701839
  • Diagnostic sensitivity and specificity of TRAP 5b as a marker of skeletal metastases in patients with breast cancer were 82 and 87%, respectively. PMID: 15514730
  • TRACP 5b activity can be considered a surrogate indicator of bone metastasis in breast cancer patients. PMID: 15153786

UK-PA (Urokinase plasminogen activator)

  • appears to be a new and independent prognostic marker in breast cancer. PMID: 2119883
  • uPA expression in breast cancer patients is under epigenetic control via methylation of its promoter. Determination of uPA promoter methylation can therefore serve as an early reliable indicator of uPA production in breast cancer patients. PMID: 15131040

YB-1 (Y-box binding protein 1)

  • a marker of tumor aggressiveness and response to adjuvant chemotherapy in breast cancer. PMID: 15703814

YKL-40

  • determination of serum YKL-40 can be used as a prognostic marker related to the extent of disease and survival of patients with recurrence of breast cancer. PMID: 7577068

Other Breast Cancer Markers

  • Changes of cerebrospinal fluid tumor marker levels may predict response to treatment and survival of carcinomatous meningitis in patients with advanced breast cancer. PMID: 15965274
  • FDG-PET is a useful technique for detecting recurrent breast cancer suspected from asymptomatically elevated tumor markers levels and has an important clinical impact on the management of these patients. PMID: 12324574
  • Overall mammographic density seems to represent a general marker of breast cancer risk that is not specific to breast side or location of the eventual cancer. PMID: 17220330
  • DNA methylation of particular genes in pretherapeutic sera of breast cancer patients, especially of RASSF1A/APC, is more powerful than standard prognostic parameters. PMID: 14633683
  • Positive FBL is associated with early manifestation of breast cancer and may be considered as a tool for the screening of breast cancer in high risk women. PMID: 9232610
  • Our data do not support the usefulness of the PHI assay for early detection of the metastases in breast cancer. PMID: 9378161
  • the ratio of 16 alpha-OHE1/2-OHE1 may provide a marker for the risk of breast cancer. PMID: 8593862
  • urinary testosterone is a prognostic indicator of early breast cancer recurrence in node-positive patients. PMID: 8400317

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