Implications of Different CA 15-3 Levels according to Breast Cancer Subtype at Initial Diagnosis of Recurrent or Metastatic Breast Cancer

Abstract

<i>Background:</i> CA 15-3 is derived from proteolytic shedding of the extracellular domain of mucin 1 (MUC1) glycoprotein. Luminal subtype breast cancer shows a higher expression in MUC1 genes, and a positive relationship between MUC1 expression and estrogen receptor (ER) expression has been reported. In this study, we attempted to determine the difference of CA 15-3 level according to the subtype of breast cancer. <i>Methods:</i> From January 2000 to December 2009, a total of 707 patients who were diagnosed with metastatic or recurrent breast cancer at Samsung Medical Center were included in this study. Among these, 536 patients with available clinical data including pretreatment CA 15-3 and immunohistochemistry for ER, progesterone receptor (PgR) and hormone receptor 2 (HER2) were analyzed in this study. Patients were classified into 3 groups according to their receptor status: ER-positive (ER+) and/or PgR+ irrespective of HER2 (HR+), ER–/PgR–/HER2+ (HER2-enriched) and ER–/PgR–/HER2– (triple negative, TN). <i>Results:</i> The supranormal values of CA 15-3 were frequently observed in HR+ breast cancer compared to other types (45.6% for HR+, 24.4% for HER2-enriched and 28.8% for TN; p < 0.001). The increase of marker levels differed significantly among the 3 groups (24 U/ml for HR+, 13 U/ml for HER2-enriched and 18 U/ml for TN; p < 0.001). <i>Conclusions:</i> The increase of both marker levels and the frequency of supranormal values of CA 15-3 were more frequently observed in HR+ breast cancer, which is positively associated with MUC1 expression. These results could potentially serve as a basis for expanding the clinical implications of CA 15-3 in the field of clinical trials for novel targeted therapies in breast cancer.

MUC1 and metastatic cancer

“…The incidence of lung, liver and peritoneal metastases was and basal, although in each of these cancer types, expression is highest in those tumors that have metastasized. 9,12 In other hormonally responsive cancers, including ovarian and prostate, a similar overexpression of MUC1 is observed in advanced disease. In ovarian cancer, patients with metastatic, treatment-resistant disease display elevated levels of MUC1, with greater than 90% of these patients producing antibodies to MUC1.…”

Natural Killer Cell Mediated Antibody-Dependent Cellular Cytotoxicity in Tumor Immunotherapy with Therapeutic Antibodies

“…However, in this study and in another study from Dahan et al investigating combined cetuximab-chemotherapy treatment, the FcγRIIIa-158F allele rather than the FcγRIIIa-158V allele had a favorable influence on overall and progression-free survival (Zhang et al, 2007; Dahan et al, 2011). Beyond that, a recent study found no association of clinical outcome in a patient cohort of 107 mCRC patients treated with cetuximab and chemotherapy and FcγRIIIa-F158V and FcγRIIa-H131R polymorphisms (Park et al, 2012). These discrepancies related to the predictive value of the FcγRIIIa-F158V polymorphism on cetuximab treatment are difficult to explain and indicate a demand for further elaborated investigations in larger patient cohorts.…”

Serum tumor markers and PET/CT imaging for tumor recurrence detection

“…An increase in CA15-3 level is most commonly observed in hormone receptor positive breast cancer (HR?) whereas the incidence of CA15-3 elevation is lowest in the HER2-enriched type of disease [15][16][17]. In addition, elevation of CA15-3 proved more common and pronounced in breast cancer with three or more metastatic sites, when compared to breast cancer with single metastasis and in patients with pleural metastasis at the time of diagnosis.…”