acid-phosphatase and Carcinoma--Ductal--Breast

Patients with locally advanced breast cancer treated with neoadjuvant chemotherapy are at risk of cancer treatment-induced bone loss and consequently of increased skeletal morbidity. In addition, this situation could be worsened by the fact that only a minority of patients with breast cancer have sufficient vitamin D. A comprehensive evaluation of bone homeostasis is critical in this context. We retrospectively evaluated the serum levels of calcium, vitamin D, TRAIL, RANK ligand (RANKL), Osteoprotegerin (OPG), Bone TRAP, CrossLaps and DKK1 in 77 patients (median age: 50 years; range 25-74), with locally advanced breast cancer treated in our institute with anthracyclines-taxane neoadjuvant chemotherapy (7 cycles of 21 days/each) between March 2007 and August 2008. Serum samples were collected before the first (baseline) and the last treatment cycle. Variations and correlations between biomarker levels were evaluated. At baseline, 79.5 % of patients had vitamin D insufficiency (<30 ng/ml), increasing to 97.4 % at the end of the neoadjuvant chemotherapy (p < 0.0001). Calcium and RANKL serum concentrations were also significantly decreased, while OPG was significantly increased, resulting in lower RANKL/OPG ratio. Calcium and vitamin D, RANKL and vitamin D and RANKL and OPG levels were significantly correlated (Spearman's coefficient r = 0.2721, p = 0.0006; r = 0.1916, p = 0.002; and r = -0.179, p = 0.03, respectively). Nearly all included patients suffered from vitamin D insufficiency by the end of the neoadjuvant chemotherapy with changes in the calcium/RANKL/OPG axis that are evocative of deregulation of a functional regulatory mechanism. Further studies are needed to determine how drugs modulate this regulatory mechanism to preserve bone homeostasis in patients with breast cancer.

Topics: Acid Phosphatase; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Bone and Bones; Breast Neoplasms; Calcium; Carcinoma, Ductal, Breast; Chemotherapy, Adjuvant; Collagen; Cyclophosphamide; Docetaxel; Epirubicin; Female; Fluorouracil; Humans; Intercellular Signaling Peptides and Proteins; Isoenzymes; Middle Aged; Neoadjuvant Therapy; Osteoprotegerin; Peptide Fragments; Prevalence; RANK Ligand; Retrospective Studies; Statistics, Nonparametric; Tartrate-Resistant Acid Phosphatase; Taxoids; TNF-Related Apoptosis-Inducing Ligand; Vitamin D; Vitamin D Deficiency

Salivary duct carcinoma (SDC) is an uncommon, pathologically distinct entity characterized by its morphologic resemblance to ductal carcinoma of the breast and highly aggressive behavior. Approximately two thirds of patients die within 4 years of initial diagnosis despite aggressive, combined surgical resection and radiotherapy. Review of the literature indicates that androgen receptor (AR), a marker frequently detected in prostatic carcinoma, is expressed in over 90% of SDCs, whereas two common breast carcinoma markers, estrogen and progesterone receptors (ER and PR), are expressed in only 1.3% and 6% of the tumors, respectively, by immunohistochemistry. This hormonal profile suggests that SDC, in contrast to its histiologic similarity to ductal carcinoma of the breast, is immunophenotypically more related to prostatic carcinoma. To substantiate this hypothesis, we performed immunohistochemical staining of 13 cases of SDC for the presence of AR and two prostatic markers, prostate specific antigen (PSA) and prostatic acid phosphatase (PAP). Our results showed multifocal, scattered, moderate immunostaining for PAP and diffuse, moderate immunostaining for PSA in seven (58.3%) and two (16.7%) cases, respectively. These results create a potential diagnostic challenge to surgical pathologists who are dealing with a metastatic adenocarcinoma of AR+/PSA+/-/PAP+/- phenotype, particularly in male patients of unknown primary. Metastatic salivary duct carcinoma should be given serious thought if clinical investigation fails to reveal a prostatic primary. The immunophenotypic homology that exists between SDC and prostatic carcinoma also suggests that antiandrogen therapy as used in the treatment of prostatic carcinoma might be beneficial in patients with metastatic SDC when all other conventional modalities fail.

Topics: Acid Phosphatase; Adult; Aged; Aged, 80 and over; Carcinoma, Ductal, Breast; Carcinoma, Intraductal, Noninfiltrating; Female; Humans; Immunoenzyme Techniques; Male; Middle Aged; Prostate-Specific Antigen; Receptors, Androgen; Salivary Ducts; Salivary Gland Neoplasms