RESUMEN
A 52-year-old woman underwent modified radical mastectomy and axillary lymph node resection for right breast cancer (stage IIB). Afterwards FEC therapy (5-FU 500 mg/m/2, epirubicin 75 mg/m2, cyclophosphamide 500 mg/m2) x 4, docetaxel therapy (60 mg/m2) x 4 and radiation of the illness side collarbone, upper and lower lymph nodes were enforced for adjuvant therapy after the operation. Furthermore, administration of aromatase inhibitor (anastrozole) and trastuzumab was started due to the postoperative pathological diagnosis of hormone receptor-positive and HER2 (score 3+). This became an urgent hospital admission because of the sudden escape power from impaired consciousness due to the articulation disorders and limb weakness when trastuzumab was administered nine times. It was diagnosed by MRI examination and the cerebrospinal fluid cytology as meningeal carcinomatosis of breast cancer, and she died on the 31st recurrence of disease. A serious relapse may be caused in a case of fast-progressing breast cancer like this while being administered trastuzumab as an adjuvant treatment.
Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Carcinomatosis Meníngea/secundario , Anticuerpos Monoclonales Humanizados , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Quimioterapia Adyuvante , Progresión de la Enfermedad , Resultado Fatal , Femenino , Humanos , Carcinomatosis Meníngea/tratamiento farmacológico , Persona de Mediana Edad , TrastuzumabRESUMEN
We have investigated protein kinase C (PKC) signaling, a putative differentiation-related and metastasis suppressor gene Cap43/NDRG1/Drg-1, and Y-box binding protein-1 (YB-1) to identify new molecular targeting for breast cancer. PKC is a family of serine/threonine kinases that is involved in the regulation of cell growth. We have demonstrated that PKC caused G(1) arrest in a breast cancer cell line through a mechanism involving a PKC-ERK MAPK-JNK-Rb protein signaling pathway. We have also characterized a novel mechanism through which all-trans retinoic acid (ATRA) and antineoplaston, anticancer drug, caused cell growth inhibition in breast cancer cells through effects on intracellular pathways. ATRA decreased the expression of PKCalpha, as well as reduced ERK MAPK phosphorylation, and consequently caused G(1) arrest. Antineoplaston caused the down-regulation of PKCalpha protein expression, resulting in inhibition of ERK MAPK phosphorylation, with resultant inhibition of Rb phosphorylation leading to G(1) arrest. PKC signaling represents a promising target for development of novel therapeutic agents. Cap43 is known as N-myc downstream-regulated gene 1 (NDRG1). Treatment with estradiol (E(2)) significantly decreased the expression of Cap43 in ER-alpha-positive breast cancer cell lines. Co-administration of tamoxifen abrogated the E(2)-induced downregulation of Cap43 in ER-alpha-positive cell lines. These results suggested that Cap43 may hold the potential of being a molecular marker to determine the therapeutic efficacy of anti-estrogenic anticancer agents in breast cancer. YB-1 is a member of the cold shock domain protein family. The expression of nuclear YB-1 was correlated with HER2 positively in clinical specimens of human breast cancer. Immunostaining studies showed that nuclear YB-1 expression was an independent prognostic factor of overall survival. Expression of nuclear YB-1 played an essential role in acquirement of malignant characteristics through HER2-dependent pathways in breast cancer patients. PKC, Cap43 and YB-1 may be useful in new molecular-targeting diagnosis and therapeutics in breast cancer.