Elevated serum CA15-3 levels correlate with positive estrogen receptor and initial favorable outcome in patients who died from recurrent breast cancer.

BACKGROUND: The clinical usefulness of circulating tumor markers in breast cancer as recurrence indicators during follow-up or monitoring treatment response is still an open question. There are some patients with normal tumor marker levels who have apparent recurrence foci. In this study, we evaluated the relationships between CEA or CA15-3 levels and clinicopathological factors or outcome in patients who had died from recurrent breast cancer. METHODS: Two hundred-twenty deceased patients who had had recurrent or advanced breast cancer and who had been treated between 1986 and 2000 were enrolled in a retrospective study. Serum CEA and CA 15-3 were measured regularly during the clinical course until death. RESULTS: The rates of CEA and CA15-3 positivity were 41.4% and 50.9% at the time of recurrence, and rose to 67.3% and 76.8% after recurrence, respectively. The CA15-3 and CEA positivity rates significantly correlated with ER and PgR status. Serum CA15-3 status correlated significantly with survival after recurrence. Patients with CA15-3 negativity had poorer prognoses than CA15-3 positive patients. Multivariate analysis revealed that CA15-3 status was one of the significant factors for survival after recurrence. CONCLUSIONS: Tumor markers, especially CA15-3, might reflect the biological characteristics of tumors such as ER or PgR status, and may be useful prognostic predictors in recurrent breast cancer. Elevated CA15-3 levels correlated with positive estrogen receptor and favorable outcome in deceased patients with recurrent breast cancer.

[A case of recurrent breast cancer with lung metastasis and overexpression of HER2 that responded to UFT and cyclophosphamide combination therapy after sequential treatments with epirubicin, taxanes, and trastuzumab].

We describe a 57-year-old woman who underwent modified mastectomy for right breast cancer (T2N0M0) with overexpression of HER2, in whom lung metastasis developed 3 years after operation. She received sequential chemotherapy, including epirubicin plus cyclophosphamide, docetaxel, paclitaxel and trastuzumab, but the lung lesion progressed after transiently showing a partial response. Oral treatment with UFT and cyclophosphamide was begun as fifth-line treatment. The lung tumor shrank after 2 months, and a partial response has been maintained during continued treatment with UFT and cyclophosphamide. No adverse effects have occurred. We regard combination therapy with oral UFT and cyclophosphamide to be useful for the management of metastatic breast cancer, even in heavily pretreated cases with overexpression of HER2.

Higher plasma vascular endothelial growth factor levels correlate with menopause, overexpression of p53, and recurrence of breast cancer.

PURPOSE: Vascular endothelial growth factor (VEGF) is an important factor involved in angiogenesis. Many studies have reported that the expression of VEGF in breast cancer is an unfavorable prognostic factor. However, there are few studies that have analyzed blood VEGF levels because most used serum VEGF, generally thought to originate from platelets. We measured plasma VEGF levels, which evaluate the level of tumor-derived VEGF, in various breast diseases. METHOD: We analyzed 15 patients with benign breast disease, 187 patients with primary breast cancer, 32 patients with no postoperative recurrence, and 56 patients with recurrence. Plasma VEGF levels were measured by ELISA. RESULTS: Plasma VEGF levels were higher in malignant than in benign breast disease, and were also high in patients with recurrence or distant metastasis. In primary cases, higher VEGF levels were clearly correlated with menopause and overexpression of p53, and postmenopausal patients with high levels had a significantly lower disease-free survival rate. CONCLUSION: These results suggest that plasma VEGF levels in breast cancer have a clinical significance in that they are associated with the extent or metastasis of malignant lesions and are involved in angiogenesis in postmenopausal patients.

[Early phase II dose-finding study of exemestane in postmenopausal patients with advanced/recurrent breast cancer].

Exemestane was administered orally to postmenopausal women with advanced/recurrent breast cancer at a dose of 10 mg/day or 25 mg/day once daily for more than 8 weeks in order to evaluate the drug's anti-tumor effects and safety in a dose-finding study. The response rate (CR + PR) in the 10 mg and 25 mg group was 25.0% (8/32) and 31.4% (11/35), respectively, demonstrating no significant differences between the two groups, yet a higher efficacy rate was observed in 25 mg group. The efficacy rate in hormone-treatment-resistant patients within the 10 mg and 25 mg groups was 14.3% (3/21) and 26.1% (6/23), respectively, demonstrating more than a 20% response rate in 25 mg group. Incidences of the adverse events of which relevance to the drug could not be excluded were 30.6% (11/36) in the 10 mg group. 13.9% (5/36) in the 25 mg group and 22.2% (16/72) in the total group. The major adverse events were, hot flashes, numbness of the limbs, nausea, headache etc. Abnormal findings in clinical laboratory tests were as follows: ALP increase; GOT increase; GPT increase; gamma-GTP increase; total cholesterol increase; urinary sediment present. Abnormal findings in endocrine function were as follows: aldosterone decrease; testosterone.cortisol.DHEA-S decrease. But discontinuation due to abnormal laboratory findings was not found. No abnormal findings in physical tests were observed. A significant decrease in plasma estrogen concentration at week 4 was observed in both the 10 mg and 25 mg groups compared with baseline. These low levels were maintained throughout the study period. On the basis of these results, the efficacy of exemestane 25 mg/day was verified to be slightly higher than 10 mg/day. In addition the safety profile had no major adverse events to notice. In these patients with advanced/recurrent breast cancer, 25 mg/day was recommended as the most appropriate dose to be used clinically.

An evaluation of predictive factors involved in clinical or pathological response to primary chemotherapy in advanced breast cancer.

BACKGROUND: The usefulness of primary chemotherapy has been widely recognized and applied to routine clinical practice to improve prognosis by downstaging. Nevertheless, none of many trials has been able to show a positive effect of primary chemotherapy in terms of prognosis, and predictive factors of outcome have not been defined and are still under investigation. METHODS: Primary chemotherapy was given to 50 patients with advanced breast cancer. Predictive factors involved in clinical or pathological response to primary chemotherapy (3 cycles of CE(F) therapy ) were investigated. RESULTS: The response rate in all patients was 56.0% (CR: 3 patients PR: 25 patients) and 64.1% in patients without distant metastases. MIB-1 was related to the clinical response and EIC (extensive intraductal component) was related to the pathological response; the response was high in patients with EIC negative tumors. Responders had tumors with higher proliferative activity, which decreased significantly after chemotherapy. Patients with a decrease of more than 30% in proliferative activity after chemotherapy had significantly higher disease-free survival rates. CONCLUSION: The proliferative activity and EIC status were useful predictors of clinical or pathological response to primary chemotherapy. A decrease in proliferative activity by chemotherapy significantly correlated with clinical response and reflected a favorable prognosis. The number of patients benefiting from primary chemotherapy might steadily increase by detecting these predictive factors.