To evaluate the efficacy of gemcitabine-based chemotherapy, particularly in patients with anthracycline- and taxane-pretreated 2^nd-line or greater metastatic breast cancer, and to compare gemcitabine monotherapy (G) with two gemcitabine-based doublets, gemcitabine/vinorelbine (GV) and gemcitabine/capecitabine (GX).

Of 124 consecutive patients who progressed after anthracycline- and taxane-containing chemotherapy, 58 received G alone, 38 received GV, and 28 received GX; their outcomes were analyzed retrospectively.

The median number of prior metastatic chemotherapy regimens was 2 (range 0~4). Visceral metastases were observed in 65 patients (51.4%). The overall response rate was 19.3% (21 partial responses). After a median follow-up period of 21.4 months, the overall survival was 7.6 months (95% CI: 5.5~9.6 months) and the median time to progression was 3.1 months (95% CI: 2.0~4.2 months). Compared with monotherapy (G), com - bination therapy with vinorelbine or capecitabine (GV/GX) was associated with a significantly higher response rate (8.2% vs. 28.3%, p=0.008) and a significantly longer median time to progression (2.8 vs. 3.5 months; p=0.028), but overall survival did not differ between the groups (7.4 vs. 8.2 months, respectively; p=0.54). Most of the adverse treatment-related events were mild to moderate in intensity. The most common adverse event was hematologic toxicity. Multivariate analysis showed that poor performance status and a short disease-free interval were independent prognostic factors for impaired overall survival.

The combination of gemcitabine with vinorelbine or capecitabine was an active and well-tolerated treatment option for taxane- and anthracycline-pretreated 2^nd-line or greater metastatic breast cancer patients, and gemcitabine-based doublets were more beneficial than gemcitabine monotherapy in alleviating symptoms for these patients.

The benefit of consolidation high-dose chemotherapy (HDC) for high-risk primary breast cancer is controversial. We evaluated the efficacy and safety of consolidation HDC with cyclophosphamide, thiotepa and carboplatin (CTCb) followed by autologous stem-cell transplantation (ASCT) in resected breast cancer patients with 10 or more positive lymph nodes.

Between December 1994 and April 2000, 22 patients were enrolled. All patients received 2 to 6 cycles of adjuvant chemotherapy after surgery for breast cancer. The HDC regimen consisted of cyclophosphamide 1,500 mg/m²/day, thiotepa 125 mg/m²/day and carboplatin 200 mg/m²/day intravenous for 4 consecutive days.

With a median follow-up of 58 months, 11 patients recurred and died. The median disease-free survival (DFS) and median overall survival (OS) were 49 and 69 months, respectively. The 5-year DFS and OS rates were 50% and 58%, respectively. The 12 patients with 10 to 18 involved nodes had better 5-year DFS (67%) and OS (75%) than 10 patients with more than 18 involved nodes (30% and 38%, respectively). The most common grade 3 or 4 nonhematologic toxicity was diarrhea, which occurred in 5 patients (23%). No treatment-related death was observed.

Consolidation HDC with CTCb followed by ASCT for resected breast cancer with more than 10 positive nodes had an acceptable toxicity but does not show promising survival.

The benefit of high-dose chemotherapy (HDC) for metastatic breast cancer (MBC) is controversial. We evaluated the efficacy and safety of HDC with cyclophosphamide, thiotepa, and carboplatin (CTCb) followed by autologous stem-cell transplantation (ASCT) for MBC patients.

From September 1994 to December 1999, 23 MBC patients were enrolled. All the patients received 2 to 10 cycles of induction chemotherapy. Before transplantation, 12 patients were in complete response (CR), nine were in partial response (PR), and two had progressive disease (PD). The HDC regimen consisted of cyclophosphamide 1,500 mg/m²/day, thiotepa 125 mg/m²/day and carboplatin 200 mg/m²/day intravenously for 4 consecutive days.

After ASCT, 13 patients (56%) had a CR, five (22%) had a PR, three (13%) had no change, while two (9%) showed a PD. Seventeen patients relapsed or progressed during the median follow-up of 78 months. The median progression-free survival (PFS) time was 11 months and the median overall survival (OS) time was 23 months. The 5-year PFS and OS rates were 22% and 25%, respectively. On the multivariate analyses, less than 4 involved lymph nodes was predictive of a better PFS and OS.

HDC with CTCb for MBC has acceptable toxicity; however, this treatment does not show a survival benefit.

To determine whether COX-2 expression is associated with clinicopathological parameters, including c-erb-B2 overexpression and angiogenesis, and the disease-free survival of patients with operable breast cancer.

Paraffin-embedded tissue samples were selected from 205 patients surgically resected for breast cancer, between 1991 and 1997, and followed-up for at least 4 years. Samples were immunohistochemically stained with antibodies to COX-2, c-erb-B2 and CD34.

COX-2 and c-erb-B2 expressions were detected in 118/205 (57.6%) and 58/205 (28.3%) patients, respectively. COX-2 expression was significantly higher in c-erb-B2 positive than c-erb-B2 negative tumors (75.9% vs. 49.7%, p-value 0.001). COX-2 expression was positively correlated with microvessel count (13.3±8.0 vs. 6.6±7.0, p-value 0.050), but not with other clinicopathological characteristics, including tumor size, involved axil lary lymph nodes and estrogen or progesterone receptor status. Although COX-2 expression itself was not a prognostic marker, breast cancer patients with tumors that co-expressed both COX-2 and c-erb-B2 had a poorer 5-year disease-free survival rate than those that did not (60.2% vs. 78.3%, p-value 0.0527).

Our data suggest that COX-2 expression occurs frequently in c-erb-B2 positive breast cancer, and co-expression of COX-2 and c-erb-B2 may be a useful prognostic marker in patients with operable breast cancer.