HER-3 status by immunohistochemistry in HER-2-positive metastatic breast cancer patients treated with trastuzumab: correlation with clinical outcome.

AIMS AND BACKGROUND: HER-3 signaling might contribute to resistance to trastuzumab. To clarify the role of HER-3 in HER-2-positive breast cancer, it is important to evaluate the level of HER-3 and its correlations with clinical outcome in metastatic breast cancer patients treated with trastuzumab. METHODS: HER-3 status by immunohistochemistry was evaluated in HER-2-positive metastatic breast cancer patients treated with trastuzumab-based therapy at our institution. Two scorings were utilized for interpreting staining for HER-3, and the correlation between HER-3 status and clinical outcome was evaluated. RESULTS: We evaluated HER-3 status in 61 of 76 HER-2-positive metastatic breast cancers treated with trastuzumab-based therapy at our institution from 4/1999 to 3/2006. We observed 55.2% objective responses; median time to progression and overall survival from start of trastuzumab therapy were 9.6 months (0.921-78.87) and 29.1 months (1.4-129.5+), respectively. With a cutoff of 50% staining tumor cells, we found 30 HER-3-negative and 31 HER-3-positive tumors. HER-3 status was not significantly associated with clinical outcome, but a shorter time to progression and overall survival were observed in patients with HER-3-positive tumors. CONCLUSIONS: HER-3 status by immunohistochemistry was not significantly associated with clinical outcome in HER-2-positive metastatic breast cancer patients. Further studies are necessary to evaluate the prognostic and predictive role of HER-3.

Central nervous system metastases in HER-2 positive metastatic breast cancer patients treated with trastuzumab: incidence, survival, and risk factors.

BACKGROUND: A higher incidence of central nervous system (CNS) metastases in HER-2-positive metastatic breast cancer (MBC) has recently been reported. MATERIALS AND METHODS: Aims of this observational study were to evaluate the incidence of CNS metastases in HER-2-positive MBC patients, to define the outcome of patients with CNS metastases, and to identify the risk factors for CNS relapse. RESULTS: Between April 1999 and June 2005 we treated 122 consecutive HER-2-positive MBC patients with chemotherapy and trastuzumab. At a median follow-up of 28 months from the occurrence of metastatic disease, 43 patients (35.2%) developed CNS metastases. The median time to death from the diagnosis of CNS metastases was 23.46 months. At multivariate analysis we found that only premenopausal status at diagnosis of breast cancer and visceral metastases as the dominant site at relapse were significantly associated with a higher risk for CNS metastases. CONCLUSION: The CNS metastasis incidence is very high in HER-2-positive MBC, but the survival after CNS relapse in these patients is longer than in patients unselected for HER-2 status, because of the better control of extracranial disease obtained by trastuzumab. The identified risk factors for CNS relapse could allow us to select a subgroup of HER-2-positive MBC patients as candidates for active surveillance for CNS progression (by computed tomography or magnetic resonance imaging) and/or as candidates for accrual in trials of prevention of CNS relapse.

Double-blind evaluation of analgesic efficacy of orally administered diclofenac, nefopam, and acetylsalicylic acid (ASA) plus codeine in chronic cancer pain.

The analgesic efficacy and toxicity of oral diclofenac sodium 50 mg (q.i.d.) vs. nefopam 60 mg (q.i.d.) and a combination of 640 mg ASA and 40 mg codeine (q.i.d.) in cancer patients with moderate to severe chronic pain has been evaluated in a randomized double-blind study. Planned duration of treatment was 10 days. Pain intensity was evaluated by a visual analog scale. The length of patient participation in the trial, the patient's final global evaluation and the incidence of side effects were also evaluated. Ninety-nine patients were enrolled in the study. All treatments produced a statistically significant pain relief (P less than 0.01) without differences among groups but only 26 of 99 patients (26.3%) completed the planned treatment period. Mean time in the study was 4.65 days. Inefficacy and side effects were the main reasons for premature treatment interruption. Patients treated with nefopam had a significantly shorter period in the study than patients treated with the other 2 treatments. Adverse effects were slightly more frequent with the nefopam and ASA + codeine regimens. The 3 therapeutic regimens appear to be similar as to analgesic efficacy, but diclofenac presents the advantage of a slightly better safety profile than nefopam and the ASA + codeine combination.