Single-agent gemcitabine as second- and third-line treatment in metastatic breast cancer.

In the present study, 25 patients with breast cancer pretreated with one or two anthracycline-based regimens for visceral metastases were enrolled. Patients were treated with gemcitabine 1250 mg/m2 on days 1, 8 and 15, q28d. Nine patients received gemcitabine as second-line treatment, whereas 16 patients received gemcitabine as third-line cytotoxic treatment, respectively. In the second-line setting, two (22%) patients gained PR (RR 22%) and four (44%) patients experienced SD (P=0.2), respectively. In the third-line-setting, one (6%) patient gained CR, one patient PR (6%) and four patients (25%) SD, respectively, resulting in a response rate (RR) of 12%. In the second-line-setting, median time to progression was 5.1 +/- 4.0 months (range: 1.6-13.9) versus 3.5-2.5 months (range: 1.3-10.4) in the third-line-setting. Median overall survival was 12.6 +/- 9.1 months (range: 3.9-30.8) versus 7.5 +/- 6.7 months (range: 2.0-26.0), respectively. Overall, no patient experienced treatment limiting toxicities. We conclude from the present study that gemcitabine induced an overall RR of 16% following prior treatment with anthracyclines. However, median time to progression and median overall survival were limited. In the search for efficacious treatment of patients with metastatic breast cancer, gemcitabine constitutes a valid tool in anthracycline-resistant disease and thus might represent a valuable option for combination chemotherapy in controlled trials in this condition.

Attitude towards prophylactic surgery and effects of genetic counselling in families with BRCA mutations. Austrian Hereditary Breast and Ovarian Cancer Group.

The intent of this study was to evaluate the effect that an awareness of being a BRCA1 or BRCA2 mutation carrier has on the attitude towards prophylactic surgery and on developing depression symptoms. Thirty-five families were selected on the basis of previously detected BRCA1 or 2 mutations and 90 family members were given the appropriate questionnaires. Prophylactic mastectomy (PM) was considered by 21% of the Austrian mutation carriers (29% affected and 8% non-affected carriers). The majority of affected and non-affected carriers expected PM to impair the quality of their life. Fifty per cent would undergo prophylactic oophorectomy (53% affected and 46% non-affected carriers). The self-rating depression scale indicated that following mutation result disclosure the depression scores of carriers decreased (40 baseline vs 38 after result disclosure, P = 0.3), whereas, for non-carriers, scores increased (36 baseline vs 40 after result disclosure, P = 0.05). We conclude that information about carrier status is not associated with increased depression symptoms in mutation carriers. In non-carriers, depression scores increased slightly, probably reflecting survivor guilt. The option of having PM was associated with a negative impact on the quality of life and was declined by the majority of Austrian mutation carriers.

BRCA1-related breast cancer in Austrian breast and ovarian cancer families: specific BRCA1 mutations and pathological characteristics.

We identified 17 BRCA1 mutations in 86 Austrian breast and ovarian cancer families (20%) that were screened for mutations by denaturing high-performance liquid chromatography (DHPLC) and the protein truncation test (PTT). Eleven distinct mutations were detected, 4 of them (962del4, 2795del4, 3135del4 and L3376stop) not previously reported in families of non-Austrian origin. In addition, 6 rare missense mutations (allele frequency < 1%) with unknown biological effects were identified. Four mutations occurred more than once in the Austrian population: 2795del4 (3 times), Cys61Gly (3 times) 5382insC (2 times) and Q1806stop (2 times). Haplotype analysis of the 4 recurrent mutations suggested a common ancestor for each of these. Thirty-four breast cancer cases from 17 families with BRCA1 mutations were further analyzed. We observed a low median age of onset (39.5 years). Sixty-eight percent of all BRCA1 breast cancer cases had negative axillary lymph nodes. This group showed a significant prevalence of a negative estrogen and progesterone receptor status and stage I tumors compared with an age-related, node-negative control group. The prevalence of grade III tumors was marginally significant. Survival analysis either with a control group matched for age (within 5 years), grade, histologic subtype and estrogen receptor status, or with an age-related, node-negative comparison group, showed no statistical difference.