Survival after adding capecitabine and trastuzumab to neoadjuvant anthracycline-taxane-based chemotherapy for primary breast cancer (GBG 40--GeparQuattro).

BACKGROUND: The GeparQuattro study showed that adding capecitabine or prolonging the duration of anthracycline-taxane-based neoadjuvant chemotherapy from 24 to 36 weeks did not increase pathological complete response (pCR) rates. Trastuzumab-treated patients with HER2-positive disease showed a higher pCR rate than patients with HER2-negative disease treated with chemotherapy alone. We here present disease-free (DFS) and overall survival (OS) analyses. PATIENTS AND METHODS: Patients (n = 1495) with cT ≥ 3 tumors, or negative hormone-receptor status, or positive hormone-receptor and clinically node-positive disease received four times epirubicin/cyclophosphamide and were thereafter randomly assigned to four times docetaxel (Taxotere), or four times docetaxel/capecitabine over 24 weeks, or four times docetaxel followed by capecitabine over 36 weeks. Patients with HER2-positive tumors received 1 year of trastuzumab, starting with the first chemotherapy cycle. Follow-up was available for a median of 5.4 years. RESULTS: Outcome was not improved for patients receiving capecitabine (HR 0.92; P = 0.463 for DFS and HR 93; P = 0.618 for OS) as well as for patients receiving 36 weeks of chemotherapy (HR 0.97; P = 0.818 for DFS and HR 0.97; P = 0.825 for OS). Trastuzumab-treated patients with HER2-positive disease showed similar DFS (P = 0.305) but a significantly better adjusted OS (P = 0.040) when compared with patients with HER2-negative disease treated with chemotherapy alone. Recorded long-term cardiac toxicity was low. CONCLUSIONS: Long-term results, similar to the results of pCR, do not support the use of capecitabine in the neoadjuvant setting in addition to an anthracycline-taxane-based chemotherapy. However, the results support previous data showing a benefit of trastuzumab as predicted by higher pCR rates.

[Chemoprevention of breast cancer: a literature review and report on the current status in Germany]. / Medikamentöse Prävention des Mammakarzinoms: eine Ubersicht über die Literatur und den Stand in Deutschland.

The prevention of breast cancer is increasingly of focus in health-politics policies and has gained a valid position in the area of medical intervention. Data from a current meta-analysis of all four randomised Tamoxifen prevention studies illustrate a reduction of 38 % (Odds ratio 0.62; 95 % CI 0.42-0.89) in the incidence of breast cancer. This observation lead to registration of this drug in the USA for the prevention of breast cancer in women with a calculated 5-year risk of > 1.66 %. In addition to Tamoxifen, further substances are currently being tested with the aim of improving the therapeutic index whilst reducing incidence and mortality rates. These are primarily substances which have proven efficacy in the treatment of breast cancer (other antioestrogens, aromatase inhibitors and GnRH-analogues) or those whose mechanism of action predict a preventative effect (retinoids, phytooestrogens, substitution preparations e. g. Tibolone). In Germany, chemoprevention is currently only to be recommended within study protocols, as to date no substance is approved in the indication 'prevention of breast cancer'. A essential contribution to the accrual of valid data is the conduct of breast cancer prevention trials. The participation of women with high risk of breast cancer in Germany is, in contrast to comparable international studies, problematic. Data on the current knowledge and attitude of the female population towards such trials (gathered via a questionnaire of the DACH in 7 000 women) show that only 19.5 % of the women questioned during a consultation with a gynaecologist were aware of the possibility of active chemoprevention. However, 55.3 % stated that they would be prepared to take such a substance, were chemoprevention possible. Studies for both pre- and post-menopausal women with increased risk of breast cancer are currently active in Germany (GISS and IBIS-II of the study group GABG - German Adjuvant Breast cancer Group). An intensive information campaign to raise public awareness of breast cancer risk amongst women and their physicians is planned in conjunction with the IBIS-II study (www.brustkrebsvorbeugen.de). Latest literature recommendations for prevention of breast cancer (Chlebowski et al.) have been assessed.