WITHDRAWN: Combined epirubicin and vinorelbine as first-line therapy in metastatic breast cancer: a pilot study performed by the Danish Breast Cancer Cooperative Group.

The publisher regrets that this is an accidental duplication of an article that has already been published in The Breast, 12 (2003) 42-50, doi:10.1016/S0960-9776(02)00180-7. The duplicate article has therefore been withdrawn.

Combined epirubicin and vinorelbine as first-line therapy in metastatic breast cancer: a pilot study performed by the Danish Breast Cancer Cooperative Group.

This pilot study investigated the tolerability and efficacy of increasing doses of epirubicin and vinorelbine as first-line chemotherapy for metastatic breast cancer. Acute toxicity was manageable at all dose levels for combinations of epirubicin 60-90 mg/m2 on day 1 and vinorelbine 15-25 mg/m2 on days 1 and 8 repeated every 3 weeks. Myelotoxicity was the most frequent toxic event, with a significant increase in grade 4 leukopenia from 0% at dose level 1 (60+15 mg/m2) to 26% at dose level 6 (90+25 mg/m2). Signs of acute or chronic cardiotoxicity grades 2-4 were seen in 15% of the patients and included arrhythmia and decreased function. No significant association was established between dose and nonhematological toxicity. Objective responses were observed in 49 of the 99 evaluable patients (49.5%, 95% CI 39.9-59.2), 18 being complete and 31 partial responses. Responses were observed at all six dose levels. In conclusion, acute toxicity was manageable at all dose levels for combinations of epirubicin 60-90 mg/m2 on day 1 and vinorelbine 15-25 mg/m2 on days 1 and 8. In the treatment of advanced breast cancer, improvement of the antitumor efficacy by the addition of vinorelbine to epirubicin remains to be demonstrated in a randomized phase III trial.

Late treatment-related morbidity in breast cancer patients randomized to postmastectomy radiotherapy and systemic treatment versus systemic treatment alone.

Late treatment-related morbidity after mastectomy and adjuvant systemic treatment with and without postoperative irradiation was assessed in 84 patients randomized in the Danish Breast Cancer Cooperative Group Trials 82b and c. A structured interview and physical examination, using a standardized assessment sheet, constructed on the basis of the late effects normal tissues (LENT) scoring system, was used. The median length of follow-up from mastectomy was 9 years (range 6-13 years). Lymphedema was measured in 14%, of the irradiated patients versus 3% of the non-irradiated patients (NS). Slightly decreased shoulder morbidity was measured in 45% of the irradiated women versus 15% of the non-irradiated patients, but moderate or more severe impairment was seen in only 5% of the irradiated patients and in none of the non-irradiated patients (p = 0.004). Seventeen percent of the irradiated patients and 2% of the non-irradiated patients found that impairment of shoulder movement caused symptoms (p = 0.001).

Treatment of breast-cancer-related lymphedema with or without manual lymphatic drainage--a randomized study.

A prospective randomized study was carried out to investigate whether the addition of manual lymphatic drainage (MLD) to the standard therapy could improve treatment outcome in women with lymphedema of the ipsilateral arm after breast cancer treatment. Forty-two patients were randomly assigned to receive standard therapy or standard therapy plus MLD 8 times in 2 weeks and training in self-massage. The standard therapy consisted of use of a compression garment, exercises and information about lymphedema and skin care. The efficacy of treatment was evaluated by reduction in lymphedema volume during treatment and by improvement in symptoms potentially related to lymphedema. The patients were followed-up for a total of 12 months. The study showed that both groups obtained a significant reduction in edema and that MLD did not contribute significantly to reduce edema volume.

Morbidity and mortality of ischaemic heart disease in high-risk breast-cancer patients after adjuvant postmastectomy systemic treatment with or without radiotherapy: analysis of DBCG 82b and 82c randomised trials. Radiotherapy Committee of the Danish Breast Cancer Cooperative Group.

BACKGROUND: Radiotherapy in addition to systemic treatment after mastectomy prolongs survival in high-risk breast-cancer patients. However, adjuvant radiotherapy has a potential association with ischaemic heart disease. We assessed morbidity and mortality from ischaemic heart disease in patients treated with postmastectomy radiotherapy. METHODS: Between 1982 and 1990, we randomly assigned 3083 women at high risk of breast cancer, after mastectomy, adjuvant systemic treatment with (n=1538) or without (n=1545) radiotherapy. An anterior photon field was used against the periclavicular region and the axilla. The chest wall was treated through two anterior shaped electron fields, one including the internal mammary nodes. The intended dose was 48-50 Gy in 22-25 fractions, at four to five fractions per week. We obtained information on morbidity and mortality of ischaemic heart disease over a median of 10 years. Analysis was by intention to treat. FINDINGS: More women in the no-radiotherapy group than in the radiotherapy group died of breast cancer (799 [52.5%] vs 674 [44.2%]), whereas similar proportions of each group died from ischaemic heart disease (13 [0.9%] vs 12 [0.8%]). The relative hazard of morbidity from ischaemic heart disease among patients in the radiotherapy compared with the no-radiotherapy group was 0.86 (95% CI 0.6-1.3), and that for death from ischaemic heart disease was 0.84 (0.4-1.8). The hazard rate of morbidity from ischaemic heart disease in the radiotherapy group compared with the no-radiotherapy group did not increase with time from treatment. INTERPRETATION: Postmastectomy radiotherapy with this regimen does not increase the actuarial risk of ischaemic heart disease after 12 years.