(2006) Incidence, pattern and timing of brain metastases among patients with advanced breast cancer treated with trastuzumab, Acta Oncologica, 45:2,[196][197][198][199][200][201]

No abstract

In the Kingdom of Saudi Arabia (KSA), breast cancer constitutes 18% of all cancers in Saudi women. Whilst locally advanced breast cancer disease is unusual in Western countries, it constitutes more than 40% of all non-metastatic breast cancer in KSA. The relative frequency of locally advanced disease among our breast cancer population and the lack of a uniform consensus in the literature about its optimal management have prompted this retrospective analysis of the medical records of patients with Stage III breast cancer patients seen at King Faisal Specialist Hospital and Research Center between 1981 and 1991. In all, 315 patients were identified. Their median age +/- SD was 46 +/- 11.6 years which is distinctly different from the 60-65 years median age in industrial Western nations. Most patients were younger than 50 years (64%) and premenopausal (62%). Patients were approximately equally divided between Stage IIIA and Stage III B. Patients received multimodality treatment, including surgery, adjuvant chemotherapy, tamoxifen, and adjuvant radiotherapy. Sixty-one patients were excluded from survival analysis as they were considered lost to follow-up. Of the remaining 254 patients, 73 (29%) were alive and disease free, and 18 patients (7%) were alive but with evidence of the disease. The remaining 163 (64%) had died from breast cancer or its related complications. Their median overall survival (OS) was 54 months, (95% CI, 27 to 121 months) and the median progression-free survival (PFS) was 28.8 months (95% CI, 14.2 to 113 months). Cox proportional hazard model identified Stage III B and the number of positive axillary lymph nodes as poor predictors of OS and PFS. Radiotherapy was the only adjuvant modality that affected survival favourably. The prognosis of patients with Stage III disease remains poor despite the use of a multimodality approach. The overall young age of our patients may have contributed to the poor outcome. Moreover, the adverse effect of Stage III B disease (as compared with Stage III A) and axillary nodal status was evident. Whilst the favourable effect of radiotherapy on survival was demonstrated, the lack of independent efficacy of other modalities (adjuvant chemotherapy and tamoxifen) or the apparent deleterious effect of neoadjuvant chemotherapy should be addressed with discretion in such retrospective analysis. Optimal management of patients with locally advanced breast cancer disease should be appraised in well designed, prospective, randomised studies.

Summary.-The transplantability of a xenografted human adenocarcinoma has been examined in mice that had been immune-suppressed by thymectomy and whole -body irradiation and the results have been compared with transplantation into athymic (nude) mice. Two alternative techniques were used to prevent marrow failure following whole-body irradiation: reconstituting the animals with a marrow graft, or protecting them by an injection of cytosine arabinoside (Ara-C) 2 days before the irradiation. The results show that the Ara-C-prepared mice were more receptive to transplantation than marrow-grafted or nude mice, and they were the only animals that developed regional metastases from implanted xenografts. Some recovery of immunity occurred in both types of immune-suppressed mice, which was evident more than 5 weeks after immune-suppression and which was more marked in females than in males. It was concluded that the immune-suppressed mice were superior to nude mice for short-term experiments but they may be less satisfactory for long-term experiments.DURING the past 5 years we have been engaged in a programme of research on the growth and response to treatment of human tumours grafted into immunesuppressed mice. The results that we have published so far (Pickard, Cobb and Steel, 1975;Kopper and Steel, 1975; Courtenay et al., 1976) were obtained with mice that had been immune-suppressed by a standard technique of thymectomy, wholebody irradiation, and marrow reconstitution. Within the past 18 months we have explored methods of improving the level of immune suppression, and this paper describes our results. MATERIAL AND METHODSOriginal method of immune suppression.-The original technique involved thymectomy at 3-4 weeks of age. Male and female mice of the Institute of Cancer Research colony of CBA/lac mice were used, and have continued to be employed throughout the work described here. The thymectomy was performed under ether anaesthesia. The mouse was laid out in a supine position, head towards the operator, and a 5-7 mm incision was made in the skin overlying the suprasternal notch. The neck muscles were pulled apart with 2 pairs of forceps and the sternum was split to a distance of 3 mm using sharppointed scissors. The 2 lobes of the thymus could then be easily seen and were quickly sucked out through a glass tube connected via a glass collecting-chamber to a rotary vacuum pump. Finally, the skin was closed with a single metal Michel clip, and the animal was immediately placed in a warm box while it recovered from the anaesthetic. A skilled operator could perform a thymectomy by this technique in about 1 min, with an operative mortality of less than 500.Two weeks after thymectomy the mice were given 900 rad whole-body irradiation from a 60Co source, and on the same day they received an i.v. injection of syngeneic marrow cells. The standard inoculum of nucleated marrow cells was in excess of 5 x 106. Marrow from non-thymectomized donors was used, on the basis of the work of Miller, Doak and Cross (1963). Tumour implant...