Riva Borovik

BACKGROUND: There have been many randomised trials of adjuvant prolonged polychemotherapy among women with early breast cancer, and an updated overview of their results is presented. METHODS: In 1995, information was sought on each woman in any randomised trial that began before 1990 and involved treatment groups that differed only with respect to the chemotherapy regimens that were being compared. Analyses involved about 18,000 women in 47 trials of prolonged polychemotherapy versus no chemotherapy, about 6000 in 11 trials of longer versus shorter polychemotherapy, and about 6000 in 11 trials of anthracycline-containing regimens versus CMF (cyclophosphamide, methotrexate, and fluorouracil). FINDINGS: For recurrence, polychemotherapy produced substantial and highly significant proportional reductions both among women aged under 50 at randomisation (35% [SD 4] reduction; 2p<0.00001) and among those aged 50-69 (20% [SD 3] reduction; 2p<0.00001); few women aged 70 or over had been studied. For mortality, the reductions were also significant both among women aged under 50 (27% [SD 5] reduction; 2p<0.00001) and among those aged 50-69 (11% [SD 3] reduction; 2p=0.0001). The recurrence reductions emerged chiefly during the first 5 years of follow-up, whereas the difference in survival grew throughout the first 10 years. After standardisation for age and time since randomisation, the proportional reductions in risk were similar for women with node-negative and node-positive disease. Applying the proportional mortality reduction observed in all women aged under 50 at randomisation would typically change a 10-year survival of 71% for those with node-negative disease to 78% (an absolute benefit of 7%), and of 42% for those with node-positive disease to 53% (an absolute benefit of 11%). The smaller proportional mortality reduction observed in all women aged 50-69 at randomisation would translate into smaller absolute benefits, changing a 10-year survival of 67% for those with node-negative disease to 69% (an absolute gain of 2%) and of 46% for those with node-positive disease to 49% (an absolute gain of 3%). The age-specific benefits of polychemotherapy appeared to be largely irrespective of menopausal status at presentation, oestrogen receptor status of the primary tumour, and of whether adjuvant tamoxifen had been given. In terms of other outcomes, there was a reduction of about one-fifth (2p=0.05) in contralateral breast cancer, which has already been included in the analyses of recurrence, and no apparent adverse effect on deaths from causes other than breast cancer (death rate ratio 0.89 [SD 0.09]). The directly randomised comparisons of longer versus shorter durations of polychemotherapy did not indicate any survival advantage with the use of more than about 3-6 months of polychemotherapy. By contrast, directly randomised comparisons did suggest that, compared with CMF alone, the anthracycline-containing regimens studied produced somewhat greater effects on recurrence (2p=0.006) and mortality (69% vs 72% 5-year survival; log-rank 2p=0.02). But this comparison is one of many that could have been selected for emphasis, the 99% CI reaches zero, and the results of several of the relevant trials are not yet available. INTERPRETATION: Some months of adjuvant polychemotherapy (eg, with CMF or an anthracycline-containing regimen) typically produces an absolute improvement of about 7-11% in 10-year survival for women aged under 50 at presentation with early breast cancer, and of about 2-3% for those aged 50-69 (unless their prognosis is likely to be extremely good even without such treatment). Treatment decisions involve consideration not only of improvements in cancer recurrence and survival but also of adverse side-effects of treatment, and this report makes no recommendations as to who should or should not be treated.

Seven cases of soft tissue sarcoma developing after primary or postoperative radiotherapy for breast carcinoma are reported. The sarcomas occurred within the irradiated volume, after a latent period of 4-26 years. These cases conform well to established criteria for the diagnosis of radiation-induced sarcoma. Chemotherapy, consisting of the four-drug combination CYVADIC (cyclophosphamide, vincristine, adriamycin, DTIC) was employed in six of the seven patients. Only two of them achieved partial remission, lasting only 2 and 3 months, respectively. The effectiveness of adriamycin-containing chemotherapy regimens in soft tissue sarcomas as well as the remote hazard of radiation-related sarcoma in primary or postoperative breast irradiation are discussed.

Forty-five patients with advanced ovarian carcinoma without prior chemotherapy were treated with cisplatin-Adriamycin (doxorubicin) combination, 50 mg/m2 intravenously, for 11 cycles. Second-look operation (SLO) was performed in patients without evidence of disease at the end of chemotherapy. Abdominopelvic irradiation was administered to those found to have microscopic or minimal disease (tumor less than 2 cm) at SLO. Forty patients were evaluable. Chemotherapy induced complete response in 56.7% and partial response in 16.7%. In 25% of the reoperated patients, no tumor was found; 30% had microscopic disease; 25% had minimal disease; and 20% had larger tumors. Two-year survival rate was 45%. The residual tumor left at initial operation, the histologic grade, and the response to chemotherapy influenced survival. Toxicity was moderate. There were three treatment-related deaths (one due to sepsis, one due to cardiotoxicity, and one at SLO, respectively). Radiotherapy was poorly tolerated after chemotherapy. The median duration of follow-up was 21.5 months. Further follow-up is needed to study the long-term benefits of this multimodal approach.

The aim of the present study was to determine the efficacy of transvaginal color flow imaging as a screening tool for ovarian cancer. Six hundred patients with previous breast carcinoma were screened for ovarian cancer. Screening was performed using transvaginal sonography with color flow imaging. Serum CA 125 levels were measured in patients with abnormal sonographic findings. Eighty-three percent of the ovaries were detected in the premenopausal patients by ultrasonographic scanning and only 26% of the ovaries were detected in the postmenopausal patients. Intraovarian blood vessels were detected in 11% of the premenopausal women. The PI was less than 1 in 80% of these ovaries, but, on repeated examinations, the values of PI increased in all the blood vessels to greater than 1. Intraovarian blood vessels were detected in 1.8% of the normal ovaries observed in the postmenopausal women, but PI was always greater than 1. Eleven women with complex ovarian cysts (not simple) and one woman with enlarged ovaries underwent explorative laparotomy. In three women, primary malignant ovarian tumors were diagnosed and in one woman metastatic ovarian cancer was diagnosed. The specificity of sonography in detecting malignant ovarian tumors was 97.5% and the positive predictive value was 25%. The specificity of color flow imaging in detecting primary malignant ovarian tumors was 99.8% and the positive predictive value was 60%. In selected groups of women, screening for ovarian cancer with transvaginal color flow imaging may be justified.