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Breast cancer marker distinguishes lesions
US
cancer
institute halts tamoxifen
The National Cancer Institute (NCI) has stopped ahead of schedule a clinical trial on long-term-efficacy of adjuvant tamoxifen therapy for pre-menopausal and postmenopausal women with axillary-
node-negative,
:
study
and Safety Monitoring Committee finished their analysis. 1166 women who had already received tamoxifen (20 mg/day) without relapse for 5 years were randomised to receive either drug for an additional 5 years or placebo. Based on actuarial estimates at 4 years of follow-up, researchers found that 5 years of tamoxifen gave a disease-free survival rate of 92%, as against 86% in: patients scheduled to receive 10 years of therapy. NCI pointed out that the results were unchanged whether or not 66 ineligible patients recruited from St Luc’s Hospital in Montreal were included in the , analysis (see Lancet Dec 2, p 1483).
;
oestrogen-receptor-posi-
tive breast cancer. Preliminary results of the study, Protocol B-14 of the National Surgical Adjuvant Breast and Bowel Project, showed no significant difference in survival in women taking tamoxifen for 5 years compared with women similarly treated for more than 5 years. NCI reported the results as a "clinical announcement" mailed to 22 000 US oncologists soon after the study’s Data
FDA approves tretinoin for treatment of APL The US Food and Drug Administration : has approved all-trans retinoic acid : (ATRA, tretinoin), a vitamin A derivative. : for the treatment of acute promyelocytic : leukaemia. The drug, to be marketed by Roche Laboratories under the name : Vesanoid, is the first retinoid to be : approved as a cancer treatment in the : United States. Vitamin A and other retinoids are : known to play important roles in normal embryogenesis, cell growth, and differen- : tiation. ATRA has been shown to induce remissions in patients with acute promye- : locytic leukaemia (APL) whose cells have : t(15;17) translocation. This translocation : : causes a fusion gene, PMLlRAR-a. RARa factor retinoic a is and transcription acid receptor. PML is less well under- : stood but also seems to be a DNA-binding protein. The protein product of the PMLlRAR-a fusion gene inhibits cell differentiation and promotes cell survival in the absence of retinoic acid.
,
Data just published by the Italian Medical Association (FNOMCeO, Federazione Nazionale degli Ordini dei Medici Chirurghi e degli Odontoiatri) show how the unrelenting growth in numbers of doctors in the country has given Italy one doctor for every 185 inhabitants. At one to 246 the north-western valley of Aosta has the lowest ratio. The ratio is one to 143 in Rome and Latium. In 1964 this ratio was one to 683 (at the start of the century it was one to 1480). A fourfold increase in the number of doctors in the past 30 years was paralleled by little increase in the population, now 57 million inhabitants. Of the more than 308 000 doctors now registered, 60 000 are unemployed and many more reported to be underemployed. In addition, threequarters of the 34 000 dentists are medical doctors who switched to dentistry. Every year the universities confer final
1552
David H Frankel
Breast
Although the mechanism of action of ATRA remains unclear, the drug induces terminal differentiation of the primitive derived from the promyelocytes leukaemia clone, allowing the re-estabnormal lishment of polyclonal haematopoeic populations in the bone : marrow and peripheral blood. Vesanoid was approved for the induction of remission in patients with acute promyelocytic leukaemia characterised by the presence of the t(15;17) translocation and/or the presence of the PML/RAR-&agr;; : gene who are refractory to, or who have: relapsed from, anthracycline chemotherapy, or for whom anthracycline-based : chemotherapy is contraindicated. Virtually all patients experience some side-effects from the treatment and about 25% develop retinoic-acid-APL syndrome, which should be treated at the first sign with steroids, said the FDA. :
cancer
distinguishes
marker lesions
Researchers in the United States report that they have may have found an early molecular marker that can be used to distinguish non-malignant breast lesions from breast carcinomas (Nature Medicine 1995; 1:1257-60). The marker is a measurement of the level of expression of mRNA of the cyclin Dl gene. Cyclin D
proteins
are
cell-cycle regulators thought
influence the progression of the cell cycle from G1 to the S phase. In the study, cyclin D mRNA expression was measured in 94 human breastbiopsy specimens using radiolabelled probes. The specimens included tissue with lesions that fell into four categories: (1) tissue with lesions thought to confer no or slightly increased risk of breast cancer, such as fibrocystic changes, sclerosing adenosis, and typical hyperplasia ; (2) tissue with atypical ductal Michael McCarthy hyperplasia, which confers a four-to-fivefold risk of breast cancer; (3) tissue with doctors ductal carcinoma in situ (DCIS), including non-comedo forms, which are poten: medical degrees on some 9000 candibut can remain : dates. At the beginning of the 1980s the tially malignant uncommitted to invasion and metastasis, FNOMCeO had started to appeal to the and non-comedo forms, which are consid: government to limit admissions to medto : ical schools in line with the nation’s ered be a committed precursor to invasive breast cancer; and, (4) tissue with : capacity to accommodate newly graduated physicians. Admission to medical . invasive breast cancer. The researchers found cyclin D mRNA : schools, which until the end of the 1960s: was overexpressed in only 18% of lesions of classical secrequired completion : ondary studies has since been practically in the first group of lesions, which confer : unlimited, irrespective of the high school no or only a slightly increased risk of degree obtained. Hence the number of cancer. Cyclin D mRNA overexpression doctors is as great as that in . was also found to be only 18% with atypiunemployed : : the generously manned hospitals of the . cal ductal hyperplasia. In contrast, cyclin : Italian national health service. Whatever D mRNA overexpression was much more : solution were to be adopted now, it is common in the carcinomas, being found depressing to consider that many physiin 76% of non-comedo forms of DCIS, : cians presently unemployed (and who 87% in comedo forms of DCIS, and 83% : never were employed) might well never . in invasive breast carcinoma lesions. escape this condition.
!
Italy supersaturated with
The clinical announcement reported similar results from the second phase of a Scottish trial of adjuvant tamoxifen not yet published. In that study, 70% of women who received tamoxifen for 5 years survived disease-free, compared with 62% who took it longer. Though the trends in disease-free survival between the two cohorts did not reach statistical significance in either trial, NCI investigators were satisfied they had sufficient evidence. "The B-14 data", they wrote, "taken together with the results of the Scottish trial, provide no evidence of benefit for continuing tamoxifen beyond 5 years".
to
;
;
;: ,
;
Bruno Simini
Michael
McCarthy
cancer
institute halts tamoxifen
The National Cancer Institute (NCI) has stopped ahead of schedule a clinical trial on long-term-efficacy of adjuvant tamoxifen therapy for pre-menopausal and postmenopausal women with axillary-
node-negative,
:
study
and Safety Monitoring Committee finished their analysis. 1166 women who had already received tamoxifen (20 mg/day) without relapse for 5 years were randomised to receive either drug for an additional 5 years or placebo. Based on actuarial estimates at 4 years of follow-up, researchers found that 5 years of tamoxifen gave a disease-free survival rate of 92%, as against 86% in: patients scheduled to receive 10 years of therapy. NCI pointed out that the results were unchanged whether or not 66 ineligible patients recruited from St Luc’s Hospital in Montreal were included in the , analysis (see Lancet Dec 2, p 1483).
;
oestrogen-receptor-posi-
tive breast cancer. Preliminary results of the study, Protocol B-14 of the National Surgical Adjuvant Breast and Bowel Project, showed no significant difference in survival in women taking tamoxifen for 5 years compared with women similarly treated for more than 5 years. NCI reported the results as a "clinical announcement" mailed to 22 000 US oncologists soon after the study’s Data
FDA approves tretinoin for treatment of APL The US Food and Drug Administration : has approved all-trans retinoic acid : (ATRA, tretinoin), a vitamin A derivative. : for the treatment of acute promyelocytic : leukaemia. The drug, to be marketed by Roche Laboratories under the name : Vesanoid, is the first retinoid to be : approved as a cancer treatment in the : United States. Vitamin A and other retinoids are : known to play important roles in normal embryogenesis, cell growth, and differen- : tiation. ATRA has been shown to induce remissions in patients with acute promye- : locytic leukaemia (APL) whose cells have : t(15;17) translocation. This translocation : : causes a fusion gene, PMLlRAR-a. RARa factor retinoic a is and transcription acid receptor. PML is less well under- : stood but also seems to be a DNA-binding protein. The protein product of the PMLlRAR-a fusion gene inhibits cell differentiation and promotes cell survival in the absence of retinoic acid.
,
Data just published by the Italian Medical Association (FNOMCeO, Federazione Nazionale degli Ordini dei Medici Chirurghi e degli Odontoiatri) show how the unrelenting growth in numbers of doctors in the country has given Italy one doctor for every 185 inhabitants. At one to 246 the north-western valley of Aosta has the lowest ratio. The ratio is one to 143 in Rome and Latium. In 1964 this ratio was one to 683 (at the start of the century it was one to 1480). A fourfold increase in the number of doctors in the past 30 years was paralleled by little increase in the population, now 57 million inhabitants. Of the more than 308 000 doctors now registered, 60 000 are unemployed and many more reported to be underemployed. In addition, threequarters of the 34 000 dentists are medical doctors who switched to dentistry. Every year the universities confer final
1552
David H Frankel
Breast
Although the mechanism of action of ATRA remains unclear, the drug induces terminal differentiation of the primitive derived from the promyelocytes leukaemia clone, allowing the re-estabnormal lishment of polyclonal haematopoeic populations in the bone : marrow and peripheral blood. Vesanoid was approved for the induction of remission in patients with acute promyelocytic leukaemia characterised by the presence of the t(15;17) translocation and/or the presence of the PML/RAR-&agr;; : gene who are refractory to, or who have: relapsed from, anthracycline chemotherapy, or for whom anthracycline-based : chemotherapy is contraindicated. Virtually all patients experience some side-effects from the treatment and about 25% develop retinoic-acid-APL syndrome, which should be treated at the first sign with steroids, said the FDA. :
cancer
distinguishes
marker lesions
Researchers in the United States report that they have may have found an early molecular marker that can be used to distinguish non-malignant breast lesions from breast carcinomas (Nature Medicine 1995; 1:1257-60). The marker is a measurement of the level of expression of mRNA of the cyclin Dl gene. Cyclin D
proteins
are
cell-cycle regulators thought
influence the progression of the cell cycle from G1 to the S phase. In the study, cyclin D mRNA expression was measured in 94 human breastbiopsy specimens using radiolabelled probes. The specimens included tissue with lesions that fell into four categories: (1) tissue with lesions thought to confer no or slightly increased risk of breast cancer, such as fibrocystic changes, sclerosing adenosis, and typical hyperplasia ; (2) tissue with atypical ductal Michael McCarthy hyperplasia, which confers a four-to-fivefold risk of breast cancer; (3) tissue with doctors ductal carcinoma in situ (DCIS), including non-comedo forms, which are poten: medical degrees on some 9000 candibut can remain : dates. At the beginning of the 1980s the tially malignant uncommitted to invasion and metastasis, FNOMCeO had started to appeal to the and non-comedo forms, which are consid: government to limit admissions to medto : ical schools in line with the nation’s ered be a committed precursor to invasive breast cancer; and, (4) tissue with : capacity to accommodate newly graduated physicians. Admission to medical . invasive breast cancer. The researchers found cyclin D mRNA : schools, which until the end of the 1960s: was overexpressed in only 18% of lesions of classical secrequired completion : ondary studies has since been practically in the first group of lesions, which confer : unlimited, irrespective of the high school no or only a slightly increased risk of degree obtained. Hence the number of cancer. Cyclin D mRNA overexpression doctors is as great as that in . was also found to be only 18% with atypiunemployed : : the generously manned hospitals of the . cal ductal hyperplasia. In contrast, cyclin : Italian national health service. Whatever D mRNA overexpression was much more : solution were to be adopted now, it is common in the carcinomas, being found depressing to consider that many physiin 76% of non-comedo forms of DCIS, : cians presently unemployed (and who 87% in comedo forms of DCIS, and 83% : never were employed) might well never . in invasive breast carcinoma lesions. escape this condition.
!
Italy supersaturated with
The clinical announcement reported similar results from the second phase of a Scottish trial of adjuvant tamoxifen not yet published. In that study, 70% of women who received tamoxifen for 5 years survived disease-free, compared with 62% who took it longer. Though the trends in disease-free survival between the two cohorts did not reach statistical significance in either trial, NCI investigators were satisfied they had sufficient evidence. "The B-14 data", they wrote, "taken together with the results of the Scottish trial, provide no evidence of benefit for continuing tamoxifen beyond 5 years".
to
;
;
;: ,
;
Bruno Simini
Michael
McCarthy