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Breast-cancer changes predicted for next decade
SCIENCE AND MEDICINE
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nce again, a study has turned up poor results for a calcium antagonist, raising further questions about this embattled class of drugs. However, firm evidence against the drugs remains elusive. The primary goal of the Appropriate Blood Pressure Control in Diabetes (ABCD) trial is to compare intensive antihypertensive treatment with moderate treatment in patients with diabetes. As a secondary goal, the effect of the ACE inhibitor enalapril was compared with that of the calcium antagonist nisoldipine. After 5 years follow-up, the US Data and Safety Monitoring Committee called for nisoldipine treatment to be stopped in the subgroup of 470 hypertensive patients with type-2 diabetes because of an excess of fatal and non-fatal myocardial infarctions (MIs): 25 in the nisoldipine group compared with five in the enalapril group (N Engl J Med 1998; 338: 645–52). After adjusting for differences in risk factors between the two groups, patients taking nisoldipine were 7·0 times more likely to have an MI than those taking enalapril. In the absence of a placebo group it is impossible to say whether the study shows a harmful effect of the calcium antagonist or a beneficial effect of the ACE inhibitor. The researchers, led by Raymond Estacio (University of Colorado, Denver, USA), offer one hint—the rate of MIs in the nisoldipine group was similar to that seen in historical controls. But even if they are not causing harm, some observers believe calcium antagonists should be used more sparingly. They should be “drugs of last resort in the treatment of people with high blood pressure”, says Michael Alderman (Albert Einstein College of Medicine, Bronx, NY, USA), noting the overwhelming amount of evidence in favour of diuretics, -blockers, and ACE inhibitors. What bothers Alderman is the “absence of good data comparing these drugs with the established drug classes. Remember”, he says, “the drugs didn’t come out yesterday. I suspect that the reasons for the failure to have more positive information are not trivial”.
Larry Husten
THE LANCET • Vol 351 • March 7, 1998
Breast-cancer changes predicted for next decade pening the 6th International Conference on Adjuvant Therapy of Primary Breast Cancer in St Gallen, Switzerland (Feb 25–28), Umberto Veronesi (Milan, Italy) predicted that, in the next decade, breast lesions will be detected at earlier stages, with about 50% of women presenting with T1 cancers. This changing patient population will lead to a change in treatment strategies. The sentinel node is the first node draining the cancer, and tumour cells in the node can be visualised by use of dyes or radiographic techniques. Charles Cox (Tampa, Florida) summarised world experience to date of sentinel-node mapping. Of 731 cases, sensitivity was 95% and the false-negative rate was 3·1%. “In experienced hands”, he added, “the false-negative rate approaches zero”. A risk factor is a characteristic that is linked with an increased or decreased risk of disease (eg, gender is a risk factor for breast cancer). A risk determinant is a risk factor that,
O
if changed, would alter the frequency or nature of the disease (eg, exposure to ionising radiation in early life). Peter Boyle (Milan, Italy) drew on this distinction, saying that risk factors may be seen as disease markers while a risk determinant is a cause. Reproductive variables are risk factors for breast cancer—early menarche, late menopause, and late child-bearing increase risk. But, said Boyle, these variables do not lend themselves to public-health interventions. Expressing data as populationattributable risk, Boyle and coworkers attribute about a third of breast cancers in Italy to potentially modifiable risk factors—eg, alcohol, diet, physical activity. “Intervention on these factors could, in principle, help to avoid 10 000 of the 30 000 breast-cancer cases which occur in Italy each year and thereby avoid about 3500 Italian breast-cancer deaths every year”, Boyle concluded. David McNamee
Antigen presentation key to melanoma vaccines showed objective cancer regression. ollowing hard on the heels of a Only 17% of patients treated with recent report that there is no eviIL-2 alone showed tumour regression dence that sunscreens are protective (Nat Med 1998; 4: 321–27). against melanoma development, two Frank Nestle (University of Zurich new papers paint a more hopeful picMedical School, ture for treatment Switzerland) and of melanoma. US colleagues used researchers report an alternative the evaluation of approach to a melanoma vacensure efficient cine made from a presentation of synthetic peptide, melanoma antiwhile a European gens to the team report vacciimmune system. nation with denThe researchers dritic cells loaded pulsed dendritic with melanoma Vaccination prospects look hopeful cells—antigenlysates. presenting cells specialised for the In the USA, Steven Rosenberg and induction of a primary T-cell his team (National Cancer Institute, response—with tumour lysate or a Bethesda, MD, USA) previously cocktail of peptides known to be identified immunodominant peptides recognised by cytotoxic T cells. 16 in melanoma-associated antigen patients with advanced melanoma gp100. To improve antigen presentawere immunised with autologous tion, the researchers introduced an dendritic cells. Delayed-type hyperaminoacid substitution into one of sensitivity was induced to peptidethese peptides, g209-217. Ten out of pulsed dendritic cells in 11 patients, 11 patients immunised with the subobjective tumour responses were seen stituted peptide, g209-2M, develin five (Nat Med 1998; 4: 328–32). oped reactivity against g209-217 and Further clinical trials are needed to against melanoma cells. There was show clinical efficacy and impact on no objective tumour reduction in any long-term survival, write the authors. of these patients, but in a further 31 patients treated with g209-2M and interleukin-2 (IL-2), 42% of patients Jane Bradbury
F
National Medical Slide Bank
Calcium antagonist stopped in ABCD study
731
O
nce again, a study has turned up poor results for a calcium antagonist, raising further questions about this embattled class of drugs. However, firm evidence against the drugs remains elusive. The primary goal of the Appropriate Blood Pressure Control in Diabetes (ABCD) trial is to compare intensive antihypertensive treatment with moderate treatment in patients with diabetes. As a secondary goal, the effect of the ACE inhibitor enalapril was compared with that of the calcium antagonist nisoldipine. After 5 years follow-up, the US Data and Safety Monitoring Committee called for nisoldipine treatment to be stopped in the subgroup of 470 hypertensive patients with type-2 diabetes because of an excess of fatal and non-fatal myocardial infarctions (MIs): 25 in the nisoldipine group compared with five in the enalapril group (N Engl J Med 1998; 338: 645–52). After adjusting for differences in risk factors between the two groups, patients taking nisoldipine were 7·0 times more likely to have an MI than those taking enalapril. In the absence of a placebo group it is impossible to say whether the study shows a harmful effect of the calcium antagonist or a beneficial effect of the ACE inhibitor. The researchers, led by Raymond Estacio (University of Colorado, Denver, USA), offer one hint—the rate of MIs in the nisoldipine group was similar to that seen in historical controls. But even if they are not causing harm, some observers believe calcium antagonists should be used more sparingly. They should be “drugs of last resort in the treatment of people with high blood pressure”, says Michael Alderman (Albert Einstein College of Medicine, Bronx, NY, USA), noting the overwhelming amount of evidence in favour of diuretics, -blockers, and ACE inhibitors. What bothers Alderman is the “absence of good data comparing these drugs with the established drug classes. Remember”, he says, “the drugs didn’t come out yesterday. I suspect that the reasons for the failure to have more positive information are not trivial”.
Larry Husten
THE LANCET • Vol 351 • March 7, 1998
Breast-cancer changes predicted for next decade pening the 6th International Conference on Adjuvant Therapy of Primary Breast Cancer in St Gallen, Switzerland (Feb 25–28), Umberto Veronesi (Milan, Italy) predicted that, in the next decade, breast lesions will be detected at earlier stages, with about 50% of women presenting with T1 cancers. This changing patient population will lead to a change in treatment strategies. The sentinel node is the first node draining the cancer, and tumour cells in the node can be visualised by use of dyes or radiographic techniques. Charles Cox (Tampa, Florida) summarised world experience to date of sentinel-node mapping. Of 731 cases, sensitivity was 95% and the false-negative rate was 3·1%. “In experienced hands”, he added, “the false-negative rate approaches zero”. A risk factor is a characteristic that is linked with an increased or decreased risk of disease (eg, gender is a risk factor for breast cancer). A risk determinant is a risk factor that,
O
if changed, would alter the frequency or nature of the disease (eg, exposure to ionising radiation in early life). Peter Boyle (Milan, Italy) drew on this distinction, saying that risk factors may be seen as disease markers while a risk determinant is a cause. Reproductive variables are risk factors for breast cancer—early menarche, late menopause, and late child-bearing increase risk. But, said Boyle, these variables do not lend themselves to public-health interventions. Expressing data as populationattributable risk, Boyle and coworkers attribute about a third of breast cancers in Italy to potentially modifiable risk factors—eg, alcohol, diet, physical activity. “Intervention on these factors could, in principle, help to avoid 10 000 of the 30 000 breast-cancer cases which occur in Italy each year and thereby avoid about 3500 Italian breast-cancer deaths every year”, Boyle concluded. David McNamee
Antigen presentation key to melanoma vaccines showed objective cancer regression. ollowing hard on the heels of a Only 17% of patients treated with recent report that there is no eviIL-2 alone showed tumour regression dence that sunscreens are protective (Nat Med 1998; 4: 321–27). against melanoma development, two Frank Nestle (University of Zurich new papers paint a more hopeful picMedical School, ture for treatment Switzerland) and of melanoma. US colleagues used researchers report an alternative the evaluation of approach to a melanoma vacensure efficient cine made from a presentation of synthetic peptide, melanoma antiwhile a European gens to the team report vacciimmune system. nation with denThe researchers dritic cells loaded pulsed dendritic with melanoma Vaccination prospects look hopeful cells—antigenlysates. presenting cells specialised for the In the USA, Steven Rosenberg and induction of a primary T-cell his team (National Cancer Institute, response—with tumour lysate or a Bethesda, MD, USA) previously cocktail of peptides known to be identified immunodominant peptides recognised by cytotoxic T cells. 16 in melanoma-associated antigen patients with advanced melanoma gp100. To improve antigen presentawere immunised with autologous tion, the researchers introduced an dendritic cells. Delayed-type hyperaminoacid substitution into one of sensitivity was induced to peptidethese peptides, g209-217. Ten out of pulsed dendritic cells in 11 patients, 11 patients immunised with the subobjective tumour responses were seen stituted peptide, g209-2M, develin five (Nat Med 1998; 4: 328–32). oped reactivity against g209-217 and Further clinical trials are needed to against melanoma cells. There was show clinical efficacy and impact on no objective tumour reduction in any long-term survival, write the authors. of these patients, but in a further 31 patients treated with g209-2M and interleukin-2 (IL-2), 42% of patients Jane Bradbury
F
National Medical Slide Bank
Calcium antagonist stopped in ABCD study
731