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Genes described that may help protect against cancer development
SCIENCE AND MEDICINE
Second drug said to reduce breast-cancer risk
J
ust 2 weeks after US researchers announced that tamoxifen had reduced breast-cancer incidence by almost half in women at high risk for the disease (see Lancet, April 11, p 1107), news has broken that raloxifene, a selective oestrogenreceptor modulator approved in the USA for treatment of osteoporosis, may also reduce breast-cancer risk. Results of two studies, obtained by financial analysts, were reported on April 20 on the front page of the Wall Street Journal even though the results were under embargo until the meeting of the American Society of Clinical Oncology
(ASCO) later this month (May 16–19). In response to the media reports, ASCO released abstracts for the studies but warned that the data in the abstracts were several months old and very preliminary. The researchers have been asked not to comment until after presenting their data at the meeting. The first study—lead author Victor Jordan (R H Lurie Cancer Center, Chicago, IL, USA)—combined safety data from randomised trials of raloxifene for treatment of osteoporosis involving more than 12 000 postmenopausal women. According to the abstract, there
was a 58% reduction in breastcancer risk among women on raloxifene compared with those on placebo. Median exposure to the drug was only 28 months. Steven Cummings (University of California, San Francisco, CA, USA) and colleagues looked at data from an osteoporosis trial involving 7700 women. After a median followup of 28·9 months, the researchers found that there was a 75% reduction in breast-cancer risk among women taking the drug compared with those taking placebo. Michael McCarthy
Genes described that may help protect against cancer development ot all smokers get lung cancer, and not everyone with a fibrepoor diet gets colon cancer. Scientists think that genetic variations in carcinogen metabolism may be behind these different susceptibilities. Two new reports lend support to this idea. Roland Wolf (Ninewells Hospital, Dundee, UK) and colleagues are studying glutathione S-transferase (GST). One subclass of this detoxifying enzyme, pi-class GST, has been implicated in tumour development. The scientists now report that mice in which both copies of the pi-class GST gene have been removed develop three to four times more skin
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cancers when painted with a carcinogen and a tumour promoter than do wild-type mice (Proc Natl Acad Sci USA 1998; 95: 5275–80). The authors say that the difference in tumour incidence “provides direct evidence that a single gene involved in drug metabolism can have a profound effect on tumorigenicity” and shows that GST may be an important determinant in cancer susceptibility. Another enzyme highlighted this week is microsomal epoxide hydrolase. David Harrison and his team at the University of Edinburgh, UK, tested whether people with bowel cancer had a less active variant of this
detoxifying enzyme than healthy people. The results released, by the UK Cancer Research Campaign on April 27, show that a less active form of epoxide hydrolase is present in 5% of the general population but in 20% of people with bowel cancer. These preliminary results “indicate an association, not a mechanism”, cautions Harrison. “Similarly, the Dundee results are not conclusive proof of why only some people get lung cancer. Any implication that these results may rapidly lead to a cure to cancer is probably hype.” Jane Bradbury
More effort needed to halt osteoporotic bone loss on prednisolone 7·5 mg or more per teroid-induced osteoporosis is a day for 6 months or longer should be problem that is not being effectargeted for prophylactic therapy for tively tackled”, said Jonathan Tobias bone loss. Vitamin D (Bristol, UK) at the and calcium suppleBritish Society for mentation should Rheumatology meetbe considered in ing in Brighton, UK all patients. Post(April 22–24). About menopausal women 0·5% of the general and premenopausal population is receiving women with ovarianlong-term steroid therhormone deficiency apy, but in a general should start hormone practice survey only replacement therapy about 14% had taken (HRT). Alendronate some form of prevensodium and etidronate tive treatment for bone Prevention instead of repair should also be considloss, he reported. ered for prevention or treatment of Steroid use leads to an increased steroid-induced osteoporosis. risk of fractures, and patients with Patrick Garnero (Lyon, France) rheumatoid disease are especially reported that the C-terminal (CTX) vulnerable since about half are and N-terminal (NTX) peptides of long-term users of steroids. But who type-1 collagen were helpful bioshould be treated for bone loss and chemical markers for prediction of how? Tobias suggested that patients
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THE LANCET • Vol 351 • May 2, 1998
bone loss in osteoporosis. In the OFELY study of 1000 women in Lyon after 4 years of follow-up, postmenopausal women (none of whom was on HRT) with abnormal urinary CTX or NTX peptide values—ie, greater than those in premenopausal women—lost two to five times more bone that those in whom marker values were normal. CTX and free deoxypyridinoline have also proved highly predictive of hip-fracture rate in osteoporosis, independent of bone mass. The gold standard for monitoring bone-loss treatment is repeat measurements of bone-mineral density over at least 2 years, but Garnero noted that biochemical bone markers could be useful in monitoring treatment more quickly, and in identification of who will respond to therapy. Stephanie Clark
1335
Second drug said to reduce breast-cancer risk
J
ust 2 weeks after US researchers announced that tamoxifen had reduced breast-cancer incidence by almost half in women at high risk for the disease (see Lancet, April 11, p 1107), news has broken that raloxifene, a selective oestrogenreceptor modulator approved in the USA for treatment of osteoporosis, may also reduce breast-cancer risk. Results of two studies, obtained by financial analysts, were reported on April 20 on the front page of the Wall Street Journal even though the results were under embargo until the meeting of the American Society of Clinical Oncology
(ASCO) later this month (May 16–19). In response to the media reports, ASCO released abstracts for the studies but warned that the data in the abstracts were several months old and very preliminary. The researchers have been asked not to comment until after presenting their data at the meeting. The first study—lead author Victor Jordan (R H Lurie Cancer Center, Chicago, IL, USA)—combined safety data from randomised trials of raloxifene for treatment of osteoporosis involving more than 12 000 postmenopausal women. According to the abstract, there
was a 58% reduction in breastcancer risk among women on raloxifene compared with those on placebo. Median exposure to the drug was only 28 months. Steven Cummings (University of California, San Francisco, CA, USA) and colleagues looked at data from an osteoporosis trial involving 7700 women. After a median followup of 28·9 months, the researchers found that there was a 75% reduction in breast-cancer risk among women taking the drug compared with those taking placebo. Michael McCarthy
Genes described that may help protect against cancer development ot all smokers get lung cancer, and not everyone with a fibrepoor diet gets colon cancer. Scientists think that genetic variations in carcinogen metabolism may be behind these different susceptibilities. Two new reports lend support to this idea. Roland Wolf (Ninewells Hospital, Dundee, UK) and colleagues are studying glutathione S-transferase (GST). One subclass of this detoxifying enzyme, pi-class GST, has been implicated in tumour development. The scientists now report that mice in which both copies of the pi-class GST gene have been removed develop three to four times more skin
N
cancers when painted with a carcinogen and a tumour promoter than do wild-type mice (Proc Natl Acad Sci USA 1998; 95: 5275–80). The authors say that the difference in tumour incidence “provides direct evidence that a single gene involved in drug metabolism can have a profound effect on tumorigenicity” and shows that GST may be an important determinant in cancer susceptibility. Another enzyme highlighted this week is microsomal epoxide hydrolase. David Harrison and his team at the University of Edinburgh, UK, tested whether people with bowel cancer had a less active variant of this
detoxifying enzyme than healthy people. The results released, by the UK Cancer Research Campaign on April 27, show that a less active form of epoxide hydrolase is present in 5% of the general population but in 20% of people with bowel cancer. These preliminary results “indicate an association, not a mechanism”, cautions Harrison. “Similarly, the Dundee results are not conclusive proof of why only some people get lung cancer. Any implication that these results may rapidly lead to a cure to cancer is probably hype.” Jane Bradbury
More effort needed to halt osteoporotic bone loss on prednisolone 7·5 mg or more per teroid-induced osteoporosis is a day for 6 months or longer should be problem that is not being effectargeted for prophylactic therapy for tively tackled”, said Jonathan Tobias bone loss. Vitamin D (Bristol, UK) at the and calcium suppleBritish Society for mentation should Rheumatology meetbe considered in ing in Brighton, UK all patients. Post(April 22–24). About menopausal women 0·5% of the general and premenopausal population is receiving women with ovarianlong-term steroid therhormone deficiency apy, but in a general should start hormone practice survey only replacement therapy about 14% had taken (HRT). Alendronate some form of prevensodium and etidronate tive treatment for bone Prevention instead of repair should also be considloss, he reported. ered for prevention or treatment of Steroid use leads to an increased steroid-induced osteoporosis. risk of fractures, and patients with Patrick Garnero (Lyon, France) rheumatoid disease are especially reported that the C-terminal (CTX) vulnerable since about half are and N-terminal (NTX) peptides of long-term users of steroids. But who type-1 collagen were helpful bioshould be treated for bone loss and chemical markers for prediction of how? Tobias suggested that patients
“
Science Photo Library
S
THE LANCET • Vol 351 • May 2, 1998
bone loss in osteoporosis. In the OFELY study of 1000 women in Lyon after 4 years of follow-up, postmenopausal women (none of whom was on HRT) with abnormal urinary CTX or NTX peptide values—ie, greater than those in premenopausal women—lost two to five times more bone that those in whom marker values were normal. CTX and free deoxypyridinoline have also proved highly predictive of hip-fracture rate in osteoporosis, independent of bone mass. The gold standard for monitoring bone-loss treatment is repeat measurements of bone-mineral density over at least 2 years, but Garnero noted that biochemical bone markers could be useful in monitoring treatment more quickly, and in identification of who will respond to therapy. Stephanie Clark
1335