May 23, 2008 (ScienceDaily) — A unique genetic signature can alert physicians to high-risk breast tumors that are masquerading as low-risk tumors, according to research at Washington University School of Medicine in St. Louis and collaborating institutions. Although these tumors are apparently estrogen-receptor positive - meaning they should depend on estrogen to grow - they don't respond well to anti-estrogen therapy.
Until now, doctors had no way to know these tumors would be unresponsive because their pathology is deceptive - the tumors appear to be more easily treatable estrogen-receptor-positive tumors, but they rapidly lose their estrogen receptors. The researchers demonstrated that the chance for cancer recurrence in such patients is significantly higher, and standard post-operative care with long-term anti-estrogen therapy is often not effective. The genetic signature defined by the researchers will permit doctors to identify their high-risk patients and direct them to more effective therapy.
"These tumors are like wolves in sheep's clothing," says Matthew Ellis, M.D., Ph.D., associate professor of medicine in the Division of Medical Oncology and a faculty member at the Siteman Cancer Center. "When these patients come in, their tumors test positive for estrogen receptors, so they are started on anti-estrogen treatment with the thought that they will do fine. But these tumors don't depend on estrogen at all for growth and will keep growing during the therapy. Now we have a robust way to identify such tumors soon after diagnosis."
The researchers findings will be presented June 2 at 10:45 a.m. CT at the 2008 American Society of Clinical Oncology Annual Meeting in Chicago.
"We've been interested in how to predict relapse in patients with estrogen-receptor-positive breast cancer," Ellis says. "So we looked for genetic expression profiles associated with relapse, but we took a very different approach from previous studies that addressed this question."
Instead of just profiling gene expression in patients' tumors at diagnosis, Ellis and colleagues at a number of other comprehensive cancer centers, also tested tumor gene expression one month after the start of treatment with letrozole, an aromatase inhibitor that blocks the body's estrogen production. All the study participants had been diagnosed with estrogen-receptor-positive tumors and were put on letrozole therapy to shrink tumors before surgery.
"It makes intuitive sense that the genetic features of the tumor in the presence of letrozole reflect the tumor's response to the drug and would be much more predictive of outcome than its features in the absence of the drug," explains Ellis, a Washington University oncologist at Barnes-Jewish Hospital.
The team first identified the 50-gene signature using pretreatment tumor samples. They compared gene expression in tumors of patients with estrogen-receptor-positive tumors who had good outcomes to those whose outcomes were poor.
Then they initiated a five-year clinical trial to assess the predictive ability of the gene expression profile when it was obtained after one month of letrozole therapy. In a study of 56 postmenopausal women with estrogen-receptor-positive stage 2 or 3 breast tumors, Ellis's group demonstrated that the post-letrozole genetic expression signature in the 50-gene set was much more predictive than the pretreatment genetic profile. Based on the post-letrozole profile, they found they could rank tumors as low-, medium- and high-risk.
In the low-risk group, 81 percent of patients had a complete or partial response to treatment, which in addition to presurgical letrozole treatment included surgery followed by letrozole and radiation or chemotherapy at their doctors' discretion. In the medium-risk group, 70 percent had this favorable response; while in the high-risk group, only 25 percent responded to therapy.
Overall, 15 percent of study participants had high-risk estrogen-receptor-positive tumors that were shown to later switch to estrogen-receptor-negative tumors. Such tumors did not shrink during anti-estrogen treatment as do most estrogen-receptor-positive tumors, and patients with these tumors were far more likely to relapse. Two-thirds of high-risk patients experienced a relapse compared to 6 percent to 8 percent of the low- and medium-risk groups.
The research team plans to patent the gene-expression profile and make it available for use through University Genomics, a company co-owned by Washington University, the University of Utah and the University of North Carolina.
A clinical test for the high-risk gene expression signature is projected to be available for diagnostic use later this year and will be validated in clinical trials. Information about the test will be distributed at the ASCO meeting at the ARUP Laboratories (Associated Regional and University Pathologists Inc.) booth. ARUP is a national full-service reference laboratory owned by the University of Utah that will perform the gene-expression test.
Ellis says that it should be easy to incorporate the test into standard breast-cancer therapy protocols. As soon as patients are diagnosed with estrogen-receptor-positive breast cancer, they would be placed on an anti-estrogen agent like letrozole. Then their tumors would be retested at the time of surgery to see if the gene-expression test indicates that their tumor has responded to the anti-estrogen agent.
"Those with resistant tumors would be shifted immediately following surgery to chemotherapy designed for patients with high-risk breast cancer," Ellis says. "That's extraordinarily powerful and a potentially big advance in individualized care."
Funding from the National Cancer Institute and the Avon Foundation supported this research.
June 26, 2008 -- All women could soon be offered a genetic test which would tell them whether they were likely or unlikely to contract breast cancer, scientists will say today.
The test could have profound implications for the NHS breast screening programme. Researchers from Cambridge University say that women whose test result shows they are at high risk could be called for screening at a much younger age, while those at low risk could defer mammograms until they are 55 or older.
The test could be a simple mouth swab, said Dr Paul Pharoah from Cambridge University's department of oncology. The technology, used already by commercial DNA profiling agencies, exists to do it now. "To design a test is relatively straightforward if the powers that be thought it was worthwhile," he said.
In a paper published today in the New England Journal of Medicine, Pharoah and colleagues say that there are seven genetic variants - apart from the well-known, if rare, high-risk genes such as BRCA1 and BRCA2 - which have been discovered to increase a woman's risk of breast cancer, particularly if she has certain combinations of them. More are still being discovered.
The scientists say testing women in this way, perhaps around the age of 30, to find out whether they are at high or low risk, could improve NHS screening.
Currently, women are invited for their first mammogram at the age of 50, although a pilot has been set up to trial screening at 45. But aiming screening at all 50-year-old women may not be the most effective way to save lives, as some younger women could have a higher risk than some women of 55.
Deferring their mammogram might suit some women. Controversy continues over breast screening after analyses of the original trials by scientists from the Cochrane Collaboration, who say the benefits are not clear-cut and that significant numbers of women are given a false positive result, causing anxiety and in some cases leading to unnecessary treatment.
Pharoah and colleagues say that women who get a genetic test result suggesting they are low risk should not be compelled to forgo screening - it would have to be their choice.
Low risk does not mean no risk. The variants so far discovered account probably for a third of all the genetic components of breast cancer. The paper identifies seven, five of which were found by the Cambridge team, but two more have come to light since it was written. Within the next 10 years, Pharoah estimates that scientists may have pinpointed half of them, but the rest will be more difficult to identify, he believes.
Lifestyle factors, such as the age at which women have children and whether they breastfeed, also play a major role. Those factors could be take into account to get a more accurate picture of the risk.
Professor Sir Bruce Ponder, director of Cancer Research UK's Cambridge Research Institute at the university and lead author of the paper, said: "It is very exciting to see workable and affordable approaches to genetic screening for breast cancer on the horizon. We expect such technology to develop very fast in the next decade, so it's important that we start thinking about how best to apply these advances."
He said that if a genetic test could identify women who would benefit most from screening and early diagnosis, "we have every prospect to being able to reduce the number of deaths from breast cancer".
A Department of Health spokesman last night welcomed the research "which shows how we may be able to use genetic information in the future to identify those at higher risk of developing breast cancer".
Jeudi 9 octobre 2008 -- Maladie connue depuis l’Antiquité, le cancer continue à faire des centaines de milliers de victimes chaque année dans le monde, et la seule arme efficace demeure le diagnostic précoce. “Chaque année nous enregistrons entre 5 000 et 7 000 nouveaux cas de cancer du sein en Algérie”, a déclaré le Dr Dilem, spécialiste en sénologie au Centre Pierre-et-Marie-Curie (CPMC), lors d’une conférence de presse organisée hier à la maison de la presse Tahar-Djaout par l’association Nour Doha d’aide aux personnes atteintes de cancer. Si le cancer du sein est le thème de cette manifestation, car octobre est le mois mondial de cette pathologie, il n’en demeure pas moins que le problème de la prise en charge des cancéreux a été abordée. Mme Gasmi, la présidente de l’association, rappelle que la cancer est une maladie grave, mais invite les femmes de plus de 45 ans à ne pas hésiter à faire, chaque année, une mammographie pour éloigner tout danger. “Certes, le cancer est grave, mais plus il est pris en charge tôt, plus les chances de survie augmentent”, déclare la présidente de l’association Nour Doha.
Si les raisons de l’apparition du cancer restent un mystère, les médecins estiment que les impacts environnementaux du monde moderne (obésité, cholestérol, la prise de contraceptif, l’abandon de l’allaitement maternel par les femmes, les irradiations, etc.), peuvent être des facteurs favorisant l’apparition des néoplasies. En Algérie, ces facteurs inhérents à la vie moderne existent, car le niveau de vie des citoyens évolue, le mode de vie change et la femme est aujourd’hui active. Le cancer du sein est devenu la première cause de mortalité chez la femme. Cela a conduit l’OMS à déclarer tous les mois d’octobre “mois du cancer du sein”. Il s’agit en premier d’une volonté de sensibilisation envers les femmes qui sont invitées à se rendre chez les médecins pour le dépistage. “Les femmes ne doivent pas refuser le dépistage par peur du cancer. Une masse palpée n’est pas toujours une tumeur maligne, mais il faut consulter. D’ailleurs, la prise en charge précoce du cancer offre plus de chances de survie”, ajoute le Dr Dilem qui est aussi le président du Conseil scientifique de l’association.
Si la prise en charge des cancers à leur début offre des avantages certains aux patients, cela est aussi bénéfique pour la collectivité : le traitement d’un cancer avancé est plus onéreux sans pour autant offrir de chances supplémentaires de survie. “Selon le Pr Bouzid, la prise en charge d’un cas de cancer du sein revient à 300 millions de centimes”, rappelle le Dr Dilem. Bien entendu, les spécialistes refusent de créer une atmosphère de cancérophobie chez les femmes, mais ils les encouragent tout de même à consulter.
La prise en charge dans les hôpitaux algériens se fait avec des médicaments et des équipements (appareils de radiothérapie) utilisés dans les pays développés. Les jeunes femmes bénéficient même d’une reconstitution mammaire (sein artificiel).
“Nous avons déjà réalisé une centaine de reconstitutions mammaires au CPMC, et il ne faut pas considérer cette opération comme une intervention de chirurgie esthétique”, explique le président du Conseil scientifique de l’association Nour Doha. Si les médecins recommandent le dépistage, sur le terrain les femmes rencontrent mille difficultés pour faire une mammographie, le nombre de mammographes étant très en deçà des besoins réels d’un pays comme l’Algérie. Mme Gasmi se félicite des mesures qui seront adoptées en 2009 : la contractualisation entre les hôpitaux et la Caisse nationale de la Sécurité sociale (Cnas) qui va créer 6 nouveaux centres d’imagerie médicale. Ces centres seront chargés, entre autres, du dépistage du cancer du sein. La présidente de l’association se plaint des pénuries de drogues de chimiothérapie qui pénalisent les malades.
Toujours à propos des drogues de chimiothérapie, le Dr Dilem espère que les pouvoirs publics permettront l’introduction en Algérie des nouveaux médicaments qui ont prouvé leur efficacité dans les pays développés. “Aujourd’hui, nous en sommes à la thérapie ciblée et de nouvelles molécules ont été développées pour le traitement spécifique de certains cancers”, explique le Dr Dilem. Ce dernier loue aussi les avantages du vaccin contre le cancer du col de l’utérus et souhaite que les jeunes filles algériennes en bénéficient. Il n’oublie pas de rappeler que le diagnostic précoce est le meilleur moyen de lutter contre tous les cancers.
CHICAGO, November 6, 2008: Women who have a history of migraine headaches are far less likely to develop breast cancer than other women, U.S. researchers said Thursday.
The study was the first to look at the relationship between breast cancer and migraines, and its findings may point to new ways of reducing a woman's breast cancer risk, they said.
"We found that, overall, women who had a history of migraines had a 30 percent lower risk of breast cancer compared to women who did not have a history of such headaches," said Dr. Christopher Li, whose findings appear in the journal Cancer Epidemiology, Biomarkers and Prevention.
Li, of the Fred Hutchinson Cancer Research Center in Seattle, said the reduction in risk was for the most common types of breast cancers: those driven by hormones like estrogen and progesterone.
Hormones also play a role in migraines, a brutal type of headache often accompanied by nausea, vomiting and heightened sensitivity to light and sound. Women are two to three times more likely than men to get migraines.
Although it is not exactly clear why women with a history of migraines had a lower risk for breast cancer, Li and colleagues suspect that hormones play a role. "Women who have higher levels of estrogen in their blood have higher levels of breast cancer," Li said in a telephone interview.
He added that migraines are often triggered by low levels of estrogen, such as when levels of the hormone fall during a woman's menstrual cycle.
Women who get migraines "may have a chronically lower baseline estrogen," Li said. "That difference could be what is protective against breast cancer."
For the study, Li and his colleagues analyzed data from two studies of 3,412 post-menopausal women in the Seattle area, 1,938 of whom had been diagnosed with breast cancer and 1,474 of whom had no history of breast cancer. Women in the study provided information on their migraine history.
They found women who had reported a clinical diagnosis of migraines had a 30 percent lower risk of developing hormonally sensitive breast cancers.
"Migraines are typically most severe among pre-menopausal women," Li said. "This study was all post-menopausal women."
Favorites
Digg
Del.icio.us
Furl
Magnolia
StumbleUpon
Google
Yahoo MyWeb
Linear Mode
