Update: 15.09.2008
Many women 'do not check breasts'
Only 35% of women regularly check their breasts for signs of cancer - and 23% seldom or never do, a survey suggests.
The charity Breakthrough Breast Cancer surveyed 2,005 women aged between 18 and 64.
Over a third (37%) who reported not checking their breasts regularly said they did not know how to check - or what to look out for.
Nearly 46,000 UK women are diagnosed with breast cancer each year - making it the UK's most common form of cancer.
Breakthrough is launching a campaign to encourage more women to check their breasts regularly for changes, and to report anything suspicious to their doctor.
Early diagnosis of breast cancer offers the best chance of successful treatment.
Dr Sarah Cant, from Breakthrough, said: "We know that the earlier breast cancer is diagnosed the more likely it is that treatment will be successful.
"Checking your breasts isn’t complicated and there’s no need to follow a fancy routine.
"Just be familiar with how they look and feel normally."
The Breakthrough survey revealed widespread confusion over what signs to look out for when examining the breasts.
The majority of women (88%) recognised that lumps could be a possible sign of the disease.
However, only 12% of those surveyed identified changes in skin texture, such as puckering or dimpling of the skin, as a potential warning sign.
Just 7% knew that a sudden inversion of the nipple was something that should be reported to a doctor, and a mere 5% were aware that changes in the size or shape of a breast could be a sign of cancer.
In the UK, the focus is on breast "awareness", rather than more complex and involved checks.
Experts say there is no evidence that rigorous monthly "self-examination" reduces breast cancer deaths and it can lead to unnecessary biopsies.
Instead, women are advised to get to know what is normal for them, and feel their breasts regularly for signs of any changes.
Update: 21.07.2008
Australian women urged to be 'breast aware'
National Breast and Ovarian Cancer Centre is urging Australian women to be ‘breast aware’ and to report any changes in the look or feel of their breasts to their general practitioner without delay.
The advice comes as Australian women may be confused by new research from the Cochrane Collaboration showing no benefit in breast self-examination – a structured, taught approach to examining the breasts.
“What these studies show is that there is no benefit to being taught a specific technique to check your breasts,” said Director of National Breast and Ovarian Cancer Centre Dr Helen Zorbas.
“However, we know that more than half of all breast cancers are found as a result of a change in the look or feel of the breast, so it is vital that women know their bodies and see their GP without delay if they notice something new or unusual for them.
“Women can be ‘breast aware’ and get to know the normal look and feel of their breasts through everyday activities like showering, dressing or simply looking in the mirror.
“The fact that there is no right or wrong way to check your breasts is actually a very empowering message for women who may have been reluctant to check their breasts in the past for fear that they were doing it the wrong way,” said Dr Zorbas.
Breast changes to be aware of include:
a new lump or lumpiness, especially if it’s only in one breast
a change in the size or shape of your breast
a change to the nipple, such as crusting, ulcer, redness or inversion
a nipple discharge
a change in the skin of your breast such as redness or dimpling
an unusual pain that doesn’t go away.
Update: 16.07.2008
Breast check confusion a problem
Women remain confused about the right way to check their breasts for early signs of cancer, says a charity.
Experts say there is no evidence that rigorous monthly "self-examination" reduces breast cancer deaths and it can lead to unnecessary biopsies.
In the UK, the focus is on breast "awareness", rather than more complex and involved checks.
However, Breast Cancer Breakthrough says some UK women rely on US-based websites recommending self-examination.
The Department of Health has not endorsed breast self-examination since the early 1990s, but US authorities still do.
Women who follow the programme often closely check their breasts on the same day in each monthly cycle, feel them using a certain pressure, in a standing and lying position, and can view them from different profiles using a mirror.
They are told to write down details of anything they find in a diary.
The Cochrane review looked at all the available evidence on the success of self-examination programmes, principally two large studies of a total of 388,535 women in Russia and China, half of whom self-examined, while the other half did not.
The death rates from breast cancer were the same in both groups, while there were almost twice the number of biopsy operations - used to take a tissue sample for analysis - in the self-examination group.
This, said the researchers, suggested that self-examination could be leading to more women receiving unnecessary biopsies.
"At present, screening by breast self-examination or physical examination cannot be recommended," they wrote.
'Unaware of advice'
Despite recommendations against self-examination in the UK, charity Breakthrough Breast Cancer said there were still likely to be many women who believed this was the right way to check their breasts.
Dr Sara Cant said: "There is a lot of information out there from the US, and this is easily obtained on the internet - and there are UK sites where this advice is given, usually with the best of intentions.
"On top of this, some women who started examining their breasts this way before the advice changed in the 1990s may be unaware that new advice has been issued."
She said that the best way for a woman to check her breasts was not to follow a strict examination routine, but to get to know what is normal for her, and feel them regularly for signs of any changes.
"We call it TLC - touch, look and check. This approach, coupled with regularly attending breast screening when invited, and modern treatments, has significantly reduced breast cancer mortality."
Update: 08.07.2008
Researchers Develop a Method to Evaluate Variations Identified in Breast Cancer Susceptibility Genes
Using mouse embryonic stem cells, researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, have developed a new method to evaluate which mutations, or changes, in a gene known to increase breast cancer susceptibility, may lead to cancer. The new test, called a functional assay, is more comprehensive and reliable than most current methods. This new test could become a useful and viable tool for genetic counselors, and may have implications beyond cancer. The researchers believe that this test could also be useful for analyzing mutations found in other human disease-related genes. The results of this research will be published in the August 2008 issue of Nature Medicine and appear online July 6, 2008.
The proteins produced by the BRCA1 (BReast CAncer gene 1) and BRCA2 genes normally help to maintain the integrity of the cell's genetic material and function as tumor suppressors. For over a decade, it has been known that alterations or defects in BRCA1, BRCA2, and their associated proteins are linked to increased risks of early onset familial breast and ovarian cancers. Studies have shown that a woman who has a mutation in one of these genes has a 35 to 85 percent risk of developing breast cancer by age 70, compared to the average American woman's lifetime risk of 12.3 percent.
Some individuals who want to know if they have inherited a mutation in a gene such as BRCA1 or BRCA2 that will increase their risk of developing breast or ovarian cancer are now choosing to go for genetic testing. Such tests can provide reassuring information to those who do not have harmful mutations, and can be helpful to those with harmful BRCA1 or BRCA2 mutations because when they know that they are at risk, they can work with their physicians to find the course of action that is best for them.
"However, think about those individuals who are tested and find out that they have an unclassified [minor or previously unknown] change in these genes, and they do not know what it means," said senior author Shyam Sharan, Ph.D. of the NCI's Center for Cancer Research. "There is reason to believe that a significant number of women fall into this category, and our assay is likely to improve our understanding of unclassified mutations because it allows for analysis of all types of BRCA2 mutations."
Existing methods to distinguish between harmful and minor, or neutral, alterations in the BRCA1 and BRCA2 genes are based on data from segregation analysis, which looks at genetic alterations in families with a high incidence of cancer, and uses gene sequencing to detect the presence of a genetic variation. However, this approach has limitations. Most alterations, or variants, are rare, and familial data can be insufficient, resulting in a lack of a suitable test to assess more than 1,900 known BRCA1 and BRCA2 variations. In addition, there is currently no suitable way to evaluate minor or less common mutations in the BRCA1 and BRCA2 genes. This new functional assay expands the ability to analyze mutations in the BRCA2 gene by examining the effect that these variations have on the cell.
The new test looks for the functional significance of variations in BRCA2 using mouse embryonic stem cells. Mouse Brca2 is essential for the viability of mouse embryonic stem cells, and the assay is based on the ability of the human BRCA2 gene to complement the loss of the Brca2 gene in the mouse cells. When introduced into a Brca2-deficient mouse embryonic stem cell in laboratory experiments, functionally normal human BRCA2 variants can compensate for the mouse Brca2 deficiency. On the other hand, harmful or deleterious variants of human BRCA2 do not have this ability, leading to their identification in this test.
Lead author of this paper, Sergey Kuznetsov, Ph.D., generated a set of cells in which one copy of the BRCA2 gene is inactivated or knocked out, and the other remains active but can be inactivated later. The researchers then introduced human genetic material, taking care to maintain all of the coding sequences and regulatory elements of the BRCA2 gene. When genetic material with neutral variants of human BRCA2 was introduced, the researchers were able to subsequently remove the remaining copy of the mouse BRCA2 without compromising the viability of the cell. The addition of genetic material with harmful variants, however, resulted in either cell death or deficient DNA repair. Therefore, the assay can be used to examine genetic material with minor or previously unknown variants. If a human variation does not alter the function of the mouse BRCA2, the risk of developing cancer is probably the same as that of the rest of the population, but if the change is disruptive, the risk of developing cancer increases significantly. The researchers are also working on development of a similar test for BRCA1 variants.
The researchers hope that other human disease gene functions may be evaluated in a similar fashion using this type of analysis. This represents an efficient method of analysis in which three to five gene variants can be analyzed in two to three months. The researchers have provided preliminary validation of the functional assay by testing 17 variants, and have established the reproducibility of the technique for BRCA2. They caution, however, that only when this technique is FDA approved for use in a clinical setting will it be available to patients for diagnostic testing.
The technology behind this new assay is available for further research, and Dr. Sharan's laboratory is interested in collaborating with commercial organizations to further develop it as a product under the appropriate NIH agreements.
Update: 05.07.2008.
Molecular Breast Imaging Shows Potential as MRI Alternative
BALTIMORE, June 26 (MedPage Today) -- Molecular breast imaging may be a more cost-effective follow-up approach to mammography than MRI for high-risk women and those with dense tissue, according to a small retrospective study.
The two imaging techniques had a sensitivity exceeding 90% and specificity of about 50%, Carrie B. Hruska, Ph.D., of the Mayo Clinic in Rochester, Minn., reported at the Era of Hope meeting here, sponsored by the Department of Defense Breast Cancer Research Program.
Although mammography remains a reliable screening and diagnostic test for breast cancer, the imaging technique has reduced sensitivity in some high-risk women and those with dense breast tissue. Increasingly, breast MRI is being used in women who are not well served by mammography, said Dr. Hruska.
However, the high cost of MRI and need for a high level of interpretative expertise prohibit routine use for breast evaluation.
Molecular breast imaging, a nuclear medicine technique, employs specialized gamma cameras to detect the preferential uptake of the radiotracer technetium-99 sestamibi in breast disease, said Dr. Hruska.
The imaging technique's accuracy is unaffected by breast-tissue density and costs a quarter to a sixth of a bilateral breast MRI. Moreover, interpretation of molecular breast imaging exams is considerably less complex compared with MRI.
Given the potential advantages of molecular breast imaging, Dr. Hruska and colleagues retrospectively reviewed records of 48 women who had both breast MRI and molecular breast imaging within a 30-day period. Six patients had screening MRI because of increased risk for breast cancer and the remaining 42 had MRI to evaluate areas of concern left unresolved by mammography or to determine disease extent.
Imaging accuracy was determined by biopsy results or by follow-up status at 15 months for women who did not undergo biopsies.
Subsequently, 54 malignancies were diagnosed in 32 patients, 15 of them with multifocal or multicentric disease. MRI detected 53 of 54 lesions in 31 patients for a sensitivity of 98% compared with 94% for molecular breast imaging, which detected 51 of 54 cancers in 30 patients.
MRI led to correct characterization of nine of 16 true-negative results specificity, and molecular breast imaging ruled out cancer in eight of the 16 cases. False-positive results with MRI led to further evaluation of 12 patients with MRI and to nine biopsies of benign lesions. False-positives with molecular breast imaging prompted evaluation of 11 patients and seven biopsies of benign lesions.
MRI and molecular breast imaging interpretations were concordant for the presence of disease and number of cancer foci in 47 of 48 patients. The single case of discordance occurred in a patient whose MRI exam identified two cancer foci that were missed by molecular breast imaging.
Dr. Hruska reported no disclosures.
Primary source: Department of Defense Era of Hope Meeting Source reference: Hruska CB, et al "Comparison of molecular breast imaging and breast MRI for diagnostic and screening applications" Department of Defense Breast Cancer Research Program: Era of Hope 2008.
Update: 26.06.2008.
Bone drug works for breast cancer survivors
NEW YORK (Reuters Health) - Risedronate, better known by the brand name Actonel, is effective for maintaining or improving the bone strength of women who have had chemotherapy for breast cancer, researchers report.
They explain in the Journal of Clinical Oncology that add-on chemotherapy has prolonged survival for women with breast cancer. However, chemotherapy brings on early menopause, which leads to the bone-thinning disease osteoporosis and to bone fractures.
To investigate the usefulness of risedronate in combating these effects, Dr. Susan L. Greenspan of the University of Pittsburgh and colleagues assigned 87 women who had undergone chemotherapy to take risedronate or a placebo once a week.
Many of the women in the study were also taking a so-called aromatase inhibitor such as letrozole to reduce the odds of a cancer relapse, and this made a difference to bone density.
For example, by the end of the 24-month study, women in the placebo group had a significant reduction in bone density of 4.8 percent at the spine and 2.8 percent at the hip if they were on an aromatase inhibitor. Those in the placebo group who were not taking an aromatase inhibitor maintained bone density at the spine, but had a significant 1.2 percent loss at the hip.
For women given risedronate, spine bone density fell by 2.4 percent and remained stable at the hip if they were also taking an aromatase inhibitor. The greatest improvement was seen in women on risedronate who were not taking an aromatase inhibitor: spine bone density rose by 2.1 percent and there was a 2.2 percent increase at the hip.
Risedronate "proved to be effective with or without the use of an aromatase inhibitor," Greenspan and her colleagues conclude.
Further studies, they add, are needed to see whether these improvements in bone density "translate to fracture reduction for these patients."
Update: 26.06.2008.
Study finds weight-loss surgery cuts cancer risk
WASHINGTON (Reuters) - Morbidly obese patients who undergo weight-loss surgery greatly reduce their risk of cancer, according to a study providing fresh evidence of health benefits from these increasingly common operations.
Researchers from McGill University in Montreal found that the people who underwent bariatric surgery saw reductions in particular in the risk for breast and colon cancer. Many people see dramatic weight loss after such surgery.
People who are deemed morbidly obese typically are at least 100 pounds (45 kg) overweight. The researchers tracked 1,035 such patients who had bariatric surgery for five years. They also monitored 5,746 patients who matched the surgery group in age, sex and weight but did not have this surgery.
Those who underwent bariatric surgery had about an 80 percent lower risk of developing cancer, the study showed.
"The evidence is mounting that weight loss through weight-loss surgery, if you are extremely obese, is extremely beneficial both to your health as well as to your quality of life," Dr. Nicolas Christou, McGill's head of bariatric surgery who led the study, said in a telephone interview on Thursday.
In addition to cutting the incidence of breast cancer by about 85 percent and colon cancer by about 70 percent, those who underwent bariatric surgery also saw reductions in the risk for pancreatic cancer, skin cancer, uterine cancer and non-Hodgkin's lymphoma, the researchers said.
Obesity raises the risk for several types of cancer, including cancers of the breast, colon, esophagus and kidney, as well as numerous other diseases.
The study buttresses findings published last year in the New England Journal of Medicine that obese people who have bariatric surgery have a lower risk of death from heart disease, diabetes as well as cancer compared to obese people who do not have such surgery.
Bariatric surgery alters the digestive system's anatomy to cut the volume of food that can be eaten and digested.
In Christou's study, presented at a meeting of the American Society for Metabolic & Bariatric Surgery, most of the patients had gastric bypass surgery, which leaves the stomach smaller and permits food to bypass part of the small intestine.
"There's an old misconception that this is cosmetic surgery. But actually, people who are overweight don't live as long because a lot of them develop weight-related health problems that shorten their lives. What we see in all these studies is that when people lose the weight, their health gets better," said Dr. Daniel Gagne of the Western Pennsylvania Hospital in Pittsburgh, who presented another study at the meeting.
An estimated 205,000 people underwent bariatric surgery in the United States last year.
Other studies unveiled at the meeting also described health benefits in people who lost weight after bariatric surgery.
Gagne's study showed that most patients with asthma and arthritis were able to stop taking steroids to treat the conditions within about a year of having bariatric surgery.
The study involved 49 morbidly obese patients who were taking steroids and other immunosuppressant medications to treat chronic inflammatory diseases and autoimmune diseases.
New York University researchers showed that losing less than half of excess weight within a year of bariatric surgery was enough for patients to see dramatic improvements in type 2 diabetes, hypertension, high cholesterol and sleep apnea.
Update: 19.06.2008.
Facility Traits Affect Screening Mammography Accuracy
BETHESDA, -- Screening mammography facilities that have their ducks in a row are significantly more likely to interpret images accurately than institutions with looser attributes.
Higher accuracy of interpretation was associated with facilities that offered only screening mammography, had a breast imaging specialist to interpret mammogram, and performed single reading, said Stephen Taplin, M.D., of the National Cancer Institute. Such institutions also conducted two or more audit reviews a year.
"Identifying facility structures and process that influence interpretive performance could be a foundation for improving the quality of mammography interpretive performance and choices among mammography facilities," Dr. Taplin and colleagues concluded in the June 18 issue of the Journal of the national Cancer Institute.
Patient and radiologist characteristics have been shown to affect mammographic interpretive performance. However, the characteristics examined account for only 10% of the variation in performance, the authors said.
Variation among mammography facilities has not been examined carefully, if at all, Dr. Taplin and colleagues continued. Identification of facility-specific factors that affect interpretive performance could help patients and physicians make better informed decisions about choosing a mammography facility and could inform the facilities about changes in practice that could improve interpretive performance.
Dr. Taplin and colleagues examined factors influencing interpretive performance at 44 mammography facilities that performed 484,463 screening mammograms on 237,669 women from 1996 to 2002. Breast cancer was diagnosed in 2,686 women during follow-up.
The 44 facilities had a mean sensitivity of 79.6% and a mean specificity of 90.2%. Mean positive predictive value was 4.1%. Investigators calculated positive predictive value on the basis of the likelihood that cancer would be found among women referred for biopsy, and the mean among the facilities was 38.8%.
The facilities' interpretive performance varied significantly with respect to specificity (P<0.001), positive predictive value (P<0.001), and the biopsy-defined positive predictive value (P=0.002). Additionally, the authors identified four facility characteristics that significantly influenced interpretative performance, as defined by area under the curve:
Screening mammograms only, versus screening and diagnostic mammograms (0.943 versus 0.911, P=0.006).
Interpretation by a breast imaging specialist versus not (0.932 versus 0.905, P=0.004).
Single reading versus independent double reading versus consensus double reading (0. 925 versus 0.915 versus 0.887, P=0.034).
Audit reviews at least twice annually versus annually or unknown (0.929 versus 0.904 versus 0.900, P=0.018).
Neither facility volume nor method of audit review influenced performance.
The study had a number of limitations including missing data, possible unaccounted differences among women and radiologists, and inability to assess differences in double-reading methods. The finding of poorer interpretive performance in facilities doing double readings is not consistent with other studies.
"Understanding how facility characteristics influence interpretive accuracy is important because it could allow women and physicians to choose a mammography facility based on characteristics that are more likely to be associated with higher quality," the authors said. "Radiologists could also change the facilities' structure or processes to include practices that improve interpretive accuracy."
Update: 19.06.2008.
Raloxifene (Evista) Reduces Risk of ER-Positive Invasive Breast Cancer
SAN FRANCISCO, -- Treatment with raloxifene (Evista) reduced the risk of receptor-positive invasive breast cancer by more than half among women enrolled in a randomized study of heart disease prevention.
Patients randomized to the selective estrogen receptor modulator had 55% fewer invasive estrogen receptor-positive breast cancers than women in the placebo group, Deborah Grady, M.D., of the University of California San Francisco, and colleagues reported in the June 18 issue of the Journal of the National Cancer Institute.
The reduction in receptor-positive disease accounted for virtually all of the 44% overall reduction in invasive breast cancer previously reported from the study.
Neither invasive receptor-negative breast cancer nor noninvasive breast cancer was reduced by raloxifene treatment.
The findings also are consistent with those from a trial of raloxifene to prevent osteoporotic fractures in postmenopausal women.
"Raloxifene appeared to be most effective in reducing the incidence of breast cancer during the first four years of treatment," the authors said. "Moreover, the effect of treatment appeared to be similar across subgroups defined by age, reproductive history, and breast cancer risk status."
The findings came from the Raloxifene Use for the Heart (RUTH) trial, which involved 10,101 women with coronary heart disease or who were at high risk for CHD.
The primary results of the trial showed no effect of raloxifene on heart disease risk, but 44% overall reduction in the risk of invasive breast cancer.
The findings followed those from the Multiple Outcomes of Raloxifene Evaluation (MORE) trial, which involved 7,705 postmenopausal women with osteoporosis. Among women treated for four years, raloxifene reduced the risk of invasive breast cancer by 72% compared with placebo.
In the current study, Dr. Grady and colleagues analyzed the RUTH data to determine the effects of raloxifene on breast cancer by histologic type, tumor stage, lymph node status, and tumor grade and size.
The original findings from RUTH included a 44% reduction in the hazard ratio for invasive breast cancer in women treated with raloxifene. The reduction translated into the prevention of 1.2 invasive breast cancers per 1,000 women treated for one year.
Dr. Grady and co-authors found that the overall reduction in the risk of invasive breast cancer reflected a hazard ratio of 0.45 (95% CI 0.28 to 0.72) in the subgroup of women with hormone receptor-positive tumors.
The magnitude of the overall reduction in the risk of invasive breast cancer was similar across subgroups defined by age, body mass index, family history of breast cancer, prior use of postmenopausal hormones, and five-year estimated risk of invasive breast cancer.
Raloxifene was associated with an increased risk of venous thromboembolism and fatal stroke in RUTH.
Assuming that the relative risks of the trial apply to women in the general population, the authors suggested the best risk:benefit ratio would occur in women with a high risk of breast cancer and osteoporosis and a low risk of venous thromboembolism and stroke.
They also pointed out that participants in the RUTH trial were selected because they either had known coronary disease or were at high risk for coronary disease.
"Thus, it is possible," they wrote, "that the ?ndings of the RUTH trial may not be able to be generalized to women who are not at high risk for coronary disease."
Update: 11.06.2008.
New Study of Targeted Therapies for Breast Cancer Establishes Model for Global Clinical Trials
Two targeted medications designed to treat an aggressive form of breast cancer are being tested in a new study involving 8,000 participants in 50 countries across six continents -- a clinical trial that investigators hope will provide a new model for global cancer research. This trial, dubbed ALTTO (Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization study), will be one of the first global initiatives in which two large, academic breast cancer research networks covering different parts of the world have jointly developed a study in which all care and data collection are standardized, regardless of where patients are treated. The networks are The Breast Cancer Intergroup of North America (TBCI), based in the United States, and the Breast International Group (BIG) in Brussels, Belgium. TBCI consists of six National Cancer Institute (NCI)-funded clinical trials cooperative groups. NCI is part of the National Institutes of Health.
ALTTO is designed to answer the most pressing questions regarding use of two widely used cancer agents: whether one agent is more effective, which agent is safer for patients, and what benefit will be derived by taking the drugs separately, in tandem order, or together? The trial is a randomized, Phase III study, which is considered a gold standard method for proving drug effectiveness.
The two agents tested in ALTTO are drugs designed to treat HER2-positive tumors, which is a particularly aggressive form of cancer that affects approximately 20 percent to 25 percent of breast cancer patients. Both agents, trastuzumab (Herceptin) and lapatinib (Tykerb), have already been approved by the U.S. Food and Drug Administration for use for treatment of HER2-positive breast cancer. ALTTO will provide the first head-to-head comparison of trastuzumab and lapatinib in the earliest, most treatable stages of cancer. It will also be one of the first large-scale studies to evaluate lapatinib's effectiveness in treating early breast cancer.
HER2-positive breast cancer is caused by an excess of HER2 genes or by over-production of its protein, the HER2 cell surface receptor. Trastuzumab consists of large antibodies that once injected into patients, latch on to the portion of the HER2 protein that sits on the outer surface of the cancer cell whereas lapatinib acts by entering a cancer cell and binding to the part of the HER2 protein that lies beneath the surface of the cell.
The trial is unusual in that it has two different designs depending on whether patients with stage I or stage II breast cancer have already been treated with chemotherapy. The study thus will compare four different regimens of targeted therapy administered over a 52-week period. Patients will be randomized to receive either trastuzumab or lapatinib alone, or trastuzumab followed by lapatinib, or the two treatments in combination.
"There have been major improvements in the management of patients with early breast cancer in the last few years, so this new study builds on this knowledge and sets an example of the new era: good science, good worldwide collaboration," said Edith Perez, M.D., an oncologist in the North Central Cancer Treatment Group (NCCTG) at Mayo Clinic in Jacksonville, Fla., who will lead the study for TBCI. "It may be that using two treatments that work in different ways against HER2-positive breast cancer offers a complementary strategy that is more powerful than either drug alone."
ALTTO will be one of the first trials of its scope in which translational research -- taking science from bench to bedside -- plays a critical role, investigators say. In ALTTO, biological material will be collected from thousands of patients in order to determine a tumor profile that responds best to the drugs -- information that could lead to individualized patient care and, possibly, to development of next generation agents.
"The difference between this study and many that came before it is that the collection of biological materials occurs as the trial is being conducted, not as an afterthought. While there are exceptions, not many companies or organizations have been willing to invest in that kind of research before," said Martine J. Piccart, M.D., Ph.D., professor of oncology at the Université Libre de Bruxelles, Belgium, and lead investigator for BIG, which she founded in 1996. "Now we have the chance to optimize therapy with powerful drugs in order to provide the best treatment possible for each of our patients."
Perez and Piccart led the development team of the ALTTO trial and will act as the study's co-principal investigators. On behalf of BIG and TBCI, these two lead investigators have been working toward collaborative clinical studies for a number of years. The ALTTO study, they say, represents a new paradigm that blends the high standards of both systems in order to test the latest breast cancer treatments as efficiently as possible in thousands of women worldwide.
"The NCI greatly appreciates the work that Mayo Clinic, TBCI and BIG are doing to help advance our understanding of the complex mechanisms that underlie different types of breast cancer," said Jo Anne Zujewski, M.D., a senior investigator in the clinical investigations branch at NCI. "We hope that this model of international collaboration is one which we can build upon in the future."
Lapatinib, in combination with the chemotherapy drug capecitabine, was approved by the U.S. Food and Drug Administration in March 2007 for the treatment of advanced or metastatic HER2-positive breast cancer in patients who had received prior therapy with three agents -- an anthracycline, a taxane and Herceptin. GlaxoSmithKline is providing the study drug, as well as additional financial support for the ALTTO trial. All drugs carry potential side effects, and more information of side effects for lapatinib and trastuzumab can be found in the Q A at http://www.cancer.gov/newscenter/pressreleases/ALTTOQandA. NCI and GSK also provided comment and input on the design of the study.
NCCTG will act as the treatment base for ALTTO in North America. BIG is a network of 41 non-U.S. research groups from around the world. Its Brussels-based BrEAST Data Center is providing centralized data management for the global study (including the United States). The other members of TBCI include the Eastern Cooperative Oncology Group (ECOG), the Cancer and Leukemia Group B (CALGB), the Southwest Oncology Group (SWOG), the American College of Surgeons Oncology Group (ACOSOG), and the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG).
To date, more than 300 centers around the world have enrolled patients into ALTTO. Full enrollment is expected to involve about 500 centers in the United States and more than 800 centers in Europe and the rest of the world.
Update: 11.06.2008.
Lifespan cheer for breast cancer
Women with early stage breast cancer revealed by screening are likely to live as long as someone who has never had the disease, figures show.
The NHS Cancer Screening Programme audit confirms detection of the disease in its early stages is vital.
Overall, six out of ten women diagnosed after screening and treated had the same survival rates as the general population.
Experts urged women not to miss screening appointments.
The audit results give an overall picture of the success of the strategy of screening and treatment, rather than a guarantee of cure in every case, as the disease will still come back in a small number of women detected early.
In all, 61% of cancers detected following a mammogram are given an "excellent" or "good" prognosis by doctors based on the size of the tumour and how far it has spread.
After treatment, these patients on average are predicted to have the same lifespan as women who have never had cancer.
However, two out of three breast cancers are not detected by screening, and these are not covered by the audit results.
Professor Julietta Patnick, who runs the NHS Breast Screening Programme, said that the extension of the scheme by 2012 to cover more women would increase the number found early.
"Huge strides have been made over the past two decades, and more women than ever before are surviving breast cancer, many of whom have benefited from early detection."
Mr Martin Lee, the President of the Association of Breast Surgery, who also helped draw up the report, said it was "vital" that women were aware of the survival rates for breast cancers detected early.
"I would encourage all women who are invited to be screened to attend," he said.
Increased demand
The report also looked at long-term survival for women with more aggressive cancers already past the early stages of development - those not given an "excellent" or "good" prognosis after being detected during screening.
Fifteen years after diagnosis, 86% of these women were still alive, and specialists say that survival is likely to have improved even further since then.
Dr Alexis Willett from Breakthrough Breast Cancer said: "It's excellent news that women with early breast cancer found through screening can live as long as those never affected by the disease.
"As more women become eligible to attend, breast screening services will face increased demand.
"Sufficient resources must be put in place to meet this challenge so even more women can benefit from this life saving service."
A spokesman for Cancer Research UK said: "Results like this demonstrate just how much breast screening matters.
"We've known for some time that the breast screening programme has been saving thousands of lives, but to hear that it's having such a long-term impact is exceptionally good news."
Update: 09.06.2008.
30 Percent Increase In Breast Imaging Of Low-Risk Women As A Result Of Kylie's Breast Cancer
Use of mammography and breast ultrasound procedures soared by over 30 per cent among women aged 25-44 in the six months following Kylie Minogue's breast cancer diagnosis, says a new study from the University of Melbourne.
There was also a sharp rise in the number of women aged 25-34 years who underwent breast biopsies - but this surge in screening activity did not lead to the detection of more cases of breast cancer.
The study, published this week in the International Journal of Epidemiology, is the first to use Medicare data to examine the impact of the intense publicity that surrounded this announcement on breast imaging, biopsies and operations to remove breast tumors.
Study leader Dr Margaret Kelaher, from the University of Melbourne's Melbourne School of Population Health, and colleagues found that in the six months following Minogue's diagnosis in April 2005:
Breast imaging in 25-34 year old women rose by 33 per cent;
Breast biopsies in women 25-34 increased by 46 per cent;
Breast imaging in women aged 35-44 rose by 25 per cent;
Biopsies in women aged 35-44 increased by 37 per cent.
However, the rates of operations to remove breast cancers did not change significantly, suggesting that the flurry of screening activity led to many "false positives".
"Raising women's awareness of the need to get screened is a generally good thing," Dr Kelaher said.
"But these findings suggest that thousands of additional imaging procedures and biopsies did not improve breast cancer detection among young women.
"It appears there has been a situation where publicity has led to many low risk women using - and probably overusing - screening services.
"We need to improve the targeting of health messages and the confidence of women and their doctors in early breast cancer detection recommendations."
Dr Kelaher said the publicity could have raised doctors' perception about breast cancer risk and increased concerns, both medical and legal, about missed diagnoses in younger women.
The researchers also suggest that the influx of low-risk women into the screening system may have damaging effects by reducing the system's capacity to deal with higher risk women.
Dr Kelaher said Kylie Minogue had been a great ambassador for breast cancer awareness, but the publicity surrounding her case highlighted the need for better efforts at "managing the message."
"The visibility of a celebrity's illness provides an opportunity to address a huge health problem like breast cancer," she said.
"But when that celebrity is from a low risk group, it also has the potential to undercut the appropriateness and cost effectiveness of health service delivery.
"Consultation between a celebrity's PR team and public health agencies on how to shape and disseminate the information could help create a message with the best chances of furthering the quality of care and sound public health practice."
Dr Julie Miller, consultant surgeon at the Royal Melbourne Hospital and senior lecturer in the Department of Surgery at the University of Melbourne, is a co-author of the study.
"It's important that women are breast-aware, and consult their doctor if they are concerned about any changes in their breasts,'' Dr Miller said.
"However there is no role for routine screening of women under 40 who do not have symptoms or a strong family history.
"This study shows that all the extra worry and expense was unwarranted and that the current recommendations for breast cancer screening are appropriate."
Breast MRI scans 'commonly wrong'
Lumps detected in women at a high risk of breast cancer using hi-tech MRI scans overwhelmingly turn out to be false alarms, a Dutch study suggests.
But while researchers found five out of six scans which suggested a problem were wrong, they were nonetheless very effective at spotting invasive cancers.
And while false-positives caused anxiety, the study did not find women were rashly opting for mastectomies.
The findings were published in the Annals of Oncology.
Women with certain genes have as much as an 85% risk of breast cancer.
In the UK, NHS guidelines say that a woman with a family history of the disease may be offered yearly MRI scans if her doctors think it is appropriate, in addition to the recommended mammogram.
MRI scans - which use magnetic resonance imaging - are more sensitive than standard mammograms, and as such are seen as particularly effective in picking up early breast cancers in younger women with denser breast tissue.
Gene mutation
But this very sensitivity is what makes them more likely to spot abnormalities which may turn out to be completely benign.
Researchers at the Hereditary Cancer Clinic at Nijmegen Medical Centre followed 196 women with the BRCA1 or BRCA2 gene mutation which has been linked to breast cancer.
On their first visit, they were asked whether they had a preference for ongoing surveillance in the form of scans, or whether they would rather have their breasts removed as a precaution.
About 30% said they wanted a protective mastectomy, three expressed no preference and the others wanted regular check-ups.
All also went on to receive a scan. About 83% of the MRI scans which appeared to detect a tumour were later found to be so-called "false positives".
However, the positive scan appeared to do little to sway decisions on breast removal.
Some 90% of the group who had wanted a mastectomy went on to have one, while fewer than a third of those who received a positive result and had originally opted for surveillance opted for breast removal.
"The final decision to actually undergo prophylactic mastectomy appeared to be determined more frequently by a woman's prior preference than by a positive scan," said Dr Nicoline Hoogerbrugge, who led the research.
There was little information available about how women made the choice, she added. "Both genetic counselling and breast cancer surveillance are events in the entire decision-making process, but appear to have a limited impact."
Effective
But the researchers did confirm that the MRI scan was more effective in picking up genuine tumours and pre-cancerous developments.
The proportion of true-positives for mammography was 41%, while for MRI it was 60%. There was little difference between the two when it came to providing the all clear, with both equally unlikely to suggest there was nothing wrong when a growth was in fact present.
Breakthrough Breast Cancer said the findings should not curtail access to MRI scans for those women at high risk.
"MRI, together with mammography, is the most effective form of screening for this group of women although this method can result in false positives," said head of policy Dr Sarah Rawlings.
"It is vital that all those eligible have access to this service and also receive clear and accurate information about the risks and benefits of MRI so they can make an informed decision."
Breast Cancer Care clinical director Dr Emma Pennery said: "While MRIs can result in false positive findings, this is far outweighed by their ability to detect tumours earlier in their development compared to mammography in high risk groups."
Breast cancer is a malignant (cancerous) growth that begins in the tissues of the breast. Over the course of a lifetime, one in eight women will be diagnosed with breast cancer.
Early symptoms of Breast Cancer
- Breast Cancer no Early symptoms!!
Symptoms of inflammatory breast cancer:
Breast lump or breast mass noted upon breast exam -- usually painless, firm to hard and usually with irregular borders
Lump or mass in the armpit
A change in the size or shape of the breast
Abnormal nipple discharge
Usually bloody or clear-to-yellow or green fluid
May look like pus (purulent)
Change in the color or feel of the skin of the breast, nipple, or areola
Dimpled, puckered, or scaly
Retraction, "orange peel" appearance
Redness
Accentuated veins on breast surface
Change in appearance or sensation of the nipple
Pulled in (retraction), enlargement, or itching
Breast pain, enlargement, or discomfort on one side only
Any breast lump, pain, tenderness, or other change in a man
Symptoms of advanced disease are bone pain, weight loss, swelling of one arm, and skin ulceration
In the center of the human female breast is the protruding nipple, which is surrounded by a pigmented circular area called the areola. Internally, the breast is composed of milk glands surrounded by fatty tissue and some connective tissue. Produced by the lobules in the interior of the breast, milk is carried to the nipple by a collection of tubes known as ducts. Breast cancers may start in the milk glands, milk ducts, fatty tissue, or connective tissue. Cancers of the breast are the most common cancers in women, affecting 1 in every 8 American women who live to age 80.
Signs and tests
Any worrisome breast changes should be confirmed and investigated by a medical professional. After getting as much information as possible about the symptom and any risk factors, the physician performs a physical examination including both breasts, armpits, and the area of the neck and chest. Additional tests and treatment may then be recommended:
X-ray mammography may help identify the breast mass.
Ultrasound (sonogram) can show whether the lump is solid or fluid-filled.
Needle aspiration or needle biopsy of breast lumps can demonstrate if they are fluid-filled and provide material to send to the laboratory for analysis. In the case of very small abnormalities visible only on mammography, special techniques are necessary.
A surgical biopsy or breast lump removal provides a portion or all of a breast lump for laboratory study.
If breast cancer is diagnosed, additional testing is performed, including chest X-ray and blood tests. Surgery, radiation, chemotherapy, or a combination of these may then be recommended, not only for treatment, but also to help determine the stage of disease. Staging is important to help guide future treatment and follow-up, and to give some idea of what to expect in the future.
Stages of Breast Cancer (from the American Joint Committee on Cancer):
STAGE 0. In Situ ("in place") disease in which the cancerous cells are in their original location within normal breast tissue (Early symptoms of Breast Cancer). Known as either DCIS (ductoral carcinoma in situ) or LCIS (lobular carcinoma in situ) depending on the type of cells involved and the location, this is a pre-cancerous condition, and only a small percentage of early DCIS tumors progress to become invasive cancers. There is some controversy within the medical community on how to best treat DCIS.
STAGE I. Tumor less than 2 cm in diameter with no spread beyond the breast
STAGE IIA. Tumor 2 to 5 cm in size without spread to axillary (armpit) lymph nodes or tumor less than 2 cm in size with spread to axillary lymph nodes
STAGE IIB. Tumor greater than 5 cm in size without spread to axillary lymph nodes or tumor 2 to 5 cm in size with spread to axillary lymph nodes
STAGE IIIA. Tumor smaller than 5 cm in size with spread to axillary lymph nodes which are attached to each other or to other structures, or tumor larger than 5 cm in size with spread to axillary lymph nodes
STAGE IIIB. The tumor has penetrated outside the breast to the skin of the breast or of the chest wall or has spread to lymph nodes inside the chest wall along the sternum
STAGE IV. A tumor of any size with spread beyond the region of the breast and chest wall, such as to liver, bone, or lungs
Many additional factors besides staging can influence the recommended treatment and the likely outcome. These can include the precise cell type and appearance of the cancer, whether the cancer cells respond to hormones, and the presence or absence of genes known to cause breast cancer.
Causes, incidence and risk factors
There are several different types of breast cancer.
Ductal carcinoma begins in the cells lining the ducts that bring milk to the nipple and accounts for more than 75% of breast cancers.
Lobular carcinoma begins in the milk-secreting glands of the breast but is otherwise fairly similar in its behavior to ductal carcinoma. Other varieties of breast cancer can arise from the skin, fat, connective tissues, and other cells present in the breast.
Some women have what is known as HER2-positive breast cancer. HER2, short for human epidermal growth factor receptor-2, is a gene that helps control cell growth, division, and repair. When cells have too many copies of this gene, cell growth speeds up. It’s believed that HER2 plays a key role in turning healthy cells into cancerous ones. Some women with breast cancer have too much HER2, and are therefore considered HER2-positive. Research suggests that women with HER2-positive breast cancer have a more aggressive disease and a higher risk of recurrence than those who have HER2 negative breast cancer.
Risk Factors for Breast Cancer Include:
Age and Gender -- As with most cancers, age is a significant factor. In fact, 77% of new cases and 84% of breast cancer deaths occur in women aged 50 and older. More than 80% of breast cancer cases occur in women over 50. Less than 1% of breast cancers occur in men. The risk of breast cancer is clearly related to hormonal influences, but how these affect the disease and particularly types of the disease is not yet clear.
Genetic Factors and Family History of Breast Cancer -- Some families appear to have a genetic tendency for breast cancer. Two variant genes have been found that appear to account for this: BRCA1 and BRCA2. The genes p53 and BARD1 also appear to be important.
Researchers have identified several other defective genes that may cause breast cancer, including BRCA3 and Noey2 (which is a disease inherited only from the father's side of the family). These discoveries suggest that breast cancer occurs when the body’s anti-cancer surveillance and control systems, which normally get rid of abnormal cells, fail to work. The body's reduced ability to get rid of abnormal cells leads to damage that gradually accumulates. Women carrying mutated BRCA1 and/or BRCA2 genes start with pre-existing dysfunction of this system and have a "head start" in this damaging process. Hormones are important because they encourage cell growth. High levels of hormones during a woman's reproductive years, especially when they are not interrupted by the hormonal changes of pregnancy, appear to increase the chances that genetically damaged cells will grow and cause cancer.
Early Menstruation and Late Menopause -- Women who get their periods early (before age 12) or went through menopause late (after age 55) are at higher risk. Also, women who have never had children or who had them only after the age of 30 have an increased risk.
Oral Contraceptives (birth control pills) -- Birth control pills may slightly increase the risk for breast cancer, depending on age, length of use, and other factors. No one knows how long the effects of the pill last after stopping it.
Hormone Replacement Therapy(HRT) -- Use of HRT has been shown to increase the risk of breast cancer.
Obesity -- Obesity is controversial as a risk factor. Some studies report obesity as a risk of breast cancer, possibly associated with higher levels of estrogen production in obese women.
Alcohol Consumption -- Significant alcohol use (more than 1-2 drinks a day) has been associated with an increased risk of breast cancer.
Chemicals -- Some studies have pointed to exposure to estrogen-like chemicals that are found in pesticides and other industrial products as a possible increased risk of breast cancer.
DES -- Women who took diethylstilbestrol (DES) to prevent miscarriage may have an increased risk of breast cancer after age 40.
Radiation -- People exposed to radiation, particularly during childhood, may face an increased risk for breast cancer in adulthood. Especially at risk are those that received chest irradiation for prior cancers.
Additional Risk Factors -- Some studies show previous breast, uterine, ovarian, or colon cancer, and a strong history of cancer in the family may increase the risk for breast cancer. Such history may indicate genetic factors described above.
The Gail Model is a simple breast cancer risk assessment tool that is available online and takes into account the most important risk factors. A number of other models are also used.
TREATMENT
Treatment of breast cancer depends on a woman’s age and health as well as the type, extent, and location of the tumor, and if the cancer has remained in the breast or has spread to other parts of the body. Treatment may include surgery, radiation, chemotherapy, hormone therapy, or a combination of treatments.
Most women with breast cancer will have some type of surgery. If only the lump and some surrounding breast tissue are removed, leaving most of the breast intact, the procedure is called a partial mastectomy, or lumpectomy. In a simple mastectomy, only the affected breast is removed. A modified radical mastectomy involves the removal of the entire breast and some of the underarm lymph nodes near the breast. Surgery that removes the breast, lymph nodes, and chest wall muscles under the breast is called a radical mastectomy.
For women who have had a partial mastectomy, doctors generally recommend radiation therapy. Radiation therapy uses high-energy rays or particles that destroy cancer cells that may remain in the breast, chest wall, or underarm area after surgery.
Physicians use specialized X-ray images of the breast called mammograms to early detect tumors and other breast abnormalities before they can be felt as lumps. Mammograms detect many breast tumors in their early stages, before they have a chance to spread to other parts of the body. Because catching and treating a cancerous breast tumor early significantly improves a woman’s chance of survival, the American Cancer Society recommends that women age 40 and over have an annual screening mammogram.
Studies have shown that lumpectomy combined with radiation therapy is as effective as mastectomy in treating early-stage breast cancer—there is no difference in survival rates of women treated with either of these two approaches. For this reason many women choose the less-invasive method of lumpectomy followed by radiation to avoid the complete removal of a breast. But this breast-conserving treatment is not an option for all women with breast cancer, including those who have already had radiation therapy to the affected breast or those with two or more areas of cancer in the same breast that are too far apart to be removed through one surgical incision. In some cases mastectomy is a woman’s only choice. Many women choose to have breast reconstruction surgery right after a mastectomy to restore the breast’s appearance.
If doctors find that cancer cells have spread to lymph nodes, then they will recommend chemotherapy. In chemotherapy, a patient receives cancer-fighting drugs that travel through the body to slow the growth of cancer cells or kill them. Even if no cancer cells are found in tissues other than the breast, chemotherapy may be given in addition to surgery to reduce the risk that breast cancer will recur. It also may be used as the primary treatment for women with more advanced cases of breast cancer to reduce the size of the tumor for more manageable surgical removal. In these cases, high doses of chemotherapy kill cancer cells, but they also kill stem cells, blood-producing cells in the bone marrow. Some women in advanced stages of breast cancer may undergo chemotherapy followed by a bone-marrow transplant to restore healthy stem cells, although it is not yet clear whether this procedure helps prolong a woman’s survival.
Hormone therapy exploits some of the chemicals the body naturally produces. For example, some breast cancer cells thrive on the hormone estrogen, which is produced in the ovaries. Hormone therapy slows the growth of such cells by preventing them from using estrogen. One of the drugs employed in hormone therapy is tamoxifen, which can prevent breast cancer from recurring in a majority of women. Tamoxifen has also been shown to reduce the risk of breast cancer in women who carry a mutation in the BRCA2 gene, which produces tumors that require estrogen to grow. Tamoxifen does not reduce the risk in women who carry the BRCA1 gene, which produces tumors not affected by estrogen. Tamoxifen may also prevent new cancers from forming in the other breast. Tamoxifen’s chemical cousin, raloxifene, has shown similar results in preliminary studies. The most radical forms of hormone therapy are the removal of the ovaries by surgery or the virtual destruction of the ovaries by radiation treatments to prevent these organs from secreting estrogen.
While tamoxifen blocks estrogen from being used by breast-cancer cells to stimulate further growth, other types of drugs under investigation reduce the amount of estrogen available in the body of postmenopausal women. At menopause (the permanent cessation of menstruation) the ovaries cease to produce estrogen, but estrogen production continues in other tissues, including breast tissue. Scientists are exploring the effectiveness of aromatase inhibitors and aromatase inactivators—drugs that suppress estrogen production by preventing the final step in estrogen synthesis. Studies show that aromatase inhibitors and inactivators, taken in combination with tamoxifen, reduce the size of breast tumors. Smaller tumor size means that patients can undergo less radical surgery.
Another drug recently approved for treating breast cancer is a monoclonal antibody called trastuzumab, marketed under the brand name Herceptin. This drug targets cells that overproduce HER-2, a protein implicated in about one-third of all breast cancer cases. Herceptin suppresses rapid tumor growth, enhancing the effectiveness of chemotherapy.
Women with a family history of breast cancer may choose to undergo genetic testing to determine if they carry mutated forms of the BRCA1 or BRCA2 genes (Early Symptoms). There is no way to know for sure if a woman who carries these genes will develop breast cancer, but statistics show that about 50 to 60 percent of women with these mutations will develop the disease by the age of 70. Although there is no sure-fire way to prevent breast cancer, women who test positively for these genes may elect to take precautions that may lower their risk of developing the disease. For example, they may decrease the level of fat and alcohol in their diets and eat more fruits and vegetables—foods that have been shown to decrease an individual’s risk of developing most types of cancer. Recent studies show that in women who are at very high risk for breast cancer, prophylactic mastectomies significantly lower this risk. In this procedure, surgeons remove both breasts before any signs of breast cancer are detected to remove the vulnerable tissue before cancer can take hold.
PROGNOSIS
The five-year survival rate (a measure used to monitor persons who are living five years after diagnosis of cancer) for American women diagnosed with localized breast cancer increased from 72 percent in the 1940s to 96 percent in the late 1990s. If the cancer has spread to adjacent tissue, the five-year survival rate falls to 78 percent. For women who have been treated for breast cancer, the outlook is increasingly optimistic, especially with regular follow-up examinations by a physician and frequent breast self-examination.
The clinical stage of breast cancer is the best indicator for prognosis (probable outcome), in addition to some other factors. Five-year survival rates for individuals with breast cancer who receive appropriate treatment are approximately:
95% for stage 0
88% for stage I
66% for stage II
36% for stage III
7% for stage IV
The axillary (armpit) lymph nodes are the main passageway that breast cancer cells must use to reach the rest of the body. Their involvement at any time strongly affects the prognosis.
Chemotherapy and hormone therapy can improve prognosis in all patients and increase the likelihood of cure in patients with stage I, II, and III disease.
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