Abstract
The US FDA has recently approved a new gene-based test designed to predict a woman's chance of cancer recurrence after a diagnosis of early breast cancer.
A new molecular prognostic test, marketed as Mammaprint®, uses a sample from a surgically removed breast tumor to predict whether a woman is at low or high risk of distant metastasis in the next 5–10 years.
“Clearance of the MammaPrint test marks a step forward in the initiative to bring molecular-based medicine into current practice,” commented Andrew C von Eschenbach, head of the US FDA. “MammaPrint results will provide patients and physicians with more information about the prospects for the outcome of the disease. This information will support treatment decisions.”
The test, developed by Agendia, a laboratory in Amsterdam (The Netherlands), utilizes DNA microarray technology to determine the level of activity of 70 genes known to be associated with breast cancer prognosis, and uses an algorithm to classify them into high or low risk of recurrence. MammaPrint has been available in Europe since 2005.
Those women who are classed as high risk by the test have a 23% chance of cancer metastasis after 5 years and a 29% chance after 10 years. Women classed as low risk have a 95 and 90% chance of remaining free from cancer recurrence after 5 and 10 years, respectively.
“This information has to be used very carefully by physicians in the context of what they know about the history of the patient, the diagnostic options and the treatment options”, emphasized Steven Gutman, director of the FDA's Office of In Vitro Diagnostic Device Evaluation and Safety in the Center for Devices. “This is a complex test that requires use by people who know their business.”
The approval of the test has generated some controversy, with experts urging caution. Len Lichtenfield, deputy chief medical officer at the American Cancer Society “This test isn't better than other tests that do the same thing. The thing that makes I it stand out is that it has FDA approval.”
“This is a first step in a long process”, he continued. “The goal of that process is to do a test that will tell us, ‘Yes, you need adjuvant therapy or, no, you don't,’ and say it with 99.9% accuracy. We are not there yet. We don't know, at this point, whether or not this is a test that should influence the decisions that women land their doctors should be making with regard to adjuvant therapy,” he concluded.
MammaPrint is the first in vitro diagnostic multivariate index assay to be approved by the US FDA, who will be publishing a policy in the next few months to clarify what type of data are needed for approval of future genetic profiling tests in breast cancer.
Source: FDA press release. Available at www.fda.gov (2007).
UK women too often overweight when they conceive
Researchers in the UK have found a high level of obesity in women at the start of their pregnancy, which could potentially be detrimental to the health of both the mother and her baby.
The maternity records of over 35,000 women were analyzed to elucidate the relationships between socioeconomic and demographic factors, and maternal obesity over a period of 15 years. The percentage of women who were clinically obese at the start of their pregnancy rose from 9 to 16% over 15 years. In addition, the analysis suggested that the rate of increase is accelerating, leading the investigators to predict a 22% rate of maternal obesity within the next few years.
Women who were older and from poor areas were more likely to be obese at the start of their pregnancy.
Previous research has shown that maternal obesity is a risk factor for cesarean section, miscarriage, thromboembolism, pre-eclampsia, maternal death and stillbirth.
“Maternal obesity is something that has crept up on us”, commented study author John Wilkinson, urging officials to consider the greater strain this “public health time bomb” is causing on healthcare resources.
Source: Heslehurst N, Lang R, Rankin J, Wilkinson J, Summerbell C: Obesity in pregnancy: a study of the impact of maternal obesity on NHS maternity services. BJOG 114 (2), 187–194 (2007).
In brief…
Jiang X, Ellison SJ, Alarid ET, Shapiro DJ: Oncogene (2007) (Epub ahead of print).
Describes a mechanism behind the proliferative effect of estrogen on some tumors. The study found that estrogen not only enhances cell proliferation and metastasis, but also shields the cancer cells from the immune system. The binding of estrogen to its receptor forms a complex that promotes expression of an inhibitory molecule, proteinase inhibitor 9 (PI-9). PI-9 inhibits granulazomes in natural killer cells, which play an important part in destroying tumor cells. The researchers hope that this new data may eventually lead to new therapies for estrogen-dependent tumors.
Geiger AM, Thwin SS, Lash TL et al.: Cancer (2007) (Epub ahead of print).
Confirms that radiotherapy following breast-conserving surgery is a viable treatment option for older women with early breast cancer. The study analyzed data from 1837 women aged 65 years and over, who were diagnosed with early stage breast cancer. As in younger women, older women need to receive radiotherapy after lumpectomy in order to ensure that it is as effective as mastectomy. The authors conclude that breast-conserving surgery followed by radiotherapy should be a treatment option in all women except those with a very short life expectancy.
Griggs JJ, Culakova E, Sorbero ME et al.: J. Clin. Oncol. 25(3), 277–284 (2007).
Demonstrates that poorer, less educated women were more likely to be given intentionally lowered chemotherapy doses by their clinician. It is known that these women have lower survival rates than average and this study presents a potential causative factor. The authors suggest that clinicians may fear that these patients, with fewer social and financial resources, are less likely to tolerate the full doses, which often cause unpleasant side effects.
Pregnancy hypertension may lead to heart disease in later life
Women who suffer from high blood pressure, gestational diabetes or pre-eclampsia during pregnancy may be at a greater risk of developing atherosclerosis and coronary disease after the menopause, according to a study recently published in Hypertension.
The study, conducted by researchers in The Netherlands, suggests that blood pressure problems during pregnancy could act as an early warning to identify women at increased risk of heart disease.
“For some women, pregnancy functions the same way as stress tests, such as an oral glucose tolerance test,” explained the senior author of the study, Michiel L Bots.
“In an oral glucose tolerance test you stress, the system that deals with a person's glucose balance,” he continued. “If the system does not function properly, glucose goes up to excessive levels. It is a means to identify those at high risk of developing diabetes. Similarly, gestational diabetes, pregnancy-induced hypertension and pre-eclampsia provide an opportunity to identify individuals with an increased risk of type-2 diabetes mellitus and cardiovascular disease at an early age.”
The study involved 491 healthy postmenopausal women enrolled in the Predictors of Response to Cardiac Resynchronization Therapy (PROSPECT) study, 31% of whom had experienced pregnancy-associated high blood pressure in the past. Several years later, computed tomography was used to measure coronary artery calcification, an indicator of risk for coronary disease. Coronary calcification was 57% more prevalent in women who had experienced high blood pressure during pregnancy, including mild and severe hypertension, and pre-eclampsia.
“Usually it is assumed that development of high blood pressure during pregnancy has no long-term consequences since it subsides after pregnancy”, commented Bots. “Our research and that of others may have important implications for the management of women who have high blood pressure in pregnancy.”
Source: Sabour S, Franx A, Rutten A et al.: High blood pressure in pregnancy and coronary calcification. Hypertension (2007) [Epub ahead of print].
Many breast cancer patients do not complete their full course of tamoxifen
Up to a quarter of breast cancer patients discontinue treatment with tamoxifen during the first year of a 5-year regimen, with women aged under 40 years or over 75 years being most likely to quit early.
“We now know that there are a considerable number of women who stop taking their tamoxifen early”, reported study author Thomas I Barron, Trinity College Dublin (Ireland).
The study reviewed pharmacy databases to check whether the study population of 2800 breast cancer patients filled their prescriptions for tamoxifen. Only around 31% of patients completed the full 5-year course of the drug.
Researchers were surprised at the high drop-out rates, which they hypothesize to be due to the long regimen and the sometimes severe side effects. They stress that only a full course of tamoxifen gives optimum protection from cancer recurrence and recommend women seek advise from their healthcare provider if unpleasant side effects occur.
Source: Barron TI, Connolly R, Bennett K, Feely J, Kennedy MJ: Early discontinuation of tamoxifen: a lesson for oncologists. Cancer (2007) (Epub ahead of print).
Black women in the USA often do not receive mammogram results
It has long been known that black women in the USA tend to have a later stage of breast cancer at diagnosis, and a new study by researchers at the Yale University Medical School (CT, USA), has suggested a potential contributory factor: black women are more likely to experience inadequate communication of their mammography results than white women.
“Communication of the results seems to break down more for black women than for white women”, commented lead researcher Beth A Jones.
The study found that black women were less likely to report having received their results and more likely to misunderstand them.
“Black women were about twice as likely to get inadequate communication [on their mammogram results],” Dr Jones explained.
The study involved 411 black and 734 white women in Connecticut (USA) who received a mammogram from 1996–1998. The women were interviewed as to their understanding of their mammogram results, which were then compared with the actual results from their medical records.
Black American women are not gaining the full benefit of mammography screening for breast cancer, often not receiving or not understanding the results of their mammogram.
A total of 21% of black and 11% of white women had experienced inadequate communication of results, the majority of these reporting that they had never received their results, while some women's interpretation of their results was different from that given in the official test results. Of those women in whom there was a discrepancy between actual and reported results, 31% of black women, but only 6% of white women had an abnormal mammogram, and so were in danger of delaying a breast cancer diagnosis.
It remains unclear as to why black women were more likely to experience inadequate communication of results, but the authors suggest that both healthcare providers and women themselves need to take responsibility for communication of mammogram results. Healthcare providers should ensure that patient addresses are up-to-date and remind women to look out for their results and call the clinic if they do not receive or understand them.
Source: Jones BA, Reams K, Calvocoressi L, Dailey A, Kasl SV, Liston NM: Adequacy of Communicating results from screening mammograms to African–American and white women. Am. J. Public Health (2007) [Epub ahead
Risk factors for incontinence change over time
The risk factors for urinary incontinence shift as women age, with past pregnancies, diabetes and uterine fibroids being more important in younger middle-aged women, while excess weight and poor overall health were key factors in older women.
A new study followed 3300 American women with an average age of 46 years over a period of 5 years, who were questioned yearly regarding their health, lifestyle and quality of life.
The researchers hope that knowledge regarding how risk factors change over time in middle-aged women will help those treating these distressing conditions.
Source: Waetjen LE, Liao S, Johnson WO et al.: Factors associated with prevalent and incident urinary incontinence in a cohort of midlife women: a longitudinal analysis of data: study of women's health across the nation. Am. J. Epidemiol. 165(3), 309–318 (2007).
Experts worried as mammography rates fall in the USA
Mammography screening rates among women aged 40 years and over are falling, according to new data from the US Centers for Disease Control. Between 2000 and 2005 the number of women reporting having had a mammogram in the last 2 years, as recommended by US public health officials, dropped by 1.8%, translating to 1.1 million fewer US women receiving this potentially life-saving screening test.
“We're hoping it's just a dip, because we don't want to see the declines,” stated study author Blythe Ryerson. “It's too early to tell if it is going to continue, but we're certainly going to be watching the numbers.”
Len Lichtenfield, deputy chief medical officer of the American Cancer Society, is also concerned by the latest figures. “We have been noting for some time a gradual decrease in women getting mammograms, and we've been concerned. The bottom line is, fewer women are getting mammograms, fewer breast cancers are detected early. That means more late detection, fewer treatment options and a poorer prognosis for survival.”
Source: Centers for Disease Control and Prevention: Use of mammograms among women aged >40 years – United States, 2000–2005. MMWR Morb. Mortal. Wkly Rep. 56(3), 49–51 (2007).
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