Breast cancer gene carriers need dual screening

NEW YORK (Reuters Health) — Among women with BRCA1 gene mutations, which are known to increase the risk of breast cancer, annual screening with both mammography and MRI is associated with better survival when compared with screening with either method alone, new research indicates. The trade-offs, however, are a high rate of false-positive results, which lead to unnecessary biopsies.

The findings were based on data from 22 studies that included 8,139 women who carried the BRCA1 gene. In addition, the researchers developed a prediction model based on data from the Surveillance Epidemiology and End Results (SEER) Program (1975-1980) and the Breast Cancer Surveillance Consortium.

The results indicated that annual combined screening with mammography plus MRI increased the average life expectancy by 1.38 years compared with follow-up only without screening tests (clinical surveillance). The false-positive rate was 84.0 percent.

"For women who carry BRCA1 gene mutations, adding annual MRI to annual mammography has a clear benefit in terms of projected life expectancy and breast cancer mortality reduction," lead author Dr. Janie M. Lee told Reuters Health. "Whether the trade-offs related to MRI screening are acceptable to women at increased risk of developing breast cancer is still being investigated."

In the general population, the lifetime risk of breast cancer for women is 13 percent. In BRCA1 mutation carriers, by contrast, this risk can be as high as 80 percent.

Strategies to reduce this high risk have included preventative mastectomy, removal of the ovaries (to lower levels of oestrogen which can encourage breast cancer growth), preventive chemotherapy, and more frequent office visits, according to the report in the journal Radiology.

Younger women, especially those of childbearing age, are often reluctant to undergo preventative mastectomy, the investigators point out. Preventative chemotherapy might be a suitable choice, but unfortunately no studies to date have shown it to reduce breast cancer mortality. That leaves increased surveillance.

According to the report, mammography is not nearly as sensitive at detecting breast cancers in BRCA1 mutation carriers as it is in the general population. Previous research has shown that MRI can achieve higher sensitivity than mammography, but whether this translates into reduced breast cancer mortality is unclear.

Due to the long length of follow-up and the large number of patients required, the authors note that it is unlikely that any trial will ever investigate whether MRI screening can reduce breast cancer mortality. This prompted Lee, from Massachusetts General Hospital in Boston, and colleagues to conduct the current decision analysis.

The average life expectancy was 71.15 years, the report indicates, and with clinical surveillance alone, the average diameter of breast cancers at diagnosis was 2.6 centimeters. Using annual screening with mammography, MRI, or both, the average tumour diameter at diagnosis fell to 1.9, 1.3, and 1.1 centimeters, respectively.

Compared with clinical surveillance, all three imaging-based screening strategies increased life expectancy and reduced mortality from breast cancer. Again, the most pronounced benefit was with mammography plus MRI.

In addition to the high false-positive rate seen with mammography plus MRI screening, nearly one in three women underwent one or more biopsies for what turned out to be benign disease. The false-positive rates and negative biopsy results with the other screening strategies were also increased, but not as high as that seen with the combined approach.

More research is required to find the optimal sequence and frequency for screening tests for breast cancer, and to "minimise the potentially negative effects on women's health-related quality of life when screening with increased intensity is pursued," Lee noted.

She added that her team is "currently working to extend our model of breast cancer natural history and screening in BRCA1 gene mutation carriers to women who carry BRCA2 mutations, and women whose lifetime risk of breast cancer exceeds 20 percent — these women are defined by the American Cancer Society as being at 'high-risk' of developing breast cancer".

Total cholesterol tied to risk of plaque rupture

NEW YORK (Reuters Health) — In individuals without symptoms who have thickened walls of the carotid arteries, two major arteries located on each side of the neck that provide blood and oxygen to the brain, the total blood levels of cholesterol are strongly associated with the presence a lipid, or fat-based," core within plaque, which have a vulnerability to rupture, researchers report.

"We know that a lipid core, made up of fatty dead tissue deposits, within an atherosclerotic plaque puts the plaque at risk for causing an adverse clinical event, such as a stroke if the plaque is in the carotid artery or a heart attack if the plaque is in the coronary artery," lead investigator Dr. Bruce A. Wasserman told Reuters Health.

To identify factors associated with a lipid core, Wasserman of Johns Hopkins School of Medicine, Baltimore, and colleagues examined subjects taking part in a study of atherosclerosis, also referred to as hardening of the arteries. All of the subjects were free of cardiovascular disease and were among participants with the thickest carotid artery walls, as determined by ultrasound.

The researchers used MRI and analysis software to assess the composition of 214 plaques with a thickness of at least 1.5 millimeter and found a lipid core in 151 (71 percent) of these plaques, according to the report, published in the medical journal Stroke.

Compared with patients with the lowest levels of total blood cholesterol, those with medium levels had a 2.8-fold increased risk of having a lipid core, after factoring in the possible effects of age, sex, high blood pressure and diabetes. Study participants with the highest cholesterol levels had a 4.6-fold increased risk of having a plaque with a lipid core.

None of the cardiovascular risk factors other than high serum cholesterol was associated with having a lipid core.

"Our study suggests that a person's cholesterol level is the most important risk factor for developing this dangerous feature of plaque," concluded Wasserman. "This supports the notion that lowering one's cholesterol prevents its formation and might reduce one's risk for such a clinical event."

Hepatitis C a risk factor for lymphoma

NEW YORK (Reuters Health) — Canadian researchers have confirmed an association between hepatitis C virus (HCV) infection and an increased risk of non-Hodgkin's lymphoma, according to their report in the International Journal of Cancer.

Dr. John J. Spinelli of the British Columbia Cancer Agency, Vancouver, and colleagues note that studies have indicated HCV infection may double the risk of non-Hodgkin's lymphoma. To investigate this relationship, the researchers conducted a population-based study in British Columbia, involving 795 patients with newly diagnosed lymphoma and 697 subjects without lymphoma.

In 2.4 percent of the patients with non-Hodgkin's lymphoma were also infected with HCV compared with 0.7 percent of the comparison subjects. The greatest non-Hodgkin's lymphoma risk was for diffuse large B-cell lymphoma and marginal zone lymphoma, with 7.3-fold and 6.1-times the risk.

The researchers note that the prevalence of HCV infection in the province, estimated to be about 1.5 percent, is nearly twice the national rate, "likely due to a high rate of injection drug use." Nevertheless, they point out, the non-Hodgkin's lymphoma risk for HCV infection remained after adjusting for injection drug use.

Spinelli told Reuters Health that a possible connection between HCV and non-Hodgkin's lymphoma was first suggested in the 1990s and subsequent investigation has helped to confirm this.

"Our study," he concluded, "provides further evidence that there is indeed an association between HCV infection and the risk of non-Hodgkin's lymphoma."

Vitamin E may raise TB risk in smokers

NEW YORK (Reuters Health) — The use of vitamin E supplements appears to increase the risk of tuberculosis in some middle-aged smokers, according to a study in the British Journal of Nutrition.

In the overall analysis, vitamin E use did not affect the odds of tuberculosis in smokers. In people who smoked at least 20 cigarettes per day and consumed diets high in vitamin C, however, vitamin E supplements more than doubled the risk.

Vitamin E is a widely used dietary supplement believed to enhance immune function, note authors Dr. Harri Hemila and Dr. Jaakko Kaprio. However, trials in human subjects have shown unpredictable effects of vitamin E on various infectious diseases.

To examine the impact of vitamin E use on the risk of tuberculosis, the two researchers from the University of Helsinki in Finland analysed data from the ATBC (Alpha-Tocopherol, Beta-Carotene Cancer Prevention) Study.

The study participants were 29,023 male smokers, ages 50 to 69 years, who were randomly assigned to take daily supplements containing vitamin E, beta-carotene, vitamin E plus beta-carotene, or inactive placebo.

During a follow-up period of around six years, 174 cases of tuberculosis were diagnosed. Overall, neither vitamin E nor beta-carotene supplements affected the risk of tuberculosis.

However, as noted, the combination of smoking 20 or more cigarettes per day and consuming a diet rich in vitamin C and vitamin E supplements more than doubled the risk of tuberculosis. Further analysis showed that the increased risk was restricted to the first year after vitamin E supplementation began.

"Although vitamin E may be beneficial in restricted population groups, those groups are poorly defined so far," Hemila and Kaprio point out.

"The consumption of vitamin E supplements by the general population should be discouraged because there is evidence of harm for some people," they conclude.

Acupuncture may help relieve menstrual pain

NEW YORK (Reuters Health) — Acupuncture can help relieve menstrual pain and improve the quality of life for some women, a new study from Germany shows.

Because the acupuncture patients were compared with a control group who received no therapy, rather than a "sham," or fake, version of the treatment, the placebo effect could have played a role, Dr. Claudia M. Witt of Charite University Medical Center in Berlin and her colleagues acknowledge.

"Nevertheless, our study showed that acupuncture was beneficial for women if offered as part of the health insurance system," the researchers write in the American Journal of Obstetrics & Gynecology.

Non-steroidal anti-inflammatory drugs, or NSAIDs, are standard treatment for menstrual pain, but they carry the risk of side effects, Witt and her team note in their report. Acupuncture and acupressure have been found helpful in treating other types of pain, so the researchers tested whether acupuncture delivered by doctors — as it typically is in Germany — would help with dysmenorrhoea.

Since 2000, the researchers note, the nation's health insurers have recommended that acupuncture to relieve pain only be covered by insurance if it is delivered as part of a study to investigate its effectiveness.

The researchers enrolled 201 women who agreed to be randomly assigned to acupuncture or no treatment.

After three months of treatment, which included an average of about 10 sessions, the average pain score was 3.1 in the acupuncture group, compared with 5.4 in the control group, using a pain scale of one to 10, with 10 being the worst pain.

Among women given acupuncture, 63.4 percent reported at least a 33 percent improvement in their symptoms, while 24 percent of women in the control group did.

Based on these findings, the researchers conclude that "acupuncture should be considered as a viable option in the management of these patients."

Language problems seen with anti-migraine drug

NEW YORK (Reuters Health) — Migraine patients taking topiramate, a drug used to stave off the debilitating headaches, may experience disturbances in language, according to a recent report.

Thinking difficulties have been reported in patients taking topiramate, the authors explain, but they have never been defined and assessed with the aid of standardised tests.

Dr. Francesca Coppola from the University of Perugia, Italy and associates investigated the occurrence of language disturbances in 30 migraine patients treated with topiramate, sold under the trade name Topamax, compared with patients treated with other drugs or untreated patients.

Eight patients in the topiramate group experienced language problems compared with none of the patients in the other groups.

Language disturbances generally occurred within the first month of treatment, were of mild severity, and did not require further adjustment of dosages or discontinuation of topiramate.

The disturbances included difficulty finding words, slowing of verbal expression, changes of one word with another with the same meaning, need to search for the right word, production of nonexistent words deriving from the fusion of two words, or occasional difficulty in naming objects.

The presence of anxiety or depression worsened performance on some of the tests, the report indicates.

In light of these findings, the researchers call for further studies comparing topiramate with similar drugs.