Day: 12/08/2010

Radiotherapy and Tamoxifen Show Long-Term Benefits in Locally Excised Ductal Carcinoma In Situ

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A Lancet Oncology study confirms that radiotherapy provides long-term benefits to women with locally excised ductal carcinoma in situ (DCIS), and provides new evidence that tamoxifen helps prevent recurrence as well.

In the study, conducted in the U.K., Australia, and New Zealand, some 1700 women who’d undergone complete local excision of DCIS were randomized to radiotherapy, tamoxifen, both, or neither. During roughly 13 years’ follow-up, there were 376 breast cancer diagnoses.

Radiotherapy conferred a nearly 60% reduction in diagnoses, compared with no radiotherapy; benefits were limited to decreases in ipsilateral invasive cancer and ipsilateral DCIS, with no effects on contralateral disease. In addition, tamoxifen conferred about a 30% reduction in diagnoses, with benefits seen for ipsilateral DCIS and contralateral disease. Tamoxifen did not appear to benefit women who also received radiotherapy.

A commentator, however, says we may be overtreating DCIS, given that larger, higher-grade tumors pose the greatest recurrence risk. He suggests that for lower-risk disease, “the best course might be to monitor for recurrence and offer adjuvant treatment only as needed.”

source: lancet oncology

Low-Dose Aspirin Might Not Interfere with Immunochemical Fecal Occult Blood Tests

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Aspirin, currently on the list of drugs to avoid before undergoing screening for fecal occult blood, might not interfere with immunochemical forms of the test, according to a JAMA study.

As part of their preparation for screening colonoscopy, some 2000 patients were asked about regular use of drugs, including low-dose aspirin. All patients underwent two different immunochemical fecal occult blood tests (iFOBTs) to measure hemoglobin and hemoglobin-haptoglobin.

Based on the colonoscopy findings, iFOBT sensitivity results for advanced neoplasms were as follows:

  Hemoglobin Hemoglobin-Haptoglobin
Aspirin users 70.8% 58.3%
Aspirin nonusers 35.9% 32.0%

Specificities were slightly lower for aspirin users than nonusers (e.g., 85.7% vs. 91.1% for the hemoglobin-haptoglobin test).

The authors conclude: “Our study strongly suggests that use of low-dose aspirin does not hamper testing for fecal occult blood by immunochemical tests. On the contrary, our findings raise the hypothesis that test performance may be enhanced by temporary use of low-dose aspirin, a hypothesis that needs replication in larger samples and followed up in further research.”

Soluble Guanylate Cyclase Activation With Cinaciguat: A New Approach to the Treatment of Decompensated Heart Failure

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Hingorany S et al. – Derangements of the cascade may play an important role in the pathophysiology of heart failure (HF) and other diseases. Organic nitrates, which derive their action from their metabolic conversion to nitric oxide, exploit this pathway therapeutically. They are a mainstay of treatment for acute HF, but the development of tolerance with chronic administration limits their long–term efficacy. The development of a novel class of soluble guanylate cyclase (sGC) activators has shown in both animal and preliminary clinical trials to improve hemodynamics without tolerance, while preserving renal function in patients with HF. A phase II clinical program using the sGC activator cinaciguat is now in progress in patients with symptomatic HF to further evaluate the efficacy and safety of this treatment approach.

Marked cerebral atrophy is correlated with kidney dysfunction in nondisabled adults

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The relationship between kidney dysfunction, such as chronic kidney disease (CKD), and brain morphology has attracted increasing attention, but the association between kidney dysfunction and cerebral atrophy has yet to be determined. The purpose of this study was to clarify the relationship between kidney function and a substantial degree of cerebral atrophy. A total of 610 consecutive Japanese adults without neurological disorders who had undergone health screening tests of the brain were studied prospectively. Magnetic resonance imaging was performed using a 1.5-T scanner. Using a computer-assisted processing system, the percentage of cerebrum atrophy (%Cerebrum atrophy) was calculated as an index of cerebral atrophy. Atrophy was defined as >2 s.d.s below the mean %Cerebrum atrophy. The glomerular filtration rate (GFR) was estimated using the revised equations for estimated GFR from serum creatinine in Japan. Kidney function variables included the GFR value and the prevalence of subjects with GFR <60 ml min−1 per 1.73 m2. Cerebral atrophy was found in 25 (4.1%) cases. Univariate analysis showed that age, male sex, hypertension, each kidney function variable, white matter hyperintensities and lacunae were associated with cerebral atrophy. On logistic regression analysis, GFR (odds ratio (OR), 0.64; 95% confidence interval (CI), 0.42–0.98) and GFR <60 ml min−1 per 1.73 m2 (OR, 5.93; 95% CI, 1.82–19.27) were significantly associated with cerebral atrophy. On sub-analysis, GFR <60 ml min−1 per 1.73 m2 was significantly associated with cortical atrophy (OR, 3.23; 95% CI, 1.15–9.11). Decreased GFR was significantly associated with cerebral atrophy, indicating that treatment of CKD may control age-related degenerative processes of the brain.

source: the journal of hypertension research

Finger Length a Clue to Prostate Cancer Risk

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Dec. 1, 2010 — Men whose index finger is longer than their ring finger are at a lower risk of prostate cancer than those with a finger pattern the other way round, according to a new study in the British Journal of Cancer.

The relative length of the first and third fingers is set before birth, and it is thought to relate to the levels of sex hormones the baby is exposed to in the womb. Babies exposed to less of the male sex hormone testosterone are more likely to have longer index fingers.

Finger Length and Prostate Cancer

Over a 15-year period, researchers from The University of Warwick and The Institute of Cancer Research (ICR) collected data on finger length in 1,524 patients with prostate cancer as well as 3,044 healthy people. Men were shown pictures of hands with different finger lengths and asked to identify the one most like their own right hand.

The most common finger length pattern, seen in more than half the men in the study, was a shorter index than ring finger. Men whose index and ring fingers were the same length (about 19%) had a similar prostate cancer risk to those with a shorter index than ring finger. However, men whose index fingers were longer than their ring finger were 33% less likely to have prostate cancer.

Risk reduction was even greater in men aged under 60, say the researchers, who found that this younger group were 87% less likely to be in the prostate cancer group.

Testosterone Exposure

The researchers believe that being exposed to less testosterone before birth helps protect against prostate cancer later in life. The phenomenon is thought to occur because the genes HOXA and HOXD control both finger length and development of sex organs.

“Our results show that relative finger length could be used as a simple test for prostate cancer risk, particularly in men aged under 60,” says joint senior author Professor Ros Eeles from the ICR and The Royal Marsden NHS Foundation Trust. “This exciting finding means that finger pattern could potentially be used to select at-risk men for ongoing screening, perhaps in combination with other factors such as family history or genetic testing.”

The study was funded by Prostate Cancer Research Foundation and Cancer Research UK.

Diagnosing Prostate Cancer

Helen Rippon, head of research at The Prostate Cancer Charity in the U.K., says in an emailed statement: “Diagnosis of prostate cancer is not a simple affair and the best blood test we have, known as a PSA test, tells us only that something might be wrong with the prostate, not whether it is cancerous or not. Anything that adds to our knowledge about whether a man is likely to develop prostate cancer or not is to be welcomed, especially when it is something as easy as looking at the length of his fingers.

“This research also adds to the growing body of evidence that the balance of hormones we are exposed to before birth influences our health for the rest of our lives.”

Rippon says men who check their hands and find they have a shorter index finger should not be unduly concerned. “They share this trait with more than half of all men and it does not mean they will definitely develop prostate cancer in later life,” she says.

Mammographic Surveillance In Women Younger Than 50 Years Who Have a Family History of Breast Cancer

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This study showed evidence of reduction in advanced stage breast cancer incidence with annual mammographic surveillance in women aged 40–49 years who have a family history of breast cancer. Thus, breast…

Background: Evidence supports a reduction in mortality from breast cancer with mammographic screening in the general population of women aged 40–49 years, but the effect of family history is not clear. We aimed to establish whether screening affects the disease stage and projected mortality of women younger than 50 years who have a clinically significant family history of breast cancer.

Methods: In the single-arm FH01 study, women at intermediate familial risk who were younger than 50 years were enrolled from 76 centres in the UK, and received yearly mammography. Women with BRCA mutations were not explicitly excluded, but would be rare in this group. To compare the FH01 cohort with women not receiving screening, two external comparison groups were used: the control group of the UK Age Trial (106 971 women aged 40–42 years at recruitment, from the general population [ie, average risk], followed up for 10 years), and a Dutch study of women with a family history of breast cancer (cancer cases aged 25–77 years, diagnosed 1980–2004). Study endpoints were size, node status, and histological grade of invasive tumours, and estimated mortality calculated from the Nottingham prognostic index (NPI) score, and adjusted for differences in underlying risk between the FH01 cohort and the control group of the UK Age Trial. This study is registered with the National Research Register, number N0484114809.

Findings: 6710 women were enrolled between Jan 16, 2003, and Feb 28, 2007, and received yearly mammography for a mean of 4 years (SD 2) up until Nov 30, 2009; surveillance and reporting of cancers is still underway. 136 women were diagnosed with breast cancer: 105 (77%) at screening, 28 (21%) symptomatically in the interval between screening events, and three (2%) symptomatically after failing to attend their latest mammogram. Invasive tumours in the FH01 study were significantly smaller (p=0•0094), less likely to be node positive (p=0•0083), and of more favourable grade (p=0•0072) than were those in the control group of the UK Age Trial, and were significantly less likely to be node positive than were tumours in the Dutch study (p=0•012). Mean NPI score was significantly lower in the FH01 cohort than in the control group of the UK Age Trial (p=0•00079) or the Dutch study (p<0•0001). After adjustment for underlying risk, predicted 10-year mortality was significantly lower in the FH01 cohort (1•10%) than in the control group of the UK Age Trial (1•38%), with relative risk of 0•80 (95% CI 0•66–0•96; p=0•022).

Interpretation: Yearly mammography in women with a medium familial risk of breast cancer is likely to be effective in prevention of deaths from breast cancer.

source: Lancet oncology