Other highlights in the May 13 JNCI

Familial Breast Cancer Risk Continues Throughout a Woman’s Life Women who have a sister diagnosed with breast cancer are at an increased risk of developing the disease throughout their lives. The increased risk is most pronounced in younger women, regardless of the age at which the first sister was diagnosed.

Women who have a first degree relative affected by breast cancer are at increased risk for the disease, but it is unclear how a woman’s risk varies with her current age and the age at which her relative was diagnosed.

To find out, Marie Reilly, Ph.D., and colleagues at the Karolinska Institute in Stockholm analyzed a national family database that is linked to the national cancer register. They compared the breast cancer incidence between 1958 and 2001 in 23,654 sisters of breast cancer patients and in 1,732,775 women who did not have a sister with breast cancer.

The familial risk was highest for young women, aged 20 to 39, with a 6.6-fold increase in the risk of breast cancer diagnosis, compared with similarly aged women who did not have a sister with breast cancer. The excess risk declined to approximately two-fold for women aged 50 and older. For the sisters of a breast cancer patient, the risk of diagnosis was similar regardless of whether she was approaching the age at which her sister had been diagnosed or had already passed it.

“Sisters of women diagnosed with breast cancer still have an increased risk of breast cancer 20 years after diagnosis of the sister, suggesting that women live with the burden of familial breast cancer for their lifetime,” the authors write.

Contact: Marie Reilly, marie.reilly@ki.se, 46852483982

Exercise in Adolescent and Young Women Is Associated With a Lower Risk of Premenopausal Breast Cancer

Women who engaged in leisure-time exercise between the ages of 12 and 35 have a lower risk of developing premenopausal cancer than do women who were less active.

Several studies have shown that regular exercise is associated with a lower risk of postmenopausal breast cancer, but few studies have looked at the impact of exercise on premenopausal disease.

In this cohort study, Graham Colditz, M.D., of Washington University School of Medicine in St. Louis and colleagues examined exercise and the likelihood of developing breast cancer in a group of 64,777 women participating in the Nurses’ Health Study II. The researchers asked participants to fill out questionnaires on their physical activity starting from age 12. With six years of follow-up, 550 participants have been diagnosed with breast cancer.

The age-adjusted incidence rates for breast cancer was 194 cases per 100,000 person-years in the least active women versus 136 cases in the most active. Women whose activity was equivalent to 3.25 hours per week of running or 13 hours per week of walking had a relative 23 percent reduced risk of disease compared with women who had been less active.

“These results suggest that consistent physical activity during a woman’s lifetime is associated with decreased breast cancer risk. Unlike many risk factors for breast cancer, physical activity is an exposure that can be modified,” the authors write.

Contact: Judy Martin, martinju@msnotes.wustl.edu, (314) 286-0105

Access to Oncologist Does Not Explain the Disparity in Rectal Cancer Outcomes

Access to medical oncologists does not account for racial differences in outcomes for elderly patients with rectal cancer.

Previous studies have shown that black patients with rectal cancer have poorer survival than white patients, and they are less likely to receive adjuvant chemotherapy.

To find out if black patients are less likely than white patients to be referred to a medical oncologist or radiation oncologist following surgery for rectal cancer, Arden Morris, M.D., of the University of Michigan in Ann Arbor and colleagues analyzed information from the SEER (Surveillance, Epidemiology, and End Results) database linked to Medicare data. They identified 134 black patients and 2,582 white patients aged 66 years or older who were treated for rectal cancer between 1992 and 1999.

Black patients were as likely to be referred to a medical oncologist as white patients (73.1 percent versus 74.9 percent). However, black patients were less likely than white patients to undergo chemotherapy (54.1 percent versus 70.2 percent) or to undergo radiation therapy (73.7 percent versus 83.4 percent). This trend was more pronounced among younger, healthier black patients, who would be the most likely to benefit from such therapy.

The reasons for the differences in care remain unclear. “Health-care providers play a crucial role in recommending and helping patients navigate treatment options. However, none of the provider characteristics that we examined was associated with racial difference in receipt of adjuvant therapy,” the authors write.

Contact: Nicole Fawcett, nfawcett@med.umich.edu, (734) 764-2220

New Guidelines Proposed for Clinical Trials in Liver Cancer

An expert panel convened by the American Association for the Study of Liver Diseases has developed a set of guidelines for clinical trials that test new therapies in patients with hepatocellular carcinoma, the most common liver tumor and the third leading cause of cancer-related death globally.

Well-designed clinical trials are important for the assessment of any new therapy. That need is particularly acute in liver cancer, as the underlying liver disease that affects most of these patients can complicate interpretation of trial results. Additionally, heterogeneity of inclusion criteria and the development of new targeted agents pose challenges in this disease. A common agreement on trial design, end points, and classification of the disease is proposed.

The new guidelines specify that researchers should use time-to-event primary endpoints in phase II trials, but they should rely on overall survival as the main endpoint in phase III trials. Clinical endpoints that are most likely to be influenced by the underlying liver problems, such as progression- and disease-free survival, should be avoided. The panel also specifies what treatments should be used in the control arms for various stages of disease. Additionally, patient selection for the trials should be based on the Barcelona-Clinic Liver Cancer staging system, and new drugs should be tested initially on only patients who have good liver function.

“These rec¬ommendations are intended to provide a framework as of 2008 that will evolve as new evidence becomes available, including more pre¬cise information on the natural history of [hepatocellular carcinoma], novel therapies, and predictive biomarkers,” the authors write.

Contact: Josep Llovet, jmllovet@clinic.ub.es, +34 (93) 227-9156

Endoscopic Sphincterotomy Is Not Associated With Risk of Cholangiocarcinoma

Endoscopic sphincterotomy is not associated with an increased long-term risk of cholangiocarcinoma, or cancer of the bile ducts.

Endoscopic retrograde cholangiography (ERC) is used to diagnosis disorders of the bile ducts, pancreas, and gallbladder. If a problem is found during ERC, the surgeon may be able to treat it by performing a sphincterotomy of the ampulla of Vater during the procedure. Because sphincterotomy can lead to intestinal reflux and chronic inflammation, there has been concern that it may increase the incidence of subsequent cholangiocarcinoma.

Frank Viborg Mortensen, D.M.Sc., of the Aarhus University Hospital in Noerrebrogade, Denmark, and colleagues compared the rates of cholangiocarcinoma in 10,690 patients who had ERC with sphincterotomy with those of 10,690 patients who had undergone ERC alone, using data entered into the Danish National Patient Registry between 1977 and 2003.

Patients who had undergone ERC with sphincterotomy had a decreasing incidence of cholangiocarcinoma over time, with 404 cases per 100,000 person-years in the first year, 79 in the second year, 42 in years 3–5, and 27 after year 5. The numbers were similar for patients who had undergone ERC alone: 458 in the first year, 12 in the second, 10 in years 3–5, and 19 after year 5.

The researchers conclude that the high incidence in the patients with ERC plus sphincterotomy in years 1–5 were due to undiagnosed cancers at the time of the initial procedure. “The fact that cholangiocarcinoma incidence rates were similar for ERC patients with and without sphincterotomy from 5 years after ERC indicates that reflux after sphincterotomy does not have a causal role in the development of these cancers,” the authors write.

Contact: Frank Viborg Mortensen, Fvmor@as.aaa.dk, +45 86 11 02 10

Also in the May 13 JNCI:

• http://www.eurekalert.org/emb_releases/2008-05/jotn-pim050808.php

Source: Journal of the National Cancer Institute