Oct. 6 Issue Transcript
Issue 19 of the Journal of the National Cancer Institute includes a study on liver cancer reduction from HBV vaccinations and a study and accompanying editorial on prostate cancer overdiagnosis. This issue also includes a study on SNPs linked with prostate cancer in Japanese men; a study on surgeon training on the breast cancer sentinel node; a study looking at mastectomy decisions among breast cancer patients; and finally a review of the literature on biomarkers for outcome of EGFR-targeted therapy for metastatic colorectal cancer.
Cases of Liver Cancer Reduced in a Younger Population Vaccinated for HBV
A 20-year follow-up study revealed a dramatic drop in liver cancer cases among 6- to 19-year-olds who were vaccinated for the hepatitis B virus at birth, according to a study published online September 16.
In July 1984, a universal vaccination program was initiated among newborn children in Taiwan to prevent the hepatitis B virus infection, which can predispose to the development of hepatocellular carcinoma.
For this study, Mei-Hwei Chang, of the Department of Pediatrics, National Taiwan University Hospital in Taipei, and colleagues collected data from almost 2,000 patients with hepatocellular carcinoma who were aged 6-29 years at diagnosis in Taiwan between 1983 and 2004. Age- and sex-specific incidence were compared among vaccinated and unvaccinated birth cohorts with regression models.
Sixty-four cases of hepatocellular carcinoma were found among people vaccinated in almost 38 million person-years versus 444 cancers among unvaccinated people in almost 80 million person-years.
A few individuals have developed liver cancer despite the program. Analysis of their records shows that most of these patients, however, were not given enough doses of the vaccine, or were insufficiently protected when they were born to hepatitis B-infected mothers.
Overdiagnosis Since Introduction of Prostate Cancer Screening
The introduction of prostate-antigen screening, or PSA, has resulted in over 1 million additional men over the last 23 years being diagnosed and treated for prostate cancer—most of whom were likely overdiagnosed, researchers reported in a study published online August 31.
Overdiagnosis has been associated with early diagnosis in prostate cancer, but there have been no previous national estimates of its magnitude.
Using data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results program, H. Gilbert Welch, of the White River Junction VA and The Dartmouth Institute for Health Policy & Clinical Practice., and Peter C. Albertsen, of the University of Connecticut, examined age-specific prostate cancer incidence rates to determine the excess (or deficit) in the number of American men diagnosed and treated in each year after 1986. PSA screening was introduced in 1987.
According to the study, an additional 1.3 million men were diagnosed—that would otherwise have never been diagnosed absent screening—and more than 1 million have been treated since 1986. The increased diagnosis has been most dramatic among younger men: more than tripling since 1986 in men aged 50-59 and more than a sevenfold increase in men under age 50.
In an accompanying editorial, Otis W. Brawley, chief medical officer of the American Cancer Society, discusses how screening practices for prostate cancer have surged over the last 20 years, despite little evidence that it has saved lives.
According to Brawley, the highly pushed early-detection message has skewed public opinion and de-legitimized the questions concerning screening, causing many men to be overdiagnosed. Mortality has decreased since the early 1990s, the editorialist points outs, but reasons for this decline are unclear.
SNPs Linked with Prostate Cancer Confirmed in Japanese Men Too
A third of the previously identified single-nucleotide polymorphisms, or SNPs, associated with prostate cancer in men of European or African ancestry were also associated with prostate cancer in a Japanese population, according to a study published online September 2.
Genome-wide association studies have primarily been performed in populations of European ancestry, but little is known if the associations discovered in one population are relevant for other populations.
In this study, Matthew L. Freedman, of the Department of Medical Oncology at the Dana-Farber Cancer Institute in Boston, and colleagues evaluated 23 SNPs previously reported to be associated with prostate cancer risk and clinical covariates (tumor aggressiveness and age at diagnosis, for example) in almost 1350 Japanese men.
A total of seven SNPs were associated with increased risk of prostate cancer in this study population, but no associations were found with disease aggressiveness or age at diagnosis. Men with six or more risk alleles had substantially higher risk for prostate cancer than men with two or fewer alleles.
In an accompanying editorial, John P.A. Ioannidis, of the Department of Hygiene and Epidemiology, University of Ioannina School of Medicine in Greece, said that these data reinforce the idea that discovered variants are often simply population-specific markers that need far more study to confirm as functional culprits.
However, the editorialist points out, population diversity could have implications about the use of information from these studies for predictive purposes. “…this is just the beginning,” the editorialist writes. “The findings need to be replicated again and then again validated.”
Surgeon Training Found Effective in Breast Cancer Sentinel Lymph Node Trial
Training methods for surgeons who perform breast cancer sentinel lymph node resection were found to be effective in almost 97% of surgeons assessed, according to a study published online August 24.
The randomized National Surgical Adjuvant Breast and Bowel Project B-32 trial is evaluating whether sentinel lymph node resection can achieve the same outcomes as axillary lymph node resection but with fewer side effects.
In this study, David N. Krag, of the Department of Surgery, College of Medicine, University of Vermont in Burlington, and colleagues assessed the effectiveness of three training methods (core-trained, site trained, and expedited training) for the sentinel node resection, as well as overall protocol compliance and their relationship to technical outcomes.
Out of the 261 surgeons approved to randomly assign patients to the B-32 trial, 224 trained surgeons had an overall success rate of 96.9%, with no statistically significant difference among the three training groups. Among all surgeons, a statistically significant positive association was observed between the average number of procedural errors and the false-negative rate.
Mastectomy Decisions Among Racially and Ethnically Diverse Breast Cancer Patients
Women diagnosed with nonmetastatic breast cancer who were concerned about body image and their spouse’s opinion were less likely to have a mastectomy than those who placed less concern on these issues, according to new study published online August 31. Overall, patients who were more involved in the decision making about their treatment were more likely to have a mastectomy, regardless of racial or ethnic group.
Sarah T. Hawley, of the Division of General Medicine, Department of Internal Medicine at the University of Michigan in Ann Arbor, Ann Arbor VA Medical Center and Cancer Surveillance and Outcomes Research Team, and colleagues evaluated the association between patient decision involvement and receipt of surgery among racially and ethnically diverse patients, as well as patients’ attitudes about surgery and the role of family and friends in treatment choices.
Researchers identified over 3,000 women diagnosed with nonmetastatic breast cancer from June 2005 through February 2007 who were reported to the Los Angeles or Detroit Surveillance, Epidemiology, and End Results registries. The primary factors analyzed in the choice of surgical options were patient involvement in decision making, race or ethnicity, concern about recurrence, the effects of radiation, the impact of surgery on body image, and the role of others in decision making.
Researchers found that patient attitudes about surgery, as well as the opinion of family and friends, contribute to the surgical choices made by women with breast cancer. Greater patient involvement in decision making was associated with greater receipt of mastectomy in all racial and ethnics groups.
Also, women who considered the chance of recurrence or radiation side effects very important were more likely to receive mastectomy initially than those who were less concerned. Those who reported that concern about body image and their spouse’s opinion were very important factors in their surgery decision were less likely to receive mastectomy initially than those who were less concerned.
The last article is a literature review on Biomarkers for Outcome of EGFR-Targeted Therapy for Metastatic Colorectal Cancer
Monoclonal antibodies against the epidermal growth factor receptor, or EGFR, are used to treat EGFR-positive metastatic colorectal cancer. Such tumors are identified by immunostaining. However, only approximately 10% of such chemotherapy-refractory tumors respond to monotherapy with anti-EGFR monoclonal antibodies, indicating that other biomarkers are needed to identify tumors likely to respond to these antibodies.
Salvatoer Siena, of The Falck Division of Medical Oncology, Department of Oncology in Milan, Italy, and colleagues reviewed studies assessing alterations of various oncogenes, including KRAS, BRAF, PIK3CA, as well as PTEN protein expression, in signaling pathways downstream of EGFR as possible biomarkers.
Tumors with KRAS mutations or tumors carrying wild-type KRAS but having mutations in BRAF or PIK3CA or the loss of PTEN protein expression appear to be associated with resistance to EGFR-targeted monoclonal antibody therapy.
They conclude that use of KRAS mutations as a biomarker to determine whether a tumor will respond to anti-EGFR therapy is the first step toward individualized treatment of patients with metastatic colorectal cancer.
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