Breast Density and Mammography Sensitivity

A study funded by NCI and the American Cancer Society published in the October 5 Journal of the National Cancer Institute, shows that increased breast tissue density and rapid tumor growth are associated with decreased mammogram sensitivity and missed cancers in women aged 40-49.

Mammography is recommended for women who are in their 40s and older, but is less sensitive at detecting breast cancer in women at the younger end of this scale. To determine specific reasons for the lack of sensitivity, the research team, led by Dr. Diana S.M. Buist at Group Health Cooperative in Seattle, studied 576 women from the Breast Cancer Screening Program who were diagnosed with invasive breast cancer from 1988-1993. The women completed breast cancer risk factor questionnaires upon enrollment in the study and at the time of each subsequent mammogram; all diagnosed tumors were evaluated for the rate of tumor growth. At 12 and 24 months following the subject's baseline mammogram, researchers evaluated mammogram sensitivity while accounting for menopause status, body mass index, family history of breast cancer, hormone therapy use, time since last mammogram, tumor markers, breast density, and quality of mammographic images.

Researchers found that breast density accounted for most of the reduction (68 percent) in mammogram sensitivity in women aged 40-49 when looking at cancers occurring within 12 months. However, when these women were evaluated at 24 months, breast density accounted for 38 percent of the decline in sensitivity, while rapid tumor growth accounted for a 30 percent reduction.

Says Dr. Stephen Taplin of NCI, who also worked on the study, "These data begin to provide greater insight into how to improve mammography for women ages 40-49, and why a 2-year interval may be less effective. However, it is a study of detection, not mortality. Improvements must be tested for their effect on mortality."

Drug Combo Improves Outcomes in Prostate Cancer

Metastatic prostate cancer, found in 10-20 percent of men diagnosed with the disease each year, has a median survival period of less than a year. Patient care focuses on pain relief via radiation, narcotics, corticosteroids, and the chemotherapy drug mitoxantrone. However, two recent studies in the October 7 New England Journal of Medicine have found that a new chemotherapy regimen can improve survival and quality of life for these men.

In the first study, a combination of docetaxel with prednisone every 3 weeks, compared with mitoxantrone with prednisone at the same frequency, improved median survival (up to 18.9 months) and quality of life, while decreasing pain and serum PSA levels. Led by researchers at the University of Toronto and the Southwest Oncology Group, the study was sponsored by Aventis. Patients who received docetaxel showed better outcomes than those who received mitoxantrone, but the authors note that it was "at the cost of a higher incidence of adverse effects," including neutropenic fevers, cardiovascular and neurologic events, nausea, and metabolic disturbances.

The second study compared 3-week doses of docetaxel with estramustine to 3-week doses of mitoxantrone with prednisone. The trial, led by researchers at Columbia University and cosponsored by Aventis and NCI, found that the docetaxel combination increased median survival to 17.5 months and lowered mortality by 20 percent. The authors noted an increased rate of adverse events with docetaxel similar to those in the first study, and wrote, "These factors must be balanced when one is considering...first-line therapy for men with metastatic, androgen-independent prostate cancer."

Effectiveness of Shorter Therapy for Wilms' Tumor

Researchers from the International Society of Paediatric Oncology found that reducing the course of postoperative chemotherapy to 4 weeks produced equivalent survival rates compared with the standard 18-week treatment for stage I Wilms' tumor. Results of their 7-year study were published in the October 2 Lancet.

Wilms' tumor, a type of kidney cancer that affects infants and children, is considered curable in most cases, but common chemotherapy drugs have been associated with toxic effects to the liver and heart. Reducing intensity of chemotherapy by shortening treatment may reduce side effects and cost.

Researchers enrolled and randomized 410 patients between the ages of 6 months and 18 years with stage I intermediate-risk or anaplastic Wilms' tumor between 1993-2000. Event-free survival at 2 years was 91.4 percent in the standard group and 88.8 percent in the experimental group. Event-free survival at 5 years was similar: 88.3 percent in the standard group and 87 percent in the experimental group.

The authors wrote that "reduction of postoperative chemotherapy is feasible for patients with stage I intermediate-risk or anaplastic Wilms' tumor while maintaining 2-year, event-free survival at about 90 percent and 5-year overall survival at about 95 percent."

Arylamines and Bladder Cancer Risk in Nonsmokers

Results of a recent study indicate that exposure to arylamines, a family of known carcinogens previously associated with the increased risk of bladder cancer in smokers, is also a risk factor for bladder cancer in nonsmokers. The report, by Dr. Jinping Gan and colleagues at Massachusetts Institute of Technology, was published in the October 6 Journal of the National Cancer Institute.

Metabolites of certain drugs and pesticides, arylamines are found in cigarette smoke, permanent hair dyes, and other environmental sources. Studies have shown that cigarette smoking may contribute to at least 50 percent of current bladder cancer cases in the United States. However, previous research has also indicated that 4-ABP, a specific arylamine, is associated with bladder cancer in nonsmokers.

In this study, funded in part by NCI, researchers quantitatively measured the levels of arylamine adducts in the blood of 298 subjects with confirmed bladder cancer and 308 control subjects to assess exposures to nine different arylamines. Their results indicated that in addition to 4-ABP, three other arylamines may be independent risk factors for bladder cancer in nonsmokers. The authors note that exposure to arylamines may be the causal factor for most cases of bladder cancer in humans and conclude that because "arylamines may account for a substantial proportion of bladder cancers among the general population, identification of the environmental sources of these compounds is needed."