Low Levels of "Good" Cholesterol Increase Breast Cancer Risk

Postmenopausal, overweight, and obese women with low levels of the so-called "good" cholesterol (HDL-C) are at increased risk for breast cancer, according to the results of a large study of Norwegian women published in the August 4 Journal of the National Cancer Institute and funded by the Norwegian Cancer Society.

Researchers at the University of Tromsø in Norway reported on 38,823 women who had been followed for up to 21 years after initial health screenings in the 1970s and 1980s. "We found the risk of postmenopausal breast cancer among overweight and obese women [with the highest levels of HDL-C] was one-third the risk of women [with the lowest levels of HDL-C]," the study stated. This finding was not observed for postmenopausal women of normal weight or for premenopausal women of any weight status. The researchers assumed menopause to have occurred at age 50 for women in the study.

The risk of postmenopausal breast cancer "was strongest among those who gained weight" during the study's follow-up period, the researchers noted. The researchers also noted the increasing prevalence worldwide of "metabolic syndrome," characterized by factors that include obesity, glucose intolerance, high serum triglycerides, hypertension, and low levels of HDL-C.

The study's findings "suggest an interaction between metabolic disturbances (e.g., overweight or obesity and low serum HDL-C) in postmenopausal breast carcinogenesis," the researchers said. They did not find evidence of the "same strong risk associated with total serum cholesterol for postmenopausal breast cancer as we did with HDL-C." Low HDL-C may also be a marker of altered sex steroid hormones that may be increasing breast cancer risk in combination with metabolic syndrome factors.

Augmentation of Gene Related to Drug Response in Metastatic Breast Cancer

Researchers at UCLA's David Geffen School of Medicine, along with colleagues in Germany, have found that patients who have breast cancer that is positive for HER2/neu overexpression had better survival rates with a paclitaxel-based chemotherapy, compared with a cyclophosphamide-based therapy. Supported by Bristol-Myers Squibb and the Revlon/UCLA Women's Cancer Research Program, the study's results appeared in the August 4 Journal of the National Cancer Institute.

The research team, led by Dr. Dennis Slamon, re-examined a breast cancer treatment trial that had compared two different chemotherapies: epirubicin-paclitaxel (ET) and epirubicin-cyclophosphamide (EC). A total of 297 patients with metastatic breast cancer were included in this retrospective subset analysis, where initial comparisons showed little difference between ET and EC. When researchers categorized patients into HER2/neu-positive and HER2/neu-negative groups, they found that HER2/neu-positive patients had a better initial response to chemotherapy, but a worse survival prognosis than HER2/neu-negative patients. When ET and EC treatments were compared separately, HER2/neu-positive patients who received ET had both a higher initial response to treatment and a better survival prognosis than those who received EC. The researchers noted that a paclitaxel-based "regimen such as ET may provide a preferential benefit to women with HER2/neu-positive tumors."

NCI Communicates Information on First Prostate Cancer Prevention Trial

An article in the July-August issue of Urologic Oncology describes the communication techniques used by NCI to deliver information to the public about the results of the Prostate Cancer Prevention Trial (PCPT). The results of this trial indicated that a daily 5 milligram dose of the drug finasteride (Proscar) could reduce a man's risk of developing prostate cancer by 25 percent - the first time an intervention was shown to reduce the risk of this common disease. However, men who took finasteride and developed prostate cancer appeared to have an increased risk of developing high-grade disease.

Begun in November 1993, funded by NCI, and coordinated by the Southwest Oncology Group (SWOG), PCPT enrolled almost 19,000 men over a 10-year period. The trial was expected to run until June 2004 but was stopped in May 2003 because of conclusive results that were published in the July 17 New England Journal of Medicine. NCI used social marketing and public relations principles to communicate the complex results of this study to trial participants, the public, and health professionals directly and via intermediaries in the media, professional medical societies, and advocacy groups.

SWOG notified study participants via letter, while NCI held a national press conference to announce the results, produced a video news release for use by television stations, provided graphics describing the results, created a Web site dedicated to the study, and sent preview e-mails to medical professionals and cancer advocacy groups. This multifaceted approach resulted in international television, radio, Internet, and print media coverage, the majority of which reflected the intended message.

"More needs to be done to familiarize the population with the concept of cancer prevention," wrote the authors. "It is only through public understanding of the process of carcinogenesis, coupled with interventions that truly stop or reverse the process, that cancer prevention will become as widely accepted as disease prevention in other chronic illnesses."

Diets of Mexican Women May Increase Their Breast Cancer Risk

Women in Mexico City who have breast cancer reported a significantly higher intake of total calories, proteins, carbohydrates, sucrose, and fructose than a comparison group of women, according to a new study. In research published in the August Cancer Epidemiology Biomarkers and Prevention, the authors suggested that Mexican women with the highest carbohydrate intake had more than twice the risk of breast cancer than women with the lowest carbohydrate intake. The strength of the association between sucrose intake and risk of breast cancer was lower among those with a high intake of insoluble fiber.

The authors, funded by the American Institute for Cancer Research and other organizations, wrote that breast cancer mortality in Mexico almost doubled between 1979 and 2000. Given the high prevalence of obesity and type II diabetes in the country, researchers at Mexico's Instituto Nacional de Salud Pública suspected the country's high carbohydrate intake might be associated with breast cancer risk. While earlier studies in England and Italy showed no association between sugar intake and breast cancer, obesity and weight gain as an adult are clearly established as risk factors for postmenopausal breast cancer in the United States.

Study subjects included 475 women diagnosed with breast cancer and 1,391 controls who had lived in Mexico City for a year or more. The women completed a multiple-choice food questionnaire that asked them how often they had eaten various foods over the previous year. Accounting for socioeconomic status, age, family history of breast cancer, age at first birth, number of births, and, in some cases, body mass index, the researchers found that women in the top 25 percent of carbohydrate consumers were 2.2 times more likely to be diagnosed with breast cancer than those in the bottom 25 percent.

The researchers write that Mexico City is "an area with dietary patterns distinct from those of affluent Western countries." In Mexico City, women eat more carbohydrates (57 percent of total energy intake in this study) than women in the United States, for example, where more fat and animal protein are consumed, the authors noted.

In a press release from the American Association of Cancer Research, study co-author Dr. Walter Willett, Fredrick John Stare Professor of Epidemiology and Nutrition at the Harvard School of Public Health, noted the study's limitations. "This study raises important questions about high carbohydrate diets, particularly among populations or individuals prone to insulin resistance. However, one study is not enough to make major changes in diet, and more work on this topic is urgently needed," Willett said.

Warning Issued on Clot Risk Related to Bevacizumab

The Food and Drug Administration (FDA) late last week posted a warning letter from Genentech, Inc. to health care providers about an increased risk of clot-related adverse events in patients taking bevacizumab (Avastin), a cancer therapy that targets vascular endothelial growth factor, which plays an important role in ensuring blood supply for tumor maintenance and growth. The letter from the drug's manufacturer states: "...there is evidence of an increased risk of serious arterial thromboembolic events including cerebrovascular accidents (stroke), myocardial infarctions, transient ischemic attacks, and angina related to the use of Avastin. The risk of fatal arterial thrombotic events is also increased."

The letter advises clinicians to permanently discontinue use of bevacizumab in patients with metastatic colorectal cancer who experience an arterial thromboembolic event during treatment. It also explains that in randomized, active-controlled studies of bevacizumab, patients who received infusional 5-FU-based chemotherapy plus bevacizumab had an approximately two-fold higher risk of serious clotting events, "with an estimated overall risk of up to 5 percent." Genentech says it is developing a revised package insert for bevacizumab that contains more detailed information on clotting events. The full text of the Genentech letter and the current bevacizumab package insert are available on the FDA Web site at www.fda.gov/medwatch/SAFETY/2004/safety04.htm#avastin.