ONCOLOGY Vol 12 No 3

To determine the most effective strategies for the treatment of postmenopausal hormone dependent breast cancer, we recently developed a model system in nude mice. In this model, estrogen receptor-positive human breast cancer cells (MCF-7) stably transfected with the aromatase gene are inoculated into ovariectomized, immunosuppressed (nude) mice.

Toremifene (Fareston) received FDA approval in 1997 for the first-line treatment of postmenopausal women with estrogen receptor (ER)-positive or -unknown metastatic breast cancer. Phase II and III trials have demonstrated that first-line therapy with toremifene, 60 mg/d, is as effective and as well tolerated as tamoxifen (Nolvadex), 20 or 40 mg/d, in such patients.

Various ongoing double-blind clinical trials are evaluating the use of tamoxifen (Nolvadex) as chemoprevention for breast cancer. A total of over 24,000 healthy women have been randomized to these trials, and it should be possible, by the year 2000, to detect any preventive effect of tamoxifen in healthy women. Furthermore, with the large numbers of women involved, it should be possible to evaluate prevention in subgroups of participants according to risk of the disease, particularly those women carrying high-risk genes, such as BRCA1 and BRCA2.

Tamoxifen is by far the most clinically tested antiestrogenic drug currently used as adjuvant therapy for breast cancer and it continues to provide considerable benefit in this setting. The balance from clinical trials indicates a strong association between the use of tamoxifen and an increase in uterine tumors (three to sixfold). In rats, tamoxifen is a mutagenic, genotoxic hepatocarcinogen.

When results from the phase II trials of toremifene (Fareston) and tamoxifen (Nolvadex) in metastatic breast cancer were published, the Finnish Breast Cancer Group began to plan the first trial of toremifene in an adjuvant setting. This multicenter, randomized trial is comparing toremifene (40 mg/d) to tamoxifen (20 mg/d) in postmenopausal lymph node-positive breast cancer patients.

Letrozole (Femara) is a nonsteroidal aromatase inhibitor that is approximately 10,000 times as potent as aminoglutethimide in vivo. Two pivotal multinational phase III trials have compared letrozole (0.5 and 2.5 mg/d) against megestrol acetate and aminoglutethimide, respectively, in patients with locally advanced or metastatic breast cancer.

The new generation of potent steroidal and nonsteroidal inhibitors of the enzyme aromatase act by decreasing estrogen production throughout the body in postmenopausal women. The most potent of these agents may also inhibit estrogen synthesis within metastatic breast cancer tissue.

Clinical practice guidelines for gynecologic oncology were developed under the direction of the Medical Practice and Ethics Committee of the Society of Gynecologic Oncologists (SGO) in concert with national trends in medical care in the United States. The members of this committee are listed in Table 1, along with other individuals who contributed to the development of the guidelines. The guidelines, which were distributed in booklet form to the SGO membership in 1996, are being reprinted in this and successive issues of ONCOLOGY for distribution to the oncology community at large.

Scientists at Norris Comprehensive Cancer Center of the University of Southern California (USC) have found a new fork in a much-studied genetic pathway, and their work may lead to new cancer therapies, according to the center’s director.

The chairpersons of six National Cancer Institute (NCI)-sponsored cooperative groups have announced the formation of a new entity called the Coalition of National Cancer Cooperative Groups, Inc. The coalition was formed to establish a common platform upon which the cooperative groups can operate, while remaining complementary to the work already being performed within the existing NCI structure.

Researchers looking at a group of leukemia patients have found that a genetic defect that they discovered 2 years ago serves as an early warning signal, calling for a more aggressive approach to treatment in these patients.

Toremifene (Fareston), the first new antiestrogen agent for treating advanced breast cancer available in the United States in more than 19 years, is as effective as tamoxifen (Nolvadex) in clinical trials and potentially safer, Richard Gams, md, professor of internal medicine and director of hematology/oncology, Ohio State University, said at a teleconference sponsored by Schering-Plough to introduce the recently approved agent.

In the next 5 to 10 years, we may have the answer to the question of whether vaccines can fulfill their promise to become an effective treatment for melanoma, predict Brian J. Czerniecki, md, PhD, and Isabelle Bedrosian, md, in the latest issue of The Melanoma Letter, a publication of The Skin Cancer Foundation. These researchers are experimenting with a new kind of vaccine to combat disseminated melanoma.

A steroid drug enhances the ability of a vitamin D analog to kill cancer while reducing a potentially serious side effect of vitamin D therapy, according to investigators at the University of Pittsburgh Cancer Institute (UPCI). Their findings on dexamethasone and the vitamin D derivative, 1,25-dihydroxyvitamin-D³ (1,25-D³), in an animal model were reported in the January 21, 1998, issue of the Journal of the National Cancer Institute.

College students who smoke not only are endangering their health but also are likely to have adopted other risky behaviors. A new study by researchers at Dana-Farber Cancer Institute and the Harvard School of Public Health has found that college students who smoke are more likely to use marijuana and other illegal drugs, to be sexually promiscuous, and to be uninvolved in sports and athletic activities.

New research has found the gene responsible for Peutz-Jeghers syndrome, a rare inherited disorder that can lead to cancer in many different organs. Unexpectedly, the work may also have uncovered a new category of tumor-suppressor genes.

The aromatase inhibitor letrozole (Femara), at a dosage of 2.5 mg once daily, is an effective therapy for advanced breast cancer in postmenopausal women whose disease progresses following antiestrogen therapy, according to data published in the February 1998 Journal of Clinical Oncology. The study was conducted by the Letrozole International Trial Group and was sponsored by Novartis Pharmaceuticals Corporation.

Approximately 10% of all epithelial ovarian carcinoma cases are associated with inheritance of an autosomal-dominant genetic mutation conferring a predisposition to cancer with variable penetrance. Two such manifestations

Pharmacoeconomics and outcomes research are two new sciences that are beginning to affect the practice of oncology. As cost awareness in cancer care becomes acute, practicing oncologists must understand how to apply these sciences to their practices. This publication represents the proceedings of the symposium, Economics and Quality of Life in Oncology Clinical Practice, which was held on November 19, 1997, on the occasion of the EORTC meeting during The First European Conference on the Economics of Cancer. The presentations at the symposium provided an overview of some studies that have begun to explore the variety of activities comprising outcomes assessment, and how such data can be used to help deliver high quality patient care in a cost-conscious environment.

Cancer researchers and clinicians need to adopt a new attitude toward race classifications as interracial parentage in the United States continues to increase. “I want to uncouple race and genetics,” stated Edison Liu, MD, at the 1997 Biennial Symposium on Minorities, the Medically Underserved, and Cancer held in Washington, DC.

Postmenopausal minority women can be successfully recruited for a program to reduce dietary fat and can achieve significant changes in their eating habits, stated Carolyn K. Clifford, phd, at the 1997 Biennial Symposium on Minorities, the Medically Underserved, and Cancer in Washington, DC.

Of acute-care doctors and nurses responding to a national survey, 62% said that clinically hopeless patients have a “dignified death” in the hospital only “sometimes.” Another 33% said that this scenario occurs “frequently,” and just 5% said “always.”

Women must make lung cancer as hot and as female a public issue as they have made breast cancer, urged a cancer expert speaking at the 1997 Biennial Symposium on Minorities, the Medically Underserved, and Cancer in Washington, DC. Five years from now, twice as many women will die of lung cancer than of breast cancer, warned Paul Bunn, Jr., md, Grohne/Stapp Chair in Cancer Research and director of the University of Colorado Cancer Center.

Jefferson Medical College researchers have created what they believe may prove to be an effective ovarian cancer vaccine made from a patient’s own cancer cells. After testing the vaccine on 11 patients, each with advanced disease, the scientists are encouraged after seeing an initial immune reaction. That tells them that the vaccine is effectively stimulating the immune system into action.

Diet is a well-established factor in cancer prevention. According to two Baylor College of Medicine researchers, cultural factors play a more powerful role than cost in determining the food choices of people with low incomes. Speaking at the 1997 Biennial Symposium on Minorities, the Medically Underserved, and Cancer, the researchers said that blacks and Hispanics typically eat a less healthy diet than whites, but not because of cost.

Women who undergo breast reconstruction following mastectomy for breast cancer express strong satisfaction with a novel surgical approach, reported a surgeon at Georgetown University Medical Center in the January 1998 issue of Plastic and Reconstructive Surgery.

In the largest study of its kind to date, Ohio State University researchers have shown that the stress women experience after breast cancer diagnosis and surgery can weaken their immune response, based on at least three different biochemical indicators.

Regardless of their race, poor rural Americans face similar problems that make it extremely difficult for them to receive adequate health care, reported two experts at the 1997 Biennial Symposium on Minorities, the Medically Underserved, and Cancer in Washington, DC. Many rural Americans are white working poor, noted Linda Linville, phd, assistant director for cancer control at the University of Kentucky Markey Cancer Center in Lexington. Although they technically do not belong to a racial minority, white working poor individuals generally are among the medically underserved.

Scientists at the American Health Foundation’s Nutritional Carcinogenesis Division, under the direction of Dr. Bandaru S. Reddy, division chief and associate director of the Foundation’s Naylor Dana Institute, Valhalla, New York, and Dr. Karen Seibert of Searle Research & Development, St. Louis, Missouri, described an exceptionally strong inhibitor of colon cancer development in an animal model assay in the February 1, 1998, issue of Cancer Research.

Because many types of cancers metastasize to the lungs, early detection may affect both tumor staging and treatment planning. On the other hand, it is also important to refrain from subjecting patients to procedures that