© 2004 by Oxford University Press
© 2004 Oxford University Press
IN THIS ISSUE |
Drugs directed at cancer-specific targets, such as imatinib mesylate in chronic myeloid leukemia, have the potential to favorably influence patient outcomes by decreasing toxicity and improving disease control. However, recent laboratory and clinical data raise questions about whether new anticancer agents will effectively target relevant subsets of cancer cells. In a commentary, Jones et al. (p. 583) discuss the biologic distinction between cancer stem cells—the rare population of cells that give rise to malignancies—and the differentiated cells that characterize the disease. They note that therapies that target mature cancer cells are unlikely to produce long-term remissions unless they also target the rare cancer stem cells responsible for maintaining the disease. They stress that the development of new anticancer treatments should take into account the pathogenesis and biology of the diseases being treated, and that survival, rather than response, should remain a primary endpoint of therapeutic efficacy in studies of such new treatments.
Chlamydia psittaci and Ocular Adnexal Lymphomas
Several infectious agents have been implicated in the pathogenesis of mucosa-associated lymphoid tissue (MALT) lymphomas. To determine whether Chlamydiae infection is associated with the development of ocular adnexal lymphomas, which are MALT lymphomas, Ferreri et al. (p. 586) investigated the presence of Chlamydia psittaci, C. trachomatis, and C. pneumoniae DNA by polymerase chain reaction in both tumor tissue and peripheral blood mononuclear cells (PBMCs) from ocular adnexal lymphoma patients and from two groups of control subjects. They found that 80% of the lymphoma samples but only 0% and 12% of samples from the two control groups were positive for C. psittaci DNA. All lymphoma samples were negative for C. trachomatis and C. pneumoniae DNA. In addition, 43% of the patients with C. psittaci–positive lymphomas carried C. psittaci DNA in their PBMCs, whereas none of the control subjects did. Four patients with C. psittaci–positive ocular adnexal lymphomas were treated with the antibiotic doxycycline, and two showed lymphoma regression.
In an editorial, Jaffe (p. 571) notes that MALT lymphomas appear to be the result of immune responses gone awry, resulting in clonal expansion of B cells. Jaffe points out that the question of how chronic antigen stimulation by infectious agents leads to B-cell proliferation and to the specific translocations that characterize most MALT lymphomas has yet to be answered.
Implementation of a Smoking Cessation Intervention
The Agency for Healthcare Research and Quality Smoking Cessation Clinical Practice Guideline recommends that all clinicians strongly advise their patients who use tobacco to quit. Katz et al. (p. 594) conducted a randomized, controlled trial of a 2-month-long intervention to implement the Guideline at eight primary care clinics among 2163 adult patients who smoked at least one cigarette per day. The intervention included a tutorial for intake clinicians (nurses or medical assistants), a modified vital signs stamp that prompted intake clinicians to discuss smoking with patients, an offer of free nicotine replacement therapy, and proactive telephone counseling. The authors found that patients at clinics that received the intervention were more likely to report being abstinent at the 2-month and 6-month follow-up assessments than patients at clinics that did not receive the intervention.
In an editorial, Schnoll and Engstrom (p. 573) discuss these results in the context of the role of physician-based practices in the treatment of nicotine addiction. They cite the need for studies that explore whether a similar intervention would be applicable to other types of medical practices and that assess Guideline implementation in medical practices with limited resources.
Projected Cost-Effectiveness and Benefits of an HPV Vaccine
Human papillomavirus (HPV) vaccine may be commercially available soon, and so Goldie et al. (p. 604) used a computer-based model of HPV natural history and cervical cancer to explore clinical benefits and cost-effectiveness of introducing an HPV16/18 vaccine into a population with an organized cervical cancer screening program. For a vaccine that is 90% effective, vaccination at age 12 years combined with cytologic screening every 3 years beginning at age 25 years is more effective than our current screening program, would provide a 94% reduction in the lifetime risk of cervical cancer, and costs approximately $60,000 per quality-adjusted life year compared with the next best strategy of vaccination and cytologic screening every 5 years beginning at age 21 years. They conclude that a program of vaccination that permits a later age of screening initiation and a less frequent screening interval is likely to be a cost-effective use of health care resources.
Lower-Category Benign Breast Disease and Breast Cancer Risk
Lower-category benign breast disease, as defined in the report by Wang et al. (p. 616), encompasses all benign breast disease except atypical ductal and atypical lobular hyperplasia and ductal and lobular carcinoma in situ. The report reveals that women with lower-category benign breast disease were at an increased risk of subsequent invasive breast cancer than those without the disease. The study included 11,307 women, of whom 1376 had lower-category benign breast disease. The study showed that the relative risk of developing breast cancer was approximately 1.6 times that of women without the disease. In women aged 50 years or older, the risk was approximately 1.95 times that of women without the disease. The authors also found that this risk was independent of other key epidemiologic breast cancer risk factors.
Tamoxifen and Breast Density in High-Risk Women
Although mammographic breast density is associated with the risk of breast cancer and is influenced by hormone levels, the effects of tamoxifen on breast density in healthy women are unclear. Cuzick et al. (p. 621) investigated the effects of tamoxifen on breast density in healthy women in a trial of tamoxifen for breast cancer prevention in women at increased risk for this disease. They found that tamoxifen treatment was associated with reduced breast density, most of which occurred during the first 18 months of treatment. The tamoxifen-associated reduction in breast density was apparent in all subgroups, particularly among younger women. Tamoxifen reduced breast density 13.4% in women aged 45 years or younger at entry, whereas tamoxifen reduced breast density 1.1% in women older than 55 years at entry.
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