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© Oxford University Press 2008.
IN THIS ISSUE
Factors Associated with Receipt of Sentinel Lymph Node BiopsySentinel lymph mode biopsy (SLNB) is less invasive than axillary lymph node dissection and has fewer adverse effects. Chen et al. (p. 462) assessed the demographic, clinical, and facility-related factors associated with receipt of SLNB in patients with early-stage breast cancer, and they also assessed trends in these factors over time. They found that, among the study population of 490,899 women, the use of SLNB increased from 26.8% in 1998 to 65.5% in 2005. Factors associated with a lower likelihood of receiving SLNB included being older, being a member of a racial/ethnic minority, or having no health insurance or certain government health insurance plans. The authors also found that, from 1998 through 2005, SLNB use increased in all groups. However, disparities in SLNB receipt that were based on non-clinical factors persisted.
In an editorial, Edge (p. 449) reviews the history of SLNB, noting that it was adopted before trials had proven it accurate and safe. He also points out that the ongoing disparities identified by the authors in the use of SLNB by racial/ethnic group, socioeconomic stratum, and health insurance status are disappointing if not entirely surprising.
Increased Recurrence Risk with HRT in Breast Cancer Survivors
In 2002, the Women’s Health Initiative study established that use of combined estrogen with progesterone as hormone replacement therapy (HRT) increases breast cancer risk among healthy postmenopausal women. Shortly afterward, two Scandinavian randomized trials, both designed to determine whether use of HRT increases risk of new breast cancer events among breast cancer survivors, were stopped on the basis of a pooled safety assessment. Holmberg et al. (p. 475) now report the results of one of these Scandinavian studies, the HABITS study, after extended follow-up for a median of 4 years. They found that breast cancer survivors who have taken HRT are more than twice as likely to experience a breast cancer recurrence as breast cancer survivors who manage climacteric symptoms without HRT.
In an editorial, Pritchard (p. 451) discusses the ways in which these randomized trials have revolutionized dogma concerning the proper treatment of peri- and postmenopausal women. She points out that previously held beliefs concerning the use of HRT were based on observational studies, which have inherent weaknesses, and that more data from randomized trials are necessary for many areas of clinical practice in which observational studies may have been misleading.
Inadequate Analysis of Group-Randomized Trials
Group-randomized trials—in which groups rather than patients are assigned to interventions—have become increasingly common in cancer research. Because the outcomes in members of a group may be highly correlated, care must be taken to analyze these trials appropriately. Murray et al. (p. 483) reviewed reports of group-randomized trials that focused on cancer prevention for the appropriateness of the design and statistical analyses. Relatively few of the reports contained correct methods for sample size calculations, and 42% contained analyses that were not appropriate to the study design. A number of studies completely ignored the fact that assignment was by group and not by individual.
In an accompanying editorial, Church (p. 452) underscores the need for collaboration between statisticians and researchers if the kinds of errors identified by the authors are to be avoided and the public's confidence in the medical community's recommendations is to be maintained.
Performance of Cervical Cancer Screening Methods
In a randomized trial of cervical cancer screening methods, Ronco et al. (p. 492) assigned women to conventional cytology or to human papillomavirus (HPV) testing with referral to colposcopy for confirmation if their test result was positive. Among women aged 35–60, HPV testing was more likely than cytology to identify women who had cervical lesions with an acceptable increase in the likelihood of a false-positive result. However, the authors found that among women aged 25–34, many of the lesions detected by the more sensitive HPV test were destined to regress. They suggest that repeat testing may be advisable for younger women who test positive for HPV.
Natural History of Carcinogenic HPV Infections
As new molecular tests for HPV infection are developed, more women will undergo cervical screening with such tests. However, most cervical infections with carcinogenic HPV types are transient and do not increase a woman's risk for cervical cancer. To gain a better understanding of the natural history of HPV infection, Rodriguez et al. (p. 513) analyzed data on 800 infections in 599 women who were enrolled in a population-based cohort in Costa Rica and were screened regularly for HPV and cervical cytology. Most carcinogenic HPV infections detected at enrollment cleared rapidly, with two-thirds clearing by 12 months. However, among infections with carcinogenic HPV types that lasted for at least 12 months, 21% led to a diagnosis of cervical intraepithelial neoplasia grade 2 or worse (CIN2+) by 30 months. Among women under age 30, 53% of persistent HPV16 infections led to a diagnosis of CIN2+ by 30 months. The authors suggest that patients with normal cytology and initial positive HPV results be managed with watchful waiting to avoid unnecessary treatment of infections that will resolve spontaneously.
Chemokine Signaling in Head and Neck Cancers
Metastatic squamous cell carcinoma of the head and neck (SCCHN) cells have been shown to express CCR7, the receptor for the C–C chemokines CCL19 and CCL21, which could facilitate tumor cell access to the lymphatic system and spread to lymph nodes. Wang et al. (p. 502) report that metastatic tumors from SCCHN patients expressed higher levels of CCL19 and CCL21 than corresponding primary tumors and that blockade of CCR7 decreased the viability of SCCHN cells grown from the metastatic tumors. Furthermore, exposure of these metastatic SCCHN cells to CCL19 increased their resistance to cisplatin by a mechanism that was dependent on AKT activation. Analysis of the growth of SCCHN cells in mice deficient in CCL19 and CCL21 expression indicated that both paracrine and autocrine signaling may play a role in CCR7-mediated enhancement of SCCHN proliferation. The authors suggest that increased CCR7 expression may contribute to metastasis and resistance of SCCHN tumors to chemotherapy.
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Del.icio.us What's this?
J Natl Cancer Inst 2008 100: 513-517.
J Natl Cancer Inst 2008 100: 462-474.
J Natl Cancer Inst 2008 100: 475-482.
J Natl Cancer Inst 2008 100: 502-512.
J Natl Cancer Inst 2008 100: 449-450.
J Natl Cancer Inst 2008 100: 492-501.
J Natl Cancer Inst 2008 100: 483-491.
J Natl Cancer Inst 2008 100: 452-453.
J Natl Cancer Inst 2008 100: 451-452.
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