Fertility Preservation Guidelines Issued by ASCO

Fertility preservation options should be addressed by oncologists and physicians as part of standard care for cancer patients who are in their reproductive years, according to guidelines developed by the American Society of Clinical Oncology (ASCO) and published in the June 20 Journal of Clinical Oncology.

"As part of education and informed consent before cancer therapy, oncologists should address the possibility of infertility with patients treated during their reproductive years and be prepared to discuss possible fertility preservation options or refer appropriate and interested patients to reproductive specialists," the authors noted. "Clinician judgment should be employed in the timing of raising this issue, but discussion at the earliest possible opportunity is encouraged."

ASCO convened an expert panel on the issue in light of evidence that many oncologists either do not discuss the possibility of treatment-related infertility "or do so suboptimally." The panel reviewed medical literature and databases spanning 1997 to 2005, and found evidence that fertility preservation is of great importance to many patients and properly addressing the issue "was a positive factor in patients coping emotionally with cancer."

Sperm and embryo cryopreservation are considered standard practice and are widely available, the guidelines state. Other available fertility preservation methods - such as ovarian tissue preservation - "should be considered investigational and be performed in centers with the necessary expertise."

The expert panel, noting the "paucity" of large, randomized trials of fertility methods, "encourages additional well-designed studies evaluating methods of fertility preservation in people with cancer to help answer these questions."

Loss of Gene Function Indicated in Familial Juvenile Polyposis

People with a genetic disorder called familial juvenile polyposis (FJP) are predisposed to development of both noncancerous gastrointestinal polyps and gastrointestinal cancer. The human tumor-suppressor gene SMAD4 is thought to contribute to tumorigenesis in patients with this disorder. A new study from the NCI Center for Cancer Research's Laboratory of Cell Regulation and Carcinogenesis published in the June 22 Nature implicates loss of the SMAD4 protein-dependent signaling in T cells as a cause of tumor formation in patients with FJP.

The investigators developed mouse models with the Smad4 gene deleted either in T cells or in epithelial cells. Mice lacking the Smad4 protein in their T cells developed gastrointestinal abnormalities like those found in FJP, including a thickening of the mucosal surface and the infiltration of plasma cells (antibody-producing immune cells) into the inner layer of the intestines. Mice lacking Smad4 protein expression in epithelial cells did not develop gastrointestinal abnormalities. Epithelial cancers were found in 94 to 100 percent of mice from model lines lacking the Smad4 gene in their T cells, but not in mice from model lines lacking Smad4 in their epithelial cells.

Further in vitro studies suggested that loss of Smad4-dependent signaling in mouse T cells led to an increased production of certain cytokines, substances produced by the immune system that cause an increase in the number of plasma cells and stromal (connective tissue) cells. Altogether, state the investigators, their data "implicate defects in SMAD4-mediated signaling in T cells in the pathogenesis of FJP…Therapeutic strategies that target the activation and function of T cells may represent an effective form of preventive therapy that will potentially delay or obviate the need for aggressive surgical intervention."

Reducing Risk of HPV Infection in Young Women

Researchers, reporting in the June 22 New England Journal of Medicine on a small prospective study designed to test the impact of condom use by partners of women new to sexual intercourse, found a 70 percent risk reduction for HPV infection. The effect was found in women whose partners used condoms 100 percent of the time 8 months prior to the study, compared with those using condoms less than 5 percent of the time. Fourteen women in that group developed cervical squamous intraepithelial lesions, compared with none in the 100 percent condom-use group. Lead author Dr. Rachel L. Winer and colleagues, of the University of Washington, conclude that "the association was strong and increased with the increasing frequency of condom use, suggesting a causal, protective effect."

Gene Suppresses Non-Small-Cell Lung Cancer Tumors

Scientists have identified several dozen tumor suppressor genes (such as p53 in many tumor types and BRCA1/BRCA2 in breast cancer) which, when active, block the proliferation of cells. Results in the June 21 JNCI suggest that a recently discovered DnaJ-like heat shock protein known as HLJ1 (also known as DNAJB4) belongs on the list due to its inhibitory effects on the development of non-small-cell lung cancer (NSCLC).

Dr. Meng-Feng Tsai, of the National Taiwan University Hospital in Taipei, Taiwan, and colleagues previously identified HLJ1 as a member of the heat shock protein 40 family that helps cells survive stresses such as chemotherapy. The current study was designed to demonstrate the impact of HLJ1 on NSCLC, using multiple and converging lines of evidence from cellular, genetic, and clinical tests.

The researchers restored HLJ1 expression to NSCLC cells in vitro and found that cell proliferation, anchorage-independent growth, tumorigenesis, cell motility, and invasion were all inhibited. With microarray and downstream pathway analysis, they identified a novel and plausible tumor suppressor mechanism. They also looked at the biopsied tissue of 71 Chinese NSCLC patients, 55 of whom had lower HLJ1 expression within the tumor than in surrounding tissue. These patients were followed, and the group with higher HLJ1 expression in their tumors had 53 percent less risk of recurrence and 62 percent better survival.

In an accompanying editorial, Drs. Adriana Albini and Ulrich Pfeffer, of the National Cancer Research Institute in Genoa, Italy, noted "Tumor suppressor genes for NSCLC are eagerly sought for both our understanding of lung cancer biology and the need of a prognostic marker."