Earlier Breast Cancer Screening Recommended for Hispanic Women
Women of Mexican origin should be considered at high risk for early-onset, premenopausal breast cancer, according to researchers at The University of Texas MD Anderson Cancer Center.
The researchers surveyed 714 Hispanic women in the Houston area who were drawn from an ongoing, population-based cohort study. One hundred nineteen of these women reported having been diagnosed with breast cancer, and 50% of these had been diagnosed before age 50 years.
The U.S. Preventive Services Task Force guidelines were revised in 2009 to recommend that breast cancer screening, including mammograms, begin at age 50 years for the general population. These guidelines have been controversial, and MD Anderson continues to recommend screening beginning at age 40 years for women at average risk or at a younger age for women with certain risk factors.
“If a one-size-fits-all screening program is implemented as the task force recommends, we fear a large number of breast cancer cases won’t be picked up at an early stage, especially with the growth of the Hispanic population in this country,” said Melissa Bondy, Ph.D., a professor in the Department of Epidemiology and the senior author of the study’s report in the journal Cancer.
A multivariate analysis of the women’s survey responses revealed that the strongest risk factors for breast cancer were a family history of the disease, level of acculturation, and having been born in Mexico.
The researchers noted that the level of acculturation was based on whether the participants mostly spoke English, which is one aspect of an acculturation process that includes other lifestyle changes that might affect breast cancer risk. Other breast cancer risk factors found by the analysis included being single and being without health insurance. The researchers wrote that their results—along with those of previous studies showing that Hispanic women are more likely to be diagnosed with an advanced stage of breast cancer and more likely to die of breast cancer than are non-Hispanic white women—demonstrate the need for policies that target screening, education, and treatment in the Hispanic population.
SUMO Is Important for DNA Damage Repair
The small protein SUMO (small ubiquitin-related modifier) is an important component in the mechanism that repairs DNA damage caused by chemotherapy in cancer cells, according to a new study done by a research team at MD Anderson Cancer Center.
In the study led by Edward T. H. Yeh, M.D., a professor in and chair of the Department of Cardiology, investigators determined how SUMO modification alters the activity of RPA70, a component of the replication protein A (RPA) complex that protects and maintains DNA.
In the August 13 issue of Molecular Cell, the investigators showed that the modification of RPA70 by SUMO is essential to repair DNA double-strand breaks. These breaks in DNA are one of the ways that ionizing radiation and chemotherapeutic drugs like camptothecin kill cancer cells.
In undamaged cells, RPA70 is accompanied by a protein called SENP6 that prevents SUMO modifications. Upon DNA damage, RPA70 leaves this inhibitory partner and begins to accumulate SUMO. This SUMO modification allows RPA70 to initiate DNA damage repair.
To understand the interaction between RPA70 and SUMO, researchers modified RPA70 to eliminate its SUMO conjugation sites. Dr. Yeh said, “If a mutant protein that cannot be modified by SUMO is substituted for RPA70, the cells are much more sensitive to chemotherapy and ionizing radiation.”
Without SUMO modification, RPA70 has difficulty initiating DNA repair. This mechanism could be particularly important in cancers that resist standard treatments. Understanding the role of SUMO and RPA70 in cancer cells may offer new therapeutic targets.
Regional Care Centers Make Cancer Treatment Easily Accessible
In an effort to make cancer care easily accessible to patients, MD Anderson Cancer Center now provides treatment at six regional care facilities in the greater Houston area in addition to its main campus in the Texas Medical Center.
Peter Pisters, M.D., who serves as medical director of the regional care centers and as a professor in the Department of Surgical Oncology, said the goals of the regional care center initiative are to increase the convenience and accessibility of cancer treatment for patients while maintaining the same level of quality as MD Anderson’s facilities in the Texas Medical Center. “We’re offering laboratory and medical oncology services, radiotherapy, and—soon—surgical services,” he said.
At the regional care facilities, patients receive treatment from MD Anderson faculty physicians who work directly with referring physicians to tailor individual patients’ treatment plans.
These regional care facilities include multidisciplinary clinics in the Bay Area, Sugar Land, Katy, and the Woodlands and radiation treatment centers in Richmond and Bellaire. MD Anderson also has domestic and international radiation treatment facilities in Albuquerque, New Mexico, and in Istanbul, Turkey.
SIK2 Plays Critical Role in Chemotherapy Resistance
Salt-inducible kinase 2 (SIK2) is important for cell division and may control chemotherapy response in some ovarian cancers, according to research conducted at The University of Texas MD Anderson Cancer Center. Although many ovarian cancers respond to taxane-based chemotherapy, others do not respond for reasons that are poorly understood.
Robert C. Bast, Jr., M.D., vice president of translational research at MD Anderson and the senior author of the study’s report, has been searching for new ways to enhance chemotherapy sensitivity in tumors. “In our search for proteins that are responsible for that sensitivity, we found that SIK2 was required for cell division and that its inhibition offers a novel approach to improving chemotherapy for ovarian cancer,” Dr. Bast said.
In the report published in the August issue of Cancer Cell, Dr. Bast and Ahmed Ashour Ahmed, M.D., Ph.D., a former postdoctoral fellow in Dr. Bast’s lab and now a faculty member at Oxford University, conducted a large siRNA screen to identify proteins that can alter sensitivity to the taxane paclitaxel. The researchers identified SIK2 as a taxane resistance factor. Generally, taxanes kill cancer cells by inhibiting mitosis.
During normal cell division, centrosomes move to opposite ends of the cell and serve as anchor points for microtubules. These microtubules then pull chromosomes into each daughter cell. Closer analysis revealed that SIK2 controls this process. Since taxanes inhibit mitosis by affecting microtubule function, this finding agrees with the theory that SIK2 is a taxane resistance factor. Previously, SIK2 was known primarily as a modulator of glucose metabolism during recovery from starvation.
Besides offering the possibility of improving the response of some cancers to taxanes, these findings add to the emerging body of evidence that cancer cell metabolism and mitosis functions are coupled.An understanding of this coupling may provide many new targets for cancer therapeutics. SIK2 is overexpressed in approximately 30% of ovarian cancers and is associated with a poor prognosis. Reducing SIK2 protein enhances paclitaxel’s antitumor activity in cell culture and in xenografts. The next step is to develop SIK2 inhibitors for laboratory studies of ovarian cancer therapy.
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Other articles in OncoLog, November-December 2010 issue: