Young Women With Early-Stage Breast Cancer More Likely To Die
In a national study presented at the 2008 American College of Surgeons (ACS) Clinical Congress, a researcher reported that "women under 40 years of age diagnosed with Stage I breast cancer are 44 percent more likely to die than older women." According to Julie A. Margenthaler, MD, assistant professor of surgery, Washington University School of Medicine, St. Louis, MO, "These are women with similar size tumor and lymph node status. The characteristics of the tumor itself, however, portend a poorer prognosis.
"We think we should devote much of our future research to finding out what tumor biology is accounting for these deaths," Dr. Margenthaler said. "Clearly we can make a huge impact in the lives of these young women and save a lot of years."
According to Dr. Margenthaler, treating young women with breast cancer is something of a subspecialty and is a great personal interest, as many of her patients fall into this category. She explained that physicians have long been aware that young women with breast cancer under the age of 40 or 45 tend to have poorer survival outcomes than older women. This disparity in survival had typically been attributed to younger women being diagnosed with late-stage disease. "This conclusion makes sense," she said, "considering that young women are not being screened regularly with routine mammograms. In fact, most young women are not diagnosed until they discover a mass they can feel and that tends to mean a higher stage than if the mass is found as a small size on a mammogram."
However, Dr. Margenthaler suspected that the poor outcomes of her young patients were related to factors beyond the lack of routine screening and clinicians not detecting early tumors. She and her colleagues decided to review past medical literature and look at the statistics a little differently.
The research team conducted a retrospective study of 243,012 patients diagnosed with breast cancer in the 1988C2003 Surveillance, Epidemiology, and End Results (SEER) program. Of these, 6.4 percent were under 40 years of age and 93.6 percent were 40 and older. They looked at all young women with Stage I cancers and compared them with older women with Stage I cancers. They performed the same review for Stages II, III, and IV.
In the study presented at the ACS Clinical Congress, Dr. Margenthaler said she was surprised to learn that the highest mortality disparity between young and older women was actually in early-stage disease -- not late-stage disease. Specifically, women under 40 diagnosed with Stages I and II cancers are 44 percent and 9 percent, respectively, more likely to die than older women in the same stage of the disease.
There was no difference by age for those diagnosed with Stage III cancers. Women under 40 diagnosed with Stage IV cancers, however, are 15 percent less likely to die than their older counterparts. Dr. Margenthaler believes this finding makes sense as well, in that Stage IV cancer has already spread and usually has a poor prognosis. Chemotherapy and radiation can help to control symptoms, but a younger woman may tolerate aggressive therapies like those better than, perhaps, a 70-year-old woman can.
Overall, when all stages are incorporated into the analysis, women under age 40 are 39 percent more likely to die from breast cancer than older women. This breakdown was based on a hazards ratio survival analysis, which is the standard analysis for this type of study.
Dr. Margenthaler further explained that the tumors of women under 40 tended to be estrogen- and progesterone-negative, which often lead to poorer outcomes. That is the case because these tumors do not respond to the antiestrogen therapies now available, such as tamoxifen. Young women also are more likely to carry a gene called HER2NEU, which is found in all the cells of the human body. Some cancers make extra copies of this gene, which also is associated with poorer outcomes, higher rates of recurrence, and metastatic spread.
Dr. Margenthaler believes that socioeconomic factors may play a role too, considering the fact that most of the young women in this study were African American and unmarried. Piggybacking on tumor types and socioeconomic status are factors related to genetics. Indeed, about 20 percent of young women diagnosed with breast cancer have a significant family history of the disease. Unfortunately, hereditary breast cancers tend to have a poorer outcome than nonhereditary types.
Dr. Margenthaler is hopeful that this research will increase the awareness of this sub-population of breast cancer patients, so the oncology community can begin to focus on factors that can increase their survival. She pointed out that these individuals have been largely neglected in the past because they represent a minority in the overall scheme of things.
"If you look at the entire United States, only 6 to 10 percent of all breast cancers are diagnosed in women under 40," Dr. Margenthaler said. "If you think about years lost in that population, though, this finding is very significant. Many of these women are pregnant when they are diagnosed, and they have young children. Not only will research into tumor biology make a huge impact in the lives of those diagnosed with early-stage breast cancer, but these results will trickle down and positively affect late-stage disease as well."
Dr. Margenthaler and her colleagues have recently begun a study examining some of the tumors removed from their own patients under 40. They are looking for specific markers or genes that might be related to worst outcomes, such as resistance to chemotherapy regimens.