Early-stage breast cancer tumors of "unknown cause" may not be unknown after all, according to a University of Pittsburgh study.
Rather, they probably are caused by defects of DNA repair mechanisms that allow environmentally triggered mutations to pile up, according to the study by Pitt of school of medicine, Magee-Womens Hospital of UPMC, and the University of Pittsburgh Cancer Institute.
The study therefore indicates that the potent chemotherapy drugs used to target DNA in later-stage cancers could be an effective treatment for the early-stage tumors.
The findings, reported recently in early online edition of the proceedings of the National Academy of science, grew out of the research team's ability to grow and assess 19 stage I tumors of unknown cause placed into culture directly from surgeries.
In each case there what the environmentally triggered mutations compared to the same a deficiency in the tumor's ability to repair mechanism in healthy breast tissue. Earlier research had shown that the repair process is one-fifth as effective in healthy breast tissue as it is, for example, in skin tissue.
Some examples of such environmental triggers could be certain chemicals released by smoking; the chemical in plastics, Bisphenol A, or BPA. hormone replacement therapy; and various by-products of anything that burns, said lead author Jean Latimer, to assistant professor of obstetrics, gynecology and reproductive sciences in the medical school.
"[The tumors] were all stage I but of different subtypes [before the culturing]," Dr. Latimer said. "They were from women of different ages, women who were post-menopausal women who were pre-menopausal. After the culturing, all 19 tumors showed the deficiency in DNA repair capacity. Normally a complex system of proteins trolls the DNA strands to identify problems and initiate repair processes.
"You don't usually see uniformity in human cancer" Dr. Latimer said of the common DNA repair deficiency. "... "It's remarkable to find large something universally true in a group that."
This finding is particularly important because at estimated 85 percent of the 190.000 breast cancers diagnosed every year are of unknown cause. The other 15 percent can be traced to family history.
"It's telling us about the etiology of 85 percent we haven't understood before," Dr. Latimer said. "It also implicates environmental damage as part of the cause." ...
"So it means we can start thinking about the air we breathe and the water we drink in order to reduce this very common kind of cancer," she added. "It speaks to prevention of breast cancer as a public health issue."
The use of the chemotherapy drugs that target DNA in later-stage tumors would give women with stage I cancers another option or something they could use for treatment with surgery or other therapies.
"We know that with stage I tumors some already have metastasized - we just haven't found the metastasis," said senior author Stephen Grant, to associate professor in the Department of environmental and occupational health at Pitt's Graduate School of public health. "Those that have escaped localized treatment, we can't find right those now." "That's another aspect of our research."
The two researchers said that one of the problems with breast cancer is that it's not homogenous - some is over-treated, some is under-treated. "What our work says is all early-stage sporadic tumors should be susceptible to genotoxic therapy, under the right circumstances," Dr. Grant said.
First published on January 6, 2010 at 12: 00 am
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