Not All Breast Cancers Created Equal

Genetics may determine diagnosis, treatment

MONDAY, Sept. 8, 2003 (HealthDayNews) -- Not all breast cancer tumors are alike, and not all play by the same rules. And that, in turn, may dramatically affect the course of the disease and the choice of treatment.

That's the suggestion of a new study in the Oct. 15 issue of Cancer, which is available online Sept. 8. Here, researchers highlight the impact of possible biological differences in the tumors of women whose cancer is linked to the BRCA1 gene mutation -- an inherited genetic defect that appears to produce highly aggressive tumors.

"What this finding speaks to is a difference in tumor biology. And the consequence of that is we may need to apply a different set of rules when investigating, for example, the benefits of screening, early detection and treatment, in carriers of BRCA1," says study author William D. Foulkes, director of cancer genetics at McGill University in Montreal.

Foulkes says that, in the past, most breast tumors were believed to be quite predictable, with a common correlation between tumor size, the spread of the cancer cells to the nearby lymph nodes, and the severity of the disease itself. But contrary to this accepted cancer logic, the new study found that even when tumors are small or the breast cancer doesn't invade lymph nodes, women with the BRCA1 gene mutation still frequently experience a virulent and aggressive form of this disease.

"Now research shows not all tumors play by the same rules, and that when a genetic mutation is present, as in BRCA1, the rules are different. And that fact can affect detection, prevention, as well as treatment," Foulkes says.

The study utilized research gathered between 1975 and 1997 from 10 medical centers in the United States, Canada and Switzerland. The research group, led by Foulkes, looked at a total of 1,555 women with invasive breast cancer.

Of the group, 276 women carried the BRCA1 gene, 136 had the BRCA2 gene (a slightly less aggressive gene mutation) and 1,143 women had no known genetic link to breast cancer.

Each patient's disease was categorized according to the size of her tumor. Based on that, the researchers used a mathematical calculation to estimate the chance of lymph node involvement. When lymph nodes are involved, it generally indicates a more aggressive form of the disease and the need for more dramatic follow-up treatment, including chemotherapy.

The result: As expected, Foulkes' team found a significant correlation between tumor size and lymph node involvement in the women who did not carry any gene mutations, as well as for women who carried the BRCA2 gene. Specifically, the larger the tumor, the greater the chance the cancer would invade lymph nodes.

But the calculations did not apply to the cancer patients who carried the BRCA1 genetic mutation.

For these women, Foulkes says, the conventional breast cancer factors -- tumor size and lymph node involvement -- did not appear to predict the course of disease. Ultimately, he says, this may indicate an entirely new and different disease progression when gene mutations are a part of the diagnostic picture.

Breast cancer expert Dr. Julia Smith says the study represents an important new direction in breast cancer diagnosis and ultimately may affect the treatment of many different types of cancers.

"It is all about tumor biology -- and the prognosis of this disease is all about tumor biology. More and more we are realizing that not all tumors behave or act the same way and that in many instances you cannot apply general rules of treatment simply based on a diagnosis of breast cancer," Smith says.

While this is not the first study to support this idea, Smith says this research is very important because it is one of the largest trials to arrive at this conclusion. And the simplicity of its finding has potentially far-reaching effects.

"There were certainly some additional factors that could have made this finding even stronger, including analyzing the tumors for sensitivity to estrogen and progesterone, and a greater consideration of the fact that because so many centers were used to garner the research, not all lymph node dissections were conducted in the same way," Smith says.

Still, she believes the study suggests a new approach in the treatment of breast cancer: "One tumor at a time, one woman at a time, making decisions on a case-by-case basis," Smith says.

More information

To learn more about BRCA1 and inherited risks of breast cancer, visit The National Cancer Institute. For more about how all breast cancers develop, see The American Cancer Society.

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