Predicting Breast Cancer Recurrence
In the past month, a slew of important new studies have identified certain combinations of therapies that may minimize the risk of breast cancer recurrence. Other studies have focused on identifying recurrences at much earlier-and thus more treatable-stages. Here is a sampler.
A study presented at the recent 2nd European Breast Cancer Conference in Brussels, Belgium, showed that adjuvant (additional) treatments for breast cancer, such as radiotherapy, chemotherapy and, in particular, the hormone treatment tamoxifen, prevent later relapses in breast cancer patients.
Oxford's Sir Richard Peto presented the composite results of 300 randomized trials that included approximately 200,000 patients. "This is the first time we've had good evidence on the effects of treatment on 15-year survival," Peto said.
The most promising results came from Great Britain, where tamoxifen has been widely used since the 1980s. Deaths from breast cancer in middle-aged women in the U.K. have fallen by 30 percent over the past decade, he said.
Peto noted that the use of such adjuvant therapies reduces relapses because they also directly target dormant disease. Therefore, he said, you don't only get a benefit while you are currently receiving the adjuvant therapy. You also get an additional benefit accumulating in the 5 or 10 years after you've stopped because of its impact on disease that you can't see during your initial treatment.
Peto also argued for the use of combination therapies, particularly hormonal therapy and chemotherapy. "If a woman has estrogen receptor-positive disease, then hormonal treatment works well," he said. "But so does chemotherapy. These aren't mutually exclusive. It's not a question of which is better ... one shouldn't let the use of one therapy preclude the use of the other."
Similar findings by Dutch researchers were presented at both the European Society for Therapeutic Radiology and Oncology conference in Istanbul and the American Society for Therapeutic Radiology and Oncology conference in Boston.
Dr. Harry Bartelink of The Netherlands Cancer Institute in Amsterdam and colleagues found that an additional booster dose of radiation therapy given to patients with stage I or II breast cancer dramatically reduced their risk of recurrence. They studied 5,569 women who received an initial dose of 50 Gy of radiation treatment to the whole breast. Those women who received a "booster" dose of 16 Gy of radiation had a nearly 50 percent reduced chance of recurrence within the median follow-up period of five years.
Specifically, the findings showed that women between 41 and 50 years of age who received the booster radiation dose had a 48 percent reduction in local recurrence rates, while those younger than 40 years old experienced a 54 percent reduction. The overall survival rate for all patients was 91 percent after the five-year follow-up period.
In a presentation at the recent 25th congress of the European Society of Medical Oncology in Milan, Italy, Dr. Pier Francesco Fernucci of the European Institute of Oncology in Milan announced that the presence of a tumor suppressor gene called "maspin" appears to indicate a reduced risk of breast cancer recurrence.
Fernucci and his colleagues studied 48 high-risk, node-positive breast cancer patients who had surgery followed by chemotherapy. They measured the expression of a range of substances associated with breast cancer and observed that higher levels of maspin seemed to protect patients from a relapse. This was especially true in 10 of the women who had 20 or more lymph nodes affected by cancer. After a 15-month follow-up period, eight of these patients with high maspin levels had not relapsed. The two women with low maspin levels had developed secondary cancers of the lung and liver.
Fernucci said he hoped this research would lead to a standard test, "helping doctors to identify at least some women with a higher risk of relapse."
Another study, published in the journal Cancer, noted that an antigen called Serum CYFRA 21-1 may be an extremely sensitive marker for breast cancer recurrence.
Dr. Bunzo Nakata and colleagues at Osaka City University Medical School in Osaka, Japan, measured blood serum levels of CYFRA 21-1 in 147 women with breast cancer. They found that CYFRA 21-1 was a poor marker for stage I and II breast cancer, indicating that this antigen "cannot be used for screening or early diagnosis."
However, the sensitivity of CYFRA 21-1 was found to be a significant, independent predictor of breast cancer recurrence in later stage cancers, with sensitivities of 60 percent and 64.2 percent in women with stage IV and recurrent tumors, respectively.
Nakata suggested that CYFRA 21-1 "could be helpful in monitoring for recurrence of the disease and also for judging the effects of treatments, including resection, chemotherapy and radiation." He added that CYFRA 21-1 was also a good predictor of eventual prognosis, with patients with high serum levels of the marker having shorter disease-free survival.
Finally, another article appearing in the journal Cancer cautioned that the incomplete initial diagnosis and primary care of patients with breast cancer results in significant increases in disease recurrence and mortality.
Dr. Timothy Lash of the Boston University School of Public Health and colleagues collected data on 494 women between 45 to 90 years of age who were diagnosed and treated for breast cancer between 1984 and 1986. The researchers determined that 24 percent of the patients "received less than definitive prognostic evaluation" and 27 percent "received less than definitive therapy."
They defined prognostic evaluation as axillary lymph node dissection, evaluation of estrogen receptor status, and tissue examination. For women with local disease, definitive primary care meant mastectomy or breast-conserving surgery plus radiation therapy within 5 months of surgery. For women with regional disease, chemotherapy and/or hormonal therapy was required.
Lash's team determined that women who did not receive a definitive evaluation were 1.7 times as likely to experience disease recurrence and 2.2 times as likely to die during the first five years of follow-up.
SOURCES:
25th Congress of the European Society of Medical Oncology, Milan, Italy, October 20, 2000
Cancer, September 15, 2000; 89:1285-1290
Annual meeting of the American Society for Therapeutic Radiology and Oncology, October 24, 2000, Boston, Massachusetts
European Society for Therapeutic Radiology and Oncology meeting, September 19, 2000, Istanbul, Turkey
Cancer, October 15, 2000; 89:1739-1747
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