When the BRCA1 and BRCA2 genes for breast and ovarian cancers were first identified and a screening blood test became available, the discoveries provoked a debate as to whether there was an advantage to learning one's risk. Apparently the value has been demonstrated in the first study of women who have been followed after being identified as carriers of a BRCA genetic mutation.

Researchers at Memorial Sloan-Kettering Cancer Center say they now have strong evidence that breast and ovarian cancers can be detected at early stage in women at the highest hereditary risk. Their findings were published in The Journal of Clinical Oncology.

"These results provide the first prospective evidence that BRCA testing can lead to interventions that result in the diagnosis of early-stage breast and ovarian cancers," said Dr. Kenneth Offit, Chief of the Clinical Genetics Service at Memorial Sloan-Kettering and senior author of the study.

For BRCA mutation carriers, there is a markedly increased risk for early-onset breast cancer and an increased lifetime risk for ovarian cancer. In addition, there is an increased risk for subsequent malignancies in breast cancer survivors and an increased risk for developing male breast cancer.

The study looked at 251 individuals, including 233 women, who were identified as having mutations in the BRCA1 or BRCA2 after testing and counseling at Sloan-Kettering. The participants received uniform recommendations for intensified screening and preventive surgery in the context of genetic counseling. Over the course of the study, 21 women were diagnosed with early breast or ovarian cancers.

There were 165 women identified to be at risk for breast cancer that chose increased surveillance. Breast cancer was detected in twelve patients in this group, with nine of the tumors diagnosed at the earliest stage. Half of these breast cancers were detected by mammography (including one by MRI) and half were detected by physical examination during the interval between annual mammograms.

"These results illustrate the importance of a comprehensive approach to breast cancer screening including self examinations in addition to breast imaging and physician examinations," said Lauren Scheuer, a senior genetic counselor at MSKCC and lead author of the study. "Further research is necessary to determine whether more frequent breast imaging may be warranted in women at hereditary risk."

Twenty-nine women chose to undergo preventive removal of breast tissue (risk-reducing or prophylactic mastectomy) to reduce their risk of developing breast cancer. Of these women, two were found to have unsuspected early-stage breast cancers at the time of surgery.

Among the 89 women with intact ovaries who chose surveillance, twice yearly transvaginal ultrasound and a CA-125 blood test were recommended to screen for ovarian cancer. In this group, five ovarian cancers were detected. All of the ovarian cancers were found at an earlier stage than typical for this disease, which tends to be diagnosed after the cancer has spread to other areas. Among the 90 women who chose preventive removal of their ovaries (salpingo-oophorectomy), two early-stage ovarian cancers were also discovered.

"However, the finding of several unsuspected breast and ovarian cancers at the time of "preventive" surgery highlights the limitations of screening, and justifies continued consideration of these surgeries," said Dr. Mark Robson, a breast oncologist at Sloan-Kettering and co-author of the report.

Although the study shows that early-stage cancers may be diagnosed by screening and surgery following genetic testing, the authors caution that the follow-up period, with a mean of 24.8 months, is short and the long-term outcome for this group of women is not yet known. In particular, this study does not address whether surgery decreases the rate of subsequent cancers.

"Further studies will be needed to measure outcomes after surgery and early detection, however, our preliminary results are encouraging. They underscore the importance of genetic counseling and education for women with proven risk factors for breast and ovarian cancer," said Scheuer.

SOURCES:
The Journal of Clinical Oncology, March 1, 2002; 20(5):1260-1268
Memorial Sloan-Kettering Cancer Center (http://www.mskcc.org)