When the BRCA1 and BRCA2 genes for breast and ovarian cancers were first identified and a screening blood test became available, a debate ensued as to whether there was an advantage to learning one’s risk. Recently, the value of such testing was demonstrated in a study in women who were followed after being identified as carriers of a BRCA genetic mutation. Researchers at Memorial Sloan-Kettering Cancer Center have provided strong evidence that breast and ovarian cancers can be detected at an early stage in women at highest hereditary risk. Results of the study were published in a recent issue of the Journal of Clinical Oncology (20:1260-1268, 2002).
When the BRCA1 and BRCA2 genes for breast and ovariancancers were first identified and a screening blood test became available, adebate ensued as to whether there was an advantage to learning one’s risk.Recently, the value of such testing was demonstrated in a study in women whowere followed after being identified as carriers of a BRCA genetic mutation.Researchers at Memorial Sloan-Kettering Cancer Center have provided strongevidence that breast and ovarian cancers can be detected at an early stage inwomen at highest hereditary risk. Results of the study were published in arecent issue of the Journal of Clinical Oncology (20:1260-1268, 2002).
"These results provide the first prospective evidence that BRCA testingcan lead to interventions that result in the diagnosis of early-stage breast andovarian cancers," said Dr. Kenneth Offit, chief of the Clinical GeneticsService at Memorial Sloan-Kettering and senior author of the study.
Intensified Screening, Prophylactic Surgery
The study enrolled 251 individuals, including 233 women identified as havingmutations in the BRCA1 or BRCA2 genes. Participants received uniformrecommendations for intensified screening and preventive surgery in the contextof genetic counseling. Over the course of the study, 21 women were diagnosedwith early breast or ovarian cancer.
Among the women identified as being at risk for breast cancer, 165 choseincreased surveillance. Breast cancer was detected in 12 of these patients, with9 of the tumors diagnosed at the earliest stage. Half of these breast cancerswere detected by mammography (including one by magnetic resonance imaging) andhalf by physical examination during the interval between annual mammograms.
Moreover, to reduce their risk of developing breast cancer, 29 women chose toundergo prophylactic mastectomy. Of these women, two were found to haveunsuspected early-stage breast cancer at the time of surgery.
"These results illustrate the importance of a comprehensive approach tobreast cancer screening including self examinations in addition to breastimaging and physician examinations," said Lauren Scheuer, a senior geneticcounselor at Memorial Sloan-Kettering and lead author of the study."Further research is necessary to determine whether more frequent breastimaging may be warranted in women at hereditary risk."
Earlier-Stage Ovarian Cancer Discovered
For the 89 women with intact ovaries who chose surveillance, screening withtwice yearly transvaginal ultrasound and a CA-125 blood test was recommended.The five ovarian cancers detected in this group were all found at an earlierstage than typical for this disease, which tends to be diagnosed after thecancer has metastasized. Among the 90 women who chose to undergosalpingo-oophorectomy, two early-stage ovarian cancers were also discovered.
"However, the finding of several unsuspected breast and ovarian cancersat the time of ‘preventive’ surgery highlights the limitations of screening,and justifies continued consideration of these surgeries," said Dr. MarkRobson, a breast oncologist at Memorial Sloan-Kettering and coauthor of thereport.
Long-Term Outcome Unknown
Although the study shows that early-stage cancers may be diagnosed byscreening and surgery following genetic testing, the authors caution that thefollow-up period, with a mean of 24.8 months, is short and the long-term outcomefor this group of women is not yet known. In particular, this study does notaddress whether surgery decreases the rate of subsequent cancers.
"Further studies will be needed to measure outcomes after surgery andearly detection. However, our preliminary results are encouraging. Theyunderscore the importance of genetic counseling and education for women withproven risk factors for breast and ovarian cancer," said Ms. Scheuer.