MRI Surveillance Is Promising Option for Certain BRCA Mutation Carriers

Magnetic resonance imaging (MRI) surveillance of young women with BRCA mutations at an experienced center reliably detects the vast majority of cancers at an early stage and thus is a viable alternative to risk-reducing mastectomy, according to Canadian investigators who evaluated this approach in nearly 500 mutation carriers.

The study was reported at the symposium by Kavitha Passaperuma, MD, of Sunnybrook-Odette Cancer Center at the University of Toronto, Canada, who was among 18 oncology fellows receiving a merit award at the gathering for outstanding abstracts.

“Surveillance, as an alternative to risk-reducing mastectomy, can only be justified if the cancers detected in screened women are at an early stage, such that the systemic recurrence rate is less than 10%,” Passaperuma said. “Current guidelines recommend the combination of annual MRI plus mammography for surveillance of women with BRCA mutations, but there are many unanswered questions.”

For example, is annual screening sufficient for young women with BRCA1 mutations, is surveillance mammography alone adequate for women aged 50 and older with BRCA mutations, and can long-term systemic recurrence rates of <10% be expected?

The study was an updated analysis of rates of sensitivity, specificity, stage distribution, treatment, and recurrence rates from the group’s prospective surveillance study of 496 women with BRCA mutations between November 1997 and June 2009.

Surveillance protocol included annual mammography, MRI and ultrasound, and semiannually clinical breast exams. All imaging was done on the same day at a single tertiary center. Ultrasound screening was discontinued in 2004 due to low sensitivity and specificity. All imaging studies were read independently by a specialized, blinded radiologist. A positive screen was defined as Breast Imaging Reporting and Data System (BI-RADS) score of 0.3 to 5.0, which was confirmed with biopsy.

At a median follow-up of 5 years, there were 53 screen-detected cancers, 1 interval cancer, and 3 incidental cancers found at prophylactic mastectomy.

The 1 instance of interval cancer was a stage 1 cancer in a BRCA1 carrier. This yielded an interval cancer rate of 2%, which amounts to 1 interval cancer per 797 screening person-years for BRCA1carriers <45 years of age, Passaperuma said.

Overall specificity was 97% for mammography, 90% for MRI, and 87% for the 2 modalities combined. There was substantial improvement in the specificity of MRI after the first round of screening (82% vs 93%).

“The sensitivity of mammography was no better in women aged 50 and older than in younger women, about 20% in each age group,” Passaperuma noted.

Overall sensitivity was 20% for mammography, 91% for MRI, and 94% for the combined modalities. Sensitivities were similar for BRCA1 and BRCA2 mutation carriers with each modality. Mammography also had low sensitivity for invasive cancers and ductal carcinoma in situ (DCIS), the study found.

On the first screen, 22 cancers were detected, for a prevalence rate of 4%. Only four (10%) invasive cancers were node positive. Mean size of invasive tumors was 10.8 mm for prevalent and 8.7 mm for incident tumors. All incident tumors were stage T0 or T1.

“Many women with incident cancers did not require systemic therapy,” Passaperuma added.

Overall survival was 92%, and several deaths were not related to breast cancer. The ipsilateral relapse rate was 11%, all radiologically confirmed second primary cancers arising in discrete locations from the initial cancers. Only 1 case of distant recurrence and breast cancer-related death was seen, in a prevalent node-positive cancer.

The investigators estimated the long-term systemic recurrence rate to be <10%, particularly for incident cancers, 97% of which were DCIS or stage 1 in this study.

Elisa Port, MD, an oncologic surgeon at Mount Sinai Hospital, New York, New York, discussed the paper at the meeting and commented that she agreed that surveillance is a reasonable alternative to prophylactic mastectomy for women with BRCA mutations, “with the understanding that early detection is a goal, not a guarantee, and even with early detection systemic therapy may be needed.”

More Info»2010 Breast Cancer Symposium Abstract 5, http://tiny.cc/v9hsi