A large, Dutch study of women at increased risk for hereditary breast cancer has found that magnetic resonance imaging (MRI) was superior to mammography in early detection of tumours in women either harbouring mutations in the BRCA genes or at high risk for cancer because of family history. The study, published online November 15, 2010, in the Journal of Clinical Oncology, did not look at MRI as a standard screening technique for all women, but rather only those considered at risk.

"In women at increased risk of breast cancer due to a genetic susceptibility, MRI has been the cornerstone of intensive surveillance. The study confirms that with a longer follow-up period, the sensitivity of MRI is still strongly superior to mammography," said lead author Dr Jan G. M. Klijn, Emeritus Professor of Medical Oncology at the Erasmus University in Rotterdam, The Netherlands.

In this long-term follow-up of the Dutch MRI Screening study (MRISC), researchers evaluated the long-term results of screening 2,157 women at risk for hereditary breast cancer – including separate analyses of 599 BRCA1 and BRCA2mutation carriers.

In the study, women with a cumulative lifetime risk (CLTR) for breast cancer greater than 15 percent were screened for cancer using biannual clinical breast examination and annual mammography and MRI. Participants were divided into three subgroups: those who carried a gene mutation and had a 50 percent to 85 percent CLTR, and two groups with a family history of breast cancer without a known gene mutation, including those considered at high risk (30 percent to 50 percent CLTR) or at moderate risk (15 percent to 30 percent CLTR). The median follow-up time was 4.9 years from study entry.

They found that mammography was more than twice as sensitive in detecting cancer in BRCA2 mutation carriers (61.5 percent) than in BRCA1 mutation carriers (25.0 percent), and that MRI was better than mammography in detecting cancer in BRCA1 mutation carriers (66.7 percent). MRI was slightly more sensitive in BRCA2 mutation carriers (69.2 percent).

"BRCA1-associated tumours behave completely different from BRCA2-associated tumours and those from other high-risk groups," Klijn said. "Such BRCA1 tumours tend to be in women at a younger age at diagnosis, have lower mammographic sensitivity, are larger in size, and more frequently are aggressive, 'triple negative' cancers."

Mutations in BRCA1 or BRCA2 genes can be found in approximately 25 percent of women with a family history of breast cancer. Previous studies had shown that MRI screening appeared to be about twice as sensitive as mammography screening in detecting tumours in women with a susceptibility to breast cancer. While most screening guidelines now recommend MRI screening in BRCA1 and BRCA2 mutation carriers, there is no consensus regarding the best screening protocol for all at-risk groups with respect to the four screening methods – mammography, MRI, ultrasound and clinical breast examination. There is also little agreement on which at-risk groups should be screened.

The study was the first prospective report on mortality in these groups of women who underwent this screening protocol. Investigators found low mortality; only four women with invasive breast cancer, all with a BRCA1/BRCA2 gene mutation, died after a median of five years after diagnosis. None of the women in the other risk groups (those women without a documented gene mutation) died or showed distant recurrence. They also showed that 6 years after diagnosis, there was an overall survival of 93 percent in 42 BRCA1/BRCA2 mutation carriers who developed invasive breast cancer during screening, which seems to be an improvement compared to the overall survival of patients in previous studies (74 percent in 26 non-randomized studies with a median follow-up of 5 years) screened only with mammography or not screened at all.

"Now we have an indication for the first time of how safe intensive surveillance is and how it may reduce mortality," Klijn said. He noted that while some women opt for prophylactic mastectomy – which can prevent breast cancer nearly 100 percent of the time – intensive surveillance with MRI can be a reasonable alternative for high-risk women not opting for such surgery.

The authors suggest that changes in screening recommendations may be considered for BRCA1 mutation carriers – including a possible biannual MRI – in addition to the use of newer adjuvant therapeutic regimens and future targeted therapies, such as PARP inhibitors. The study results also support the use of MRI screening in other risk groups without a BRCA1/BRCA2 mutation.

Source: American Society of Clinical Oncology