MRI MAMMOGRAPHY SUPERIOR FOR HIGH RISK WOMEN

November 22, 2010 — Magnetic resonance imaging (MRI) appears to be more effective than mammography in detecting early breast cancer in women at high risk for breast cancer. Dutch researchers found that with a follow-up period of approximately 5 years, the sensitivity of MRI is still superior to that of mammography in women with BRCA mutations.

The study was published online November 15 in the Journal of Clinical Oncology.

"In view of the quite high percentage of interval cancers within the BRCA1 group and larger tumors at diagnosis — probably due to more rapid tumor growth — a more intensive screening protocol might be considered to improve screening results," said lead author Jan G.M. Klijn, MD, PhD, emeritus professor of medical oncology at the Erasmus University in Rotterdam, the Netherlands.

Dr. Klijn noted that with the current screening regimen, the observed death rate is already much lower than expected. "You can think about an MRI twice a year, but this will be more costly and a burden for the women, certainly in the United States," he told Medscape Medical News. "Another possibility is alternating an MRI scan and mammography every 6 months. There are other different potential schemes, depending on the type of risk group; we are now looking into the feasibility of such approaches."

For high-risk women, MRI should replace screening mammography, explained Dr. Klijn. "In general, for young screened women with a familial/genetic predisposition, the MRI scan — not mammography — is the corner stone of intensive surveillance," he said. "In other words, mammography is supplementary/additive to MRI, not vice versa."

MRI Improves Detection

The study cohort consisted of 2157 women, 599 of whom were carriers of a pathogenic gene mutation; 422 with BRCA1, 172 with BRCA2, and 5 with PTEN/TP53. There were 1069 women in the high-risk group and 489 women in the moderate-risk group.

A total of 98 malignant tumors were detected in 94 women; of these, 97 were breast cancers, 78 (80%) were invasive, and 19 (20%) were ductal carcinoma in situ (DCIS). The majority (n = 78) of breast cancers were detected with screening.

The overall rate of detection was 10.4 per 1000 woman-years at risk. The highest rate was observed in BRCA2 mutation carriers (39.2 per 1000), which was due partly to the high incidence of DCIS in this subgroup (7.4 per 1000).

Overall, results from both screening methods were available for 75 breast cancers; 32 (43%) were detected only with MRI screening (16 of the 32 mutation carriers), and 5 were also detected with clinical breast exam. Nineteen breast cancers (25%) were detected with both MRI and mammography, and 12 (16%) were detected only with mammography (including 8 cases of DCIS).

The sensitivity was 20.6% for clinical breast exam, 41.3% for mammography, and 70.7% for MRI. The difference in sensitivity between mammography and MRI was significant, the authors note (P = .0016). When only invasive cancers were included in the analysis, MRI sensitivity increased to 77.4% and mammography sensitivity decreased to 35.5% (n = 62; P < .00005).

Conversely, mammography sensitivity was much higher than MRI sensitivity in DCIS (69.2% vs 38.5%), but the difference was not significant because of the small number in this group (n = 13; P = .388).

Differences in BRCA1/2

When analyzed by mutation carrier, mammography sensitivity was significantly lower (P = .04) in BRCA1 (25.0%) than in BRCA2 (61.5%) mutation carriers. "Strikingly," the authors point out, the sensitivity of MRI was much higher than that of mammography in BRCA1 mutation carriers (n = 24; 66.7% vs 25.0%; P = .0129). It was only slightly higher in BRCA2 mutation carriers (n = 13; 69.2% vs 61.5%; P = 1.0).

Cumulative distant metastasis-free and overall survival at 6 years in all 42 BRCA1/2 mutation carriers with invasive breast cancer were 83.9% (95% confidence interval [CI], 64.1 to 93.3) and 92.7% (95% CI, 79.0 to 97.6), respectively; both survival outcomes were 100% in the familial groups (n = 43).

"The investigators have conducted the largest trial of MRI screening in high-risk individuals, and their new [finding] — that MRI screening appears to be preferentially useful in BRCA1 mutation carriers, compared with BRCA2 — has potentially practice-changing implications," said Andrew D. Seidman, MD, member of the American Society of Clinical Oncology Cancer Communications Committee, in a statement.

"The favorable overall survival in all high-risk groups reported suggests that careful MRI screening is not only superior to mammography alone, but may be an attractive alternative to risk-reducing prophylactic mastectomy for some women," he added.

The study was supported by the Dutch government and the Cancer Genomics Center, the Netherlands. The authors have disclosed no relevant financial relationships.

J Clin Oncol. Published online November 15, 2010. Abstract