Optimizing Screening MRI for Women With High Risk of Breast Cancer

The utility of annual MRI plus mammogram was investigated in a new meta-analysis delivered at this year’s San Antonio Breast Cancer Symposium, with the goal of optimizing use of MRI by considering potential for overdiagnosis and tailoring to age and risk group.

Presented by Madeleine Tilanus-Linthorst, MD, PhD, of the Department of Surgery at Erasmus University Medical Center in the Netherlands, “Screening for High-risk Patients: Does Everyone Need Annual MRI With Mammogram?,” sought to answer how to best optimize MRI, answering questions such as: how effective is MRI screening for high-risk women? Should we screen with yearly imaging women aged 25 years or 40 years until 70 years who have different high-risk profiles? And when screening women with BRCA1/2 via MRI, when is mammogram needed?

“To reduce mortality, all guidelines advise women with very-high breast cancer risk, due to a pathogenic variant [PV] in BRCA1/2 or chest wall irradiation between ages 10 and 30 years, annual screening with MRI and 2D or 3D mammography,” Tilanus-Linthorst stated. “We need to balance the possible benefit with the disadvantages.” She added that various studies have produced mix results on the value that mammography adds to MRI screening for different risk and age groups.

How effective is MRI screening for high-risk women?

In an analysis of 2857 women—990 with BRCA1 and 739 with BRCA2 with a history of screening MRI (mean ages, 38 and 42 years, respectively) and 722 with BRCA1 and 406 with BRCA2 who had preventive mastectomy (mean ages, 34 and 36 years, respectively)—more cancers were seen among the patients with BRCA1 and MRI screen (268) compared with patients with BRCA2 and MRI screen (144) and those with BRCA1 who underwent preventive mastectomy (8).

At age 65, comparable survival rates were seen among the BRCA2 group (98% with MRI screening and 100% with preventive mastectomy), suggesting a potential survival benefit from either method at that age and higher mortality among BRCA1 carriers.

A second analysis between BRCA1 and BRCA2 carriers, which compared outcomes from MRI plus mammography (study group) vs mammography alone (controls), showed a 70% reduced risk of death (HR, 0.30; 95% CI, 0.08-1.13) for BRCA1 study group participants vs controls, with those with a familial risk having an even greater reduced risk, at 79% (HR, 0.21; 95% CI, 0.04-0.95). In comparison, those with BRCA2 in the study group only had a 26% reduced risk (HR, 0.74; 95% CI, 0.12-4.45) vs controls.

Should we screen with yearly imaging from age 25 years or 40 years until 70 years?

Noting that tumors grow twice as slow in those aged 40 years vs aged 25 years, Tilanus-Linthorst stated also that women who are BRCA1/2 PV carriers tend to have tumors that at both ages grow twice as fast compared with women who have moderate or average cancer risk. Breaking this down, a tumor undetected at 2 mm could grow to 5 mm and one undetected at 4 mm could grow to 10 mm.

Therefore, considering the risk by age, she detailed the following screening recommendations:

• BRCA1/2 PV carrier aged 25/30 to 45 years: once every 6 to 8 months
• BRCA1/2 PV carrier aged 45 to 65 years: yearly
• BRCA1 PV carrier older than 65 years: biennially
• Moderate risk aged 35/40 to 50 years: yearly
• Moderate/average risk aged 50 to 65 years: biennially
• Moderate/average risk aged 65 to 75 years: once every 3 or 4 years

Additional research in this area compared outcomes between patients with BRCA1/2 younger than 50 years (n = 1514) or 50 years and older (n = 437) who underwent yearly MRI plus mammogram. In the former, 141 cancers were detected (10.7%) and in the latter, 43 (10.2%). Corresponding mammography sensitivity rates were 40% and 38%; MRI, 87% and 85%; and both, 93% and 94%.

A third study of breast cancers (86, BRCA1; 50, BRCA2) in patients older than 60 years compared outcomes from annual or annual/biennial mammography. Fifty-six and 57 cancers, respectively, were detected; 20% and 40% (P = .016) were interval cancer; and 21% and 53% (P = .001) were late-stage cancers.

When screening women with BRCA1/2 via MRI, when is mammogram needed?

First considering women with BRCA1, using data from 2014 and 2018, Tilanus-Linthorst noted that research from a pair of studies showed that yearly MRI plus yearly mammography detected 93 breast cancers among patients with BRCA1 at a sensitivity of 93.6% for MRI and 51.1% for mammography.

Next, considering women with BRCA2, using data from 2018 and 2020, she noted that yearly MRI plus yearly mammography picked up 85 cancers among patients with BRCA2 at a sensitivity of 86% for MRI and 50% for mammography. Only 1 case of ductal carcinoma in situ was detected via mammography in patients younger than 40, while in those 50 years and older, mammography found 7 instances of breast cancers, for results of 16% increased sensitivity.

A study published in 2020, containing data on 8782 women with high risk of developing breast cancer—115 breast cancers were found among 1885 BRCA1/2 PV carriers—who were screened between 2011 and 2016 in Ontario, detailed findings among patients aged 30 to 39, 40 to 49, and 50 to 69 years, found higher sensitivity when using MRI plus mammography vs MRI alone:

• 30 to 39 years: 100% vs 96.8% (P = .99)
• 40 to 49 years: 94.2% vs 91.3% (P = .31)
• 50 to 69 years: 92.7% vs 83.5% (P = .02)

Specificity results, however, were lower when both detection methods were used:

• 30 to 39 years: 78% vs 86%
• 40 to 49 years: 80% vs 87%
• 50 to 69 years: 88% vs 93%

What does this research boil down to? Tilanus-Linthorst listed several recommendations for optimizing MRI use with mammography, and these recommendations differ by risk and age.

Among patients who are BRCA1/2 carriers, those aged 25 to 40 years should get MRIs yearly or more often, those aged 40 to 50 years should get a yearly MRI, those 50 years and older should get a yearly MRI and a biennial mammogram, and those 65 years and older may want to consider alternating yearly MRIs and mammograms.

Among patients with a moderate risk of breast cancer, those aged 35 to 60 years should get a yearly MRI and at age 60 switch to biennial mammograms. However, patients aged 35 to 60 years with a familial risk should get an MRI every 18 months (starting at age 40 years or 5 years before the youngest case in the family) and at age 60 switch to biennial mammograms or from ages 35 to 50, get a yearly MRI (starting at age 40 years or 5 years before the youngest case in the family), switch to biennial MRIs from ages 50 to 60 years, and at ages 60 and older, switch to biennial mammograms.

Reference

Tilanus-Linthorst MMA. Screening for high-risk patients: does everyone need annual MRI with mammogram? Presented at: SABCS; December 6-10, 2022; San Antonio, Texas.