Is a breast MRI with or without contrast recommended for a patient with a PALB2 (Partner And Localizer of BRCA2) gene mutation and family history of breast cancer with asymmetry on a mammogram?

Breast MRI WITH Contrast for PALB2 Mutation with Asymmetry on Mammogram

A patient with a PALB2 mutation and family history of breast cancer who has asymmetry on mammogram should undergo breast MRI WITH intravenous gadolinium contrast, as PALB2 carriers have a 49-91% lifetime breast cancer risk and qualify for annual supplemental MRI screening starting at age 25-30. 1, 2, 3

Why Contrast is Essential

• Breast MRI without contrast has no role in breast cancer screening or evaluation - the entire diagnostic capability of breast MRI depends on dynamic contrast enhancement to differentiate malignant from benign tissue. 1

• Malignant lesions enhance more rapidly than normal parenchymal tissue (typically within 1-3 minutes post-injection), and the uptake/washout pattern is critical for identifying cancer. 1

• Dynamic contrast-enhanced MRI (DCE-MRI) allows assessment of both lesion appearance and enhancement kinetics, which are essential for discriminating malignant from benign conditions. 1

PALB2 Mutation Risk Profile

• PALB2 mutations confer extremely high breast cancer risk: the c.3113G>A mutation specifically carries a hazard ratio of 30.1, with cumulative risk of 49% by age 50 and 91% by age 70. 3

• PALB2 carriers have breast cancer risks comparable to BRCA2 mutation carriers (45-65% lifetime risk), placing them firmly in the high-risk category requiring intensive surveillance. 1, 3

• Women with PALB2 mutations meet the threshold for annual MRI screening (≥20% lifetime risk) recommended by the American Cancer Society and ACR. 1, 2

Management Algorithm for This Patient

Immediate Next Steps:

1. Complete workup of the mammographic asymmetry first - perform targeted ultrasound of the asymmetric area, as ultrasound detects 93-100% of cancers occult on mammography and has a combined negative predictive value >97% when both modalities are benign. 1, 4

2. If ultrasound shows a suspicious finding, proceed directly to image-guided core biopsy before MRI, as biopsy-related changes will confuse and limit subsequent MRI interpretation. 4

3. If ultrasound is negative or shows only benign findings, then proceed to contrast-enhanced breast MRI to complete high-risk screening evaluation. 1, 2

Long-term Surveillance Protocol:

• Annual contrast-enhanced breast MRI starting at age 25-30 for PALB2 mutation carriers. 1, 2

• Annual mammography starting at age 30-40 (can be delayed to age 40 if annual MRI is performed reliably). 1, 2

• Clinical breast examination every 6 months for women with increased lifetime risk. 1

Technical Requirements for High-Quality MRI

The ACR and NCCN specify that breast MRI screening requires: 1

• Dedicated breast coil (not body, chest, or abdominal coils) 1
• Radiologists experienced in breast MRI interpretation 1
• Capability to perform MRI-guided needle sampling and wire localization of MRI-detected findings 1

Critical Evidence on MRI Performance in High-Risk Women

• MRI sensitivity in high-risk populations is 68-90% compared to only 37% for mammography and 37% for ultrasound in BRCA/high-risk women. 1

• In the FaMRIsc trial of women with familial risk (≥20% lifetime risk), MRI screening detected significantly more cancers than mammography (40 vs 15), with smaller invasive tumors (median 9mm vs 17mm) and less frequent node-positive disease (17% vs 63%). 5

• MRI detects cancers at earlier stages: 48% of MRI-detected cancers were stage T1a-T1b versus only 7% with mammography in high-risk women. 5

Common Pitfalls to Avoid

• Never order MRI without contrast - it provides no diagnostic value for breast cancer screening or evaluation. 1

• Do not skip the ultrasound evaluation of the mammographic asymmetry - complete the standard diagnostic workup before proceeding to supplemental screening MRI. 4

• Do not perform biopsy before imaging if additional imaging (MRI) is planned, as post-biopsy changes obscure interpretation. 4

• Recognize that MRI has higher false-positive rates (6.3% biopsy rate with 19.5% cancer yield) compared to mammography (2.2% biopsy rate with 34.7% cancer yield), but this is acceptable given the substantially higher cancer detection rate in high-risk women. 1

Why Family History Alone is Insufficient

• While this patient has family history of breast cancer, the PALB2 mutation is the primary risk determinant - PALB2 c.3113G>A carriers have 30-fold increased breast cancer risk independent of family history. 3

• Some women with ≥10% risk of BRCA/PALB2 mutations may have <20% calculated lifetime breast cancer risk using family history models alone, potentially excluding them from MRI screening if genetic testing is not performed. 6

• The presence of a confirmed PALB2 mutation eliminates any ambiguity - this patient definitively qualifies for high-risk MRI surveillance regardless of family history details. 1, 2