What is the recommended screening workup for a 25-year-old female with a BRCA1 (Breast Cancer Gene 1) mutation and a family history of ovarian and breast cancer?

From the Guidelines

For a 25-year-old female with BRCA1 mutation and family history of ovarian and breast cancer, screening should begin with clinical breast exams every 6-12 months starting at age 25, and annual breast MRI should be performed between ages 25-29, with annual mammography added at age 30. The most recent and highest quality study, published in 2021 1, recommends that women with BRCA1/2 pathogenic or likely pathogenic variants should have training in breast awareness with regular monthly practice starting at 18 years of age, and clinical breast examinations should be conducted every 6–12 months, beginning at 25 years of age. Between the ages of 25 and 29 years, annual breast MRI screening with contrast is preferred over mammogram, and between 30 and 75 years of age, annual mammogram and breast MRI with contrast should both be done. Additionally, transvaginal ultrasound and CA-125 blood testing for ovarian cancer screening should begin between ages 30-35, though these have limited sensitivity. Risk-reducing bilateral mastectomy should be discussed as it decreases breast cancer risk by 90-95%, and risk-reducing bilateral salpingo-oophorectomy (removal of ovaries and fallopian tubes) is recommended between ages 35-40 after childbearing is complete, reducing ovarian cancer risk by 80-90% 1. Oral contraceptives can be considered for those who retain their ovaries, as they reduce ovarian cancer risk by approximately 50% 1. Regular follow-up with both a breast specialist and gynecologic oncologist is essential, as BRCA1 carriers have a 55-72% lifetime risk of breast cancer and 39-44% risk of ovarian cancer, with earlier onset than the general population. Some key points to consider include:

• The importance of breast awareness and regular monthly practice starting at 18 years of age
• The preference for annual breast MRI screening with contrast between ages 25-29
• The addition of annual mammography at age 30
• The limited sensitivity of transvaginal ultrasound and CA-125 blood testing for ovarian cancer screening
• The discussion of risk-reducing bilateral mastectomy and risk-reducing bilateral salpingo-oophorectomy
• The consideration of oral contraceptives for those who retain their ovaries.

From the Research

Screening Routine for BRCA1+ 25yo Female with Family History of Ovarian and Breast Cancer

• The screening routine for a BRCA1+ 25-year-old female with a family history of ovarian and breast cancer typically involves a combination of imaging modalities and clinical examinations 2, 3, 4, 5.
• Annual screening with mammography, magnetic resonance imaging (MRI), and clinical breast examination (CBE) is recommended, starting at age 25 3, 4.
• MRI is more sensitive for detecting breast cancers than mammography, ultrasound, or CBE alone in BRCA1 and BRCA2 mutation carriers 3, 5.
• The combination of MRI and mammography has a higher sensitivity (94%) compared to mammography alone (39%) 4.
• Ultrasound and CBE may not add significant benefit to the screening regimen, but can be used as secondary modalities to evaluate suspicious findings on MRI or mammography 4, 5.
• Women with a family history of breast cancer who test negative for BRCA1 or BRCA2 mutations may still have an elevated risk of breast cancer (approximately four-fold) and may be candidates for intensified breast screening with MRI 6.

Key Findings

• MRI detects more breast cancers than mammography, ultrasound, or CBE alone in BRCA1 and BRCA2 mutation carriers 3, 5.
• The combination of MRI and mammography has a higher sensitivity than mammography alone 4.
• Women with a family history of breast cancer who test negative for BRCA1 or BRCA2 mutations may still have an elevated risk of breast cancer 6.

Screening Modalities

• Mammography: annual screening starting at age 25 3, 4.
• MRI: annual screening starting at age 25, more sensitive than mammography for detecting breast cancers in BRCA1 and BRCA2 mutation carriers 3, 4, 5.
• Ultrasound: may be used as a secondary modality to evaluate suspicious findings on MRI or mammography 4, 5.
• CBE: annual screening starting at age 25, may not add significant benefit to the screening regimen 3, 4.