What is the recommended breast screening for women with disease-causing genetic variants (mutations)?

National Comprehensive Cancer Network (NCCN) guidelines recommend annual screening MRI beginning by age 25, with the addition of mammography beginning at age 30, in women who are known to carry pathogenic/likely pathogenic variants in BRCA1 or BRCA2 (unless the woman has had bilateral mastectomy), and in women who are untested first-degree relatives of those with known pathogenic/likely pathogenic variants (see table below) [1].

Women who are known to carry or are first-degree untested relatives of individuals with less common disease-causing variants [such as those associated with Li-Fraumeni syndrome (TP53); Bannayan-Riley-Ruvalcaba syndrome or Cowden syndrome (PTEN); hereditary diffuse gastric cancer (CDH1); Peutz-Jeghers syndrome (STK11); Neurofibromatosis type 1 (NF1); or Fanconi anemia (PALB2)] are also recommended for annual screening MRI, with age to start depending on the variant (see table below). Women with NF1 have elevated risk only through age 50: supplemental MRI should stop beyond age 50 for these women. For women with disease-causing variants in genes other than NF1, supplemental MRI screening should continue until age 75, after which screening should continue on an individual basis [1].

In addition to pathogenic/likely pathogenic variant carriers and their untested first-degree relatives, annual screening MRI is recommended in addition to mammography/tomosynthesis in the following subgroups of women:

• Women with a calculated lifetime risk (LTR) of breast cancer of 20% or greater are recommended to begin annual screening MRI. Starting age varies according to different guidelines [2-5] but may be as early as age 25-30 [4]. Any of the models used to predict risk of a pathogenic variant [Tyrer-Cuzick (IBIS), Penn II, BOADICEA, BRCAPRO], or the Claus model, but NOT the Gail model, can be used to estimate lifetime risk for purposes of annual screening MRI eligibility.
• Women with prior chest radiation therapy (such as for Hodgkin disease) between ages 10 and 30 are at high risk for developing breast cancer [2-6], similar to BRCA1 or BRCA2 carriers, and are recommended for annual screening MRI starting at age 25 or 8 years after the chest radiation therapy, whichever is later.
• Women with a personal history of breast cancer and dense breasts and/or diagnosis by age 50 [3, 4]. All women diagnosed with breast cancer at or before age 50 and treated with breast-conserving therapy have a ≥ 20% risk for a new breast cancer [4].
• Annual MRI may be considered in addition to annual mammography or tomosynthesis in women with a personal history of breast cancer diagnosed after age 50 or without dense breasts [4], and/or a history of LCIS or prior atypia (ADH, ALH, atypical papilloma) [3, 4].

NCCN Breast Cancer Screening Guidelines in Women Who Carry or Are First-Degree Untested Relatives of Individuals with Pathogenic Variants or Variants Known or Likely to Increase Breast Cancer Risk [1]

^a For women with pathogenic/likely pathogenic variants who are treated for breast cancer and have not had bilateral mastectomy, screening should continue as described until age 75 (other than for women with NF1^f). After age 75, management should be considered on an individual basis [1].

^b Start at age 20 or the age of the earliest diagnosed breast cancer in the family if younger than age 20.

^c Begin at age 25, or starting age may be individualized based on family history of a breast cancer diagnosis before at 30. From age 25-29 years, breast MRI alone is recommended. Adding mammography at age 30 is preferred due to the potential risk of radiation exposure in pathogenic/likely pathogenic variant carriers under age 30. Mammography can be performed from ages 25-29 years only if MRI is unavailable.

^d Start at stated age or 5-10 years before the earliest known breast cancer in the family (whichever comes first), or based on specific pathogenic/likely pathogenic variant.

^e There are currently no data to suggest an increased breast cancer risk after age 50 years in women with NF1; therefore, MRI screening may discontinue at 50 years of age in this group. In addition, the presence of breast neurofibromas may lead to false-positive MRI results; more data on sensitivity and specificity of MRI in women with NF1 is needed.

^f Start at stated age or 10 years before the earliest known breast cancer in the family (whichever comes first).

^g The use of MRI in these patients depends on a number of risk factors, including family history, age, breast density, and patient preference.