What is the recommended breast screening for women with disease-causing 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 mutations in BRCA1 or BRCA2 (unless the woman has had bilateral mastectomy), and in women who are first-degree relatives of known mutation carriers but who are themselves untested (see table below) [1].

Women who are known to carry or are first-degree untested relatives of individuals with less common disease-causing mutations [such as those associated with Li-Fraumeni syndrome (TP43); 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 beginning between ages 20-35, depending on the mutation (see table below). Women with known pathogenic mutations in ATM, CHEK2, or BARD1 should consider annual MRI starting at age 40 or 5-10 years before the earliest known breast cancer in the family (whichever comes first). Women with NF1 have elevated risk only through age 50: supplemental MRI should stop beyond age 50 for these women and at least by age 75 for women with other pathogenic mutations.*

In addition to disease-causing mutation 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 by age 25-30 [2, 3]. Any of the models used to predict risk of a pathogenic mutation [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 screening MRI guidelines.
• Women with prior chest radiation therapy (such as for Hodgkin disease) between ages 10 and 30 are at high risk for developing breast cancer [2-5], 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. 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 [3, 5].
• 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, and/or a history of LCIS or prior atypia (ADH, ALH, atypical papilloma) [3, 5].

* After 75 years of age, management should be considered on an individual basis [1].

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

^aFor 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].

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

^cBegin at age 25, or starting age may be individualized based on family history of a breast cancer diagnosis before at 30

^dStart at stated age or 5-10 years before the earliest known breast cancer in the family (whichever comes first).

^eScreening recommendations only apply to individuals with a clinical diagnosis of Neurofibromatosis type 1 (NF1).

^fThere 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.