What constitutes a significantly strong breast cancer family history?

What Constitutes a Significantly Strong Breast Cancer Family History?

A significantly strong family history of breast cancer includes having multiple affected first-degree relatives (especially diagnosed before age 50), having relatives with bilateral breast cancer, male breast cancer, or ovarian cancer, or belonging to high-risk ethnic groups such as Ashkenazi Jewish descent. 1

Key Elements of a Strong Family History

Number and Relationship of Affected Relatives

• Having one first-degree relative (mother, sister, daughter) with breast cancer increases risk by approximately 1.7-fold 2
• Having two or more first-degree relatives with breast cancer increases risk by 2.5-fold or greater 3
• Risk increases with the number of affected relatives in the family and closeness of the relationship 1

Age at Diagnosis of Affected Relatives

• Having a first-degree relative diagnosed before age 50 confers higher risk (RR 1.69) compared to diagnosis at age 50 or older (RR 1.37) 2
• Women with either a mother or sister diagnosed before age 50 have a relative risk of 1.70, significantly higher than those with relatives diagnosed at age 50 or older (RR 1.30) 2, 4
• Early-onset breast cancer in family members strongly suggests a hereditary component 1

Specific Cancer Types in Family

• Family history of ovarian cancer at any age increases breast cancer risk 1
• Male breast cancer in the family significantly increases risk and suggests possible BRCA mutations 1
• Multiple primary cancers in the same individual (e.g., bilateral breast cancer) 1
• Other related cancers in the family such as pancreatic, prostate, or melanoma may indicate hereditary syndromes 1

High-Risk Criteria According to NCCN Guidelines

The National Comprehensive Cancer Network (NCCN) considers the following as significantly strong family history warranting genetic evaluation:

• Individual from a family with a known BRCA1/BRCA2 or other breast cancer susceptibility gene mutation 1
• Personal history of breast cancer diagnosed at age 45 or younger 1
• Personal history of breast cancer diagnosed at age 50 or younger with one or more close blood relatives with breast cancer at any age 1
• Personal history of breast cancer at any age with two or more close blood relatives with breast and/or ovarian cancer at any age 1
• Personal history of two breast primaries when first breast cancer diagnosis occurred before age 50 1
• Personal history of ovarian/fallopian tube/primary peritoneal cancer 1
• Close male blood relative with breast cancer 1

Ethnic Considerations

• Ashkenazi Jewish heritage increases risk of carrying BRCA1/2 mutations 1
• Other founder populations with increased risk include Icelandic, Swedish, Hungarian, and Dutch 1
• For these populations, requirements for genetic testing may be lessened (e.g., breast or ovarian cancer at any age) 1

Family Structure Considerations

• Limited family structure (fewer than 2 first- or second-degree female relatives or female relatives not surviving beyond age 45) may lead to underestimation of familial risk 1, 3
• Family history should be evaluated on both maternal and paternal sides independently 1
• A family history score that accounts for expected number of cases based on family size and age structure may provide better risk discrimination than conventional parameters 3

Clinical Implications

• Women with strong family history should be referred for genetic counseling and possible testing 1
• Women with a significantly strong family history may benefit from enhanced screening protocols including earlier initiation of mammography and consideration of MRI screening 1
• Risk-reducing strategies such as chemoprevention with tamoxifen may be considered for high-risk women 5
• Family history assessment should be updated periodically as new cancer diagnoses in the family may change risk status 1

Common Pitfalls in Family History Assessment

• Focusing only on maternal side and ignoring paternal family history 1
• Not accounting for small family size or limited information about family members 1
• Overlooking the significance of age at diagnosis of affected relatives 2, 4
• Failing to consider ethnic background that may influence genetic risk 1
• Not reassessing family history periodically as new cancer diagnoses occur 1