What are the highest risk factors for breast cancer in a female patient undergoing screening?

From the Guidelines

The highest risk factors for breast cancer in a female patient undergoing screening include a known genetic mutation such as BRCA1 or BRCA2, a personal history of breast cancer, and a family history of breast cancer, especially in first-degree relatives, as these factors significantly increase the risk of developing breast cancer 1. When evaluating the risk of breast cancer, several key factors are considered, including:

• Age over 50 years
• Personal history of breast cancer
• Family history of breast cancer, especially in first-degree relatives
• Known genetic mutations such as BRCA1 and BRCA2
• Previous chest radiation therapy
• Certain high-risk breast lesions on prior biopsies, like atypical hyperplasia or lobular carcinoma in situ
• Early menarche (before age 12)
• Late menopause (after age 55)
• Never having children or having first child after age 30
• Long-term hormone replacement therapy
• Dense breast tissue
• Lifestyle factors such as alcohol consumption and obesity These risk factors are crucial to identify during screening as they may warrant more intensive surveillance, earlier initiation of screening, additional imaging modalities beyond mammography (such as MRI), or consideration of chemoprevention strategies 1. The cumulative effect of multiple risk factors significantly increases a woman's overall risk, and risk assessment tools like the Gail model or Tyrer-Cuzick model can help quantify this risk to guide screening and prevention strategies 1. It is essential to note that the ACR recommends annual screening mammography beginning no later than 40 years of age for women at intermediate risk and that women should continue screening mammography as long as they remain in overall good health and are willing to undergo the examination and subsequent testing or biopsy, if an abnormality is identified 1.

From the FDA Drug Label

“High risk” is defined as women at least 35 years of age with a 5 year predicted risk of breast cancer ≥ 1.67%, as calculated by the Gail Model. Examples of combinations of factors predicting a 5 year risk ≥ 1.67% include:

• One first degree relative with a history of breast cancer, 2 or more benign biopsies, and a history of a breast biopsy showing atypical hyperplasia;
• At least 2 first degree relatives with a history of breast cancer, and a personal history of at least 1 breast biopsy;
• LCIS
• Age 40 or older and any of the following combination of factors:
  • One first degree relative with a history of breast cancer, 2 or more benign biopsies, age at first live birth 25 or older, and age at menarche 11 or younger;
  • At least 2 first degree relatives with a history of breast cancer, and age at first live birth 19 or younger;
  • One first degree relative with a history of breast cancer, and a personal history of a breast biopsy showing atypical hyperplasia
• Age 45 or older and any of the following combination of factors:
  • At least 2 first degree relatives with a history of breast cancer and age at first live birth 24 or younger;
  • One first degree relative with a history of breast cancer with a personal history of a benign breast biopsy, age at menarche 11 or less and age at first live birth 20 or more
• Age 50 or older and any of the following combination of factors:
  • At least 2 first degree relatives with a history of breast cancer;
  • History of 1 breast biopsy showing atypical hyperplasia, and age at first live birth 30 or older and age at menarche 11 or less;
  • History of at least 2 breast biopsies with a history of atypical hyperplasia, and age at first live birth 30 or more
• Age 55 or older and any of the following combination of factors:
  • One first degree relative with a history of breast cancer with a personal history of a benign breast biopsy, and age at menarche 11 or less;
  • History of at least 2 breast biopsies with a history of atypical hyperplasia, and age at first live birth 20 or older.
• Age 60 or older and: Five-year predicted risk of breast cancer ≥ 1.67%, as calculated by the Gail Model.

The factors with the highest risk for breast cancer in a female patient undergoing screening include:

• Family history: Having at least 2 first-degree relatives with a history of breast cancer
• Personal history of breast biopsies: Having a history of at least 2 breast biopsies with a history of atypical hyperplasia
• Age: Being 60 or older with a 5-year predicted risk of breast cancer ≥ 1.67%, as calculated by the Gail Model
• LCIS (Lobular Carcinoma In Situ): Having a history of LCIS
• Atypical hyperplasia: Having a personal history of a breast biopsy showing atypical hyperplasia 2

From the Research

Risk Factors for Breast Cancer

The following are some of the highest risk factors for breast cancer in a female patient undergoing screening:

• Family history of breast cancer, particularly in first-degree and second-degree relatives 3, 4
• Presence of a high-risk germline mutation, such as BRCA1 or BRCA2 5, 6, 7
• History of thoracic radiation treatment between 10-30 years of age 5
• High breast density 3
• Personal history of breast cancer or certain non-cancerous breast conditions 5

High-Risk Populations

Women with a ≥20% lifetime risk of breast cancer are considered high-risk and may benefit from additional screening and prevention strategies 5

• BRCA1 and BRCA2 mutation carriers may benefit from chemoprevention with tamoxifen or raloxifene to reduce their risk of breast cancer 6, 7

Screening Recommendations

Women at high risk for breast cancer are recommended to undergo annual screening mammography and adjunctive annual screening breast MRI 5

• Pregnant and lactating patients at average risk for breast cancer are recommended to undergo age-appropriate screening mammography 5