• About 5 – 10% of all breast cancers have germline mutations.
  • American Society for Breast Surgeons recommends that all women aged 25 yrs or more undergo formal risk assessment for breast cancer.
  • National Comprehensive Cancer Network does not recommend universal germline genetic testing for all breast cancer patients.

Breast Cancer Risk Tools & Models

Family History Assessment Tool (FHAT)

  • High Sensitivity (94%) low Specificity (51%)
  • Does not predict the likelihood of developing breast cancer.
  • Just acts as a screening tool for referral to genetic testing.
  • Incorporates criteria of either First/Second/Third degree relative with breast cancer.

Breast Cancer Risk Assessment Tool (BCRAT)

  • Estimates the risk of developing invasive breast cancer in the next five years.
  • Breast Cancer Risk Assessment Tool
  • Underestimates risk in black women & those with atypical hyperplasia

Claus Model

  • Does not include nonhereditary risk factors in determining lifetime risk of developing breast cancer.
  • Should be used only in women with at least 1 female first or second degree relative with breast cancer.
  • Claus Risk Assessment Model

BRCAPRO

  • Predicts probability of carrying BRCA1 or BRCA2 mutations, development of invasive breast cancer or ovarian cancer.
  • The model relies on
  • Family history of breast and ovarian cancers
  • Age at diagnosis
  • Race and ethnicity of each family member
  • Treatment
  • BRCAPRO is a part of the BayesMendelTM risk prediction models.
  • PanelPro Software

BOADICEA

  • Breast & Ovarian Analysis of Disease Incidence & Carrier Estimation Algorithm.
  • It’s a computer program that is used to calculate the risk of breast & ovarian cancer based on their family history.
  • Risk factors used in BOADICEA.

Tyrer-Cuzick Model

  • It estimates patient’s risk of BRCA1 or BRCA2 mutation and the risk of developing invasive & in-situ breast cancer by using genetic & hormonal risk factors.
  • It is useful in populations at high risk.
  • It overestimates invasive cancer risk in women with lobular carcinoma in situ & atypical hyperplasia.
  • It gives two separate risks – one for the risk of developing breast cancer over the next 10 years, and the risk over lifetime (until age 80).
  • Tyrer-Cuzick Calculator

Germline Genetic Testing

  • 30% of generically linked breast cancers are made up by BRCA1 & BRCA2.
  • Samples for testing – Blood or Buccal mucosa or Saliva (blood being most reliable)
  • Five possible outcomes

Screening for Breast Cancer in high-risk groups

2022 NCCN GUIDELINES INVOLVES SCREENING FOR INDIVIDUALS WITH LIFETIME RISK OF >50% CHANCE OF BREAST CANCER (BRCA1, BRCA2, CDH1, PALB2, PTEN, TP53).

BRCA1 & BRCA2

  • Awareness at age 18
  • Clinical breast examination every 6 months from age 25.
  • Annual Breast MRI with contrast/Mammogram from age 25 to 29.
  • Age 30 to 75 – Annual Mammogram with consideration of tomosynthesis + Annual Breast MRI with contrast.
  • > 75 yrs – Annual MRI with contrast.

TP53

  • Awareness at age 18
  • Clinical breast examination every 6 months from age 20 or at the age of earliest diagnosed breast cancer in the family if younger than 20 yrs.
  • Annual Breast MRI with contrast/Mammogram from age 25 to 29.
  • Age 30 to 75 – Annual Mammogram with consideration of tomosynthesis + Annual Breast MRI with contrast.
  • > 75 yrs – Annual MRI with contrast.

CDH1, PALB2, PTEN

  • Annual Mammogram with consideration for tomosynthesis and breast MRI with contrast from age 30 yrs.

2022 NCCN GUIDELINES INVOLVES SCREENING FOR INDIVIDUALS WITH LIFETIME RISK OF 20 TO 50% CHANCE OF BREAST CANCER (ATM, BARD1, CDH1, CHEK2, NF1).

  • Annual screening mammogram with consideration for tomosynthesis and breast MRI with contrast.
  • CDH1 & NF1 – at age 30 yrs.
  • ATM, BARD1, CHEK2 – at age 40 yrs.

Other screening modalities

  • Whole Breast Ultrasonography (WBUS)
  • Contrast Enhanced Mammography (CEM)
  • Options include – Simple Mastectomy, Skin-sparing Mastectomy, Nipple-sparing Mastectomy.
  • In a study conducted by Heemskerk-Gerritsen and Colleagues,
  • Breast cancer specific survival of women at age 65 years with BRCA1 mutation was 93% for patients receiving surveillance as the modality vs 99.7% for those undergoing BRRM.
  • BRCA2 – Corresponding figures were 98% & 100%.
  • Role of Breast conservation Surgery in BRCA1 & BRCA2 carriers is controversial.
  • Recent studies have demonstrated the benefits of one year of adjuvant Poly adenosine diphosphate-ribose Polymerase Inhibitor(PARPi) therapy.
  • Women with TP53 and homozygous ATM mutations are advised to avoid Radiation therapy.