- 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.