Breast Cancer Genetics & Family History

The vast majority of breast problems are not inherited (passed on from parent to child). However, certain types of breast problem, and/or having a relative with a breast problem (family history) can be an indication of increased risk.

Identifying any increased risk or inherited problem is important because additional monitoring may be necessary to catch problems early.

We can help you understand your personal risk of developing breast cancer, and also offer genetic testing for abnormal genes such as BRCA1, BRCA2, and PLAB2.

The majority of breast cancers arise spontaneously (without any apparent cause) – with known risk factors that include exposure to hormones (oestrogen), reproductive history (no pregnancy or late first pregnancy) and lifestyle practices. However, a significant proportion (20-30%) of cancers will have an inherited (genetic) component, with family history remaining the strongest risk factor.

Approximately 5-10% of breast cancer will have a strong inherited component that can be divided according to strength of penetrance (extent to which a gene variation or mutation exhibits signs and symptoms of disease):


High Penetrance Genes

  • BRCA1
  • BRCA2
  • PALB2
  • TP53
  • PTEN
  • STK11
  • CDH1

Moderate Penetrance Genes

  • ATM
  • CHEK2
  • NF1
  • BARD1

Low Penetrance Genes

The advent of Genome wide association studies has rapidly enabled the identification of over 100 breast cancer single nucleotide polymorphisms (SNPs) that cause a small individual increase or decrease in breast cancer risk and work in a multiplicative manner (polygenic risk score).


The human BRCA1 gene (Chromosome 17 – codes for the breast cancer type 1 susceptibility protein) is involved in DNA repair. In the general population, approximately 1 in 500-900 will carry a mutation (pathogenic variant) in the BRCA1 gene – accounting for 7-10% of familial breast cancers. Those with a mutation in the gene will have a lifetime risk of breast cancer of approximately 60-85% and up to 60% for developing ovarian cancer. There is a rapid increase in breast cancer incidence in early childhood that plateaus and remains constant throughout the remaining adult life.

Approximately 70-80% of BRCA1 related breast cancers are ‘triple negative’ (not sensitive to oestrogen, progesterone and HER2 negative).



This DNA repair gene is situated on Chromosome 13.

Lifetime breast cancer risk has a wider range (40-85%) compared to BRCA1, and a slightly lower risk of developing ovarian cancer (20-30%) (14). Approximately 1 in 400-800 women carry a mutation that accounts for 10% of familial breast/ovarian cancer.

Other cancers are more commonly associated including:

Cholangiocarcinoma, melanoma, pancreatic cancer, gastric cancer and prostate cancer. Approximately 10% of Male breast cancer is associated with a BRCA2 mutation, a trend not seen in BRCA1 mutations.

Genetic Testing and Assessment of Risk

  • Genetic testing is now widely acceptable in the context of breast cancer. Individuals considering testing need to understand the following:
  • What genes are being tested and why
  • What are the possible result outcomes
  • What does genetic testing mean for my family
  • Understand how to access Breast Surgeon / Geneticist / Psychologist / Genetics Counsellor
  • What is and what is not offered in the NHS / Independent Sector
  • How to access risk-reducing strategies (surgery and other) in the NHS and Independent Sector
  • What appropriate screening is required – for the individual and the family

Risk of breast cancer is a combination of:

  • Family history and breast cancer genetics
  • Density of breast tissue on a mammogram (over 40s)
  • Lifestyle – modification of this can reduce up to a third of Breast Cancers
  • Exposure to hormones

There is growing concern about “Direct to Consumer” (DTC) genetic testing – online tests as a way to “find out what your DNA says.” Testing kits typically contain instructions and equipment for collecting a saliva sample, which customers post to the DTC company for analysis.

There is the risk of “clinical misinformation” if genetic testing remains unregulated. It is important to have access to healthcare professionals with experience of cancer genetics. The services we aim to offer are:

  • Breast Cancer risk assessment – using a combination of validated risk scores, gene testing, mammographic density assessment, SNP testing
  • Counselling for BRCA1/ BRCA2 / PALB2 / TP53 / PTEN / CDH / STK11 / ATM / BRIP2
  • Breast Cancer risk assessment in Lynch Syndrome / Cowden’s
  • Family History breast cancer assessment
  • Lifestyle advice to reduce breast cancer risk
  • Risk reducing mastectomy and reconstruction
  • Breast Screening
  • Referral to a “One stop” clinic for breast symptoms

How Can We Help?

Speak to our Acclaimed Oncologists and Surgeons

"Treat your patients as you would like your family members to be treated and you won’t go too far wrong."
Naren Basu
Lead Consultant Oncoplastic Breast Surgeon