What Are the Genetic Causes of Breast Cancer?

What Are the Genetic Causes of Breast Cancer?

Familial Breast Cancer

Breast cancer is a disease that occurs with the uncontrolled growth and differentiation of cells in the breast. It is the most common type of cancer in the world and is seen in one of every 8 women.

According to the report of WHO (World Health Organization), 2.3 million women were diagnosed with breast cancer in 2020 and 685,000 patients died due to breast cancer. The incidence increases with increasing age.

Signs and Symptoms

  • A painless mass or thickening in the breast or armpit
  • Change in the size, shape or appearance of the breast
  • pitting, redness of the skin surrounding the nipple or nipple (areola)
  • Abnormal nipple discharge

Risk Factors for Breast Cancer

  • Female gender
  • Rising age
  • Obesity
  • Radiation exposure
  • Smoking and alcohol use
  • Reproductive history (early menstruation, first pregnancy age above 30, etc.)
  • Familial predisposition

Familial Breast Cancer

About 5-10% of breast cancer cases are familial (inherited from mother or father). Familial breast cancer is most commonly caused by mutations (errors) in the BRCA1 or BRCA2 genes.

BRCA1 and BRCA2 are genes involved in repairing damaged DNA. Our cells have 2 copies, each inherited from a different parent. Mutations in one of these genes can cause cancer in organs such as the breast, ovary, fallopian tube, peritoneum, pancreas, prostate, and skin. People who carry these mutations, inherited from their parents, tend to develop cancer at an earlier age than those without the mutation.

How much do mutations in BRCA1 or BRCA2 increase the risk of breast and ovarian cancer?

A woman with a mutation in BRCA1 or BRCA2 has a significantly increased risk of developing breast and/or ovarian cancer throughout her life. However, the degree of increase varies depending on the mutation.

MBreast Cancer

  • About 13% of women will get breast cancer at some point in their lives.
  • 55-72% of women with harmful variants in the BRCA1 gene develop breast cancer by age 70-80.
  • 45-69% of women with harmful variants in the BRCA2 gene develop breast cancer by the age of 70-80.
  • Patients with harmful variants in the BRCA1 or BRCA2 genes have an increased risk of developing cancer in the other breast over time.

Ovarian Cancer

  • About 1.2% of women will develop ovarian cancer at some point in their lives.
  • 39-44% of women with harmful variants in the BRCA1 gene develop ovarian cancer by the age of 70-80.
  • 11-17% of women with harmful variants in the BRCA2 gene develop ovarian cancer by the age of 70-80.

What other cancers are associated with deleterious variants in the BRCA1 and BRCA2 genes?

Genetic counseling and genetic testing for BRCA1 and BRCA2 variants In particular, people with a family or personal history of cancer should consult with a Medical Genetics physician before and after the test.

What do BRCA1 and BRCA2 genetic test results mean?

BThe RCA1 and BRCA2 mutation test is evaluated in the light of current knowledge and yields several possible results: a positive result (pathogen, probable pathogen), a negative result (benign, probable benign), or variant of unknown significance (VUS).

Positive Result

  • A positive test result indicates that the person carries a known deleterious variant (typically called "pathogenic" or "probably pathogenic" variants in laboratory test reports) in the BRCA1 or BRCA2 genes and has an increased risk of developing certain cancers.
  • However, it cannot tell whether or when the person being tested will develop cancer. Some people who carry a harmful BRCA1 or BRCA2 variant never develop cancer.
  • Man or woman who carries a harmful BRCA1 or BRCA2 variant can pass it on to their children, even if they do not develop cancer themselves.
  • Very rarely, an individual may carry a harmful variant that is absent from both parents. This variant is called the de novo (or "new") variant.
  • A positive test result has important implications for family members, including future generations.

Negative Result

  • There is a known harmful change in the BRCA1 or BRCA2 genes in the family, but this variant is not observed in the person tested; means that this person does not inherit the harmful variant in the family and will not pass it on to their children.
  • A person's risk of developing cancer is considered to be equivalent to the incidence of cancer in the general population.
  • However, in the evaluation of cancer risk, besides genetic factors, the existence of other factors that may increase the risk of cancer should also be considered.

Variant of Unknown Significance (VUS) Result

  • Sometimes finds a variant in the BRCA1 or BRCA2 genes that has not been previously associated with cancer and is rare in the population. This variant is called the "variant of unknown significance" or VUS. Because it is not yet known whether this genetic change is harmful.
  • Over time, as more research is done and more people tested, more will be learned about these uncertain changes.
  • Until the interpretation of the variant is clarified, the variant is periodically re-evaluated in the light of current data. In such cases, risk management should be based on family history and other risk factors.

What are the benefits of genetic testing?

  • Provides advanced screening, early diagnosis and follow-up.
  • It is also important for the individual to understand their potential risk of developing other cancers in the future.
  • The risky individuals in the family are determined and screening, risk-reducing behavioral choices and early diagnosis are provided to them.
  • The option of surgery to reduce the risk of developing cancer is offered.
  • Protective drug therapy can be applied and information about mutations may be important in treatment selection.