Breast cancer is a complex disease with various risk factors, including age, family history, lifestyle, and genetics. BRCA1 and BRCA2 mutations, discovered in the 1990s, are crucial in breast cancer diagnosis and prevention. While most cases are not directly linked to inherited genetics, a subset of individuals carry mutations in these genes, increasing their susceptibility. This exploration delves into the genetic underpinnings of breast cancer, their role, and their impact on individuals and their families.

Factors for Breast Cancer
Genetic mutations, particularly BRCA1 and BRCA2, play a crucial role in breast cancer diagnosis and treatment decisions. Let's explore the significance of these mutations in breast cancer.

• Hereditary Risk Factors: BRCA1 and BRCA2 are genes responsible for repairing DNA damage in cells. When mutations occur in these genes, it can lead to a higher risk of breast cancer. Individuals with a family history of breast or ovarian cancer are more likely to carry these mutations.


• Increased Breast Cancer Risk: Carrying BRCA1 or BRCA2 mutations significantly elevates an individual's lifetime risk of developing breast cancer. Women with these mutations have a 45-65% chance of developing breast cancer by the age of 70, compared to the general population's 12% risk.


• Ovarian Cancer Risk: BRCA1 and BRCA2 mutations are also associated with an increased risk of ovarian cancer. Women with these mutations have a 39-46% lifetime risk of ovarian cancer compared to 1.3% in the general population.


• Younger Age of Diagnosis: Carriers of BRCA1 and BRCA2 mutations tend to develop breast cancer at a younger age than non-carriers. This earlier onset can impact diagnosis, treatment, and long-term survival.


• Aggressive Tumor Types: BRCA1-associated breast cancers are often characterised by aggressive features, including high-grade tumors and triple-negative breast cancer (TNBC), which can be more challenging to treat.


• Screening and Early Detection: Individuals with BRCA1 or BRCA2 mutations benefit from personalised screening and surveillance programs. This includes more frequent mammograms, breast MRIs, and clinical breast exams to detect cancer at an earlier, more treatable stage.


• Treatment Decisions: The presence of BRCA mutations can influence treatment decisions. For instance, BRCA-associated breast cancers may respond better to certain chemotherapy drugs, such as platinum-based therapies or PARP inhibitors.


• Genetic Counseling and Testing: Genetic counselling and testing can identify BRCA1 and BRCA2 mutations. Knowledge of one's mutation status can help individuals make informed decisions about their health, family planning, and cancer risk management.


• Family Risk Assessment: Identifying a BRCA1 or BRCA2 mutation in one family member can prompt testing and risk assessment for other family members. This cascade testing can help identify individuals at risk and guide their healthcare decisions.


• Research and Advancements: The study of BRCA1 and BRCA2 mutations has led to significant advancements in breast cancer research. Insights gained from these mutations have paved the way for targeted therapies and a deeper understanding of the disease.

What do the BRCA1 and BRCA2 Genes entail?
BRCA1 and BRCA2 are two important genes that are associated with an increased risk of breast cancer, as well as ovarian cancer and some other cancers. Here's a brief overview of these genes and their role in breast cancer:

BRCA1 (Breast Cancer gene 1):
BRCA1 is a tumor suppressor gene, which means it normally helps regulate cell growth and prevent the formation of tumors. Mutations in the BRCA1 gene can lead to an increased risk of breast cancer. Women with BRCA1 mutations have a significantly higher lifetime risk of developing breast cancer compared to those without these mutations. BRCA1 mutations are also associated with an increased risk of ovarian cancer and other types of cancer.

BRCA2 (Breast Cancer gene 2):
Like BRCA1, BRCA2 is another tumor suppressor gene. It plays a role in DNA repair and stability. Mutations in the BRCA2 gene are also associated with an increased risk of breast cancer, although the risk is somewhat lower compared to BRCA1 mutations. BRCA2 mutations are also linked to an increased risk of ovarian cancer, as well as prostate cancer and some other cancers.

BRCA1 and BRCA2 mutations increase cancer risk, and genetic testing aids in family history management. Advances in genetic testing offer personalized cancer risk assessment and management.

How is BRCA1 and BRCA2 gene involvement measurement used in breast cancer diagnosis?
BRCA1 and BRCA2 gene involvement measurement can be done in two ways:

Genetic testing: Genetic testing is a direct method for measuring BRCA1 and BRCA2 gene involvement in breast cancer diagnosis, identifying mutations that increase the risk. It's recommended for individuals with a strong family history or those diagnosed at a young age.

Tumor testing: Tumor testing measures BRCA1 and BRCA2 gene involvement in breast cancer diagnosis by examining changes in breast cancer tissue. Although not as accurate as genetic testing, it may be useful for individuals with a strong family history of breast cancer who cannot undergo genetic testing.

BRCA1 and BRCA2 Genes Mutations
BRCA1 gene mutations can spike the likelihood of breast cancer in women to 60-80%, along with elevating the risk of ovarian cancer in women and prostate cancer in men. Meanwhile, BRCA2 gene mutations, found in about 35% of families with early-onset breast cancer in women, also increase the risk of ovarian cancer in women and breast cancer in men.

Breast cancer triggered by BRCA1 mutations stands out with higher incidence, a brisk mitotic rate, and increased lymphatic infiltration compared to sporadic breast cancer. It's more prone to lacking ER, PR, and HER-2 neu receptor expression, and often bears a somatic mutation in the P53 gene.

Carriers of BRCA1 or BRCA2 gene mutations face heightened risks of other cancers like colon, prostate, pancreatic, melanoma, and gastric cancers. Novel mutations in these genes are exceedingly rare, with just around 2000 mutations discovered so far. These mutations take various forms, including small insertions, deletions, nonsense mutations, missense mutations, premature transcription termination, and splicing abnormalities. Deletion and insertion mutations can disrupt the reading frame, while splicing mutations result in non-functional proteins. According to BIC (Breast Information Core), most of the mutations implicated in breast cancer involve the creation of truncated proteins through nonsense, frame shift, and splicing mutations.
Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4972064/

Conclusion: BRCA1 and BRCA2 genes play a crucial role in the breast cancer puzzle. Understanding their significance empowers individuals and healthcare professionals in making informed decisions about screening, prevention, and treatment. Genetic testing reveals these mutations, aiding risk assessment and proactive strategies. While these mutations may increase breast cancer risk, awareness and knowledge allow individuals to take control of their health and work towards a future where breast cancer is less formidable. To know more - please contact us at +91(79) 49006800 or visit www.unipath.in