Guest Author: Ms Payal Manek
Specialist Genetic Counselor, Strand Life Sciences
Breast cancer is now the most common cancer in most cities in India. Many personal and environmental factors like gender, age, ethnic background, previous diagnosis of breast cancer and hormonal and reproductive factors contribute to a person’s risk of developing breast cancer.
In some families, clusters of individuals with breast cancers are seen across and through one or two generations. Such cancers are called hereditary cancers and known to be associated with inherited gene mutations. Hereditary breast cancers tend to develop earlier in life and are more likely to affect both breasts.
In general, individuals with hereditary breast cancer syndromes are at an increased risk of being affected with multiple cancers, not just breast cancer. Also, the unaffected/healthy members of these families can carry mutations in their genes that greatly increase their lifetime risk to many cancers. Affected members of these families, given their high risk of developing cancer, should be under lifelong surveillance and need to be offered preventive management options.
Cancer risks vary by syndrome
A very high risk to breast cancer is caused due to inherited mutations in BRCA1 and BRCA2 genes. They cause Hereditary Breast and Ovarian Cancer syndrome that are also associated with increased cancer risk in ovaries, male breast cancer, pancreatic and prostate cancer.
A significantly increased risk of breast cancer is also a feature of several rare genetic syndromes. These include Cowden syndrome, which is most often caused by mutations in the PTEN gene; hereditary diffuse gastric cancer, which results from mutations in the CDH1 gene; Li-Fraumeni syndrome, which is caused by mutations in the TP53 gene; and Peutz-Jeghers syndrome, which typically results from mutations in the STK11 gene.
Elevated risk to breast cancer is caused by mutations in some genes including ATM, CHEK2, NBN, NF1, PALB2.
Genetic test outcomes have real benefits for patients and their families
It is good to understand that some genes, when they malfunction, can cause cancers. How is this knowledge going to help common people, you ask? Genetic tests are designed to identify gene mutations which put an individual at a higher risk of developing a cancer. A negative test result can provide a sense of relief and reduce the anxiety of the individual or family members. It can reduce the need for, or at least the intensity of, check-ups, screening and preventive therapy. A positive test result is also a win-win situation! It can help in therapy and current disease management, earlier disease detection, and more targeted surveillance. Importantly, it can also serve as an effective prevention strategy by motivating a person to make behavioural changes that lower their chances of getting cancer.
The list of genes that are associated with hereditary breast cancers include ATM, BRCA1, BRCA2, BRIP1, CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, NBN, NF1, PALB2, PMS2, PTEN, RAD51C, RAD51D, STK11*, TP53 – all covered in the Strand Hereditary Cancer Test. Yet, scientific researchers continue to investigate and identify more genes, which is why this list is constantly updated.
The most common breast cancer syndromes along with their causative genes and lifetime breast cancer risks (compared to the population average risk of 12%) are summarized in this table.
|Syndrome||Genes||Increased breast cancer risk|
|Hereditary Breast and Ovarian Cancer (HBOC)||BRCA1||46-87%|
|Hereditary Diffuse Gastric Syndrome (HDGS)||CDH1||39-52%|
|Li Fraumeni Syndrome||TP53||27%|
For all these syndromes, doctors have agreed a schedule of recommended management options that apply both for existing cancer patients and those that wanted to know their personal risk and were found to be mutation carriers. In all such cases, bi-annual clinical breast examinations as well as mammograms and breast MRIs performed alternately every six months are recommended to catch any cancer incidence or recurrence as early as possible.
Note: This information was collated from published references and international guidelines which can be provided on request. It is not intended to be medical advice and you should always consult a doctor with your specific concerns.