THE VAST MAJORITY OF THOSE WITH BREAST CANCER report no family history of the disease. Despite this observation, universal genetic testing benefited patients with breast cancer and their physicians in implementing effective precision treatments and personalized disease management, according to study results published in JAMA Network Open. Today we look at breast cancer and inherited genes.
A range of factors contributes to your chance of getting breast cancer. You may be able to reduce some risks, while others you might have no control over. Today we explore the risk from inherited genes.
Breast cancer basics
Breast cancer is common, representing the second most commonly diagnosed cancer among women in the United States. Only skin cancer is more prevalent.
Approximately one in eight women in the USA will develop breast cancer. This number translates to an estimated 276,000 new cases of invasive breast cancer annually.
Male breast cancer represents less than one percent of all breast cancer diagnoses. Epidemiologists estimate there will be about 2,600 new breast cancer cases each year.
Here are the numbers for our British counterparts: Around 55,000 women and 370 men are diagnosed with breast cancer annually.
The affected number includes 46,000 in England, 4,700 in Scotland, 2,800 in Wales, and 1,500 in Northern Ireland. An additional 7,000 will be found in the United Kingdom annually with ductal carcinoma in situ (DCIS or intraductal carcinoma), an early non-invasive breast cancer form.
In Australia, 20,640 women and 212 men will develop breast cancer in 2022. Breast cancer is the second most commonly diagnosed cancer in Australia. Approximately one in seven women will be diagnosed with breast cancer.
Hereditary breast cancer basics
Approximately five to 10 percent of breast cancer (and 10 to 15 percent of ovarian cancers) are hereditary. Hereditary cancers are ones in which cancer runs in your family. Changes in certain genes that you inherited from a parent can be involved in cancer initiation.
Hereditary breast cancers tend to develop earlier in life (than non-inherited, sporadic) cases. New (primary) tumors are more likely to develop in both breasts.
Genes, made of DNA, are the software that creates instructions to build and maintain our cells. The DNA instructs the body what traits parents pass to their children, including hair and eye color, blood type, and the risks of getting certain diseases. We inherit one set of genes from our mother and one from our father.
Particular gene mutations associated with breast cancer appear more common among certain geographic or ethnic groups; for example, individuals of Ashkenazi (central or eastern European) Jewish heritage and people of Norwegian, Icelandic, or Dutch ancestry can have a higher risk.
BRCA genes
Cancer occurs when there are mutations in critical genes — ones that regulate cell growth and division or repair damaged DNA. When such changes in the genes occur, cells can grow and divide uncontrollably, forming a tumor.
Most breast cancer cases acquire these gene changes during a person’s lifetime and occur only in certain breast cells. Such mutations are known as somatic mutations.
Less frequently, gene mutations are in virtually all of the body’s cells, increasing breast cancer risk. These genetic changes are germline mutations, typically inherited from a parent. Germline mutations, changes in other genes, and environmental/lifestyle factors also influence breast cancer risk.
We sometimes see breast cancer clusters in families, a phenomenon associated with an inherited mutation in particular genes, such as BRCA1 or BRCA2 (BReast CAncer gene #1 or #2).
Genes such as BRCA are “high penetrance” ones; I mean that they are associated with a high risk of breast or ovarian cancer and a moderate risk of prostate and pancreas cancer.
Not all who have a BRCA mutation will develop cancer, but having such a gene mutation increases the cancer risk. For example, about 50 percent of women with a BRCA1 or BRCA2 mutation will be diagnosed with breast cancer by age 70, compared with seven out of 100 in the general USA population.
In addition, approximately 30 percent of women with a BRCA1 or BRCA2 mutation will get ovarian cancer by age 70. This percent represents high risk compared with fewer than one in 100 in the general USA population.
Those with a family history of breast cancer or inherited changes in BRCA genes have a higher breast cancer risk. Your healthcare team can guide you about ways to decrease your risk, including surgery (such as a prophylactic (risk-reducing) breast removal or prophylactic removal of the ovaries and fallopian tubes.
Others at high risk may consider medicines that block or decrease your body’s estrogen. Finally, screening tests are typically enhanced (for example, earlier breast cancer screenings, mammograms, and breast magnetic resonance imaging (MRI)).
A 2022 analysis discovered that BRCA1 variant genes appeared to be associated with biliary tract cancer, increasing the risk by over 17 times. Pathogenic variants in BRCA2 appeared to be associated with a 5.6-times higher risk of the esophagus. Finally, variants in BRCA1 and BRCA2 appear to increase stomach (gastric) cancer risk by 5.2- and 4.7 times, respectively.
Moreover, men with BRCA mutations have an increased risk of melanoma, breast, pancreas, and prostate cancer.
BRCA genes produce proteins involved in repairing damaged DNA. These genes are tumor suppressors, given that they help keep cells from growing and dividing fast or uncontrolled. Mutations in these genes impair DNA repair, allowing a cell to grow and divide without control.
Other genes
While BRCA gene mutations get most of the attention, several other genetic syndromes significantly increase breast cancer risk. Here are selected examples of higher-risk genetic syndromes:
- Cowden syndrome (typically caused by mutations in the PTEN gene)
- Hereditary diffuse gastric cancer (caused by CDH1 gene mutations)
- Li-Fraumeni syndrome (usually caused by mutations in the TP53 gene)
- Peutz-Jeghers syndrome (typically the result of mutations in the STK11 gene).
Mutations in these genes can also increase the risk of other types of cancer.
Other so-called “low or moderate penetrance” genes may play a role in breast cancer. Mutations in these genes appear to make only small to moderate contributions to breast cancer risk. Learn about other genes at this useful site:
https://medlineplus.gov/genetics/condition/breast-cancer/#synonyms
Many families cannot find the genetic changes associated with hereditary breast cancer. Research continues to identify these genes.
Finally, we have also identified numerous personal and environmental factors that can contribute to breast cancer risk for an individual.
Breast cancer risk factors include age, sex, ethnicity, a personal history of breast cancer, certain breast tissue changes, and reproductive and hormonal factors. A history of breast cancer in related family members can affect risk, as can exposure to cancer-causing (carcinogenic) compounds.
Genetic testing and breast cancer patients
A recent study suggests that we should do germline genetic testing for all patients with breast cancer. American researchers wondered how well the National Comprehensive Cancer Network (NCCN) guidelines predicted which patients have pathogenic germline variants.
A 2018 study showed that of almost 1,000 patients, there appeared to be no difference in the rate of pathogenic germline variants between patients with breast cancer who met NCCN criteria versus those who did not. Using the NCCN guidelines is associated with missing nearly half of pathogenic germline mutations for breast cancer patients.
The new study reveals this disturbing statistic:
Sixty-four percent of those with a genetic variant associated with an increased breast cancer risk did not meet NCCN testing criteria.
Offers senior study author Dr. Edward Esplin: “[These findings] led to physicians considering genetic testing beneficial for one-third of patients with either negative or variants of uncertain significance results.”
This investigation is the first prospective study to show the clinical utility of universal germline genetic testing for patients with breast cancer. I think that it may be time for universal genetic testing for those with breast cancer.
Thank you for joining me in this look at genetic testing for breast cancer patients. Thank you for joining me for this look at breast cancer and genes. If you enjoyed this piece, please sign up to follow me on this blog site. One more thing:
The information I provided in this blog is for educational purposes only and does not substitute for professional medical advice. Please consult a medical professional or healthcare provider if you seek medical advice, diagnoses, or treatment. I am not liable for risks or issues associated with using or acting upon the information in this blog.
