The Sequence 10/28-11/3
Understanding Second Primary Cancer Risks in BRCA Carriers
Understanding Second Primary Cancer Risks in BRCA Carriers
Pathogenic, or harmful, genetic variants in the BRCA1 or BRCA2 genes cause 5% to 10% of all breast cancer cases. People with pathogenic variants in BRCA1 or BRCA2 have a diagnosis of hereditary breast and ovarian cancer syndrome (HBOC). Even in the name itself, it’s pretty clear that this syndrome increases risk for at least two different types of cancer: breast and ovarian. In reality, HBOC syndrome increases risk for multiple cancers beyond those two. It follows that people with HBOC are at greater risk for second primary cancers (SPCs) than the general population. Today, I’ll discuss a study analyzing the relative and absolute risks of SPC after breast cancer in BRCA1 and BRCA2 pathogenic variant carriers.
What is a second primary cancer?
It’s important to distinguish SPC from cancer that has metastasized or spread from one area of the body to another. An SPC is the development of an unrelated cancer in a person previously diagnosed with cancer. According to the National Cancer Institute, one in five people diagnosed with cancer has had previous cancer diagnoses.
To use HBOC as an example, someone could have been previously diagnosed with breast cancer and then develop ovarian cancer later in life. Another example would be if someone was previously diagnosed with cancer in the left breast and then develops a different type of cancer in the right breast. This would be referred to as a second primary malignancy because it is not related to the first diagnosis. People with inherited predispositions for certain types of cancers, such as HBOC, are inherently at greater risk for SPCs, one of many reasons genetic testing for hereditary cancer is so important.
What are the known second primary cancer risks in BRCA carriers?
For individuals with pathogenic variants in BRCA1/2, the known SPC risks include an increased likelihood of developing a second primary breast cancer, as well as cancers like ovarian, fallopian tube, peritoneal, male breast, pancreatic, and prostate cancers. Several studies have reported higher rates of contralateral breast cancer in individuals with pathogenic variants in BRCA1/2; especially among women whose initial breast cancer occurs at a young age. In a literature review of studies on contralateral breast cancer risk after a first primary invasive breast cancer in females with pathogenic variants in BRCA1/2, the cumulative 5-year risk of contralateral breast cancer was 15% in BRCA1 and 9% in BRCA2 variant carriers. The risk increased with time since initial diagnosis, with the 10-year risk increasing up to 27% and 19%, respectively. However, the risks for other SPCs after breast cancer in BRCA1/BRCA2 pathogenic variant carriers has not been thoroughly studied.
What did the new study find?
The recent study followed 25,811 females and 480 males diagnosed with breast cancer and tested for germline BRCA1/BRCA2 pathogenic variants. Compared with females without BRCA1/BRCA2 variants on testing, BRCA1 carriers had elevated incidence of contralateral breast cancer, ovarian, combined nonbreast/ovarian, and colorectal SPC risks. BRCA2 carriers had elevated incidence of contralateral breast cancer, ovarian, and pancreatic SPC risks. Ten-year cumulative risks in BRCA1 carriers were 16%, 6.3%, and 7.8% for contralateral breast cancer, ovarian, and combined nonbreast/ovarian cancer respectively. Ten-year cumulative risks in BRCA2 carriers were 12%, 3.0%, and 6.2% for contralateral breast cancer, ovarian, and combined nonbreast/ovarian cancer respectively. In comparison, ten-year cumulative risks for non-carriers were and 3.6%, 0.4%, and 4.9% for contralateral breast cancer, ovarian, and combined nonbreast/ovarian cancer respectively. Additionally, male BRCA2 carriers had higher contralateral breast cancer and prostate SPC risks than noncarriers.
What’s the takeaway?
Individuals with pathogenic variants in BRCA1 or BRCA2 are at a significantly increased risk of developing SPCs after a breast cancer diagnosis. This study confirms what we knew about carriers having a higher risk of contralateral breast cancer compared to non-carriers, and introduces data surrounding the elevated risks of ovarian and colorectal cancers, as well as other non-breast or ovarian cancers. Understanding these elevated risks is crucial for proactive cancer screening and management strategies in individuals with pathogenic variants in BRCA1 or BRCA2.
Newsletter Sources:
Images: https://www.canva.com/photos/MACFVVKXB0s/
https://www.yalemedicine.org/conditions/hereditary-breast-and-ovarian-cancer-syndrome-hboc
https://www.cancer.gov/publications/dictionaries/cancer-terms/def/second-primary-cancer
https://ascopubs.org/doi/abs/10.1200/JCO.24.01146?af=R&utm_source=Sailthru&utm_medium=email&utm_campaign=Scan%20Weds%202024-10-30&utm_term=The%20Scan%20Bulletin
https://www.patientpower.info/navigating-cancer/secondary-primary-cancer
https://dceg.cancer.gov/research/what-we-study/second-cancers#:~:text=Nearly%20one%20in%20five%20cancers%20diagnosed%20today,of%20morbidity%20and%20mortality%20among%20cancer%20survivors.
https://www.ncbi.nlm.nih.gov/books/NBK1247/#:~:text=BRCA1%2D%20and%20BRCA2%2Dassociated%20hereditary%20breast%20and%20ovarian%20cancer%20(,cancer%2C%20pancreatic%20cancer%2C%20and%20melanoma
https://pubmed.ncbi.nlm.nih.gov/25467311/
https://www.verywellhealth.com/what-is-a-second-primary-cancer-2248872
https://pubmed.ncbi.nlm.nih.gov/26700119/
https://pubmed.ncbi.nlm.nih.gov/32037537/
https://theweeklysequence.substack.com/p/the-sequence-826-91