A study suggests that there are differences in the characteristics of cancers linked to a BRCA1 mutation compared to those of cancers linked to a BRCA2 mutation in men.
The research was published online on July 2, 2020, by the journal JAMA Oncology. Read the abstract of “Characterization of the Cancer Spectrum in Men With Germline BRCA1 and BRCA2 Pathogenic Variants: Results From the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA).”
About genetic mutations
A germline variant is a change, or mutation, in a gene that is inherited from your parents and is in all your DNA.
“Pathogenic” means the mutation is harmful and usually linked to a disease — in many cases, cancer.
Two of the most well-known genes that can mutate and raise the risk of breast and/or ovarian cancer are BRCA1 and BRCA2. Women who inherit a harmful mutation in either of these genes — from their mothers or their fathers — have a much higher-than-average risk of developing breast cancer and/or ovarian cancer. Men with these mutations have an increased risk of breast cancer, especially if the BRCA2 gene is affected, and possibly of prostate cancer. Many inherited cases of breast cancer have been associated with mutations in these two genes.
The function of the BRCA genes is to keep breast cells growing normally and prevent any cancer cell growth. But when these genes contain mutations that are passed from generation to generation, they do not function normally and breast cancer risk increases. Overall, mutations in the BRCA1 and BRCA2 genes may account for up to 10% of all breast cancers, or 1 out of every 10 cases.
While breast cancer in men is rare, it does happen. Less than 1% of all breast cancers are diagnosed in men. Research suggests that BRCA1 mutations account for up to 2% of breast cancers in men and BRCA2 mutations account for up to 13% of breast cancers in men.
Because the number of men diagnosed with breast cancer is small, there is limited information on the characteristics of cancers linked to BRCA1 and BRCA2 mutations in men, as well as whether each mutation is linked to different cancer characteristics. That’s why the researchers did this study.
About the study
To do the study, the researchers looked at information from people recruited from cancer genetic clinics from 1966 to 2017. The study included 6,902 men from 33 countries and found that:
- 3,651 men had a BRCA1 mutation
- 3,251 men had a BRCA2 mutation
All the information is part of a database maintained by the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). The goal of CIMBA is to give researchers enough participant information to conduct large studies on the effects of BRCA1 and BRCA2 mutations.
All the men in the study were older than 18. The information collected on each man included:
- year of birth
- age at cancer diagnosis, if diagnosed
- primary tumor site
- clinical information on the cancer
About 77% of the men classified themselves as white.
The main goal of the study was to compare cancer diagnoses between men with a BRCA1 mutation and men with a BRCA2 mutation.
Overall, 1,376 men (19.9%) were diagnosed with cancer:
- 454 men (12.4%) with a BRCA1 mutation were diagnosed with cancer
- 922 men (28.4%) with a BRCA2 mutation were diagnosed with cancer
Of the 1,144 men with one cancer diagnosis:
- 50 men with a BRCA1 mutation and 330 men with a BRCA2 mutation were diagnosed with breast cancer
- 83 men with a BRCA1 mutation and 190 men with a BRCA2 mutation were diagnosed with prostate cancer
- 283 men with a BRCA1 mutation and 208 men with a BRCA2 mutation were diagnosed with cancer other than breast or prostate
Of the 206 men with two cancer diagnoses:
- 0 men with a BRCA1 mutation and 24 men with a BRCA2 mutation were diagnosed with breast cancer in both breasts
- 4 men with a BRCA1 mutation and 49 men with a BRCA2 mutation were diagnosed with breast and prostate cancer
- 8 men with a BRCA1 mutation and 51 men with a BRCA2 mutation were diagnosed with breast cancer and a second cancer that wasn’t breast or prostate
- 23 men with a BRCA1 mutation and 46 men with a BRCA2 mutation were diagnosed with prostate cancer and a second cancer that wasn’t breast or prostate
- 1 man with a BRCA1 mutation and 0 men with a BRCA2 mutation were diagnosed with two cancers other than breast and prostate
Of the 26 men with three cancer diagnoses:
- 0 men with a BRCA1 mutation and 5 men with a BRCA2 mutation were diagnosed with breast cancer in both breasts and prostate cancer
- 0 men with a BRCA1 mutation and 7 men with a BRCA2 mutation were diagnosed with breast cancer in both breasts and a third cancer other than breast and prostate
- 1 man with a BRCA1 mutation and 0 men with a BRCA2 mutation were diagnosed with prostate cancer and two other cancers that were not breast or prostate
- 1 man with a BRCA1 mutation and 12 men with a BRCA2 mutation were diagnosed with breast, prostate, and a third cancer that was not breast or prostate
The researchers noted that all the men diagnosed with breast cancer in both breasts had a BRCA2 mutation.
Both breast and prostate cancers were diagnosed more frequently in men with a BRCA2 mutation than in men with a BRCA1 mutation.
Overall, being diagnosed with any type of cancer was linked to a higher likelihood of having a BRCA2 mutation than a BRCA1 mutation.
Similarly, being diagnosed with more than one cancer was linked to a higher likelihood of having a BRCA2 mutation than a BRCA1 mutation.
For men diagnosed with a first cancer that was not breast or prostate cancer, the average age at first diagnosis was 61.8 for men with a BRCA1 mutation and 56.5 for men with a BRCA2 mutation.
“Our results highlight specific, unique differences in the cancer spectrum of male BRCA2 vs BRCA1 [mutation] carriers,” the researchers wrote. “Being affected with cancer and developing multiple cancer types at younger ages was associated with a higher probability of being a BRCA2 [mutation] carrier.”
What this means for you
The researchers believe that this is the largest study done so far on men with a BRCA1 or BRCA2 mutation. The results show that the characteristics of cancers diagnosed in men with a BRCA2 mutation are different from the characteristics of cancers diagnosed in men with a BRCA1 mutation.
If you’re a man, you’re much more likely to have a BRCA1 or BRCA2 mutation if:
- You have female relatives on either your mother's or father's side of the family who had breast cancer diagnosed before age 50.
- There is both breast and ovarian cancer on the same side of the family or in a single individual.
- There are other cancers in your family in addition to breast, such as prostate, melanoma, pancreatic, stomach, uterine, thyroid, colon, and/or sarcoma.
- Women in your family have had cancer in both breasts.
- You are of Ashkenazi Jewish (Eastern European) heritage.
- A man in your family has had breast cancer.
If you are a man and know that you have a BRCA1 or BRCA2 mutation or have a strong family history of breast or prostate cancer, it’s recommended that you have a breast exam by your doctor every year and do a monthly breast self-exam.
It’s also very important that you be aware of any signs that might indicate breast cancer.
Talk to your doctor right away about any changes in your breasts, including:
- nipple pain
- inverted nipple
- nipple discharge
- sores on the nipple and/or areola area
- enlarged lymph nodes under the arm
Because many men don’t consider the possibility that they may develop breast cancer, they may wait a year or longer to talk to their doctor after noticing a breast symptom. This means the cancer is diagnosed at a later stage.
For more information, visit the Breastcancer.org pages on Male Breast Cancer.
If you're a man who has been diagnosed with breast cancer and would like to talk with others, join the Breastcancer.org Discussion Board forum Male Breast Cancer.
Written by: Jamie DePolo, senior editor
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