Triple-negative breast cancer (TNBC) – which when examined by a pathologist lacks expression of the estrogen receptor, the progesterone receptor, and HER2 – accounts for a little more than 1 out of every 7 breast cancer cases. Not infrequently, it occurs in younger women and also is the most common breast cancer type in women with a Hereditary Breast and Ovarian Cancer-predisposing BRCA1 gene mutation.
The connection between BRCA1 mutations and TNBC has led clinical researchers and cancer geneticists to question whether the presence of TNBC in a young women should be utilized clinically as a signal that she should be offered testing for genetic predisposition to Hereditary Breast and Ovarian Cancer. This is potentially quite important information, as the identification of a BRCA1 mutation in the woman often can impact both clinical management decisions for the breast cancer and have implications for future health decision-making for both the woman with breast cancer and other family members who may be at risk.
In most countries where it is available, BRCA1 and BRCA2 testing is often limited by either insurance reimbursement or other logistical constraints to women who based on personal and family history of cancer are determined by expert interpretation and/or clinical algorithms to have greater than a ~10-20 percent chance of having a mutation. Recently, a number of small studies have assessed the frequency of BRCA1 mutations in series of women with TNBC who in some cases were selected based on additional cancer family history or young age. In general, these studies have suggested that BRCA1 mutations are relatively frequent in this group even when unselected for age or family history. A new study from Dr. Nazneen Rahman and colleagues in the United Kingdom is the largest study to date and has significant implications for decisions about eligibility for BRCA testing.
The Researchers Studied More Than 300 Triple-Negative Breast Cancer Cases from the U.K.
In all, 308 TNBC cases were collectively studied by the researchers. These were drawn from several different studies. A subset were from studies that were unselected with respect to likelihood of BRCA mutations, and another subset were from studies that should be enriched for patients with BRCA mutations (because of use of family history and/or young age at breast cancer diagnosis as entry criteria for the study).
BRCA1 Mutations Were Relatively Common – Even in the Unselected TNBC Cases
BRCA1 mutations were found in 45 of the 308 women (15%) in this study. As would be expected, they were more frequent in the women from the studies where the entry criteria selected for women with a higher likelihood of having a mutation. For women from these studies who were younger than 50 at the time of their TNBC diagnosis, 23% were found to have a BRCA1 mutation.
However, the most interesting finding was that women from the studies where there was no selection for mutation likelihood still had a rather high chance of having a BRCA1 mutation. Overall, this group had a 9.4% chance of having a mutation – just a shade under the 10% figure that is often used as a cutoff for reimbursement or for accessing genetic services in many countries. Most importantly, the women from the unselected group diagnosed with TNBC before age 50 had a 19% chance of having a BRCA1 mutation! Many of these women would not have been tested if current U.K. criteria for genetic testing eligibility were applied.
Bottom Line Implications for Young Women with Triple-Negative Breast Cancer
1. Regardless of family history of cancer, if you were diagnosed with a triple-negative breast cancer before age 50, your chance of having a BRCA1 mutation is likely in the ballpark of 20% or about 1 in 5. If this sounds like you, please look into options for genetic counseling and testing as it may have important implications for your healthcare and also for your relatives.
2. As the group of women with TNBC in general had a BRCA1 mutation rate that was just a hair under 10%, women with TNBC diagnosed at 50 or older should consider discussing their personal and family history of cancer with a genetics provider, as women like this who have a significant family history of breast and/or ovarian cancer or multiple primary cancers should be considered for genetic testing.
3. As DNA sequencing is getting much cheaper, we are moving towards a world in which genetic diagnostics should become much cheaper. In most countries, this is likely to happen much more slowly for BRCA1 and BRCA2 testing because intellectual property currently limits the degree of competition in the space. At some point in the future, cutoffs for genetic testing eligibility will no longer make sense after the cost of the diagnostic testing gets low enough.
4. Consensus document development committees, third-party payors, public health bodies and others developing recommendations for BRCA1/2 testing eligibility need to carefully consider the data from this new study, and at a minimum, encourage and pay for BRCA testing (particularly BRCA1) for all individuals diagnosed with a triple-negative breast cancer before age 50. Additionally, as the frequency of BRCA1 mutations in triple-negative breast cancer cases was nearly 10% when all TNBC cases were considered regardless of age, it may be worth considering whether any individual with TNBC should be tested regardless of family history.
How We Know This:
Robertson L, Hanson H, Seal S, et al. BRCA1 testing should be offered to individuals with triple-negative breast cancer diagnosed below 50 years. British Journal of Cancer 2012 (published online before print Feb 14 2012)
You may also be interested in BRCAscoop.com – our site focused on issues relevant to individuals who already know they have BRCA1 and BRCA2 mutations.