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Age at diagnosis predicts risk for contralateral breast cancer in BRCA carriers
BRCA1/2–positive women who are diagnosed with a first breast cancer when aged younger than 41 years appeared at greater risk for contralateral breast cancer, according to findings from a study conducted in the Netherlands.
Although it is known women with a BRCA1/2 mutation are at greater risk for contralateral breast cancer, the published 10-year risk estimates vary from 16% to 40%.
“The message that I hope clinicians and patients will take home from our research is that they should consider age at onset for risk prediction in BRCA1/2 mutation carriers,” Marjanka K. Schmidt, PhD, group leader of the division of molecular pathology at the Netherlands Cancer Institute-Antoni van Leeuwenhoek in Amsterdam, told HemOnc Today. “Although some breast cancer patients carrying a BRCA1/2 mutation are at relatively high risk for breast cancer, for certain subgroups this risk may not be as high as previously thought.”
Marjanka K. Schmidt
Schmidt and colleagues sought to prospectively determine age-specific and overall estimates of contralateral breast cancer risk among young patients with breast cancer among BRCA1/2 carriers vs. noncarriers. They also evaluated the impact of risk factors other than age.
The researchers identified 6,294 patients with breast cancer who were treated between 1970 and 2003 in 10 centers in the Netherlands. A majority of women did not harbor BRCA1/2 mutations (95.7%), whereas 3.2% harbored BRCA1 mutations and 1.1% harbored BRCA2 mutations.
After a median follow-up of 12.5 years, there were 578 incidences of contralateral breast cancers in the study population. These data equated to a significantly increased standardized incidence ratio (SIR) of contralateral breast cancer compared with the general population (SIR = 3.01; 95% CI, 2.77-3.27).
The 10-year cumulative risk for contralateral breast cancer was 21.1% (95% CI, 15.4-27.4) for BRCA1 carriers, 10.8% (95% CI, 4.7-19.6) for BRCA2 carriers and 5.1% (95% CI, 4.5-5.7) for noncarriers. Thus, the risk for contralateral breast cancer was two- to threefold higher among BRCA1 (HR = 3.31; 95% CI, 2.41-4.55) and BRCA2 (HR = 2.17; 95% CI, 1.22-3.85) than among noncarriers.
Age at time of diagnosis appeared to significantly predict risk for contralateral breast cancer only among women who harbored BRCA1 or BRCA2 mutations. Patients diagnosed when aged younger than 41 years had a 10-year cumulative contralateral breast cancer risk of 23.9% (BRCA1, 25.5%; BRCA2; 17.2%) compared with 12.6% (BRCA1, 15.6%, BRCA2, 7.2%) for those aged 41 to 49 years (HR = 1.89; 95% CI, 1.09-3.29). This association did not persist among noncarriers (HR = 1.06; 95% CI, 0.89-1.28).
Adjustments made for time interactions with oophorectomy, other second primaries of the breast or ovaries, local or regional recurrence, treatment given for the first breast cancer or estrogen receptor status of the first breast cancer did not alter the results.
When researchers reviewed previously published studies, they identified 10-year contralateral breast cancer risk estimates that ranged from 24% to 31% for women aged younger than 40 years at diagnosis (BRCA1, 24%-32%; BRCA2, 17%-29%) and from 8% to 21% for those aged older than 40 years (BRCA1, 11%-52%; BRCA2, 7%-18%).
“The data obtained by our team could be used to fine-tune online decision tools designed to help clinicians and patients decide upon the best course of action,” Schmidt said. “However, I think what’s very important now, is to develop absolute risk curves using prospective data from more recently diagnosed patients for patient counseling, including information about family history of breast cancer.”– by Anthony SanFilippo
For more information:
Marjanka K. Schmidt, PhD, can be reached at mk.schmidt@nki.nl.
Disclosure: One researcher reports an employment and leadership role with and stock or other ownership in Agendia NV. All other researchers and van den Broek reported no relevant financial disclosures.