Risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: a 30-year semi-prospective analysis

Abstract

BRCA1 and BRCA2 mutation carriers have an increased risk of contralateral breast cancer after primary breast cancer. Risk reduction strategies are discussed after assessment of risk factors for developing contralateral breast cancer. We assessed potential risk factors that could be of use in clinical practice, including the novel use of single nucleotide polymorphisms (SNP) testing. 506 BRCA1 and 505 BRCA2 mutation carriers with a diagnosis of breast cancer were observed for up to 30 years. The risk of a contralateral breast cancer is approximately 2-3% per year, remaining constant for at least 20 years. This was similar in both BRCA1 and BRCA2 carriers. Initial breast cancer before age 40-years was a significant risk factor, which was more pronounced in BRCA1 patients. The effect of risk-reducing oophorectomy on contralateral breast cancer risk may be overestimated because of bias. No significant association was found between overall breast cancer risk SNP score and contralateral breast cancer development. Young mutation carriers, particularly those with BRCA1 mutations, who develop breast cancer have a significantly higher risk of developing contralateral breast cancer, remaining constant for over 20 years. Contralateral risk-reducing mastectomy should be considered in this group, in particular as there is a survival benefit. Caution is advised when counselling women considering risk-reducing oophorectomy as, after accounting for statistical bias, the associated risk reduction was found to be non-significant, and potentially smaller than has been previously reported. SNP testing did not add any further discriminatory information when assessing contralateral breast cancer risk.

Contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers in a large cohort of unselected Chinese breast cancer patients

“…Most previous studies reported that BRCA1 and BRCA2 mutation carriers had a 25–42% and 18–32% risk to develop CBC after 10 years of the first breast cancer among Caucasian women or Jewish, respectively . In our study, the 10‐year cumulative risk of CBC was relatively lower.…”

“…Breast cancer patients carrying a deleterious BRCA1 or BRCA2 germline mutation have a high risk of developing primary contralateral breast cancer (CBC), with a 10‐year cumulative risk ranging from 10.8% to 42.0% . The broad range observed may be owing to the different study designs, ethnic populations and number of mutation carriers.…”

“…The broad range observed may be owing to the different study designs, ethnic populations and number of mutation carriers. Many studies recruit BRCA1/2 mutation carriers from a genetic test clinic, in which the mutation carriers may have a strong family history of breast cancer or early onset breast cancer, therefore the risk of CBC may be overestimated . Precise evaluation of the risk of CBC is crucial for optimal management for individuals with a BRCA1/2 mutation.…”

“…Moreover, the risk of CBC varies in different ethnic populations of BRCA1/2 mutation carriers . The penetrance and spectrum of BRCA1 and BRCA2 mutations in Chinese women are different from those in Caucasian women, and the breast cancer risk was approximately 37% by age 70 in BRCA1/2 mutation carriers in Chinese women compared to 45–66% in Caucasian women .…”

Outcomes and risk of subsequent breast events in breast‐conserving surgery patients with BRCA1 and BRCA2 mutation

“…These results were in line with the majority of published studies that derived the conclusion of no difference in local recurrence, 36 whereas increased incidence of CBC was associated with BRCA1/2 mutation. 4,22,[37][38][39][40][41] Till now, comprehensive research has been administrated to seek optimum prevention of CBC in BRCA mutation carriers.…”