Abstract P2-07-05: Risk of metachronous contralateral breast cancer: Systematic review and meta-analysis
Authors: Akdeniz D , Schmidt MK , McCool D , van den Broek AJ , Hauptmann M , Seynaeve CM , Steyerberg EW , Hooning MJ 
Published: March 2017

Abstract
Introduction
Over the last 2 decades, an increasing number of primary breast cancer (PBC) patients opted for a risk reducing contralateral mastectomy, to minimize risk of subsequent contralateral breast cancer (CBC). Therefore, accurate risk estimates of CBC are important for patient tailored counseling and decision making regarding treatment. Currently, CBC risk estimates are determined by BRCA1/2 mutation status, age at PBC diagnosis and family history. For other risk factors, results are inconclusive.
We therefore aimed to quantify the association with CBC risk for patient, tumor and treatment related factors as reported in the literature.
Methods
Medline was searched for publications on CBC risk by one reviewer (DA). We focused on associations between CBC risk and BRCA1/2 and CHEK2*1100delC mutations, SNPs, risk-reducing salpingo-oophorectomy and various factors at PBC diagnosis: family history of breast cancer (BC), age, BMI, menopausal status, mammographic density, TNM-stage, receptor status, morphology, administered radiotherapy and adjuvant systemic treatment.
Eligible papers were published in English between 01-01-1990 and 01-04-2015, investigated female patients with invasive early BC and reported relative risk (RR) estimates (i.e., hazard ratios, relative risks or odds ratios).
We combined RR estimates using a random effects model. Heterogeneity was assessed using the I2 statistic. Forest plots for crude and adjusted estimates were generated stratifying for mutation status (i.e., BRCA1, BRCA2, CHEK2*1100delC), non-carriers and unselected patients (i.e., population/hospital based cohorts).
Results
After screening of 1,423 papers for title and abstract, 173 eligible papers were fully read, and 96 papers fulfilled the inclusion criteria.
Both in the unselected group and in the BRCA1 and BRCA2 groups, administration of adjuvant endocrine therapy (vs. not), was associated with decreased CBC risk (RR, 0.62 (95% CI 0.55-0.69), 0.55 (95% CI 0.39-0.77), and 0.62 (95% CI 0.40-0.95), respectively). Adjuvant chemotherapy was associated with reduced CBC risk in unselected patients (RR 0.73; 95% CI 0.62-0.86).
CBC risk was increased in unselected patients who received radiotherapy at age&lt;40 years (vs. not) (RR 1.33; 95% CI 1.18-1.49), had a lobular (vs. ductal) PBC (RR 1.70; 95% CI 1.33-2.16), had a T2/T3 (vs. T1) PBC (RR 1.15; 95%CI 1.01-1.30), with BMI &gt;30 (vs. &lt;25) at PBC (RR 1.50; 95% CI 1.27-1.76) or had a positive family history for BC (vs. not) (RR 1.82; 95% CI 1.35-2.46). For the other factors of interest we did not observe any effects on CBC risk.
For CHEK2*1100delC mutation carriers and non-carriers, information on factors affecting CBC risk was scarce. In non-carriers, the RR for adjuvant chemotherapy was 0.60 (95% CI 0.53-0.68).
Conclusions
In unselected patients, adjuvant systemic treatment for PBC decreases CBC risk while a lobular morphology of PBC, high BMI, and a family history of BC increase the risk of CBC. Data is scarce for carriers of a BRCA1/2 or CHEK2*1100delC mutation and non-carriers. This review identifies prognostic factors to consider for individualized CBC risk estimation which may support medical decision making in BC patients.
Citation Format: Akdeniz D, Schmidt MK, McCool D, van den Broek AJ, Hauptmann M, Seynaeve CM, Steyerberg EW, Hooning MJ. Risk of metachronous contralateral breast cancer: Systematic review and meta-analysis [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-07-05.