Adjuvant systemic therapy for breast cancer in BRCA1/BRCA2 mutation carriers in a population-based study of risk of contralateral breast cancer.
Given the greatly elevated risks of contralateral breast cancer (CBC) observed in breast cancer patients who carry mutations in BRCA1 and BRCA2, it is critical to determine the effectiveness of standard adjuvant therapies in preventing CBC in mutation carriers. The WECARE study is a matched, case-control study of 708 women with CBC as cases and 1,399 women with unilateral breast cancer (UBC) as controls, including 181 BRCA1/BRCA2 mutation carriers. Interviews and medical record reviews provided detailed information on risk factors and breast cancer therapy. All study participants were screened for BRCA1 and BRCA2 mutations using denaturing high-performance liquid chromatography (DHPLC) to detect genetic variants in the coding and flanking regions of the genes. Conditional logistic regression was used to compare the risk of CBC associated with chemotherapy and tamoxifen in BRCA1/BRCA2 mutation carriers and non-carriers. Chemotherapy was associated with lower CBC risk both in non-carriers (RR = 0.6 [95% CI: 0.5-0.7]) and carriers (RR = 0.5 [95% CI: 0.2-1.0]; P value = 0.04). Tamoxifen was associated with a reduced CBC risk in non-carriers (RR = 0.7 [95% CI: 0.6-1.0]; P value = 0.03). We observed a similar but non-significant reduction associated with tamoxifen in mutation carriers (RR = 0.7 [95% CI: 0.3-1.8]). The tests of heterogeneity comparing carriers to non-carriers did not provide evidence for a difference in the associations with chemotherapy (P value = 0.51) nor with tamoxifen (P value = 0.15). Overall, we did not observe a difference in the relative risk reduction associated with adjuvant treatment between BRCA1/BRCA2 mutation carriers and non-carriers. However, given the higher absolute CBC risk in mutation carriers, the potentially greater impact of adjuvant therapy in reducing CBC risk among mutation carriers should be considered when developing treatment plans for these patients.
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Mail Stop M4-B874, Seattle, WA 98109-1024, USA. kreding@u.washington.edu
Kerryn W
KW
Reding
Jonine L
JL
Bernstein
Bryan M
BM
Langholz
Leslie
L
Bernstein
Robert W
RW
Haile
Colin B
CB
Begg
Charles F
CF
Lynch
Patrick
P
Concannon
Ake
A
Borg
Sharon N
SN
Teraoka
Therese
T
Törngren
Anh
A
Diep
Shanyan
S
Xue
Lisbeth
L
Bertelsen
Xiaolin
X
Liang
Anne S
AS
Reiner
Marinela
M
Capanu
Kathleen E
KE
Malone
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D016022:Case-Control Studies; D017024:Chemotherapy, Adjuvant; D004252:DNA Mutational Analysis; D003718:Denmark; D005260:Female; D006801:Humans; D016013:Likelihood Functions; D016015:Logistic Models; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000517:prevention & control*; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D018426:SEER Program; D013629:Tamoxifen / Q000008:administration & dosage; D016896:Treatment Outcome; D014481:United States; D055815:Young Adult
D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D013629:Tamoxifen