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. 2023 Jun;199(2):335-347.
doi: 10.1007/s10549-023-06919-x. Epub 2023 Apr 5.

Caveolin-1 genotypes as predictor for locoregional recurrence and contralateral disease in breast cancer

Christopher Godina  1 , Helga Tryggvadottir  1   2 , Ana Bosch  1   2 , Signe Borgquist  1   3 , Mattias Belting  1   2   4 , Karolin Isaksson  5 , Helena Jernström  6
Affiliations

Caveolin-1 genotypes as predictor for locoregional recurrence and contralateral disease in breast cancer

Christopher Godina et al. Breast Cancer Res Treat. 2023 Jun.

Abstract

Purpose: Caveolin-1 (CAV1) has been implicated in breast cancer oncogenesis and metastasis and may be a potential prognosticator, especially for non-distant events. CAV1 functions as a master regulator of membrane transport and cell signaling. Several CAV1 SNPs have been linked to multiple cancers, but the prognostic impact of CAV1 SNPs in breast cancer remains unclear. Here, we investigated CAV1 polymorphisms in relation to clinical outcomes in breast cancer.

Methods: A cohort of 1017 breast cancer patients (inclusion 2002-2012, Sweden) were genotyped using Oncoarray by Ilumina. Patients were followed for up to 15 years. Five out of six CAV1 SNPs (rs10256914, rs959173, rs3807989, rs3815412, and rs8713) passed quality control and were used for haplotype construction. CAV1 genotypes and haplotypes in relation to clinical outcomes were assessed with Cox regression and adjusted for potential confounders (age, tumor characteristics, and adjuvant treatments).

Results: Only one SNP was associated with lymph node status, no other SNPs or haplotypes were associated with tumor characteristics. The CAV1 rs3815412 CC genotype (5.8% of patients) was associated with increased risk of contralateral breast cancer, adjusted hazard ratio (HRadj) 4.26 (95% CI 1.86-9.73). Moreover, the TTACA haplotype (13% of patients) conferred an increased risk for locoregional recurrence HRadj 2.24 (95% CI 1.24-4.04). No other genotypes or haplotypes were associated with clinical outcome.

Conclusion: CAV1 polymorphisms were associated with increased risk for locoregional recurrence and contralateral breast cancer. These findings may identify patients that could derive benefit from more tailored treatment to prevent non-distant events, if confirmed.

Keywords: Caveolin-1; Contralateral breast cancer; Genotype; Locoregional breast cancer recurrence.

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Conflict of interest statement

Ana Bosch has received institutional honoraria from Pfizer, Roche, and Lilly for consultation and lectures. She has participated in Advisory Board meetings for Pfizer and Novartis. Co-founder and chair of the board for SACRA therapeutics. The other authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Flowchart of included and excluded patients
Fig. 2
Fig. 2
Genomic region of CAV1 along with linkage disequilibrium heatmap and visual illustration of the linkage relationship between CAV1 SNPs. Continuous lines indicate common combinations while dotted lines indicate less likely combinations. Frequencies of CAV1 SNPs, combined genotypes, diplotypes, and haplotypes for the 1017 breast cancer patients
Fig. 3
Fig. 3
Kaplan–Meier estimates of (a, c) locoregional recurrence-free interval with corresponding (b, d) forest plots of adjusted hazard ratios (95% confidence intervals), contralateral breast cancer-free interval (e, g) with corresponding (f, h) forest plots of adjusted hazard ratios (95% confidence intervals) in relation to the CAV1 rs3815412 genotype and TTACA haplotype in all patients. The number of patients is indicated at each time-point. The study is ongoing; thus, the number of patients decreases with time
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