Table 1.
The cohorts and covariates included in the meta-analysis of genotype at SNP rs1800469 and the presence of late fibrosis after radiotherapy to the breast.
| Trial | n | Genotyping platform | Fibrosis endpoint | Covariates included for fibrosis residual | Endpoints in STAT | Covariates included for STAT residual | Length of follow-up (years) | Refs. |
|---|---|---|---|---|---|---|---|---|
| RAPPER | 1010 | Fluidigm | Breast shrinkage (photos) | Age Breast volume Chemotherapy Boost |
Breast shrinkage (photos) Telangiectasia Oedema Pigmentation Pain Oversensitivity |
Acute toxicity week 3 Boost Smoker status DM Breast volume Actual volume 107% Post-op infection Surgical cosmesis |
2 | [12] |
| LeND wide Local excision | 493 | SNPlex | LS fibrosis | Age Chemotherapy Boost EQD2 Gy |
LS pain LS fibrosis LS telangiectasia LS oedema LS atrophy |
Boost Smoker DM Chemotherapy Hypertension EQD2 Gy |
1.5–7 | [14,15] |
| MARIERAD study | 389 | MassArray iPlex | RTOG fibrosis | Age BMI Boost EQD2 Gy |
Telangiectasia Fibrosis in operation site |
Boost dose Smoker DM BMI EQD2 Gy |
>5 | [15] |
| Post-mastectomy DBCG2 | 234 | ABI TaqMan | LS Fibrosis | Age EQD2 Gy Chemotherapy (concurrent) |
Variable | [16] | ||
| RACE | 190 | ABI 3730 automated sequencer | Breast shrinkage (photos) | Age Boost Estimated breast volume Chemotherapy EQD2 Gy |
Breast shrinkage (photos) Telangiectasia Oedema Breast symptoms (QoL) |
Boost Chemotherapy Estimated breast volume Surgical deficit EQD2 Gy |
2 & 5 | [17] |
| LeND mastectomy | 134 | SNPlex | LS fibrosis | Age Chemotherapy EQD2 Gy |
LS pain LS fibrosis LS telangiectasia |
Smoker DM Chemotherapy EQD2 Gy |
1.5–7 | [14,15] |
| Gene-PARE | 92 | DHPLC | RTOG palpation | Age EQD2 Gy |
RTOG visual exam RTOG palpation |
Acute toxicity week 5 Smoker DM EQD2 Gy |
>2 | [18] |
| TGFB prospective study in Sant Pau Hospital, Barcelona | 78 | Sanger sequencing | RTOG subcutaneous tissue | Age BMI Chemotherapy Boost EQD2 Gy |
RTOG skin RTOG subcutaneous tissue |
Acute toxicity Boost Smoker DM Chemotherapy BMI Total dose Surgical cosmesis |
2 | |
| Hamburg Fibrosis breast | 69 | RFLP | LS fibrosis | Age Chemotherapy EQD2 Gy |
2 | [7,21] | ||
| Post-mastectomy DBCG1 | 41 | ABI SNaPshot | LS fibrosis | Age EQD2 Gy |
Variable | [19] | ||
| Post-lumpectomy pre-START trial | 52 | ABI SNaPshot/Taqman | Induration | Age Breast size Chemotherapy Boost EQD2 Gy |
1–5 | [20] |
Abbreviations: ABI, Applied Biosystems™; RFLP, Restriction Fragment Length Polymorphism; DHPLC, Denaturing High-Performance Liquid Chromatography; LS, LENT-SOM (Late effects on Normal Tissues-Subjective Objective Management); RTOG, Radiation Therapy Oncology Group; DM, diabetes mellitus; BMI, body mass index; QoL, Quality of Life; Post-op, post-operative; EQD2 Gy, equivalent dose in 2 Gy fractions; RAPPER, Radiogenomics: Assessment of Polymorphisms for Predicting the Effects of Radiotherapy; LeND, Leicester Nottingham Derby; MARIERAD, Mammakarzinom-Risikofaktoren-Erhebung” – Mammary Carcinoma Risk Factor Investigation Radiotherapy; DBCG, Danish Breast Cancer Group; RACE, Radiation Complications and Epidemiology; Gene-PARE, genetic predictors of Adverse Radiotherapy Effects; START, Standardisation of Breast Radiotherapy.