Table 3.
| Association between clinical feature and overall IBE (DCIS or invasive) | Association between clinical feature and invasive IBE | |||
|---|---|---|---|---|
| Shamliyan et al. 2010 [66] | Wang et al. 2011 [67] | Zhang et al. 2016 [68] | Visser et al. 2019 [69] | |
| Objective | Association between clinical feature and overall clinical outcome (overall IBE and mortality) | Association between clinical feature and overall recurrence rates (DCIS and/or invasive) | Association between clinical feature and invasive breast cancer recurrence rates | Association between clinical feature and invasive breast cancer recurrence rates |
| Inclusion criteria | n/s | Minimum 100 cases per study (excluding biomarker analyses) | Minimum 100 cases per study, females only, HR, OR, or RR data with 95% CI, outcome data on ipsilateral invasive breast cancer | At least 1 year follow-up, more than 10 invasive recurrences in cohort |
| Number of publications included | 133 | 37 | 18 | 40 |
| Number of RCT's | 5 | 5 | 5 | 5 RCT + 1 nRCT (non-randomized- ECOG trial E5194) |
| Number of observational studies | 64 | 26 | 13 | 31 |
| Pre-menopausal status and/or age | All studies consistently showed young age as a risk predictor of IBE, with one RCT finding women under 49 to have a 117% increased risk of IBE (HR = 2.17, 95% CI = 1.61 to 2.94). Similarly, premenopausal women are at significantly increased risk of invasive IBE compared to postmenopausal women | Not assessed | Not assessed | Premenopausal status significantly increased risk of invasive IBE (ES: 1.59: 95% CI: 1.20–2.11) |
| Race | Unadjusted results show African American DCIS patients have significantly increased mortality (RR = 1.35, 95% CI = 1.12 to 1.62) and invasive IBE (RR = 1.50 95% CI = 1.2 to 2) rates compared to Caucasian women | Not assessed | Not assessed | African American women have a significantly increased risk of invasive IBE (ES: 1.43: 95% CI: 1.15–1.79) |
| Mode of detection | RCT showed risk of IBE is significantly increased for symptomatic DCIS patients (RR = 1.9, 95% CI = 1.36 to 2.65) compared to patients detected by mammography | Women with palpable mass or other symptoms were significantly associated with an increased risk of IBE (HR = 1.35, 95% CI = 1.12–1.62) | A significant association between symptomatic (or non-screen detected) DCIS and increased risk of invasive IBE compared to screen detected DCIS (HR = 1.38, 95% CI = 1.12–1.63) | Detection by palpitation was significantly associated with increased risk of invasive IBE (ES: 1.84: 95% CI: 1.47–2.29) |
| Patient BMI | Overweight (RR = 2.3, 95% CI = 1.1 to 4.8) and obese (RR = 5.0, 95% CI = 1.1 to 10.8) patients are at significantly increased risk of invasive IBE | Not assessed | Not assessed | Not assessed |
| Family history | Risk of IBE was significantly associated with positive family history of breast cancer (HR = 3.08, 95% CI = 1.04 to 9.1) | Not assessed | Not assessed | Not assessed |
| Mammographic breast density | NSABB project B17 trial found that IBE rates are higher in women with higher breast density compared to women with lower breast density (RR = 2.8, 95% CI = 1.3–2.8) | Not assessed | Not assessed | Not assessed |
| Tumor size | Tumor size positively correlated with high risk of IBE, however not significant | Significant association between increased tumor size and increased risk of IBE (HR = 1.63 95% CI = 1.30–2.06) * | Inconsistent results among studies, no association | Not assessed |
| Surgical margins | Significant association between positive margins and increased risk of IBE. Margins greater or equal to 10 mm were associated with the largest reduction of risk (98%) | Significant association between positive margins and increased risk of IBE (HR = 2.25, 95% CI = 1.77–2.85) * | Significant association between positive margins and increased risk of invasive IBE (HR = 1.36, 95% CI = 1.04–1.69) I2 = 39.7 | Significant association between positive margins and increased risk of invasive IBE (ES: 1.63: 95% CI: 1.14–2.32) |
| Nuclear grade | Significant association between high grade and increased risk of IBE (HH = 2.04, 95% CI = 1.63–2.56) | Significant association between high grade and increased risk of IBE (HR = 1.81, 95% CI = 1.53–2.13) | Non-significant association between high grade (HR = 1.04; 95% CI = 0.84–1.24) and increased risk of invasive IBE | Significant association between high grade and increased risk of invasive IBE (ES: 1.36: 95% CI: 1.04–1.77) |
| Multifocality | Not assessed | Significant association between multifocality and increased risk of IBE (HR = 1.95, 95%CI = 1.59–2.40) | Non-significant association between multifocality and increased risk of invasive IBE (HR = 1.34, 95% CI = 0.82–1.87) | Not assessed |
| Comedo necrosis | For lumpectomy patients, there is a significant association between comedonecrosis and increased risk of IBE (HR of 2.16, 95% CI = 1.26–3.69) | Significant association between comedonecrosis and increased risk of IBE (HR = 1.71, 95% CI = 1.36-.16) * | Non-significant association between comedonecrosis and increased risk of invasive IBE (HR = 1.18, 95% CI = 0.98–1.37) I2 = 4.2 | Non-significant association between comedonecrosis and increased risk of invasive IBE (HR = 1.25, 95% CI = 0.98–1.6) |
| ER positivity | Non-significant association between ER positivity and reduced risk of IBE | Significant association between ER positivity and reduced risk of IBE (HR = 0.39, 95% CI = 0.18–0.86) | Non-significant association between ER positivity and decreased risk of invasive IBE (HR = 0.74), 95% CI = 0.36–1.12) | No association found |
| PR positivity | Not assessed | Non-significant association between PR positivity and reduced risk of IBE (HR = 0.56, 95% CI = 0.25–1.24) | Non-significant association between PR positivity and decreased risk of invasive IBE (HR = 0.89), 95% CI = 0.47–1.31) | Non-significant association between PR positivity and reduced risk of invasive IBE (HR = 0.80, 95% CI = 0.61–1.05) |
| HER2 amplification | Significant association between HER2 positivity and increased risk of IBE | Significant association between HER2 positivity and increased risk of IBE (HR = 3.07, 95% CI = 1.32, 7.12) | Non-significant association between HER2 positivity and increased risk of invasive IBE (HR = 1.25, 95% CI = 0.7–1.81) | Non-significant association between HER2 positivity and increased risk of invasive IBE (HR = 1.1, 95% CI = 0.75–1.62) |
| Van Nuys prognostic index (VNPI) | Women in higher risk categories had higher rates of IBE, the greatest increase was seen comparing women with VNPI scores of 5–7 to women with scores of 3–4, with HR of 8.4 (3.34–21.13) | Not assessed | Not assessed | Not assessed |
DCIS Ductal carcinoma in situ, IBE Ipsilateral breast event, n/s Not specified, HR Hazard ratio, RR Risk ratio, CI Confidence interval, ES Pooled estimate, RCT Randomized controlled trial, ER Estrogen receptor, PR Progesterone receptor, HER2 Human epidermal growth factor receptor 2, VNPI Van Nuys prognostic index
*Significant degree of heterogeneity between studies