Background
Methods
Eligibility criteria
Study selection and data collection
Patient age (years) | Follow-up (years) | ||||||||
---|---|---|---|---|---|---|---|---|---|
Study and publication year | Collection of patient data | Study design | Country | Mean or median | Range | Diagnosed at ≤ 40 years (%) | Number of eligible cases (Adjusted)a
| Mean or median | Adjusteda
|
Betsill-1978 [32] | 1940–1950 | R | US | 48.2 | 34–59 | 20c
| 8 | 18f
| 10 |
Millis-1975 [19] | 1948–1968 | R | UK | 47 | 39–79 | 20 | 16 | >15 | 10 |
Sanders-2005 [29] | 1950–1968 | R | US | 52b
| 33–80 | 25 | 25 | 31 | 10 |
Wanebo-1974 [23] | 1953–1972 | R | US | 53 | 22–86 | NR | 14 | ≥10 | 10 |
Sunshine-1985 [17] | 1960–1972 | R | US | ABO | NR | 28d
| 85 | >10 | >10 |
Akashi-Tanaka-2000 [20] | 1962–1995 | R | JP | 47b
| 19–92 | NR | 13 | 13.4 | 10 |
Eusebi-1994 [30] | 1964–1976 | R | IT | 48.6 | 24–77 | 24 | 71 | 17.5f
| 10 |
Simpson-1992 [22] | 1967–1977 | R | US | NR | NR | NR | 30 | 17.7f
| 10 |
Solin-1996 [27] | 1967–1985 | R | EU/US | 50 | 26–82 | NR | 270 | 10.3 | 10.3 |
Lagios-1989 [24] | 1972–1980 | R | US | 54 | 16–85 | NR | 20 | 10.3 | 10.3 |
Collins-2005 [31] | 1973–1991 | R | US | 55 | 39–63 | 7.7 | 13 | 17.4f
| 10 |
Lara-2003 [21] | 1974–1992 | R | US | 56 | 31–82 | NR | 73 | 19f
| 10 |
Tunon-de-Lara-2010 [18] | 1974–2003 | R | FR | 36.3 | 18–40 | 100 | 207 | 13.3 | 13.3 |
Di Saverio-2008 [25] | 1976–2006 | R | IT | ABO | NR | 8.5 | 186 | 10.8f
| 10.8 |
Ward-1992 [28] | 1979–1983 | R | US | 58.4b
| NR | NR | 11 | >10f
| 10 |
Shaitelman-2012 [33] | 1980–1993 | R | US | NR | NR | 20.7 | 145 | 19.3 | 10 |
Ottesen-2000 [13] | 1982–1989 | P | DK | 48^ | 29–85 | NR | 168 | 10 | 10 |
Holmes-2011 [34] | 1983–2002 | R | US | 55.5 | NR | 34e
| 141 | 10.2 | 10.2 |
Fisher-2001 [9] (B-17) | 1985–1990 | P + RCT | US | ABO | NR | NR | 813 | 10.8 | 10.8 |
Vidali-2012 [16] | 1985–2000 | R | IT | 55 | 29–84 | 5.5 | 586 | 11.3 | 11.3 |
Bijker-2006 [10] | 1986–1996 | P + RCT | EU | 53 | 25–76 | 6.4 | 1010 | 10.5 | 10.5 |
Cuzick-2011 [11] | 1990–1998 | P + RCT | UK/ANZ | ABO | NR | 3.3d
| 1694 | 12.7 | 12.7 |
Owen-2013 [14] | 1990–1999 | P + R | CA | 55 | 27–92 | 8.6 | 637 | 12 | 12 |
Wapnir-2011 [12] (B-24) | 1991–1994 | P + RCT | US | 55 | NR | 17.3 | 1184 | 13.6 | 10 |
Rudloff-2009 [26] | 1991–1995 | R | US | 55 | 26–89 | 15.6d
| 91 | 11 | 11 |
Rakovitch-2013 [15] | 1994–2003 | R | CA | 56 | 20–85 | 12.4 | 1893 | 10 | 10 |
Data items and endpoints
Summary measures and statistical analysis
Meta-analysisa
| Meta-regressionb
| ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Unadjusted | Adjusted for weighted mean age & period, & 10-year follow-up | ||||||||||
Treatment | Groups | DCIS cases | Local recurrence or death | Rate (%) & 95 % CI | Model |
P heterog | I2 heterogc
| Rate (%) & 95 % CI | Rate (%) & 95 % CI | Odds ratio |
P
|
All local recurrence | |||||||||||
Model P-value |
P < 0.0001 |
P < 0.0001 |
P < 0.0001 | ||||||||
Biopsy | 4 | 117 | 28 | 35.8 | R | <0.001 | 83.6 | 29.8 | 27.8 | 14.15 | <0.001 |
13.4–58.2 | 15.9–43.8 | 8.4–47.1 | 5.26–38.03 | ||||||||
BCS | 11 | 2605 | 653 | 25.2 | R | <0.001 | 86.7 | 23.9 | 25.5 | 12.59 | <0.001 |
19.8–30.6 | 18.0–29.9 | 18.1–32.9 | 6.28–25.26 | ||||||||
BCS + RT | 13 | 5746 | 716 | 13.0 | R | <0.001 | 78.4 | 12.7 | 13.6 | 5.79 | <0.001 |
10.9–15.1 | 9.6–15.8 | 9.8–17.4 | 2.90–11.55 | ||||||||
Mastectomy | 8 | 936 | 22 | 3.0 | F = R | ns | 53.6 | 2.6 | 2.6 | 1.00 | |
0.9–5.0 | 1.0–4.2 | 0.8–4.50 | - | ||||||||
Total | 36 | 9404 | 1419 | ||||||||
Linear trend treatment |
P < 0.001 |
P < 0.001 |
P < 0.001 | ||||||||
Invasive local recurrence | |||||||||||
Model P-value |
P < 0.0001 |
P < 0.0001 |
P < 0.0001 | ||||||||
Biopsy | 4 | 117 | 21 | 26.6 | R | <0.01 | 77.1 | 21.0 | 10.9 | 6.83 | <0.001 |
9.5–43.8 | 10.4–31.7 | 3.2–18.5 | 2.91–16.04 | ||||||||
BCS | 11 | 2601 | 290 | 11.0 | R | <0.01 | 64.7 | 10.6 | 10.7 | 6.72 | <0.001 |
8.6–13.4 | 7.8–13.4 | 8.0–13.4 | 3.83–11.80 | ||||||||
BCS + RT | 10 | 5499 | 357 | 7.4 | R | <0.001 | 80.1 | 6.7 | 6.7 | 4.00 | <0.001 |
5.2–9.5 | 5.1–8.4 | 5.4–8.0 | 2.26–7.08 | ||||||||
Mastectomy | 8 | 853 | 19 | 2.5 | R | <0.05 | 58.1 | 2.1 | 1.8 | 1.00 | |
0.49–4.5 | 0.8–3.4 | 0.8–2.8 | |||||||||
Total | 33 | 9070 | 687 | ||||||||
Linear trend treatment |
P < 0.001 |
P < 0.001 |
P < 0.001 | ||||||||
Breast cancer deaths | |||||||||||
Model P-value |
P = 0.3670 |
P = 0.1689 |
P = 0.1689 | ||||||||
Biopsy | 4 | 117 | 6 | 5.2 | F = R | ns | 18.5 | 4.9 | 2.7 | 2.02 | 0.262 |
0.3–10.0 | 0.5–9.3 | 0.0–6.0 | 0.59–6.91 | ||||||||
BCS | 9 | 2296 | 59 | 2.6 | F = R | ns | 0 | 2.3 | 2.0 | 1.5 | 0.256 |
1.9–3.2 | 1.4–3.3 | 0.9–3.1 | 0.75–3.02 | ||||||||
BCS + RT | 10 | 3751 | 83 | 2.4 | R | <0.001 | 73.0 | 2.2 | 1.9 | 1.41 | 0.319 |
1.5–3.4 | 1.5–2.9 | 1.2–2.6 | 0.72–2.77 | ||||||||
Mastectomy | 8 | 936 | 18 | 2 | R | ns | 9.1 | 1.9 | 1.3 | 1.00 | |
0.9–3.1 | 0.7–3.1 | 0.3–2.3 | - | ||||||||
Total | 31 | 7100 | 166 | ||||||||
Linear trend treatment |
P = 0.2281 |
P = 0.0685 |
P = 0.0685 |
Meta-analysisa
| Meta-regressionb
| ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Unadjusted | Adjusted for weighted mean age & period, & 10-year follow-up | ||||||||||
Treatment | Groups | DCIS cases | Local recurrence or death | Rate (%) & 95%CI | Model |
P heterog | I2 heterogc
| Rate (%) & 95 % CI | Rate (%) & 95 % CI | OR |
P
|
All local recurrence | |||||||||||
Model P-value |
P = 0.0002 |
P = 0.0003 |
P = 0.0003 | ||||||||
CS(alone) | 10 | 2038 | 541 | 25.9 | R | <0.001 | 85.5 | 24.9 | 25.1 | 3.12 | 0.001 |
19.9–32.0 | 19.1–30.6 | 18.3–31.9 | 1.62–6.00 | ||||||||
CS + TAM(no RT) | 1 | 567 | 112 | 19.8 | R | <0.001 | 86.7 | 19.7 | 24.7 | 3.05 | 0.024 |
16.5-23.0 | 7.1–32.3 | 7.9–41.5 | 1.16–8.04 | ||||||||
CS + RT(no TAM) | 11 | 4809 | 630 | 14.9 | R | <0.001 | 78.4 | 13.8 | 14.1 | 1.52 | 0.190 |
11.8-18.0 | 10.6–16.9 | 10.3–17.8 | 0.81–2.86 | ||||||||
CS + RT + TAM | 2 | 937 | 86 | 9.2 | F = R | ns | 53.6 | 8.5 | 9.7 | 1.00 | |
7.3-11.0 | 3.9–13.2 | 4.4–15.0 | - | ||||||||
Total | 24 | 8351 | 1369 | ||||||||
Linear trend treatment |
P < 0.001 |
P < 0.0001 |
P < 0.0001 | ||||||||
Invasive local recurrence | |||||||||||
Model P-value |
P = 0.0005 |
P < 0.0001 |
P < 0.0001 | ||||||||
CS(alone) | 10 | 2038 | 241 | 11.4 | R | <0.05 | 60.1 | 11.2 | 11.3 | 2.61 | 0.001 |
8.8–14.1 | 8.8–13.7 | 8.9–13.8 | 1.71–3.97 | ||||||||
CS + TAM(no RT) | 1 | 567 | 49 | 8.6 | - | - | - | 8.6 | 11.0 | 2.52 | 0.001 |
6.7–10.6 | 4.1–13.1 | 6.2–15.8 | 1.44–4.41 | ||||||||
CS + RT(no TAM) | 8 | 4562 | 317 | 7.7 | R | <0.001 | 79.0 | 7.4 | 7.2 | 1.59 | 0.022 |
5.9–9.5 | 5.8–8.9 | 6.1–8.3 | 1.07–2.35 | ||||||||
CS + RT + TAM | 2 | 937 | 40 | 4.3 | F = R | ns | <0 | 4.1 | 4.7 | 1.00 | |
3.0–5.6 | 2.2–6.0 | 3.0–6.4 | - | ||||||||
Total | 21 | 8104 | 647 | ||||||||
Linear trend treatment |
P < 0.0001 |
P < 0.0001 |
P < 0.0001 | ||||||||
Breast cancer deaths | |||||||||||
Model P-value |
P = 0.6160 |
P = 0.4152 |
P = 0.4152 | ||||||||
CS(alone) | 8 | 1729 | 40 | 2.3 | F = R | ns | <0 | 2.1 | 2.1 | 1.15 | 0.734 |
1.6-3.0 | 1.1–3.1 | 0.9–3.2 | 0.52–2.51 | ||||||||
CS + TAM(no RT) | 1 | 567 | 19 | 3.4 | - | - | - | 3.3 | 4.0 | 2.24 | 0.128 |
2.1–4.6 | 0.6–5.9 | 0.2–7.7 | 0.79–1.27 | ||||||||
CS + RT(no TAM) | 8 | 2814 | 67 | 2.7 | R | <0.001 | 76.4 | 2.3 | 2.2 | 1.21 | 0.613 |
1.4–3.9 | 1.5–3.2 | 1.2–3.1 | 0.58–2.54 | ||||||||
CS + RT + TAM | 2 | 937 | 16 | 1.7 | R | ns | <0 | 1.6 | 1.8 | 1.00 | |
0.9–2.5 | 0.5–2.8 | 0.6–3.0 | - | ||||||||
Total | 19 | 6047 | 142 | ||||||||
Linear trend treatment |
P = 0.8591 |
P = 0.5586 |
P = 0.5586 |