Table 2.
Univariate results of molecular markers associated with type of subsequent tumor event (invasive cancer or ductal carcinoma in situ [DCIS])
| Factor‡ | No subsequent tumor event† (N = 408) % (No.) | Local invasive (N = 109) % (No.) | Risk of local invasive HR† (95 % CI) | Regional/metastatic invasive (N = 44) % (No.) | Risk of regional/metastic invasive HR (95 % CI) |
|---|---|---|---|---|---|
| Estrogen receptor (ER) | |||||
| Negative | 19 (37) | 17 (12) | 0.7 (0.4–1.3) | 31 (10) | 1.7 (0.8—3.6) |
| Positive | 81 (158) | 83 (60) | 1.0 (referent) | 69 (22) | 1.0 (referent) |
| Progesterone receptor (PR) | |||||
| Negative | 21 (35) | 31 (23) | 1.2 (0.8–2.0) | 34 (10) | 1.5 (0.7—3.2) |
| Positive | 79 (131) | 69 (52) | 1.0 (referent) | 66 (19) | 1.0 (referent) |
| p53 | |||||
| Positive | 10 (16) | 13 (9) | 1.0 (0.5–2.0) | 18 (6) | 1.6 (0.7—4.0) |
| Negative | 90 (146) | 87 (62) | 1.0 (referent) | 82 (27) | 1.0 (referent) |
| ERBB2 oncoprotein | |||||
| Positive | 13 (27) | 17 (13) | 0.9 (0.5–1.7) | 29 (10) | 1.9 (0.9—3.9) |
| Negative | 87 (175) | 83 (63) | 1.0 (referent) | 71 (24) | 1.0 (referent) |
| Ki67 | |||||
| Positive§ | 36 (59) | 57 (30) | 1.5 (0.9–2.6) | 61 (11) | 1.8 (0.7–4.3) |
| Negative | 64 (103) | 43 (23) | 1.0 (referent) | 39 (7) | 1.0 (referent) |
| p16 | |||||
| Positive | 31 (42) | 56 (34) | 1.9 (1.2–3.2) | 66 (21) | 2.8 (1.4—5.8) |
| Negative | 69 (91) | 44 (27) | 1.0 (referent) | 34 (11) | 1.0 (referent) |
| Cyclooxygenase-2 (COX-2) | |||||
| Positive | 45 (63) | 41 (24) | 0.9 (0.5–1.5) | 52 (13) | 1.4 (0.7–3.1) |
| Negative | 55 (76) | 59 (35) | 1.0 (referent) | 48 (12) | 1.0 (referent) |
| p16/Ki67 | |||||
| Positive/positive | 9 (12) | 23 (11) | 1.4 (0.7–3.0) | 33 (8) | 2.9 (1.3–7.1) |
| Positive/negative | 20 (25) | 19 (9) | 1.5 (0.7–3.1) | 21 (5) | 1.7 (0.6–4.8) |
| All other groupings | 71 (91) | 57 (27) | 1.0 (referent) | 46 (11) | 1.0 (referent) |
| COX-2/Ki67 | |||||
| Positive/positive | 17 (22) | 20 (11) | 1.0 (0.5–2.0) | 30 (7) | 1.8 (0.7–4.4) |
| All other groupings | 83 (106) | 80 (45) | 1.0 (referent) | 70 (16) | 1.0 (referent) |
| Ki67/COX-2 | |||||
| Positive/positive | 17 (22) | 20 (11) | 1.0 (0.5–2.0) | 30 (7) | 1.8 (0.7–4.4) |
| Negative/positive | 23 (30) | 18 (10) | 0.9 (0.5–1.8) | 17 (4) | 1.0 (0.4–3.0) |
| All other groupings | 59 (76) | 62 (35) | 1.0 (referent) | 52 (12) | 1.0 (referent) |
| p16/COX-2 | |||||
| Positive/negative | 8 (11) | 27 (16) | 2.3 (1.3–4.1) | 21 (6) | 1.7 (0.7–4.1) |
| All other groupings | 92 (124) | 73 (44) | 1.0 (referent) | 79 (22) | 1.0 (referent) |
| p16/COX-2/Ki67 | |||||
| Positive/positive/negative | 11 (13) | 10 (5) | 0.9 (0.3–2.2) | 20 (4) | 2.5 (0.8–7.6) |
| Negative/negative/positive | 17 (20) | 20 (10) | 0.6 (0.2–1.2) | 5 (1) | 0.3 (0.04–2.3) |
| Negative/negative/negative | 29 (33) | 14 (7) | 1.0 (0.8–1.3) | 5 (1) | 1.1 (0.8–1.6) |
| Positive/positive/positive | 7 (8) | 12 (6) | 0.9 (0.4–2.1) | 30 (6) | 3.3 (1.2–9.0) |
| All other groupings | 36 (41) | 45 (23) | 1.0 (referent) | 40 (8) | 1.0 (referent) |
| P16/Cox-2/ER/ERBB2 | |||||
| Pos/pos/pos/neg | 11 (15) | 19 (11) | 1.9 (1.0–3.7) | 4 (1) | 0.4 (0.05–2.6) |
| Pos/pos/neg/neg | 2 (2) | 2 (1) | 0.7 (0.1–5.3) | 8 (2) | 4.6 (0.98–21.8) |
| Pos/pos/pos/pos | 3 (4) | 3 (2) | 0.8 (0.2–3.8) | 11 (3) | 3.6 (1.1–11.7) |
| Pos/pos/neg/pos | 2 (3) | 0 (0) | 0 | 11 (3) | 6.5 (2.3–18.2) |
| All other groupings | 82 (109) | 76 (44) | 1.0 (referent) | 65 (17) | 1.0 (referent) |
Adjusted for diagnosis age
Patients with subsequent DCIS event or who died of cause other than breast cancer are considered competing risks but data not shown (N = 435)
Control subjects were a random sample of women with ductal carcinoma in situ who did not have a subsequent tumor event and were frequency matched by year of diagnosis to the case subjects, who were women who had a subsequent tumor event
Of the 774 patients (including DCIS subsequent events and dead of cause other than breast cancer), 17 % had missing data for ER status, 17 % for PR status, 17 % for p53 status, 17 % for ERBB2, 60 % for Ki67, 60 % for p16, 62 % for COX-2
More than 10 % positive cells