Competing risks of death in younger and older postmenopausal breast cancer patients

Table 1 Number of deaths by treatment arm and factor subgroups n (%)

Factor	Number of patients	Breast cancer	Other cause1	P-value2
Treatment
Tamoxifen	329 (50)	50	32
Tamoxifen
+ Octreotide LAR	329 (50)	56	23	0.40
Age
< 70	544 (83)	85	37
≥ 70	114 (17)	21	18	0.004
BMI
< 25	185 (28)	30	7
25-30	221 (34)	29	20
> 30	213 (32)	41	24	0.02
Tumour size
T1	382 (58)	38	26
≥ T2, unknown	276 (42)	68	29	< 0.0001
Nodal status
N0	346 (53)	39	29
N1, N2, Nx	312 (47)	67	26	0.002

¹Nine patients are excluded with unknown type of death;

²P-value is based on Pearson chi-square test.

Table 2 Competing risks assessment of factors associated with death

Factor	Association with death		Association by type of death
	χ21	P-value	χ22	P-value
Treatment (TAM, TAM + OCT)	0.52	0.77
Age (yr)	7.90	0.02	4.73	0.03
Race (white, other)	1.85	0.40
ECOG performance status (0, other)	0.56	0.75
Tumour size (T1, ≥ T2, unknown)	10.55	0.01	4.22	0.04
Nodal status (N0, N1, N2, Nx)	12.79	0.002	0.38	0.543
Surgery (segmental mastectomy, other)	0.04	0.98
IGF-1 (continuous)	1.17	0.56
IGFBP-3 (continuous)	0.19	0.91
C-peptide (continuous)	3.86	0.15
Weight (kg)	0.27	0.88
BMI (continuous)	1.38	0.50
Vitamin D (continuous)	1.05	0.59
Number of positive nodes
(0, Nx, 1-3+, ≥ 4+)	19.43	< 0.0001	0.02	0.893
Hormone receptor status (ER-PR-,
unknown, ER+ and/or PR+)	5.11	0.08	4.19	0.04
Adjuvant chemotherapy (no, yes)	2.39	0.30

¹Hypothesis H1: Factor does not affect type or time to death. Test criterion was the likelihood ratio criterion that has an approximately chi-square distribution on 2 df (- X²²). Only factors with an indication of statistical significance were considered in H2; ²Hypothesis H2: Factor effect is the same for two causes of death. Test criterion was the likelihood ratio criterion that has an approximately chi-square distribution on 1 df (- Χ²¹);

³Hypothesis H3: As H2 was not rejected, there is evidence of a common effect on both types of death, or on all cause mortality, which was tested by the third hypothesis, H3. H3 is that the factor has no effect on time of death. Test criterion was the likelihood ratio criterion that has an approximately chi-square distribution on 1 df (- Χ²¹). H3 P-value for nodal status and for number of positive nodes was < 0.0001.

Table 3 Multivariate factor effects by type of death

Factor1	β(SE)2	95%CI2	P-value3
Breast cancer survival4
Treatment (Tamoxifen, Tamoxifen + Octreotide LAR)	0.0008(0.17)	[-0.33, 0.33]	1.00
Adjuvant chemotherapy (no, yes)	0.2553 (0.20)	[-0.14, 0.65]	0.20
Number of positive nodes
(0, Nx, 1-3, ≥ 4+)	-0.2524 (0.08)	[-0.41,-0.10]	0.002
Hormone receptor status (ER-PR-, unknown ER/PR, ER+ and/or PR+)	0.2821 (0.13)	[0.03,0.54]	0.03
Tumour size (T1, ≥ T2, unknown)	-0.6521 (0.18)	[-1.00,-0.30]	0.0003
Other Cause Survival
Treatment (Tamoxifen, Tamoxifen + Octreotide LAR)	0.1236 (0.18)	[-0.23, 0.48]	0.49
Adjuvant Chemotherapy (no, yes)	-0.0703 (0.23)	[-0.52, 0.38]	0.76
Number of positive nodes
(0, Nx, 1-3, ≥ 4+)	-0.0723 (0.08)	[-0.23, 0.08]	0.38
Hormone receptor status (ER-PR-, unknown ER/PR, ER+ and/or PR+)	-0.3852 (0.26)	[-0.89,0.12]	0.13
Age (years)	-0.0389 (0.01)	[-0.06,-0.02]	0.002
BMI (continuous)	-0.0395 (0.01)	[-0.06,-0.02]	0.01

¹Cause-specific survival model was built using ln(survival time) having linear function of β x (factor values). The model had forced inclusion of treatment and stratification factors (adjuvant chemotherapy, nodal status, and hormone receptor status) with step-wise forward inclusion of other baseline factors;

²β is effect of factor; SE is standard error; CI is confidence interval assuming β is approximately normally distributed;

³P-value is that for a Wald statistic;

⁴Higher values of continuous C-peptide were associated with worse BrCa (P = 0.08).

Table 4 Survival at 5 and 10 yr

Factor	5 yr1	10 yr1
Breast cancer survival
Treatment
Tamoxifen	0.94	0.85
Tamoxifen + Octreotide LAR	0.94	0.85
Tumour size
T1	0.96	0.89
≥ T2, unknown	0.90	0.78
Nodal status
N0	0.96	0.89
N1, N2, Nx	0.90	0.78
Other cause survival
Treatment
Tamoxifen	0.98	0.94
Tamoxifen + Octreotide LAR	0.99	0.95
Age
60	0.99	0.95
70	0.97	0.90
BMI
25	0.99	0.96
30	0.98	0.94
35	0.98	0.91
40	0.97	0.88
45	0.95	0.84

¹Survival for is adjusted for the effects of other factors: treatment, stratification and other significant factors.