Patients
By researching the SEER database, a total of 698363 malignant mammary carcinoma patients was identified from January 1, 2004 to December 12, 2016. Of which ,426 NECB patients were collected and 295 patients finally enrolled in study. The demographic and clinical characteristics of eligible NECB and IDCB patients were shown in the Table 1 before the PSM. Significant differences were identified between NECB and IDCB patients population with regarding to age at diagnosis, sex, primary site, SEER stage, T stage, N stage, distant metastasis, molecular subtype, rate of surgical method, rate of chemotherapy and rate of radiation. But, there was no significant differences shown in race and marital status. Compared to IDCB patients, NECB patients were more elder (41.7% vs 53.2%, p < 0.0001). NECB patients presented with greater frequency of distant stage than IDCB patients(25.1% vs 5.9%, p < 0.0001). There was more triple negative type in NECB patients than that in IDCB patients(14.9% vs 6.4%, p < 0.001). The proportion of received surgery or radiation was less in NECB compared to those in IDCB, respectively. In contrast, Patients treated with chemotherapy in NECB was more than that in IDCB (52.9% vs 44.2%, p < 0.003).
Table 1
The demographic and clinical characteristics of eligible NECB and IDCB patients before the propensity score-match.
Characteristics | NECB | IDCB | p |
Age (%) | | | |
≤ 60 years | 123(41.7) | 223381(53.2) | < 0.001 |
༞60 years | 172(58.3) | 196810(46.8) | |
Sex (%) | | | |
Female | 289(98.0) | 416917(99.2) | 0.034 |
Male | 6(2.0) | 3274(0.8) | |
Race (%) | | | |
Black | 43(14.6) | 48304(11.5) | 0.094 |
White | 231(78.3) | 330295(78.6) | |
Other/ Unknown | 21(7.1) | 41592(9.9) | |
Primary Site (%) | | | |
Central portion0 | 10(3.4) | 25102(6.0) | < 0.001 |
Upper-inner | 28(9.5) | 50008(11.9) | |
Lower-inner | 11(3.7) | 23848(5.7) | |
Upper-outer | 90(30.5) | 143516(34.2) | |
Lower-outer | 22(7.5) | 30287(7.2) | |
Overlapping lesion | 63(21.4) | 92656(22.1) | |
Breast,NOS | 71(24.1) | 54774(13.0) | |
Marital status (%) | | | |
Married | 230(78.0) | 337286(80.3) | 0.459 |
Unmarried | 51(17.3) | 61856(14.7) | |
Unknown | 14(4.7) | 21049(5.0) | |
SEER Stage (%) | | | |
Regional | 81(27.5) | 127597(30.4) | < 0.001 |
Localized | 134(45.4) | 264073(62.8) | |
Distant | 74(25.1) | 24848(5.9) | |
Unknown | 6(2.0) | 3673(0.9) | |
T stage (%) | | | |
T0 | 1(0.3) | 275(0.1) | < 0.001 |
T1 | 63(21.4) | 242299(57.7) | |
T2 | 104(35.3) | 115467(27.5) | |
T3 | 29(9.8) | 17477(4.2) | |
T4 | 12(4.1) | 11005(2.6) | |
Unknown | 86(29.2) | 33668(8.0) | |
N stage (%) | | | |
N0 | 159(53.9) | 266194(63.4) | < 0.001 |
N1 | 65(22.0) | 96607(23.0) | |
N2 | 12(4.1) | 23708(5.6) | |
N3 | 22(7.5) | 16677(4.0) | |
Unknown | 37(12.5) | 17005(4.0) | |
Metastasis (%) | | | |
M0 | 215(72.9) | 394997(94.0) | < 0.001 |
M1 | 66(22.4) | 18279(4.4) | |
Unknown | 14(4.7) | 6915(1.6) | |
Molecular subtype | | | |
Luminal A | 84(28.5) | 147791(35.2) | < 0.001 |
Luminal B | 16(5.4) | 26341(6.3) | |
Triple Negative | 44(14.9) | 27081(6.4) | |
Unknown | 151(51.2) | 218978(52.1) | |
Surgery (%) | | | |
Yes | 206(69.8) | 389733(92.8) | < 0.001 |
No/unknown | 89(30.2) | 30458(7.2) | |
Radiation (%) | | | |
Yes | 132(44.7) | 214740(51.1) | 0.033 |
No/unknown | 163(55.3) | 205451(48.9) | |
Chemotherapy (%) | | | |
Yes | 156(52.9) | 185668(44.2) | 0.003 |
No/unknown | 139(47.1) | 234523(55.8) | |
Survival Analysis Of Necb
The rates of OS were decreased in patients not treated with radiation compared with those treated with radiation (1-year 68.6% vs 83.8%,3-year 52.9% vs 68.6%, 5-year 48.9% vs 58.9%) (Fig. 1A and B). The 1-year, 3-year, 5-year rates of OS in patients received chemotherapy was 80.6% ,67.3% and 65.1%, respectively, compared with patients who had not received chemotherapy(1-year 76.2%, 3-year 62.1%, 5-year 55.6%,respectively)(Fig. 1C and D). In the 3-year survival analysis, the rates of DSS of patients undergone surgery were over two times of patients who were not undergone surgery(73.6% vs 34.0%)(Fig. 1E and F). To OS, the rates of patients undergone surgery were nearly three times of patients who were not undergone surgery (73.6% vs 25.7%). The 5- year rates were also with greater difference.
Survival Analysis After Psm
Each NECB patients were matched with five IDCB patients data to gain more sight of baseline demographic and diagnostic differences by all variables as age at diagnosis, sex, race, marital status, primary site, SEER stage, T stage, N stage, distant metastasis, molecular subtype, rate of surgical method, chemotherapy and radiation. After matching, good balance with no significant difference was observed between the NECB and IDCB patients groups(Table 2).
Table 2
The demographic and clinical characteristics of eligible NECB and IDCB patients after the propensity score-match.
Characteristics | NECB | IDCB | p |
Age (%) | | | |
≤ 60 years | 123(41.7) | 642(43.5) | 0.607 |
༞60 years | 172(58.3) | 833(56.5) | |
Sex (%) | | | |
Female | 289(98.0) | 1454(98.6) | 0.603 |
Male | 6(2.0) | 21(1.4) | |
Race (%) | | | |
Black | 43(14.6) | 236(16.0) | 0.609 |
White | 231(78.3) | 1116(75.7) | |
Other/ Unknown | 21(7.1) | 123(8.3) | |
Primary Site (%) | | | |
Central portion | 10(3.4) | 72(4.9) | 0.754 |
Upper-inner | 28(9.5) | 114(7.7) | |
Lower-inner | 11(3.7) | 68(4.6) | |
Upper-outer | 90(30.5) | 464(31.5) | |
Lower-outer | 22(7.5) | 97(6.6) | |
Overlapping lesion | 63(21.4) | 332(22.5) | |
Breast,NOS | 71(24.1) | 328(22.2) | |
Marital status (%) | | | |
Married | 230(78.0) | 1137(77.1) | 0.582 |
Unmarried | 51(17.3) | 245(16.6) | |
Unknown | 14(4.7) | 93(6.3) | |
SEER Stage (%) | | | |
Regional | 81(27.5) | 475(32.2) | 0.284 |
Localized | 134(45.4) | 623(42.2) | |
Distant | 74(25.1) | 333(22.6) | |
Unknown | 6(2.0) | 44(3.0) | |
T stage (%) | | | |
T0 | 1(0.3) | 0(0.0) | 0.097 |
T1 | 63(21.4) | 317(21.5) | |
T2 | 104(35.3) | 506(34.3) | |
T3 | 29(9.8) | 129(8.7) | |
T4 | 12(4.1) | 108(7.3) | |
Unknown | 86(29.2) | 415(28.1) | |
N stage (%) | | | |
N0 | 159(53.9) | 739(50.1) | 0.609 |
N1 | 65(22.0) | 374(25.4) | |
N2 | 12(4.1) | 79(5.4) | |
N3 | 22(7.5) | 109(7.4) | |
Unknown | 37(12.5) | 174(11.8) | |
Metastasis (%) | | | |
M0 | 215(72.9) | 1112(75.4) | 0.660 |
M1 | 66(22.4) | 298(20.2) | |
Unknown | 14(4.7) | 65(4.4) | |
Molecular subtype | | | |
Luminal A | 84(28.5) | 442(30.0) | 0.679 |
Luminal B | 16(5.4) | 90(6.1) | |
Triple Negative | 44(14.9) | 184(12.5) | |
Unknown | 151(51.2) | 759(51.5) | |
Surgery (%) | | | |
Yes | 206(69.8) | 1007(68.3) | 0.647 |
No/unknown | 89(30.2) | 468(31.7) | |
Radiation (%) | | | |
Yes | 132(44.7) | 585(39.7) | 0.119 |
No/unknown | 163(55.3) | 890(60.3) | |
Chemotherapy (%) | | | |
Yes | 156(52.9) | 819(55.5) | 0.442 |
No/unknown | 139(47.1) | 656(44.5) | |
Table 3
Univariate survival analysis (Kaplan-Meier) in subgroups of patients according to characteristics
Parameter | DSS | OS |
| HR (95% CI) | p | HR (95% CI) | p |
Age | | 0.417 | | 0.331 |
≤ 60 years | 1 | | 1 | |
༞60 years | 1.178(0.793–1.748) | | 1.186(0.840–1.675) | |
Sex | | 0.745 | | 0.561 |
Male | 1 | | 1 | |
Female | 1.262(0.311–5.123) | | 1.514(0.374–6.129) | |
Race | | 0.578 | | 0.530 |
White | 1 | | 1 | |
Black | 1.188(0.702–2.008) | | 1.120(0.700-1.791) | |
Other*/Unknown | 1.371(0.687–2.735) | | 1.384(0.761–2.518) | |
Primary Location | | 0.702 | | 0.785 |
other | 1 | | 1 | |
inner | 1.110(0.615–2.003) | | 1.162(0.689–1.958) | |
outer | 0.875(0.574–1.334) | | 0.962(0.667–1.387) | |
Marital status | | 0.179 | | 0.685 |
Married | 1 | | 1 | |
Unmarried | 0.653(0.364–1.172) | | 0.910(0.579–1.430) | |
Unknown | 1.472(0.680–3.185) | | 1.297(0.631–2.664) | |
SEER Stage | | 0.133 | | 0.203 |
Regional | 1 | | 1 | |
Localized | 1.354(0.846–2.164) | | 1.403(0.922–2.136) | |
Distant | 0.847(0.476–1.506) | | 1.012(0.619–1.654) | |
Unknown | 2.341(0.706–7.763) | | 2.038(0.622–6.681) | |
T stage | | 0.045 | | 0.017 |
Tis-T2 | 1 | | 1 | |
T3-T4 | 0.415(0.199–0.867) | | 0.423(0.225–0.795) | |
Unknown | 1.007(0.660–1.537) | | 1.017(0.703–1.470) | |
N stage | | 0.003 | | 0.002 |
N0 | 1 | | 1 | |
N1-3 | 0.888(0.569–1.386) | | 0.798(0.540–1.178) | |
Unknown | 2.194(1.303–3.694) | | 1.951(1.222–3.113) | |
Metastasis | | 0.008 | | 0.060 |
M0 | 1 | | 1 | |
M1 | 0.795(0.485–1.302) | | 0.897(0.595–1.352) | |
Unknown | 2.738(1.306–5.742) | | 2.223(1.069–4.620) | |
Molecular subtype | | 0.842 | | 0.666 |
Luminal A | 1 | | 1 | |
Luminal B | 1.052(0.440–2.512) | | 1.264(0.641–2.599) | |
Triple Negative | 0.905(0.498–1.644) | | 0.884(0.519–1.505) | |
Unknown | 0.831(0.533–1.294) | | 0.857(0.581–1.266) | |
Surgery | | 0.000 | | 0.000 |
No/Unknown | 1 | | 1 | |
Yes | 0.241(0.162–0.358) | | 0.221(0.155–0.314) | |
Radiation | | 0.074 | | 0.025 |
No/Unknown | 1 | | 1 | |
Yes | 0.698(0.471–1.035) | | 0.674(0.477–0.951) | |
Chemotherapy | | 0.195 | | 0.025 |
No/Unknown | 1 | | 1 | |
Yes | 0.775(0.526–1.140) | | 0.680(0.485–0.954) | |
*Including American Indian/Alaskan native, and Asian/Pacific Islander, and others |
unspecified. |
The NECB patients demonstrated significantly poorer survival compared to IDCB patients in both DSS (p < 0.0001) and OS (P < 0.0001)(Fig. 2). Actuarial 1-year, 3-year and 5-year DSS rates were 80.1%, 64.9%, and 60.8% vs. 91.6%, 80.4%, and 71.9%, respectively. The 1-year, 3-year and 5-year actuarial OS for the NECB and IDCB group were 75.5%, 60.9%, and 53.4% vs. 89.2%, 74.0%, and 63.4%, respectively.
Univariate And Multivariate Survival Analysis Of Necb
In univariate survival analysis, advanced T stage, N stage and metastasis status were found that related as to survival of NECB patients(Table 2). Patients received radiation therapy had an estimated 32.6% reduced risk of death of NECB (HR = 0.673, 95%CI,0.477–0.951, p = 0.025). NECB patients treated with chemotherapy had an estimated 32.0% reduced risk of death compared to those who had not received chemotherapy or chemotherapy history unknown (HR = 0.68, 95% CI, 0.477–0.951, p = 0.025). Surgery were demonstrated significantly improved the DSS (HR = 0.241, 95%CI, 0.162–0.358, p < 0.0001) and OS (HR = 0.221, 95%CI, 0.155–0.314, p < 0.0001)in NECB patients. Age at diagnosis, sex, race, primary tumor location, marital status and SEER stage were not significant risk variables for NECB. As regarding to different molecular subtype, no statistically significant OS and DSS were identified among NECB patients in univariate survival analysis.
In multivariate survival analysis, Tis-T2, age < 60 ,black race and no distant metastasis were independently associated with improved DSS and OS after adjusting all variables(Table 4). Female patients were reported with a better OS (HR = 0.523,95% CI, 0.302–0.907, p = 0.021). Compared to regional SEER stage, localized SEER stage patients were related to better DSS(HR = 0.621, 95% CI,0.437–0.883, p = 0.008). Chemotherapy and surgery served as positive survival factors in the DSS and OS of NECB patients, independently. Interestingly, the multivariate analysis outcomes of Luminal A type and triple negative type were contrast with univariate analysis. Triple negative type patients were correlated with worse DSS (HR = 2.113; 95% CI, 1.555–2.908, p < 0.0001) and OS (HR = 1.974; 95% CI, 1.496–2.606, p < 0.0001).
Table 4
Multivariate analysis of disease-specific survival (DSS) and overall survival (OS) predictors using Cox proportional hazard model
Parameter | DSS | OS |
| HR (95% CI) | p | HR (95% CI) | p |
Age( ≧ 60 years) | 1.336(1.102–1.619) | 0.003 | 1.678(1.422–1.980) | 0.000 |
Sex (Female) | 1.009(0.404–2.524) | 0.984 | 0.523(0.302–0.907) | 0.021 |
Race | | | | |
Black vs. White | 1.519(1.198–1.925) | 0.001 | 1.431(1.169–1.752) | 0.001 |
Other*/Unknown vs. White | 0.657(0.440–0.981) | 0.040 | 0.713(0.511–0.994) | 0.046 |
Primary Location | | | | |
Upper-inner vs. Central portion | 1.360(0.793–2.332) | 0.263 | 1.148(0.740–1.779) | 0.539 |
Lower-inner vs. Central portion | 0.842(0.438–1.621) | 0.607 | 0.884(0.518–1.507) | 0.650 |
Upper-outer vs. Central portion | 0.854(0.534–1.336) | 0.510 | 0.912(0.624–1.332) | 0.633 |
Lower-outer vs. Central portion | 0.966(0.542–1.722) | 0.908 | 1.045(0.659–1.656) | 0.853 |
Overlapping lesion vs. Central portion | 1.193(0.745–1.908) | 0.463 | 1.143(0.783–1.668) | 0.488 |
Breast,NOS vs. Central portion | 1.138(0.716–1.808) | 0.585 | 1.097(0.754–1.598) | 0.628 |
Marital status | | | | |
Unmarried vs. Married | 1.071(0.838–1.369) | 0.583 | 1.153(0.937–1.420) | 0.179 |
Unknown vs. Married | 0.498(0.299–0.830) | 0.007 | 0.700(0.477–1.027) | 0.068 |
SEER Stage | | | | |
Localized vs. Regional | 0.621(0.437–0.883) | 0.008 | 0.849(0.636–1.133) | 0.267 |
Distant vs. Regional | 0.997(0.522–1.906) | 0.994 | 1.129(0.668–1.909) | 0.650 |
Unknown vs. Regional | 0.850(0.397–1.817) | 0.675 | 0.966(0.531–1.757) | 0.909 |
T stage | | | | |
T3-T4 vs. Tis-T2 | 1.507(1.112–2.042) | 0.008 | 1.436(1.123–1.836) | 0.004 |
Unknown vs. Tis-T2 | 0.827(0.380–1.803) | 0.633 | 1.046(0.617–1.773) | 0.868 |
N stage | | | | |
N1-3 vs. N0 | 1.085(0.828–1.422) | 0.555 | 1.052(0.827–1.338) | 0.682 |
Unknown vs. N0 | 1.161(0.804–1.677) | 0.426 | 1.255(0.904–1.742) | 0.175 |
Metastasis | | | | |
M1 vs. M0 | 4.396(1.671–11.562) | 0.003 | 2.412(1.186–4.903) | 0.015 |
Unknown vs. M0 | 2.317(1.050–5.116) | 0.038 | 1.103(0.636–1.913) | 0.726 |
Molecular subtype | | | | |
Luminal B vs. Luminal A | 0.695(0.419–1.153) | 0.159 | 1.102(0.748–1.624) | 0.624 |
Triple Negative vs. Luminal A | 2.113(1.555–2.908) | 0.000 | 1.974(1.496–2.606) | 0.000 |
Unknown vs. Luminal A | 1.254(0.983–1.599) | 0.068 | 1.311(1.069–1.607) | 0.009 |
Surgery (Yes) | 0.405(0.331–0.495) | 0.000 | 0.381(0.322–0.450) | 0.000 |
Radiation (Yes) | 0.894(0.725–1.102) | 0.292 | 0.862(0.723–1.028) | 0.098 |
Chemotherapy (Yes) | 0.793(0.649–0.970) | 0.024 | 0.660(0.559–0.780) | 0.000 |
Pathological group (IDC) | 0.706(0.562–0.887) | 0.003 | 0.741(0.608–0.902) | 0.003 |
*Including American Indian/Alaskan native, and Asian/Pacific Islander, and others |
unspecified. |