DOI: https://doi.org/10.21203/rs.3.rs-415600/v1
Background: Occult breast cancer is a rare breast tumor, whose prognostic nomogram model has not been established. Thus, we aim to develop and validate a nomogram for evaluating the overall survival (OS) and cancer-specific survival (CSS) of patients with occult breast cancer.
Methods: Between 2004 and 2015, 704 eligible occult breast cancer patients were screened from the Surveillance, Epidemiology, and End Results (SEER) database using specific inclusion and exclusion criteria and then included in the surveillance. They were randomly divided into a training cohort (n = 494) and a validation cohort (N = 210). Univariate and multivariate Cox analyses were performed to explore independent prognostic factors and establish two survival-related nomograms. Area under the curve (AUC), consistency index (C index), internal and external validation calibration curve, decision curve analysis (DCA), Kaplan-Meier analysis, and subgroup analysis were used to evaluate the nomogram.
Results: A total of seven variables were considered to be independent prognostic factors for overall survival (OS) and cancer-specific survival (CSS): age, chemotherapy, radiotherapy, Progesterone receptor (PR) status, N stage, number of lymph node examinations, and number of positive lymph nodes. In the training cohort, the OS nomogram-predicted AUC for three, five, and ten years were 0.792, 0.775, and 0.783, respectively, while those of the CSS nomogram were 0.807, 0.817, and 0.812, respectively. The calibration chart showed excellent agreement between the actual and the nomogram-predicted survival rates in both the training and validation cohorts. The C-index values of the OS nomogram in the training and validation cohorts were 0.762 and 0.782, respectively, while those of the CSS nomogram were 0.786 and 0.816, respectively. DCA and subgroup analysis proved the usefulness of nomograms.
Conclusion: The developed nomogram provided a comprehensive visual model of the risk of each prognostic factor. It can be conveniently used as a personalized prediction tool for the prognosis of occult breast cancer patients.
Table 1. Patients’ detailed general information (n = 704)
|
Characteristic
|
Training Cohort (n = 494)
|
|
Validation Cohort (n = 210) |
|
|
|
N |
% |
N |
% |
|
Age(years) 25-54 55-74 >74 |
179 261 54 |
36.2 52.8 10.9 |
82 105 23 |
39.0 50.0 11.0 |
|
Race White Black Other Unknown |
386 65 40 3 |
78.1 13.2 8.1 0.6 |
175 24 11 0 |
83.3 11.4 5.2 0 |
|
Laterality Left Right Bilateral Other |
245 208 1 40 |
49.6 42.1 0.2 8.1 |
103 88 2 17 |
49.0 41.9 1.0 8.1 |
|
Marital status Married Not married b Other |
266 213 15 |
53.8 43.1 3.0 |
129 77 4 |
61.4 36.7 1.9 |
|
Grade I and II III and IV Unknown |
22 119 353 |
4.5 24.1 71.5 |
11 42 157 |
5.2 20.0 74.8 |
|
Nodal stage N1 N2 N3 |
311 85 98 |
63.0 17.2 19.8 |
127 31 52 |
60.5 14.8 24.8 |
|
Estrogen receptor status Positive Negative Others |
252 193 49 |
51.0 39.1 9.9 |
106 83 21 |
50.5 39.5 10.0 |
|
Progesterone receptor status Positive Negative Others |
168 266 60 |
34.0 53.8 12.1 |
66 120 24 |
31.4 57.1 11.4 |
|
HER-2 status Positive Negative Others |
73 158 263 |
14.8 32.0 53.2 |
30 65 115 |
14.3 31.0 54.8 |
|
Surgery Lumpectomy Mastectomy None Unknown |
65 148 274 7 |
13.2 30.0 55.5 1.4 |
21 74 113 2 |
10.0 35.2 53.8 1.0 |
|
Radiation Yes No |
265 229 |
53.6 46.4 |
102 108 |
48.6 51.4 |
|
Chemotherapy Yes No/Unknown |
397 97 |
80.4 19.6 |
161 49 |
76.7 23.3 |
|
No. of examined lymph nodes 0 1-3 4-9 10- Unknown |
12 72 62 271 77 |
2.4 14.6 12.6 54.9 15.6 |
6 28 26 123 27 |
2.9 13.3 12.4 58.6 12.9 |
|
No. of positive lymph nodes 0 1-3 4-9 10- Unknown |
13 240 76 53 112 |
2.6 48.6 15.4 10.7 22.7 |
3 108 29 32 38 |
1.4 51.4 13.8 15.2 18.1 |
Table 2. Survival analyses of overall survival for occult breast cancer patients in training cohort
|
Variables
|
Univariate
|
multivariate |
|
|
|
P |
HR(95%CI) |
P |
|
Age(years) 25-54 55-74 >74 |
<.001 |
Reference 1.564(.934-2.620) 3.392 (1.837-6.260) |
<.001
.089 <.001 |
|
Race White Black Other Unknown |
.480
|
|
|
|
Laterality Left Right Bilateral Other |
.069 |
|
|
|
Marital status Married Not married b Other |
.049 |
Reference 1.186 (.775-1.816) 1.971 (.552-7.035) |
.484
.432 .296 |
|
Grade I and II III and IV Unknown |
.322 |
|
|
|
Nodal stage N1 N2 N3 |
<.001 |
Reference 1.054(.373-2.976) 2.444 (1.235-4.839) |
.023
.921 .010 |
|
Estrogen receptor status Positive Negative Others |
<.001 |
0.660 (0.381-1.143) Reference 2.434 (0.300-19.772) |
.210 .138
.405 |
|
Progesterone receptor status Positive Negative Others |
.002 |
0.359 (0.182-0.709) Reference 0.295 (.039-2.239) |
.008 .003
.238 |
|
HER-2 status Positive Negative Others |
.248 |
|
|
|
Surgery Lumpectomy Mastectomy None Unknown |
.234 |
|
|
|
Radiation Yes No |
.003 |
0.525 (0.327-0.841) Reference |
.007 .007
|
|
Chemotherapy Yes No/Unknown |
<.001 |
0.519(0.318-0.848) Reference |
.009 .009 |
|
No. of examined lymph nodes 0 1-3 4-9 10- Unknown |
<.001 |
Reference 2.709(0.649-11.307) 1.276(0.260-6.269) 0.760 (0.185-3.116) 0.947(0.332-2.702) |
.018
.172 .764 .703 .918 |
|
No. of positive lymph nodes 0 1-3 4-9 10- Unknown |
<.001 |
Reference 2319.823(0-7.402e+40) 8129.127(0-2.601e+41) 6231.362(0-1.990e+41) 7272.320(0-2.329e+41) |
.090
.860 .838 .843 .840 |
Table 3. Survival analyses of cancer-specific survival for occult breast cancer patients in training cohort
|
Variables
|
Univariate
|
multivariate |
|
|
|
P |
HR(95%CI) |
P |
|
Age(years) 25-54 55-74 >74 |
<.001 |
Reference 1.194(0.680-2.097) 2.519 (1.260-5.037) |
.021
.537 .009 |
|
Race White Black Other Unknown |
.400
|
|
|
|
Laterality Left Right Bilateral Other |
.093 |
|
|
|
Marital status Married Not married b Other |
.092 |
|
|
|
Grade I and II III and IV Unknown |
.356 |
|
|
|
Nodal stage N1 N2 N3 |
<.001 |
Reference 1.589(0.477-5.290) 3.118 (1.490-6.522) |
.010
.451 .003 |
|
Estrogen receptor status Positive Negative Others |
<.001 |
0.572 (0.291-1.122) Reference 4.206e+03(0-3.401e+44) |
.263 .104
.862 |
|
Progesterone receptor status Positive Negative Others |
.008 |
0.428 (0.193-0.951) Reference 0 (0-1.616e+39) |
.263 .104
.862 |
|
HER-2 status Positive Negative Others |
.404 |
|
|
|
Surgery Lumpectomy Mastectomy None Unknown |
.267 |
|
|
|
Radiation Yes No |
.013 |
0.445 (0.256-0.773) Reference |
.004 .004
|
|
Chemotherapy Yes No/Unknown |
.009 |
0.642(0.356-1.157) Reference |
.140 .140 |
|
No. of examined lymph nodes 0 1-3 4-9 10- Unknown |
<.001 |
Reference 2.994(0.600-14.926) 2.177(0.383-12.363) 0.505(0.100-2.548) 1.152(0.381-3.482) |
.006
.181 .380 .408 .802 |
|
No. of positive lymph nodes 0 1-3 4-9 10- Unknown |
<.001 |
Reference 2.246e+03(0-3.193e+48) 8.235e+03(0-1.175e+49) 1.395e+04(0-1.985e+49) 9.836e+03(0-1.403e+49) |
.026
.884 .865 .857 .862 |