Clinicopathological characteristics of the patients. A total of 1855 patients diagnosed with IMPC after surgery were included in this study. Patients were randomly divided via a 7:3 ratio into two sets: a training set (n = 1300) for nomogram building, and a validation set (n = 555) for model validation. Next, the clinical and pathological characteristics of the patients in the training set were described in detail. The median age of primary diagnosis for the entire population was 62 (22–96) years old. The majority of patients were white (78.2%), and 98.5% were female. The breast cancer subtype was HR+/HER2- (luminal A) in 52.7% of patients, HR+/HER2+ (luminal B) in 11.2%, HR-/HER2+ (HER2 enriched) in 2.8% and HR-/HER2- (triple negative) in 2.7%. Since the Seer database has only recorded HER2 status since 2010, the HER2 status was not known for patients (30.6%) before that date. A total of 41.4% of screened patients after surgery were stage I, 37.3% were stage II, 20% were stage III, and 1.3% were stage IV. A total of 52.4% of the patients received breast-conserving surgery (BCS), and the rest underwent mastectomy. The majority of patients developed breast cancer that was located on the upper-outer region (29.5%), and most tumors were ≤ 20 mm (58.4%). The proportions of patients who underwent chemotherapy and radiotherapy were 48.9% and 55.1%, respectively. The demographic and clinical characteristics of the study participants based on dataset classification are shown in Table 1.
Table 1
Characteristics of IMPC of breast patients after surgery.
Variables | Total cohort | Training cohort | Validation cohort |
| N = 1855 | N = 1300 | N = 555 |
| n | % | n | % | n | % |
Age | | | | | | |
༜62 | 953 | 51.4 | 655 | 50.4 | 298 | 53.7 |
≥ 62 | 902 | 48.6 | 645 | 49.6 | 257 | 46.3 |
Race | | | | | | |
Black | 223 | 12 | 153 | 11.8 | 70 | 12.6 |
Other | 189 | 10.2 | 131 | 10.1 | 58 | 10.5 |
White | 1443 | 77.8 | 1016 | 78.2 | 427 | 76.9 |
Sex | | | | | | |
Female | 1827 | 98.5 | 1281 | 98.5 | 546 | 98.4 |
Male | 28 | 1.5 | 19 | 1.5 | 9 | 1.6 |
Marital status | | | | | | |
Unmarried | 765 | 41.2 | 522 | 40.2 | 243 | 43.8 |
Married | 1004 | 54.1 | 719 | 55.3 | 285 | 51.4 |
Unknown | 86 | 4.6 | 59 | 4.5 | 27 | 4.9 |
Breast subtype | | | | | | |
HR+/HER2- (Luminal A) | 960 | 51.8 | 685 | 52.7 | 275 | 49.5 |
HR+/HER2+ (Luminal B) | 210 | 11.3 | 145 | 11.2 | 65 | 11.7 |
HR-/HER2+ (HER2 enriched) | 56 | 3 | 37 | 2.8 | 19 | 3.4 |
HR-/HER2- (Triple Negative) | 50 | 2.7 | 35 | 2.7 | 15 | 2.7 |
Recode not available | 579 | 31.2 | 398 | 30.6 | 181 | 32.6 |
ER | | | | | | |
Negative | 187 | 10.1 | 130 | 10 | 57 | 10.3 |
Positive | 1668 | 89.9 | 1170 | 90 | 498 | 89.7 |
PR | | | | | | |
Negative | 393 | 21.2 | 276 | 21.2 | 117 | 21.1 |
Positive | 1462 | 78.8 | 1024 | 78.8 | 438 | 78.9 |
HER-2 | | | | | | |
Negative | 1010 | 54.4 | 720 | 55.4 | 290 | 52.3 |
Positive | 266 | 14.3 | 182 | 14 | 84 | 15.1 |
Recode not available | 579 | 31.2 | 398 | 30.6 | 181 | 32.6 |
Stage | | | | | | |
Ⅰ | 748 | 40.3 | 538 | 41.4 | 210 | 37.8 |
Ⅱ | 706 | 38.1 | 485 | 37.3 | 221 | 39.8 |
Ⅲ | 377 | 20.3 | 260 | 20 | 117 | 21.1 |
Ⅳ | 24 | 1.3 | 17 | 1.3 | 7 | 1.3 |
Laterality | | | | | | |
Left | 941 | 50.7 | 655 | 50.4 | 286 | 51.5 |
Right | 914 | 49.3 | 645 | 49.6 | 269 | 48.5 |
Surgery | | | | | | |
BCS | 964 | 52 | 681 | 52.4 | 283 | 51 |
Mastectomy | 891 | 48 | 619 | 47.6 | 272 | 49 |
Radiotherapy | | | | | | |
No | 833 | 44.9 | 584 | 44.9 | 249 | 44.9 |
Yes | 1022 | 55.1 | 716 | 55.1 | 306 | 55.1 |
Chemotherapy | | | | | | |
No | 930 | 50.1 | 664 | 51.1 | 266 | 47.9 |
Yes | 925 | 49.9 | 636 | 48.9 | 289 | 52.1 |
Tumor size | | | | | | |
≤ 20 | 1086 | 58.5 | 759 | 58.4 | 327 | 58.9 |
20–50 | 598 | 32.2 | 422 | 32.5 | 176 | 31.7 |
༞50 | 171 | 9.2 | 119 | 9.2 | 52 | 9.4 |
Primary site | | | | | | |
Central portion of breast/Nipple | 124 | 6.7 | 90 | 6.9 | 34 | 6.1 |
Lower-inner | 135 | 7.3 | 95 | 7.3 | 40 | 7.2 |
Lower-outer | 143 | 7.7 | 104 | 8 | 39 | 7 |
Upper-inner | 260 | 14 | 174 | 13.4 | 86 | 15.5 |
Upper-outer | 553 | 29.8 | 384 | 29.5 | 169 | 30.5 |
other | 640 | 34.5 | 453 | 34.8 | 187 | 33.7 |
Prognostic factors. As is shown in Table 2, cox regression analysis was performed on the training set. Factors that were statistically significant in the univariate analysis were subjected to multiple covariance diagnosis, and strong covariance was found between T, N, M stage and clinical stage of the tumor; therefore, we did not include T, M stage and lymph node status in the cox multifactor regression model. Ultimately, age ≥ 62 (P < 0.001), negative ER (P = 0.004), stage III (P = 0.044), and stage IV (P < 0.001) were related to a significantly increased risk of IMPC patients after surgery. In contrast, marital status (P < 0.001), white or other race (P = 0.002), chemotherapy (P < 0.001) and radiotherapy (P = 0.002) were associated with a significant reduction in risk. Kaplan–Meier analysis with the log rank test was performed for the above factors using the "survival" package of R software, and the same statistical results were obtained (Fig. 1). The study also found no significant difference in survival time among patients treated with two modalities of surgery. These results identified factors that may predict the occurrence of IMPC after surgery.
Table 2
Univariate and multifactorial Cox analysis of risk factors in IMPC of breast patients.
Characteristics | | Univariate analysis | | Multivariate analysis |
| | HR (95% CI) | P value | | HR (95% CI) | P value |
Age | | | | | | |
༜62 | | Reference | | | Reference | |
≥ 62 | | 2.730(2.057–3.622) | < 0.001* | | 2.460(1.812–3.340) | < 0.001* |
Race | | | | | | |
Black | | Reference | | | Reference | |
Other | | 0.299(0.161–0.556) | < 0.001* | | 0.362(0.192–0.684) | 0.002* |
White | | 0.512(0.367–0.716) | < 0.001* | | 0.578(0.409–0.816) | 0.002* |
Sex | | | | | | |
Female | | Reference | | | | |
Male | | 1.773(0.729–4.309) | 0.206 | | | |
Marital status | | | | | | |
Unmarried | | Reference | | | Reference | |
married | | 0.378(0.288–0.497) | < 0.001* | | 0.475(0.359–0.629) | < 0.001* |
unknown | | 0.466(0.218–0.997) | 0.049* | | 0.661(0.307–1.425) | 0.291 |
Breast subtype | | | | | | |
HR+/HER2- (Luminal A) | | Reference | | | | |
HR+/HER2+ (Luminal B) | | 0.833(0.473–1.468) | 0.527 | | | |
HR-/HER2+ (HER2 enriched) | | 0.668(0.211–2.113) | 0.492 | | | |
HR-/HER2- (Triple Negative) | | 3.891(2.166–6.988) | < 0.001* | | | |
Recode not available | | 1.014(0.737–1.396) | 0.932 | | | |
Stage | | | | | | |
Ⅰ | | Reference | | | Reference | |
Ⅱ | | 1.082(0.796–1.471) | 0.616 | | 1.154(0.752–1.772) | 0.511 |
Ⅲ | | 1.501(1.065–2.114) | 0.020* | | 1.726(1.016–2.931) | 0.044* |
Ⅳ | | 12.909(7.014–23.759) | < 0.001* | | 10.223(4.731–22.089) | < 0.001* |
T | | | | | | |
1 | | Reference | | | | |
2 | | 1.390(1.037–1.862) | 0.027* | | | |
3 | | 1.674(1.027–2.727) | 0.039* | | | |
4 | | 6.289(4.085–9.681) | < 0.001* | | | |
N | | | | | | |
0 | | Reference | | | | |
1 | | 0.878(0.642–1.201) | 0.416 | | | |
2 | | 1.003(0.625–1.610) | 0.990 | | | |
3 | | 1.779(1.204–2.628) | 0.004* | | | |
M | | | | | | |
0 | | Reference | | | | |
1 | | 11.440(6.373–20.536) | < 0.001* | | | |
ER | | | | | | |
Negative | | Reference | | | Reference | |
Positive | | 0.466(0.335–0.650) | < 0.001* | | 0.507(0.322-0.800) | 0.004* |
PR | | | | | | |
Negative | | Reference | | | Reference | |
Positive | | 0.587(0.443–0.776) | < 0.001* | | 0.792(0.537–1.168) | 0.239 |
HER-2 | | | | | | |
Negative | | Reference | | | | |
Positive | | 0.717(0.428–1.201) | 0.206 | | | |
Recode not available | | 0.912(0.669–1.243) | 0.561 | | | |
Lymph | | | | | | |
Negative | | Reference | | | | |
Positive | | 1.314(0.987–1.749) | 0.062 | | | |
No examined | | 3.186(2.185–4.645) | < 0.001* | | | |
Historic stage | | | | | | |
Localized | | Reference | | | | |
Regional | | 0.976(0.741–1.285) | 0.864 | | | |
Distant | | 4.282(2.770–6.617) | < 0.001* | | | |
Positive node | | | | | | |
༜4 | | Reference | | | | |
≥ 4 | | 3.098(2.203–4.356) | < 0.001* | | | |
Unknown/No examined | | 1.729(1.253–2.386) | 0.001* | | | |
Primary site | | | | | | |
Central portion of breast | | Reference | | | | |
Lower-inner | | 0.872(0.378–2.012) | 0.749 | | | |
Lower-outer | | 1.683(0.820–3.453) | 0.156 | | | |
Upper-inner | | 0.859(0.418–1.764) | 0.679 | | | |
Upper-outer | | 1.522(0.810–2.860) | 0.191 | | | |
other | | 1.169(0.622–2.197) | 0.628 | | | |
Laterality | | | | | | |
Left | | Reference | | | | |
Right | | 0.883(0.681–1.144) | 0.345 | | | |
Surgery | | | | | | |
BCS | | Reference | | | | |
Mastectomy | | 1.220(0.942–1.581) | 0.132 | | | |
Radiotherapy | | | | | | |
No | | Reference | | | Reference | |
Yes | | 0.592(0.456–0.769) | < 0.001* | | 0.652(0.449–0.853) | 0.002* |
Chemotherapy | | | | | | |
No/unknown | | Reference | | | Reference | |
Yes | | 0.554(0.424–0.724) | < 0.001* | | 0.557(0.402–0.771) | < 0.001* |
Tumor size | | | | | | |
≤ 20 | | Reference | | | Reference | |
20–50 | | 1.401(1.057–1.858) | 0.019* | | 1.339(0.888–2.018) | 0.163 |
༞50 | | 2.256(1.523–3.342) | < 0.001* | | 1.866(1.054–3.303) | 0.032* |
Development and validation of nomogram. To demonstrate the interrelationship between the variables, we constructed a nomogram predicting OS by integrating independent predictors. The results of nomogram showed that stage was the main factor affecting prognosis, followed by race, age, ER status, marital status, chemotherapy, and radiotherapy (Fig. 2). The prognostic models for the two groups were examined by plotting receiver operating characteristic (ROC) curves (Fig. 3). The AUCs of the training group were 0.792, 0.762 and 0.744 for 3 years, 5 years and 10 years, respectively (Fig. 3a-c), while those of the validation group were 0.766, 0.725 and 0.717, respectively (Fig. 3d-f). The C-index of this nomogram was 0.756 (95% confidence interval: 0.723–0.789), and the C-index of external validation was 0.742 (95% confidence interval: 0.693–0.791), indicating an accurate prognostic prediction of survival outcomes.
Next, the calibration curves and decision curve analyses (DCA) for the 3-year, 5-year, and 10-year OS were plotted for the training and validation sets. The generation of DCA curves validated the safety of the nomogram and has value for clinical application (Fig. 4a-f). The results of the calibration curves showed a strong agreement between the predictions of the nomogram and the actual observations of the 3-year, 5-year, and 10-year OS, indicating that the model was consistent (Fig. 5a-f). In summary, this nomogram model has good clinical application value in predicting the prognosis of IMPC patients after surgery.
Risk Assessment. According to the OS of postoperative risk of breast cancer, we divided the patients into three groups by “coxph” function, including low-risk group and high-risk group. By plotting Kaplan–Meier survival curves for each group, we found that the results of both the training and validation sets showed statistically significant differences in OS for patients with different risk levels (P < 0.001) (Fig. 6a-b). These results demonstrated the strong predictive value of this risk grouping system for the postoperative prognosis of IMPC patients, further demonstrating the application of this prognostic model.