Prognostic Factors and a Nomogram Predicting Survival in Patients with Breast Ductal Carcinoma in situ with Microinvasion: A Population-Based Study

Abstract

Purpose: Ductal carcinoma in situ with microinvasion (DCISM) can be challenging to balance the risks of overtreatment versus undertreatment. We aim to identify prognostic factors in patients with DCISM and construct a nomogram to predict breast cancer-specific survival (BCSS).

Materials and methods: A retrospective cohort study of women diagnosed with DCISM from 1988 to 2015 who were identified in the Surveillance, Epidemiology and End Results database. Clinical variables and tumor characteristics were evaluated, and Cox proportional-hazards regression was performed. A nomogram was constructed from the multivariate logistic regression to combine all the prognostic factors to predict the prognosis of DCISM patients at 5 years, 10 years, and 15 years.

Results: We identified 5438 total eligible breast cancer patients with a median and max survival time of 78 and 227 months, respectively. Here, patients with poorer survival outcomes were those diagnosed between 1988 and 2001, African-American race, under 40 years of age, higher tumor N stage, progesterone receptor-negative tumor, and received no surgery. The nomogram was constructed by the seven variables and passed the calibration and validation steps. The area under the receiver operating characteristic (ROC) curve (AUC) of both the training set and the validating set (5-year AUC: 0.77 and 0.88, 10-year AUC: 0.75 and 0.73, 15-year AUC: 0.72 and 0.65). Receiving chemotherapy was associated with a better BCSS (hazard ratio, HR=0.45, 95% confidence interval, 95% CI = 0.23-0.89), especially in patients with estrogen receptor (ER) negative, progesterone receptor (PR) negative (HR = 0.35, 95% CI = 0.13-0.97) and ER+PR-/ER-PR+ DCISM (HR = 0.07, 95% CI = 0.01-0.59).

Conclusion: Our current study is the first to construct nomograms of patients with DCISM which could help physicians identify breast cancer patients that more likely to benefit from more intensive treatment and follow-up. Chemotherapy might benefit patients with ER-PR- and ER+PR-/ER-PR+ DCISM.

Keywords: breast cancer; ductal carcinoma in situ; microinvasion; nomogram; survival.

Figure 1

Flowchart of the case selection process in the study.

Figure 2

Nomogram to calculate risk score and predict 5-year, 10-year, and 15-year BCSS probability. By summing the points identified on the top scale for each independent variable and drawing a vertical line from the total points scale to the 5-year, 10-year, and 15-year BCSS, the corresponding survival probability can be obtained. Age, 1 = under 40 years, 2 = 41–50 years, 3 = 51–70 years, 4 = over 70 years; Race, 1 = Caucasian, 2 = African American, 3 = American Indian/Alaska Native or Asian/Pacific Islander; Year of diagnosis, 1 = 1988–2001, 2 = 2002–2015; AJCC 6th N stage, 0 = N0 stage, 1 = N1 stage, 2 = N2 stage, 3 = N3 stage; Surgery, 0 = no surgery, 1 = lumpectomy, 2 = mastectomy; Chemotherapy, 0 = no, 1 = yes; PR status, 0 = negative, 1 = positive.

Figure 3

ROC curves and calibration plots for predicting BCSS. ROC curves of the nomogram predicting prognosis in the training set (A) and the validating set (B). Calibration curves comparing predicted and actual BCSS proportions at 5-year (C), 10-year (D), and 15-years (E), separately. Each point in the plot refers to a group of patients, with the nomogram predicted probability of survival shown on x axis and actual survival proportion shown on y axis. Distributions of predicted survival probabilities are plotted at the top. Error bars represent 95% confidence intervals. (F) 5-year, 10-year and 15-year BCSS in patients with each subtype of breast ductal carcinoma in situ with microinvasion.

Figure 4

The survival curves for DCISM patients with and without chemotherapy and radiotherapy after 1:1 matching. (A) Kaplan-Meier curve depicting the association between chemotherapy and breast DCISM. Kaplan-Meier curve depicting the association between chemotherapy and breast DCISM in ER+PR+ (B), ER+PR-/ER-PR+ (C) and ER-PR- subgroup (D). (E) Kaplan-Meier curve depicting the association between radiotherapy and breast DCISM.