Triple-negative and HER2 positive ductal carcinoma in situ of the breast: characteristics, behavior, and biomarker profile

Abstract

We compared the characteristics, clinical behavior, and biomarker profile between HER2 positive (HER2+) and triple-negative (TN) ductal carcinoma in situ (DCIS) which are considered more aggressive than other DCIS subtypes. In addition, we explored the impact of these features on its potential of progression to invasive breast carcinomas. Cases of DCIS diagnosed at the Department of Pathology, Singapore General Hospital from 1994 to 2010 were identified. TN and HER2+ DCIS cases formed the study cohort. Immunohistochemistry (IHC) was performed for ER, PR, HER2, CK14, EGFR, and p53. Comparisons of clinicopathological features, IHC results, and clinical outcomes were performed between the two groups. We evaluated 145 HER2+ and 85 TN DCIS cases. HER2 positive DCIS had significantly higher nuclear grade (p < 0.001) and more frequent necrosis (p < 0.001) than TN DCIS. HER2 positive DCIS also harbored significantly higher rates of nuclear p53 immunoreactivity (p = 0.002) than TN DCIS. Younger patients (age < 40) with HER2+ and TN DCIS demonstrated statistically significant worse invasive DFS than older women (p < 0.001). Multivariate cox regression analysis (HR 15.08, 95% CI 12.79-81.45, p = 0.002) also confirmed these findings. In addition, younger patients (age < 40) with HER2+ DCIS experienced significantly poorer prognosis when p53 was also positive (p = 0.033). HER2+ DCIS had more aggressive pathological characteristics compared to TN DCIS; accumulation of mutant p53 could possibly be contributory. Age was an independent predictor of aggressive biological behavior of HER2+ and TN DCIS. We demonstrated that younger patients with p53 positive HER2+ DCIS had significantly adverse clinical outcome.

Comparative analysis of clinicopathological characteristics of central necrotizing breast cancer and basal cell-like breast cancer

“…The most prominent feature of CNC is that the center of the tumor was accompanied by extensive necrosis, and the necrotic zone was usually surrounded by residual cancer tissue distributed in ribbons. Such a wide area of necrosis also suggests that CNC is more malignant and more aggressive ( 1 , 22 , 23 ). The Ki-67 index of residual cancer cells in the zonal distribution around the necrotic area was relatively low, which may be due to the existence of slow-cycling quiescent cells or senescent cells in these residual cancer cells.…”

Molecular subtyping reveals uniqueness of prognosis in breast ductal carcinoma in situ patients with lumpectomy

“…However, HR-HER2- DCIS does not have the worst prognosis among these four molecular subtypes. It was reported to have less aggressive features than HR-HER2+ DCIS [ 33 ]. In our study, HR-HER2- cases have a higher grade and more comedo necrosis than HR+HER2+ cases ( Table 1 ).…”

The impact of HER2-directed targeted therapy on HER2-positive DCIS of the breast

“…Although DCIS has been thought to be single disease entity, there is evidence that DCIS, much like invasive breast cancer, encompasses a broad and heterogenous group of diseases that can be differentiated by varying degrees of biological aggressiveness [6]. For example, classifying DCIS similarly to IBC may be a way to determine prognoses based on disease biology [7,8]. However, individualizing treatment options and management based on this information is still controversial.…”

“…However, there is growing interest in using HER2-targeted therapy for HER2-amplified DCIS patients. While there is conflicting evidence on the effect of HER2 positivity on disease characteristics and patient outcomes [7,8,[12][13][14][15][16][17], there remains strong interest in the role of HER2-targeted therapy. The National Surgical Adjuvant Breast and Bowel Project (NSABP) is currently running a clinical trial (B-43) examining the effect of trastuzumab on the risk of in-breast tumor recurrence for patients with HER2 positive DCIS [4].…”