The prognostic role of HER2 expression in ductal breast carcinoma in situ (DCIS); a population-based cohort study

Abstract

BackgroundHER2 is a well-established prognostic and predictive factor in invasive breast cancer. The role of HER2 in ductal breast carcinoma in situ (DCIS) is debated and recent data have suggested that HER2 is mainly related to in situ recurrences. Our aim was to study HER2 as a prognostic factor in a large population based cohort of DCIS with long-term follow-up.MethodsAll 458 patients diagnosed with a primary DCIS 1986–2004 in two Swedish counties were included. Silver-enhanced in situ hybridisation (SISH) was used for detection of HER2 gene amplification and protein expression was assessed by immunohistochemistry (IHC) in tissue microarrays. HER2 positivity was defined as amplified HER2 gene and/or HER2 3+ by IHC. HER2 status in relation to new ipsilateral events (IBE) and Invasive Breast Cancer Recurrences, local or distant (IBCR) was assessed by Kaplan-Meier survival analyses and Cox proportional hazards regression models.ResultsPrimary DCIS was screening-detected in 75.5 % of cases. Breast conserving surgery (BCS) was performed in 78.6 % of whom 44.0 % received postoperative radiotherapy. No patients received adjuvant endocrine- or chemotherapy. The majority of DCIS could be HER2 classified (N = 420 (91.7 %)); 132 HER2 positive (31 %) and 288 HER2 negative (69 %)). HER2 positivity was related to large tumor size (P = 0.002), high grade (P < 0.001) and ER- and PR negativity (P < 0.001 for both). During follow-up (mean 184 months), 106 IBCRs and 105 IBEs were identified among all 458 cases corresponding to 54 in situ and 51 invasive recurrences. Eighteen women died from breast cancer and another 114 had died from other causes. The risk of IBCR was statistically significantly lower subsequent to a HER2 positive DCIS compared to a HER2 negative DCIS, (Log-Rank P = 0.03, (HR) 0.60 (95 % CI 0.38–0.94)). Remarkably, the curves did not separate until after 10 years. In ER-stratified analyses, HER2 positive DCIS was associated with lower risk of IBCR among women with ER negative DCIS (Log-Rank P = 0.003), but not for women with ER positive DCIS.ConclusionsImproved prognostic tools for DCIS patients are warranted to tailor adjuvant therapy. Here, we demonstrate that HER2 positive disease in the primary DCIS is associated with lower risk of recurrent invasive breast cancer.

The Relationships between HER2 Overexpression and DCIS Characteristics

“…The expression of high Ki67 level (>14%) in DCIS is an independent predictor of invasive recurrence, as reported in a study of Kerlikowske et al (10). This trial show that patients with ER-negative and HER2-positive DCIS expressing high levels of Ki67 (>10%) have higher risk of local DCIS recurrence than other patient groups (10). This agree to our results, because in our analysis patients affected by HER2-positive DCIS have a higher index of cell proliferation (Ki67 >14%, p = 0.003) and express lower levels of ER (p = 0.0006) and PgR (p = 0.0009) compared to HER2-negative ones.…”

“…The literature suggests that patients with HER2‐amplified DCIS have more frequently high nuclear grade (G3) DCIS and this aspect is related to an increased risk of relapse, but the prognostic role of HER2‐overexpression in DCIS is still not fully solved. In fact some studies suggested that HER2 plays a major role in the transition from DCIS to IDC, while others did not . The presence of comedonecrosis and calcifications within the tumor is predictive of recurrence regardless of HER2 status, as opposed to the presence of cancerization of lobules which is more frequent in HER2‐positive patients (p = 0.049).…”

Morphopathological and immunohistochemical features of a pure mucinous breast carcinoma – Case report

“…If for IBC, the negative impact on prognosis of HER2neu overexpresion is well establised, its role is still debate in DCIS [33]. The study of Borgquist S. et al proved that its positivity is associated with lower risk of recurrent invasive BC [34]. Recently, it was demonstrated that HER2neu amplification implies a high risk for DCIS recurrence [35].…”

Response to HER2 status might be independent determinant associated with no residual disease at surgical resection in patients with DCIS

“…It remains completely speculative at the present time how much, if any, HER2 status would add in addition to grade on predicting the likelihood of no residual disease at surgical resection. Most studies to date have suggested an increased risk of recurrence for HER2 positive DCIS and one study a lower risk of invasive recurrence . Thus far the studies are only hypothesis generating and our work cannot further contribute to answering this specific question.…”

“…Most studies to date have suggested an increased risk of recurrence for HER2 positive DCIS 3,4 and one study a lower risk of invasive recurrence. 5 Thus far the studies are only hypothesis generating and our work cannot further contribute to answering this specific question. We look forward to future studies addressing this issue.…”