Responsiveness of adjacent ductal carcinoma in situ and changes in HER2 status after neoadjuvant chemotherapy/trastuzumab treatment in early breast cancer: Results from the GeparQuattro study (GBG 40).

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 6-6
Author(s):  
G. Von Minckwitz ◽  
S. Darb-Esfahani ◽  
S. Loibl ◽  
J. B. Huober ◽  
H. Tesch ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Her2 Status ◽  
Her2 Overexpression ◽  
Her2 Expression ◽  
Her2 Positive ◽  
Complete Eradication

6 Background: Adjacent ductal carcinoma in situ (DCIS) is in found in approximately 45% of invasive ductal carcinomas (IDC) of the breast. Pure DCIS overexpresses HER2 in approximately 45%. There is uncertainty whether adjacent DCIS impacts on the response to neoadjuvant chemotherapy and trastuzumab as well as whether HER2 expression in IDC component or adjacent DCIS changes throughout treatment. Methods: Core biopsies and surgical tissue from participants of the GeparQuattro study with HER2-positive IDC were centrally examined for the area of invasive ductal component and adjacent DCIS before and after receiving neoadjuvant anthracycline-taxane-trastuzumab containing chemotherapy. HER2 overexpression in IDC and adjacent DCIS was quantified separately by immunohistochemistry using the Ventana automated staining system. Pathological complete response (pCR) was defined as no residual invasive or non-invasive tumor tissue. Results: Fifty nine (37.3%) of 158 IDCs presented with adjacent DCIS at diagnosis. These tumors showed lower regression grades than pure IDC (p=0.033). Presence of adjacent DCIS was an independent negative predictor of pCR (odds ratio 0.42 [95% CI 0.2-0.9], p=0.027). Adjacent DCIS area decreased from pre-treatment to surgery (r=0.205) with 30 (50.8%) IDCs with adjacent DCIS showing complete eradication of adjacent DCIS. HER2 status of adjacent DCIS was highly correlated with HER2 status of IDC component before (r=0.892) and after treatment (r=0.676). Degree of HER2 overexpression of the IDC component decreased in 16 (33.3%) out of 49 patients without a pCR. These 16 IDCs showed lower RGs compared to the 33 IDCs with unchanged HER2 expression (p=0.055). Conclusions: HER2-positive IDCs with adjacent DCIS is less responsive to neoadjuvant chemotherapy and trastuzumab compared to pure IDC. However, complete eradication of adjacent DCIS is frequently observed. HER2-overexpression of the invasive ductal component decreases in a subset of tumors, which showed less tumor regression.

Comparison of Radiation With or Without Concurrent Trastuzumab for HER2-Positive Ductal Carcinoma In Situ Resected by Lumpectomy: A Phase III Clinical Trial

2021 ◽  
pp. JCO.20.02824
Author(s):  
Melody A. Cobleigh ◽  
Stewart J. Anderson ◽  
Kalliopi P. Siziopikou ◽  
Douglas W. Arthur ◽  
Rachel Rabinovitch ◽  
...  
Keyword(s):  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Menopausal Status ◽  
Eastern Cooperative Oncology Group ◽  
Phase Iii ◽  
Her2 Status ◽  
P Value ◽  
Her2 Positive

PURPOSE Preclinical studies report that trastuzumab (T) can boost radiotherapy (RT) effectiveness. The primary aim of the B-43 trial was to assess the efficacy of RT alone vs concurrent RT plus T in preventing recurrence of ipsilateral breast cancer (IBTR) in women with ductal carcinoma in situ (DCIS). PATIENTS AND METHODS Eligibility: Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, DCIS resected by lumpectomy, known estrogen receptor (ER) and/or progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) status by centralized testing. Whole-breast RT was given concurrently with T. Stratification was by menopausal status, adjuvant endocrine therapy plan, and nuclear grade. Definitive intent-to-treat primary analysis was to be conducted when either 163 IBTR events occurred or all accrued patients were on study ≥ 5 years. RESULTS There were 2,014 participants who were randomly assigned. Median follow-up time as of December 31, 2019, was 79.2 months. At primary definitive analysis, 114 IBTR events occurred: RT arm, 63 and RT plus T arm, 51 (hazard ratio [HR], 0.81; 95% CI, 0.56 to 1.17; P value = .26). There were 34 who were invasive: RT arm, 18 and RT plus T arm, 20 (HR, 1.11; 95% CI, 0.59 to 2.10; P value = .71). Seventy-six were DCIS: RT arm, 45 and RT plus T arm, 31 (HR, 0.68; 95% CI, 0.43 to 1.08; P value = .11). Annual IBTR event rates were: RT arm, 0.99%/y and RT plus T arm, 0.79%/y. The study did not reach the 163 protocol-specified events, so the definitive analysis was triggered by all patients having been on study for ≥ 5 years. CONCLUSION Addition of T to RT did not achieve the objective of 36% reduction in IBTR rate but did achieve a modest but statistically nonsignificant reduction of 19%. Nonetheless, this trial had negative results. Further exploration of RT plus T is needed in HER2-positive DCIS before its routine delivery in patients with DCIS resected by lumpectomy.

Significance of HER2/neu overexpression in pure ductal carcinoma in situ: A clinicopathologic study with long-term follow-up.

2013 ◽  
Vol 31 (26_suppl) ◽  
pp. 85-85
Author(s):  
Zeina Al-Mansour ◽  
Thomas Stockl ◽  
Ashraf Khan ◽  
Richard Horner ◽  
Ediz Cosar ◽  
...  
Keyword(s):  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Disease Recurrence ◽  
Nuclear Grade ◽  
Her2 Overexpression ◽  
Her2 Positive ◽  
High Nuclear Grade

85 Background: The prognostic value of HER2 (c-ERB2) overexpression in invasive breast cancer is well known, and correlates with aggressivene behavior. HER2 overexpression was reported in 13-56% of ductal carcinoma in-situ (DCIS). The significance of HER2 overexpression in DCIS has yet to be elucidated. The aim of this study was to correlate HER2 status with known prognostic indicators of DCIS and to evaluate whether the HER2 overexpression correlates with disease recurrence. Methods: All cases of DCIS diagnosed at our institution between 2000 and 2005 were retrieved. Cases without follow-up, those treated with mastectomy or those with concurrent invasive component were excluded. Clinicopathologic data were collected, including age at time of diagnosis, size of the lesion, nuclear grade, presence of comedo necrosis, margin status, estrogen (ER) and progesterone receptor (PR) status, type of adjuvant treatment received and length of follow-up. A representative block from each case was immunostained using the Hercept test. Slides were reviewed by 2 pathologists and interpreted in accordance with ASCO/CAP guidelines. Equivocal cases were reflexed for FISH testing. Results: A total of 152 cases were examined. Mean follow-up period was 77 months (range 12 to 138 months). HER2 was overexpressed in 49 cases (33%), and was significantly associated with high nuclear grade and presence of comedo necrosis. HER2-positive patients were more likely to be ER and PR negative. HER2 positive and negative patients did not differ significantly with respect to age at presentation or size of DCIS. On univariate analysis, HER2-type DCIS showed a higher risk of recurrence (P=0.037), however, this trend did not reach statistical signifance on multivariate analysis. Conclusions: HER2 overexpression was found to be associated with high nuclear grade, comedo necrosis as well as negativity for ER and PR but not with age or the size of DCIS. Patients with HER2-type DCIS (ER/PR-, HER2+) had a higher risk of disease recurrence than other types. However, after adjusting for all the other clinical variables, the molecular phenotype did not withhold its statistical significance as an independent predictor for recurrence.

Histiocytoid Ductal Carcinoma In Situ of the Breast: Not All Intraductal Foamy Cells Are Macrophages!

2019 ◽  
Vol 27 (8) ◽  
pp. 872-875
Author(s):  
Hélène Dano ◽  
Christine Galant ◽  
Maude Coyette ◽  
Mieke R. Van Bockstal
Keyword(s):  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Clear Cell ◽  
Ductal Carcinoma ◽  
Screening Mammography ◽  
Her2 Overexpression ◽  
Breast Cancers ◽  
Cell Component ◽  
Diagnostic Challenge

With the advent of screening mammography, the incidence of ductal carcinoma in situ (DCIS) has increased. DCIS accounts for around 20% of breast cancers diagnosed at present. The histiocytoid variant of clear cell DCIS is a rare subtype of DCIS, characterized by epithelial cells with a clear and foamy cytoplasm. Histiocytoid DCIS serves as a potential diagnostic pitfall, since it can be easily mistaken for intraductal collections of foamy macrophages. In this article, we report a particular case of biphasic DCIS, characterized by an extensive histiocytoid-type clear cell component and a conventional “non-clear” cell component. Both components presented with HER2 protein overexpression. We discuss the diagnostic challenge and differential diagnosis of clear cell DCIS, as well as the role of HER2 overexpression in DCIS pathogenesis.

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