Pathobiologic Findings in DCIS of the Breast: Morphologic Features, Angiogenesis, HER-2/neu and Hormone Receptors

Claus, Elizabeth B.; Chu, Peiguo; Howe, Christine L.; Davison, Tracey L.; Stern, David F.; Carter, Darryl; DiGiovanna, Michael P.

doi:10.1006/exmp.2001.2366

Cited by 69 publications

(62 citation statements)

References 72 publications

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“…Only one prior study has reported upon the frequency of HER2 overexpression in ERpositive DCIS. In that study of 219 cases, Claus et al, 23 using separate immunostains for ER and HER2, found that 19% of ER-positive DCIS also showed HER2 overexpression. Further details about these cases are not provided.…”

Section: Discussionmentioning

confidence: 99%

“…1,56 We also found, as have others, an inverse relationship between ER expression and HER2 overexpression in most cases of DCIS. 10,23,24,35 However, to our knowledge, ours is the first study to utilize double immunostaining to assess ER expression and HER2 overexpression in relation to each other within individual cases of DCIS. Our results indicate that overall, approximately 10% of the DCIS cases we studied showed simultaneous ER expression and HER2 overexpression.…”

Section: Discussionmentioning

confidence: 99%

“…While studies of patients with DCIS have generally shown an inverse relationship between ER expression and HER2 overexpression, 10,23,24,35 details of the relationship between ER and HER2 expression in individual examples of DCIS has previously received little attention. The purpose of this study, therefore, was to assess the frequency of ER expression and HER2 overexpression in DCIS in relation to each other and in relation to DCIS grade, and to determine the frequency and histologic correlates of HER2 overexpression in ER-positive DCIS.…”

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confidence: 99%

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HER2 protein overexpression in estrogen receptor-positive ductal carcinoma in situ of the breast: frequency and implications for tamoxifen therapy

Collins

Schnitt

2005

Modern Pathology

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Recent clinical data have suggested that the efficacy of tamoxifen in reducing the risk of local recurrence following lumpectomy and radiation therapy in patients with ductal carcinoma in situ (DCIS) is limited to patients with estrogen receptor (ER)-positive lesions. However, it is currently not known if HER2 protein overexpression might be associated with reduced tamoxifen benefit in patients with ER-positive DCIS, as has been suggested in patients with ER-positive invasive breast cancer and in preclinical models. Moreover, the frequency of HER2 overexpression in ER-positive ductal carcinoma in situ has not been previously evaluated in detail. To address this issue, we studied ER expression and HER2 overexpression in 148 cases of DCIS using a sensitive double immunostaining technique and assessed the frequency of ER expression and HER2 overexpression in relation to each other and in relation to DCIS grade. Overall, ER expression was seen in 114 cases (77%) and HER2 protein overexpression was seen in 42 cases (28%). Of 114 ER-positive ductal carcinoma in situ, 14 (12%) showed concurrent HER2 protein overexpression, and all 14 of these DCIS lesions were of high nuclear grade. In addition, in all 14 ER-positive DCIS cases that showed HER2 overexpression, double immunostaining demonstrated that ER and HER2 protein were coexpressed by the same neoplastic cells. We conclude that a subset of ER-positive DCIS show concomitant overexpression of HER2 protein.Whether or not HER2 overexpression is associated with a diminished response to tamoxifen in patients with ER-positive DCIS will require investigation in clinical outcome studies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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HER2 protein overexpression in estrogen receptor-positive ductal carcinoma in situ of the breast: frequency and implications for tamoxifen therapy

Collins

Schnitt

2005

Modern Pathology

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“…30,31,34 -36 HER-2/neu expression has been shown to be particularly high in DCIS of the comedocarcinoma subtype and/or high-grade DCIS. 29,[32][33][34][35] Features strongly associated with HER-2/neu expression (high-grade tumor, the presence of necrosis, and overexpression of Ki-67, indicating an increased proliferation rate) are all aggressive features that have been reported to correlate with recurrence. It is interesting to note that even though patients in our younger group demonstrated no difference in tumor grade or the presence of necrosis compared with patients in our older group, they were more likely to be HER-2/neu positive.…”

Section: Discussionmentioning

confidence: 99%

“…Reports from other groups of hormone-receptor positivity in DCIS have ranged from 60% to 74%. 34,39 This difference may be partially a result of different age cutoff values because the young group in other studies often only included patients age Ͻ 35 years.…”

Section: Discussionmentioning

confidence: 99%

Differences in the pathologic and molecular features of intraductal breast carcinoma between younger and older women

Rodrigues

Dillon

Carter

et al. 2003

Cancer

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BACKGROUNDPatients diagnosed with ductal carcinoma in situ (DCIS) at a young age appear to have a different natural history and biology, including a higher local relapse rate, than patients diagnosed later in life. The current study compared various pathologic and molecular features of DCIS arising in a cohort of young women with those of DCIS arising in a cohort of older women to identify potential biologic differences between these two populations of patients.METHODSThe study population consisted of 20 patients age < 42 years and 34 patients age > 60 years who were treated at Yale University School of Medicine with breast‐conserving therapy (BCT) and whose archival paraffin blocks were available and had sufficient tumor for staining. The original slides from each case were reviewed and the most representative specimen block from each case was processed for immunohistochemical staining. Pathologic characteristics evaluated for each case included histology, grade, and presence of necrosis. Paraffin‐embedded sections were immunohistochemically evaluated for expression of HER‐2/neu, estrogen receptor (ER), progesterone receptor (PR), bcl‐2, cyclin D1, Ki‐67, and p53.RESULTSAlthough there was no difference in pathologic features of the tumors between the two groups, HER‐2/neu was found to be overexpressed in a greater percentage of the younger population (P = 0.06). There was no apparent difference in expression of the other markers. Of note, HER‐2/neu expression was correlated with high nuclear grade (P = 0.004), necrosis (P = 0.06), and ER and PR negativity (P = 0.01 and P = 0.03, respectively) in the combined population.CONCLUSIONSThe current study data suggested that HER‐2/neu overexpression in younger patients may characterize a biologic difference in their tumor and may partially contribute to their higher risk of recurrence. Further studies are needed to assess whether this difference holds independent of grade and to evaluate the prognostic significance of HER‐2/neu overexpression in DCIS. Cancer 2003;97:1393–1403. © 2003 American Cancer Society.DOI 10.1002/cncr.11204

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Treatment with infliximab for a child with Behçet's disease

Saulsbury¹,

Mann²

2003

Arthritis & Rheumatism

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BACKGROUND Patients diagnosed with ductal carcinoma in situ (DCIS) at a young age appear to have a different natural history and biology, including a higher local relapse rate, than patients diagnosed later in life. The current study compared various pathologic and molecular features of DCIS arising in a cohort of young women with those of DCIS arising in a cohort of older women to identify potential biologic differences between these two populations of patients. METHODS The study population consisted of 20 patients age < 42 years and 34 patients age > 60 years who were treated at Yale University School of Medicine with breast‐conserving therapy (BCT) and whose archival paraffin blocks were available and had sufficient tumor for staining. The original slides from each case were reviewed and the most representative specimen block from each case was processed for immunohistochemical staining. Pathologic characteristics evaluated for each case included histology, grade, and presence of necrosis. Paraffin‐embedded sections were immunohistochemically evaluated for expression of HER‐2/neu, estrogen receptor (ER), progesterone receptor (PR), bcl‐2, cyclin D1, Ki‐67, and p53. RESULTS Although there was no difference in pathologic features of the tumors between the two groups, HER‐2/neu was found to be overexpressed in a greater percentage of the younger population (P = 0.06). There was no apparent difference in expression of the other markers. Of note, HER‐2/neu expression was correlated with high nuclear grade (P = 0.004), necrosis (P = 0.06), and ER and PR negativity (P = 0.01 and P = 0.03, respectively) in the combined population. CONCLUSIONS The current study data suggested that HER‐2/neu overexpression in younger patients may characterize a biologic difference in their tumor and may partially contribute to their higher risk of recurrence. Further studies are needed to assess whether this difference holds independent of grade and to evaluate the prognostic significance of HER‐2/neu overexpression in DCIS. Cancer 2003;97:1393–1403. © 2003 American Cancer Society. DOI 10.1002/cncr.11204

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Pathobiologic Findings in DCIS of the Breast: Morphologic Features, Angiogenesis, HER-2/neu and Hormone Receptors

Cited by 69 publications

References 72 publications

HER2 protein overexpression in estrogen receptor-positive ductal carcinoma in situ of the breast: frequency and implications for tamoxifen therapy

HER2 protein overexpression in estrogen receptor-positive ductal carcinoma in situ of the breast: frequency and implications for tamoxifen therapy

Differences in the pathologic and molecular features of intraductal breast carcinoma between younger and older women

Treatment with infliximab for a child with Behçet's disease

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