Oestrogen receptor expression in ductal carcinoma in situ of the breast: relationship to flow cytometric analysis of DNA and expression of the c-erbB-2 oncoprotein

Poller, David; Snead, David; Roberts, Elsa; Galea, M.; Bell, Jane M.; Gilmour, A; Elston, C. W.; Blamey, R.W.; Ellis, Ian O.

doi:10.1038/bjc.1993.305

Cited by 66 publications

(33 citation statements)

References 24 publications

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“…10,13,37 Although data are limited, several studies have not found this relation in patients with DCIS. 29,36,38 We also did not find a difference in ER expression with respect to age. In fact, our data showed a slightly higher percentage of patients in the younger group to be hormone receptor positive.…”

Section: Discussionmentioning

confidence: 54%

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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Section: Discussionmentioning

confidence: 54%

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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“…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%

“…1, HER2 protein overexpression has been reported in approximately 40% of DCIS, and in most studies is significantly more common in lesions of high-grade than in low-grade lesions. 1,10,[12][13][14][15][16][17][18][19][20][21] Until fairly recently, information regarding biomarker expression in DCIS was largely of academic interest, since the presence or absence of expression of any of these markers did not impact upon patient management decisions. However, in December 2002, Allred et al 45 presented the results of a study assessing the relationship between ER expression in DCIS and local recurrence in patients who had been treated by lumpectomy and radiation therapy, with or without tamoxifen.…”

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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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“…21) 2) Larger breast tumors, in which most tumor cells survive hypoxia, tend to be ER-negative. 22) 3) Breast tumors expressing a high level of VEGF, in which VEGF is presumably up-regulated by hypoxia, tend to be ERnegative and resistant to antiestrogen therapy.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia Reduces Hormone Responsiveness of Human Breast Cancer Cells

Kurebayashi¹,

Otsuki

Moriya

et al. 2001

Japanese Journal of Cancer Research

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Resistance to hormonal therapy frequently occurs following successful treatment in breast cancer. The mechanism responsible for this acquired resistance is still unknown. It has been suggested that a hypoxic tumor microenvironment promotes malignant progression of cancer, i.e., hypoxia may promote estrogen-independent growth (a more malignant phenotype) of breast cancer. To clarify this hypothesis, the effects of hypoxia on the growth responses to hormonal agents and the expression levels of estrogen receptor (

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Oestrogen receptor expression in ductal carcinoma in situ of the breast: relationship to flow cytometric analysis of DNA and expression of the c-erbB-2 oncoprotein

Cited by 66 publications

References 24 publications

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

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

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

Hypoxia Reduces Hormone Responsiveness of Human Breast Cancer Cells

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