Cell biological factors in ductal carcinoma in situ (DCIS) of the breast-relationship to ipsilateral local recurrence and histopathological characteristics

Ringberg, Anita; Anagnostaki, Lola; Anderson, Harald; Idvall, Ingrid; Fernö, Mårten

doi:10.1016/s0959-8049(01)00165-4

Cited by 100 publications

(95 citation statements)

References 41 publications

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“…The results we obtained were in agreement with other studies that reported an association between grade I and ER-positive tumor characteristics and between grade III and ER-negative tumor characteristics [39,40]. The ER/PR status showed less contribution to the bimodality phenomenon than grade.…”

Section: Discussionsupporting

confidence: 92%

Breast cancer as heterogeneous disease: contributing factors and carcinogenesis mechanisms

Kravchenko

Akushevich

Seewaldt

et al. 2011

Breast Cancer Res Treat

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The observed bimodal patterns of breast cancer incidence in the U.S. suggested that breast cancer may be viewed as more than one biological entity. We studied the factors potentially contributing to this phenomenon, specifically focusing on how disease heterogeneity could be linked to breast carcinogenesis mechanisms. Using empirical analyses and population-based biologically motivated modeling, age-specific patterns of incidence of ductal and lobular breast carcinomas from the SEER registry (1990)(1991)(1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002)(2003) were analyzed for heterogeneity and characteristics of carcinogenesis, stratified by race, stage, grade, and estrogen (ER)/progesterone (PR) receptor status. The heterogeneity of breast carcinoma age patterns decreased after stratification by grade, especially for grade I and III tumors. Stratification by ER/PR status further reduced the heterogeneity, especially for ER(?)/PR(-) and ER(-)/(-) tumors; however, the residual heterogeneity was still observed. The number of rate-limiting events of carcinogenesis and the latency of ductal and lobular carcinomas differed, decreasing from grade I to III, with poorly differentiated tumors associated with the least number of carcinogenesis stages and the shortest latency. Tumor grades play important role in bimodal incidence of breast carcinoma and have distinct mechanisms of carcinogenesis. Race and cancer subtype could play modifying role. ER/PR status contributes to the observed heterogeneity, but is subdominant to tumor grade. Further studies on sources of ''remaining'' heterogeneity of population with breast cancer (such as genetic/epigenetic characteristics) are necessary. The results of this study could suggest stratification rather than unification of breast cancer prevention strategies, risk assessment, and treatment.

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Section: Discussionsupporting

confidence: 92%

Breast cancer as heterogeneous disease: contributing factors and carcinogenesis mechanisms

Kravchenko

Akushevich

Seewaldt

et al. 2011

Breast Cancer Res Treat

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“…Studies of marker expression with respect to age in patients with DCIS are very limited, and to our knowledge there have been no reports of increased expression of HER-2/neu in younger DCIS patients. In one of the few studies to address this issue, Ringberg et al 29 found no association of age with expression of HER-2/neu, ER, PR, bcl-2, p53, or Ki-67.…”

Section: Discussionmentioning

confidence: 99%

“…Although Perin et al 30 did not find any molecular marker, including HER-2/neu, to significantly correlate with outcome in patients with pure DCIS, they did report a trend between high recurrence rate and both HER-2/neu and p53 overexpression. In their analysis of a group of patients with DCIS treated with lumpectomy alone, Ringberg et al 29 reported that the recurrence-free interval was shorter in patients with p53 accumulation, high Ki-67, or low bcl-2 on univariate analysis, although no significant association with HER-2/neu was demonstrated.…”

Section: Discussionmentioning

confidence: 99%

“…To our knowledge, there have been only a few studies examining the prognostic significance of these various molecular markers in patients with DCIS. 29,30 In their analysis of a group of patients with DCIS treated with lumpectomy alone, Ringberg et al 29 reported that the recurrence-free interval was shorter in patients with p53 accumulation, high Ki-67 expression, or low bcl-2 expression on univariate analysis. At the 1999 Consensus Conference on the treatment of DCIS, several panelists presented their own investigational experience with the use of prognostic markers; HER-2/neu expression was reported to demonstrate statistical significance for recurrence, and Ki-67 and p53 to display potential predictive value.…”

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confidence: 99%

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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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“…Several retrospective studies (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24) have reported outcome from DCIS managed by lumpectomy, with or without breast irradiation, and mastectomy. As expected, lumpectomy alone resulted in consistently higher rates of LR (range, 8%-34%) in comparison with patients treated by lumpectomy and breast radiation (range, 0%-17%).…”

Section: Selection Of Breast-conserving Surgery Vs Mastectomymentioning

confidence: 99%

Local Control of Ductal Carcinoma In Situ Based on Tumor and Patient Characteristics: The Surgeon's Perspective

Newman

2010

JNCI Monographs

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).Ductal carcinoma in situ (DCIS) is a disease whose manifestations are largely confined to in-breast pathology. Management strategies therefore focus on various combinations of local therapy: mastectomy, lumpectomy alone, and lumpectomy followed by breast irradiation. Although DCIS does not carry an inherent risk of distant organ metastasis, optimal local control is essential because any in-breast or chest wall recurrence may occur as an invasive lesion. Local recurrence has been reported following breast-conserving surgery as well as mastectomy. Breast radiation is therefore generally recommended following breastconserving surgery, and in selected circumstances, mastectomy may be the preferred treatment strategy. This article reviews the surgical and associated clinicopathologic issues related to initial biopsy and perioperative planning that should be considered for all DCIS cases to optimize local control.

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Cell biological factors in ductal carcinoma in situ (DCIS) of the breast-relationship to ipsilateral local recurrence and histopathological characteristics

Cited by 100 publications

References 41 publications

Breast cancer as heterogeneous disease: contributing factors and carcinogenesis mechanisms

Breast cancer as heterogeneous disease: contributing factors and carcinogenesis mechanisms

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

Local Control of Ductal Carcinoma In Situ Based on Tumor and Patient Characteristics: The Surgeon's Perspective

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