Histological and biological evolution of human premalignant breast disease.

Allred, D. Craig; Mohsin, Syed K.; Fuqua, Suzanne A.W.

doi:10.1677/erc.0.0080047

Cited by 355 publications

(275 citation statements)

References 86 publications

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“…38 It appears that greater genetic similarity lies between columnar cell change and tubular carcinoma than between columnar cell atypia and tubular carcinoma. 39,40 This brings forth a more robust and factcompatible hypothesis that would explain the majority of instances of columnar cell atypia without eliminating the possibility of progression, only rendering it a statistically much less likely event once an isolated columnar cell atypia lesion is formed.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathologic characteristics of carcinomas that develop after a biopsy containing columnar cell lesions

Boulos

Dupont

Schuyler

et al. 2011

Cancer

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BACKGROUND: Columnar cell lesions are frequently associated with atypical ductal hyperplasia, lobular neoplasia, and tubular carcinoma, and have been suggested as a precursor lesion for low-grade carcinomas. However, in longterm follow-up studies, columnar cell lesions are associated with only a slight increase in later breast cancer development. If columnar cell lesions are precursor lesions, one would expect subsequent cancers to develop at the same site as the biopsy and to be preferentially of low grade. The goal of this article is to review the clinical and pathologic features of carcinomas that develop after a diagnosis of columnar cell lesion to try to establish whether these lesions are precursors to low-grade invasive carcinoma. METHODS: The authors reviewed biopsies containing columnar cell lesions, using the criteria of Schnitt and Vincent-Salomon, from 77 women in the Nashville Breast Cohort who developed subsequent breast carcinoma. Clinicopathologic features including laterality, type, and grade of the subsequent cancer were recorded. RESULTS: Breast cancer developed a median of 11 years after initial biopsy. The median age at diagnosis was 60 years. The majority of invasive carcinomas were of no special type and of intermediate grade. Moreover, the carcinomas were as likely to occur in the contralateral breast as in the breast that was originally diagnosed with columnar cell lesion, regardless of columnar cell lesion subtype (P ¼ .48). CONCLUSIONS: Carcinoma subsequent to columnar cell lesions may occur in either breast and tends to show a similar grade and type distribution as sporadic breast cancer. These findings argue against columnar cell lesions being a true precursor for lowgrade invasive carcinoma.

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Section: Discussionmentioning

confidence: 99%

Clinicopathologic characteristics of carcinomas that develop after a biopsy containing columnar cell lesions

Boulos

Dupont

Schuyler

et al. 2011

Cancer

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“…41 In situ neoplastic lesions are considered to represent early stages in the multistep process of carcinogenesis. 42,43 A positive correlation has been suggested to exist between incidence of in situ breast cancers and overall breast cancer incidence in a particular population. 44 The prognosis among patients with histologically similar in situ lesions varies.…”

Section: Discussionmentioning

confidence: 99%

Expression of UGT2B7, a UDP-Glucuronosyltransferase Implicated in the Metabolism of 4-Hydroxyestrone and All-Trans Retinoic Acid, in Normal Human Breast Parenchyma and in Invasive and in Situ Breast Cancers

Gestl¹,

Green²,

Shearer³

et al. 2002

The American Journal of Pathology

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Glucuronidation, mediated by UDP-glucuronosyltransferases (UGTs), affects the actions and disposition of diverse endo-and xenobiotics. In the case of catecholestrogens (CEs), glucuronidation is likely to block their oxidation to quinone estrogens that are the putative mediators of CEs' actions as initiators of cancers. The goal of this study was to determine whether UGT2B7, the isoenzyme with a high affinity for 4-hydroxyestrone, is expressed in human breast parenchyma. Glucuronidation of 4-hydroxyestrone has relevance to breast carcinogenesis because quinone metabolites of 4-hydroxylated CEs can form potentially mutagenic depurinating DNA adducts, and because in breast tissue estrone is likely to be the predominant estrogen available for 4-hydroxylation. Using reverse transcriptase-polymerase chain reaction, immunocytochemistry, immunoblot analyses, and assays of glucuronidation of 4-hydroxyestrone, we show that UGT2B7 is expressed in human mammary epithelium, and that its expression is dramatically reduced in invasive breast cancers. In many in situ carcinomas, however, 4-hydroxyestrone immunostaining was not only preserved but even more intense than in normal mammary epithelium. The finding of reduced UGT2B7 protein and glucuronidation of 4-hydroxyestrone in invasive cancers suggests a tumor-suppressor function for the enzyme. Recent identification of all-trans retinoic acid as a substrate of UGT2B7 suggests that this function includes the generation of retinoyl-␤-glucuronide, a potent mediator of actions of retinoids important for maintaining epithelia in a differentiated state. Current knowledge does not provide any ready explanation for the apparent increase in UGT2B7 expression in carcinomas in situ. However, this finding, together with reduced immunostaining at loci showing breach of the basement membrane (microinvasion), suggests involvement of UGT2B7-catalyzed reaction(s) in protection against invasion of surrounding tissue by cancer cells.

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“…Although DCIS is pre-malignant (Pinder and Ellis, 2003), the modest improvement in breast cancer mortality attributable to such screening (Mandelblatt et al, 2009;Nelson et al, 2009) has suggested that many DCIS cases never progress to invasive disease, raising questions about the contribution of DCIS to the natural history of sporadic IDC (Allred et al, 2001;Burstein et al, 2004). In tumours containing both IDC and DCIS (IDC-DCIS), it is unclear whether the IDC component arises directly from DCIS; in tumours lacking DCIS, however, it is assumed that IDC arises de novo.…”

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confidence: 99%

Presence of an in situ component is associated with reduced biological aggressiveness of size-matched invasive breast cancer

et al. 2010

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BACKGROUND: The metastatic propensity of invasive ductal carcinoma (IDC) of the breast correlates with axillary node involvement and with expression of the proliferation antigen Ki-67, whereas ductal carcinoma in situ (DCIS) is non-metastasising. To clarify whether concomitant DCIS affects IDC prognosis, we compared Ki-67 expression and node status of size-matched IDC subgroups either with DCIS (IDC-DCIS) or without DCIS (pure IDC). METHODS: We analysed data from 1355 breast cancer patients. End points were defined by the association of IDC (with or without DCIS) with grade, nodal status, Ki-67, and ER/HER2. RESULTS: Size-matched IDC-DCIS was more likely than pure IDC to be screen detected (P ¼ 0.03), to occur in pre-menopausal women (P ¼ 0.002), and to be either ER-positive (P ¼ 0.002) or HER2-positive (Po0.0005), but less likely to be treated with breast-conserving surgery (P ¼ 0.004). Grade and Ki-67 were lower in IDC-DCIS than in pure IDC (P ¼ 0.02), and declined as the DCIS enlarged (Po0.01). Node involvement and lymphovascular invasion in IDC-DCIS increased with the size ratio of IDC to DCIS (Po0.01). A 60-month cancer-specific survival favoured IDC-DCIS over size-matched pure IDC (97.4 vs 96.0%). CONCLUSION: IDC co-existing with DCIS is characterised by lower proliferation and metastatic potential than size-matched pure IDC, especially if the ratio of DCIS to IDC size is high. We submit that IDC-DCIS is biologically distinct from pure IDC, and propose an incremental molecular pathogenesis of IDC-DCIS evolution involving an intermediate DCIS precursor that remains dependent for replication on upstream mitogens.

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Histological and biological evolution of human premalignant breast disease.

Cited by 355 publications

References 86 publications

Clinicopathologic characteristics of carcinomas that develop after a biopsy containing columnar cell lesions

Clinicopathologic characteristics of carcinomas that develop after a biopsy containing columnar cell lesions

Expression of UGT2B7, a UDP-Glucuronosyltransferase Implicated in the Metabolism of 4-Hydroxyestrone and All-Trans Retinoic Acid, in Normal Human Breast Parenchyma and in Invasive and in Situ Breast Cancers

Presence of an in situ component is associated with reduced biological aggressiveness of size-matched invasive breast cancer

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