scholarly journals Intraductal Proliferative Lesions of the Breast—Terminology and Biology Matter: Premalignant Lesions or Preinvasive Cancer?

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Leopoldo Costarelli ◽  
Domenico Campagna ◽  
Maria Mauri ◽  
Lucio Fortunato
Keyword(s):  
Ductal Carcinoma ◽  
Intraepithelial Neoplasia ◽  
Premalignant Lesions ◽  
Flat Epithelial Atypia ◽  
Low Grade ◽  
Usual Ductal Hyperplasia ◽  
Morphological Criteria ◽  
Ductal Hyperplasia ◽  
Malignant Lesions ◽  
Molecular Aspects

Morphological criteria for the diagnosis of intraductal proliferative lesions of the breast have been an object of research and much controversy, and its terminology is rather confusing. Knowledge of the molecular aspects of this disease probably necessitates further research to clarify if these entities can be identified as breast cancer precursors or as a malignant preinvasive disease. These issues are of great interest not only for their biological implications, but also to the clinician who must understand the disease and direct therapies. Molecular studies have shown that epitheliosis (usual ductal hyperplasia) is not monoclonal, while malignant lesions (atypical ductal hyperplasia, flat epithelial atypia, low-grade and high-grade intraductal carcinoma) constantly show these characteristics. These malignant lesions, classified with a DIN grading system (ductal intraepithelial neoplasia), are not obligate precursors of invasive ductal carcinoma and do not represent different evolving grades in a linear model of cancerogenesis. Breast cancerogenesis probably has different pathways with different morphologic precursors.

scholarly journals Estrogen Receptor and Cytokeratin 5 Are Reliable Markers to Separate Usual Ductal Hyperplasia From Atypical Ductal Hyperplasia and Low-Grade Ductal Carcinoma In Situ

2016 ◽  
Vol 140 (7) ◽  
pp. 686-689 ◽  
Author(s):  
Anthony P. Martinez ◽  
Cynthia Cohen ◽  
Krisztina Z. Hanley ◽  
Xiaoxian (Bill) Li
Keyword(s):  
Estrogen Receptor ◽  
Progesterone Receptor ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Atypical Ductal Hyperplasia ◽  
Low Grade ◽  
Usual Ductal Hyperplasia ◽  
Ductal Hyperplasia ◽  
Cytokeratin 5

Context.—High–molecular weight cytokeratins, such as cytokeratin 5 (CK5), are helpful to distinguish usual ductal hyperplasia (UDH) from atypical ductal hyperplasia (ADH) or low-grade ductal carcinoma in situ (DCIS). Few studies have looked at combining CK5 with estrogen receptor (ER) to differentiate UDH from ADH. Objective.—To evaluate the expression pattern of CK5 and ER as single or combined markers to separate UDH from ADH and low-grade DCIS. Design.—A total of 23 ADH, 10 low-grade DCIS, and 32 UDH whole-tissue slides were stained for ER, CK5, progesterone receptor (PR), and Bcl-2. Nuclear staining of ER and PR was scored as diffuse (>80%), focal (10%–80%), or negative (<10%). Cytoplasmic staining of CK5 and Bcl-2 was scored as diffuse (>60%), focal (10%–60%), or negative (<10%). Differences in staining patterns were evaluated. Results.—For ER staining: 94% of ADH/DCIS cases showed a diffuse staining pattern, whereas none of the 32 UDH cases showed diffuse staining. For CK5 staining: 96% of ADH/DCIS cases were negative or focally positive, whereas all 32 UDH cases had diffuse staining. The combination of ER and CK5 increased the sensitivity (94% to 97%). For PR staining: 11 of 23 ADH cases (48%), 6 of 10 DCIS cases (60%), and 4 of 32 UDH cases (13%) showed diffuse staining. Bcl-2 staining showed no statistical significance (P = .73). Conclusions.—Although morphology remains the gold standard, ER and CK5 are useful makers to differentiate UDH from ADH. Progesterone receptor staining may have limited value, and Bcl-2 staining is not useful.

Flat Epithelial Atypia of the Breast

2008 ◽  
Vol 132 (4) ◽  
pp. 615-621 ◽  
Author(s):  
Melinda F. Lerwill
Keyword(s):  
Time Course ◽  
Ductal Carcinoma ◽  
Flat Epithelial Atypia ◽  
Low Grade ◽  
Tubular Carcinoma ◽  
Ductal Cells ◽  
Ductal Hyperplasia ◽  
Atypical Cells ◽  
Architectural Characteristics ◽  
Epithelial Atypia

Abstract Flat epithelial atypia is a presumably neoplastic alteration of terminal duct-lobular units that is characterized by the replacement of the native luminal epithelium by ductal cells demonstrating low-grade cytologic atypia. The atypical cells maintain a “flat” pattern of growth without evidence of architectural atypicality. Morphologic, immunohistochemical, and molecular investigations support that flat epithelial atypia represents an early step in the evolution of low-grade ductal carcinomas. It is frequently seen in association with atypical ductal hyperplasia, low-grade ductal carcinoma in situ, invasive tubular carcinoma, and lobular neoplasia. The risk for subsequent breast carcinoma remains to be defined, but flat epithelial atypia likely represents a nonobligate precursor with an extended time course to progression. Certain benign alterations may superficially mimic its appearance; careful attention to cytologic and architectural characteristics can help one distinguish these unrelated entities from flat epithelial atypia.

Histological Assessment of Breast Lesions Identified Exclusively by Magnetic Resonance

2014 ◽  
Vol 80 (10) ◽  
pp. 944-947
Author(s):  
Victoria O'connor ◽  
Elizabeth Arena ◽  
Joslyn Albright ◽  
Nefertiti Brown ◽  
Ryan O'connor ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Magnetic Resonance ◽  
Breast Biopsy ◽  
Ductal Carcinoma ◽  
Low Grade ◽  
Breast Lesions ◽  
Significant Family History ◽  
Ductal Hyperplasia ◽  
Significant Pathology

Radiologic–pathologic correlation of lesions diagnosed by magnetic resonance (MR) is precluded by insufficient data on histological characteristics of lesions suspicious on MR but not visible on concurrent mammogram or ultrasound. The objective of this study was to describe histological features of breast lesions diagnosed exclusively by MR. The participants underwent MR-guided breast biopsy between 2007 and 2012 for a suspicious lesion not identified by mammography or ultrasound. Histology slides were interpreted retrospectively by a breast pathologist. Of 126 patients (126 lesions), 34 (27%) had new breast cancer, 51 (40.5%) previous breast cancer, and 41 (32.5%) dense breasts or a significant family history of breast cancer. MR identified 23 (18.3%) invasive cancers: 20 were Grade 1 and 17 were ductal. Of the 126 lesions, 16 (13%) were ductal carcinoma in situ (DCIS), four were atypical ductal hyperplasia and atypical lobular hyperplasia (3%), and 68 (54%) were benign. Fifteen biopsies (12%) had no significant pathology. Five DCIS lesions were upgraded to T1 invasive cancers. Approximately 30 per cent of suspicious lesions detected exclusively by MR are invasive or in situ cancers that are predominantly low grade. Further studies are needed to determine if malignant lesions can be prospectively distinguished by MR characteristics.

Transitions Between Flat Epithelial Atypia and Low-grade Ductal Carcinoma In Situ of the Breast

2012 ◽  
Vol 36 (8) ◽  
pp. 1247-1252 ◽  
Author(s):  
Sebastian Aulmann ◽  
Lisa Braun ◽  
Friederike Mietzsch ◽  
Thomas Longerich ◽  
Roland Penzel ◽  
...  
Keyword(s):  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Flat Epithelial Atypia ◽  
Low Grade ◽  
Epithelial Atypia

scholarly journals Prevalence of c-myc expression in breast lesions associated with microcalcifications detected by routine mammography

2009 ◽  
Vol 127 (2) ◽  
pp. 66-70 ◽  
Author(s):  
Renato Coimbra Mazzini ◽  
Simone Elias ◽  
Afonso Celso Pinto Nazário ◽  
Cláudio Kemp ◽  
Ângela Flávia Logullo
Keyword(s):  
Breast Imaging ◽  
Ductal Carcinoma ◽  
Percutaneous Biopsy ◽  
Screening Mammography ◽  
University Hospital ◽  
Premalignant Lesions ◽  
Breast Lesions ◽  
Benign Lesions ◽  
Cross Sectional ◽  
Malignant Lesions

CONTEXT AND OBJECTIVE: Genetic abnormalities in cell proliferation-regulating genes have been described in premalignant lesions. The aims here were to evaluate c-myc protein expression in non-palpable breast lesions associated with microcalcifications, detected by screening mammography, and to compare these results with histopathological, clinical and epidemiological variables. DESIGN AND SETTING: Analytical cross-sectional study, with retrospective data collection, in a university hospital in São Paulo. METHODS: Seventy-nine female patients who underwent routine mammography between 1998 and 2004 were studied. Lesions classified by the Breast Imaging Reporting and Data System (BI-RADS) as 4 or 5 underwent percutaneous biopsy using a large-core needle. Ninety-eight lesions were studied anatomopathologically. Paraffin blocks properly representing the lesions were selected for immunohistochemical analyses using the streptavidin-biotin-peroxidase technique with monoclonal mouse c-myc antibodies. RESULTS: Among the 98 lesions, 29 (29.6%) contained malignant neoplasia; 40 (40.8%) had a positive immunohistochemical reaction for c-myc. When the groups were divided between lesions without atypias versus atypical lesions plus malignant lesions, 31.03% of the 58 lesions without atypias were positive for c-myc and 55% of the 40 malignant and atypical lesions (P = 0.018). Comparing the atypical lesions with ductal carcinoma in situ versus the benign lesions without atypias, c-myc was present in 51.61% of the 31 atypical lesions and 31.03% of the benign lesions without atypias (P = 0.057). CONCLUSION: C-myc protein was more frequently expressed in atypical and malignant lesions than in benign lesions without atypias. C-myc expression correlated with the presence of atypias (P = 0.018).

Subareolar Sclerosing Ductal Hyperplasia

2016 ◽  
Vol 25 (1) ◽  
pp. 4-11 ◽  
Author(s):  
Esther Cheng ◽  
Timothy M. D’Alfonso ◽  
Maria Arafah ◽  
Rebecca Marrero Rolon ◽  
Paula S. Ginter ◽  
...  
Keyword(s):  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Lobular Carcinoma ◽  
Low Grade ◽  
Solitary Lesion ◽  
Ductal Hyperplasia ◽  
Long Term Follow Up ◽  
Initial Description

Subareolar sclerosing duct hyperplasia (SSDH) remains to be fully characterized nearly 20 years after initial description. Thirty-five SSDH cases diagnosed over a 16-year period (January 2000 to December 2015) were reviewed. All patients were female (mean age = 59 years, range = 18-80) who had presented with a unilateral solitary lesion (left 22, right 13) with a mean size of 1.3 cm (range = 0.4-3.0 cm), and showed florid and papillary epithelial hyperplasia with dense sclerosis without involvement of nipple or areolar epidermis. Significant lesions concurrent within SSDH included low-grade adenosquamous carcinoma (n = 1), ductal carcinoma in situ (DCIS; n = 1), lobular carcinoma in situ (LCIS; n = 1), and atypical ductal hyperplasia (ADH; n = 13). No case of SSDH recurred in a mean follow-up of 44 months (range = 6-189). Subsequent significant lesions occurred in 6 patients: DCIS (n = 3; ipsilateral 2, contralateral 1), ipsilateral ADH (n = 2), and ipsilateral atypical lobular hyperplasia (n = 1). Long-term follow-up for patients with SSDH is indicated as DCIS can occur subsequently in either breast.

scholarly journals Is Carboxypeptidase B1 a Prognostic Marker for Ductal Carcinoma In Situ?

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1726
Author(s):  
Charu Kothari ◽  
Alisson Clemenceau ◽  
Geneviève Ouellette ◽  
Kaoutar Ennour-Idrissi ◽  
Annick Michaud ◽  
...  
Keyword(s):  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Breast Tissue ◽  
Ductal Carcinoma ◽  
Mrna Level ◽  
Gene Signature ◽  
Low Grade ◽  
Tissue Samples ◽  
Ductal Hyperplasia

Ductal carcinoma in situ (DCIS) is considered a non-obligatory precursor for invasive ductal carcinoma (IDC). Around 70% of women with atypical ductal hyperplasia (ADH) undergo unnecessary surgery due to the difficulty in differentiating ADH from low-grade DCIS. If untreated, 14–60% of DCIS progress to IDC, highlighting the importance of identifying a DCIS gene signature. Human transcriptome data of breast tissue samples representing each step of BC progression were analyzed and high expression of carboxypeptidase B1 (CPB1) expression strongly correlated with DCIS. This was confirmed by quantitative PCR in breast tissue samples and cell lines model. High CPB1 expression correlated with better survival outcome, and mRNA level was highest in DCIS than DCIS adjacent to IDC and IDC. Moreover, loss of CPB1 in a DCIS cell line led to invasive properties associated with activation of HIF1α, FN1, STAT3 and SPP1 and downregulation of SFRP1 and OS9. The expression of CPB1 could predict 90.1% of DCIS in a cohort consisting of DCIS and IDC. We identified CPB1, a biomarker that helps differentiate DCIS from ADH or IDC and in predicting if a DCIS is likely to progress to IDC, thereby helping clinicians in their decisions.

scholarly journals Randomized Placebo Controlled Trial of Low-Dose Tamoxifen to Prevent Local and Contralateral Recurrence in Breast Intraepithelial Neoplasia

2019 ◽  
Vol 37 (19) ◽  
pp. 1629-1637 ◽  
Author(s):  
Andrea DeCensi ◽  
Matteo Puntoni ◽  
Aliana Guerrieri-Gonzaga ◽  
Silvia Caviglia ◽  
Franca Avino ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Intraepithelial Neoplasia ◽  
Hazard Ratio ◽  
Number Needed To Treat ◽  
Ductal Hyperplasia ◽  
Patient Reported

PURPOSE Tamoxifen administered for 5 years at 20 mg/d is effective in breast cancer treatment and prevention, but toxicity has limited its broad use. Biomarker trials showed that 5 mg/d is not inferior to 20 mg/d in decreasing breast cancer proliferation. We hypothesized that a lower dose given for a shorter period could be as effective in preventing recurrence from breast intraepithelial neoplasia but have a lower toxicity than the standard dose. PATIENTS AND METHODS We conducted a multicenter randomized trial of tamoxifen, 5 mg/d or placebo administered for 3 years after surgery in women with hormone-sensitive or unknown breast intraepithelial neoplasia, including atypical ductal hyperplasia and lobular or ductal carcinoma in situ. The primary end point was the incidence of invasive breast cancer or ductal carcinoma in situ. RESULTS Five hundred women 75 years of age or younger were included. After a median follow-up of 5.1 years (interquartile range, 3.9-6.3 years), there were 14 neoplastic events with tamoxifen and 28 with placebo (11.6 v 23.9 per 1,000 person-years; hazard ratio, 0.48; 95% CI, 0.26 to 0.92; P = .02), which resulted in a 5-year number needed to treat of 22 (95% CI, 20 to 27). Tamoxifen decreased contralateral breast events by 75% (three v 12 events; hazard ratio, 0.25; 95% CI, 0.07 to 0.88; P = .02). Patient-reported outcomes were not different between arms except for a slight increase in frequency of daily hot flashes with tamoxifen ( P = .02). There were 12 serious adverse events with tamoxifen and 16 with placebo, including one deep vein thrombosis and one stage I endometrial cancer with tamoxifen and one pulmonary embolism with placebo. CONCLUSION Tamoxifen at 5 mg/d for 3 years can halve the recurrence of breast intraepithelial neoplasia with a limited toxicity, which provides a new treatment option in these disorders.

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