scholarly journals Copy number profiling of oncogenes in ductal carcinoma in situ of the male breast

2018 ◽  
Vol 25 (3) ◽  
pp. 173-184 ◽  
Author(s):  
Marijn A Vermeulen ◽  
Shusma C Doebar ◽  
Carolien H M van Deurzen ◽  
John W M Martens ◽  
Paul J van Diest ◽  
...  
Keyword(s):  
Copy Number ◽  
Ductal Carcinoma ◽  
Male Breast ◽  
Breast Carcinogenesis ◽  
Poor Overall Survival ◽  
Aberration Frequency ◽  
Number Ratio ◽  
Significant Difference ◽  
Copy Number Ratio

Characterizing male breast cancer (BC) and unraveling male breast carcinogenesis is challenging because of the rarity of this disease. We investigated copy number status of 22 BC-related genes in 18 cases of pure ductal carcinoma in situ (DCIS) and in 49 cases of invasive carcinoma (IC) with adjacent DCIS (DCIS-AIC) in males using multiplex ligation-dependent probe amplification (MLPA). Results were compared to female BC and correlated with survival. Overall, copy number ratio and aberration frequency including all 22 genes showed no significant difference between the 3 groups. Individual unpaired analysis revealed a significantly higher MTDH copy number ratio in IC compared to DCIS-AIC and pure DCIS (P = 0.009 and P = 0.038, respectively). ADAM9 showed a significantly lower copy number aberration frequency in male BC, compared to female BC (P = 0.020). In DCIS-AIC, MTDH, CPD, CDC6 and TOP2A showed a lower frequency of copy number increase in males compared to females (P < 0.001 for all 4 genes). In IC, CPD gain and CCNE1 gain were independent predictors of poor overall survival. In conclusion, male DCIS and IC showed a similar copy number profile for 21 out of 22 interrogated BC-related genes, illustrating their clonal relation and the genetically advanced state of male DCIS. MTDH showed a higher copy number ratio in IC compared to adjacent and pure DCIS and may therefore play a role in male breast carcinogenesis. Differences were detected between male and female DCIS for 4 genes pointing to differences in breast carcinogenesis between the sexes.

scholarly journals Loss of Y-Chromosome during Male Breast Carcinogenesis

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 631 ◽  
Author(s):  
Marie Colombe Agahozo ◽  
Mieke A. M. Timmermans ◽  
Hein F. B. M. Sleddens ◽  
Renée Foekens ◽  
Anita M. A. C. Trapman-Jansen ◽  
...  
Keyword(s):  
Y Chromosome ◽  
Carcinoma In Situ ◽  
Fluorescent In Situ Hybridization ◽  
Ductal Carcinoma ◽  
Male Breast ◽  
Early Event ◽  
Breast Carcinogenesis ◽  
Prognostic Effect ◽  
Number Of Patients

Loss of Y-chromosome (LOY) is associated with increased cancer mortality in males. The prevalence of LOY in male breast cancer (BC) is unknown. The aim of this study is to assess the presence and prognostic effect of LOY during male BC progression. We included male BC patients diagnosed between 1989 and 2009 (n = 796). A tissue microarray (TMA) was constructed to perform immunohistochemistry and fluorescent in situ hybridization (FISH), using an X and Y probe. We also performed this FISH on a selected number of patients using whole tissue slides to study LOY during progression from ductal carcinoma in situ (DCIS) to invasive BC. In total, LOY was present in 12.7% (n = 92) of cases, whereby LOY was associated with ER and PR negative tumors (p = 0.017 and p = 0.01). LOY was not associated with the outcome. Using whole slides including invasive BC and adjacent DCIS (n = 22), we detected a concordant LOY status between both components in 17 patients. In conclusion, LOY is an early event in male breast carcinogenesis, which generally starts at the DCIS stage and is associated with ER and PR negative tumors.

scholarly journals Promoter hypermethylation in ductal carcinoma in situ of the male breast

2019 ◽  
Vol 26 (6) ◽  
pp. 575-584 ◽  
Author(s):  
Marijn A Vermeulen ◽  
Carolien H M van Deurzen ◽  
Shusma C Doebar ◽  
Wendy W J de Leng ◽  
John W M Martens ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ductal Carcinoma ◽  
Methylation Status ◽  
Promoter Hypermethylation ◽  
Female Breast Cancer ◽  
Male Breast ◽  
Breast Carcinogenesis ◽  
Female Breast ◽  
Dependent Probe

Ductal carcinoma in situ (DCIS) of the male breast is very rare and has hardly been studied molecularly. In males, we compared methylation status of 25 breast cancer-related genes in pure DCIS (n = 18) and invasive breast carcinoma (IBC) with adjacent DCIS (DCIS-AIC) (n = 44) using methylation-specific multiplex ligation-dependent probe amplification. Results were compared to female breast cancer (BC). There were no significant differences in methylation features between male pure DCIS, DCIS-AIC and IBC after correction for multiple comparisons. In paired analysis of IBC and adjacent DCIS, CADM1 showed a significantly higher absolute methylation percentage in DCIS (P = 0.002). In cluster analysis, two clusters stood out with respectively infrequent and frequent methylation (GATA5, KLLN, PAX6, PAX5, CDH13, MSH6 and WT1 were frequently methylated). Compared to female DCIS, methylation was in general much less common in male DCIS, especially for VHL, ESR1, CDKN2A, CD44, CHFR, BRCA2, RB1 and STK11. In contrast, THBS1 and GATA5 were more frequently methylated in male DCIS. In conclusion, there is frequent methylation of GATA5, KLLN, PAX6, PAX5, CDH13, MSH6 and WT1 in male DCIS. Since there was little change in the methylation status for the studied genes from pure male DCIS to DCIS-AIC and IBC, methylation of these seven genes is more likely to occur early in male breast carcinogenesis. Based on the current markers male DCIS seems to be an epigenetically more advanced precursor of male BC, although in comparison to its female counterpart it appears that fewer loci harbor methylation, pointing to differences between male and female breast carcinogenesis with regard to the studied loci.

scholarly journals Pure Ductal Carcinoma in Situ in The Male Breast: A Rare Entity

2020 ◽  
Vol 16 (1) ◽  
pp. 77-80
Author(s):  
Saida Sakhri ◽  
◽  
Olfa Jaidane ◽  
Malek Bouhani ◽  
Olfa Adouni ◽  
...  
Keyword(s):  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Male Breast ◽  
Rare Entity

Ductal carcinoma in situ of the male breast. Analysis of 31 cases

1997 ◽  
Vol 33 (1) ◽  
pp. 35-38 ◽  
Author(s):  
B. Cutuli ◽  
J.M. Dilhuydy ◽  
B. De Lafontan ◽  
J. Berlie ◽  
M. Lacroze ◽  
...  
Keyword(s):  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Male Breast

scholarly journals Comparative Performance of Breast Cancer Human Epidermal Growth Factor Receptor 2 Fluorescence In Situ Hybridization and Brightfield In Situ Hybridization on College of American Pathologists Proficiency Tests

2018 ◽  
Vol 142 (10) ◽  
pp. 1254-1259 ◽  
Author(s):  
Katherine B. Geiersbach ◽  
Julia A. Bridge ◽  
Michelle Dolan ◽  
Lawrence J. Jennings ◽  
Diane L. Persons ◽  
...  
Keyword(s):  
Breast Cancer ◽  
In Situ Hybridization ◽  
Fluorescence In Situ Hybridization ◽  
Proficiency Testing ◽  
Copy Number ◽  
Fish Analysis ◽  
Proficiency Tests ◽  
Comparative Performance ◽  
Significant Difference

Context.— Fluorescence in situ hybridization (FISH) and brightfield in situ hybridization (ISH) are 2 clinically approved laboratory methods for detecting ERBB2 (HER2) amplification in breast cancer. Objective.— To compare the performance of FISH and brightfield ISH on proficiency testing administered by the College of American Pathologists Laboratory Accreditation Program. Design.— Retrospective review was performed on 70 tissue core samples in 7 separate proficiency testing surveys conducted between 2009 and 2013. Results.— The samples included 13 consensus-amplified tissue cores, 53 consensus-nonamplified cores, and 4 cores that did not reach consensus for FISH and/or brightfield ISH. There were 2552 individual responses for FISH and 1871 individual responses for brightfield ISH. Consensus response rates were comparable for FISH (2474 of 2524; 98.0%) and brightfield ISH (2135 of 2189; 97.5%). The FISH analysis yielded an average HER2 copy number per cell that was significantly higher (by 2.86; P = .02) compared with brightfield ISH for amplified cores. For nonamplified cores, FISH yielded slightly, but not significantly, higher (by 0.17; P = .10) HER2 copy numbers per cell. There was no significant difference in the average HER2 to control ratio for either consensus-amplified or consensus-nonamplified cores. Participants reported “unable to analyze” more frequently for brightfield ISH (244 of 2453; 9.9%) than they did for FISH (160 of 2684; 6.0%). Conclusions.— Our study indicates a high concordance rate in proficiency testing surveys, with some significant differences noted in the technical performance of these assays. In borderline cases, updated American Society of Clinical Oncology/College of American Pathologists cutoff thresholds that place greater emphasis on HER2 copy number per cell could accentuate those differences between FISH and brightfield ISH.

Impact of margin status and re-excision on local control in patients undergoing breast-conservation therapy for ductal carcinoma in situ.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 57-57
Author(s):  
Talha Shaikh ◽  
Tianyu Li ◽  
Fatima Sheikh ◽  
Colin T. Murphy ◽  
Nicholas Zaorsky ◽  
...  
Keyword(s):  
Local Control ◽  
Ductal Carcinoma In Situ ◽  
Hormonal Therapy ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Breast Conservation ◽  
Breast Conservation Therapy ◽  
Significant Difference ◽  
The Impact

57 Background: The purpose of this study was to identify the impact of final surgical margin (SM) status, SM width, and re-excision on outcomes in patients with ductal carcinoma in situ (DCIS) undergoing breast conservation therapy (BCT). Methods: The study population consisted of women diagnosed with DCIS undergoing BCT between 1989-2014. All women received adjuvant whole breast radiation plus a boost. The primary endpoint was local control (LC) defined as an ipsilateral breast failure. A negative SM was defined as > 2 mm, close SM was defined as > 0 to < 2 mm, and a positive SM was defined as tumor at the inked SM. Cox proportional hazards model was used to determine predictors of outcomes on multivariate analysis (MVA). Actuarial incidence of LC was estimated using the Kaplan-Meier method. Results: A total of 498 patients were included. The median age was 58 (range 30-91) and the median follow-up was 8.3 years (3 months-27 years). A total of 400 patients had a final negative SM, 87 had a close SM, and 11 had a positive SM. A total of 172 patients received adjuvant hormonal therapy, 265 patients required at least one re-excision. Patients with positive or close SMs were more likely to receive a radiation dose > 60 Gy (p < 0.001) and undergo re-excision (p < 0.01). The 10-year LC rates were not significantly different between patients with a negative (93.5%), close (91.8%), or positive (100%) SM (p = 0.57). There was no difference in 10-year LC rates according to a SM width of 0-1 mm (100%), > 1 to 2 mm (88.5%), or > 2 mm (93.5%) (p = 0.85). On univariate analysis, there was no significant difference in LC when comparing negative versus close or positive (p = 1.0) SMs. There was no difference in LC in patients undergoing re-excision for initial close or positive SMs (p = 0.55). On MVA, after controlling for age, dose, hormonal therapy, comedo subtype, and grade, there were no factors associated with LC. Conclusions: This large single-institution experience demonstrates that risks of local failure remain poorly characterized. Re-excision and whole breast radiation plus boost resulted in excellent LC for women with DCIS. Our data suggests that trials aimed at personalized de-intensified local therapy are warranted.

scholarly journals Differential copy number aberrations in novel candidate genes associated with progression from in situ to invasive ductal carcinoma of the breast

2012 ◽  
Vol 51 (12) ◽  
pp. 1067-1078 ◽  
Author(s):  
Shaoxi Liao ◽  
Mohamed M. Desouki ◽  
Daniel P. Gaile ◽  
Lori Shepherd ◽  
Norma J. Nowak ◽  
...  
Keyword(s):  
Candidate Genes ◽  
Invasive Ductal Carcinoma ◽  
Copy Number ◽  
Ductal Carcinoma ◽  
Carcinoma Of The Breast ◽  
Copy Number Aberrations

scholarly journals Ductal carcinoma in situ of the male breast

Cancer ◽  
1994 ◽  
Vol 74 (4) ◽  
pp. 1289-1293 ◽  
Author(s):  
Mauricio G. Camus ◽  
Megha G. Joshi ◽  
Gasan Mackarem ◽  
Arthur K. C. Lee ◽  
Ricardo L. Rossi ◽  
...  
Keyword(s):  
Ductal Carcinoma In Situ ◽  
Carcinoma In Situ ◽  
Ductal Carcinoma ◽  
Male Breast

scholarly journals PIK3CA mutations in ductal carcinoma in situ and adjacent invasive breast cancer

2019 ◽  
Vol 26 (5) ◽  
pp. 471-482 ◽  
Author(s):  
Marie Colombe Agahozo ◽  
Anieta M Sieuwerts ◽  
S Charlane Doebar ◽  
Esther I Verhoef ◽  
Corine M Beaufort ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Invasive Breast Cancer ◽  
Ductal Carcinoma ◽  
Specific Treatment ◽  
Digital Pcr ◽  
Patient Specific ◽  
Breast Carcinogenesis ◽  
Phosphatidylinositol 3 Kinase ◽  
Pik3ca Mutations

PIK3CA is one of the most frequently mutated genes in invasive breast cancer (IBC). These mutations are generally associated with hyper-activation of the phosphatidylinositol 3-kinase signaling pathway, which involves increased phosphorylation of AKT (p-AKT). This pathway is negatively regulated by the tumor suppressor PTEN. Data are limited regarding the variant allele frequency (VAF) of PIK3CA, PTEN and p-AKT expression during various stages of breast carcinogenesis. Therefore, the aim of this study was to gain insight into PIK3CA VAF and associated PTEN and p-AKT expression during the progression from ductal carcinoma in situ (DCIS) to IBC. We isolated DNA from DCIS tissue, synchronous IBC and metastasis when present. These samples were pre-screened for PIK3CA hotspot mutations using the SNaPshot assay and, if positive, validated and quantified by digital PCR. PTEN and p-AKT expression was evaluated by immunohistochemistry using the Histo-score (H-score). Differences in PIK3CA VAF, PTEN and p-AKT H-scores between DCIS and IBC were analyzed. PIK3CA mutations were detected in 17 out of 73 DCIS samples, 16 out of 73 IBC samples and 3 out of 23 lymph node metastasis. We detected a significantly higher VAF of PIK3CA in the DCIS component compared to the adjacent IBC component (P = 0.007). The expression of PTEN was significantly higher in DCIS compared to the IBC component in cases with a wild-type (WT) PIK3CA status (P = 0.007), while it remained similar in both components when PIK3CA was mutated. There was no difference in p-AKT expression between DCIS and the IBC component. In conclusion, our data suggest that PIK3CA mutations could be essential specifically in early stages of breast carcinogenesis. In addition, these mutations do not co-occur with PTEN expression during DCIS progression to IBC in the majority of patients. These results may contribute to further unraveling the process of breast carcinogenesis, and this could aid in the development of patient-specific treatment.

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