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 ◽  
...  

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.

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21101-21101
Author(s):  
R. Bakkar ◽  
Z. Nahleh ◽  
H. Bui ◽  
S. Samaan ◽  
J. Sanders ◽  
...  

21101 Background: Tumor angiogenesis and vascularization are essential for the growth and metastasis of tumors. VEGF-C expression and peritumoral lymphocyte density (PLD) are markers of angiogenesis. They have been correlated with poor prognosis in female breast cancer (FBC). The purpose of this study is to characterize VEGF-C expression and PLD in MBC and correlate with FBC specimens. Method: We reviewed records of patients diagnosed with MBC and FBC at the Cincinnati VAMC, from 1989 to 2006. Pathology slides were retrieved. We used VEGF-C (Host Rabbit, PAD: Z-CVC7) . Imunohistochemical stains of VEGF-C were given scores of 0 to 3+ based on nuclear stains. PLD was analyzed based on the number of lymphocyte cells surrounding the tumor; score of 0 to 3+. Slides were reviewed independently by two pathologists. Results: We found nine MBC cases and selected 9 FBC cases. Mean age was 72 in the male patients and 62 in the females. Stages of disease were distributed as follows in MBC versus FBC, 11% versus 22% stage 0, 23% versus 23% stage I, 44% versus 44% stage II, and 22% versus 11% stage IV. Ductal carcinoma was the predominant histology in 88% of FBC and 88% MBC. Other histological types included papillary (1 MBC) and lobular (1 FBC). Among the invasive MBC tumors , 75 % were ER+/PR +, 13% ER+/PR-, and 12% ER -/PR- , compared to 72 % ER+/PR+, 14% ER+/PR-, and 14% ER-/PR- in FBC. Eight out of the 9 MBC cases (89%) stained positive for VEGF-C expression, compared to one FBC case (11%). The 1 male breast intraductal carcinoma was positive for VEGF-C expression, compared to none of the two intraductal FBC. PLD was more intense in male than female tumors : score 0 or 1+: 44% in MBC versus 67% in FBC , score 2+: 22% in MBC Versus 22% in FBC, and score 3+: 22% in MBC versus 11% in FBC. VEGF-C expression did not seem to correlate with ER/PR status. The median survival for patients with MBC was 4.5 years and for patients with FBC 6.9 years. Conclusion: VEGF-C expression and PLD were more pronounced in MBC versus FBC. This finding may correlate with more aggressive behavior of breast tumor cells in male patients, more intense angiogenic reaction and lower median survival. Further studies are warranted to further elucidate the role of angiogenesis in male breast cancer and explore potential antiangiogenic therapeutic modalities. No significant financial relationships to disclose.


Author(s):  
Anwitha Johns ◽  
Satish Kumar B P ◽  
Lavanya P R

Background & Objectives: Breast cancer is the second leading reason for cancer death in women. Incidence rates of male breast cancer have increased by 0.2- 1% per year. The lack of knowledge and awareness of male breast cancer leads to its detection at a late stage in men. This study is to assess the knowledge and attitude of south Indian adults towards male and female breast cancer. Methods: To assess the knowledge and attitude of adults on breast cancer, a questionnaire regarding basic knowledge and attitudes was formulated using Google forms. Numbers and percentages were formed to review categorical and nominal data. Chi-square (χ2) test was used for the comparison between the awareness of female breast cancer and male breast cancer. P < 0.05 was set as the level of significance.


2010 ◽  
Vol 28 (3) ◽  
pp. 149-165 ◽  
Author(s):  
Seng Liang ◽  
Manjit Singh ◽  
Lay-Harn Gam

Female breast cancer is one of the leading causes of female mortality worldwide. In Malaysia, breast cancer is the most commonly diagnosed cancer in women. Of the women in Malaysia, the Chinese have the highest number of breast cancer cases, followed by the Indian and the Malay. The most common type of breast cancer is infiltrating ductal carcinoma (IDC). A proteomic approach was applied in this study to identify changes in the protein profile of cancerous tissues compared with normal tissues from 18 patients; 8 Chinese, 6 Malay and 4 Indian were analysed. Twenty-four differentially expressed hydrophilic proteins were identified. We evaluated the potential of these proteins as biomarkers for infiltrating ductal carcinoma based on their ethnic-specific expressions. Three of the upregulated proteins, calreticulin, 14-3-3 protein zeta and 14-3-3 protein eta, were found to be expressed at a significantly higher level in the cancerous breast tissues when compared with the normal tissues in cases of infiltrating ductal carcinoma. The upregulation in expression was particularly dominant in the Malay cohort.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Mona M. Mohamed ◽  
Salwa Sabet ◽  
Dun-Fa Peng ◽  
M. Akram Nouh ◽  
Mohamed El-Shinawi ◽  
...  

Reactive oxygen species (ROS) play a crucial role in breast cancer initiation, promotion, and progression. Inhibition of antioxidant enzymes that remove ROS was found to accelerate cancer growth. Studies showed that inhibition of glutathione peroxidase-3 (GPX3) was associated with cancer progression. Although the role of GPX3 has been studied in different cancer types, its role in breast cancer and its epigenetic regulation have not yet been investigated. The aim of the present study was to investigate GPX3 expression and epigenetic regulation in carcinoma tissues of breast cancer patients’ in comparison to normal breast tissues. Furthermore, we compared GPX3 level of expression and methylation status in aggressive phenotype inflammatory breast cancer (IBC) versus non-IBC invasive ductal carcinoma (IDC). We found that GPX3 mRNA and protein expression levels were downregulated in the carcinoma tissues of IBC compared to non-IBC. However, we did not detect significant correlation between GPX3 and patients’ clinical-pathological prosperities. Promoter hypermethylation of GPX3 gene was detected in carcinoma tissues not normal breast tissues. In addition, IBC carcinoma tissues showed a significant increase in the promoter hypermethylation of GPX3 gene compared to non-IBC. Our results propose that downregulation of GPX3 in IBC may play a role in the disease progression.


2004 ◽  
Vol 83 (1) ◽  
pp. 77-86 ◽  
Author(s):  
William F. Anderson ◽  
Michelle D. Althuis ◽  
Louise A. Brinton ◽  
Susan S. Devesa

2019 ◽  
Vol 26 (5) ◽  
pp. 471-482 ◽  
Author(s):  
Marie Colombe Agahozo ◽  
Anieta M Sieuwerts ◽  
S Charlane Doebar ◽  
Esther I Verhoef ◽  
Corine M Beaufort ◽  
...  

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.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11618-e11618
Author(s):  
R. D. Botan ◽  
M. N. Alvares ◽  
A. Hassan

e11618 Background: Treatment for male breast cancer is based on the results of large clinical trials for female breast cancer. Although peculiar differences do exist between men and women, very little is known about the prognostic factors in male breast cancer, even though female breast cancer practical conducts are widely used in male breast cancer. The rarity of this condition makes very difficult to produce randomized trials. Methods: This study is populational and epidemiological and evaluated male breast cancer patients from January 1974 to December 2001 about its prognostic characteristics. Data were collected retrospectively and the sample has been described using descriptive statistics methods. Survival curve was built using Kaplan-Meier method. Staging system was standardized as in the sixth edition of American Joint Committee on Cancer, independently on when the diagnose was made. Due to differences throughtout 35 years on therapeutic on breast cancer, treatment options were categorized in groups to make the survival evaluation possible. Results: From 45 patients with male breast cancer, 91% presented ductal histology, 26% were negative axillary, 9.1% were T1, 25% were T2, 4.5% were T3, 50% were T4 and 12.12% presented with distant metastasis at diagnose. Seventy nine percent were submitted to radical local treatment, while 34% had not been submitted to any kind of systemic treatment (neoadjuvant, adjuvant e hormone therapy). Forty percent of patients have not presented distant recurrence, while 58.3% have not presented local recurrence. A median survival of 126 months has been observed to the analyzed population, ranging from 69–182 months. Five-year survival was 72% and 10-year survival was 54%. These data agreed with the available data in the published literature. Conclusions: Male breast cancer appears to behave biologically and clinically very similar to female breast cancer, but differences do exist and need to be elucidated. Randomized multi-center clinical trials become necessary, as systematic reviews, to build higher statistic power studies. No significant financial relationships to disclose.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6555-6555
Author(s):  
Elizabeth Shurell Linehan ◽  
Navendu D. Samant ◽  
Juleon W Rabbani

6555 Background: Male breast cancer (MBC) accounts for approximately 1% of all breast cancers. Racial disparities have not been examined in MBC. Methods: Within a large, integrated health delivery system, all adult female and male patients who were diagnosed with breast cancer from 01-01-2010 to 12-31-2018 were examined. Bivariate analysis was performed to examine clinical and demographic factors associated with breast cancer-related mortality. We conducted more detailed chart review in the MBC-only group (data period 01-01-2010 to 12-31-2019) to assess the mean time to treatment (from diagnosis to surgery, surgery to chemotherapy, and surgery to radiation) stratified by race using bivariate (t-test, one way ANOVA) analyses. Results: 32,848 female breast cancer and 226 MBC patients were evaluated; MBC patients represented 0.63% of all breast cancer patients. Between males and females, there was no statistically significant difference in race, with an overall distribution of 62% White, 19% Asian, 8% Black, and 11% Hispanic. To our knowledge, this is the largest and most racially diverse sample of MBC patients to date. MBC patients at diagnosis were significantly older (p <.0001), more obese (p < 0.0018), and sicker according to the Charlson Comorbidity Index (CCI) (p < 0.0001) compared to female breast cancer patients. Males were more likely to be diagnosed at an advanced stage (19.2%) compared to females (12.5%) (p = 0.0037). With a mean follow up of 5 years, overall mortality was statistically significantly worse in MBC (23.0%) compared to female breast cancer patients (12.0%) (p < 0.0001). Furthermore, breast cancer-related mortality was significantly higher in males (8.1%) than in females (4.5%) (p = 0.0124). In the MBC-only analysis, stage at diagnosis was not influenced by patient race. Asian and White MBC patients had the shortest mean time from diagnosis to surgery (27 and 29 days, respectively), with Hispanic MBC patients experiencing the longest time to surgery (46 days). Black MBC patients experienced the shortest mean time to chemotherapy after surgery (39 days), whereas Asian MBC patients experienced the longest time to chemotherapy (50 days). In survivorship, Black and Asian patients were least likely to undergo screening mammography (33.3%, and 43.3%, respectively), compared to 52% of White and 50% of Hispanic MBC patients. Ultimately, 13% of Asian and 11% of Hispanic MBC patients died of breast cancer, compared to 6.7% of Black and 6.2% of White MBC patients. Conclusions: While we found no statistically significant differences in mortality by race among MBC patients, our findings indicate that non-white patients had longer time to treatments, less survivorship screening, and worse disease related mortality than their white counterparts. Future study can elucidate these racial inequalities, enabling more equitable breast cancer treatment among patient subgroups.


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