The Unique Biology behind the Early Onset of Breast Cancer (original) (raw)
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Breast cancer genetics in young women: What do we know?
Mutation Research/Reviews in Mutation Research, 2017
Breast cancer (BC) in young women, generally defined in oncology as women who are 40 years of age or under, represents 2 out of 10 BC cases in developing countries. Several studies, including genetic cancer panel analyses, genome-wide association studies, expression analyses and polymorphism reports, have found that young women with BC exhibit a higher genetic susceptibility and specific genomic signature compared to postmenopausal women with BC. Thus, international guidelines recommend genetic counseling for this age population. This review presents our current knowledge of genetics and genomics with regards to young women with BC.
MicroRNA profile in very young women with breast cancer
BMC Cancer, 2014
Background: Breast cancer is rarely diagnosed in very young women (35years old or younger), and it often presents with distinct clinical-pathological features related to a more aggressive phenotype and worse prognosis when diagnosed at this early age. A pending question is whether breast cancer in very young women arises from the deregulation of different underlying mechanisms, something that will make this disease an entity differentiated from breast cancer diagnosed in older patients.
Breast cancer in young women: clinicopathological features and biological specificity
Breast, 2003
S U M M A R Y . Literature data suggest that breast cancers occurring in young patients may be different from those arising in older women. In this study the clinicopathologic characteristics of 50 patients under 40 years of age were compared with those of patients aged over 60. Patients under 40 years old more frequently had a family history of breast cancer than did older patients (24% vs 17%) and had more often used oral contraceptives (29% vs 13%); on average they had experienced menarche 1 year earlier. For early onset breast carcinomas there was a higher frequency of grade 3 tumours (38% vs 17%) and oestrogen receptor negativity (46% vs 20%). In addition, in younger patients the carcinomas were mostly DNA aneuploid (78% vs 58%), with a higher proliferation rate (48% vs 26%) and more frequent c-erbB-2 overexpression (48% vs 26%) and p53 alteration (30% vs 8%). Our data demonstrate that breast cancers arising in young women have a significantly different biopathological profile from those in older patients, with a predominance of unfavourable prognostic parameters. r
Inherited and acquired alterations in development of breast cancer
The Application of Clinical Genetics, 2011
Breast cancer is the most common cancer among women, accounting for about 30% of all cancers. In contrast, breast cancer is a rare disease in men, accounting for less than 1% of all cancers. Up to 10% of all breast cancers are hereditary forms, caused by inherited germ-line mutations in "high-penetrance," "moderate-penetrance," and "low-penetrance" breast cancer susceptibility genes. The remaining 90% of breast cancers are due to acquired somatic genetic and epigenetic alterations. A heterogeneous set of somatic alterations, including mutations and gene amplification, are reported to be involved in the etiology of breast cancer. Promoter hypermethylation of genes involved in DNA repair and hormone-mediated cell signaling, as well as altered expression of micro RNAs predicted to regulate key breast cancer genes, play an equally important role as genetic factors in development of breast cancer. Elucidation of the inherited and acquired genetic and epigenetic alterations involved in breast cancer may not only clarify molecular pathways involved in the development and progression of breast cancer itself, but may also have an important clinical and therapeutic impact on improving the management of patients with the disease.
PLoS ONE, 2013
Breast cancer in young women is more aggressive with a poorer prognosis and overall survival compared to older women diagnosed with the disease. Despite recent research, the underlying biology and molecular alterations that drive the aggressive nature of breast tumors associated with breast cancer in young women have yet to be elucidated. In this study, we performed transcriptomic profile and network analyses of breast tumors arising in Middle Eastern women to identify age-specific gene signatures. Moreover, we studied molecular alterations associated with cancer progression in young women using cross-species comparative genomics approach coupled with copy number alterations (CNA) associated with breast cancers from independent studies. We identified 63 genes specific to tumors in young women that showed alterations distinct from two age cohorts of older women. The network analyses revealed potential critical regulatory roles for Myc, PI3K/Akt, NF-κB, and IL-1 in disease characteristics of breast tumors arising in young women. Cross-species comparative genomics analysis of progression from pre-invasive ductal carcinoma in situ (DCIS) to invasive ductal carcinoma (IDC) revealed 16 genes with concomitant genomic alterations, CCNB2, UBE2C, TOP2A, CEP55, TPX2, BIRC5, KIAA0101, SHCBP1, UBE2T, PTTG1, NUSAP1, DEPDC1, HELLS, CCNB1, KIF4A, and RRM2, that may be involved in tumorigenesis and in the processes of invasion and progression of disease. Array findings were validated using qRT-PCR, immunohistochemistry, and extensive in silico analyses of independently performed microarray datasets. To our knowledge, this study provides the first comprehensive genomic analysis of breast cancer in Middle Eastern women in age-specific cohorts and potential markers for cancer progression in young women. Our data demonstrate that cancer appearing in young women contain distinct biological characteristics and deregulated signaling pathways. Moreover, our integrative genomic and cross-species analysis may provide robust biomarkers for the detection of disease progression in young women, and lead to more effective treatment strategies.
Clinical Cancer Research, 2004
Purpose: To provide a molecular rationale for negative prognostic factors more prevalent in African-American (AA) than Caucasian (Cau) women, we investigated the frequency of promoter hypermethylation in invasive ductal breast cancers in the two races. Experimental Design: HIN-1, Twist, Cyclin D2, RAR-, and RASSF1A were analyzed in DNA from 67 AA and 44 Cau invasive ductal breast cancers, stratified by age and estrogen receptor/progesterone receptor (ER/PR) status, by methylation-specific PCR. Hierarchical multiple logistic regression analysis was applied to determine estimated probabilities of methylation. Expression of HIN-1 mRNA was analyzed by in situ hybridization and quantitative reverse transcribed PCR. Results: Significant differences between races were observed in the ER؊/PR؊, age < 50 subgroup; AA tumors had higher frequency of methylation (P < 0.001) in four of five genes as compared with Cau and also a higher prevalence (80 versus 0%; P < 0.005) of three or more methylated genes per tumor. No differences in gene methylation patterns were observed across the two races for ER؉/PR؉ tumors in all ages and ER؊/PR؊ tumors in age > 50. ER؉/PR؉ status was associated with higher frequency of methylation in Cau tumors of all ages but only with the age > 50 subgroup in AA. Frequent Cyclin D2 methylation was significantly associated (P ؍ 0.01) with shorter survival time. Conclusion: ER؊/PR؊, age < 50 tumors in AA women, have a significantly higher frequency of hypermethylation than in those of Cau women. Comparative studies, such as these, could provide a molecular basis for differences in tumor progression and pathology seen in the two races.
The genetics of breast cancer: risk factors for disease
The Application of Clinical Genetics, 2011
The genetic factors known to be involved in breast cancer risk comprise about 30 genes. These include the high-penetrance early-onset breast cancer genes, BRCA1 and BRCA2, a number of rare cancer syndrome genes, and rare genes with more moderate penetrance. A larger group of common variants has more recently been identified through genome-wide association studies. Quite a number of these common variants are mapped to genomic regions without being firmly associated with specific genes. It is thought that most of these variants have gene regulatory functions, but their precise roles in disease susceptibility are not well understood. Common variants account for only a small percentage of the risk of disease because they have low penetrance. Collectively, the breast cancer genes identified to date contribute only ∼30% of the familial risk. Therefore, there is much interest in accounting for the missing heritability, and possible sources include loss of information through ignoring phenotype heterogeneity (disease subtypes have genetic differences), gene-gene and gene-environment interaction, and rarer forms of variation. Identification of these rarer variations in coding regions is now feasible and cost effective through exome sequencing, which has already identified high-penetrance variants for some rare diseases. Targeting more 'extreme' breast cancer phenotypes, particularly cases with early-onset disease, a strong family history (not accounted for by BRCA mutations), and with specific tumor subtypes, provides a route to progress using next-generation sequencing methods.
Breast Cancer in Young Patients: Same or Different Entity?
Women's Health Science Journal
Overview Breast cancer is the most common pathology in women of reproductive age; approximately 7% of breast carcinomas are diagnosed in women less than 40 years of age, corresponding to more than 40% of all malignant diseases diagnosed in this group. Genetic factors play a fundamental role in the genesis of the breast cancer in young patients. However, it is not easy to analyze them because their clinical usefulness is limited and there are multiple factors that must be considered. We conducted a retrospective study in which we included female patients of ages 40 years old or less, diagnosed with breast cancer at a private medical center during the period of January 2010 to July 2014. The protocol of the study included a complete clinical study, radiological reports as mammography and/or ultrasound image, histopathological and immunohistochemistry reports. The study included 46 patients with an average age of presentation of 37.1 years, a standard deviation (SD) of ±3.02 years and ...
Epidemiology and prognosis of breast cancer in young women
Journal of thoracic disease, 2013
Breast cancer is the most common malignancy in women with 6.6% of cases diagnosed in young women below the age of 40. Despite variances in risk factors, Age Standardized Incidence Rates of breast cancer in young women vary little between different countries. Review of modifiable risk factors shows that long-term use of oral contraceptives, low body mass index (BMI) and high animal fat diet consumption are associated with increased risk of premenopausal breast cancer. Decreased physical activity and obesity increase risks of breast cancer in postmenopausal women, but data on premenopausal women rather shows that high BMI is associated with decreased risk of breast cancer. Non-modifiable risk factors such as family history and genetic mutations do account for increased risks of breast cancer in premenopausal women. Breast cancer in young women is associated with adverse pathological factors, including high grade tumors, hormone receptor negativity, and HER2 overexpression. This has a ...