Evaluating mitochondrial DNA in patients with breast cancer and benign breast disease

Purpose

To evaluate the role of mtDNA in breast cancer.

Methods

We carried out an investigation into the mtDNA major control region or D-loop region and an essential and the largest mtDNA protein-coding gene, NADH dehydrogenase subunit 5 (ND5), together with a mitochondrial haplogroup analysis in 64 patients with breast cancer (BC) and 54 patients with benign breast disease (BBD) as controls.

Results

Mutations in D-loop region were found in 10/64 or 15.6% of patients with BC and 14/54 or 25.9% of patients with BBD, while mutations in ND5 were detected in 6/64 or 9.4% of patients with BC and 5/54 or 9.3% of patients with BBD. In addition, in patients with BBD, mtDNA mutations were more likely to rise in D-loop region and the mutations were more likely to be heteroplasmic. However, in patients with BC, those with metastatic feature were less likely to carry mutations in D-loop region. Finally, we found haplogroup M has an increased risk of breast cancer compared with haplogroup N.

Conclusion

mtDNA mutation may play a role in early stage of tumorigenesis, and mitochondrial haplogroup can also modulate breast cancer occurrence.     

Single-nucleotide polymorphisms in BER and HRR genes, XRCC1 haplotypes and breast cancer risk in Caucasian women

Purpose  

This study aimed to assess whether haplotypes in XRCC1 and SNPs in OGG1 and XRCC3 were associated with an increased risk of developing breast cancer (BC) and early adverse reactions after radiotherapy.     

Incidence of diabetes among postmenopausal breast cancer survivors

Aims/hypothesis

Evidence is emerging of an association between breast cancer and diabetes; however, it is uncertain whether diabetes incidence is increased in postmenopausal breast cancer survivors compared with women without breast cancer. The objective of this study was to determine whether postmenopausal women who develop breast cancer have a higher incidence of diabetes than those who do not develop breast cancer.

Methods

We used population-based data from Ontario, Canada to compare the incidence of diabetes among women with breast cancer, aged 55 years or older, from 1996 to 2008, with that of age-matched women without breast cancer. We used Cox proportional hazard models to estimate the effect of breast cancer on the cause-specific hazard of developing diabetes overall and in the subgroup of women who received adjuvant chemotherapy.

Results

Of 24,976 breast cancer survivors and 124,880 controls, 9.7% developed diabetes over a mean follow-up of 5.8 years. The risk of diabetes among breast cancer survivors compared with women without breast cancer began to increase 2 years after diagnosis (HR 1.07 [95% CI, 1.02, 1.12]), and rose to an HR of 1.21 (95% CI, 1.09, 1.35) after 10 years. Among those who received adjuvant chemotherapy (n?=?4,404), risk was highest in the first 2 years after diagnosis (HR 1.24 [95% CI 1.12, 1.38]) and then declined.

Conclusions/interpretation

We found a modest increase in the incidence of diabetes among postmenopausal breast cancer survivors that varied over time. In most women the risk began to increase 2 years after cancer diagnosis but the highest risk was in the first 2 years in those who received adjuvant therapy. Our study suggests that greater diabetes screening and prevention strategies among breast cancer survivors may be warranted.     

Expressions of MAGE-A10 and MAGE-A11 in breast cancers and their prognostic significance: a retrospective clinical study

Purpose  

Melanoma-associated antigens-A (MAGE-A) family is a group of well-characterized cancer/testis antigens (CTA), because they are strictly tumor specific and are shared by many kinds of tumors. However, the expression pattern of MAGE-A10 and MAGE-A11 in breast cancer patients is still unclear. The purpose of our study is to investigate the expression pattern and prognostic significance of MAGE-A10 and MAGE-A11 in breast cancer patients.     

Adipocyte-released insulin-like growth factor-1 is regulated by glucose and fatty acids and controls breast cancer cell growth in vitro

Aims/hypothesis  

Type 2 diabetes and obesity are associated with increased risk of site-specific cancers. We have investigated whether metabolic alterations at the level of adipose-derived differentiating cells may affect specific phenotypes of breast cancer cells.     

Comparison of clinicopathological characteristics and prognoses between bilateral and unilateral breast cancer

Purpose

The clinical significance of bilateral breast cancer is unclear and its influence on prognosis is controversial. We compared the characteristics and prognosis of bilateral breast cancer and unilateral breast cancer.

Methods

Our study included 4,183 patients with breast cancer who were treated at Sun Yat-sen University Cancer Center between January 1, 2000, and December 31, 2007. Bilateral breast cancer was categorized as synchronous (within 3?months) or metachronous (diagnosed after 3?months of first cancer). SPSS was used for data analysis.

Results

106 (2.5%) and 31 (0.7%) patients were diagnosed with metachronous and synchronous bilateral cancer. Women with bilateral cancer had more frequent postmenopause, HER-2 negativity, and advanced disease than in patients with unilateral cancer. Young age at diagnosis, invasive lobular carcinoma, ER/PR negativity, HER-2 positivity, radiation, large tumor size (T?>?5?cm), and stage III disease of the first cancer were risk factors for contralateral cancer. The 5-year disease-free survival and overall survival rates were 76 and 83% for unilateral cancer, while 32 and 72% for bilateral cancer (P?=?0.000 for both).

Conclusions

Bilateral cancer was associated with shorter disease-free survival and overall survival than unilateral cancer. The prognosis of metachronous bilateral cancer, especially those diagnosed within 2?years after the first cancer was significantly worse than synchronous bilateral cancer.     

Safety study of axillary reverse mapping in the surgical treatment for breast cancer patients

Purpose  

With the purpose of minimizing arm lymphedema after axillary staging surgeries in breast cancer patients, the axillary reverse mapping (ARM) technique has been developed to identify and preserve arm drainage system during axillary surgery. This study aimed to clarify risk factors for metastasis in arm lymphatic drainage system in breast cancer patients with clinically negative axillary nodes.     

Long-term effects of insulin glargine on the risk of breast cancer

Aims/hypothesis  

There have been growing concerns regarding the long-term effects of insulin glargine (A21Gly,B31Arg,B32Arg human insulin) on the risk of breast cancer.     

The AIB1 gene polyglutamine repeat length polymorphism and the risk of breast cancer development

Purpose  

Carriers of BRCA1/2 mutations are at high lifetime risk of breast cancer (BC); however, the BC onset broadly vary in individual patients. Recently, polyglutamine (poly-Q) repeat length polymorphism of the amplified in breast cancer 1 (AIB1) gene was analyzed as a risk factor influencing BC onset in BRCA1/2 mutation carriers with contradictory results.     

Analysis of common germline polymorphisms as prognostic factors in patients with lymph node-positive breast cancer

Purpose  

Women with breast cancer that initially involves local lymph nodes have a higher risk for local recurrence or developing metastases. Recent data suggest that germline polymorphism is a significant, previously unrecognized factor in breast cancer progression and metastasis. We assessed the influence of 16 selected common germline polymorphisms in disease-free survival and overall survival among 216 women diagnosed with lymph node-positive breast cancer.     

IL-8-251A>T polymorphism is associated with breast cancer risk: a meta-analysis

Objective  

IL-8-251A>T polymorphisms have been reported to influence the risk for breast cancer in many studies; however, the results still remain controversial and ambiguous. The aim of this study was to determine more precise estimations for the relationship between IL-8-251A>T polymorphisms and the risk for breast cancer.     

A literature-based meta-analysis taxane-based doublet versus single-agent taxane chemotherapy in patients with advanced breast cancer

Purpose  

Clinical trials have reported conflicting results as to whether taxane-based doublet improves outcome over single-agent taxane in patients with advanced breast cancer.     

Management of risk of breast carcinoma in postmenopausal women

Breast carcinoma is the most frequent tumor in the female population. Many factors can influence the risk of breast cancer; some of them, such as old age and breast cancer 1/2 (BRCA1/BRCA2) gene mutations, are associated with a fourfold increase in risk. A previous diagnosis of atypical ductal or lobular hyperplasia or having a first-degree relative with a carcinoma are factors associated with a two- to fourfold increase in risk. A relative risk between 1 and 2 is associated with longer exposure to endogenous hormones as a result of early menarche, late menopause and obesity, or with recent and prolonged use of hormone replacement therapy (HRT) or with behavioural factors such as high alcohol and fat intake. Is it possible to modify breast cancer risk in postmenopausal women? Risk factors related to lifestyle can be changed, even if it is not clear whether modifying these behavioural factors during the postmenopausal period will influence the overall breast cancer risk. For instance, the influence of exogenous hormones throughout life (both oral contraceptives and HRT) should be evaluated according to the individual risk-benefit ratio. The problem is even more complex for women who carry genetic mutations and for those who have close relatives with breast cancer, who may be candidates for risk reduction strategies. Prophylactic bilateral mastectomy is still controversial, but is frequently offered to or requested by this group of women and may be indicated in BRCA1/BRCA2 carriers. Chemoprevention with tamoxifen and with the new selective estrogen receptor modulators, namely raloxifene, is very promising and deserves a thorough discussion for all high-risk women.     

选择性雌激素受体调节剂对绝经后乳腺癌患者子宫内膜的影响

目的 探讨应用选择性雌激素受体调节剂(SERM)的绝经后乳腺癌患者子宫内膜病变相关因素及筛查方法.方法 分析上海市长宁区妇幼保健院2013年1月至2020年6月间84例口服SERM的绝经后乳腺癌患者因经阴道超声(TVS)发现子宫内膜增厚行宫腔镜下子宫内膜活检术患者的临床资料.结果 宫腔镜术前有13例(15.5％)患者有...     

Lifestyle interventions for cardiovascular risk reduction in women with breast cancer

Purpose

The purpose of this paper is to identify risk factors for cardiovascular disease in women with breast cancer and review healthy lifestyle behaviors as essential risk reduction strategies.

Findings

Women with breast cancer account for 22% of the 12 million cancer survivors. Women diagnosed with breast cancer often present with modifiable and non-modifiable cardiovascular risk factors and/or pre-existing co-morbid illness. Any one or a combination of these factors may increase the risk of cardiovascular disease. There is strong evidence that healthy eating and routine physical activity can reduce cardiovascular disease. Exercise improves cardiovascular fitness, body composition and quality of life in breast cancer survivors and observational studies suggest a survival benefit.

Clinical Implications:

Lifestyle interventions including a healthy diet, regular physical activity, weight management and smoking cessation should be integrated into a survivorship care plan to reduce cardiovascular disease risk and promote better health for women with breast cancer.     

Diabetes and prognosis in a breast cancer cohort

Purpose

Epidemiological studies indicated that type 2 diabetes mellitus may increase breast cancer risk and mortality. The aim of this retrospective cohort study was to examine the effect of diabetes on the clinical course and the prognosis of early stage breast cancer in relation to tumour and patient characteristics.

Methods

The cohort analyzed in this study consisted of 4,056 patients with invasive primary breast cancer. We compared overall survival, distant metastasis-free survival and local recurrence free survival between breast cancer patients with and without diabetes.

Results

In our cohort 276 breast cancer patients (6.8%) were affected by diabetes compared to 3,780 patients (93.2%) without diabetes. Women with diabetes were significantly older, had larger tumours, and a higher rate of lymph node involvement. After a follow-up period of 5?years, stratification for age and adjustment for other prognostic factors, overall mortality following breast cancer was significantly higher in diabetic breast cancer patients (hazard ratio, HR 1.92; 95% confidence interval, CI 1.49?C2.48). We found no significant differences in distant metastasis-free survival and local recurrence free survival between the two groups, but we found a slightly significant higher rate of distant metastasis in the group of patients with diabetes and oestrogen receptor negative tumours (HR 2.28; CI 1.31?C3.97).

Conclusion

In this study, patients with diabetes and oestrogen receptor negative breast cancer had a more than 2-fold higher risk for distant metastasis compared to patients without diabetes. Diabetes was also associated with an almost 2-fold increase in mortality within the 5?years follow-up period.     

Lack of association between BARD1 Cys557Ser variant and breast cancer risk: a meta-analysis of 11,870 cases and 7,687 controls

Purpose  

The BRCA1-associated RING domain (BARD1) gene has been identified as a high-penetrance gene for breast cancer, whose germline and somatic mutations were reported in both non-BRCA1/2 hereditary site-specific and sporadic breast cancer cases. Some association studies suggested that the BRAD1 Cys557Ser variant might be associated with increased risk of breast cancer, but the results remain conflicting rather than conclusive. In order to derive a more precise estimation of the relationship, this meta-analysis was performed.     

Utilization of breast cancer screening with magnetic resonance imaging in community practice

Background

Breast cancer screening with magnetic resonance imaging (MRI) may be a useful adjunct to screening mammography in high-risk women, but MRI uptake may be increasing rapidly among low- and average-risk women for whom benefits are unestablished. Comparatively little is known about use of screening MRI in community practice.

Objective

To assess relative utilization of MRI among women who do and do not meet professional society guidelines for supplemental screening, and describe utilization according to breast cancer risk indications.

Design

Prospective cohort study conducted between 2007 and 2014.

Participants

In five regional imaging registries participating in the Breast Cancer Surveillance Consortium (BCSC), 348,955 women received a screening mammogram, of whom 1499 underwent screening MRI.

Main measures

Lifetime breast cancer risk (< 20% or ≥ 20%) estimated by family history of two or more first-degree relatives, and Gail model risk estimates. Breast Imaging Reporting and Data System breast density and benign breast diseases also were assessed. Relative risks (RR) for undergoing screening MRI were estimated using Poisson regression.

Key results

Among women with < 20% lifetime risk, which does not meet professional guidelines for supplementary MRI screening, and no first-degree breast cancer family history, screening MRI utilization was elevated among those with extremely dense breasts [RR 2.2; 95% confidence interval (CI) 1.7–2.8] relative to those with scattered fibroglandular densities and among women with atypia (RR 7.4; 95% CI 3.9–14.3.) or lobular carcinoma in situ (RR 33.1; 95% CI 18.0–60.9) relative to women with non-proliferative disease. Approximately 82.9% (95% CI 80.8%–84.7%) of screening MRIs occurred among women who did not meet professional guidelines and 35.5% (95% CI 33.1–37.9%) among women considered at low-to-average breast cancer risk.

Conclusion

Utilization of screening MRI in community settings is not consistent with current professional guidelines and the goal of delivery of high-value care.

     

Detection and identification of potential biomarkers of breast cancer

Purpose  

Noninvasive and convenient biomarkers for early diagnosis of breast cancer remain an urgent need. The aim of this study was to discover and identify potential protein biomarkers specific for breast cancer.     

CNS metastases of breast cancer show discordant immunohistochemical phenotype compared to primary

Purpose

A challenge in management of breast cancer is the development of brain metastases (BM). Because of improvements in systemic therapy with longer survival of patients with advanced cancer, BM can appear at a time when extra-BM disease is under control. Development of potential preventive strategies are considered, and new developments in systemic approaches to treatment of BM, (cytotoxic/targeted therapy), are explored. In primary breast cancer, ER/PR, HER2 are important biological markers for predicting prognosis and making effective treatment decisions. Known are changes in markers due to metastases, but clinical significance is still unclear. Aim of this retrospective study is to detect changes in immunohistochemical markers of primary and BM, to recognize concordance and impact on prognosis.

Methods

Twenty-one consecutive primary breast cancer patients who developed BM and got surgical resection of BM were enrolled in this study. Matched-pair analyses of primary and BM were done with evaluation by immunostaining (ER, PR, HER2).

Results

Loss of ER/PR receptor positivity was seen in BM compared to primary (ER: 47.6 %/9.0 %; PR: 42.9 %/0 %), respectively. High concordance exists for HER2 status in primary and BM (>80 %). HER2-positive breast cancer had a shorter median interval until appearance of metastases than HER2-negative patients (32.1/39 months; p = n.s.).

Conclusion

With loss of receptor positivity (ER/PR) in BM treatment, decisions are very difficult. High concordance of HER2 status was seen in matched-pair analysis. Further studies had to investigate whether HER3/4 is a possible target for further therapy.