Breast Cancer
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Breast cancer is the most common type of cancer among women, the risk of breast cancer increases with age, it is most common after the age of 50. Each breast has 15- 20 sections (lobes), each of which has many smaller sections (lobules). The lobes and lobules are connected by thin tubes (ducts). The most frequent type of breast cancer is that starting in the ducts (ductal cancer), other types include cancer beginning in the lobes or lobules (lobular carcinoma), less common is Inflammatory breast cancer which causes the breast to be red, and swollen. The incidence of breast cancer has been increasing in Western countries, the rate of increase has been faster in younger women, however, the cause of most breast cancers remains unknown. World-wide about 794,000 women are diagnosed with breast cancer each year.

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Breast Cancer in Pregnancy
Breast Cancer Screening
Familial Breast Cancer
Lymphedema
Male Breast Cancer
Paget's Disease of the Breast

Information Patients and the Public (42 links)


Information for Health Professionals / Researchers (15 links)

See also: Molecular Biology of Breast Cancer

Breast Cancer Organisations (11 links)

See also: National Cancer Organisations

Specialist Journals (12 links)

See also: Oncology Journals

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Shah C, Vicini F, Beitsch P, et al.
The use of bioimpedance spectroscopy to monitor therapeutic intervention in patients treated for breast cancer related lymphedema.
Lymphology. 2013; 46(4):184-92 [PubMed] Related Publications
We performed a multi-institutional analysis to evaluate the ability of bioimpedance spectroscopy (BIS) to capture the impact of lymphedema treatment compared with observation alone in the management of breast cancer related lymphedema (BCRL). We utilized a retrospective review of 50 patients with breast cancer who were evaluated with BIS at baseline and following loco-regional treatment. An analysis was performed comparing changes in L-Dex scores for those patients undergoing treatment for BCRL (n=13) versus those not undergoing intervention (n=37). A second (subset) analysis was also performed on all patients with elevated L-Dex scores compared to baseline prior to undergoing loco-regional treatment (n=32). When comparing the cohort treated for BCRL to those not treated, L-Dex scores were significantly reduced (-4.3 v. 0.1, p=0.005) in the period following intervention (for treated patients). For the subset of patients with elevated L-Dex scores postoperation, the change in L-Dex score following BCRL treatment was significantly reduced (-5.8 v. 0.1, p=0.001) compared with the group observed that had elevated postsurgical L-Dex scores. In this analysis, BIS was able to detect early onset lymphedema and subsequently significant changes (reductions) in L-Dex scores directly related to intervention for BCRL compared with observation alone.


Antoniou AC, Casadei S, Heikkinen T, et al.
Breast-cancer risk in families with mutations in PALB2.
N Engl J Med. 2014; 371(6):497-506 [PubMed] Related Publications
BACKGROUND: Germline loss-of-function mutations in PALB2 are known to confer a predisposition to breast cancer. However, the lifetime risk of breast cancer that is conferred by such mutations remains unknown.
METHODS: We analyzed the risk of breast cancer among 362 members of 154 families who had deleterious truncating, splice, or deletion mutations in PALB2. The age-specific breast-cancer risk for mutation carriers was estimated with the use of a modified segregation-analysis approach that allowed for the effects of PALB2 genotype and residual familial aggregation.
RESULTS: The risk of breast cancer for female PALB2 mutation carriers, as compared with the general population, was eight to nine times as high among those younger than 40 years of age, six to eight times as high among those 40 to 60 years of age, and five times as high among those older than 60 years of age. The estimated cumulative risk of breast cancer among female mutation carriers was 14% (95% confidence interval [CI], 9 to 20) by 50 years of age and 35% (95% CI, 26 to 46) by 70 years of age. Breast-cancer risk was also significantly influenced by birth cohort (P<0.001) and by other familial factors (P=0.04). The absolute breast-cancer risk for PALB2 female mutation carriers by 70 years of age ranged from 33% (95% CI, 25 to 44) for those with no family history of breast cancer to 58% (95% CI, 50 to 66) for those with two or more first-degree relatives with breast cancer at 50 years of age.
CONCLUSIONS: Loss-of-function mutations in PALB2 are an important cause of hereditary breast cancer, with respect both to the frequency of cancer-predisposing mutations and to the risk associated with them. Our data suggest the breast-cancer risk for PALB2 mutation carriers may overlap with that for BRCA2 mutation carriers. (Funded by the European Research Council and others.).

Related: BRCA2 PALB2


Mai C, Rombaut B, Hertveldt K, et al.
Diffuse pseudoangiomatous stromal hyperplasia of the breast: a case report and a review of the radiological characteristics.
JBR-BTR. 2014 Mar-Apr; 97(2):81-3 [PubMed] Related Publications
Pseudoangiomatous stromal hyperplasia is a benign mesenchymal tumor of the breast. It is a rare condition and until a few years mainly described in pathological and surgical literature. Here, we provide a case report of PASH and an overview of its radiological features.


Friedewald SM, Rafferty EA, Rose SL, et al.
Breast cancer screening using tomosynthesis in combination with digital mammography.
JAMA. 2014; 311(24):2499-507 [PubMed] Related Publications
IMPORTANCE: Mammography plays a key role in early breast cancer detection. Single-institution studies have shown that adding tomosynthesis to mammography increases cancer detection and reduces false-positive results.
OBJECTIVE: To determine if mammography combined with tomosynthesis is associated with better performance of breast screening programs in the United States.
DESIGN, SETTING, AND PARTICIPANTS: Retrospective analysis of screening performance metrics from 13 academic and nonacademic breast centers using mixed models adjusting for site as a random effect.
EXPOSURES: Period 1: digital mammography screening examinations 1 year before tomosynthesis implementation (start dates ranged from March 2010 to October 2011 through the date of tomosynthesis implementation); period 2: digital mammography plus tomosynthesis examinations from initiation of tomosynthesis screening (March 2011 to October 2012) through December 31, 2012.
MAIN OUTCOMES AND MEASURES: Recall rate for additional imaging, cancer detection rate, and positive predictive values for recall and for biopsy.
RESULTS: A total of 454,850 examinations (n=281,187 digital mammography; n=173,663 digital mammography + tomosynthesis) were evaluated. With digital mammography, 29,726 patients were recalled and 5056 biopsies resulted in cancer diagnosis in 1207 patients (n=815 invasive; n=392 in situ). With digital mammography + tomosynthesis, 15,541 patients were recalled and 3285 biopsies resulted in cancer diagnosis in 950 patients (n=707 invasive; n=243 in situ). Model-adjusted rates per 1000 screens were as follows: for recall rate, 107 (95% CI, 89-124) with digital mammography vs 91 (95% CI, 73-108) with digital mammography + tomosynthesis; difference, -16 (95% CI, -18 to -14; P < .001); for biopsies, 18.1 (95% CI, 15.4-20.8) with digital mammography vs 19.3 (95% CI, 16.6-22.1) with digital mammography + tomosynthesis; difference, 1.3 (95% CI, 0.4-2.1; P = .004); for cancer detection, 4.2 (95% CI, 3.8-4.7) with digital mammography vs 5.4 (95% CI, 4.9-6.0) with digital mammography + tomosynthesis; difference, 1.2 (95% CI, 0.8-1.6; P < .001); and for invasive cancer detection, 2.9 (95% CI, 2.5-3.2) with digital mammography vs 4.1 (95% CI, 3.7-4.5) with digital mammography + tomosynthesis; difference, 1.2 (95% CI, 0.8-1.6; P < .001). The in situ cancer detection rate was 1.4 (95% CI, 1.2-1.6) per 1000 screens with both methods. Adding tomosynthesis was associated with an increase in the positive predictive value for recall from 4.3% to 6.4% (difference, 2.1%; 95% CI, 1.7%-2.5%; P < .001) and for biopsy from 24.2% to 29.2% (difference, 5.0%; 95% CI, 3.0%-7.0%; P < .001).
CONCLUSIONS AND RELEVANCE: Addition of tomosynthesis to digital mammography was associated with a decrease in recall rate and an increase in cancer detection rate. Further studies are needed to assess the relationship to clinical outcomes.

Related: Cancer Screening and Early Detection USA


Li X, Chen S, Sun T, et al.
The transcriptional regulation of SOX2 on FOXA1 gene and its application in diagnosis of human breast and lung cancers.
Clin Lab. 2014; 60(6):909-18 [PubMed] Related Publications
BACKGROUND: Recent study demonstrated the important contribution of SOX2 to tumorigenesis and metastasis properties of various types of cancers and strongly supported the concept that SOX2 can be used as an effective marker for diagnosis and predicting prognosis of cancer patients. However, our previous RNA-Seq results from human lung cancer cell line A549 showed that some oncogenes, including FOXA1 are negatively regulated by SOX2.
METHODS: To further verify the transcriptional regulation effect of SOX2 on FOXA1 and elucidate its application in the diagnosis of human lung and breast cancer, we performed real-time RT-PCR and Western blotting to test the regulation effect of SOX2 on the expression of FOXA1 gene. OncoPrint analysis was used to reveal the alteration of SOX2 and FOXA1 genes in breast invasive carcinoma cases and lung squamous cell carcinoma cases from the Cancer Genome Atlas (TCGA) data portal. Immunohistochemistry staining was performed to test the expression of SOX2 and FOXA1 in human breast and lung carcinoma.
RESULTS: The results showed that there is an inhibitory effect of SOX2 on the expression of FOXA1 gene. In addition, these two genes are altered in 5.8% of 484 breast invasive carcinoma cases and 46.4% of 179 lung squamous cell carcinoma cases from the Cancer Genome Atlas (TCGA) data portal, which showed an increased percentage of carcinoma cases when compared with single gene alteration. Immunohistochemistry staining of SOX2 and FOXA1 in human breast and lung carcinoma further revealed the mutual complementary effect of these two proteins in the diagnosis of carcinoma.
CONCLUSIONS: Our study revealed SOX2 as a negative upstream regulator for FOXA1 gene and demonstrated SOX2 and FOXA1 as effective dual markers in improving the diagnosis efficiency for human lung and breast tumor.

Related: Lung Cancer


Yu M, Bardia A, Aceto N, et al.
Cancer therapy. Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility.
Science. 2014; 345(6193):216-20 [PubMed] Related Publications
Circulating tumor cells (CTCs) are present at low concentrations in the peripheral blood of patients with solid tumors. It has been proposed that the isolation, ex vivo culture, and characterization of CTCs may provide an opportunity to noninvasively monitor the changing patterns of drug susceptibility in individual patients as their tumors acquire new mutations. In a proof-of-concept study, we established CTC cultures from six patients with estrogen receptor-positive breast cancer. Three of five CTC lines tested were tumorigenic in mice. Genome sequencing of the CTC lines revealed preexisting mutations in the PIK3CA gene and newly acquired mutations in the estrogen receptor gene (ESR1), PIK3CA gene, and fibroblast growth factor receptor gene (FGFR2), among others. Drug sensitivity testing of CTC lines with multiple mutations revealed potential new therapeutic targets. With optimization of CTC culture conditions, this strategy may help identify the best therapies for individual cancer patients over the course of their disease.

Related: ESR1


Abdolmohammadi A, Sears W, Rai S, et al.
Survey of primary care physicians on therapeutic approaches to lung and breast cancers.
South Med J. 2014; 107(7):437-42 [PubMed] Related Publications
BACKGROUND: Primary care physicians (PCPs) are an important part of the decision-making process in the care of patients with cancer. The survey discussed herein evaluates what percentage of academic and community PCPs recognize benefits from systemic therapy in lung and breast cancers.
METHODS: PCPs were surveyed regarding their beliefs toward systemic therapy in early- and late-stage lung and breast cancers and were asked to rate the importance of specific factors that influence their referral decisions.
RESULTS: A total of 3444 surveys were distributed, and 316 physicians (9.1%) responded: 89 academic physicians (28%) and 227 nonacademic physicians (72%). The rate of returned surveys was equal by specialty. A total of 57%, 42.1% in lung cancer and 72.6 % in breast cancer (P < 0.001) of PCPs, believe in the curative effect of systemic therapy in early stages. Sixty-six percent (58.2% in lung cancer and 75.5% in breast cancer [P < 0.001]) believe in improved disease-free survival. Although 82% believe that systemic therapy can prevent symptoms and prolong life in advanced asymptomatic disease, half (lung cancer 50.8%, breast cancer 53.1% [P = 0.5]) of the PCPs would refer symptomatic patients with advanced disease to palliative care before referral to an oncologist. The type and stage of cancer, as well as the patient's desire or reluctance to be referred to an oncologist were rated by PCPs as the most important reasons to refer patients to an oncologist (P < 0.0001).
CONCLUSIONS: Although a majority of PCPs in academia and the community acknowledge the positive effect of chemotherapy, the benefit of systemic therapy for early-stage lung cancer is less appreciated as compared with breast cancer. Patients' preferences influence PCPs significantly in the decision to refer patients to an oncologist.

Related: Lung Cancer


Clark AS, McDonald E, Lynch MC, Mankoff D
Using nuclear medicine imaging in clinical practice: update on PET to guide treatment of patients with metastatic breast cancer.
Oncology (Williston Park). 2014; 28(5):424-30 [PubMed] Related Publications
As we enter the era of personalized medicine, tests that can inform on molecular mechanisms of cancer, and on breast cancer in particular, are in high demand. We currently use DNA- or RNA-based tests of gene expression and/or immunohistochemistry to better characterize a given breast cancer and aid the clinician in selecting the best treatment options. In breast cancer, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2/neu) are established biomarkers. There are several ways to obtain information on these biomarkers, including invasive testing (biopsy), which can be challenging depending on the location. However, not all tumors that express targets identified by tissue assay will respond to directed therapy. Nuclear imaging tests can be useful in these situations. They can be used as a noninvasive method for detecting tumor, obtaining information about the biology of the tumor, and predicting which tumors will respond to targeted therapies. Here, we will review how radiolabeled glucose and estrogen analogs can be used in breast cancer patients. We focus this review on the application of positron emission tomography (PET) imaging to ER-positive metastatic breast cancer as an example of how imaging can guide breast cancer treatment.


Pilewskie ML, Morrow M
Management of the clinically node-negative axilla: what have we learned from the clinical trials?
Oncology (Williston Park). 2014; 28(5):371-8 [PubMed] Related Publications
Sentinel lymph node biopsy (SLNB) has revolutionized the surgical management of the axilla for patients with early breast cancer. SLNB initially became standard regional therapy for women who were both clinically and pathologically node-negative. Subsequently, SLNB has been established as appropriate management in patients with very low axillary tumor burden, defined as isolated tumor cells or micrometastatic disease (< 2 mm); it provides accurate staging information with no detriment to regional control. More recently, the treatment of the axilla has evolved for women with macrometastatic axillary disease. Three randomized controlled trials have compared different regional treatment strategies for patients with > 2 mm of axillary tumor burden. Here we review the evolution of SLNB for the management of clinically node-negative breast cancer, and we address the current controversies and management issues.


Mackey RV, Chandru Kowdley G
Treatment practices and outcomes of elderly women with breast cancer in a community hospital.
Am Surg. 2014; 80(7):714-9 [PubMed] Related Publications
There is a paucity of clinical data available on specific treatment in the oncogeriatric population with breast cancer. The purpose of this study was to evaluate treatment patterns and survival outcomes in the elderly to address any disparities at our community hospital. We retrospectively identified a total of 1749 patients diagnosed and treated for breast cancer at our institution between 2001 and 2011. Patient demographics, surgical treatment, stage of disease, tumor characteristics, adjuvant therapy, and 5-year survival data were obtained from tumor registry records. Comparisons between study groups were made using the Pearson χ(2) test and Student's t test. We found more favorable prognostic makers among women older than 70 years of age. Of the women with lymph node-positive disease, 84 per cent of those younger than 70 years and 33 per cent in the older than 70 years of age study group received chemotherapy. Adjuvant chemotherapy and radiation therapy were more frequently performed in the younger group. Overall 5-year survival was 90 per cent and 71 per cent for younger than 70 years and older than 70 years groups, respectively. Women older than 70 years of age have more favorable breast cancer characteristics compared with younger women and received less aggressive treatment and experienced a higher mortality rate. Prospective trials are needed to assess the impact of aggressive multimodality therapy in this oncogeriatric population.


Chiu JC, Ajmal S, Zhu X, et al.
Radioactive seed localization of nonpalpable breast lesions in an academic comprehensive cancer program community hospital setting.
Am Surg. 2014; 80(7):675-9 [PubMed] Related Publications
Wire localized excision (WLE) has been a long-standing method for localization of nonpalpable breast lesions. Disadvantages of this method include difficulty locating the wire tip in relation to borders of the lesion, imprecise placement of the wire, and the need to place the wire shortly before scheduled surgery. These shortcomings may lead to a high positive margin rate requiring re-excision to obtain clear margins for breast cancer. Radioactive seed localized excision (RSLE) of nonpalpable breast lesions has been advocated as a safe and effective alternative to WLE. The primary endpoints of the study were to compare re-excision rates between WLE and RSLE of nonpalpable breast lesions and to determine if there were any differences in volume of tissue removed. One hundred three patients were included in a retrospective review of localized breast excisions done by a single surgeon. Forty-four patients underwent WLE between April 2007 and February 2009. Fifty-nine patients underwent RSLE between September 2009 and January 2012. Margins were considered to be clear if at least 1 mm of normal tissue was obtained from the circumferential periphery of the lesion in question. RSLE resulted in a re-excision rate of 17 versus 55 per cent re-excision rate for wire localization (P < 0.001). Excision volume was greater for patients having wire localization (P = 0.074). RSLE is an effective technique for excision of nonpalpable breast lesions in the community setting. This technique allows for accurate localization and appears to allow for smaller volume of tissue to be excised.


Weber JJ, Kachare SD, Vohra NA, et al.
Regional disparities in breast cancer outcomes and the process of care.
Am Surg. 2014; 80(7):669-74 [PubMed] Related Publications
Mortality from breast cancer in eastern North Carolina (ENC) surpasses the rest of North Carolina (RNC). We sought to identify modifiable factors associated with the increased mortality of women diagnosed with breast cancer in ENC. A retrospective cohort study of women diagnosed with breast cancer in North Carolina between January 1, 2004, and December 31, 2007 (n = 27,631) was studied. There was no difference in the pathologic T (P = 0.62), N (P = 0.26), or stage grouping (P = 0.25) at diagnosis. Women in ENC were less likely to be white (P < 0.001), estrogen receptor (ER)-positive (P < 0.001), progesterone receptor (PR)-positive (P < 0.001), or to receive adjuvant chemotherapy (P = 0.02). The median survival of ENC patients was worse than RNC patients (39 vs. 43 months, P = 0.003). Improved median survival was associated with ER status (P < 0.001), PR status (P < 0.001), race/ethnicity (P < 0.001), and delivery of timely chemotherapy (P < 0.0001). ER-negative status (P = 0.01), black race (P = 0.03), and adjuvant chemotherapy within 90 days of surgery (P < 0.001) remained significant predictors of survival. The poor outcomes observed in ENC can be attributed to recognized prognostic primary patient and tumor characteristics. However, a failure in process of care remains significantly associated with poorer outcomes. Improved timing of delivery of chemotherapy could affect breast cancer mortality.


Tewari A, Chagpar AB
Worry about breast cancer recurrence: a population-based analysis.
Am Surg. 2014; 80(7):640-5 [PubMed] Related Publications
As more patients with breast cancer survive treatment, the importance of their long-term quality of life is increasing. One important concern for many survivors is fear of recurrence. To better understand worry about recurrence, we conducted a population-based statistical analysis. The National Health Interview Survey (NHIS) is the largest annual source of health information for the U.S. population. We obtained data from the 2010 survey, which asked breast cancer survivors about their fear of recurrence and quality of life. Data were analyzed using SUDAAN software. The 2010 NHIS sample represented 2,668,697 breast cancer survivors. On univariate analysis, worry about recurrence was correlated with current age (P = 0.03) and radiation therapy (P = 0.04). Worry was strongly associated with perceived risk of recurrence (P < 0.01) and decreased overall quality of life (P < 0.01) as well as lower self-reported physical (P < 0.01) and mental (P < 0.01) health and poor satisfaction with social activities and relationships (P < 0.01). On multivariate analysis, worry was not independently associated with decreased quality of life (P = 0.09). However, those who "always worried" about recurrence had a lower quality of life (odds ratio, 0.06; 95% confidence interval, 0.01 to 0.45). Worry about recurrence among breast cancer survivors is associated with age and radiation therapy and is correlated with self-reported physical health, mental health, social relationships, and overall quality of life. It is a significant predictor of decreased quality of life in those who worry the most. Screening for worry about recurrence is an important measure for the improvement of quality of life among breast cancer survivors.

Related: Male Breast Cancer USA


Zizi-Sermpetzoglou A, Kontostolis V, Moustou E, et al.
Solid neuroendocrine carcinoma of the breast: a rare tumor.
Eur J Gynaecol Oncol. 2014; 35(3):325-7 [PubMed] Related Publications
Solid Neuroendocrine carcinoma of the breast (SNECB) is a subtype of primary neuroendocrine carcinoma (NEC) of the breast with several distinctive features. In the present study, the authors report a case of 84-year old woman who was admitted in the hospital with a lump in her right breast. Mammography revealed a well-defined nodule in the outer lower quadrant of her right breast. She underwent lumpectomy and sentinel lymph node biopsy, which showed no metastasis. The histological diagnosis was solid neuroendocrine carcinoma of the breast. Microscopically, the tumor is formed from cells arranged in nests or trabeculae and separated by scant connective tissue. Immunohistochemical staining demonstrates strong positivity for NSE, chromogranin, synaptophysin, ER, and PR. The patient is still alive 14 months after diagnosis. Because of the rarity of this disease, there is no standard treatment protocol and a large variety of chemotherapy protocols have been employed in treating this disease.


Li Y, Liu C, Geng J, et al.
The texture quantitative analysis of the normal mammary parenchyma and in breast lesions: acoustic radiation force impulse (ARFI) technology.
Eur J Gynaecol Oncol. 2014; 35(3):274-9 [PubMed] Related Publications
OBJECTIVE: The purpose of this work is to investigate the feasibility of acoustic radiation force impulse (ARFI) technology in the normal mammary parenchyma and in breast lesions.
MATERIALS AND METHODS: The virtual touch tissue quantification (VTQ) value was measured on a total of 150 cases in the normal mammary parenchyma and a total of 69 cases in breast lesions (19 cases of nodules, 28 cases of fibroadenoma, and 22 cases of cancer). Then the statistic analysis was carried out on the VTQ value combined with mammographic density, ages, menstrual stages, and pathological result.
RESULTS: The VTQ value of mammary parenchyma rose with the increase of the mammographic density, and the value of VTQ had statistical differences in the comparison of group C with group B and in the comparison of group D with group C. The comparison of the VTQ value of the mammary parenchyma in patients with breast cancer and the nodule had statistical difference. The comparison of the VTQ value of the mammary parenchyma in patients with breast cancer, and the fibroadenoma had statistical difference. The value ofVTQ in masses gradually increased in the groups of nodule, fibroadenoma, and breast cancer. There was significant difference in the comparison of VTQ value of the nodule group and the fibroadenoma group with breast cancer group respectively.
CONCLUSION: ARFI-VTQ technology has some reference value in assessing mammographic density. ARFI-VTQ can be used as the quantitative indicater for differentially diagnosing the breast lesions.


Zhao G, Lin X, Zhou M, Zhao J
Relationship between exposure to extremely low-frequency electromagnetic fields and breast cancer risk: a meta-analysis.
Eur J Gynaecol Oncol. 2014; 35(3):264-9 [PubMed] Related Publications
OBJECTIVE: To comprehensively analyze the relationship between human exposure to extremely low frequency electromagnetic fields (ELF-EMFs) and breast cancer and to discuss the potential risk of ELF-EMFs to human breast cancer.
MATERIALS AND METHODS: Sixteen research reports of case-control studies which were published from 2000 to 2007 were collected. The fixed effect model (FEM) or the random effect model (REM) was chosen to calculate total ORs depending on the outcomes of the test of homogeneity (Q test): the subgroup was analyzed with the menopause and the non-menopause.
OUTCOME: Sixteen research outcome was ORDL = 1.10, 95% CI = (1.01, 1.20), the OR(MH) of the non-menopause status group was 1.25, 95% CI = (1.05, 1.49), the OR(MH) of the menopause status group was OR(MH) = 1.04, 95% CI = (0.93, 1.18).
CONCLUSION: The authors found that ELF-EMFs may be increase the risk of human breast cancer. The women's exposure to ELF-EMFs may be the risk factor of breast cancer when they are non-menopausal.


Tsubamoto H, Sonoda T, Inoue K
Impact of itraconazole on the survival of heavily pre-treated patients with triple-negative breast cancer.
Anticancer Res. 2014; 34(7):3839-44 [PubMed] Related Publications
BACKGROUND/AIM: Recurrent triple-negative breast cancer (TNBC) patients have poor prognoses and limited treatment options, especially after progression during prior chemotherapy. The present study aimed to determine the impact of itraconazole with chemotherapy in these patients.
PATIENTS AND METHODS: Medical records of recurrent TNBC patients receiving itraconazole with chemotherapy between 2008 and 2012 were retrospectively reviewed.
RESULTS: Thirteen patients who progressed during prior chemotherapy (12 with visceral organ metastases) were enrolled. All patients had received docetaxel, carboplatin, and gemcitabine with itraconazole. Additionally, 3 patients with pleural effusion and 2 with inflammatory breast cancer received bevacizumab. No febrile neutropenia, platelet transfusion, or chemotherapy-related death was observed during treatment with itraconazole. The response rate, median progression-free survival, and median overall survival were 62% (95% confidence interval (CI): 35-88%), 10.8 months (95%CI: 7.6-15.3 months), and 20.4 months (95%CI: 13.1-41.4 months), respectively.
CONCLUSION: Chemotherapy with itraconazole is promising for heavily pre-treated TNBC patients.

Related: Carboplatin Docetaxel Gemcitabine


Nakano K, Hosoda M, Yamamoto M, Yamashita H
Prognostic significance of pre-treatment neutrophil: lymphocyte ratio in Japanese patients with breast cancer.
Anticancer Res. 2014; 34(7):3819-24 [PubMed] Related Publications
BACKGROUND: The neutrophil:lymphocyte ratio (NLR) has been reported to reflect systemic inflammation and to have independent prognostic value for patients with various cancers. In this study, we analyzed the association between NLR and clinicopathological factors and verified the significance of NLR as a prognostic factor for Japanese patients with breast cancer.
PATIENTS AND METHODS: A total of 167 Japanese female patients with stage I-III breast cancer were retrospectively recruited into this study. Associations with clinicopathological factors and NLR were assessed, and disease-free survival and breast cancer-specific survival were estimated.
RESULTS: In multivariate analysis, lymph node metastases and NLR were significantly associated with disease-free survival and breast cancer-specific survival. NLR was significantly higher in patients with lower body-mass index.
CONCLUSION: Preoperative NLR may be an independent prognostic factor for survival in Japanese patients with breast cancer. Reduction of body mass index has been implicated in NLR elevation, particularly in postmenopausal women.


Kim J, Jang SG, Kwon SY, et al.
MicroRNA signature for HER2-positive breast and gastric cancer.
Anticancer Res. 2014; 34(7):3807-10 [PubMed] Related Publications
BACKGROUND/AIM: The molecular mechanism for aggressive clinical behaviour related to v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (ERBB2) amplification is not fully-understood. In particular, little is known about microRNAs in the human epidermal growth factor receptor 2 (HER2) signaling network.
PATIENTS AND METHODS: Using microRNA microarray, the microRNA profiles of 16 HER2-positive breast carcinomas were compared with those of five luminal-type breast carcinomas. Additionally, two frozen, ERBB2-amplified gastric carcinomas were compared with their adjacent normal tissue samples. MicroRNAs that were differentially expressed according to the HER2 status in breast and gastric carcinomas were identified as the HER2 microRNA signature.
RESULTS: MiR-337 and miR-302f were commonly overexpressed in HER2-postive breast and gastric cancer. MiR-139 and miR-129 were commonly underexpressed in HER2-positive breast and gastric cancer. A concordant pattern of microRNA expression was noted between discovery sets and the majority of candidate microRNAs (two out of three) in three validation sets.
CONCLUSION: Our study identified novel microRNAs that were differentially expressed according to the HER2 status across different tumor types.

Related: Signal Transduction Stomach Cancer Gastric Cancer


Fujii T, Yajima R, Takada T, et al.
Serum albumin and prealbumin do not predict recurrence in patients with breast cancer.
Anticancer Res. 2014; 34(7):3775-9 [PubMed] Related Publications
BACKGROUND: We have previously reported that prealbumin and albumin may be sensitive indicators of the risk of recurrent disease in colorectal cancer; however, the relationship between preoperative prealbumin and cancer survival has not been fully-elucidated. The purpose of this study was to examine the relationship between preoperative nutritional conditions, including prealbumin and albumin concentrations, and the risk of recurrence in cases with breast cancer.
PATIENTS AND METHODS: One hundred and fifty-seven patients who underwent breast surgery were analyzed in this study. The detection limit of the prealbumin assay was 22 mg/dl; patients were divided in analytical groups of <22 mg/dl and ≥22 mg/dl. The detection limit of the albumin assay was 4.0 g/dl; patients were divided in analytical groups of <4.0 g/dl and ≥4.0 g/dl. The clinical features of these cases were reviewed according to prealbumin and albumin levels, and statistical analysis was performed.
RESULTS: Among 157 cases in this study, five (3.2%) had disease recurrence. Out of the eligible cases, 38 (24.2%) had decreased serum prealbumin and 19 (12.1%) had decreased serum albumin preoperatively. No statistically significant association of the preoperative prealbumin level was found with the clinicopathological variables. The only statistically significant association found for preoperative albumin level was age; age was higher in patients with low albumin levels. In short, we were unable to establish a connection between preoperative prealbumin or albumin and various clinical features, including recurrence, lymph node metastasis and tumor size.
CONCLUSION: Prealbumin and albumin may be sensitive indicators of disturbances in protein metabolism, and reflect inflammation activity and malnutrition. However, our results suggest that evaluation of serum prealbumin and albumin are not useful for predicting disease aggressiveness or recurrence in breast cancer.


Levaggi A, De Maria A, Dozin B, et al.
Incidence of hepatitis in patients with evidence of past or current hepatitis B or C during chemotherapy for early breast cancer.
Anticancer Res. 2014; 34(7):3715-20 [PubMed] Related Publications
AIM/BACKGROUND: Few data are available about the prevalence of hepatitis B and C infections in early breast cancer patients and its impact on systemic treatments. The objectives of this study were to determine the incidence of positive serology for hepatitis B and C in women with early breast cancer and to assess the clinical course and its impact on liver function during adjuvant treatments.
PATIENTS AND METHODS: we retrospectively reviewed hepatitis B and C serology [HBs antigen (HBsAg), HBc antibodies (HBcAb), HBs antibodies (HBsAb) and HC (HCV) antibodies] in 746 consecutive patients with early breast cancer treated at our Institution between 2009 and 2011.
RESULTS: Among 375 evaluable patients, we identified 312 controls (83.2%) and 63 patients (16.8%) with positive serology (cases): 15 patients (4%) with HCV, 8 (2.1%) with resolved HBV without anti-HBs (HBsAg-negative, HBsAgAb-negative, HBcAgAb-positive), 36 (9.6%) with resolved HBV with anti-HBs (HBsAg-negative, HBsAgAb-positive, HBcAgAb-positive) and 4 (1%) with chronic HBV (HBsAg-positive, HBsAgAb-negative, HBcAgAb-positive). During systemic treatments, hepatitis (defined as at least a three-fold increase in serum alanine aminotransferase level) occurred in nine (20.4%) out of 44 evaluable cases and in 14 (5.9%) out of 234 evaluable controls.
CONCLUSION: Approximately 20% of patients with early breast cancer with positive serology for viral hepatitis may develop hepatitis during systemic treatment. Pre-treatment serum detection of viral hepatitis B and C antigens and antibodies may be useful in the adjuvant therapy decision-making process and for adequate monitoring of liver function during antineoplastic therapy.


Melichar B, Doležal J, Srámek V, et al.
Prevalence of perfusion defects detected by stress 99mtechnetium sestamibi myocardial perfusion single-photon emission computed tomography in asymptomatic patients with breast cancer.
Anticancer Res. 2014; 34(7):3689-94 [PubMed] Related Publications
AIM: The aim of the present study was to investigate myocardial perfusion in relation to disease history and laboratory parameters of atherosclerosis risk in asymptomatic patients with breast carcinoma.
PATIENTS AND METHODS: One-hundred and eighty-one patients with breast carcinoma were studied. Myocardial perfusion was assessed using single-photon emission computed tomography (SPECT) with 99mtechnetium sestamibi.
RESULTS: Perfusion defects were detected in 12 patients (7%). Higher body-mass index, increased concentrations of D-dimers, C-reactive protein, fibrinogen, glucose, triglycerides, and urinary albumin, a history of hypertension and of radiotherapy to the left chest wall were all associated with increased risk of perfusion defects. In a multivariate stepwise selection logistic regression model, body mass index, albuminuria and radiotherapy to the left hemithorax were significantly associated with the presence of perfusion defects.
CONCLUSION: In addition to other factors, treatment history may be associated with the presence of perfusion defects in patients with breast cancer.


Dieci MV, Piacentini F, Dominici M, et al.
Quantitative expression of estrogen receptor on relapse biopsy for ER-positive breast cancer: prognostic impact.
Anticancer Res. 2014; 34(7):3657-62 [PubMed] Related Publications
BACKGROUND: The aim of this study was to evaluate the prognostic impact of quantitative estrogen receptor (ER) expression at relapse for ER-positive breast cancer with ER-positive recurrence.
PATIENTS AND METHODS: A total of 81 patients with ER-positive primary breast cancer and ER-positive paired recurrence were included. ER expression was evaluated as the percentage of tumor cells staining for ER under immunohistochemistry. Samples were defined as ER-high (ER>50%) or ER-low (ER≥10% and ≤50%).
RESULTS: Quantitative ER expression on relapse biopsy was an independent prognostic factor for overall survival in multivariate analysis, both as a continuous (hazard ratio=0.8; 95% confidence interval=0.7-0.92, p=0.001) and as a categorical (ER-high vs. ER-low; hazard ratio=0.26; 95% confidence interval=0.11-0.59, p=0.001) variable. Patients whose status changed from ER-high (primary BC) to ER-low (relapse) had the poorest outcome, with a 10-year overall survival rate of 14%.
CONCLUSION: Even in the case of maintenance of ER-positivity on primary and relapse of breast cancer, recurrence biopsy provides prognostic information.


Fritz P, Bendrat K, Sonnenberg M, et al.
Tubular breast cancer. A retrospective study.
Anticancer Res. 2014; 34(7):3647-56 [PubMed] Related Publications
BACKGROUND: The well-characterized tubular-type of breast tumors is classified as low-risk breast cancer.
PATIENTS AND METHODS: We report on the results of a retrospective analysis on clinical and biological features of 248 tubular breast tumors including follow-up and treatment data from two German series of 21,065 breast cancer cases. The majority of tumors were stage I or stage II, ER- and PR-positive and c-erbB2-negative with a 5-year survival-rate of 96.3%. 51.3% of patients received hormonal treatment, 75.5% had post-operative radiotherapy and 11.8% were treated with a chemotherapeutical regimen.
CONCLUSION: Our retrospective analysis showed no treatment benefit for either anti-hormonal or chemotherapeutical regimens. Post-operative radiotherapy, however, improved the survival rate of patients with tubular carcinoma (log-rank=5, p=0.025). Our data suggest that post-operative radiotherapy is an important treatment to prolong survival for patients suffering from tubular breast cancer.


Ki SY, Lim HS, Lee JS, et al.
Periductal stromal tumor of the breast with synchronous bilateral breast cancer.
Anticancer Res. 2014; 34(7):3635-9 [PubMed] Related Publications
We report on a case of low-grade periductal stromal tumor of the breast with synchronous bilateral breast carcinoma. A 45-year-old woman came to our Hospital because of a palpable mass of the right breast. An approximately 5-cm mass was palpated in the upper right breast. The mammographic and sonographic findings of the palpable mass suggested the possibility of hamartoma. A 1.3-cm, irregular mass with microcalcifications was also detected in the upper outer quadrant of the right breast and a 1.3-cm irregular mass was detected in the upper outer quadrant of the left breast. Core-needle biopsy revealed bilateral breast carcinoma. The patient underwent bilateral breast-conserving surgery, including the excision of the large palpable mass in the right breast. The palpable mass in the right breast was confirmed as low-grade periductal stromal tumor and there were bilateral invasive ductal carcinomas in both upper outer breast quadrants. After surgery, the patient received adjuvant chemotherapy. At 16 months of follow-up, no recurrence was observed.


Tiemann K, Weigel MT, Alkatout I, et al.
Significance of syndecan-1 expression in ductal carcinoma in situ of the breast.
Anticancer Res. 2014; 34(7):3607-16 [PubMed] Related Publications
BACKGROUND: Fibroblast growth factor-2 (FGF-2) supports tumor progression in breast cancer. FGF-2 signaling is modulated by heparan sulfate proteoglycans, such as syndecan-1 (CD138). The exact role of CD138 in ductal carcinoma in situ of the breast (DCIS) is still uncertain. Differential expression depending on grading could suggest a role for syndecan-1 during growth and tumor progression.
MATERIALS AND METHODS: Samples of 127 cases of breast DCIS associated with follow-up data were included. CD138 staining intensity, number of positive cells, intracellular and tissue localization were examined.
RESULTS: Median follow-up was 45.4 months and median recurrence-free survival (RFS) 86 months. Age, menopausal status and previous hormone replacement therapy had no significant influence on RFS. Smoking significantly influenced RFS (p=0.008). Endocrine therapy or radiotherapy did not improve RFS. Grading was not correlated with CD138 staining intensity, but was significantly associated with the percentage of CD138-positive cells (low-vs. high-grade, p=0.043). Estrogen receptor (ER) expression did not influence staining intensity of CD138 (p=0.247), but negatively correlated with the proportion of CD138-positive cells (p=0.032). Progesterone receptor (PR) expression significantly influenced the intensity of staining (p=0.010) and the percentage of CD138-positive cells (p=0.004); both were increased in PR-negative cases. CD138 staining intensity and percentage of positive cells did not correlate with RFS. Nuclear grade and syndecan-1 staining localization were significantly associated (p=0.001). ER-positive, and PR-positive DCIS more often exhibited membrane-bound syndecan-1 than ER- or PR-negative cases (p=0.001). Nuclear grade and tissue localization of CD138 correlated significantly (p=0.005). PR influenced CD138 tissue distribution, while ER did not. Syndecan-1 localization did not statistically impact RFS.
CONCLUSION: In DCIS of different nuclear grades, tissue localization of syndecan-1 is significantly divergent, suggesting a specific effect on biology and progression of DCIS.

Related: SDC1


Takashima T, Nakayama T, Yoshidome K, et al.
Phase II study of S-1 in combination with trastuzumab for HER2-positive metastatic breast cancer.
Anticancer Res. 2014; 34(7):3583-8 [PubMed] Related Publications
AIM: We undertook a prospective phase II study to evaluate the efficacy of S-1 plus trastuzumab combination regimen for human epidermal-growth factor receptor-2 (HER2)-positive metastatic breast cancer (MBC).
PATIENTS AND METHODS: HER2-positive MBC patients received oral administration of S-1 (80 mg/m2/day, days 1 to 28, every 6 weeks) and intravenous weekly trastuzumab (2 mg/kg), according to the results of a prior Phase I trial of our group.
RESULTS: A total of 28 patients were enrolled and received a median of 3.5 (range 1-10) cycles of treatment. Overall response rate and clinical benefit rate were 53.6% and 75.0%, respectively. Progression-free survival was 30 weeks. With regard to grade 3 and 4 adverse effects, leucopenia, neutropenia, increase in serum alanine aminotransferase, and diarrhea were observed.
CONCLUSION: Combination of S-1 and trastuzumab was tolerable and had excellent efficacy with good response and disease control in this trial.

Related: Tegafur-uracil Trastuzumab (Herceptin)


Burgy M, Brossat H, Barthelemy P, et al.
First report of trastuzumab treatment after postoperative Takotsubo cardiomyopathy.
Anticancer Res. 2014; 34(7):3579-82 [PubMed] Related Publications
BACKGROUND: Trastuzumab is a humanized monoclonal antibody used for the treatment of HER2-positive breast cancer. Cardiotoxicity is a well-known adverse event of trastuzumab use but little has been documented regarding its use in patients with a history of cardiac disease.
CASE REPORT: We describe a case in which trastuzumab treatment was administered to a 40-year-old female patient with early breast cancer after acute heart failure secondary to postoperative Takotsubo cardiomyopathy. After one year of follow-up with close monitoring by echocardiography, there have been no heart-related symptoms. Additional surgery was performed because of positive resection margins at first surgery, without complications, despite the risk of recurrence of Takotsubo cardiomyopathy.
CONCLUSION: Trastuzumab can be safely administered after acute heart failure secondary to postoperative Takotsubo cardiomyopathy.

Related: Trastuzumab (Herceptin)


Flejmer AM, Josefsson D, Nilsson M, et al.
Clinical implications of the ISC technique for breast cancer radiotherapy and comparison with clinical recommendations.
Anticancer Res. 2014; 34(7):3563-8 [PubMed] Related Publications
PURPOSE: The present project studied the implications of using the irregular surface compensator (ISC) technique in comparison to three-dimensional conformal radiation therapy (3D-CRT) for breast cancer treatment. ISC is an electronic compensation algorithm that modulates the fluence across the radiation fields to compensate for irregularly-shaped surfaces and deliver a homogeneous dose to a compensation plane.
PATIENTS AND METHODS: Ten breast cancer patients (five left- and five right-sided) were planned with both techniques. The planning was done for 50 Gy in 25 fractions with 2 Gy per fraction in all patients. Physical parameters such as doses to the clinical target volume (CTV-T) and the planned target volume (PTV), heterogeneity index and doses to lung and heart were determined and compared for the treatment plans.
RESULTS: The ISC technique led to significantly better coverage of the CTV-T and PTV in almost all patients with statistically significant better homogeneity of the dose distribution. The contralateral lung and the heart receive the same dose with both ISC and 3D-CRT plans. However, ISC showed a trend towards decreasing the volumes of the ipsilateral lung irradiated with high doses.
CONCLUSION: The ISC technique leads to an improvement of the target coverage and the radiation burden of the ipsilateral lung thus allowing better compliance with the national recommendations for breast radiotherapy and increasing the potential for improved quality of life for breast cancer patients. It should therefore be preferred over 3D-CRT for breast cases with difficult dose homogeneity to the PTV or CTV-T.


Park S, Shim SM, Nam SH, et al.
CGP74514A enhances TRAIL-induced apoptosis in breast cancer cells by reducing X-linked inhibitor of apoptosis protein.
Anticancer Res. 2014; 34(7):3557-62 [PubMed] Related Publications
BACKGROUND: Despite the selectivity of Tumor necrosis factor Related Apoptosis-Inducing Ligand (TRAIL) for cancer cell killing activity, breast cancer cells are resistant to TRAIL-induced apoptosis for various reasons.
MATERIALS AND METHODS: From a functionally-characterized small-molecule dataset, CGP74514A was identified as a TRAIL sensitizer in MCF-7 breast cancer cells. Combination of sub-toxic dose of TRAIL with CGP74514A was evaluated in three TRAIL-resistant breast cancer cells, MCF-7, T47D and SK-BR-3.
RESULTS: In all tested cells, CGP74514A enhanced TRAIL sensitivity. Combination treatment triggered apoptotic events faster than single treatment. Regarding its mechanism of action, CGP74514A reduced cytosolic X-linked inhibitor of apoptosis protein (XIAP). Small interfering RNA-mediated knockdown experiments showed that reduction of XIAP is the reason of sensitization.
CONCLUSION: CGP74514A sensitized breast cancer cells to TRAIL via reduction of XIAP expression level.

Related: Apoptosis TNFSF10


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