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.
Cancer Research UK CancerHelp information is examined by both expert and lay reviewers. Content is reviewed every 12 to 18 months. Further info. Statistics for the UK, including incidence, mortality, survival, risk factors and stats related to treatment and symptom relief.
NHS / ASKVisualScience An animated video about the anatomy of the breast - part of a series of videos about breast cancer aimed at general practitioners and their patients.
Breast Cancer - Module 2: Malignant Transformation and Growth
NHS / ASKVisualScience An animated video about how cancer can develop in the breasts - part of a series of videos about breast cancer aimed at general practitioners and their patients.
Breast Cancer - Module 3: Tumour Staging
NHS / ASKVisualScience An animated video about breast cancer staging - part of a series of videos about breast cancer aimed at general practitioners and their patients.
Breast Cancer - Module 4: Signs, Symptoms and Surgery
NHS / ASKVisualScience An animated video about the signs and symptoms of breast cancer and surgery for breast cancer - part of a series of videos about breast cancer aimed at general practitioners and their patients.
Think Pink Foundation An independent, volunteer based charity whose focus is to raise funds to provide financial and emotional support, information and counseling for breast cancer patients.
Understanding Pathology for Breast Cancer
Swedish Medical Center, Seattle Sean Thornton, MD, introduces the pathology and biology of breast cancer and role of the pathologist. The presenter is from Cellnetix Laboratories and Pathology / Swedish Medical Center - a not-for-profit hospital in Seattle.
What's New in Breast Cancer Care and Treatment
Cancer.Net Dr. Julie Gralow outlines recent research progress in the care and treatment of people with breast cancer. (2012)
PubMed Central search for free-access publications about Breast Cancer MeSH term: Breast Neoplasms US National Library of Medicine PubMed has over 22 million citations for biomedical literature from MEDLINE, life science journals, and online books. Constantly updated.
Cancer Research UK CancerHelp information is examined by both expert and lay reviewers. Content is reviewed every 12 to 18 months. Further info. Statistics for the UK, including incidence, mortality, survival, risk factors and stats related to treatment and symptom relief.
Gastric Breast Cancer Editorial Office Provides secondary-research articles (editorials, perspectives, news/views etc) on best practice and future clinical and research directions prevention and early detection, multidisciplinary, evidence-based management and treatment of breast cancer and gastric cancer. International editorial board, peer reviewed and open access.
breastcancer.org A nonprofit organization which aims to provide reliable, complete, and up-to-date information about breast cancer. Information is reviewed by an Advisory Board, which includes over 60 practicing medical professionals from around the world.
Against Breast Cancer a charity aiming to increase survival after breast cancer through research into secondary spread. The site includes pages about the organisation, facts about breast cancer, lifestyle, research reports etc. Research at Middlesex and UCL Hospitals.
Avon Foundation for Women Founded in 1992, this corporate organisation has raised over $780 million donated to breast cancer programs around the world. It supports awareness and education, screening and diagnosis, access to care, support services, and scientific research.
Breakthrough Breast Cancer A national charity launched in 1991 to promote breast cancer research. It supports the Breakthrough Research Centre in London and a number of other locations in the UK. The web site includes details of research, campaigns, events etc.
Breast Cancer Care A national charity promoting awareness and providing information and support to those affected by breast cancer. The Web site includes details of services; telephone helpline, volunteer and aftercare programs, on-line booklets and factsheets.
Breast Cancer Fund The Breast Cancer Fund works to prevent breast cancer by eliminating our exposure to toxic chemicals and radiation linked to the disease. The organisation has its headquaters in San Fransisco. Thw website includes information about chemicals and risk reduction.
HER2 Support Group A non-profit organisation which aims to help members by supporting concerns and by providing links to news and current research. The site includes a message board and details of clinical trials.
This list of publications is regularly updated (Source: PubMed).
Tan M, Howard A, Cyr AE Malignant melanoma of the breast: a case report and review of the literature. Tumori. 2013 Jan-Feb; 99(1):e11-3 [PubMed]
Primary breast melanoma is a rare entity that on routine histology may be mistaken for triple-negative breast cancer. A high degree of clinical suspicion is necessary to make this diagnosis. This case report describes the presentation and treatment of primary breast melanoma.
Dincoglan F, Beyzadeoglu M, Sager O, et al. Dosimetric evaluation of critical organs at risk in mastectomized left-sided breast cancer radiotherapy using breath-hold technique. Tumori. 2013 Jan-Feb; 99(1):76-82 [PubMed]
AIMS AND BACKGROUND: The aim of the study was to evaluate the dosimetric impact of the active breathing control-moderate deep inspiration breath-hold (ABC-mDIBH) technique on normal tissue sparing in locally advanced left-sided breast cancer radiotherapy. METHODS AND STUDY DESIGN: Twenty-seven consecutive patients with left-sided locally advanced breast cancer referred to our department for adjuvant radiotherapy were enrolled in the study. Each patient was scanned at free breathing and ABC-mDIBH for radiation treatment planning. Two separate radiotherapy treatment plans were generated with and without ABC-mDIBH to investigate the dosimetric impact of ABC-mDIBH in breast cancer radiotherapy. RESULTS: Between June 2011 and February 2012, 27 consecutive patients with left-sided locally advanced breast cancer referred to our department for adjuvant radiotherapy were enrolled in the study. Dose-volume parameters of left anterior descending coronary artery, lungs, heart, contralateral breast, esophagus and spinal cord were significantly reduced with the use of ABC-mDIBH (P <0.001). CONCLUSIONS: Our study revealed that the use of ABC-mDIBH in the practice of locally advanced mastectomized left-sided breast cancer radiotherapy improves normal tissue sparing with the expected potential of decreasing treatment-related morbidity and mortality. Moreover, the resultant reduction achieved with ABC in doses to the left anterior descending coronary artery, which plays a central role in cardiac perfusion, may have implications for decreasing the potential of radiation-induced cardiac morbidity and mortality.
Bareggi CM, Consonni D, Galassi B, et al. Uncommon breast malignancies: presentation pattern, prognostic issue and treatment outcome in an Italian single institution experience. Tumori. 2013 Jan-Feb; 99(1):39-44 [PubMed]
AIMS AND BACKGROUND: Often neglected by large clinical trials, patients with uncommon breast malignancies have been rarely analyzed in large series. PATIENTS AND METHODS: Of 2,052 patients diagnosed with breast cancer and followed in our Institution from January 1985 to December 2009, we retrospectively collected data on those with uncommon histotypes, with the aim of investigating their presentation characteristics and treatment outcome. RESULTS: Rare histotypes were identified in 146 patients (7.1% of our total breast cancer population), being classified as follows: tubular carcinoma in 75 (51.4%), mucinous carcinoma in 36 (24.7%), medullary carcinoma in 25 (17.1%) and papillary carcinoma in 10 patients (6.8%). Whereas age at diagnosis was not significantly different among the diverse diagnostic groups, patients with medullary and papillary subtypes had a higher rate of lymph node involvement, similar to that of invasive ductal carcinoma. Early stage diagnosis was frequent, except for medullary carcinoma. Overall, in comparison with our invasive ductal carcinoma patients, those with rare histotypes showed a significantly lower risk of recurrence, with a hazard ratio of 0.28 (95% CI, 0.12-0.62; P = 0.002). CONCLUSIONS: According to our analysis, patients with uncommon breast malignancies are often diagnosed at an early stage, resulting in a good prognosis with standard treatment.
Leoni M, Sadacharan R, Louis D, et al. Variation among local health units in follow-up care of breast cancer patients in Emilia-Romagna, Italy. Tumori. 2013 Jan-Feb; 99(1):30-4 [PubMed]
AIMS AND BACKGROUND: This study examines the patterns of follow-up care for breast cancer survivors in one region in Italy. METHODS AND STUDY DESIGN: This retrospective analysis included 10,024 surgically treated women, with incident cases of breast cancer in the years 2002-2005 who were alive 18 months after their incidence date. Rates of use of follow-up mammograms, abdominal echogram, bone scans and chest x-rays were estimated from administrative data and compared by Local Health Unit (LHU) of residence. Logistic regression analyses were performed to assess possible "overuse", accounting for patient age, cancer stage, type of surgery and LHU of residence. RESULTS: A total of 7168 (72.1%) women received a mammogram within 18 months of their incidence date, while 6432 (64.2%) had an abdominal echogram, 3852 (38.4%) had a bone scan and 5231 (52.2%) had a chest x-ray. The rates of use of abdominal echograms, bone scans and chest x-rays were substantially higher in the population of breast cancer survivors than in the general female population. Taking account of patient age, cancer stage at diagnosis and type of surgery, multivariate analyses demonstrated significant variation in the use of these tests by LHU of residence. CONCLUSIONS: The observed variation in the use of abdominal echograms, bone scans and chest x-rays supports the conclusion that there is substantial misuse of these tests in the population of postsurgical breast cancer patients in the Emilia-Romagna region in Italy. In the absence of a documented survival benefit, overtesting has both a human and financial cost. We recommend additional review of the methods of follow-up care in breast cancer patients in the LHUs of Emilia-Romagna, with the aim of developing, disseminating and evaluating the implementation of specific guidelines targeting primary care physicians and oncologists providing care to breast cancer survivors. Patient education materials may also help to reduce unnecessary testing.
Reyal F, Feron JG, Leman Detour S, et al. The impact of poly implant prothèse fraud on breast cancer patients: a report by the institut curie. Plast Reconstr Surg. 2013; 131(4):690-5 [PubMed]
In March of 2010, French authorities suspended the use of breast implants made by the company Poly Implant Prothèse. Institut Curie is a large cancer center, and Poly Implant Prothèse was one major silicone-filled breast implant brand used. This report describes the impact of the fraudulent implants worldwide and more specifically on patient care at the authors' unit. From 2002 to 2009, the median number of Poly Implant Prothèse implants removed per year was 32. Since the first alert in March of 2010, 252 of these breast implants were removed in 2010 and 2011. The breast implants removed were mainly reported as normal, with a rupture rate of less than 5 percent before 2008. However, the annual rupture rate has increased from 2008 to 2011 (8, 14, 20, and 23 percent, respectively). The Institut Curie, in conjunction with breast cancer patients, has organized a management plan to deal with this major industrial fraud. Its surveillance program of breast cancer patients facilitated the management of patients during this difficult time.
Martinou M, Gaya A Cardiac complications after radical radiotherapy. Semin Oncol. 2013; 40(2):178-85 [PubMed]
Improvements in cancer therapy have led to increasing numbers of cancer survivors, and the long-term complications of these treatments are now becoming apparent. This article presents the current knowledge of adverse cardiovascular effects of radiotherapy to the chest. Medline literature searches relating to the cardiac complications of radiotherapy and subsequent prognosis were conducted. Potential adverse effects of mediastinal irradiation are numerous and can include coronary artery disease, pericarditis, cardiomyopathy, and valvular disease. Damage seems to be related to radiation dose, volume of irradiated heart, age at exposure, technique of chest irradiation, and patient-specific factors. The advent of technology and the newer sophisticated techniques in treatment planning and delivery are expected to decrease the incidence of cardiovascular diseases after radiation of the mediastinal structures. In any case, patients subjected to irradiation of the mediastinal structures require close multidisciplinary clinical monitoring.
Sriussadaporn S, Angspatt A Primary angiosarcoma of the breast: a case report and review of the literature. J Med Assoc Thai. 2013; 96(3):378-82 [PubMed]
Primary angiosarcoma of the breast is rare. Therefore, no randomized trial can be used as guideline for diagnosis and treatment. To achieve optimal outcome, previous reports of case series are the sources for management with expected long-term survival. The objective of the present case report is to demonstrate complete pathologic response to neoadjuvant taxanes without recurrence after two years of follow-up.
Cope S, Ouwens MJ, Jansen JP, Schmid P Progression-free survival with fulvestrant 500 mg and alternative endocrine therapies as second-line treatment for advanced breast cancer: a network meta-analysis with parametric survival models. Value Health. 2013 Mar-Apr; 16(2):403-17 [PubMed]
BACKGROUND: Ouwens et al. and Jansen have presented methods for (network) meta-analysis of survival data by using a multidimensional treatment effect as an alternative to the synthesis of constant hazards ratios, which allow for a better fit to the data and the expected survival of competing interventions for cost-effectiveness analysis. However, results may be sensitive to the assumed underlying survival function. OBJECTIVE: To estimate the expected progression-free survival (PFS) for fulvestrant 500 mg versus alternative hormonal therapies for postmenopausal women with advanced breast cancer who relapsed previously by means of a network meta-analysis of currently available randomized controlled trials using alternative underlying survival functions. METHODS: Eleven randomized controlled trials were included that evaluated fulvestrant 500 mg (n = 3), fulvestrant 250 mg (n = 5), fulvestrant 250 mg loading dose (n = 3), anastrozole 1 mg (n = 3), megestrol acetate (n = 4), letrozole 2.5 mg (n = 3), letrozole 0.5 mg (n = 3), and exemestane (n = 2). PFS percentages and numbers at risk were derived from Kaplan-Meier curves and combined by means of Bayesian network meta-analysis on the basis of the difference in the shape and scale parameters of the Weibull, log-normal, and log-logistic parametric survival functions. RESULTS: The log-normal distribution provided the best fit, suggesting that the proportional hazard assumption was not valid. Based on the difference in expected PFS, it was found that fulvestrant 500 mg is more efficacious than fulvestrant 250 mg, megestrol acetate, and anastrozole (-5.73 months; 95% credible interval [CrI]-10.67,-1.67). Expected PFS for fulvestrant 500 mg ranged from 10.87 (95% CrI 9.21, 13.07) to 17.02 (95% CrI 13.33, 22.02) months for the Weibull versus log-logistic distribution. CONCLUSIONS: Fulvestrant 500 mg is expected to be more efficacious than fulvestrant 250 mg, megestrol acetate, and anastrozole 1 mg and at least as efficacious as exemestane and letrozole 2.5 mg in terms of PFS among postmenopausal women with advanced breast cancer after failure on endocrine therapy. The findings were not sensitive to the distribution, although the expected PFS varied substantially, emphasizing the importance of performing sensitivity analyses.
Harkrider WW, Diebold AE, Maloney T, et al. An extended phase II trial of iodine-125 methylene blue for sentinel lymph node identification in women with breast cancer. J Am Coll Surg. 2013; 216(4):599-605; discussion 605-6 [PubMed]
BACKGROUND: The aim of this study was to determine if an intraoperative injection of iodine-125-labeled methylene blue ((125)I-MB) is a sensitive and effective method for detecting SLNs in women with breast cancer. STUDY DESIGN: Sixty-two women were enrolled in an extended phase II trial using (125)I-MB to guide SLNB. All patients were anesthetized and then injected subcutaneously with 1 mCi (125)I-MB in the outer quadrant of the areola. RESULTS: Radioactivity was detected in the axilla within 3 to 5 minutes. Fifty-eight of 62 (94%) patients had SLNs detected during their procedure. Mean (±SD) number of SLNs per patient was 1.8 ± 1.3 (range 0 to 6). A total of 112 nodes were dissected from 58 women; 110 of these nodes were considered sentinel. One hundred and eight (98%) nodes were hot, 98 (89%) nodes were blue, and 96 (87%) nodes were both hot and blue. Two women had complications; 1 had superficial skin staining and 1 had a superficial skin slough. Both healed uneventfully. No allergic reactions were observed. No radioactive uptake in the thyroid was seen. CONCLUSIONS: Iodine-125-labeled methylene blue can be mixed and administered in the operating room, improving hospital efficiency. Patient satisfaction is higher with (125)I-MB than with the technetium 99m sulfur colloid procedure because (125)I-MB does not produce localized burning and other adverse reactions associated with the traditional method, and 125I-MB is administered with the patient under anesthesia. Iodine-125 emits a lower-energy gamma ray than technetium 99m, lowering the surgeon's radiation exposure. Iodine-125-labeled methylene blue SLN identification is safe, cost effective, and produces equivalent outcomes compared with the traditional technique, making it an attractive alternative.
Jana D, Sarkar DK, Maji A, et al. Can cyclo-oxygenase-2 be a useful prognostic and risk stratification marker in breast cancer? J Indian Med Assoc. 2012; 110(7):429-33 [PubMed]
Cyclo-oxygenase-2 (COX-2) is a prostaglandin synthease that catalyses the synthesis of prostaglandin G2 (PGG2) and PGH2 from arachidonic acid. COX-2 plays an important role in tumourigenesis of different carcinoma types and it is thought to take part in breast carcinoma. In this study, the aim was to investigate the relationship of COX-2 with clinical parameters such as menopausal status, tumour size, grade, nodal status, Nottingham prognostic index (NPI), oestrogen receptor(ER), progesterone receptor (PR), human epidermal growth factor receptor type 2 (HER-2/ neu). The patients were divided into two groups, first group (group A) comprised 57 primary breast cancer patients and the second group (group B) comprised control group 27 patients consisting of fibro-adenoma and benign breast disease. In control groups COX-2 (0%) is not over expressed and we observed that high frequency of COX-2 (73.68%) over expressed in breast carcinoma. In high grade, large tumour size and positive lymph node metastasis, COX-2 expression rate was 78.6%, 59.5% and 90.5% respectively. COX-2 expression is directly correlated with ER negative (88.1%, p = 0.001) and also associated with higher NPI value (78.6%, p = 0.006). In invasive ductal carcinoma (IDC) COX-2 over expression had a significant relationship with HER-2/neu over expression (p < 0.001). The results indicated that COX-2 over expression correlates with aggressive phenotypic features, such as high histological grade, large tumour size, higher NPI value, ER negativity and HER-2/neu positivity.
Loganathan R, Selvaduray KR, Nesaretnam K, Radhakrishnan AK Tocotrienols promote apoptosis in human breast cancer cells by inducing poly(ADP-ribose) polymerase cleavage and inhibiting nuclear factor kappa-B activity. Cell Prolif. 2013; 46(2):203-13 [PubMed]
OBJECTIVES: Tocotrienols and tocopherols are members of the vitamin E family, with similar structures; however, only tocotrienols have been reported to achieve potent anti-cancer effects. The study described here has evaluated anti-cancer activity of vitamin E to elucidate mechanisms of cell death, using human breast cancer cells. MATERIALS AND METHODS: Anti-cancer activity of a tocotrienol-rich fraction (TRF) and a tocotrienol-enriched fraction (TEF) isolated from palm oil, as well as pure vitamin E analogues (α-tocopherol, α-, δ- and γ-tocotrienols) were studied using highly aggressive triple negative MDA-MB-231 cells and oestrogen-dependent MCF-7 cells, both of human breast cancer cell lines. Cell population growth was evaluated using a Coulter particle counter. Cell death mechanism, poly(ADP-ribose) polymerase cleavage and levels of NF-κB were determined using commercial ELISA kits. RESULTS: Tocotrienols exerted potent anti-proliferative effects on both types of cell by inducing apoptosis, the underlying mechanism of cell death being ascertained using respective IC50 concentrations of all test compounds. There was marked induction of apoptosis in both cell lines by tocotrienols compared to treatment with Paclitaxel, which was used as positive control. This activity was found to be associated with cleavage of poly(ADP-ribose) polymerase (a DNA repair protein), demonstrating involvement of the apoptotic cell death signalling pathway. Tocotrienols also inhibited expression of nuclear factor kappa-B (NF-κB), which in turn can increase sensitivity of cancer cells to apoptosis. CONCLUSION: Tocotrienols induced anti-proliferative and apoptotic effects in association with DNA fragmentation, poly(ADP-ribose) polymerase cleavage and NF-κB inhibition in the two human breast cancer cell lines.
Lamb MR, Gertsen E, Middlemas E Metaplastic breast cancer: a presentation of two cases and a review of the literature. Tenn Med. 2013; 106(2):39-41 [PubMed]
Metaplastic breast cancer has been difficult to diagnose and classify for a number of reasons. Its rarity prevents any important conclusions to be made, such as factors determining prognosis, immunohistochemistry patterns and successful treatment regimens. Here a number of studies of metaplastic breast cancer are discussed, along with the presentation of two cases.
Chen Y, Yan J, Yuan Z, et al. A meta-analysis of the relationship between lymphatic microvessel density and clinicopathological parameters in breast cancer. Bull Cancer. 2013; 100(3):1-10 [PubMed]
BACKGROUND: Breast cancer is a common malignant neoplasm that is a leading cause of cancer death in women despite recent advances in treatment and research. The role of lymphangiogenesis in breast cancer development remains a source of controversy in current research. OBJECTIVE: The relationship between lymphatic microvessel density (LMVD) and the clinicopathological parameters of breast cancer can be effectively examined by meta-analysis of recent studies. METHODS: A total of 10 relevant studies consisting of 1,044 total patients were examined by electronic searches of PubMed and Embase databases. Weighted mean difference (WMD) and 95% confidence intervals (CI) were estimated and pooled according to standard methods. LMVD data was pooled by tumor size, lymphatic node metastases, and tumor hormone receptor status of estrogen receptors (ER) and progesterone receptors (PR). RESULTS: A remarkable correlation between LMVD and lymph node metastases was observed in pooled analyses using a random-effects model (WMD: 2.72; 95%CI: 2.27, 3.16; P = 0.000). LMVD and tumor size showed a pooled WMD value of 0.00 (95%CI: -0.49, 0.50; P = 0.009), indicating no significant correlation between LMVD and tumor size. LMVD and either ER or PR status showed pooled WMD values of 0.24 (95%CI: -0.30, 0.79; P = 0.004) and -0.12 (95%CI: -0.81, 0.56, P = 0.301), respectively, also indicating no significant correlation between LMVD and ER or PR status. CONCLUSION: A close relationship was observed between LMVD and lymph node metastases, though no correlation between LMVD and other important clinicopathological parameters was apparent. The current meta-analysis suggests that LMVD may be associated with increased metastatic activity in breast cancer, though the full role of lymphangiogenesis in breast cancer remains uncertain.
Schreiter NF, Volkwein N, Schneider P, et al. Optical imaging of breast cancer using hemodynamic changes induced by valsalva maneuver. Rofo. 2013; 185(4):358-66 [PubMed]
PURPOSE: To investigate whether changes in hemodynamics induced by Valsalva maneuver can be exploited for detecting and characterizing breast lesions by optical mammography. MATERIALS AND METHODS: 30 women underwent optical imaging of the breast using a DYNOT 232 system and performing Valsalva maneuvers prior to biopsy. Changes in light absorption due to changes in oxyhemoglobin and deoxyhemoglobin concentrations were recorded volumetrically and in a time-resolved manner. The parameters full width at half maximum (FWHM), time to ten (TTT), and peak amplitude (PA) of the reconstructed concentration time curves yielded color-coded maps of the breast which were separately evaluated by two experienced readers for detection rate, degree of visibility, and detection of additional lesions. ROC analysis was performed with the evaluation results. RESULTS: 10 patients were excluded from analysis due to artifacts or inadequately performed Valsalva maneuver. The resulting 20 patients showed a clear increase in oxygenated and deoxygenated hemoglobin concentration after the onset of the Valsalva maneuver. ROC analysis yielded AUC values (0.393 - 0.779) that did not differ from random probabilities. The highest AUC values were obtained for FWHM (AUC: 0.779, detection rates [60 - 70 %], identification of additional lesions [55 - 70 %]). PA analysis had the highest detection rate (70 - 90 %) but also the highest identification of false-positive additional lesions (80 - 90 %). The concordance rates of the two readers for malignant lesions were satisfactory (0.524 - 1.0). CONCLUSION: Our study revealed susceptibility to artifacts and a large number of false-positive additional lesions, suggesting that the evaluation of hemodynamic changes after Valsalva maneuver by optical imaging is not a promising method.
Darby SC, Ewertz M, McGale P, et al. Risk of ischemic heart disease in women after radiotherapy for breast cancer. N Engl J Med. 2013; 368(11):987-98 [PubMed]
BACKGROUND: Radiotherapy for breast cancer often involves some incidental exposure of the heart to ionizing radiation. The effect of this exposure on the subsequent risk of ischemic heart disease is uncertain. METHODS: We conducted a population-based case-control study of major coronary events (i.e., myocardial infarction, coronary revascularization, or death from ischemic heart disease) in 2168 women who underwent radiotherapy for breast cancer between 1958 and 2001 in Sweden and Denmark; the study included 963 women with major coronary events and 1205 controls. Individual patient information was obtained from hospital records. For each woman, the mean radiation doses to the whole heart and to the left anterior descending coronary artery were estimated from her radiotherapy chart. RESULTS: The overall average of the mean doses to the whole heart was 4.9 Gy (range, 0.03 to 27.72). Rates of major coronary events increased linearly with the mean dose to the heart by 7.4% per gray (95% confidence interval, 2.9 to 14.5; P<0.001), with no apparent threshold. The increase started within the first 5 years after radiotherapy and continued into the third decade after radiotherapy. The proportional increase in the rate of major coronary events per gray was similar in women with and women without cardiac risk factors at the time of radiotherapy. CONCLUSIONS: Exposure of the heart to ionizing radiation during radiotherapy for breast cancer increases the subsequent rate of ischemic heart disease. The increase is proportional to the mean dose to the heart, begins within a few years after exposure, and continues for at least 20 years. Women with preexisting cardiac risk factors have greater absolute increases in risk from radiotherapy than other women. (Funded by Cancer Research UK and others.).
Dawson SJ, Tsui DW, Murtaza M, et al. Analysis of circulating tumor DNA to monitor metastatic breast cancer. N Engl J Med. 2013; 368(13):1199-209 [PubMed]
BACKGROUND: The management of metastatic breast cancer requires monitoring of the tumor burden to determine the response to treatment, and improved biomarkers are needed. Biomarkers such as cancer antigen 15-3 (CA 15-3) and circulating tumor cells have been widely studied. However, circulating cell-free DNA carrying tumor-specific alterations (circulating tumor DNA) has not been extensively investigated or compared with other circulating biomarkers in breast cancer. METHODS: We compared the radiographic imaging of tumors with the assay of circulating tumor DNA, CA 15-3, and circulating tumor cells in 30 women with metastatic breast cancer who were receiving systemic therapy. We used targeted or whole-genome sequencing to identify somatic genomic alterations and designed personalized assays to quantify circulating tumor DNA in serially collected plasma specimens. CA 15-3 levels and numbers of circulating tumor cells were measured at identical time points. RESULTS: Circulating tumor DNA was successfully detected in 29 of the 30 women (97%) in whom somatic genomic alterations were identified; CA 15-3 and circulating tumor cells were detected in 21 of 27 women (78%) and 26 of 30 women (87%), respectively. Circulating tumor DNA levels showed a greater dynamic range, and greater correlation with changes in tumor burden, than did CA 15-3 or circulating tumor cells. Among the measures tested, circulating tumor DNA provided the earliest measure of treatment response in 10 of 19 women (53%). CONCLUSIONS: This proof-of-concept analysis showed that circulating tumor DNA is an informative, inherently specific, and highly sensitive biomarker of metastatic breast cancer. (Funded by Cancer Research UK and others.).
Osti MF, Carnevale A, Bracci S, et al. Exclusive electron intraoperative radiotherapy in early-stage breast cancer: a monoinstitutional experience. Anticancer Res. 2013; 33(3):1229-35 [PubMed]
AIM: To evaluate the effectiveness of intra-operative radiotherapy (IORT) in breast cancer in terms of local control, esthetic results and disease-free survival. PATIENTS AND METHODS: From June 2007 to October 2011, 110 patients with early-stage breast cancer were submitted to quadrantectomy and IORT. A total dose of 21 Gy prescribed at 90-100% isodose was delivered in all cases. Patients were evaluated after surgery for early and late complications. RESULTS: Median follow-up was 27 (range: 2-54) months. In 10 patients (9.1%), breast ultrasound showed liponecrosis. Six patients (5.5%) developed grade 2 fibrosis. Disease-free survival rates at 2 and 3 years were 96.8% and 92.9 %. Three patients (2.7%) developed local recurrence, two patients (1.8%) distant metastasis. Two patients died. The 2- and 3-year overall survival rates were 100% and 97.3%, respectively. CONCLUSION: IORT could be an appropriate therapeutic alternative in selected patients although it remains investigational; longer follow-up to confirm these results is required.
Sheen-Chen SM, Huang CY, Chan YC, et al. An evaluation of focal adhesion kinase in breast cancer by tissue microarrays. Anticancer Res. 2013; 33(3):1169-73 [PubMed]
BACKGROUND: Many studies have shown that focal adhesion kinase (FAK) is a positive regulator of tumor progression and invasion. However, there is still very limited information about the role of FAK in breast cancer. Tissue microarrays (TMA) can analyze thousands of tissue samples in a parallel fashion with minimal damage to the origin block. This study was designed with the application of TMA to analyze the FAK status in breast cancer. PATIENTS AND METHODS: Archival tissue specimens from 98 patients with primary invasive breast cancer were selected and FAK expression was analyzed by immunohistochemical staining with TMA. The data of primary tumor staging, age, estrogen receptor status, lymph node status, histological grading and TNM staging were also collected. RESULTS: There were four patients (4.0%) with grade 1 expression in FAK, 41 patients (41.8%) with grade 2 expression in FAK and 53 patients (54.2%) with grade 3 expression in FAK. There was no significant relationship between FAK expression and age, estrogen receptor status, histological grading, primary tumor staging, lymph node status and TNM stage. By multivariate analysis, the TNM stage was found to be significantly related to the overall five-year survival rate (p<0.00001). CONCLUSION: Immunohistochemical staining with TMA is a convenient and feasible method. Unfortunately, our preliminary results fail to show meaningful prognostic value of FAK in breast cancer. A larger prospective study is warranted for further evaluation.
Kanbayashi Y, Hosokawa T, Kitawaki J, Taguchi T Statistical identification of predictors for paclitaxel-induced peripheral neuropathy in patients with breast or gynaecological cancer. Anticancer Res. 2013; 33(3):1153-6 [PubMed]
AIM: The aim of this study was to identify predictors for paclitaxel-induced peripheral neuropathy (PIPN). PATIENTS AND METHODS: We conducted a retrospective analysis of 227 patients who had been treated with paclitaxel at a single institution between January 2008 and July 2011. At the time of chemotherapy completion, the severity of PIPN was graded on a scale of 0-5, in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events v4.0. Multivariate-ordered logistic regression analysis was employed to examine the relationship between various predictive factors and the occurrence of PIPN. RESULTS: Diabetes mellitus [odds ratio (OR)=0.070], age (OR=1.991), co-administration of neurotropin (OR=3.654), co-administration of opioids (OR=0.312), co-administration of vitamin B12 (OR=2.554), co-administration of antidepressant (OR=4.754) and co-administration of gabapentinoids (OR=14.620), were significantly associated with reduction of or less serious PIPN. CONCLUSION: Our study indicates that PIPN may be alleviated by co-administration of opioids.
Rubio CA, Svane G, Ilescu G, et al. Pitfall in assessing the size of tumor phantoms on mammograms. Anticancer Res. 2013; 33(3):1131-4 [PubMed]
BACKGROUND: Tumor size is crucial for clinical management and prognosis of breast malignancies. MATERIALS AND METHODS: The gold standard-size of 12 tumor phantoms was assessed at The Department of Production Engineering. Subsequently, with a conventional ruler, seven experienced mammographers measured the largest diameter of the 12 devices in two independent trials. RESULTS: In the first trial, 30% (n=25) of the 84 values given by the seven mammographers failed to recreate the gold standard size by >1 mm and in the second, by 37% (31/84). Size was overestimated (>1 mm) in 9.5% (n=8) of 84 measurements in the first trial, and in 15.5% (14/84) in the second. Conversely, size was underestimated (>1 mm) in 20% (n=17) of 84 measurements in the first trial, and in 21% (18/84) in the second. Neither the age of the participants, nor their years of experience improved the obtained results. Discussion: The method used here raised doubts concerning the ability of discriminating size among subgroups of T1 breast tumors in mammograms. According to the TNM staging system, T1 tumors (≤2.0 cm in greatest dimension) are subdivided into T1mic: microinvasion (≤0.1 cm), T1a (>0.1 cm but not more than 0.5 cm), T1b (>0.5 cm but not more than 1.0 cm) and T1c (>1.0 cm but not more than 2.0 cm in their greatest dimension). Since the TNM staging system for breast tumors is important in therapeutic decision making, it is crucial to develop a more reliable method for tumor size assessment.
Arlicot C, Louarn AL, Arbion F, et al. Evaluation of the two intraoperative examination methods for sentinel lymph node assessment: a multicentric and retrospective study on more than 2,000 nodes. Anticancer Res. 2013; 33(3):1045-52 [PubMed]
BACKGROUND: Intraoperative frozen section (FS) and imprint cytology (IC) are currently used to detect sentinel lymph node (SLN) metastasis, allowing for complete dissection when necessary. MATERIALS AND METHODS: A 2-year retrospective chart review was performed for patients who underwent SLN procedure in five French hospitals. The FS and IC results were compared to the definitive histology in order to calculate the sensitivity, specificity and false-negative rate. These results were studied from both the surgeon's and the pathologist's point of view. RESULTS: The comparison of the FS group (n=672) and IC group (n=576) showed a lack of sensitivity for both techniques, even if it was better for FS (59.3% vs. IC=33.3%). The false-negative rate (among patients with metastases) was very high in the two groups (FS=40.7% vs. IC=66.6%), leading to high re-intervention rates (FS=40.7% vs. IC=30.2%). False-negative nodes were more often small metastases and lobular carcinoma type. CONCLUSION: The interest in intraoperative examination is questionable. To avoid intraoperative examination failures, we think that complete staging of the disease before surgical treatment would be more relevant.
Raica M, Cimpean AM, Ceausu R, et al. Interplay between mast cells and lymphatic vessels in different molecular types of breast cancer. Anticancer Res. 2013; 33(3):957-63 [PubMed]
The particularities of lymphangiogenesis in different molecular types of breast cancer are virtually unknown and the contribution of microenvironment to this process has been ever less investigated. In the present study, we evaluated the relationships between lymphatic microvessel density (LMVD), mast cell density (MCD) and the different molecular subtypes of breast cancer. Molecular classification of breast tumors by immunohistochemistry was followed by the detection of mast cells and lymphatic vessels on the same slide by immunohistochemical double-stain method, using the lymphatic endothelial cell marker D2-40 and the mast cell tryptase. Mast cells and lymphatic vessels were simultaneously counted in the tumoral and peritumoral areas and results were compared with the molecular type, grade, lymphovascular invasion and lymph node status. Significant positive correlations were found between peritumoral MCD and LMVD for the luminal type-A breast cancers (p=0.025) and also for basal-like carcinomas (p=0.029). Moreover, a significant positive correlation was found between peritumoral and intratumoral MCD for basal-like carcinomas (p=0.009) and for overall MCD and LMVD. Low or inverse correlations between MCD and LMVD were also observed in other molecular subtypes of breast cancer. Our results strongly support that mast cells in the tumor microenvironment are keyplayers, involved in the development of tumor lymphatic vessels for some molecular subtypes of breast cancer.
Yoo YD, Han DH, Jang JM, et al. Molecular characteristics of cancer stem-like cells derived from human breast cancer cells. Anticancer Res. 2013; 33(3):763-77 [PubMed] Free Access to Full Article
We characterized the cellular properties of cancer stem-like cells (CSLCs) isolated from immortalized MDA-MB453 human breast cancer cells in culture. We showed that although the expression of Octamer-binding transcription factor-4 (OCT4) correlates to stemness in these CSLCs, OCT4 knockdown does not induce their differentiation. Our results suggest that the differentiation program in MDA-MB453 CSLCs is blocked at a step upstream of the transcription of the OCT4 promoter, allowing CSLCs to maintain their population through asymmetric cell division during many repeated passages. Comparative expression analysis indicates that only a subset of genes and signaling pathways known to be associated with survival and maintenance of CSCs are selectively expressed in CSLCs, as compared with non-CSLCs fractionated from the same parental MDA-MB453 cells. These results suggest that selective expression of a limited number of genes may be sufficient for establishment and maintenance of CSLCs with high tumorigenicity.
He GH, Lu J, Shi PP, et al. Polymorphisms of human histamine receptor H4 gene are associated with breast cancer in Chinese Han population. Gene. 2013; 519(2):260-5 [PubMed]
Previous investigations indicated that histamine receptor H4 (HRH4) played important roles in many aspects of breast cancer pathogenesis, and that the polymorphisms of HRH4 gene may result in expression and functional changes of HRH4 proteins. However, the relationship between polymorphisms of HRH4 and breast cancer risk and malignant degree is unclear. In the present study, we conducted a case-control investigation among 185 Chinese Han breast cancer patients and 199 ethnicity-matched health controls. Four tag-SNPs (i.e. rs623590, rs16940762, rs11662595 and rs1421125) of HRH4 were genotyped and association analysis was performed. Odds ratios (ORs) with 95% confidence intervals (CI) were used to assess the association. We found that the T allele of rs623590 had a decreased risk of breast cancer (adjusted OR, 0.667; 95% CI, 0.486-0.913; P=0.012) while the A allele of rs1421125 had an increased risk (adjusted OR, 1.653; 95% CI, 1.139-2.397; P=0.008). Further haplotype analysis showed that the CAA haplotype of rs623590-rs11662595-rs1421125 was more frequent among patients with breast cancer (adjusted OR, 1.856; 95% CI, 1.236-2.787; P=0.003). Additionally, polymorphisms of rs623590 and rs11662595 were also correlated with clinical stages, lymph node involvement, and HER2 status. These findings indicated that the variants of rs623590, rs11662595 and rs1421125 genotypes of HRH4 gene were significantly associated with the risk and malignant degree of breast cancer in Chinese Han populations, which may provide us novel insight into the pathogenesis of breast cancer although further studies with larger participants worldwide are still needed for conclusion validation.
Haloua MH, Krekel NM, Winters HA, et al. A systematic review of oncoplastic breast-conserving surgery: current weaknesses and future prospects. Ann Surg. 2013; 257(4):609-20 [PubMed]
OBJECTIVE: The primary objectives of this systematic review on oncoplastic breast surgery (OPBS) were to evaluate the oncological and cosmetic outcomes of OPBS. The secondary objectives were to assess morbidity, quality of life, and applied algorithms. BACKGROUND: Breast-conserving therapy (BCT) has become the standard of care, and survival is now excellent. Consequently, the focus of BCT has increasingly shifted to cosmetic outcome, quality of life, and patient satisfaction. Nonetheless, excision of certain tumors still presents a considerable challenge. Specialized approaches combining oncological surgery and plastic surgery techniques are collectively referred to as OPBS. A summary of OPBS outcomes would facilitate decision-making and best treatment selection by both clinicians and patients. METHODS: Using specific inclusion and exclusion criteria to analyze 2090 abstracts on the topic of OPBS published between 2000 and 2011, the authors evaluated each study with respect to design and outcomes. RESULTS: A total of 88 articles were identified for potential inclusion and reviewed in detail by the lead authors. No randomized controlled trials were identified. Eleven prospective observational or comparative studies fulfilled inclusion criteria and were selected. In these studies, 80% to 93% of the tumors were invasive. Tumor-free resection margins were observed in 78% to 93%, resulting in a 3% to 16% mastectomy rate. Local recurrence was observed in 0% to 7% of the patients. Good cosmetic outcome was obtained in 84% to 89% of patients. However, most studies showed significant weaknesses including lack of robust design and important methodological shortcomings, negatively influencing generalizability. CONCLUSIONS: This systematic review reveals that current evidence supporting the efficacy of OPBS is based on poorly designed and underpowered studies. Given the increasing importance and application of OPBS, there is a pressing need for robust comparative studies, including both randomized controlled trials and well-designed, multicenter prospective longitudinal studies.
Arora R, Abou-Bakr A, Al Taleb A Fine needle aspiration diagnosis of a spontaneously infarcted fibroadenoma mimicking carcinoma: a case report. Anal Quant Cytol Histol. 2013; 35(1):57-60 [PubMed]
BACKGROUND: Spontaneous infarction of fibroadenoma is an extremely rare complication in a nonpregnant/nonlactating female undergoing first-time aspiration. It can be misdiagnosed as carcinoma in all aspects of triple approach used for evaluation of patients with breast lesions. CASE: A 37-year-old woman presented to the outpatient surgical clinic with a 6-month history of a breast lump that was slowly increasing in size and had become painful during the past month. There was no history of any trauma or fine needle aspiration, and she was not pregnant or lactating. Mammogram and ultrasound revealed a 2.9-cm heterogenous hypoechoic suspicious lesion. No lymph nodes were detected in the axilla. Fine needle aspiration cytology was performed, and a diagnosis of benign breast lesion with features of infarction was rendered on cytology. The lump was excised surgically, and a histological diagnosis of infarcted fibroadenoma was made. CONCLUSION: Careful and diligent search for preserved benign epithelial cells on smears is the key to recognize this entity and avoid serious therapeutic implications.
Allam MF, Abd Elaziz KM Evaluation of the level of knowledge of Egyptian women of breast cancer and its risk factors. A cross sectional study. J Prev Med Hyg. 2012; 53(4):195-8 [PubMed]
Breast cancer is considered the leading cause of cancer death among females in economically developing countries. Prevalence of breast carcinoma is high in Egypt and the cases of breast cancer constitute 29% of cancer cases treated at the national cancer institute. This study aimed at exploring the level of knowledge of Egyptian females of breast cancer and its risk factors. An interview questionnaire with 22 questions about breast cancer was developed. This questionnaire was previously published as a part of the German multicentre DACH study). A total of 600 female subjects that attended primary health care centres were enrolled in our study. The majority were located in Cairo with the mean age of 40.5 +/- 11.0. Most of our studied sample (94%) has heard about breast cancer as a disease. TV and radio were the main sources of knowledge about the disease (60%). The level of knowledge about breast cancer was limited in 80% of the subjects. Younger age subjects had a higher level of knowledge about breast cancer compared to older subjects with no significant difference statistically. The grade of knowledge about breast cancer was higher among highly educated subjects compared to less educated subjects with significant difference statistically. The highest known risk factors of breast cancer were exposure to X ray (79.5%), hormonal therapy (75.7%) and previous breast cancer disease (70.8%). This study clearly illustrates the need for a health education program directed to Egyptian females to improve the knowledge of breast cancer.
Yuen HF, Gunasekharan VK, Chan KK, et al. RanGTPase: a candidate for Myc-mediated cancer progression. J Natl Cancer Inst. 2013; 105(7):475-88 [PubMed]
BACKGROUND: Ras-related nuclear protein (Ran) is required for cancer cell survival in vitro and human cancer progression, but the molecular mechanisms are largely unknown. METHODS: We investigated the effect of the v-myc myelocytomatosis viral oncogene homolog (Myc) on Ran expression by Western blot, chromatin immunoprecipitation, and luciferase reporter assays and the effects of Myc and Ran expression in cancer cells by soft-agar, cell adhesion, and invasion assays. The correlation between Myc and Ran and the association with patient survival were investigated in 14 independent patient cohorts (n = 2430) and analyzed with Spearman's rank correlation and Kaplan-Meier plots coupled with Wilcoxon-Gehan tests, respectively. All statistical tests were two-sided. RESULTS: Myc binds to the upstream sequence of Ran and transactivates Ran promoter activity. Overexpression of Myc upregulates Ran expression, whereas knockdown of Myc downregulates Ran expression. Myc or Ran overexpression in breast cancer cells is associated with cancer progression and metastasis. Knockdown of Ran reverses the effect induced by Myc overexpression in breast cancer cells. In clinical data, a positive association between Myc and Ran expression was revealed in 288 breast cancer and 102 lung cancer specimens. Moreover, Ran expression levels differentiate better or poorer survival in Myc overexpressing breast (χ2 = 24.1; relative risk [RR] = 9.1, 95% confidence interval [CI] = 3.3 to 24.7, P < .001) and lung (χ2 = 6.04; RR = 2.8, 95% CI = 1.2 to 6.3; P = .01) cancer cohorts. CONCLUSIONS: Our results suggest that Ran is required for and is a potential therapeutic target of Myc-driven cancer progression in both breast and lung cancers.
Colfry AJ Miscellaneous syndromes and their management: occult breast cancer, breast cancer in pregnancy, male breast cancer, surgery in stage IV disease. Surg Clin North Am. 2013; 93(2):519-31 [PubMed]
Surgical therapy for occult breast cancer has traditionally centered on mastectomy; however, breast conservation with whole breast radiotherapy followed by axillary lymph node dissection has shown equivalent results. Patients with breast cancer in pregnancy can be safely and effectively treated; given a patient's pregnancy trimester and stage of breast cancer, a clinician must be able to guide therapy accordingly. Male breast cancer risk factors show strong association with BRCA2 mutations, as well as Klinefelter syndrome. Several retrospective trials of surgical therapy in stage IV breast cancer have associated a survival advantage with primary site tumor extirpation.
Black DM, Mittendorf EA Landmark trials affecting the surgical management of invasive breast cancer. Surg Clin North Am. 2013; 93(2):501-18 [PubMed]
Significant progress has been made in the surgical management of breast cancer. Most women diagnosed with early stage invasive breast cancer can now be managed with breast-conserving therapy to include a segmental mastectomy followed by radiation. Axillary lymph nodes are routinely assessed by sentinel lymph node biopsy. Axillary lymph node dissection is reserved for patients with documented nodal metastasis; however, here too progress has been made because a population of low-risk patients has been identified in whom a complete dissection is not required even in the setting of a positive sentinel lymph node. This article details the landmark clinical trials that have guided the surgical management of breast cancer.
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