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.

In the UK about 50,000 women and 400 men are diagnosed with breast cancer each year. (Source: Cancer Research UK)

This page shows only UK resources. For a more extensive list of resources from around the world see CancerIndex: Breast Cancer

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Information for Patients and the Public
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Latest Research Publications

Information Patients and the Public (8 links)


Information for Health Professionals / Researchers (4 links)

Latest Research Publications

Showing publications with corresponding authors from the UK (Source: PubMed).

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.).
Clinical Trial Service Unit, University of Oxford, Oxford
Research funded by:


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.).
Department of Oncology, University of Cambridge and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Cambridge
Research funded by:


Kalin A, Merideth MA, Regier DS, et al.
Management of reproductive health in Cowden syndrome complicated by endometrial polyps and breast cancer.
Obstet Gynecol. 2013; 121(2 Pt 2 Suppl 1):461-4 [PubMed]
BACKGROUND: Cowden syndrome is an autosomal-dominant condition associated with mutations in the tumor suppressor gene PTEN. Gynecologic malignancies are common with a 5-10% risk of endometrial cancer and 25-50% risk of breast cancer.
CASE: A 37-year-old woman with a history of breast cancer, other neoplasms, and multiple skin lesions was diagnosed with Cowden syndrome after a germline PTEN mutation was identified. The endometrium had high glucose uptake on positron emission tomography scan and was irregularly thickened on ultrasonography; biopsy revealed endometrial polyps and simple hyperplasia. Fifteen months later, hysteroscopy again confirmed numerous benign endometrial polyps.
CONCLUSION: Recurrent, multiple endometrial polyps portend a high risk of endometrial cancer in women with Cowden syndrome. Monitoring for malignancy and consideration of hysterectomy after childbearing is completed is warranted.
University College London Hospitals, London


Lee B, Lim AK, Krell J, et al.
The efficacy of axillary ultrasound in the detection of nodal metastasis in breast cancer.
AJR Am J Roentgenol. 2013; 200(3):W314-20 [PubMed]
OBJECTIVE: Recent reports indicate a lack of survival benefit for axillary lymph node dissection (ALND) versus sentinel lymph node biopsy in early breast cancer. To study this issue further, we assessed the accuracy and effectiveness of ultrasound examination in detecting axillary nodal involvement in breast cancer patients with the aim of refining our current clinical pathways.
MATERIALS AND METHODS: Ultrasound data were collected from breast cancer cases over 3 years. Images were reviewed by experienced radiologists and the following characteristics were assessed: size, morphology, hyperechoic hilum, and cortical thickness of the ipsilateral axillary nodes. The findings were correlated with histologic outcomes after ALND.
RESULTS: Two hundred twenty-four cases were included in the analysis, 113 (50.4%) of which had evidence of metastatic nodal involvement at final histology. Of these 113 cases, ultrasound findings for 59 (52.2%) were positive. The overall positive predictive value of ultrasound for detecting metastatic nodal involvement measured 0.81. The negative predictive value was 0.60. The sensitivity was 53.7%; specificity, 85.1%; and accuracy, 67.9%. The ultrasound morphologic lymph node features with the greatest correlation with malignancy were the absence of a hyperechoic hilum (p = 0.003) and increased cortical thickness (p = 0.03). Patients with a metastatic nodal burden density of at least 20% were more likely to have abnormal findings on axillary ultrasound examination (p = 0.009).
CONCLUSION: Axillary ultrasound has a low negative predictive value and negative ultrasound results do not exclude axillary node metastases with sufficient sensitivity to justify its routine clinical use. Clinical pathways need to consider an evidence-based approach, focusing on the criteria by which we select breast cancer patients for ALND.
Department of Medical Oncology, Imperial College Healthcare NHS Trust, London


Kanatas A, Velikova G, Roe B, et al.
Patient-reported outcomes in breast oncology: a review of validated outcome instruments.
Tumori. 2012; 98(6):678-88 [PubMed]
AIMS AND BACKGROUND: Patient-reported outcomes (PROs) include areas of health-related quality of life but also broader concepts such as patient satisfaction with care. The aim of this review is to give an account of all instruments with potential use in patients with a history of treatment for breast cancer (including surgery, chemotherapy and/or radiotherapy) with evidence of validation in the breast cancer population.
METHODS: All instruments included in this review were identified as PRO measures measuring breast-related quality of life and/or satisfaction that had undergone development and validation with breast oncology patients. We specifically looked for PRO measures examining patient satisfaction and/or quality of life after breast cancer treatment. Following an evaluation of 323 papers, we identified 15 instruments that were able to satisfy our inclusion criteria.
RESULTS: These instruments are the EORTC QOL-C30 and QLQ-BR23 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Breast Cancer Module), the FACT-B (Functional Assessment of Cancer Therapy-Breast Cancer), the SLDS-BC (Satisfaction with Life Domains Scale for Breast Cancer), the BIBCQ (Body Image after Breast Cancer Questionnaire), the HIBS (Hopwood Body Image Scale), the PBIS (Polivy Body Image Scale), the MBROS (Michigan Breast Reconstruction Outcomes Study) Satisfaction and Body Image Questionnaires, the BREAST-Q, the BCTOS (Breast Cancer Treatment Outcome Scale), the BCQ, the FACT-ES (Functional Assessment of Cancer Therapy-Endocrine System), the MAS (Mastectomy Attitude Scale), and the Breast Cancer Prevention Trial Symptom Checklist (BCPT).
CONCLUSIONS: Suggestions for future directions include (1) to use and utilize validated instruments tailored to clinical practice; (2) to develop a comprehensive measurement of surgical outcome requiring the combination of objective and subjective measures; (3) to aim for a compromise between these two competing considerations in the form of a scale incorporating both generalizability in cancer-related QOL and specificity in breast cancer issues.
Leeds Teaching Hospitals and St James Institute of Oncology, Leeds General Infirmary, Leeds


Sproviero D, Julien S, Burford B, et al.
Cyclooxygenase-2 enzyme induces the expression of the α-2,3-sialyltransferase-3 (ST3Gal-I) in breast cancer.
J Biol Chem. 2012; 287(53):44490-7 [PubMed] Article available free on PMC after 28/12/2013
Aberrant glycosylation is a common feature of malignant change. Changes in mucin-type O-linked glycosylation in breast cancer can result in the expression of truncated core 1-based sialylated glycans rather than the core 2-based glycans observed in normal mammary epithelium cells. This has been shown, in part, to be due to changes in the expression of glycosyltransferases, including the up-regulation of some sialyltransferases. Using the breast cancer cell line T47D, we have shown that PGE2, one of the final products of the cyclooxygenase-2 (COX-2) pathway, can induce the mRNA expression of the sialyltransferase α-2,3-sialyltransferase-3 (ST3Gal-I), resulting in increased sialyltransferase activity, demonstrated by a reduction in PNA lectin staining. Induction of COX-2 in the MDA-MB-231 breast cancer cell line also results in the increased expression of ST3Gal-I, leading to increased sialylation of the substrate of ST3Gal-I, core 1 Galβ1,3GalNAc. This effect on sialylation could be reversed by the selective COX-2 inhibitor celecoxib. The use of siRNA to knock down COX-2 and overexpression of COX-2 in MDA-MD-231 cells confirmed the involvement of COX-2 in the up-regulation of ST3Gal-I. Moreover, analysis of the expression of ST3Gal-I and COX-2 by 74 primary breast cancers showed a significant correlation between the two enzymes. COX-2 expression has been associated with a number of tumors, including breast cancer, where its expression is associated with poor prognoses. Thus, these results suggest the intriguing possibility that some of the malignant characteristics associated with COX-2 expression may be via the influence that COX-2 exerts on the glycosylation of tumor cells.
Breast Cancer Biology, King's College London, Guy's Hospital, London SE1 9RT


Sultana R, Abdel-Fatah T, Abbotts R, et al.
Targeting XRCC1 deficiency in breast cancer for personalized therapy.
Cancer Res. 2013; 73(5):1621-34 [PubMed]
XRCC1 is a key component of DNA base excision repair, single strand break repair, and backup nonhomologous end-joining pathway. XRCC1 (X-ray repair cross-complementing gene 1) deficiency promotes genomic instability, increases cancer risk, and may have clinical application in breast cancer. We investigated XRCC1 expression in early breast cancers (n = 1,297) and validated in an independent cohort of estrogen receptor (ER)-α-negative breast cancers (n = 281). Preclinically, we evaluated XRCC1-deficient and -proficient Chinese hamster and human cancer cells for synthetic lethality application using double-strand break (DSB) repair inhibitors [KU55933 (ataxia telangectasia-mutated; ATM inhibitor) and NU7441 (DNA-PKcs inhibitor)]. In breast cancer, loss of XRCC1 (16%) was associated with high grade (P < 0.0001), loss of hormone receptors (P < 0.0001), triple-negative (P < 0.0001), and basal-like phenotypes (P = 0.001). Loss of XRCC1 was associated with a two-fold increase in risk of death (P < 0.0001) and independently with poor outcome (P < 0.0001). Preclinically, KU55933 [2-(4-Morpholinyl)-6-(1-thianthrenyl)-4H-pyran-4-one] and NU7441 [8-(4-Dibenzothienyl)-2-(4-morpholinyl)-4H-1-benzopyran-4-one] were synthetically lethal in XRCC1-deficient compared with proficient cells as evidenced by hypersensitivity to DSB repair inhibitors, accumulation of DNA DSBs, G2-M cell-cycle arrest, and induction of apoptosis. This is the first study to show that XRCC1 deficiency in breast cancer results in an aggressive phenotype and that XRCC1 deficiency could also be exploited for a novel synthetic lethality application using DSB repair inhibitors. Cancer Res; 73(5); 1621-34. ©2012 AACR.
Laboratory of Molecular Oncology, Academic Unit of Oncology, School of Molecular Medical Sciences, University of Nottingham, Nottingham


O'Driscoll M
Diseases associated with defective responses to DNA damage.
Cold Spring Harb Perspect Biol. 2012; 4(12) [PubMed]
Within the last decade, multiple novel congenital human disorders have been described with genetic defects in known and/or novel components of several well-known DNA repair and damage response pathways. Examples include disorders of impaired nucleotide excision repair, DNA double-strand and single-strand break repair, as well as compromised DNA damage-induced signal transduction including phosphorylation and ubiquitination. These conditions further reinforce the importance of multiple genome stability pathways for health and development in humans. Furthermore, these conditions inform our knowledge of the biology of the mechanics of genome stability and in some cases provide potential routes to help exploit these pathways therapeutically. Here, I will review a selection of these exciting findings from the perspective of the disorders themselves, describing how they were identified, how genotype informs phenotype, and how these defects contribute to our growing understanding of genome stability pathways.
Human DNA Damage Response Disorders Group Genome Damage and Stability Centre, University of Sussex, Brighton, East Sussex BN1 9RQ


Sun PH, Ye L, Mason MD, Jiang WG
Protein tyrosine phosphatase µ (PTP µ or PTPRM), a negative regulator of proliferation and invasion of breast cancer cells, is associated with disease prognosis.
PLoS One. 2012; 7(11):e50183 [PubMed] Article available free on PMC after 28/12/2013
BACKGROUND: PTPRM has been shown to exhibit homophilic binding and confer cell-cell adhesion in cells including epithelial and cancer cells. The present study investigated the expression of PTPRM in breast cancer and the biological impact of PTPRM on breast cancer cells.
DESIGN: Expression of PTPRM protein and gene transcript was examined in a cohort of breast cancer patients. Knockdown of PTPRM in breast cancer cells was performed using a specific anti-PTPRM transgene. The impact of PTPRM knockdown on breast cancer was evaluated using in vitro cell models.
RESULTS: A significant decrease of PTPRM transcripts was seen in poorly differentiated and moderately differentiated tumours compared with well differentiated tumours. Patients with lower expression of PTPRM had shorter survival compared with those which had a higher level of PTPRM expression. Knockdown of PTPRM increased proliferation, adhesion, invasion and migration of breast cancer cells. Furthermore, knockdown of PTPRM in MDA-MB-231 cells resulted in increased cell migration and invasion via regulation of the tyrosine phosphorylation of ERK and JNK.
CONCLUSIONS: Decreased expression of PTPRM in breast cancer is correlated with poor prognosis and inversely correlated with disease free survival. PTPRM coordinated cell migration and invasion through the regulation of tyrosine phosphorylation of ERK and JNK.
Metastasis & Angiogenesis Research Group, Institute of Cancer and Genetics, Cardiff University School of Medicine, Cardiff


Wakefield A, Soukupova J, Montagne A, et al.
Bcl3 selectively promotes metastasis of ERBB2-driven mammary tumors.
Cancer Res. 2013; 73(2):745-55 [PubMed]
Bcl3 is a putative proto-oncogene deregulated in hematopoietic and solid tumors. Studies in cell lines suggest that its oncogenic effects are mediated through the induction of proliferation and inhibition of cell death, yet its role in endogenous solid tumors has not been established. Here, we address the oncogenic effect of Bcl3 in vivo and describe how this Stat3-responsive oncogene promotes metastasis of ErbB2-positive mammary tumors without affecting primary tumor growth or normal mammary function. Deletion of the Bcl3 gene in ErbB2-positive (MMTV-Neu) mice resulted in a 75% reduction in metastatic tumor burden in the lungs with a 3.6-fold decrease in cell turnover index in these secondary lesions with no significant effect on primary mammary tumor growth, cyclin D1 levels, or caspase-3 activity. Direct inhibition of Bcl3 by siRNA in a transplantation model of an Erbb2-positive mammary tumor cell line confirmed the effect of Bcl3 in malignancy, suggesting that the effect of Bcl3 was intrinsic to the tumor cells. Bcl3 knockdown resulted in a 61% decrease in tumor cell motility and a concomitant increase in the cell migration inhibitors Nme1, Nme2, and Nme3, the GDP dissociation inhibitor Arhgdib, and the metalloprotease inhibitors Timp1 and Timp2. Independent knockdown of Nme1, Nme2, and Arhgdib partially rescued the Bcl3 motility phenotype. These results indicate for the first time a cell-autonomous disease-modifying role for Bcl3 in vivo, affecting metastatic disease progression rather than primary tumor growth.
University of Cardiff School of Biosciences, Museum Avenue, Cardiff
Research funded by:


Molassiotis A, Bardy J, Finnegan-John J, et al.
Acupuncture for cancer-related fatigue in patients with breast cancer: a pragmatic randomized controlled trial.
J Clin Oncol. 2012; 30(36):4470-6 [PubMed]
PURPOSE: We aimed to assess the effectiveness of acupuncture for cancer-related fatigue (CRF) in patients with breast cancer.
PATIENTS AND METHODS: We conducted a pragmatic, randomized controlled trial comparing acupuncture with enhanced usual care. Three hundred two outpatients with breast cancer participated. We randomly assigned 75 patients to usual care and 227 patients to acupuncture plus usual care (random assignment of 1:3 respectively) with minimization controlling for baseline general fatigue and maintenance treatment. Treatment was delivered by acupuncturists once a week for 6 weeks through needling three pairs of acupoints. The usual care group received a booklet with information about fatigue and its management. Primary outcome was general fatigue at 6 weeks, measured with the Multidimensional Fatigue Inventory (MFI). Other measurements included the Hospital Anxiety and Depression Scale, Functional Assessment of Cancer Therapy-General quality-of-life scale, and expectation of acupuncture effect. Analyses were by intention to treat.
RESULTS: Two hundred forty-six of 302 patients randomly assigned provided complete data at 6 weeks. The difference in the mean General Fatigue score, between those who received the intervention and those who did not, was -3.11 (95% CI, -3.97 to -2.25; P < .001). The intervention also improved all other fatigue aspects measured by MFI, including Physical Fatigue and Mental Fatigue (acupuncture effect, -2.36 and -1.94, respectively; both at P < .001), anxiety and depression (acupuncture effect, -1.83 and -2.13, respectively; both at P < .001), and quality of life (Physical Well-Being effect, 3.30; Functional Well-Being effect, 3.57; both at P < .001; Emotional Well-Being effect, 1.93; P = .001; and Social Functioning Well-Being effect, 1.05; P < .05).
CONCLUSION: Acupuncture is an effective intervention for managing the symptom of CRF and improving patients' quality of life.
School of Nursing, Midwifery, and Social Work, University of Manchester


Jack RH, Davies EA, Renshaw C, et al.
Differences in breast cancer hormone receptor status in ethnic groups: a London population.
Eur J Cancer. 2013; 49(3):696-702 [PubMed]
BACKGROUND: Triple negative breast cancer (TNBC) is associated with different ethnic groups in the United States (US), however this has not previously been examined in a population-based study within the United Kingdom (UK).
METHODS: Electronic pathology reports from the North East London Cancer Network (NELCN) on women diagnosed with breast cancer between 2005 and 2007 were collated. The statuses of oestrogen receptor, progesterone receptor and HER-2 were extracted. Women were classified as having TNBC if all three receptor statuses were negative, and as not having TNBC if at least one receptor was positive or borderline. Logistic regression was used to quantify the association between TNBC and ethnicity, adjusting for age, year of diagnosis and socioeconomic deprivation. Overall survival in different ethnic groups was examined using Cox regression, adjusting as appropriate for age, stage of disease, triple negative status, year of diagnosis, socioeconomic deprivation and recorded treatment.
RESULTS: There were 2417 women resident in NELCN diagnosed with breast cancer between 2005 and 2007, and TNBC status was determined for 1228 (51%) women. Overall, of women who had their TNBC status determined, 128 (10%) were diagnosed with TNBC. Compared with White women, Black (odds ratio [OR]=2.81, p<0.001) and South Asian (OR=1.80, p=0.044) women with breast cancer were more likely to have TNBC. Black women had a worse age-adjusted survival than White women (hazard ratio [HR]=2.05, p<0.001). This was attenuated by further adjustment for stage of disease (1.52, p=0.032) and triple negative status (1.31, p=0.175).
CONCLUSION: Better methods of early detection may need to be developed in addition to more effective systemic treatment in order to improve outcomes for women with TNBC.
King's College London, Thames Cancer Registry, 1st Floor Capital House, 42 Weston Street, London SE1 3QD
Research funded by:


Jones DT, Lechertier T, Mitter R, et al.
Gene expression analysis in human breast cancer associated blood vessels.
PLoS One. 2012; 7(10):e44294 [PubMed] Article available free on PMC after 28/12/2013
Angiogenesis is essential for solid tumour growth, whilst the molecular profiles of tumour blood vessels have been reported to be different between cancer types. Although presently available anti-angiogenic strategies are providing some promise for the treatment of some cancers it is perhaps not surprisingly that, none of the anti-angiogenic agents available work on all tumours. Thus, the discovery of novel anti-angiogenic targets, relevant to individual cancer types, is required. Using Affymetrix microarray analysis of laser-captured, CD31-positive blood vessels we have identified 63 genes that are upregulated significantly (5-72 fold) in angiogenic blood vessels associated with human invasive ductal carcinoma (IDC) of the breast as compared with blood vessels in normal human breast. We tested the angiogenic capacity of a subset of these genes. Genes were selected based on either their known cellular functions, their enriched expression in endothelial cells and/or their sensitivity to anti-VEGF treatment; all features implicating their involvement in angiogenesis. For example, RRM2, a ribonucleotide reductase involved in DNA synthesis, was upregulated 32-fold in IDC-associated blood vessels; ATF1, a nuclear activating transcription factor involved in cellular growth and survival was upregulated 23-fold in IDC-associated blood vessels and HEX-B, a hexosaminidase involved in the breakdown of GM2 gangliosides, was upregulated 8-fold in IDC-associated blood vessels. Furthermore, in silico analysis confirmed that AFT1 and HEX-B also were enriched in endothelial cells when compared with non-endothelial cells. None of these genes have been reported previously to be involved in neovascularisation. However, our data establish that siRNA depletion of Rrm2, Atf1 or Hex-B had significant anti-angiogenic effects in VEGF-stimulated ex vivo mouse aortic ring assays. Overall, our results provide proof-of-principle that our approach can identify a cohort of potentially novel anti-angiogenic targets that are likley to be, but not exclusivley, relevant to breast cancer.
Centre for Tumour Biology, Barts Cancer Institute, Queen Mary University of London, London


Al-Rawi H, Al-Jafari M, Mathew H
Metastatic breast cancer mimicking cholecystitis. A rare clinical presentation.
Saudi Med J. 2012; 33(10):1128-30 [PubMed]
We report a case of a 61-year-old lady who presented with central chest and epigastric pain. A clinical diagnosis of cholecystitis was established, and a cholecystectomy was carried out. Microscopic examination of the gallbladder showed chronic cholecystitis and metastatic carcinoma of probable breast lobular carcinoma origin. The report was followed by further clinical and mammographic examination, which showed a focal area of thickening in the left breast. Core biopsy of this lesion confirmed the diagnosis of lobular carcinoma of the breast. Her tumor was treated with surgery followed by chemo/hormone therapy. The patient died 5 years after the cholecystectomy from disseminated breast malignancy.
Department of Histopathology, Warrington and Halton Hospitals, NHS Trust, Warrington, Cheshire


Jafferbhoy S, McWilliams B
Clinical significance and management of sentinel node micrometastasis in invasive breast cancer.
Clin Breast Cancer. 2012; 12(5):308-12 [PubMed]
Axillary node status is one of the most important prognostic indicators in patients with invasive breast cancer. Sentinel node biopsy allows an exhaustive examination of the lymph node and has led to an increased detection rate of small tumor deposits. Patients with micrometastatic deposits can have nonsentinel node involvement, including macrometastatic deposits. Sentinel node micrometastases are associated with an adverse impact on disease recurrence and survival. Axillary dissection does not offer an advantage in reducing the incidence of disease recurrence or survival. However, the long-term outcomes can be improved with the use of adjuvant chemotherapy, and it would be reasonable to consider systemic treatment in these patients.
Department of Surgery, University Hospital of North Staffordshire, Stoke on Trent


Busch S, Rydén L, Stål O, et al.
Low ERK phosphorylation in cancer-associated fibroblasts is associated with tamoxifen resistance in pre-menopausal breast cancer.
PLoS One. 2012; 7(9):e45669 [PubMed] Article available free on PMC after 28/12/2013
PURPOSE: The aim of this study was to evaluate ERK phosphorylation as a stromal biomarker for breast cancer prognosis and tamoxifen treatment prediction within a randomized tamoxifen trial.
PATIENTS AND METHODS: Tissue microarrays of two breast cancer cohorts including in total 743 invasive breast cancer samples were analyzed for ERK phosphorylation (pERK) and smooth muscle actin-alpha expression (SMAα) in cancer-associated fibroblasts (CAFs) and links to clinico-pathological data and treatment-predictive values were delineated.
RESULTS: By analyzing a unique randomized tamoxifen trial including breast cancer patients receiving no adjuvant treatment we show for the first time that patients low in ERK phosphorylation in CAFs did not respond to tamoxifen treatment despite having estrogen-receptor alpha (ERα-positive tumors compared to patients with high pERK levels in CAFs (P = 0.015, multivariate Cox regression interaction analysis). In both clinical materials we further show a significant association between pERK and SMAα, a characteristic marker for activated fibroblasts. SMAα expression however was not linked to treatment-predictive information but instead had prognostic qualities.
CONCLUSION: The data suggests that the presence of a subpopulation of CAFs, defined by minimal activated ERK signaling, is linked to an impaired tamoxifen response. Thus, this report illustrates the importance of the stroma for monitoring treatment effects in pre-menopausal breast cancer.
Breakthrough Breast Cancer Research Unit, School of Cancer, Enabling Sciences and Technology, University of Manchester, Manchester Academic Health Science Centre, Paterson Institute for Cancer Research, The Christie NHS Foundation Trust, Manchester


Lombardo Y, Filipović A, Molyneux G, et al.
Nicastrin regulates breast cancer stem cell properties and tumor growth in vitro and in vivo.
Proc Natl Acad Sci U S A. 2012; 109(41):16558-63 [PubMed] Article available free on PMC after 28/12/2013
Nicastrin (NCT) is a crucial component of the γ-secretase (GS) enzyme, which prompted investigations into its biological role in cancer. We have previously shown that nicastrin is overexpressed in breast cancer (BC), conferring worse overall survival in invasive, ERα negative patients. Here, we used 2D and 3D Matrigel, anchorage-independent growth conditions and a breast cancer xenograft mouse model to assess the impact of nicastrin on breast cancer stem cell (BCSC) propagation and invasion in vitro and tumor growth in vivo. Stable knockdown of nicastrin in HCC1806 breast cancer cells reduced cell invasion by 51.4 ± 1.7%, accompanied by a morphological change to a rounded cell phenotype and down-regulation of vimentin, Snail, Twist, MMP2, and MMP9. We observed a reduction of the pool of CD44(+)/CD24(-) and ALDH1 high breast cancer stem cells by threefold and twofold, respectively, and a reduction by 2.6-fold of the mammospheres formation. Nicastrin overexpression in nontransformed MCF10A cells caused an induction of epithelial to mesenchymal regulators, as well as a fivefold increased ALDH1 activity, a threefold enrichment for CD44(+)/CD24(-) stem cells, and a 3.2-fold enhanced mammosphere-forming capacity. Using the γ-sescretase inhibiton, Notch1/4 siRNA, and Akt inhibition, we show that nicastrin regulates breast cancer stem cells partly through Notch1 and the Akt pathway. Exploiting serial dilution transplantation of the HCC1806 cells expressing nicastrin and HCC1806 stably depleted of nicastrin, in vivo, we demonstrate that nicastrin inhibition may be relevant for the reduced tumorigenicity of breast cancer cells. These data could serve as a benchmark for development of nicastrin-targeted therapies in breast cancer.
Division of Surgery and Cancer, Department of Oncology, Imperial College London, Hammersmith Hospital Campus, London
Research funded by:


Huthwaite P, Simonetti F, Duric N
Combining time of flight and diffraction tomography for high resolution breast imaging: initial in vivo results (L).
J Acoust Soc Am. 2012; 132(3):1249-52 [PubMed]
Ultrasound tomography (UST) is being developed to address the limitations of mammography in breast cancer detection. Central to the success of UST is the possibility of obtaining high-resolution images of tissue mechanical properties across the whole breast. A recent paper [Huthwaite and Simonetti, J. Acoust. Soc. Am. 130, 1721-1734 (2011)] made use of a numerical phantom to demonstrate that sufficient image resolution can be obtained by simply treating refraction and diffraction effects in consecutive steps through the combination of ray-based time of flight and diffraction tomography. This letter presents the first experimental demonstration of the method using phantom and invivo data from a cancer patient.
Department of Mechanical Engineering, Imperial College, London, SW7 2AZ


Osborn DP, Horsfall L, Hassiotis A, et al.
Access to cancer screening in people with learning disabilities in the UK: cohort study in the health improvement network, a primary care research database.
PLoS One. 2012; 7(8):e43841 [PubMed] Article available free on PMC after 28/12/2013
OBJECTIVES: To assess whether people with learning disability in the UK have poorer access to cancer screening.
DESIGN: Four cohort studies comparing people with and without learning disability, within the recommended age ranges for cancer screening in the UK. We used Poisson regression to determine relative incidence rates of cancer screening.
SETTING: The Health Improvement Network, a UK primary care database with over 450 General practices.
PARTICIPANTS: Individuals with a recorded diagnosis of learning disability including general diagnostic terms, specific syndromes, chromosomal abnormalities and autism in their General Practitioner computerised notes. For each type of cancer screening, a comparison cohort of up to six people without learning disability was selected for each person with a learning disability, using stratified sampling on age within GP practice.
MAIN OUTCOME MEASURES: Incidence rate ratios for receiving 1) a cervical smear test, 2) a mammogram, 3) a faecal occult blood test and 4) a prostate specific antigen test.
RESULTS: Relative rates of screening for all four cancers were significantly lower for people with learning disability. The adjusted incidence rate ratios (95% confidence intervals) were Cervical smears: Number eligible with learning disability = 6,254; IRR = 0.54 (0.52-0.56). Mammograms: Number eligible with learning disability = 2,956; IRR = 0.76 (0.72-0.81); Prostate Specific Antigen: Number eligible = 3,520; IRR = 0.87 (0.80-0.96) and Faecal Occult Blood Number eligible = 6,566; 0.86 (0.78-0.94). Differences in screening rates were less pronounced in more socially deprived areas. Disparities in cervical screening rates narrowed over time, but were 45% lower in 2008/9, those for breast cancer screening appeared to widen and were 35% lower in 2009.
CONCLUSION: Despite recent incentives, people with learning disability in the UK are significantly less likely to receive screening tests for cancer that those without learning disability. Other methods for reducing inequalities in access to cancer screening should be considered.
Mental Health Sciences Unit, University College London, London
Research funded by:


Brown JE, Cook RJ, Lipton A, Coleman RE
Serum lactate dehydrogenase is prognostic for survival in patients with bone metastases from breast cancer: a retrospective analysis in bisphosphonate-treated patients.
Clin Cancer Res. 2012; 18(22):6348-55 [PubMed]
PURPOSE: Survival is highly variable in women with bone metastases from breast cancer and prognostic factors are needed. We analyzed data from a phase III trial comparing zoledronic acid (ZOL) with pamidronate in patients with breast cancer and bone metastases to identify variables prognostic for overall survival.
EXPERIMENTAL DESIGN: Patients who received ZOL (n = 435) with bone marker assessments and complete baseline data were included. Relative risks (RR) of death over 24 months were assessed using a stratified Cox regression analysis. A reduced model was generated using stepwise backward elimination until only significant (P < 0.05) variables remained.
RESULTS: Only 5 of 19 variables analyzed remained significantly prognostic for survival in the reduced multivariate model. These included age more than 50 years (RR 1.78-2.53, P ≤ 0.01 for each decade >50 versus ≤ 50); Functional Assessment of Cancer Therapy-General (FACT-G) score less than 65 units (P < 0.05 vs. ≥ 75 units); impaired (PS ≥ 1) versus fully active (PS = 0) Eastern Cooperative Oncology Group (ECOG) performance status (RR 1.74, P < 0.01); prior versus no prior chemotherapy (RR 1.97; P < 0.01), and lactate dehydrogenase (LDH) levels. Lactate dehydrogenase ≥ upper limit of normal (ULN) but < 2 × ULN correlated with a two-fold increased risk of death, and LDH > 2 × ULN correlated with a six-fold increased risk of death versus LDH < ULN (P < 0.0001 for both). Baseline bone marker levels were not significantly correlated with survival after adjustment for other significant covariates.
CONCLUSIONS: This retrospective analysis shows that LDH levels correlate strongly with survival in patients with bone metastases from breast cancer and confirms the relevance of previously described prognostic factors.
Cancer Research UK Experimental Cancer Medicine Centres at Leeds and Sheffield, Cancer Research Centre, Academic Unit of Clinical Oncology, Weston Park Hospital, Sheffield
Research funded by:


Vichapat V, Garmo H, Holmqvist M, et al.
Tumor stage affects risk and prognosis of contralateral breast cancer: results from a large Swedish-population-based study.
J Clin Oncol. 2012; 30(28):3478-85 [PubMed]
PURPOSE: The number of breast cancer survivors at risk of developing contralateral breast cancer (CBC) is increasing. However, ambiguity remains regarding risk factors and prognosis for women with CBC.
PATIENTS AND METHODS: In a cohort of 42,670 women with breast cancer in the Uppsala/Örebro and Stockholm regions in Sweden in 1992 to 2008, we assessed risk factors for and prognosis of metachronous CBC by using survival analysis. Breast cancer-specific survival for women with CBC was evaluated and compared with results for women with unilateral breast cancer (UBC) by using time-dependent Cox-regression modeling.
RESULTS: An increased risk for CBC was observed among women who had primary breast cancer with ≥ 10 involved lymph nodes compared with node-negative women (adjusted hazard ratio [HR], 1.8; 95% CI, 1.2 to 2.7). The prognosis was poorer in women with CBC than with UBC. The hazard of dying from breast cancer was especially high for women with a short interval time to CBC (adjusted HR, 2.3; 95% CI, 1.8 to 2.8 for CBC diagnosed ≤ 5 years v UBC) and gradually decreased with longer follow-up time but remained higher than the hazard originating from the primary tumor for ≥ 10 years.
CONCLUSION: Women with advanced-stage primary breast cancer had an increased risk of developing CBC. CBC is associated with an increased risk of dying from breast cancer throughout a long period of follow-up after the primary tumor. Our findings suggest that the event of CBC marks a new clinical situation in terms of investigations for metastases, treatment considerations, and follow-up strategy.
Division of Cancer Studies, King’s College London, London


Baum M
Modern concepts of the natural history of breast cancer: a guide to the design and publication of trials of the treatment of breast cancer.
Eur J Cancer. 2013; 49(1):60-4 [PubMed]
The design, analysis and interpretation of randomised controlled trials for the management of early breast cancer are to some extent predicated on the prevailing conceptual model of the disease based on its biology and cellular kinetics. Real progress became possible from the early 1970s following the challenge to a mechanistic view of the disease going back to the time of Virchow and Halsted. Improvements in local and systemic therapy that have reduced the surgical morbidity and improved on survival followed the biological revolution lead by Dr. Bernard Fisher. The rate of progress has now slowed down and a number of outlying clinical observations suggest that the time is ripe for a new revolutionary model of breast cancer with greater explanatory power. The application of non-linear mathematics (chaos theory) that is emerging in the new science of the disease suggests a new set of guidelines for the design, analysis and interpretation of clinical trials of therapy that might lead to the next stepwise progression in the management of early breast cancer.
Royal Free and UCL Medical School, Centre for Clinical Science and Technology, Clerkenwell Building, Archway Campus, Highgate Hill, London N19 5LW


Warren H, Dudbridge F, Fletcher O, et al.
9q31.2-rs865686 as a susceptibility locus for estrogen receptor-positive breast cancer: evidence from the Breast Cancer Association Consortium.
Cancer Epidemiol Biomarkers Prev. 2012; 21(10):1783-91 [PubMed]
BACKGROUND: Our recent genome-wide association study identified a novel breast cancer susceptibility locus at 9q31.2 (rs865686).
METHODS: To further investigate the rs865686-breast cancer association, we conducted a replication study within the Breast Cancer Association Consortium, which comprises 37 case-control studies (48,394 cases, 50,836 controls).
RESULTS: This replication study provides additional strong evidence of an inverse association between rs865686 and breast cancer risk [study-adjusted per G-allele OR, 0.90; 95% confidence interval (CI), 0.88; 0.91, P = 2.01 × 10(-29)] among women of European ancestry. There were ethnic differences in the estimated minor (G)-allele frequency among controls [0.09, 0.30, and 0.38 among, respectively, Asians, Eastern Europeans, and other Europeans; P for heterogeneity (P(het)) = 1.3 × 10(-143)], but no evidence of ethnic differences in per allele OR (P(het) = 0.43). rs865686 was associated with estrogen receptor-positive (ER(+)) disease (per G-allele OR, 0.89; 95% CI, 0.86-0.91; P = 3.13 × 10(-22)) but less strongly, if at all, with ER-negative (ER(-)) disease (OR, 0.98; 95% CI, 0.94-1.02; P = 0.26; P(het) = 1.16 × 10(-6)), with no evidence of independent heterogeneity by progesterone receptor or HER2 status. The strength of the breast cancer association decreased with increasing age at diagnosis, with case-only analysis showing a trend in the number of copies of the G allele with increasing age at diagnosis (P for linear trend = 0.0095), but only among women with ER(+) tumors.
CONCLUSIONS: This study is the first to show that rs865686 is a susceptibility marker for ER(+) breast cancer.
IMPACT: The findings further support the view that genetic susceptibility varies according to tumor subtype.
Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, Keppel Street, London, WC1E 7HT
Research funded by:


Pean E, Klaar S, Berglund EG, et al.
The European medicines agency review of eribulin for the treatment of patients with locally advanced or metastatic breast cancer: summary of the scientific assessment of the committee for medicinal products for human use.
Clin Cancer Res. 2012; 18(17):4491-7 [PubMed]
The European Commission issued on March 17, 2011, a marketing authorization valid throughout the European Union (EU) for eribulin (Halaven; Eisai Limited). The decision was based on the favorable opinion of the Committee for Medicinal Products for Human Use recommending a marketing authorization for the treatment of patients with locally advanced or metastatic breast cancer who have progressed after at least 2 chemotherapeutic regimens for advanced disease. Eribulin mesylate is a structurally simplified synthetic analogue of halichondrin B, which is a natural product isolated from the marine sponge Halichondria okadai (ATC code L01XX41). Eribulin is a nontaxane, microtubule dynamics inhibitor belonging to the halichondrin class of antineoplastic agents. Eribulin inhibits the growth phase of microtubules without affecting the shortening phase and sequesters tubulin into nonproductive aggregates leading to G(2)-M cell-cycle block, disruption of mitotic spindles, and, ultimately, apoptotic cell death after prolonged mitotic blockage. The recommended dose of eribulin is 1.23 mg/m(2) (equivalent to 1.4 mg/m(2) eribulin mesylate) to be administered intravenously over 2 to 5 min on days 1 and 8 of a 3-week cycle. In the pivotal trial, eribulin was associated with increased overall survival in patients with locally advanced or metastatic breast cancer who received at least 2 prior chemotherapy lines for advanced disease (median overall survival was 13.2 months in the eribulin arm vs. 10.6 months in the control arm; HR = 0.805; 95% confidence interval, 0.677-0.958; P = 0.014). The most common side effects are asthenia or fatigue and neutropenia. The objective of this article is to summarize the scientific review of the application leading to approval in the EU. The detailed scientific assessment report and product information, including the summary report and product information, including product characteristics, are available on the European Medicines Agency website.
European Medicines Agency, London


Sever AR, Mills P, Weeks J, et al.
Preoperative needle biopsy of sentinel lymph nodes using intradermal microbubbles and contrast-enhanced ultrasound in patients with breast cancer.
AJR Am J Roentgenol. 2012; 199(2):465-70 [PubMed]
OBJECTIVE: The purpose of this study was to assess whether sentinel lymph nodes (SLNs) that undergo targeted needle biopsy after identification by contrast-enhanced ultrasound (CEUS) using intradermally injected microbubbles results in more node-positive breast cancer patients being diagnosed preoperatively. Furthermore, we sought to determine whether the addition of CEUS to gray-scale sonography of the axilla reduces the number of patients having axillary lymph node (ALN) dissection as a second procedure.
SUBJECTS AND METHODS: Intradermal microbubble injection was performed in 136 breast cancer patients who had no abnormal ALNs on routine gray-scale axillary sonography. When an enhancing ALN was visualized, percutaneous sonography-guided fine-needle aspiration cytology or core needle biopsy was performed. Depending on the biopsy results, patients underwent SLN biopsy or ALN dissection. If the putative SLN biopsy was positive or a biopsy tract was seen in the excised SLN, the procedure was defined as successful.
RESULTS: SLNs were identified and biopsied in 126 of the 136 cases (93%). Seventeen patients had positive sonography-guided biopsy results (13%) and were treated with immediate ALN dissection. In seven patients, the biopsied node was the only positive node. The remaining 109 patients underwent SLN biopsy. In nine cases (8%), a positive lymph node was identified. Four of these false-negative cases had only micrometastases.
CONCLUSION: SLNs can be identified and biopsied using CEUS to increase the accuracy of preoperative axillary staging. If the needle biopsy result is negative, conventional SLN biopsy is indicated.
Department of Radiology, Maidstone Hospital, Hermitage Ln, Maidstone ME16 9QQ


Stone A, Valdés-Mora F, Gee JM, et al.
Tamoxifen-induced epigenetic silencing of oestrogen-regulated genes in anti-hormone resistant breast cancer.
PLoS One. 2012; 7(7):e40466 [PubMed] Article available free on PMC after 28/12/2013
In the present study, we have taken the novel approach of using an in vitro model representative of tamoxifen-withdrawal subsequent to clinical relapse to achieve a greater understanding of the mechanisms that serve to maintain the resistant-cell phenotype, independent of any agonistic impact of tamoxifen, to identify potential novel therapeutic approaches for this disease state. Following tamoxifen withdrawal, tamoxifen-resistant MCF-7 cells conserved both drug resistance and an increased basal rate of proliferation in an oestrogen deprived environment, despite reduced epidermal growth-factor receptor expression and reduced sensitivity to gefitinib challenge. Although tamoxifen-withdrawn cells retained ER expression, a sub-set of ER-responsive genes, including pS2 and progesterone receptor (PgR), were down-regulated by promoter DNA methylation, as confirmed by clonal bisulphite sequencing experiments. Following promoter demethylation with 5-Azacytidine (5-Aza), the co-addition of oestradiol (E2) restored gene expression in these cells. In addition, 5-Aza/E2 co-treatment induced a significant anti-proliferative effect in the tamoxifen-withdrawn cells, in-contrast to either agent used alone. Microarray analysis was undertaken to identify genes specifically up regulated by this co-treatment. Several anti-proliferative gene candidates were identified and their promoters were confirmed as more heavily methylated in the tamoxifen resistant vs sensitive cells. One such gene candidate, growth differentiation factor 15 (GDF15), was carried forward for functional analysis. The addition of 5-Aza/E2 was sufficient to de-methylate and activate GDF15 expression in the tamoxifen resistant cell-lines, whilst in parallel, treatment with recombinant GDF15 protein decreased cell survival. These data provide evidence to support a novel concept that long-term tamoxifen exposure induces epigenetic silencing of a cohort of oestrogen-responsive genes whose function is associated with negative proliferation control. Furthermore, reactivation of such genes using epigenetic drugs could provide a potential therapeutic avenue for the management of tamoxifen-resistant breast cancer.
Welsh School of Pharmacy, Redwood Building, Cardiff University, Cardiff, Wales


Glaab E, Bacardit J, Garibaldi JM, Krasnogor N
Using rule-based machine learning for candidate disease gene prioritization and sample classification of cancer gene expression data.
PLoS One. 2012; 7(7):e39932 [PubMed] Article available free on PMC after 28/12/2013
Microarray data analysis has been shown to provide an effective tool for studying cancer and genetic diseases. Although classical machine learning techniques have successfully been applied to find informative genes and to predict class labels for new samples, common restrictions of microarray analysis such as small sample sizes, a large attribute space and high noise levels still limit its scientific and clinical applications. Increasing the interpretability of prediction models while retaining a high accuracy would help to exploit the information content in microarray data more effectively. For this purpose, we evaluate our rule-based evolutionary machine learning systems, BioHEL and GAssist, on three public microarray cancer datasets, obtaining simple rule-based models for sample classification. A comparison with other benchmark microarray sample classifiers based on three diverse feature selection algorithms suggests that these evolutionary learning techniques can compete with state-of-the-art methods like support vector machines. The obtained models reach accuracies above 90% in two-level external cross-validation, with the added value of facilitating interpretation by using only combinations of simple if-then-else rules. As a further benefit, a literature mining analysis reveals that prioritizations of informative genes extracted from BioHEL's classification rule sets can outperform gene rankings obtained from a conventional ensemble feature selection in terms of the pointwise mutual information between relevant disease terms and the standardized names of top-ranked genes.
Interdisciplinary Computing and Complex Systems Research Group, University of Nottingham, Nottingham


Folkerd EJ, Dixon JM, Renshaw L, et al.
Suppression of plasma estrogen levels by letrozole and anastrozole is related to body mass index in patients with breast cancer.
J Clin Oncol. 2012; 30(24):2977-80 [PubMed]
PURPOSE: To investigate whether suppression of plasma estradiol and estrone sulfate levels by the aromatase inhibitors (AIs) anastrozole and letrozole is related to body mass index (BMI) in postmenopausal women with early estrogen receptor (ER) -positive breast cancer. Recent studies have reported that the AI anastrozole has lower effectiveness than tamoxifen in women with high BMI. This effect with high BMI might hypothetically be a result of reduced inhibition of aromatase and suppression of plasma estrogen levels and might be overcome by the use of an increased dose of anastrozole or, alternatively, the use of a more potent AI such as letrozole.
PATIENTS AND METHODS: Plasma estradiol and estrone sulfate levels from a highly sensitive radioimmunoassay were available for 44 postmenopausal patients who received anastrozole (1 mg per day) for 3 months followed by letrozole (2.5 mg per day) for 3 months or the opposite sequence. Correlations between the estrogen suppression by each AI and BMI were assessed.
RESULTS: Baseline values of estradiol and estrone sulfate were significantly correlated with BMI (r = 0.57; P < .001, and r = 0.38; P = .006, respectively). Levels of estrogen in patients receiving treatment were greater at higher levels of BMI with both AIs, but although this was significant with letrozole (r = 0.35; P = .013, and r = 0.30; P = .035 for estradiol and estrone sulfate, respectively), it was not with anastrozole. Suppression of both estrogen types was greater with letrozole across the full range of BMIs in this study.
CONCLUSION: The suppressed levels of plasma estradiol and estrone sulfate in postmenopausal women with early ER-positive breast cancer treated with the AIs anastrozole and letrozole are related to BMI.
Royal Marsden Hospital, London


English R, Metcalfe C, Day J, et al.
A prospective analysis of implementation of multi-disciplinary team decisions in breast cancer.
Breast J. 2012; 18(5):459-63 [PubMed]
Multi-disciplinary teams (MDTs) management of patients with cancer is mandatory in the United Kingdom, and auditing team decision-making by examining rates of decision implementation and reasons for nonimplementation may inform this practice. Consecutive breast cancer MDT decisions, subsequent decision implementation, and reasons for nonimplementation were prospectively recorded. Factors associated with nonimplementation of the MDT decision were analyzed with logistic regression. Of 289 consecutive MDT decisions involving 210 women, 20 (6.9%, 95% CIs 4.3%-10.5%) were not implemented. Most changed MDT decisions did so because of patient preferences (n = 13, 65%), with the discovery of new clinical information (n = 3) and individual doctor's views (n = 4) also leading to decision nonimplementation. MDT decisions were significantly less likely to be adhered to in patients with confirmed malignant disease compared to those with benign or 'unknown' disease categories (p < 0.001) and MDT decisions in older patients were significantly more likely not to be implemented than in younger patients (p = 0.002). Auditing nonimplementation of MDT recommendations and examining reasons for changed decisions is a useful process to monitor team performance and to identify factors that need more attention during the MDT meeting to ensure that the process makes optimal patient centered decisions.
University Hospitals Bristol NHS Foundation Trust, Bristol


Walker GA, Kaidar-Person O, Kuten A, Morgan DA
Radiotherapy as sole adjuvant treatment for older patients with low-risk breast cancer.
Breast. 2012; 21(5):629-34 [PubMed]
Partly as a result of screening, increasing numbers of older patients are presenting with 'low risk' breast cancer: tumours from which the likelihood of breast cancer death is minute; even so, these patients have a measurable risk of local recurrence if conservative surgery is not followed by some form of adjuvant treatment. However, it must be acknowledged that any such treatment has no detectable impact upon survival, and the value of all such interventions must be considered in the context of the individual patient's non-cancer life expectancy and the complex psychosocial factors that affect older patients. If no impact on survival can be expected and the risk of local recurrence is high enough to warrant some post-operative treatment, the most powerful agent in this respect is radiotherapy. Whilst adjuvant endocrine treatment is becoming increasingly accepted as monotherapy in low risk patients, we propose that radiotherapy should not be forgotten as an alternative which, with its attendant benefits of shorter duration and high compliance, may be more suitable for a number of patients.
Department of Clinical Oncology, Nottingham City Hospital, Hucknall Road, Nottingham NG5 1PB


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