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).
Dvinge H, Git A, Gräf S, et al. The shaping and functional consequences of the microRNA landscape in breast cancer. Nature. 2013; 497(7449):378-82 [PubMed]
MicroRNAs (miRNAs) show differential expression across breast cancer subtypes, and have both oncogenic and tumour-suppressive roles. Here we report the miRNA expression profiles of 1,302 breast tumours with matching detailed clinical annotation, long-term follow-up and genomic and messenger RNA expression data. This provides a comprehensive overview of the quantity, distribution and variation of the miRNA population and provides information on the extent to which genomic, transcriptional and post-transcriptional events contribute to miRNA expression architecture, suggesting an important role for post-transcriptional regulation. The key clinical parameters and cellular pathways related to the miRNA landscape are characterized, revealing context-dependent interactions, for example with regards to cell adhesion and Wnt signalling. Notably, only prognostic miRNA signatures derived from breast tumours devoid of somatic copy-number aberrations (CNA-devoid) are consistently prognostic across several other subtypes and can be validated in external cohorts. We then use a data-driven approach to seek the effects of miRNAs associated with differential co-expression of mRNAs, and find that miRNAs act as modulators of mRNA-mRNA interactions rather than as on-off molecular switches. We demonstrate such an important modulatory role for miRNAs in the biology of CNA-devoid breast cancers, a common subtype in which the immune response is prominent. These findings represent a new framework for studying the biology of miRNAs in human breast cancer.
Cuzick J, Sestak I, Bonanni B, et al. Selective oestrogen receptor modulators in prevention of breast cancer: an updated meta-analysis of individual participant data. Lancet. 2013; 381(9880):1827-34 [PubMed] Free Access to Full Article
BACKGROUND: Tamoxifen and raloxifene reduce the risk of breast cancer in women at elevated risk of disease, but the duration of the effect is unknown. We assessed the effectiveness of selective oestrogen receptor modulators (SERMs) on breast cancer incidence. METHODS: We did a meta-analysis with individual participant data from nine prevention trials comparing four selective oestrogen receptor modulators (SERMs; tamoxifen, raloxifene, arzoxifene, and lasofoxifene) with placebo, or in one study with tamoxifen. Our primary endpoint was incidence of all breast cancer (including ductal carcinoma in situ) during a 10 year follow-up period. Analysis was by intention to treat. RESULTS: We analysed data for 83,399 women with 306,617 women-years of follow-up. Median follow-up was 65 months (IQR 54-93). Overall, we noted a 38% reduction (hazard ratio [HR] 0·62, 95% CI 0·56-0·69) in breast cancer incidence, and 42 women would need to be treated to prevent one breast cancer event in the first 10 years of follow-up. The reduction was larger in the first 5 years of follow-up than in years 5-10 (42%, HR 0·58, 0·51-0·66; p<0·0001 vs 25%, 0·75, 0·61-0·93; p=0·007), but we noted no heterogeneity between time periods. Thromboembolic events were significantly increased with all SERMs (odds ratio 1·73, 95% CI 1·47-2·05; p<0·0001). We recorded a significant reduction of 34% in vertebral fractures (0·66, 0·59-0·73), but only a small effect for non-vertebral fractures (0·93, 0·87-0·99). INTERPRETATION: For all SERMs, incidence of invasive oestrogen (ER)-positive breast cancer was reduced both during treatment and for at least 5 years after completion. Similar to other preventive interventions, careful consideration of risks and benefits is needed to identify women who are most likely to benefit from these drugs. FUNDING: Cancer Research UK.
Nelson HD, Smith ME, Griffin JC, Fu R Use of medications to reduce risk for primary breast cancer: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2013; 158(8):604-14 [PubMed]
BACKGROUND: Medications to reduce risk for primary breast cancer are recommended for women at increased risk; however, use is low. PURPOSE: To update evidence about the effectiveness and adverse effects of medications to reduce breast cancer risk, patient use of such medications, and methods for identifying women at increased risk for breast cancer. DATA SOURCES: MEDLINE and Cochrane databases (through 5 December 2012), Scopus, Web of Science, clinical trial registries, and reference lists. STUDY SELECTION: English-language randomized trials of medication effectiveness and adverse effects, observational studies of adverse effects and patient use, and diagnostic accuracy studies of risk assessment. DATA EXTRACTION: Investigators independently extracted data on participants, study design, analysis, follow-up, and results, and a second investigator confirmed key data. Investigators independently dual-rated study quality and applicability using established criteria. DATA SYNTHESIS: Seven good- and fair-quality trials indicated that tamoxifen and raloxifene reduced incidence of invasive breast cancer by 7 to 9 cases in 1000 women over 5 years compared with placebo. New results from STAR (Study of Tamoxifen and Raloxifene) showed that tamoxifen reduced breast cancer incidence more than raloxifene by 5 cases in 1000 women. Neither reduced breast cancer-specific or all-cause mortality rates. Both reduced the incidence of fractures, but tamoxifen increased the incidence of thromboembolic events more than raloxifene by 4 cases in 1000 women. Tamoxifen increased the incidence of endometrial cancer and cataracts compared with placebo and raloxifene. Trials provided limited and heterogeneous data on medication adherence and persistence. Many women do not take tamoxifen because of associated harms. Thirteen risk-stratification models were modest predictors of breast cancer. LIMITATION: Data on mortality and adherence measures and for women who are nonwhite, are premenopausal, or have comorbid conditions were lacking. CONCLUSION: Medications reduced the incidence of invasive breast cancer and fractures and increased the incidence of thromboembolic events. Tamoxifen was more effective than raloxifene but also increased the incidence of endometrial cancer and cataracts. Use is limited by adverse effects and inaccurate methods to identify candidates. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.
Fenton JJ, Xing G, Elmore JG, et al. Short-term outcomes of screening mammography using computer-aided detection: a population-based study of medicare enrollees. Ann Intern Med. 2013; 158(8):580-7 [PubMed]
BACKGROUND: Computer-aided detection (CAD) has rapidly diffused into screening mammography practice despite limited and conflicting data on its clinical effect. OBJECTIVE: To determine associations between CAD use during screening mammography and the incidence of ductal carcinoma in situ (DCIS) and invasive breast cancer, invasive cancer stage, and diagnostic testing. DESIGN: Retrospective cohort study. SETTING: Medicare program. PARTICIPANTS: Women aged 67 to 89 years having screening mammography between 2001 and 2006 in U.S. SEER (Surveillance, Epidemiology and End Results) regions (409 459 mammograms from 163 099 women). MEASUREMENTS: Incident DCIS and invasive breast cancer within 1 year after mammography, invasive cancer stage, and diagnostic testing within 90 days after screening among women without breast cancer. RESULTS: From 2001 to 2006, CAD prevalence increased from 3.6% to 60.5%. Use of CAD was associated with greater DCIS incidence (adjusted odds ratio [OR], 1.17 [95% CI, 1.11 to 1.23]) but no difference in invasive breast cancer incidence (adjusted OR, 1.00 [CI, 0.97 to 1.03]). Among women with invasive cancer, CAD was associated with greater likelihood of stage I to II versus III to IV cancer (adjusted OR, 1.27 [CI, 1.14 to 1.41]). In women without breast cancer, CAD was associated with increased odds of diagnostic mammography (adjusted OR, 1.28 [CI, 1.27 to 1.29]), breast ultrasonography (adjusted OR, 1.07 [CI, 1.06 to 1.09]), and breast biopsy (adjusted OR, 1.10 [CI, 1.08 to 1.12]). LIMITATION: Short follow-up for cancer stage, potential unmeasured confounding, and uncertain generalizability to younger women. CONCLUSION: Use of CAD during screening mammography among Medicare enrollees is associated with increased DCIS incidence, the diagnosis of invasive breast cancer at earlier stages, and increased diagnostic testing among women without breast cancer. PRIMARY FUNDING SOURCE: Center for Healthcare Policy and Research, University of California, Davis.
Mejdahl MK, Andersen KG, Gärtner R, et al. Persistent pain and sensory disturbances after treatment for breast cancer: six year nationwide follow-up study. BMJ. 2013; 346:f1865 [PubMed]
OBJECTIVE: To examine the development of persistent pain after treatment for breast cancer and to examine risk factors associated with continuing pain. DESIGN: Repeated cross sectional study in a previously examined nationwide cohort. All eligible women who underwent surgery for primary breast cancer in Denmark in 2005 and 2006 and were examined in 2008 were surveyed again with the same questionnaire. SETTING: Surgical centres in Denmark. MAIN OUTCOME MEASURES: Prevalence, location, and severity of persistent pain after treatment for breast cancer in well defined treatment groups and changes in pain reporting and sensory disturbances from 2008 to 2012. PARTICIPANTS: In 2012, 2828 women were eligible in our database, and 108 were excluded. Exclusion criteria were death; new, recurrent, or other cancer; reconstructive breast surgery; and emigration. RESULTS: 2411 (89%) women returned the questionnaire. Prevalence of persistent pain after treatment for breast cancer ranged from 22% to 53% depending on treatment. In 2012, 903 (37%) women reported such pain, a fall from 45% in 2008. Of these, 378 (16%) reported pain of ≥ 4 on a numerical rating scale (scale 0-10), a fall from 19%. Among women reporting pain in 2008, 36% no longer reported it in 2012. In contrast, 15% of the women who did not report pain in 2008 reported it in 2012. Risk factors for having pain were axillary lymph node dissection rather than sentinel lymph node biopsy (odds ratio 2.04, 95% confidence interval 1.60 to 2.61; P<0.001) and age ≤ 49 (1.78, 1.25 to 2.54; P<0.001). No particular method of treatment or age was associated with an increase in pain from 2008 to 2012. CONCLUSIONS: Persistent pain after treatment for breast cancer remains an important problem five to seven years later. The problem is not static as it can either progress or regress with time. TRIAL REGISTRATION: Clinicaltrials.gov NCT No 01543711.
Edwards HD, Oakley F, Koyama T, Hameed O The impact of tumor size in breast needle biopsy material on final pathologic size and tumor stage: a detailed analysis of 222 consecutive cases. Am J Surg Pathol. 2013; 37(5):739-44 [PubMed]
Tumor size is a significant prognostic indicator for invasive mammary carcinoma. By current standards, this is routinely reported during pathologic evaluation of the definitive excision, but no recommendations exist for reporting tumor size in needle biopsy material. The purpose of this study is to evaluate the relationship between tumor size on breast needle biopsy specimens and that on subsequent definitive excision specimens and to evaluate the impact of the former, if any, in determining the final pathologic tumor stage. This was achieved by an evaluation of 222 consecutive cases of invasive mammary carcinoma for which both the diagnostic biopsy and definitive excision were available for review. Of 200 cases without a history of neoadjuvant therapy, there were 161 (80.5%) cases in which the tumor size on biopsy was smaller, 15 (7.5%) cases in which the sizes were equal, and 24 (12%) in which the size on biopsy was greater, including 6 (3%) cases with no residual tumor on excision. The average size change (excision size minus biopsy size) increased with increasing tumor stage, with these being significantly lower in pT1a compared with pT1b tumors (-0.14 vs. 0.17 mm; P=0.0002), pT1a/b compared with pT1c tumors (0.12 vs. 0.53 mm; P<0.0001), and pT1 compared with pT2/3 tumors (0.32 vs. 2.2 mm; P<0.001). Of the 24 cases in which tumor size on biopsy was greater than that on excision, there were 15 (7.5% of cohort) in which the tumor size on biopsy was the sole determinant of a higher final pathologic T stage. A larger tumor size on biopsy compared with that on excision was significantly associated with a lower final pathologic T stage (P<0.001) but not with patient age, histologic type, histologic grade, mitotic score, or the presence/absence of ductal carcinoma in situ. Evaluation of the remaining 22 cases also showed that there was a clear association between a history of neoadjuvant therapy and the finding of a larger size on biopsy compared with that on excision (P<0.0001). These findings indicate that tumor size on breast needle biopsy is not infrequently larger than that on excision and can also dictate the final pathologic T stage. Accordingly, it is recommended that the greatest extent of invasive carcinoma is reported in all needle biopsy specimens.
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.
French JD, Ghoussaini M, Edwards SL, et al. Functional variants at the 11q13 risk locus for breast cancer regulate cyclin D1 expression through long-range enhancers. Am J Hum Genet. 2013; 92(4):489-503 [PubMed] Article available free on PMC after 04/10/2013
Analysis of 4,405 variants in 89,050 European subjects from 41 case-control studies identified three independent association signals for estrogen-receptor-positive tumors at 11q13. The strongest signal maps to a transcriptional enhancer element in which the G allele of the best candidate causative variant rs554219 increases risk of breast cancer, reduces both binding of ELK4 transcription factor and luciferase activity in reporter assays, and may be associated with low cyclin D1 protein levels in tumors. Another candidate variant, rs78540526, lies in the same enhancer element. Risk association signal 2, rs75915166, creates a GATA3 binding site within a silencer element. Chromatin conformation studies demonstrate that these enhancer and silencer elements interact with each other and with their likely target gene, CCND1.
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.
Garcia-Closas M, Couch FJ, Lindstrom S, et al. Genome-wide association studies identify four ER negative-specific breast cancer risk loci. Nat Genet. 2013; 45(4):392-8, 398e1-2 [PubMed]
Estrogen receptor (ER)-negative tumors represent 20-30% of all breast cancers, with a higher proportion occurring in younger women and women of African ancestry. The etiology and clinical behavior of ER-negative tumors are different from those of tumors expressing ER (ER positive), including differences in genetic predisposition. To identify susceptibility loci specific to ER-negative disease, we combined in a meta-analysis 3 genome-wide association studies of 4,193 ER-negative breast cancer cases and 35,194 controls with a series of 40 follow-up studies (6,514 cases and 41,455 controls), genotyped using a custom Illumina array, iCOGS, developed by the Collaborative Oncological Gene-environment Study (COGS). SNPs at four loci, 1q32.1 (MDM4, P = 2.1 × 10(-12) and LGR6, P = 1.4 × 10(-8)), 2p24.1 (P = 4.6 × 10(-8)) and 16q12.2 (FTO, P = 4.0 × 10(-8)), were associated with ER-negative but not ER-positive breast cancer (P > 0.05). These findings provide further evidence for distinct etiological pathways associated with invasive ER-positive and ER-negative breast cancers.
Bojesen SE, Pooley KA, Johnatty SE, et al. Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer. Nat Genet. 2013; 45(4):371-84, 384e1-2 [PubMed] Article available free on PMC after 01/10/2013
TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOGs, we analyzed ∼480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer cases and controls. Leukocyte telomere measurements were also available for 53,724 participants. Most associations cluster into three independent peaks. The minor allele at the peak 1 SNP rs2736108 associates with longer telomeres (P = 5.8 × 10(-7)), lower risks for estrogen receptor (ER)-negative (P = 1.0 × 10(-8)) and BRCA1 mutation carrier (P = 1.1 × 10(-5)) breast cancers and altered promoter assay signal. The minor allele at the peak 2 SNP rs7705526 associates with longer telomeres (P = 2.3 × 10(-14)), higher risk of low-malignant-potential ovarian cancer (P = 1.3 × 10(-15)) and greater promoter activity. The minor alleles at the peak 3 SNPs rs10069690 and rs2242652 increase ER-negative (P = 1.2 × 10(-12)) and BRCA1 mutation carrier (P = 1.6 × 10(-14)) breast and invasive ovarian (P = 1.3 × 10(-11)) cancer risks but not via altered telomere length. The cancer risk alleles of rs2242652 and rs10069690, respectively, increase silencing and generate a truncated TERT splice variant.
Michailidou K, Hall P, Gonzalez-Neira A, et al. Large-scale genotyping identifies 41 new loci associated with breast cancer risk. Nat Genet. 2013; 45(4):353-61, 361e1-2 [PubMed]
Breast cancer is the most common cancer among women. Common variants at 27 loci have been identified as associated with susceptibility to breast cancer, and these account for ∼9% of the familial risk of the disease. We report here a meta-analysis of 9 genome-wide association studies, including 10,052 breast cancer cases and 12,575 controls of European ancestry, from which we selected 29,807 SNPs for further genotyping. These SNPs were genotyped in 45,290 cases and 41,880 controls of European ancestry from 41 studies in the Breast Cancer Association Consortium (BCAC). The SNPs were genotyped as part of a collaborative genotyping experiment involving four consortia (Collaborative Oncological Gene-environment Study, COGS) and used a custom Illumina iSelect genotyping array, iCOGS, comprising more than 200,000 SNPs. We identified SNPs at 41 new breast cancer susceptibility loci at genome-wide significance (P < 5 × 10(-8)). Further analyses suggest that more than 1,000 additional loci are involved in breast cancer susceptibility.
Burton H, Chowdhury S, Dent T, et al. Public health implications from COGS and potential for risk stratification and screening. Nat Genet. 2013; 45(4):349-51 [PubMed]
The PHG Foundation led a multidisciplinary program, which used results from COGS research identifying genetic variants associated with breast, ovarian and prostate cancers to model risk-stratified prevention for breast and prostate cancers. Implementing such strategies would require attention to the use and storage of genetic information, the development of risk assessment tools, new protocols for consent and programs of professional education and public engagement.
Sakoda LC, Jorgenson E, Witte JS Turning of COGS moves forward findings for hormonally mediated cancers. Nat Genet. 2013; 45(4):345-8 [PubMed]
The large-scale Collaborative Oncological Gene-environment Study (COGS) presents new findings that further characterize the genetic bases of breast, ovarian and prostate cancers. We summarize and provide insights into this collection of papers from COGS and discuss the implications of the results and future directions for such efforts.
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.
Kim WH, Chang JM, Moon WK, et al. Intraductal mass on breast ultrasound: final outcomes and predictors of malignancy. AJR Am J Roentgenol. 2013; 200(4):932-7 [PubMed]
OBJECTIVE: The purpose of this study was to retrospectively investigate the final outcomes of intraductal masses on breast ultrasound and determine the clinical and radiologic variables associated with malignancy. MATERIALS AND METHODS: A database search (2006-2008) was performed to find patients who had an intraductal mass on breast ultrasound. Histopathologic or ultrasound follow-up (> 24 months) data were available from 147 women (mean age, 49.8 years) with 163 intraductal masses. Clinical and radiologic variables (age, symptom, personal and family history, lesion size, and distance from the nipple) and pathologic results were collected. Ultrasound features of the intraductal masses were reviewed by two radiologists in consensus and classified into three morphologic types: mass incompletely filling the duct, mass completely filling the duct, and mass extending outside the duct. Involvement of a branch duct was also analyzed. Associations between variables and final outcomes were analyzed using chi-square tests and Student t tests. RESULTS: Thirteen (8%) of the 163 intraductal masses were malignant (10 ductal carcinomas in situ and three invasive ductal carcinomas). Malignancy was significantly associated with symptoms (p = 0.008) and personal history of breast cancer (p < 0.007). Malignant intraductal masses were larger than benign intraductal masses (1.4 cm vs 0.9 cm, p = 0.02). Malignant intraductal masses tended to fill the duct more completely or extend outside the duct (p < 0.001), and they more frequently involved the branch duct (p < 0.001) than did the benign intraductal masses. CONCLUSION: Our study showed that 8% of intraductal masses are malignant. Symptoms, personal history, lesion size, and ultrasound features can be possible predictors of malignancy.
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.
Alameddine RS, Otrock ZK, Awada A, Shamseddine A Crosstalk between HER2 signaling and angiogenesis in breast cancer: molecular basis, clinical applications and challenges. Curr Opin Oncol. 2013; 25(3):313-24 [PubMed]
PURPOSE OF REVIEW: Angiogenesis is an essential hallmark of cancer. Targeting angiogenesis has proven its efficacy in the modern therapeutic paradigm. HER2 positive breast cancer, in particular, is a challenging disease in which resistance to standard therapy has been attributed to parallel and downstream signaling cascades including angiogenesis. This review explores the molecular mechanisms underlying crosstalk between HER2 signaling and angiogenesis. It highlights the role of angiogenesis in the emerging resistance to anti-HER2 therapy. It surveys the current repertoire of clinical trials involving use of combination of anti-HER2 and antiangiogenic therapies. Finally, it entertains the hopes and challenges posed by this novel therapeutic approach. RECENT FINDINGS: HER2 signaling upregulates angiogenesis at different levels and by different mechanisms. A large number of clinical trials were conducted in attempt to exploit the potential benefit of the combination. Results of early phase trials were promising. However, in the late phase clinical trials, the AVEREL trial did not demonstrate a consistent benefit for bevacizumab in the HER2 positive breast cancer patient population. The BETH trial is ongoing and recruiting patients. Safety issues regarding cardiovascular toxicity of the combination have been already raised. Negative experience of dual EGFR and VEGF targeting in colon cancer cannot be overlooked. SUMMARY: Angiogenesis and HER2 signaling are closely related at the molecular level. Appraisal of efficacy of antiangiogenic therapies requires revisit of the current literature as well as following the results of ongoing trials.
Barbarino R, Janniello D, Morelli P, et al. Fatigue in patients undergoing radiation therapy: an observational study. Minerva Med. 2013; 104(2):185-91 [PubMed]
AIM: Fatigue can be defined as an unpleasant feeling of tiredness, weakness and lack of energy. It is found in about 80% of the patients receiving radiation therapy and has a significant impact on quality of life. The aim of this paper was to assess the frequency, severity and changes of fatigue before, during and after administration of a nutraceutical (mixture of whey protein with an high biological value, with an high content in native cysteine, albumin and lactoferrin in patients undergoing treatment for breast and prostate cancer. METHODS: Thirty patients (20 breast and 10 prostate ones) were enrolled in our test and they received a questionnaire about Fatigue developed by the University of Texas, MD Anderson Cancer Center, 1999. The patients who achieved a score between 4 and 6 were administered the nutraceutical (Prother) at a dose of 20 mg / day for the first 10 days of radiation treatment and then 10 mg/day for the following 20 days without considering the terms of the radiation oncology treatment. Each patient was reassessed using the same Fatigue test after 10 and 30 days from the start of the administration of nutraceutical. We enrolled 30 control patients who did not receive Prother. RESULTS: The results showed the effectiveness of Prother in all patients with moderate-to-mild fatigue. CONCLUSION: The administration of Prother has therefore been effective in terms of both improving the compliance of the radiation treatment and the quality of life.
Onitilo AA, Kar P, Engel JM, Glurich I Long-term cardiac and vascular disease outcomes following adjuvant tamoxifen therapy: current understanding of impact on physiology and overall survival. Minerva Med. 2013; 104(2):141-53 [PubMed]
The relative impact of tamoxifen therapy in women with breast cancer on overall survival, especially as it pertains to cardiac and cardiovascular outcomes, remains under debate in the literature. This review focuses specifically on outcomes of studies that examined large clinical trials with longest duration in patient follow-up relative to these parameters in which compliance with therapy could be documented. Over time, evidence supports potential cardioprotective effects and capacity of adjuvant therapy to improve lipid profiles in women treated with tamoxifen. While some benefit to cardiac health is supported, outcomes related to cardiovascular events remain variable across studies and challenging to interpret. In summary, overall survival in women treated with tamoxifen over time has increasingly shown a trend towards positive outcomes in the context of evaluation of post-treatment cardiac and vascular health. Potential mechanisms underlying the cardioprotective effects of tamoxifen are briefly discussed.
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.
Leifler KS, Svensson S, Abrahamsson A, et al. Inflammation induced by MMP-9 enhances tumor regression of experimental breast cancer. J Immunol. 2013; 190(8):4420-30 [PubMed] Article available free on PMC after 01/10/2013
Matrix metalloproteinases (MMPs) have been suggested as therapeutic targets in cancer treatment, but broad-spectrum MMP inhibitors have failed in clinical trials. Recent data suggest that several MMPs including MMP-9 exert both pro- and antitumorigenic properties. This is also the case of the natural inhibitors of MMPs, tissue inhibitor of metalloproteinases (TIMPs). The inhibitor of MMP-9 is TIMP-1, and high levels of this enzyme have been associated with decreased survival in breast cancer. Inflammation is one hallmark of cancer progression, and MMPs/TIMPs may be involved in the local immune regulation. We investigated the role of MMP-9/TIMP-1 in regulating innate antitumor immunity in breast cancer. Breast cancers were established in nude mice and treated with intratumoral injections of adenoviruses carrying the human TIMP-1 or MMP-9 gene (AdMMP-9). In vivo microdialysis for sampling of cancer cell-derived (human) and stroma-derived (murine) proteins, immunostainings, as well as cell cultures were performed. We report a dose-dependent decrease of tumor growth and angiogenesis after AdMMP-9 treatment. In addition to increased generation of endostatin, AdMMP-9 promoted an antitumor immune response by inducing massive neutrophil infiltration. Neutrophil depletion prior to gene transfer abolished the therapeutic effects of AdMMP-9. Additionally, AdMMP-9 activated tumor-infiltrating macrophages into a tumor-inhibiting phenotype both in vivo and in vitro. AdMMP-9 also inhibited tumor growth in immune-competent mice bearing breast cancers. Adenoviruses carrying the human TIMP-1 gene had no effect on tumor growth or the immune response. Our novel data identify MMP-9 as a potent player in modulating the innate immune response into antitumor activities.
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.