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

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Latest Research Publications
Breast Cancer Organisations
Specialist Journals
Breast Cancer in Pregnancy
Breast Cancer Screening
Familial Breast Cancer
Male Breast Cancer
Paget's Disease of the Breast

Information Patients and the Public (42 links)

Information for Health Professionals / Researchers (15 links)

See also: Molecular Biology of Breast Cancer

Breast Cancer Organisations (11 links)

See also: National Cancer Organisations

Specialist Journals (12 links)

See also: Oncology Journals

Latest Research Publications

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

Adriaenssens N, Buyl R, Lievens P, et al.
Comparative study between mobile infrared optoelectronic volumetry with a Perometer and two commonly used methods for the evaluation of arm volume in patients with breast cancer related lymphedema of the arm.
Lymphology. 2013; 46(3):132-43 [PubMed] Related Publications
There is no consensus on the definition of Breast Cancer Related Lymphedema of the arm (BCRL) because there are no agreed standards in measurement methods and diagnostic criteria. The main objective of this study is to compare mobile infrared optoelectronic volumetry with a Perometer with two commonly used methods for the evaluation of arm volume in patients with different degrees of BCRL. Bilateral arm volumes of eighty participants, with and without clinical BCRL, were calculated with a mobile Perometer, by water displacement, and with circumferential measurements, integrated in the frustrum, single frustrum, and disc model method. The ICC of the Perometer was between 0.997 and 0.999. The frustrum and disc model method produced the largest volume measurements and water displacement the smallest, while Perometer measures were in between. On average, volume of the dominant arm was found to be 2.2% higher than the non-dominant arm in the healthy control group, cautioning for intra- patient differences between both arms when comparing ipsilateral to contralateral arm for the diagnosis of BCRL with a threshold value. Future research would likely benefit from the use of the Perometer compared to the other arm volume evaluation tools for BCRL, and further, the single frustrum method should not be used for volume estimations of edematous arms.

Ma CX, Ellis MJ
The Cancer Genome Atlas: clinical applications for breast cancer.
Oncology (Williston Park). 2013; 27(12):1263-9, 1274-9 [PubMed] Related Publications
Advances in next-generation sequencing technologies in recent years have allowed in-depth study of somatic mutations in over 1,000 breast cancer samples.The Cancer Genome Atlas (TCGA) is the largest single genome-characterization effort to date. It is remarkable for the integration of DNA sequencing with genome-wide profiling of the epigenome, microRNAome, transcriptome, and proteome for more than 500 diverse primary untreated breast cancers. This article aims to provide an overview ofTCGA findings, with a particular focus on their potential biological relevance and therapeutic implications.

Related: Signal Transduction

Jankowitz RC, Davidson NE
Adjuvant endocrine therapy for breast cancer: how long is long enough?
Oncology (Williston Park). 2013; 27(12):1210-6, 1224 [PubMed] Related Publications
Although women with early-stage hormone receptor-positive breast cancer have low recurrence rates initially, they have a constant and unrelenting risk of relapse that extends up to 15 years despite the use of adjuvant therapy. Increasing evidence supports the use of extended endocrine therapy with either tamoxifen or an aromatase inhibitor (AI) after 5 years of initial adjuvant tamoxifen to reduce breast cancer recurrence and mortality. However, the optimal total duration of AI therapy, as well as the ideal timing of sequencing from tamoxifen to an AI, is still unclear. Potential strategies differ depending on a woman's menopausal status at the time of her initial diagnosis. Individual patient clinical factors and preferences can help with decision making until further data emerge on prolonged AI use and on potential biomarkers that can be used to tailor adjuvant endocrine treatment.

Tomas I, Kotoromanović Z, Belaj N, et al.
Computer-aided evaluation of radiologist's reproducibility and subjectivity in mammographic density assessment.
Coll Antropol. 2013; 37(4):1121-6 [PubMed] Related Publications
Mammographic density is an independent risk of breast cancer. This study has evaluated the radiologists' reproducibility and subjectivity in breast density estimation and in order to decrease the radiologists' subjective errors the computer software was developed. The very good reproducibility existed in the strong correlation with the first and the second mammogram assessment after three month period for each radiologist (correlation coefficient 0.73-1, p < 0.001). The strong correlation was present in the case of all 5 radiologists when compared among themselves and compared with software aided MDEST-Mammographic Density Estimation (correlation coefficient 0.651-0.777, p < 0.001). Detected differences in glandular tissue percentage determination occurred in the case of two experienced radiologists, out of 5 (one radiologist with more than 5 year experience and one with more than 10 year experience, p < 0.01), but in the case of breast type determination (American College of Radiology-ACR I-IV), the detected difference occurred in one radiologist with the least experience (less than 5 years, p < 0.001). It can be concluded that the estimation of glandular tissue percentage in breast density is rather subjective method, especially if it is expressed with absolute percentage, but the determination of type of breast (ARCI-IV) depends on the radiologist's experience. This study showed that software aided determination of glandular tissue percentage and breast type can be of a great benefit in the case of less experienced radiologists.

Zheng J, Wang H, Yao J, Zou X
More antitumor efficacy of the PI3K inhibitor GDC-0941 in breast cancer with PIK3CA mutation or HER2 amplification status in vitro.
Pharmazie. 2014; 69(1):38-42 [PubMed] Related Publications
PIK3CA is probably the most commonly mutated kinase in several malignant tumors. Activation of class I phosphatidylinositol 3' kinase (PI3K) regulates tumor proliferation, survival, etc. This study sought to identify whether the pan-inhibitor has more antitumor efficacy in breast cancer cells with PIK3CA Mutation or HER2 amplification than basal-like cancer cells. The proliferation of breast cancer cells was measured by MTT assay in the presence of GDC-0941. Afterwards, we determined the visible changes in signaling in the PI3K/AKT/mTOR pathway. Finally, we examined GDC-0941 effects on cell cycle, apoptosis and motility. GDC-0941 exhibited excellent inhibition on three cell lines with PIK3CA mutation or HER2 amplification. In addition, GDC-0941 resulted in decreased Akt activity. GDC-0941 downregulated the key components of the cell cycle machinery, such as cyclin D1, upregulated the apoptotic markers and inhibited cell motility on three cell lines with PIK3CA Mutation or HER2 amplification. Antitumor activity of GDC-0941 treatment amongst tumor cell lines with PIK3CA mutation and HER2 amplification may have clinical utility in patients with these oncogenic alterations.

Related: Apoptosis Signal Transduction

Pei R, Wang P, Zhou Y, et al.
Association of BRCA1 K1183R polymorphism with survival in BRCA1/2-negative chinese familial breast cancer.
Clin Lab. 2014; 60(1):47-53 [PubMed] Related Publications
BACKGROUND: To determine whether a common BRCA1 K1183R polymorphism (3667A > G) affects survival in BRCA1/2-negative Chinese familial breast cancer. We investigated the associations between the BRCA1 E1183R polymorphism and disease-free survival and clinicopathological characteristics in a cohort of 325 Chinese familial breast cancer patients without BRCA1/2 germline mutations.
METHODS: K1183R polymorphism was detected by polymerase chain reaction (PCR)-sequencing assay.
RESULTS: Among the 325 Chinese familial breast cancer patients, the frequencies of the genotypes of E1183R polymorphism were 81.5% for wild-type (AA), 14.5% for heterozygote (AG), and 4.0% for variant (GG). No significant association between the genotypes and clinicopathological characteristics was found. There was a trend association that patients with the AA genotype had a better disease-free survival than those with the AG/GG genotype in univariate analysis (p = 0.111), but patients with AA genotype had a significantly better disease-free survival than did patients with AG or GG genotype in the HER2 positive subgroup (p = 0.012).
CONCLUSIONS: The present study suggests that the AA genotype of BRCA1 K1183R polymorphism is associated with a favorable survival in HER2 positive familial breast cancer patients.

Related: BRCA1 BRCA2 Polymorphisms

Bourdeanu L, Dee V
Assessment of chemotherapy-induced nausea and vomiting in women with breast cancer: a Neuman systems model framework.
Res Theory Nurs Pract. 2013; 27(4):296-304 [PubMed] Related Publications
The importance of nursing theory and models for the development of the nursing profession is becoming increasingly evident in literature. This article demonstrates the use of the Betty Neuman Systems Model (NSM) to assess, as well as determine the predictors of chemotherapy-induced nausea and vomiting (CINV) in patients diagnosed with breast cancer receiving doxorubicin-based chemotherapy. The selection of the model for practice reflects the congruency between the level of severity of CINV and the patient-related risk factors. In addition, the NSM was used to determine the appropriate nursing interventions necessary to strengthen the flexible lines of defense and the lines of resistance in addition to maintaining system stability.

Related: Doxorubicin

Moran MS, Schnitt SJ, Giuliano AE, et al.
Society of Surgical Oncology-American Society for Radiation Oncology consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in stages I and II invasive breast cancer.
Int J Radiat Oncol Biol Phys. 2014; 88(3):553-64 [PubMed] Related Publications
PURPOSE: To convene a multidisciplinary panel of breast experts to examine the relationship between margin width and ipsilateral breast tumor recurrence (IBTR) and develop a guideline for defining adequate margins in the setting of breast conserving surgery and adjuvant radiation therapy.
METHODS AND MATERIALS: A multidisciplinary consensus panel used a meta-analysis of margin width and IBTR from a systematic review of 33 studies including 28,162 patients as the primary evidence base for consensus.
RESULTS: Positive margins (ink on invasive carcinoma or ductal carcinoma in situ) are associated with a 2-fold increase in the risk of IBTR compared with negative margins. This increased risk is not mitigated by favorable biology, endocrine therapy, or a radiation boost. More widely clear margins than no ink on tumor do not significantly decrease the rate of IBTR compared with no ink on tumor. There is no evidence that more widely clear margins reduce IBTR for young patients or for those with unfavorable biology, lobular cancers, or cancers with an extensive intraductal component.
CONCLUSIONS: The use of no ink on tumor as the standard for an adequate margin in invasive cancer in the era of multidisciplinary therapy is associated with low rates of IBTR and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease health care costs.

Related: USA

Rosenbaum L
"Misfearing"--culture, identity, and our perceptions of health risks.
N Engl J Med. 2014; 370(7):595-7 [PubMed] Related Publications
Despite knowing that heart disease kills more women each year than all cancers combined, most women fear breast cancer far more - and their health-related behavior reflects this difference. If our sense of risk is less about fact than about feeling, how do we adjust it?

Miller AB, Wall C, Baines CJ, et al.
Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial.
BMJ. 2014; 348:g366 [PubMed] Free Access to Full Article Related Publications
OBJECTIVE: To compare breast cancer incidence and mortality up to 25 years in women aged 40-59 who did or did not undergo mammography screening.
DESIGN: Follow-up of randomised screening trial by centre coordinators, the study's central office, and linkage to cancer registries and vital statistics databases.
SETTING: 15 screening centres in six Canadian provinces,1980-85 (Nova Scotia, Quebec, Ontario, Manitoba, Alberta, and British Columbia).
PARTICIPANTS: 89,835 women, aged 40-59, randomly assigned to mammography (five annual mammography screens) or control (no mammography).
INTERVENTIONS: Women aged 40-49 in the mammography arm and all women aged 50-59 in both arms received annual physical breast examinations. Women aged 40-49 in the control arm received a single examination followed by usual care in the community.
MAIN OUTCOME MEASURE: Deaths from breast cancer.
RESULTS: During the five year screening period, 666 invasive breast cancers were diagnosed in the mammography arm (n=44,925 participants) and 524 in the controls (n=44,910), and of these, 180 women in the mammography arm and 171 women in the control arm died of breast cancer during the 25 year follow-up period. The overall hazard ratio for death from breast cancer diagnosed during the screening period associated with mammography was 1.05 (95% confidence interval 0.85 to 1.30). The findings for women aged 40-49 and 50-59 were almost identical. During the entire study period, 3250 women in the mammography arm and 3133 in the control arm had a diagnosis of breast cancer, and 500 and 505, respectively, died of breast cancer. Thus the cumulative mortality from breast cancer was similar between women in the mammography arm and in the control arm (hazard ratio 0.99, 95% confidence interval 0.88 to 1.12). After 15 years of follow-up a residual excess of 106 cancers was observed in the mammography arm, attributable to over-diagnosis.
CONCLUSION: Annual mammography in women aged 40-59 does not reduce mortality from breast cancer beyond that of physical examination or usual care when adjuvant therapy for breast cancer is freely available. Overall, 22% (106/484) of screen detected invasive breast cancers were over-diagnosed, representing one over-diagnosed breast cancer for every 424 women who received mammography screening in the trial.

Related: Canada Cancer Screening and Early Detection

Metcalfe K, Gershman S, Ghadirian P, et al.
Contralateral mastectomy and survival after breast cancer in carriers of BRCA1 and BRCA2 mutations: retrospective analysis.
BMJ. 2014; 348:g226 [PubMed] Free Access to Full Article Related Publications
OBJECTIVE: To compare the survival rates of women with BRCA associated breast cancer who did and did not undergo mastectomy of the contralateral breast.
DESIGN: Retrospective analysis.
SETTING: 12 cancer genetics clinics.
PARTICIPANTS: 390 women with a family history of stage I or II breast cancer who were carriers of BRCA1 and BRCA2 mutations and initially treated with unilateral or bilateral mastectomy. 181 patients had mastectomy of the contralateral breast. Patients were followed for up to 20 years from diagnosis.
MAIN OUTCOME MEASURE: Death from breast cancer.
RESULTS: 79 women died of breast cancer in the follow-up period (18 in the bilateral mastectomy group and 61 in the unilateral mastectomy group). The median follow-up time was 14.3 years (range 0.1-20.0 years). At 20 years the survival rate for women who had mastectomy of the contralateral breast was 88% (95% confidence interval 83% to 93%) and for those who did not was 66% (59% to 73%). In a multivariable analysis, controlling for age at diagnosis, year of diagnosis, treatment, and other prognostic features, contralateral mastectomy was associated with a 48% reduction in death from breast cancer (hazard ratio 0.52, 95% confidence interval 0.29 to 0.93; P=0.03). In a propensity score adjusted analysis of 79 matched pairs, the association was not significant (0.60, 0.34 to 1.06; P=0.08). Based on these results, we predict that of 100 women treated with contralateral mastectomy, 87 will be alive at 20 years compared with 66 of 100 women treated with unilateral mastectomy.
CONCLUSIONS: This study suggests that women who are positive for BRCA mutations and who are treated for stage I or II breast cancer with bilateral mastectomy are less likely to die from breast cancer than women who are treated with unilateral mastectomy. Given the small number of events in this cohort, further research is required to confirm these findings.

Related: Canada USA

Kirkegaard T, Hansen SK, Larsen SL, et al.
T47D breast cancer cells switch from ER/HER to HER/c-Src signaling upon acquiring resistance to the antiestrogen fulvestrant.
Cancer Lett. 2014; 344(1):90-100 [PubMed] Related Publications
In this study, T47D cell lines resistant to the antiestrogen fulvestrant were established and analyzed to explore, whether a switch to HER signaling, as seen in fulvestrant resistant MCF-7 cell lines, is a general resistance mechanism. We find that parental T47D cells depend on ER and HER signaling for growth. Fulvestrant resistant T47D cells have lost ER expression and, although HER2 was over expressed, growth was only partially driven by HER receptors. Instead c-Src was important for resistant growth. Thus, the T47D and MCF-7 model system unravel different resistance mechanisms which may be important for fulvestrant resistant breast cancer patients.

Related: Signal Transduction

Al-Ali KH, El-Beshbishy HA, El-Badry AA, Alkhalaf M
Cytotoxic activity of methanolic extract of Mentha longifolia and Ocimum basilicum against human breast cancer.
Pak J Biol Sci. 2013; 16(23):1744-50 [PubMed] Related Publications
Labiatae family is represented in Saudi Arabia. The aim of the present study was to go insight to investigate the anticancer activity and antioxidative potentials of methanolic extracts of Mentha longifolia L. (ML) and Ocimum basilicum L. (OB) that grown in Madina province, western region, Saudi Arabia. OB exhibited the greater phenolic contents as mg gallic acid equivalent/g weight (mg GAE/g) for a value of 105 +/- 5.5 mg GAE/g. On the other hand, ML produced 29 +/- 3.12 mg GAE/g. The standard antioxidant vitamin E used in this experiment elicited a value of total phenolic contents equal 22 +/- 2.2 mg GAE/g. The percentage scavenging activity of against diphenylpicrylhydrazyl (DPPH) was 850 and 160% for OB and ML extracts, respectively. Vitamin E elicited% scavenging activity of against DPPH equal to 198%. Brine shrimp cytotoxic assay clearly indicated the cytotoxic effects of either ML or OB extract. The brine shrimp survival is inversely proportional to the concentration of either ML or OB extract used with LD50 191.23 and 235.50 ppm, respectively. Toxic effects on brine shrimps indicated the anticancer potential of ML or OB extract. The ML or OB extract was unable to produce pbluescript (pBS) plasmid DNA damage, while the plasmid DNA treated with EcoRI produced a single band as a result of DNA damage. Also, both ML and OB extract exhibited marked cytotoxic activity against MCF-7 cells at various concentrations (20, 40, 80, 160 and 320 microg mL(-1)). The 160 and 320 microg mL(-1) showed more cytotoxic effect against MCF-7 cells. Based on results achieved, we can concluded that, OB and ML extracts have the potency to act as powerful antioxidants and protect against DNA damage and have cytotoxic activity against MCF-7 cell line.

Hao Z, Wang Q, Wang X, et al.
Learning a structured graphical model with boosted top-down features for ultrasound image segmentation.
Med Image Comput Comput Assist Interv. 2013; 16(Pt 1):227-34 [PubMed] Related Publications
A key problem for many medical image segmentation tasks is the combination of different-level knowledge. We propose a novel scheme of embedding detected regions into a superpixel based graphical model, by which we achieve a full leverage on various image cues for ultrasound lesion segmentation. Region features are mapped into a higher-dimensional space via a boosted model to become well controlled. Parameters for regions, superpixels and a new affinity term are learned simultaneously within the framework of structured learning. Experiments on a breast ultrasound image data set confirm the effectiveness of the proposed approach as well as our two novel modules.

Zhou W, Slingerland JM
Links between oestrogen receptor activation and proteolysis: relevance to hormone-regulated cancer therapy.
Nat Rev Cancer. 2014; 14(1):26-38 [PubMed] Related Publications
Oestrogen receptor-α (ERα) is a master transcription factor that regulates cell proliferation and homeostasis in many tissues. Despite beneficial ERα functions, sustained oestrogenic exposure increases the risk and/or the progression of various cancers, including those of the breast, endometrium and ovary. Oestrogen–ERα interaction can trigger post-translational ERα modifications through crosstalk with signalling pathways to promote transcriptional activation and ubiquitin-mediated ERα proteolysis, with co-activators that have dual roles as ubiquitin ligases. These processes are reviewed herein. The elucidation of mechanisms whereby oestrogen drives both ERα transactivation and receptor proteolysis might have important therapeutic implications not only for breast cancer but also potentially for other hormone-regulated cancers.

Related: Signal Transduction

Omura Y, Jones MK, Nihrane A, et al.
More than 97% of human papilloma virus type 16 (HPV-16) was found with chrysotile asbestos & relatively smooth round tumor outline, and less than 3% was found with HPV-18 and tremolite asbestos & irregular sawtooth-like zigzag outline in breast cancer tissues in over 500 mammograms of female patients: their implications in diagnosis, treatment, and prevention of breast cancer.
Acupunct Electrother Res. 2013; 38(3-4):211-30 [PubMed] Related Publications
In the past, Human Papillomavirus Type 16 (HPV-16) was considered to be the main cause of cancer in the oropharynx and genital organs. Cervical cancer of the uterus is the most well-known cancer associated with HPV-16. Among the oncogenic HPVs, types 16 and 18 are most responsible for the majority of the HPV-caused cancers. Recently, using EMF Resonance Phenomenon between 2 identical substances, we non-invasively measured HPV-16 and HPV-18 among 25 physicians and 25 dentists and found that all 50 have HPV-16 in oral cavities and oropharynx but not HPV-18. However most dentists have a stronger infection than physicians. Among them were 2 female dentists with breast cancer containing HPV-16 and strong infections of HPV-16 in the oral cavities and oropharynx. When the author checked their breast cancer positive areas as well as the mammograms of cancer positive areas, Chrysotile Asbestos co-existed with an infection of HPV-16. We then examined over 500 published mammograms of women with malignant breast cancer published by other institutes, and we found HPV-16 in more than 97% and HPV-18 in less than 3% of the breast cancer mammograms examined. Less than 0.4% of cases were found as a variety of combination of HPV-16 & HPV-18. We also discovered that breast cancer with HPV-16 always co-exists with increased Chrysotile Asbestos deposits, and the outline of the breast cancer positive area is a relatively smooth and round or oval shape, and breast cancer with HPV-18 always co-exists with increased Tremolite Asbestos, where the tumor outline is an irregular saw-tooth like zigzag pattern. Based on these findings, better methods of diagnosis, treatment and prevention with a vaccine can be developed.

Bianchini G, Gianni L
The immune system and response to HER2-targeted treatment in breast cancer.
Lancet Oncol. 2014; 15(2):e58-68 [PubMed] Related Publications
The monoclonal antibody trastuzumab targets the growth factor receptor HER2 and has profoundly improved the course of disease and survival of women with HER2-overexpressing breast cancer. Because trastuzumab targets aberrant expression of HER2 in tumours addicted to HER2 activation, its clinical activity is credited largely to inhibition of intracellular signalling. A growing body of preclinical and clinical evidence shows that the immune system contributes substantially to the therapeutic effects of trastuzumab and other monoclonal antibodies in vivo. Furthermore, findings indicate that immune-related markers can provide useful predictive information and that increased clinical activity might follow activation of the immune system. Development of immunomodulatory drugs with remarkable activity in many solid tumours defines a scenario in which the combination of immune modulation with trastuzumab, or other HER2-directed drugs, will result in augmented response and clinical outcome.

Related: Signal Transduction Trastuzumab (Herceptin)

Bae MS, Moon WK, Chang JM, et al.
Breast cancer detected with screening US: reasons for nondetection at mammography.
Radiology. 2014; 270(2):369-77 [PubMed] Related Publications
PURPOSE: To retrospectively review the mammograms of women with breast cancers detected at screening ultrasonography (US) to determine the reasons for nondetection at mammography.
MATERIALS AND METHODS: This study received institutional review board approval, and informed consent was waived. Between 2003 and 2011, a retrospective database review revealed 335 US-depicted cancers in 329 women (median age, 47 years; age range, 29-69 years) with Breast Imaging Reporting and Data System breast density type 2-4. Five blinded radiologists independently reviewed the mammograms to determine whether the findings on negative mammograms should be recalled. Three unblinded radiologists re-reviewed the mammograms to determine the reasons for nondetection by using the reference location of the cancer on mammograms obtained after US-guided wire localization or breast magnetic resonance imaging. The number of cancers recalled by the blinded radiologists were compared with the reasons for nondetection determined by the unblinded radiologists.
RESULTS: Of the 335 US-depicted cancers, 63 (19%) were recalled by three or more of the five blinded radiologists, and 272 (81%) showed no mammographic findings that required immediate action. In the unblinded repeat review, 263 (78%) cancers were obscured by overlapping dense breast tissue, and nine (3%) were not included at mammography owing to difficult anatomic location or poor positioning. Sixty-three (19%) cancers were considered interpretive errors. Of these, 52 (82%) were seen as subtle findings (46 asymmetries, six calcifications) and 11 (18%) were evident (six focal asymmetries, one distortion, four calcifications).
CONCLUSION: Most breast cancers (81%) detected at screening US were not seen at mammography, even in retrospect. In addition, 19% had subtle or evident findings missed at mammography.

Humphrey KL, Lee JM, Donelan K, et al.
Percutaneous breast biopsy: effect on short-term quality of life.
Radiology. 2014; 270(2):362-8 [PubMed] Related Publications
PURPOSE: To examine the effects of percutaneous breast biopsy on short-term quality of life.
MATERIALS AND METHODS: The institutional review board approved this HIPAA-compliant prospective study. From December 1, 2007, through February 28, 2010, women undergoing percutaneous breast biopsy in an academic medical center were recruited to participate in a mixed-mode survey 2-4 days after biopsy. Patients described their biopsy experience by using the Testing Morbidities Index (TMI), a validated instrument for assessing short-term quality of life related to diagnostic testing. The scale ranged from 0 (worst possible experience) to 100 (no adverse effects). Seven attributes were assessed: pain or discomfort before and during testing, fear or anxiety before and during testing, embarrassment during testing, and physical and mental function after testing. Demographic and clinical information were also collected. Univariate and multivariate linear regression analyses were performed to identify significant predictors of TMI score.
RESULTS: In 188 women (mean age, 51.4 years; range, 22-80 years), the mean TMI score (±standard deviation) was 82 ± 12. Univariate analysis revealed age and race as significant predictors of the TMI score (P < .05). In the multivariate model, only patient age remained a significant independent predictor (P = .001). TMI scores decreased by approximately three points for every decade decrease in patient age, which suggests that younger women were more adversely affected by the biopsy experience.
CONCLUSION: Younger patient age is a significant predictor of decreased short-term quality of life related to percutaneous breast biopsy procedures. Tailored prebiopsy counseling may better prepare women for percutaneous biopsy procedures and improve their experience.

Barros AC, Andrade FE, Bevilacqua JL, et al.
Radicality effect of adding an interpectoral to a subpectoral approach for dissection of level III axillary lymph nodes in breast cancer.
Tumori. 2013 Jul-Aug; 99(4):500-4 [PubMed] Related Publications
AIMS AND BACKGROUND: The extent of axillary lymph node dissection for breast cancer treatment is tailored to each patient. When the surgeon assumes that full dissection, including level III, is needed, there are basically two ways for reaching the apical nodes while preserving the pectoralis muscles: a subpectoral approach, below the joined pectoralis muscles, and another that includes an additional interpectoral dissection between the muscles. We conducted a study to evaluate the radicality of dissection using these two approaches.
METHODS: To determine whether the harvest of level III axillary lymph nodes is equivalent with the different approaches, we prospectively studied 75 patients with breast cancer. Careful axillary lymph node dissection was done to as radical an extent as possible, first below the lateral edge of the joined pectoralis muscles (subpectoral approach) and sequentially after opening the space between the muscles (additional interpectoral approach). The number of patients with extra level III nodes retrieved by the addition of an interpectoral dissection as well as the number of complementary nodes obtained in such patients were determined.
RESULTS: We excised 1701 axillary lymph nodes in 75 patients (mean, 22.7). Using first the subpectoral approach, we resected 259 level III nodes in 68 patients (mean, 3.8); in 56 patients, we removed 132 additional level III nodes using the supplementary interpectoral approach (mean, 2.4). In 7 patients (9.3%), we found at least one metastatic node with the interpectoral approach. Two of these patients had positive level III nodes that were discovered only by addition of the interpectoral dissection.
CONCLUSIONS: The dissection of level III axillary nodes is more radical when an additional interpectoral dissection is performed after a subpectoral approach has been used. The exclusive subpectoral approach frequently leaves residual nodes at the apex of the axilla.

Tsoi B, Ziolkowski NI, Thoma A, et al.
Safety of tissue expander/implant versus autologous abdominal tissue breast reconstruction in postmastectomy breast cancer patients: a systematic review and meta-analysis.
Plast Reconstr Surg. 2014; 133(2):234-49 [PubMed] Related Publications
BACKGROUND: Breast reconstruction after mastectomy for breast cancer should be informed by evidence-based knowledge, such as complication rates. The authors compared the safety of tissue expander/implant reconstruction with that of autologous abdominal tissue reconstruction.
METHODS: A systematic literature review identified peer-reviewed studies published from January of 2000 to October of 2012 that compared tissue expander/implant against autologous abdominal tissue reconstruction in the MEDLINE, EMBASE, Cochrane Library, PubMed, and ProQuest Dissertations and Theses databases. Two reviewers independently screened all reports and selected the relevant articles using specific inclusion criteria. Data were extracted from the relevant articles using a standardized abstraction form.
RESULTS: Fourteen observational studies were identified that included more than 3000 reconstructed breasts. Significant differences were found between these two approaches. The relative risk associated with reconstructive failure favored autologous abdominal tissue (relative risk, 0.14; 95 percent CI, 0.06 to 0.32; I = 0 percent). Surgical-site infection was significantly lower in autologous abdominal tissue reconstruction compared with tissue expander/implant (relative risk, 0.37; 95 percent CI, 0.25 to 0.55; I = 0 percent), although skin or flap necrosis was higher in autologous abdominal tissue reconstruction compared with tissue expander/implant (relative risk, 2.79; 95 percent CI, 1.87 to 4.17). Studies were of low to moderate quality according to the Newcastle-Ottawa scale.
CONCLUSIONS: This study suggests that tissue expander/implant reconstruction has a higher risk of reconstructive failure and surgical-site infection compared with autologous abdominal tissue reconstruction. With the lack of long-term safety studies on different approaches to breast reconstruction, additional long-term comparative studies are needed to support evidence-based decision-making.

Mnif H, Charfi S, Abid N, Sallemi-Boudawara T
Mammary myofibroblastoma with leiomyomatous differentiation: case report and literature review.
Pathologica. 2013; 105(4):142-5 [PubMed] Related Publications
INTRODUCTION: Myofibroblastoma of the breast (MFB) is an unusual benign tumour that belongs to the family of benign spindle cell tumours of the mammary stroma. The detection of smooth muscle cells in MFB is explained by its histogenesis from CD34+ fibroblasts of mammary stroma capable of multidirectional mesenchymal differentiation, including smooth muscle.
AIMS: The purpose of this case is to highlight characteristics of this rare neoplasm. Immunohistochemical features, in MFB with predominant leiomyomatous differentiation, are provided to offer a practical approach to a correct diagnosis.
CASE REPORT: We report a right MFB in a 60-year-old male. The tumour was unusual due to its morphological features, with predominant leiomyomatous differentiation. Immunohistochemical findings, based on the negativity of h-caldesmon, helped in reaching a diagnosis.
CONCLUSION: The detection of leiomyomatous rather than myofibrolastic features in MFB may reflect only the predominant cell types of examined area, and this is not necessarily representative of the remaining tumour which may have a different basic cellular composition. Immunohistochemical expression of h-caldesmon is a reliable marker in distinguishing smooth muscle versus myofibrolastic cellular differentiation in spindle cells lesions of the breast.

Related: Male Breast Cancer

Vecchio GM, Cavaliere A, Cartaginese F, et al.
Intraparenchymal leiomyoma of the breast: report of a case with emphasis on needle core biopsy-based diagnosis.
Pathologica. 2013; 105(4):122-7 [PubMed] Related Publications
OBJECTIVE: We report the clinicopathologic features of a rare case of leiomyoma of the breast parenchyma in a 36-year-old female, diagnosed preoperatively at core biopsy. A complete review of the literature on the topic is provided and differential diagnostic problems are discussed.
METHODS: Standard histological examination and immunohistochemical analyses using a large panel of antibodies were performed in both the core biopsy and surgical specimen.
RESULTS: Ultrasonography revealed a well-circumscribed tumour mass without calcifications. Histological examination of the core biopsy showed proliferation of bland-looking eosinophilic spindle cells arranged in a fascicular growth pattern. Mitoses, pleomorphism and necrosis were absent. Immunohistochemistry, revealing diffuse staining for a-smooth muscle actin, desmin and h-caldesmon, confirmed the leiomiomatous nature of neoplastic cells. Histological and immunohistochemical analyses of the surgical specimen confirmed the definitive diagnosis of leiomyoma.
CONCLUSIONS: The present case emphasizes that diagnosis of leiomyoma of the breast parenchyma can be confidentially rendered on needle core biopsy. We believe that correct diagnosis is primarily dependent on the awareness that this tumour can arise in this unusual site on rare occasions.

Di Bella G, Mascia F, Ricchi A, Colori B
Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report.
Neuro Endocrinol Lett. 2013; 34(7):660-8 [PubMed] Related Publications
OBJECTIVE: The current strategies for the treatment of breast cancer are essentially based on surgery, preceded and/or followed by chemotherapy often supplemented by radiotherapy and/or the administration of hormonal therapy and monoclonal antibodies. Their combined use has made it possible to increase an overall survival but they are still penalized by adverse effects and toxicity. The marked anti-cancer effects of biological molecule such as somatostatin, melatonin, retinoid, vitamin D3 and prolactin inhibitors have been studied and documented for several decades. Their integrated and synergic action have been demonstrated, but only a few studies have as yet been carried out on their combined application in humans. The aim of the present investigation was to evaluate both the objective clinical response and toxicity of the biological multimodal treatment named Di Bella Method (DBM).
MATERIAL AND METHODS: The clinical data from a total of 20 women with a certified diagnosis of breast cancer,defined disease stage, and who independently decided to follow the DBM as first-line treatment, were retrospectively reviewed.
RESULTS: The mean age of the patients was 51 years (min 30; max 73). Twelve (12) patients (60%) presented an early stage disease, while the other 40% had a locally advanced/metastatic stage. An overall clinical benefit was achieved in 75% of cases, with 55% of complete response and 20% of partial response. For metastatic patients, the overall survival rate was 71%. The main toxicity effects included leukopenia, gastrointestinal phenomena and drowsiness.
CONCLUSIONS: The preliminary results of this report confirm the positive action of the biological treatment in terms of efficacy and survival, showing a more than favorable profile of tolerability.

Related: Cyclophosphamide

Simon R, Latreille J, Matte C, et al.
Adherence to adjuvant endocrine therapy in estrogen receptor-positive breast cancer patients with regular follow-up.
Can J Surg. 2014; 57(1):26-32 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Adjuvant hormonal therapy is crucial in the treatment of estrogen receptor-positive breast cancer. The nonadherence rate to hormonal treatment is reported to be as high as 60%. The goal of this study was to evaluate the factors evoked by the patients as well as the demographic and disease-related factors that could be associated with nonadherence to adjuvant hormonal therapy.
METHODS: All consecutive patients treated for an estrogen receptor-positive breast cancer who showed up for regular follow-up with a single breast specialist between November 2008 and April 2009 were included in the study. We assessed adherence to hormonal therapy (either with tamoxifen or aromatase inhibitor). Reasons for adherence and nonadherence were collected. Records were also reviewed for demographic and cancer characteristics and for treatment components.
RESULTS: We included 161 patients in the study; 150 (93.2%) adhered to hormonal treatment. Side effects and absence of conviction were the main reasons for nonadherence. The importance of the diagnosis of cancer, fear of recurrence and regular follow-up were reported as the main reasons for adherence.
CONCLUSION: Severity of disease and side effects are associated with nonadherence to treatment. Strict follow-up appears to be a necessary adjunct in the adherence to treatment. The association between demographic and cancer characteristics and treatment components needs further investigation. However, these factors may help identify patients at risk of nonadherence and help the oncology team.

Auweter SD, Herzen J, Willner M, et al.
X-ray phase-contrast imaging of the breast--advances towards clinical implementation.
Br J Radiol. 2014; 87(1034):20130606 [PubMed] Related Publications
Breast cancer constitutes about one-quarter of all cancers and is the leading cause of cancer death in women. To reduce breast cancer mortality, mammographic screening programmes have been implemented in many Western countries. However, these programmes remain controversial because of the associated radiation exposure and the need for improvement in terms of diagnostic accuracy. Phase-contrast imaging is a new X-ray-based technology that has been shown to provide enhanced soft-tissue contrast and improved visualization of cancerous structures. Furthermore, there is some indication that these improvements of image quality can be maintained at reduced radiation doses. Thus, X-ray phase-contrast mammography may significantly contribute to advancements in early breast cancer diagnosis. Feasibility studies of X-ray phase-contrast breast CT have provided images that allow resolution of the fine structure of tissue that can otherwise only be obtained by histology. This implies that X-ray phase-contrast imaging may also lead to the development of entirely new (micro-) radiological applications. This review provides a brief overview of the physical characteristics of this new technology and describes recent developments towards clinical implementation of X-ray phase-contrast imaging of the breast.

Related: Cancer Screening and Early Detection

Aebi S, Gelber S, Anderson SJ, et al.
Chemotherapy for isolated locoregional recurrence of breast cancer (CALOR): a randomised trial.
Lancet Oncol. 2014; 15(2):156-63 [PubMed] Related Publications
BACKGROUND: Patients with isolated locoregional recurrences (ILRR) of breast cancer have a high risk of distant metastasis and death from breast cancer. We aimed to establish whether adjuvant chemotherapy improves the outcome of such patients.
METHODS: The CALOR trial was a pragmatic, open-label, randomised trial that accrued patients with histologically proven and completely excised ILRR after unilateral breast cancer who had undergone a mastectomy or lumpectomy with clear surgical margins. Eligible patients were enrolled from hospitals worldwide and were centrally randomised (1:1) to chemotherapy (type selected by the investigator; multidrug for at least four courses recommended) or no chemotherapy, using permuted blocks, and stratified by previous chemotherapy, oestrogen-receptor and progesterone-receptor status, and location of ILRR. Patients with oestrogen-receptor-positive ILRR received adjuvant endocrine therapy, radiation therapy was mandated for patients with microscopically involved surgical margins, and anti-HER2 therapy was optional. The primary endpoint was disease-free survival. All analyses were by intention to treat. This study is registered with, number NCT00074152.
FINDINGS: From Aug 22, 2003, to Jan 31, 2010, 85 patients were randomly assigned to receive chemotherapy and 77 were assigned to no chemotherapy. At a median follow-up of 4·9 years (IQR 3·6-6 ·0), 24 (28%) patients had disease-free survival events in the chemotherapy group compared with 34 (44%) in the no chemotherapy group. 5-year disease-free survival was 69% (95% CI 56-79) with chemotherapy versus 57% (44-67) without chemotherapy (hazard ratio 0·59 [95% CI 0·35-0·99]; p=0·046). Adjuvant chemotherapy was significantly more effective for women with oestrogen-receptor-negative ILRR (pinteraction=0·046), but analyses of disease-free survival according to the oestrogen-receptor status of the primary tumour were not statistically significant (pinteraction=0·43). Of the 81 patients who received chemotherapy, 12 (15%) had serious adverse events. The most common adverse events were neutropenia, febrile neutropenia, and intestinal infection.
INTERPRETATION: Adjuvant chemotherapy should be recommended for patients with completely resected ILRR of breast cancer, especially if the recurrence is oestrogen-receptor negative.
FUNDING: US Department of Health and Human Services, Swiss Group for Clinical Cancer Research (SAKK), Frontier Science and Technology Research Foundation, Australian and New Zealand Breast Cancer Trials Group, Swedish Cancer Society, Oncosuisse, Cancer Association of South Africa, Foundation for Clinical Research of Eastern Switzerland (OSKK), Grupo Español de Investigación en Cáncer de Mama (GEICAM), and the Dutch Breast Cancer Trialists' Group (BOOG).

Related: Australia

Boros M, Ilyes A, Nechifor Boila A, et al.
Morphologic and molecular subtype status of individual tumor foci in multiple breast carcinoma. A study of 155 cases with analysis of 463 tumor foci.
Hum Pathol. 2014; 45(2):409-16 [PubMed] Related Publications
The aim of this study is to evaluate biomarker immunophenotypic heterogeneity between separate tumor foci of multiple breast carcinoma, its correlation with morphologic features and tumor grade, and its influence on the treatment. One hundred fifty-five invasive multiple breast carcinomas were retrospectively analyzed over a 6-year period (2007-2012), and the expression of estrogen (ER) and progesterone (PR) receptors, Ki-67 proliferative index, human epidermal growth factor receptor 2 expression, morphologic subtype, and tumor grading were analyzed in each tumor focus. We found mismatches in immunohistochemical features in 71 (53.78%) of 132 patients with similar histology and in 13 (56.52%) of 23 cases with different histology. When analyzing mismatches in ER and PR statuses together, in 4 (23.52%) of 17 cases, one of the tumor foci was ER or PR positive, whereas the index tumor did not express either marker. The most numerous mismatches (45 cases; 29.03%) concerned the proliferative index; in 14 cases (9.03%), the additional focus had a higher index than did the main focus, and in 9 of these cases, the additional focus displayed a histologic grade of 3. Mismatches in human epidermal growth factor receptor 2 status appeared in 25 (16.12%) cases. The histologic type of the additional foci was different from the index tumor in 23 (14.83%) cases. Assessment of all tumor foci would have determined 19 (12.25%) cases to receive different adjuvant treatments compared with what would have been indicated if only the biological status of the largest primary tumor was assessed. We strongly recommend assessing and reporting each tumor focus independently.

Related: MKI67

Wang L, Zhao Z, Meyer MB, et al.
CARM1 methylates chromatin remodeling factor BAF155 to enhance tumor progression and metastasis.
Cancer Cell. 2014; 25(1):21-36 [PubMed] Related Publications
Coactivator-associated arginine methyltransferase 1 (CARM1), a coactivator for various cancer-relevant transcription factors, is overexpressed in breast cancer. To elucidate the functions of CARM1 in tumorigenesis, we knocked out CARM1 from several breast cancer cell lines using Zinc-Finger Nuclease technology, which resulted in drastic phenotypic and biochemical changes. The CARM1 KO cell lines enabled identification of CARM1 substrates, notably the SWI/SNF core subunit BAF155. Methylation of BAF155 at R1064 was found to be an independent prognostic biomarker for cancer recurrence and to regulate breast cancer cell migration and metastasis. Furthermore, CARM1-mediated BAF155 methylation affects gene expression by directing methylated BAF155 to unique chromatin regions (e.g., c-Myc pathway genes). Collectively, our studies uncover a mechanism by which BAF155 acquires tumorigenic functions via arginine methylation.

Wang X, Roberts CW
CARMA: CARM1 methylation of SWI/SNF in breast cancer.
Cancer Cell. 2014; 25(1):3-4 [PubMed] Article available free on PMC after 13/01/2015 Related Publications
In this issue of Cancer Cell, Wang and colleagues report that CARM1, a protein arginine methyltransferase, specifically methylates BAF155/SMARCC1, a core subunit of the SWI/SNF chromatin remodeling/tumor suppressor complex. This modification facilitates the targeting of BAF155 to genes of the c-Myc pathway and enhances breast cancer progression and metastasis.

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