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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Information for Patients and the Public
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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).

Bekelman JE, Sylwestrzak G, Barron J, et al.
Uptake and costs of hypofractionated vs conventional whole breast irradiation after breast conserving surgery in the United States, 2008-2013.
JAMA. 2014; 312(23):2542-50 [PubMed] Free Access to Full Article Related Publications
IMPORTANCE: Based on randomized evidence, expert guidelines in 2011 endorsed shorter, hypofractionated whole breast irradiation (WBI) for selected patients with early-stage breast cancer and permitted hypofractionated WBI for other patients.
OBJECTIVES: To examine the uptake and costs of hypofractionated WBI among commercially insured patients in the United States.
DESIGN, SETTING, AND PARTICIPANTS: Retrospective, observational cohort study, using administrative claims data from 14 commercial health care plans covering 7.4% of US adult women in 2013, we classified patients with incident early-stage breast cancer treated with lumpectomy and WBI from 2008 and 2013 into 2 cohorts: (1) the hypofractionation-endorsed cohort (n = 8924) included patients aged 50 years or older without prior chemotherapy or axillary lymph node involvement and (2) the hypofractionation-permitted cohort (n = 6719) included patients younger than 50 years or those with prior chemotherapy or axillary lymph node involvement.
EXPOSURES: Hypofractionated WBI (3-5 weeks of treatment) vs conventional WBI (5-7 weeks of treatment).
MAIN OUTCOMES AND MEASURES: Use of hypofractionated and conventional WBI, total and radiotherapy-related health care expenditures, and patient out-of-pocket expenses. Patient and clinical characteristics included year of treatment, age, comorbid disease, prior chemotherapy, axillary lymph node involvement, intensity-modulated radiotherapy, practice setting, and other contextual variables.
RESULTS: Hypofractionated WBI increased from 10.6% (95% CI, 8.8%-12.5%) in 2008 to 34.5% (95% CI, 32.2%-36.8%) in 2013 in the hypofractionation-endorsed cohort and from 8.1% (95% CI, 6.0%-10.2%) in 2008 to 21.2% (95% CI, 18.9%-23.6%) in 2013 in the hypofractionation-permitted cohort. Adjusted mean total health care expenditures in the 1 year after diagnosis were $28,747 for hypofractionated and $31,641 for conventional WBI in the hypofractionation-endorsed cohort (difference, $2894; 95% CI, $1610-$4234; P < .001) and $64,273 for hypofractionated and $72,860 for conventional WBI in the hypofractionation-permitted cohort (difference, $8587; 95% CI, $5316-$12,017; P < .001). Adjusted mean total 1-year patient out-of-pocket expenses were not significantly different between hypofractionated vs conventional WBI in either cohort.
CONCLUSIONS AND RELEVANCE: Hypofractionated WBI after breast conserving surgery increased among women with early-stage breast cancer in 14 US commercial health care plans between 2008 and 2013. However, only 34.5% of patients with hypofractionation-endorsed and 21.2% with hypofractionation-permitted early-stage breast cancer received hypofractionated WBI in 2013.

Related: USA

Kandemir M, Zhang C, Hamprecht FA
Empowering multiple instance histopathology cancer diagnosis by cell graphs.
Med Image Comput Comput Assist Interv. 2014; 17(Pt 2):228-35 [PubMed] Related Publications
We introduce a probabilistic classifier that combines multiple instance learning and relational learning. While multiple instance learning allows automated cancer diagnosis from only image-level annotations, relational learning allows exploiting changes in cell formations due to cancer. Our method extends Gaussian process multiple instance learning with a relational likelihood that brings improved diagnostic performance on two tissue microarray data sets (breast and Barrett's cancer) when similarity of cell layouts in different tissue regions is used as relational side information.

Gómez-Campelo P, Bragado-Álvarez C, Hernández-Lloreda MJ
Psychological distress in women with breast and gynecological cancer treated with radical surgery.
Psychooncology. 2014; 23(4):459-66 [PubMed] Related Publications
OBJECTIVES: The objective of this study is to compare psychological distress (body image disturbance,self-esteem, depression, and anxiety) in women with breast or gynecological cancer treated by radical surgery. Additionally, another objective is to analyze the association between psychological distress and sociodemographic characteristics, medical history, and social support to produce a prediction model for the outcome measures.
METHODS: A cross-sectional study was carried out with 100 women who had undergone radical surgery for breast or gynecological cancer. Both groups were divided into the following: younger than 50 years old and 50 years old or older. Body Image Scale, Rosenberg's Self-Esteem Scale, Beck Depression Inventory, and Beck Anxiety Inventory were used.
RESULTS: Age had a significant main effect on psychological distress but the type of cancer did not.Younger women showed significantly greater distress than older women (p-values<0.001). A significant interaction between age and type of cancer was found, indicating that older women with breast cancer had worse body image and more depression than those with gynecological cancer (p-values 0.001); no significant differences were found between younger groups.The prediction model for increased body image disturbance and depression included the joint effect of the following variables: being younger, inactive occupational status, and post-adjuvant therapy side effects. For lower self-esteem, the variables were: being younger, post-adjuvant therapy side effects,and dissatisfaction with social support. And for higher anxiety, the sole variable included was post-adjuvant therapy side effects.
CONCLUSIONS: Both mastectomy and hysterectomy/oophorectomy cause similar psychological distress in younger women, but mastectomy causes greater distress in older women than hysterectomy/oophorectomy.

Related: Gynacological Cancers

Liu JE, Wang HY, Wang ML, et al.
Posttraumatic growth and psychological distress in Chinese early-stage breast cancer survivors: a longitudinal study.
Psychooncology. 2014; 23(4):437-43 [PubMed] Related Publications
OBJECTIVE: To describe the dynamic changes in posttraumatic growth (PTG) and psychological distress in hospitalized early-stage breast cancer (BC) survivors over a 6-month period.
METHODS: A longitudinal study design was adopted. The PTG inventory (PTGI) and distress management screening measure were used 3 months after diagnosis, then again at 6 and 9 months after diagnosis. For baseline data, 155 BC patients who were receiving chemotherapy were selected from four first-class tertiary hospitals in Beijing from April 2010 to March 2011 using a purposive sampling method. Of these, 120 BC patients completed the follow-up investigation. A repeated measures analysis of variance, followed by least significant difference post-hoc analysis, was used to compare PTG and psychological distress.
RESULTS: The total score of the PTGI was 62.72 ± 14.66 in BC survivors at 3 months after diagnosis.There was a weak negative relationship between PTG and psychological distress (r = –0.282, p<0.001).PTG increased and psychological distress decreased from 3 to 9 months after diagnosis. The PTGI scores were 63.24 ± 14.21, 68.26 ± 15.29, and 70.29 ± 16.07 at 3, 6, and 9 months after diagnosis, respectively, with distress thermometer scores of 3.62 ± 1.98, 2.59 ± 2.00, and 2.51 ± 1.00, respectively.
CONCLUSIONS: At 3 months after diagnosis, BC survivors develop PTG at a low level while they are receiving chemotherapy. PTG showed a weak negative association with psychological distress. The level of PTG shows an increasing tendency, whereas the degree of psychological distress exhibits a downward trend in the 9 months after diagnosis.

Bhatnagar S, Gazin C, Chamberlain L, et al.
TRIM37 is a new histone H2A ubiquitin ligase and breast cancer oncoprotein.
Nature. 2014; 516(7529):116-20 [PubMed] Article available free on PMC after 04/06/2015 Related Publications
The TRIM37 (also known as MUL) gene is located in the 17q23 chromosomal region, which is amplified in up to ∼ 40% of breast cancers. TRIM37 contains a RING finger domain, a hallmark of E3 ubiquitin ligases, but its protein substrate(s) is unknown. Here we report that TRIM37 mono-ubiquitinates histone H2A, a chromatin modification associated with transcriptional repression. We find that in human breast cancer cell lines containing amplified 17q23, TRIM37 is upregulated and, reciprocally, the major H2A ubiquitin ligase RNF2 (also known as RING1B) is downregulated. Genome-wide chromatin immunoprecipitation (ChIP)-chip experiments in 17q23-amplified breast cancer cells identified many genes, including multiple tumour suppressors, whose promoters were bound by TRIM37 and enriched for ubiquitinated H2A. However, unlike RNF2, which is a subunit of polycomb repressive complex 1 (PRC1), we find that TRIM37 associates with polycomb repressive complex 2 (PRC2). TRIM37, PRC2 and PRC1 are co-bound to specific target genes, resulting in their transcriptional silencing. RNA-interference-mediated knockdown of TRIM37 results in loss of ubiquitinated H2A, dissociation of PRC1 and PRC2 from target promoters, and transcriptional reactivation of silenced genes. Knockdown of TRIM37 in human breast cancer cells containing amplified 17q23 substantially decreases tumour growth in mouse xenografts. Conversely, ectopic expression of TRIM37 renders non-transformed cells tumorigenic. Collectively, our results reveal TRIM37 as an oncogenic H2A ubiquitin ligase that is overexpressed in a subset of breast cancers and promotes transformation by facilitating silencing of tumour suppressors and other genes.

Otto PM, Blecher CB
Controversies surrounding screening mammography.
Mo Med. 2014 Sep-Oct; 111(5):439-43 [PubMed] Related Publications
Screening for breast cancer with mammography has been shown in multiple randomized control trials to decrease breast cancer mortality. Despite this, there are ongoing controversies regarding the benefits and risks of mammographic screening. Different professional groups have published conflicting guidelines regarding when to start screening, how often to screen, and when to stop screening which have added to the confusion. In this article we describe the evidence supporting and challenging the efficacy of mammography and review our real world approach to breast cancer screening.

Related: Cancer Screening and Early Detection

Zervoudis S, Iatrakis G, Mares P, et al.
Breast conserving surgery in multicentric breast cancer, preliminary data of our experience.
Eur J Gynaecol Oncol. 2014; 35(5):530-4 [PubMed] Related Publications
INTRODUCTION: It is widely supported that multicentric disease of the breast (MCDB) is a contraindication of breast conservative surgery (BCS).
MATERIALS AND METHODS: This is a multicentric study (two breast cancer units from Greece, one from France) involving patients with at least two primary tumors in separate quadrants of the breast and no diffuse suspicious microcalcifications on mammography. Sixty-one patients were included in the study, but 49 were followed up to the end. Patients were randomly assigned in total mastectomy (TM) and BCS groups. End point of the study was disease-free survival rates three and five years after initial operation.
RESULTS: Three years after BCS, local recurrence (LR) was observed in two patients (7%) and one after five years (total recurrence rate: 11%). A TM was performed in these patients, and in two there was no LR or distant metastasis (DM) five years after. The third patient was disease free two-years later. Three years after TM, eight patients (36.4%) had DM and 14 (63.6%) did not (p = 0.004). Five years after TM, eight patients (36.4%) had DM and 14 patients (63.6%) di not (p = 0.03).
CONCLUSION: The results showed that conservative surgery was an alternative surgical option in multicentric breast cancer with good results regarding disease-free survival and recurrence.

Böhm J, Zikán M
Ductal carcinoma in situ: analysis of 250 cases.
Eur J Gynaecol Oncol. 2014; 35(5):525-9 [PubMed] Related Publications
BACKGROUND: In the mammography screening era, we experience increasing incidence of non-invasive lesions of the breast, particularly the ductal carcinoma in situ (DCIS). It is the authors' goal to better understand this disorder in order to be able to tailor therapy individually for each patient and, most of all, to avoid overtreatment.
MATERIALS AND METHODS: The authors analyzed all cases of DCIS diagnosed within one mammography screening unit between 2007 and 2013. Medical reports as well as a detailed case conference protocol were used to gain all required data.
RESULTS: In a seven-year period, DCIS situ has been diagnosed 250 times in 249 women. Mostly the authors were able to obtain relevant information regarding tumor size, grade, biological characteristics, as well as surgery. This data was compared with current literature.
DISCUSSION: Participating women who screen positive constitute a large patient sample. Thus, we have a large amount of clinical and histological information available for planning and conducting studies regarding DCIS as well as invasive breast cancer.

Honig A, Gehrmann M, Kranke P, et al.
Microtubule-associated protein tau correlates with estrogen receptor status but not with in vitro paclitaxel sensitivity in primary breast cancer.
Eur J Gynaecol Oncol. 2014; 35(5):503-7 [PubMed] Related Publications
BACKGROUND: Factors or signatures predicting response to chemotherapeutic agents are of great interest for breast cancer patient care. There is conflicting data regarding microtubule-associated protein tau as predictive marker of paclitaxel sensitivity. Paclitaxel plays an important role in the adjuvant and metastatic therapy of breast cancer. However, a substantial proportion of patients treated with paclitaxel do not derive benefit from this therapy. Therefore, evaluating potential predictive factors is increasingly important. The authors attempted to validate these findings in vitro utilizing the ATP tumorchemosensitivity assay (ATP-TCA).
MATERIALS AND METHODS: The in vitro drug sensitivity to paclitaxel was evaluated in 48 fresh primary breast cancer specimens using the ATP-TCA. ATP-TCA results were analysed using the area under the curve (AUC) of growth inhibition. These results were correlated with the expression of tau mRNA measured by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Tau was also compared between patients with progesterone receptor (PgR) positive and negative and estrogen receptor (ER) positive and negative breast cancer, respectively.
RESULTS: The correlation of tau with the AUC for paclitaxel was weak, Spearman Rho was -0.267 with a p-value of 0.064. As described before, multiple regression analysis confirmed T-stage (p = 0.01) and PR status (p = 0.01) as independent predictors of paclitaxel chemosensitivity. Using multiple regression analysis and defining tau mRNA expression as dependent variable estrogen receptor status as measured by immunohistochemistry was a highly significant predictor for tau mRNA expression (p < 0.001). Grade (p = 0.002) as well as PgR expression (p < 0.001) were also found to be predictors of tau mRNA expression. CON- CLUSIONS: In the present data set the authors were not able to show that MAP-tau mRNA could predict benefit from the addition of a taxane to adjuvant chemotherapy. They found that ER expression is associated with tau protein expression. Estrogen gene transcription is reported to carry weak predictive significance for endocrine sensitivity, therefore it might be worth pursuing whether, tau mRNA could possibly be a predictor for endocrine therapy response.

Related: Paclitaxel

Shi Q, Li J, Li M, et al.
The role of levonorgestrel-releasing intrauterine system for endometrial protection in women with breast cancer taking tamoxifen.
Eur J Gynaecol Oncol. 2014; 35(5):492-8 [PubMed] Related Publications
PURPOSE OF INVESTIGATION: To review the evidence concerning the efficacy of levonorgestrel-releasing intrauterine system (LNG-IUS) in preventing endometrial pathology in women treated with tamoxifen.
MATERIALS AND METHODS: Randomized controlled trials (RCTs) of women with breast cancer on tamoxifen that compared endometrial surveillance or placebo alone vs. the LNG-IUS were reviewed. The eligible trials were identified from the following electronic databases: Cochrane CENTRAL, Medline, and EMBASE. The authors extracted data on all reported outcomes and conducted meta-analyses on the endometrial polyps, endometrial hyperplasia, proliferative endometrium, and endometrium thickness.
RESULTS: According to the subgroup analysis, a significant reduction of endometrial polyps was obtained (OR = 0.22, 95% CI 0.13-0.37, p < 0.00001). The use of LNG-IUS reduced the incidence of endometrial hyperplasia (OR = 0.13, 95% CI 0.03-0.58, p = 0.007). Increased abnormal vaginal bleeding for LNG-IUS users may be an adverse aspect of LNG-IUS.
CONCLUSION: This meta-analysis confirms that endometrial hyperplasia is also reduced as well as endometrial polyp formation reduced after long-term follow-up.

Mayrovitz HN, Weingrad DN, Davey S
Tissue dielectric constant (TDC) measurements as a means of characterizing localized tissue water in arms of women with and without breast cancer treatment related lymphedema.
Lymphology. 2014; 47(3):142-50 [PubMed] Related Publications
Quantitative measurements to detect lymphedema early in persons at-risk for breast cancer (BC) treatment-related lymphedema (BCRL) can aid clinical evaluations. Since BCRL may be initially manifest in skin and subcutis, the earliest changes might best be detected via local tissue water (LTW) measurements that are specifically sensitive to such changes. Tissue dielectric constant (TDC) measurements, which are sensitive to skin-to-fat tissue water, may be useful for this purpose. TDC differences between lymphedematous and non-lymphedematous tissue has not been fully characterized. Thus we measured TDC values (2.5 mm depth) in forearms of three groups of women (N = 80/group): 1) healthy with no BC (NOBC), 2) with BC but prior to surgery, and 3) with unilateral lymphedema (LE). TDC values for all arms except LE affected arms were not significantly different ranging between 24.8 ± 3.3 to 26.8 ± 4.9 and were significantly less (p < 0.001) as compared to 42.9 ± 8.2 for LE affected arms. Arm TDC ratios, dominant/non-dominant for NOBC, were 1.001 ± 0.050 and at-risk/ contralateral for BC were 0.998 ± 0.082 with both significantly less (p < 0.001) than LE group affected/control arm ratios (1.663 ± 0.321). These results show that BC per se does not significantly change arm LTW and that the presence of BCRL does not significantly change LTW of non-affected arms. Further, based on 3 standard deviations of measured arm ratios, our data demonstrates that an at-risk arm/contralateral arm TDC ratio of 1.2 and above could be a possible threshold to detect pre-clinical lymphedema. Further prospective measurement trial are needed to confirm this value.

Choi YH, Seo KS
Correlation among bioimpedance analysis, sonographic and circumferential measurement in assessment of breast cancer-related arm lymphedema.
Lymphology. 2014; 47(3):123-33 [PubMed] Related Publications
New approaches for assessment of lymphedema using ultrasonography (US) have been introduced recently and are reported to be reliable and simple. Ultrasonography provides detailed information about physical properties of the tissue in addition to volume and size. There have been only limited studies comparing bioimpedance analysis (BIA), US, and circumferential measurement (CM), which is considered a standard measurement. The aim of this study was to determine the relationship between US, BIA, and CM. Twenty-eight patients with lymphedema after breast cancer surgery underwent BIA, US, and CM. Impedance, which reflects the amount of extracellular fluid, was measured with 1 kHz frequency in affected and unaffected arms. Circumferences were measured at 10cm proximal and distal to the elbow and a truncated cone method used to calculate estimated volumes for upper arm and forearm. We found that interlimb forearm subcutis thickness differences measured by US were highly correlated with CM measurements and that interlimb upper arm subcutis thickness differences measured by US were moderately correlated with CM measurements and BIA ratios. However, the interlimb ratio of compressibility measured by US showed no or only weak correlation with impedance measurements and circumferential measurements. Our results also show that compressibility measured by US could not be predicted from BIA or CM measurements despite a high degree of concordance among subcutis thickness measured by US, CM, and BIA.

Kerrigan D, Waters P, Ryan M, et al.
Follow-up arrangements for breast cancer patients; is it appropriate to transfer surveillance to general practitioners?
Ir Med J. 2014; 107(9):273-5 [PubMed] Related Publications
The aim of this study was to examine the evidence for hospital follow up of breast cancer survivors and to identify patient preferences for hospital or community follow-up. We surveyed General Practitioner attitudes towards community follow-up and quantified the incidence of new or recurrent cancers within a patient cohort to identify their primary symptoms and thus cancer detection in the community. A 22 item questionnaire was distributed to 101 breast cancer survivors from a cohort of 921 treated patients. A 9 item questionnaire was distributed to 81 General Practitioners. Patients are reassured by hospital outpatient appointments, n=63 (74%) but have high levels of confidence in General Practitioner follow-up, n=57 (67%). General Practitioners are equally divided regarding their support for the transfer of follow-up (51%, 49%). Ten of the 14 new cancer episodes were associated with obvious clinical signs (p < 0.05). The proposed transfer of follow-up for patients to general practice by the national cancer control programme is appropriate.

Condiotti R, Guo W, Ben-Porath I
Evolving views of breast cancer stem cells and their differentiation States.
Crit Rev Oncog. 2014; 19(5):337-48 [PubMed] Related Publications
Cellular heterogeneity is a prominent characteristic of breast cancers, and accumulating evidence indicates that variability in the differentiation state of tumor cells contributes to this phenomenon. Breast cancers are among the tumor types in which the existence of cancer stem cells has been widely supported, and specific markers, including CD44/CD24 and ALDH1, have been consistently used to identify such cells. Recent studies have revealed the potential for dynamic bidirectional transitions of breast cancer cells between differentiated and stem-like phenotypes. In addition, the potential importance of intermediate states along differentiation axes, including the epithelial-to-mesenchymal transition and the basal-luminal differentiation axis, has emerged. These findings provide a view of breast cancer stem cells that departs from the traditional unidirectional hierarchical model, as well as new insights into the mechanisms by which differentiation events contribute to breast cancer biology. Herein we discuss these advances.

Lee HJ, Seo AN, Kim EJ, et al.
HER2 heterogeneity affects trastuzumab responses and survival in patients with HER2-positive metastatic breast cancer.
Am J Clin Pathol. 2014; 142(6):755-66 [PubMed] Related Publications
OBJECTIVES: Heterogeneity of HER2 gene amplification is found in a subset of breast cancers. We investigated the impact of HER2 heterogeneity on trastuzumab responses and clinical outcomes in 112 patients with HER2-positive metastatic breast cancer.
METHODS: Regional and genetic heterogeneity of HER2 gene amplification was determined in three different areas of each tumor by immunohistochemistry and silver in situ hybridization. We also assessed the overall levels of HER2 amplification and the proportion of tumor cells with a HER2/CEP17 ratio of more than 2.2 or strong and complete membranous (3+) expression of HER2 protein.
RESULTS: HER2 regional and genetic heterogeneity based on the HER2/CEP17 ratio was confirmed in 8.7% and 2.7% of cases, respectively. Poor response to trastuzumab was associated with overall low-level or equivocal amplification, HER2 regional heterogeneity by the HER2/CEP17 ratio, the HER2/CEP17 ratio of more than 2.2 in less than 80% of tumor cells, and HER2 immunohistochemical expression of 3+ in less than 75% of tumor cells. In survival analyses, low-level or equivocal HER2 amplification, HER2 regional heterogeneity based on the HER2/CEP17 ratio, and the HER2/CEP17 ratio of more than 2.2 in less than 80% of tumor cells were associated with shorter time to progression and lower overall survival in univariate and multivariate analyses.
CONCLUSIONS: These results suggest that accurate assessment of HER2 status, including HER2 heterogeneity, is important in predicting trastuzumab responses and outcomes in patients with HER2-positive metastatic breast cancer.

Related: ERBB2 (HER2) Trastuzumab (Herceptin)

Ottini L
Male breast cancer: a rare disease that might uncover underlying pathways of breast cancer.
Nat Rev Cancer. 2014; 14(10):643 [PubMed] Related Publications
There are similarities between breast cancers that arise in men and women but there are also differences. What can be learned from male breast cancer to gain insight into breast cancer pathogenesis?

Related: Male Breast Cancer BRCA1 BRCA2 Signal Transduction

Wood WC, Alvarado M, Buchholz DJ, et al.
The current clinical value of the DCIS Score.
Oncology (Williston Park). 2014; 28 Suppl 2:C2, 1-8, C3 [PubMed] Related Publications
The management of ductal carcinoma in situ (DCIS) can be controversial. Widespread adoption of mammographic screening has made DCIS a more frequent diagnosis, and increasingly smaller, lower-grade lesions are being detected. DCIS is commonly treated with breast-conserving surgery and radiation. However, there is greater recognition that acceptable cancer control outcomes can be achieved for some patients with breast-conserving surgery alone, with radiotherapy reserved for those at higher risk of in-breast recurrence. The primary clinical dilemma is that there are currently no reliable clinicopathologic features that accurately predict which patients will have a recurrence, but risk stratification is an area of active research. Molecular profiling has the potential to assess recurrence risk based on the individual patient's tumor biology and guide treatment decisions. The DCIS Score is a 12-gene assay intended to support personalized treatment planning for patients with DCIS following local excision. It provides information on local failure risk independent of traditional clinicopathologic features. Our group of expert breast surgeons and radiation oncologists met in December 2013 at the San Antonio Breast Cancer Symposium to discuss current controversies in DCIS management and determine the potential value of the DCIS Score in managing these situations. We concluded that the DCIS Score provides clinically relevant information about personal risk that can guide patient discussions and facilitate shared decision making.

Kikuchi M, Tanino H, Kosaka Y, et al.
Usefulness of MRI of microcalcification lesions to determine the indication for stereotactic mammotome biopsy.
Anticancer Res. 2014; 34(11):6749-53 [PubMed] Related Publications
BACKGROUND: With the recent rise in mammography (MMG) screenings there has been an increase in the identification of microcalcifications without lump. Therefore, a vacuum-assisted needle biopsy under stereotactic guidance (ST-MTB) is frequently performed for diagnosis. However, ST-MTB is a highly invasive examination. In this study, we investigated the effectiveness of utilizing contrast-enhanced magnetic resonance imaging (MRI) to differentiate between benign and malignant category 3 (C3) calcifications.
MATERIALS AND METHODS: One hundred and sixty-eight patients with microcalcifications underwent contrast-enhanced MRI prior to ST-MTB in our hospital. Their MRI scans were reviewed to determine whether the contrast-enhanced MRI findings were consistent. We calculated the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of contrast-enhanced MRI.
RESULTS: No malignancy was not found in the 51 of the 168 cases analyzed by MRI. The calculated sensitivity, specificity, PPV and NPV of contrast-enhanced MRI were 84%, 82%, 58% and 95%, respectively.
CONCLUSION: Contrast-enhanced MRI for Category 3 calcified lesions would be a useful diagnostic tool for identifying ST-MTB-indicated patients.

Su CH, Hsiao CL, Chang WS, et al.
Evaluation of the contribution of cyclooxygenase 2 genotypes to breast cancer in Taiwan.
Anticancer Res. 2014; 34(11):6711-6 [PubMed] Related Publications
Overexpression of cyclooxygenase 2 (COX-2) has been suggested to be associated with breast carcinogenesis. The aim of the present study was to evaluate the contribution of genotypic polymorphisms in COX-2 to breast cancer risk of Taiwanese females. In total, 1,232 breast cancer patients and 1,232 healthy controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methodology. Six polymorphic variants of COX-2, including G-1195A (rs689466), G-765C (rs20417), T8473C (rs5275), intron 1 (rs2745557), intron 5 (rs16825748) and intron 6 (rs2066826) were examined. The results showed that the GC genotype of COX-2, G-765C was associated with a lower risk compared to the wild-type GG genotype (odds ratio(OR)=0.66, 95% confidence interval(CI)=0.53-0.83, p=0.0005). The C allele of COX-2 G-765C was significantly more frequently found in controls than in cancer patients (p=0.0006). In addition, the OR of the GG/AG+AA, GC/GG and GC/AG+AA at G-765C/Intron 1 combined genotypes compared to wild-type GG/GG genotype were 0.79 (95%CI=0.66-0.96; p=0.0166), 0.61 (95%CI=0.48-0.78; p=0.0001), and 0.71 (95%CI=0.36-1.37; p=0.3040), respectively. As for the combination of G-765C and intron 6, the OR of the GG/AG+AA, GC/GG and GC/AG+AA combined genotypes compared with wild-type GG/GG reference genotype were 0.79 (95%CI=0.62-1.01; p=0.0561), 0.63 (95%CI=0.50-0.81; p=0.0003), and 0.68 (95%CI=0.38-1.21; p=0.1897), respectively. Our results indicate that the C allele of COX-2, G-765C was associated with a decreased risk of breast cancer in Taiwan, and could serve as an early detection and predictive marker for breast cancer risk.

Related: COX2 (PTGS2)

Skondra M, Gkioka E, Kostakis ID, et al.
Detection of circulating tumor cells in breast cancer patients using multiplex reverse transcription-polymerase chain reaction and specific primers for MGB, PTHRP and KRT19 correlation with clinicopathological features.
Anticancer Res. 2014; 34(11):6691-9 [PubMed] Related Publications
AIM: The aim of this study was to correlate the clinicopathological features of breast cancer patients with the positive detection of parathyroid hormone-related protein (PTHRP), cytokeratin protein 19 (KRT19) and mammaglobin (MGB) using a multiplex reverse transcription polymerase chain reaction (RT-PCR) assay developed to detect circulating tumor cells (CTCs) in peripheral blood of patients with breast cancer.
PATIENTS AND METHODS: Peripheral blood samples were collected from 54 breast cancer patients and 20 healthy blood donors. Subsequently, the samples were processed for RNA extraction and analyzed for the expression of PTHRP, KRT19 and MGB using specific primers and multiplex RT-PCR.
RESULTS: The positive detection rates in breast cancer patients for PTHRP, KRT19 and MGB were 68.5%, 63% and 22.2% and for healthy donors 10%, 0% and 10%, respectively. The statistical analysis revealed that PTHRP- and KRT19-positive detections correlated with the diagnosis of breast cancer while the combined positive detections of PTHRP-plus-KRT19 correlated with the presence of distant metastasis, especially with bone metastasis. Moreover, positive detections of KRT19 correlated with high proliferation rate of breast cancer tumors. MGB-positive detections did not add any diagnostic advantage in such analysis.
CONCLUSION: Multiplex-PCR based detection of CTCs using PTHRP and KRT19 primers can provide useful information for the disease.

Aurilio G, Bagnardi V, Graffeo R, et al.
Does immediate breast reconstruction after mastectomy and neoadjuvant chemotherapy influence the outcome of patients with non-endocrine responsive breast cancer?
Anticancer Res. 2014; 34(11):6677-83 [PubMed] Related Publications
BACKGROUND/AIM: In breast cancer (BC) patients, breast surgery followed by immediate breast reconstruction (IBR) might favour recurrences and metastases due to extensive surgical manipulation. We retrospectively investigated whether IBR after mastectomy and neoadjuvant chemotherapy (NT) influenced the outcome in patients with early and locally advanced oestrogen receptor (ER)-negative BC.
PATIENTS AND METHODS: Between 1995 and 2006, 133 BC patients received NT followed by total mastectomy, 59 of whom underwent IBR. Patients receiving IBR (IBR group) were compared to patients who did not receive IBR (no-IBR group) over a prolonged median follow-up time (8.2 years).
RESULTS: Patients receiving IBR were on average younger than patients not receiving IBR (p<0.001). The percentage of patients with positive clinical nodal status (cN) was 19% in the IBR group and 7% in no-IBR group (p=0.036), whereas patients without IBR were more frequently diagnosed as clinical T4 (59% vs. 15%, p<0.001). The 5-year cumulative incidence of locoregional recurrences were 14% in the no-IBR group and 21% in the IBR group. The hazard of locoregional events, adjusted for age, clinical T and cN, was significantly greater in the IBR group than in the no-IBR group (hazard ratio (HR)=2.77, p=0.045). The 5-year cumulative incidences of distant metastases were similar in the two groups (p=0.414).
CONCLUSION: IBR following total mastectomy in patients with ER-negative disease after NT is associated with a worse rate of local relapses. More insight in mechanisms of wound healing and extent of surgery is required to further investigate this observation.

Related: Cyclophosphamide Methotrexate

Schneeweiss A, Seitz J, Smetanay K, et al.
Efficacy of nab-paclitaxel does not seem to be associated with SPARC expression in metastatic breast cancer.
Anticancer Res. 2014; 34(11):6609-15 [PubMed] Related Publications
AIM: To evaluate the predictive value of the expression of the secreted protein acidic and rich in cysteine (SPARC) for nab-paclitaxel in metastatic breast cancer (MBC).
PATIENTS AND METHODS: Forty-four patients with progressive MBC were prospectively treated with nab-paclitaxel. Expression of SPARC in tumor cells was assessed by an immunoreactive score, integrating staining intensity and percentage of positive tumor cells; expression in stroma based on staining intensity. SPARC serum levels were determined before 1st and 2nd cycle of nab-paclitaxel and at progression. By applying several cut-offs the association between SPARC expression or serum levels and clinical end-points was analyzed.
RESULTS: No clear association between expression of SPARC in primary or metastatic tumor tissue or in serum and any clinical end-point could be detected regardless of the various cut-offs applied.
CONCLUSION: Efficacy of nab-paclitaxel in MBC does not seem to be associated with expression of SPARC in tumor tissues or serum.

Related: Paclitaxel SPARC

Song G, Hsiao H, Wang JL, et al.
Differential impact of tumor-infiltrating immune cells on basal and luminal cells: implications for tumor invasion and metastasis.
Anticancer Res. 2014; 34(11):6363-80 [PubMed] Related Publications
BACKGROUND/AIM: Regarding the impact of tumor-infiltrating immune cells on tumor cells, many contradictory reports have been published. We have hypothesized that these controversies result from differences in tissue types and tumor stages, in which immune cells are variably distributed and differentially associated with epithelial cells. Our current study compared the pattern and frequency of physical association of tumor-infiltrating immune cells with different parenchymal cells of human breast and prostate tumors harboring normal, hyperplastic, in situ, and invasive components.
MATERIALS AND METHODS: The cytological, biological, and molecular alterations were assessed with double immunohistochemistry, double fluorescent labeling, apoptosis assay, and gene expression profiling.
RESULTS: Our study detected several previously undescribed features: (i) over 95% of infiltrating immune cells were seen within normal, hyperplastic, or in situ cancer structures with focally-disrupted capsules, and fewer than 5% were found within invasive cancer; (ii) over 95% of normal, hyperplastic, and in situ cancerous epithelial cells were physically shielded from immune cells by the surrounding myoepithelial or basal cell layer; (iii) about 90% of myoepithelial or basal cells physically associated with immune cells and such residual cells within focally disrupted layers exhibited distinct degeneration, including apoptosis, necrosis, and reduced expression of tumor suppressor p63; (iv) epithelial cells overlying focally disrupted tumor capsules surrounded by immune cells had substantially higher proliferation than their adjacent counterparts, and some of the proliferating cells were arranged as tongue-like projections invading the stroma; and (v) microdissected cells overlying focally disrupted tumor capsules had more than 5-fold higher expression of stem cell lineage markers KIT and NCOR2.
CONCLUSION: Tumor-infiltrating immune cells are primarily associated with degenerated myoepithelial or basal cells causing focal disruptions of the capsule, which selectively favor proliferation, invasion, and dissemination of the overlying tumor stem cells.

Related: Apoptosis Basal Cell Carcinoma Prostate Cancer

Mishra MN, Vangara KK, Palakurthi S
Transcriptional targeting of human liver carboxylesterase (hCE1m6) and simultaneous expression of anti-BCRP shRNA enhances sensitivity of breast cancer cells to CPT-11.
Anticancer Res. 2014; 34(11):6345-51 [PubMed] Related Publications
BACKGROUND: The major factor limiting the efficacy of breast cancer chemotherapy is multidrug resistance due to overexpression of the breast cancer resistance protein ATP-binding cassette, sub-family G (WHITE), member 2 (ABCG2). We hypothesized that conversion of camptothecin-11 (CPT-11) to its highly cytotoxic metabolite SN-38 by a mutant human carboxyl esterase (hCE1m6) specifically in cancer cells and inhibition of ABCG2 by anti-ABCG2 short hairpin RNA, leads to accumulation of a higher concentration of SN-38, resulting in higher therapeutic efficacy and less toxicity to normal cells.
MATERIALS AND METHODS: A mutant human carboxyl esterase hCE1m6 with human telomerase reverse transcriptase promoter was integrated into the VISA (VP16-Gal4-WPRE) amplification system. The plasmid was transfected into MCF-12A, MDA-MB-231, and MCF-7 cells using JetPRIME®. Cancer-specific expression of hCE1m6 in breast cancer cell lines was tested by real-time polymerase chain reaction (real time-PCR) and western blot. In vitro conversion of CPT-11 to SN-38 was evaluated on lysates of transfected cells. Cytotoxicity of CPT-11 against cells transfected with the plasmid was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay.
RESULTS: Real-time PCR and western blot analysis revealed that hCE1m6 was expressed only in breast cancer cells, MCF-7 and MDA-MB-231, but not in the normal MCF-12A breast cell line. From the CPT-11 conversion assay on cell lysates, it was found that expressed hCE1m6 in cancer cells was able to effectively convert CPT-11 to SN-38.
CONCLUSION: Breast cancer cell lines transfected with hCE1m6 showed an increased susceptibility to CPT-11 in comparison to MCF-12A cells.

Related: Apoptosis ABCG2 Irinotecan

Chui PL, Abdullah KL, Wong LP, Taib NA
Prayer-for-health and complementary alternative medicine use among Malaysian breast cancer patients during chemotherapy.
BMC Complement Altern Med. 2014; 14:425 [PubMed] Article available free on PMC after 04/06/2015 Related Publications
BACKGROUND: The inclusion of prayer-for-health (PFH) in the definition of complementary alternative medicine (CAM) has resulted in higher levels of CAM use. The objective of this study was to assess PFH and CAM use among breast cancer patients undergoing chemotherapy.
METHODS: A cross-sectional study was performed at two chemotherapy providers. Patients were questioned about use of three categories of CAM, mind-body practices (MBPs), natural products (NPs) and traditional medicine (TM). PFH was also examined separately from CAM to better characterise the patterns of CAM and PFH used during chemotherapy.
RESULTS: A total of 546 eligible patients participated in the study; 70.7% (n = 386) reported using some form of CAM, and 29.3% (n = 160) were non-CAM users. When PFH was excluded as a CAM, fewer patients reported the use of CAM (66.1%; n = 361). The total number of patients who used MBPs decreased from 342 to 183. The most common CAM use category was NPs (82.8%), followed by MBPs (50.7%), and TM (35.7%). CAM users were more likely to have a tertiary education (OR 2.11, 95% CI 1.15-3.89 vs. primary/lower), have household incomes > RM 3,000 (≈944 USD) per month (OR 2.32, 95% CI 1.40-3.84 vs. ≤RM 3,000 (≈944 USD)), and have advanced cancer (OR 1.75, 95% CI 1.18-2.59 vs. early stage cancer), compared with non-CAM users. The CAM users were less likely to have their chemotherapy on schedule (OR 0.24, 95% CI 0.10-0.58 vs. chemotherapy postponed) than non-CAM users. Most MBPs were perceived to be more helpful by their users, compared with the users of NPs and TM.
CONCLUSION: CAM use was prevalent among breast cancer patients. Excluding PFH from the definition of CAM reduced the prevalence of overall CAM use. Overall, CAM use was associated with higher education levels and household incomes, advanced cancer and lower chemotherapy schedule compliance. Many patients perceived MBP to be beneficial for improving overall well-being during chemotherapy. These findings, while preliminary, clearly indicate the differences in CAM use when PFH is included in, and excluded from, the definition of CAM.

Related: Complementary Therapies

Alderman A, Gutowski K, Ahuja A, et al.
ASPS clinical practice guideline summary on breast reconstruction with expanders and implants.
Plast Reconstr Surg. 2014; 134(4):648e-55e [PubMed] Related Publications
LEARNING OBJECTIVES: After reading this article, participants should be able to: 1. Understand the evidence regarding the timing of expander/implant breast reconstruction in the setting of radiation therapy. 2. Discuss the implications of a patient's risk factors for possible outcomes and complications of expander/implant breast reconstruction. 3. Implement proper prophylactic antibiotic protocols. 4. Use the guidelines to improve their own clinical outcomes and reduce complications.
SUMMARY: In March of 2013, the Executive Committee of the American Society of Plastic Surgeons approved an evidence-based guideline on breast reconstruction with expanders and implants, as developed by a guideline-specific work group commissioned by the society's Health Policy Committee. The guideline addresses ten clinical questions: patient education, immediate versus delayed reconstruction, risk factors, radiation therapy, chemotherapy, hormonal therapy, antibiotic prophylaxis, acellular dermal matrix, monitoring for cancer recurrence, and oncologic outcomes associated with implant-based reconstruction. The evidence indicates that patients undergoing mastectomy should be offered a preoperative referral to a plastic surgeon. Evidence varies regarding the association between postoperative complications and timing of postmastectomy expander/implant breast reconstruction. Evidence is limited regarding the optimal timing of expand/implant reconstruction in the setting of radiation therapy but suggests that irradiation to the expander or implant is associated with an increased risk of postoperative complications. Evidence also varies regarding the association between acellular dermal matrix and surgical complications in the setting of postmastectomy expander/implant reconstruction. Data support the use of an appropriate preoperative antibiotic, but antibiotics should be discontinued within 24 hours of the procedure, unless a surgical drain is present. Furthermore, postmastectomy expander/implant breast reconstruction does not adversely affect oncologic outcomes.

Connell TF
Patient-activated controlled expansion for breast reconstruction using controlled carbon dioxide inflation: confirmation of a feasibility study.
Plast Reconstr Surg. 2014; 134(4):503e-11e [PubMed] Related Publications
BACKGROUND: Women with breast cancer or those at high risk of developing breast cancer because of familial history of the disease or genetic mutations are frequently indicated for therapeutic or prophylactic mastectomy. Prosthetic reconstruction of the breast with placement of tissue expanders followed by implants offers favorable aesthetic and psychological results while adding only minimal additional surgical intervention. This study describes the confirmatory phase of an earlier feasibility trial that involved seven women who successfully underwent patient-activated controlled expansion for breast reconstruction with 10 AeroForm patient-controlled tissue expanders.
METHODS: A prospective, open-label, single-arm, single-surgeon confirmatory study in Perth, Australia, evaluated outcomes of two-stage breast reconstruction using the investigational device. Each subject administered a preset 10-cc dose of carbon dioxide gas using a remote dosage controller, three times each day, with a 3-hour lockout between doses until full expansion was achieved.
RESULTS: Thirty-three women with breast cancer, family history, or predisposition because of the BRCA1 or BRCA2 gene mutation underwent pedicled latissimus dorsi flap procedures with placement of 61 carbon dioxide-based tissue expanders. The mean number of days for subjects to achieve desired expansion was 17 ± 5. Operating the dosage controller was described by the surgeon as very easy in 94 percent of the cases and by 97 percent of the subjects. No serious adverse events were reported.
CONCLUSION: This study confirms that the AeroForm breast tissue expander has demonstrated the ability to provide, relative to saline expanders, a needle-free, patient-controlled, convenient, and time-saving method of tissue expansion.

Sun CS, Cantor SB, Reece GP, et al.
Helping patients make choices about breast reconstruction: a decision analysis approach.
Plast Reconstr Surg. 2014; 134(4):597-608 [PubMed] Article available free on PMC after 01/10/2015 Related Publications
Decision analysis can help breast reconstruction patients and their surgeons to methodically evaluate clinical alternatives and make hard decisions. The purpose of this article is to help plastic surgeons guide patients in making decisions though a case study in breast reconstruction. By making good decisions, patient outcomes may be improved. This article aims to illustrate decision analysis techniques from the patient perspective, with an emphasis on her values and preferences. The authors introduce normative decision-making through a fictional breast reconstruction patient and systematically build the decision basis to help her make a good decision. The authors broadly identify alternatives of breast reconstruction, propose types of outcomes that the patient should consider, discuss sources of probabilistic information and outcome values, and demonstrate how to make a good decision. The concepts presented here may be extended to other shared decision-making problems in plastic and reconstructive surgery. In addition, the authors discuss how sensitivity analysis may test the robustness of the decision and how to evaluate the quality of decisions. The authors also present tools to help implement these concepts in practice. Finally, the authors examine limitations that hamper adoption of patient decision analysis in reconstructive surgery and health care in general. In particular, the authors emphasize the need for routine collection of quality-of-life information, out-of-pocket expense, and recovery time.

Cordeiro PG, Albornoz CR, McCormick B, et al.
The impact of postmastectomy radiotherapy on two-stage implant breast reconstruction: an analysis of long-term surgical outcomes, aesthetic results, and satisfaction over 13 years.
Plast Reconstr Surg. 2014; 134(4):588-95 [PubMed] Related Publications
BACKGROUND: Postmastectomy radiation therapy is increasingly indicated in patients with node-positive breast cancer. The authors prospectively evaluated long-term outcomes in patients with two-stage implant-based reconstruction and postmastectomy radiation therapy to the permanent implant.
METHODS: A cohort of 1415 patients operated on by a single surgeon from 1998 to 2010 was evaluated annually. Outcomes were recorded prospectively. Complication rates were compared between irradiated and nonirradiated implants, including reconstructive failure (implant loss), complications (e.g., capsular contracture), aesthetic results, and satisfaction. Predicted implant loss and replacement rates were examined by irradiation status with Kaplan-Meier analysis and the log-rank test.
RESULTS: A total of 2133 breast implant reconstructions with a mean follow-up of 56.8 months (range, 12 to 164 months) were included. Three hundred nineteen implants received radiation. Implant loss occurred in 9.1 percent of irradiated implants and 0.5 percent of nonirradiated implants (p < 0.01). Capsular contracture grade IV was present in 6.9 percent of irradiated and 0.5 percent of nonirradiated implants (p < 0.01). There was no difference between groups regarding implant replacement. Ninety-two percent of irradiated patients had good to excellent aesthetic result, and 94.2 percent would choose implants again. Predicted implant loss rates were 17.5 percent and 2.0 percent for irradiated and nonirradiated implants, respectively, at 12 years (p < 0.01), and predicted implant replacement rates were 12.7 percent and 8.8 percent, respectively, at 8 years (p = not significant).
CONCLUSIONS: This is the largest prospective long-term outcomes evaluation in women with immediate tissue expander/implant reconstruction and postmastectomy radiation therapy. Most patients had a good to excellent aesthetic result and preserve their reconstruction at 12 years.

Deperas-Kaminska M, Bajinskis A, Marczyk M, et al.
Radiation-induced changes in levels of selected proteins in peripheral blood serum of breast cancer patients as a potential triage biodosimeter for large-scale radiological emergencies.
Health Phys. 2014; 107(6):555-63 [PubMed] Related Publications
The threat of a large scale radiological emergency, where thousands of people may require fast biological dosimetry for the purpose of triage, makes it necessary to search for new, high throughput biological dosimeters. The authors tested an assay based on the quantitative analysis of selected proteins in peripheral blood serum. They were particularly interested in testing proteins that are specific to irradiation of skin, as these can be used in cases of partial body exposure. Candidate proteins were identified in an earlier study with mice, where skin of the animals was exposed to different doses of radiation and global expression of serum proteins was analyzed. Eight proteins were found, the expression of which showed a consistent dose-response relationship. Human analogues of these proteins were identified, and their expression was measured in peripheral blood serum of 16 breast cancer patients undergoing external beam radiotherapy. The proteins were Apolipoprotein E; Apolipoprotein H; Complement protein 7; Prothrombinase; Pantothenate Kinase 4; Alpha-2-macroglobulin; Fetuin B and Alpha-1-Anti-Chymotrypsin. Measurements were carried out in blood samples collected prior to exposure (control), on the day after one fraction (2 Gy), on the day after five fractions (10 Gy), on the day after 10 fractions (20 Gy), and 1 mo after 23-25 fractions (total dose of 46-50 Gy). Multivariate analysis was carried out, and a multinomial logistic regression model was built. The results indicate that the combined analysis of Apolipoprotein E, Factor X, and Pantothenate Kinase 4 allows discriminating between exposure to 2 Gy and lower and between 10 Gy and higher. The discrimination is possible up to 1 mo after exposure.

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