The Breast - Articles in Press

Breast reconstruction following mastectomy for invasive breast cancer is strongly influenced by demographic factors in women in Victoria, Australia - Corrected Proof

R.J. Bell, P.J. Robinson, P. Fradkin, M. Schwarz, S.R. Davis — 2012-05-18

Abstract: This study explored factors associated with the likelihood of reconstruction after unilateral mastectomy and the wellbeing of women after reconstruction.Data were from a questionnaire completed on average 1.8 years after diagnosis by 1429 women in the BUPA Health and Wellbeing After Breast Cancer Study. Logistic regression was used to model factors associated with reconstruction. The Psychological General Wellbeing Questionnaire was used to assess wellbeing.A total of 25.4% of 366 women who had a unilateral mastectomy had undergone a reconstruction nearly two years after diagnosis. Being younger (p<0.001), educated beyond school (p<0.04), living in the metropolitan area (p<0.001), having private health insurance (p=0.003), not having dependent children (p=0.004) and not having radiotherapy (p<0.001) explained just over 40% of the variation in reconstruction status. There was a modest difference between women who did and did not have a reconstruction in terms of wellbeing. Demographic factors strongly influence the likelihood of reconstruction after mastectomy.

The impact of immediate breast reconstruction on post-mastectomy lymphedema in patients undergoing modified radical mastectomy - Corrected Proof

2012-05-18

Abstract: The aim of this study was to assess the impact of immediate breast reconstruction (IBR) with autologous tissue on the development of post-mastectomy lymphedema in patients undergoing modified radical mastectomy (MRM). A retrospective chart review was performed for early-stage breast cancer patients who underwent MRM between January 2001 and December 2009. Patients were categorized into two groups based on whether or not they underwent IBR. The incidence of lymphedema was assessed and compared. A total of 712 patients underwent MRM, which included 117 patients undergoing IRB. There were no significant differences between two groups except for a lower body mass index in the reconstruction group. Comparing the incidence of lymphedema using multivariate logistic regression analysis, the reconstruction group had a significantly lower incidence of lymphedema (p-value = 0.023). Breast cancer patients who underwent MRM with IBR had a significantly lower incidence of lymphedema than those in the non-reconstruction group.

Effect of surgeon's caseload on the quality of surgery and breast cancer recurrence - Corrected Proof

Päivi Peltoniemi, Heini Huhtala, Kaija Holli, Liisa Pylkkänen — 2012-05-17

Abstract: The aim of this study was to evaluate the effects of the caseloads of individual surgeons on breast cancer primary care and outcome. The extent of primary breast cancer and axillary surgery and the appearance of local recurrences were evaluated for 1377 women operated in Pirkanmaa region between 1.1.1997 and 31.12.2001 and followed- up at least until 31.12.2008 or death. Caseloads of each surgeon were divided into three categories: over 550, 100–200 and under 60. Breast conserving surgery was performed more often by surgeons with the highest (OR 1.32) and the middle (OR 1.54) caseload volumes compared to those with the lowest volumes (p = 0.018). Surgeons with the lowest caseloads also dissected fewer lymph nodes (mean 9.4 versus 11.2 in the highest and 10.9 in the middle caseload volumes; p ≤ 0.001). There were no differences in recurrences between the groups during the mean follow-up time of 8.9 years.

Is conservative surgery a good option for patients with “triple negative” breast cancer? - Corrected Proof

2012-05-14

Abstract: Background: Triple negative breast cancers (negative estrogen receptor, progestagen receptor and no overexpression of HER2) seems to be more aggressive than other breast carcinoma subtypes. Therefore, it is necessary to analyze if a more aggressive surgical treatment should be offered to this subgroup of patients.Patients and methods: The Castellon Cancer Registry Database (C.Valenciana, Spain) was used to identify eligible breast cancer patients. Female patients who were diagnosed and/or treated from January 2000 to December 2008 with primary, invasive, unilateral breast cancer at our hospital were included. A total of 410 patients make up the study population. Kaplan–Meier curves and log-rank tests were used to estimate 5-year local recurrence functions and to compare them across strata. Cox proportional hazards models were used to calculate hazard ratios and 95% confidence intervals to fit the effect of conservative surgery and other independent variables on local recurrence.Results: Median follow-up time was 60 months (1–127 months). A total of 21 patients (5%) presented a local recurrence during follow-up. There was a 9% difference in terms of local recurrence between conservative and non-conservative techniques for triple negative patients, whereas such difference was only 1% for no triple negative patients. On univariate analysis for local recurrence, only tumor size and lymph node metastasis were statistically associated with local recurrence. All other variables (type of surgery, triple negative status, molecular classification, tumor grade, age, adjuvant treatments, and total number of analyzed lymph nodes) were not statistically significant. On multivariate analysis, independent prognostic factors were breast conservative surgery (HR 4.62 95%CI 1.12–16.82), number of positive lymph nodes (HR 1.07 95%CI 1.01–1.17) and millimetre tumor size (HR 1.02 95%CI 1.01–1.06). In contrast, triple negative status trended to be a risk factor but without statistical significance (HR 1.59 95%CI 0.42–8.04).Conclusions: It was not possible to find statistically significant differences between conservative and non-conservative surgery for triple negative breast cancer. However, a trend was observed for higher recurrence rates after breast conservative surgery for this group of patients. Prospective clinical trials are needed to confirm this observation.

Breast cancer and HSP90 inhibitors: Is there a role beyond the HER2-positive subtype? - Corrected Proof

Leticia De Mattos-Arruda, Javier Cortes — 2012-05-07

Abstract: HSP90 inhibitors have shown great promise as therapeutic targets because they have the potential to suppress multiple signaling pathways simultaneously, and many are currently under clinical development. Because HER2 is known to be a client protein sensitive to inhibition of the HSP90 chaperone complex, HSP90 inhibitors have been studied in HER2-positive breast cancer and have shown promising results. In this article, we revisit HSP90 inhibitors in the context of breast cancer and discuss some notable preclinical data that reveal potential roles in both hormonal receptor-positive and triple negative breast tumor subtypes.

Interest and attitudes of patients, cancer physicians, medical students and cancer researchers towards a spectrum of genetic tests relevant to breast cancer patients - Corrected Proof

Natalie Ngoi, Soo-Chin Lee, Mikael Hartman, Lay-Wai Khin, Andrea Wong — 2012-05-07

Abstract: The perspectives of patients and healthcare professionals towards breast cancer genetic tests that are becoming increasingly available is unexplored in Asians. We surveyed the interest and attitudes of 200 breast cancer patients, 67 cancer physicians, 485 medical students and cancer researchers towards three genetic tests, BRCA1/2 mutation, CYP2D6 genotype and Oncotype DX testing, using hypothetical scenarios. Approximately 60% of patients expressed initial interest in each genetic test, although the majority reversed their decisions once test limitations were conveyed, with <15% maintaining interest in each test. Cancer physicians were most likely to recommend BRCA1/2 mutation testing (73%) and least likely to recommend CYP2D6 genotyping (12%), while patients were more likely to choose Oncotype DX testing (28%) over CYP2D6 (21%) and BRCA1/2 testing (15%). Cost concerns, low educational level and lack of prior awareness of genetic testing were the main barriers against breast cancer genetic testing among Asian patients.

Toll-like receptors gene polymorphisms may confer increased susceptibility to breast cancer development - Corrected Proof

2012-05-04

Abstract: Toll-like receptor (TLR) activation may be an important event in tumor cell immune evasion. TLR2 and TLR4 gene polymorphisms have been related to increased susceptibility to cancer development in various organs.261 patients and 480 health individuals were investigated for genotype and allelic frequencies of a 22-bp nucleotide deletion (−196 to −174del) in the promoter of TLR2 gene as well as two polymorphisms causing amino acid substitutions (Asp299Gly and Thr399Ile) in TLR4 gene.As far as (−196 to −174del) in TLR2 gene is concerned ins/del and del/del genotypes and del allele were significantly more frequent in breast cancer patients compared to healthy controls. Considering Asp299Gly replacement of TLR4 gene, Gly carriers (Asp/Gly & Gly/Gly genotype) and Gly allele were overrepresented among the breast cancer cases.The −174 to −196del of TLR2 gene and Asp299Gly of TLR4 gene polymorphisms may confer an increased susceptibility to breast cancer development.

Sequential versus concurrent anthracyclines and taxanes as adjuvant chemotherapy of early breast cancer: A meta-analysis of phase III randomized control trials - Corrected Proof

2012-04-30

Abstract: Purpose: We performed a meta-analysis of Phase III randomized trials to compare treatment outcomes for early-stage breast cancer patients receiving adjuvant chemotherapy with sequential or concurrent anthracyclines and taxanes.Methods: All Phase III randomized trials comparing adjuvant chemotherapy of sequential or concurrent anthracyclines and taxanes in early-stage breast cancer patients were considered eligible. A total of three trials that enrolled 8728 women were analyzed. A pooled analysis was accomplished and event-based risk ratios (RR) with 95% confidence intervals (95%CI) were derived. The significant differences in disease-free survival (DFS) and overall survival (OS) were explored. A heterogeneity test was applied as well.Results: Among three eligible trials, significant differences in favor of sequential regimen were seen in DFS (RR: 0.90; 95%CI: 0.84 to 0.98; P = 0.01) and in OS (RR: 0.88; 95%CI: 0.79 to 0.98; P = 0.02).Conclusion: Considering all the available Phase III trials, sequential adjuvant chemotherapy for early breast cancer seems to add a significant benefit in both DFS and OS over concurrent regimens.

High Ki67 expression is a risk marker of invasive relapse for classical lobular carcinoma in situ patients - Corrected Proof

2012-04-23

Abstract: Background: The clinical management of lobular carcinoma in situ lesions remains challenging. Our aim was to evaluate the risk of relapse for lobular carcinoma in situ (LCIS) patients, diagnosed on mammography performed for microcalcifications and according to proliferation assessed by Ki67 staining.Methods: A series of 47 patient's files with LCIS and followed in our institution were retrospectively selected. All patients underwent lumpectomy without radiation therapy. The expression of E-cadherin, estrogen receptor (ER), progesterone receptor (PR), EGFR and Ki67 were determined. Four different classes were then defined with the following criteria: ER+ and Ki67 ≤ 10%; ER+, Ki67 > 10%; ER−; ER-PR− and EGFR+.Results: Patient's mean age was 51.3 yrs. The majority of the lesions were classical LCIS (97%). All cases were E-cadherin either negative (71%) or weak and incomplete (29%). Among the 44 evaluable cases, 34 cases were ER or PR positive with KI67 ≤ 10% (79%), 9 cases ER positive with KI67 > 10% (21%), 1 case was ER and PR negative and expressed EGFR. At five years, all patients were alive, 1/34 ER positive and Ki67 low experienced a relapse contrasting with 3 out of 9 ER positive and Ki67 high (3 invasive carcinomas including 2 ductal and 1 lobular) (p = 0.0054).Conclusion: In this retrospective study, we observed a higher risk of relapse associated with a high proliferative activity of classical LCIS. If confirmed in larger series, this observation suggests that radiation therapy or hormonotherapy could be discussed for patients with Ki67 high classical LCIS in order to decrease their risk of relapse.

Metastatic breast cancer: We do need primary cost data - Corrected Proof

J. Bonastre, P. Jan, Y. Barthe, S. Koscielny — 2012-04-23

Abstract: The lifetime cost of metastatic breast cancer is a key component for the economic evaluations of targeted therapies and biomarkers. In the literature, only few cost studies are available and provide discordant cost estimates for the management of metastatic recurrences. Our objective was to assess the lifetime costs of metastatic breast cancer and to investigate cost variability using primary cost data. We used individual data from a cohort of 290 French women treated at the Gustave Roussy Institute and who had died between 2005 and 2008. We separately analysed the determinants for survival after metastatic recurrence and for the monthly cost using two different models. The mean survival time after recurrence was 24.8 months. The mean hospital cost per patient amounted to € 36,516 and the mean cost per month € 3764. We identified three prognostic factors: age at breast cancer diagnosis, the histological grade and the site of the first recurrence. The factors significantly associated with the cost per month were hospitalisation in a palliative care unit, trastuzumab treatment, the number of sites of recurrence and whether or not the patient had died during the last hospital stay. We identified cost drivers of the lifetime costs of metastatic breast cancer. This provides useful information for the design of future economic studies. We also provide cost estimates in homogeneous subgroups of patients defined by patient characteristics and by the type of care received.

Increased mean corpuscular volume of erythrocytes predicts the response to metronomic cyclophosphamide, capecitabine and bevacizumab treatment: Is it true for capecitabine treatment or more? - Corrected Proof

Cagatay Arslan, Kadri Altundag — 2012-04-23

We read with great interest the article by Dellapasqua et al. about the increased erythrocyte mean corpuscular volume (MCV) with metronomic cyclophosphamide, capecitabine and bevacizumab treatment as a predictor of response. The authors had found that 61% (42 of 69) of the metastatic breast cancer patients developed macrocytosis on the 24th week of the treatment and had chosen that time point as a landmark on which patient rate had reached a plateau for macrocytosis (MCV ≥ 100 fl). Time to progression was longer among patients who developed macrocytosis than patients who did not (72 vs. 43 weeks).

Axillary and systemic treatment of patients with breast cancer and micrometastatic disease or isolated tumor cells in the sentinel lymph node - Corrected Proof

2012-04-20

Abstract: Background: After introduction of sentinel node biopsy (SNB) in patients with breast cancer a higher proportion of micrometastases and isolated tumor cells are being detected. Prognostic impact and clinical relevance of this minimal nodal involvement is under debate and substantial variation in the use of axillary surgery and/or systemic adjuvant treatment could be expected.Methods: Data from the population-based Eindhoven Cancer Registry were used on all (n = 9038) women who underwent SNB for invasive breast cancer from 1996 to 2008 and medical files were studied to determine the role of minimal nodal involvement in the decision to use adjuvant systemic treatment.Results: Forty-five percent of 172 patients with isolated tumor cells and 76% of 605 patients with micrometastases received adjuvant systemic treatment. Thirty-five of 59 patients with isolated tumor cells and 153 of 193 patients with micrometastases received systemic therapy based on primary tumor characteristics. The remainder probably received adjuvant therapy based on presence of minimal nodal involvement. Thirty-seven percent of the patients with isolated tumor cells underwent an axillary lymph node dissection compared to 75% when micrometastases were present. Multivariate analyses showed a significantly higher chance of receiving systemic treatment when isolated tumor cells (OR 1.5 (95% CI, 1.05–2.15)) or micrometastases (OR 10.7 (95% CI, 8.56–13.27)) were present, compared to a negative lymph node status.Conclusion: The debate on necessity of performing completion ALND and administration of systemic therapy in patients with minimal nodal involvement is reflected by the treatment patterns observed in our population-based study.Synopsis: Describing time-trends and predictors of axillary and systemic treatment of patients with breast cancer and micrometastases or isolated tumor cells in their sentinel lymph node(s).

Immediate breast reconstruction with prostheses after conservative treatment plus intraoperative radiotherapy. Long term esthetic and oncological outcomes - Corrected Proof

2012-04-19

Abstract: Electron intraoperative radiotherapy (ELIOT) has been introduced for breast conservative treatment (BCT) with promising oncological outcome. Thus, immediate breast reconstruction with prosthesis after BCT became possible due to minimal radiation effect on local tissue from ELIOT. We reported oncological and esthetical results of 29 BCT patients who had immediate implant reconstruction plus 21 Gy-ELIOT as the sole radiation treatment. All patients had prosthesis in ipsilateral breast and had simultaneous contralateral augmentation for symmetrical procedure. The average age was 52.3 years. There were stage Ia thirteen cases, stage Ib seven cases, stage IIa six cases and stage IIIb one case and two cases of intraepithelial neoplasia. From 54.2 (36–88) months follow up, the capsular contracture grading in the reconstructed breast from ELIOT-side is comparable with non-irradiated contralateral side. There was one patient who developed local recurrence (LR) and later on dead with breast related event (LR = 0.76% per year). There was no primary ipsilateral carcinomas and distant metastasis.

Alcohol, acetaldehyde and breast cancer risk - Corrected Proof

Bernard Friedenson — 2012-04-18

The study of Wang et al is valuable even though it conflicts with clear biochemistry that predicts elevated breast cancer risks associated with alcohol intolerant genotypes. BRCA1/2 mutation carriers may be unduly susceptible. Why has this been so difficult to demonstrate and why do studies conflict? Other genes may be involved but dietary and environmental acetaldehyde could easily be confounders. Some alcoholic beverages have dangerously high levels of acetaldehyde. Even some “non-alcoholic” beverages and food produced or preserved by fermentation contain small amounts of ethanol and high, mutagenic (>100 mM) concentrations of acetaldehyde. These include dairy products like yogurts, fermented soy products (e.g. soy sauces), tofu, fermented vegetables (e.g. Chinese pickles and kimchi), vinegar and homemade beers. Ethanol can reach 300 mM and acetaldehyde can reach 3500 mM, far above mutagenic levels. Poor oral hygiene amplifies cancer risks further. Worldwide screening for thousands of foods for dangerously high acetaldehyde levels has already been advocated.

Secretory carcinoma of the breast: Results from the survival, epidemiology and end results database - Corrected Proof

2012-04-12

Abstract: Background: Secretory carcinoma of the breast is a rare breast cancer that is associated with incidence at a young age and an indolent course. The role for breast conservation and adjuvant radiation is unknown.Methods: The SEER database was reviewed and 83 patients were identified with secretory carcinoma of the breast between the years 1983 and 2007. Baseline characteristics were compared with χ2 or Fisher’s exact test. Overall survival (OS) and cause-specific survival (CSS) were estimated using the Kaplan–Meier method. Analyses were performed using PASW Statistics, version 18.Results: Median follow-up was 70 months. Median patient age was 53 years (range 11–86 years). 29 patients (34.9%) had involved regional lymph nodes. 39 patients (47.0%) underwent lumpectomy and 44 patients (53.0%) underwent mastectomy. 35 patients (42.2%) received radiation. Patients receiving radiation were more likely to have undergone lumpectomy, and the use of radiation increased over time. 5-year OS was 87.2%; 10-year OS was 76.5%. 5-year CSS was 94.4%; 10-year CSS was 91.4%. Among the lumpectomy patients, 25 patients (64.1%) received radiation. For lumpectomy patients, those who did not receive radiation had a 5-year OS of 92.9% and 10-year OS of 72.2% while patients who did receive radiation had a 5-year OS of 95.5% and 10-year OS of 85.9%. Only 1 patient treated with lumpectomy only died of cancer (92.9% CSS) and no patients treated with lumpectomy and radiation died of cancer (100% CSS).Conclusions: Secretory carcinoma of the breast commonly occurs at a later age than previously recognized, and is associated with good long-term survival.

Breast reconstruction using permanent BeckerTM expander implants: An 18 year experience - Corrected Proof

S.C.J. Goh, A.L. Thorne, G. Williams, S.A.M. Laws, R.M. Rainsbury — 2012-04-12

Abstract: Background: Single-stage reconstruction using permanent expander implants is an established technique following mastectomy. Short and long-term outcome data following breast reconstruction using Becker™ tissue expanders is limited.Method: A retrospective case note review of patients undergoing expander-based procedures between 1989 and 2007 was undertaken. Data recorded included postoperative symptoms and complications, the use of radiotherapy, revisional surgery, and device failure.Results: Three hundred and thirteen expanders were used in 276 patients with a mean age of 48.3 (17–78) years, over the 18 year study period. The mean follow up period was 64.6 (1–199) months. 256 Becker™ expanders were used during 175 latissimus dorsi (LD) and 52 subpectoral (SP) reconstructions, 13 contralateral augmentations and 16 implant replacements. The postoperative infection rate was 5.8%, leading to an expander loss rate of 3.8%. The use of prophylactic antibiotics was associated with an increased postoperative infection rate (p = 0.046). Six haematomas (2.5%) and 12 cases of skin envelope necrosis (5.0%) required unscheduled intervention.Symptoms of pain, distortion and hardness were experienced by 21.3% of patients, and radiotherapy was associated with a significantly higher risk of adverse symptoms (p < 0.0001). No patient developed symptomatic implant rupture or silicone granuloma but 17.9% of reconstructions underwent revisional surgery, the rate being highest following SP reconstruction (p = 0.029). Nine patients developed injection port complications (3.8%), and the overall device failure rate was 1.3%. The original expander has been retained by 74.2% of women.Conclusion: The Becker™ permanent expander is a reliable implant associated with a low complication rate and a high retention rate when used during breast reconstruction.

Quantifying the number of lymph nodes identified in one-stage versus two-stage axillary dissection in breast cancer - Corrected Proof

Olaf E. Damgaard, Maj-Britt Jensen, Niels Kroman, Tove F. Tvedskov — 2012-04-11

Abstract: Purpose: To establish whether a different number of lymph nodes is identified in a delayed versus an immediate axillary lymph node dissection (ALND) in breast cancer patients.Methods: Using data from the Danish National Patient Register and the Danish Breast Cancer Cooperative Group Database we identified 864 breast cancer patients with sentinel lymph node dissection (SLND) and delayed ALND and 7393 breast cancer patients with SLND and immediate ALND operated between 2002 and 2010. We compared the number of lymph nodes identified in the two groups by a student's t-test.Results: The mean number of lymph nodes identified in patients with immediate and delayed ALND was 16.55 and 15.59, respectively. This difference was statistically significant (P < 0.0001).Conclusion: The number of lymph nodes identified in breast cancer patients is slightly reduced if delayed ALND is performed. However, the difference is small and considered to be without clinical significance.

Survival and clinicopathological characteristics of breast cancer patient according to different tumour subtypes as determined by hormone receptor and Her2 immunohistochemistry. A single institution survey spanning 1998 to 2010 - Corrected Proof

2012-04-09

Abstract: As far as recent breast cancer molecular subtype classification is concerned, much work has dealt with clinical outcomes for triple negative and Her2 patients. Less is known about the course of patients in the remaining subtypes. Molecular classification based on immunohistochemistry is widely available and correlates well with genetic microarray assessment, but at a lower cost. The aim of our investigation was to correlate immunohistochemical subtypes of breast cancer with clinical characteristics and patient outcomes.Since 1998, 1167 patients operated for 1191 invasive breast tumours were included in our database. Patients were regularly followed up until March 2010. Disease-free survival, overall mortality, and breast cancer-specific mortality at 5 years were calculated for the cohort.72% of tumours were ER+PR±HER2− group, 13% triple negative (ER−PR−HER2−), 10% ER+PR±HER2+ group, and 5% Her2 (ER−PR−HER2+). Cancer-specific survival was 94.2% for the ER+PR+HER2− subtype, 84.8% for the Her2 subtype, 83.3% for the ER+PR−HER2− subtype, and 78.6% for triple negatives. Distant metastases prevalence ranged from 7% to 22% across subtypes, increasing stepwise from ER+PR+HER2−, ER+PR+HER2+, ER+PR−HER2−, ER+PR−HER2+, ER−PR−HER2+ through triple negative. Small, low-grade tumours with low axillary burden were more likely to belong to the ER+PR±HER2− group. Conversely, larger high-grade tumours with significant axillary burden were more likely to belong to Her2 or triple negative groups. ER+PR±HER2− group patients with negative PR receptors performed more like Her2 or triple negative than like the rest of ER+PR±HER2± groups patients.Molecular classification of breast tumours based only on immunohistochemistry is quite useful on practical clinical grounds, as expected. ER+PR±HER2− group patients with negative PR receptors seem to be at high risk and deserve further consideration.

Immunohistochemical features of claudin-low intrinsic subtype in metaplastic breast carcinomas - Corrected Proof

2012-04-05

Abstract: Purpose: The claudin-low molecular subtype of breast cancer includes triple negative invasive carcinomas, with a high frequency of metaplastic and medullary features. The aim of this study was to evaluate the immunohistochemistry expression of claudins in a series of metaplastic breast carcinomas. We also assessed other claudin-low features, such as the cancer stem cell-like and epithelial-to-mesenchymal transition phenotypes.Results: The majority of the cases showed weak or negative staining for membrane claudins expression. We found 76.9% (10/13) low expressing cases for claudin-1, 84.6% (11/13) for claudin-3 and claudin-4, and 92.3% (12/13) for claudin-7. Regarding the cancer stem cell marker ALDH1, 30.8% (4/13) showed positive staining. We also showed that the majority of the cases presented a CD44+CD24−/low phenotype, positivity for vimentin and lack of E-cadherin expression. Interestingly, these claudin-low molecular features were specific of the mesenchymal component of metaplastic breast carcinomas, since its frequency was very low in other breast cancer molecular subtypes, as luminal, HER2-overexpressing and non-metaplastic triple negative tumors.Conclusions: The negative/low expression of claudins and E-cadherin, high levels of vimentin, and the breast cancer stem cell phenotype suggests that metaplastic breast carcinomas have similar features to the ones included in the claudin-low molecular subtype, specially their mesenchymal components.

Breast cancer related lymphedema in patients with different loco-regional treatments - Corrected Proof

2012-03-29

Abstract: Introduction: Lymphedema, a sequela of breast cancer and breast cancer therapy, changes functional abilities and may affect a patient's psychosocial adjustment and overall quality of life. Aim of this prospective observational study was to determine the rate of mid-term and late time period lymphedema in breast cancer patients with different loco-regional treatments, and factors associated with lymphedema.Materials and methods: Patients surgically treated for early-stage breast cancer were prospectively enrolled in the study. Demographic, clinical, pathological, and loco-regional treatments data of patients and lymphedema rates were recorded. Patients were divided into six groups regarding different loco-regional treatments. Pre- and postoperative (12 months, and median 64 months after surgery) circumferences of arms were recorded.Results: 218 patients, all female with a median age of 48 (19–82) years, were included in the study. The numbers of patients in breast conservation surgery group (BCS) (N = 104), mastectomy group (N = 114), sentinel lymph node biopsy group (SLNB) (N = 80), axillary lymph node dissection group (ALND) (N = 138), group with radiotherapy (RT) (N = 88) and group without radiotherapy (N = 130). Incidence of lymphedema after surgery in mid-term period was 24.8%. The rate of lymphedema at 64 months median follow-up time was 7.3%. (BCS: 11.1%, 4.2% and 0.5%; Mastectomy: 15.0%, 3.2% and 1.4%; SLNB: 8.0%, 1.9% and 0.5%; ALND: 18.0%, 5.3% and 1.4%; RT: 14.7%, 6.3% and 1.4%; without RT: 11.4%, 2.1% and 0.5%). When we excluded patients with both mid-term and late term lymphedema, only four patients developed lymphedema at late time, then re-calculated late term lypmhedema rate was 1.8%. The factors affecting the lymphedema was ALND and radiotherapy (RT) and no lymphedema was detected in patients underwent breast conserving surgery and SLNB. Age and body mass index were not related to lymphedema at any time.Conclusion: The incidence of lymphedema gradually increased in time and a quarter of patients experienced the complication at the end of year. The rate of lymphedema in patients with ALND was significantly higher than patients with SLNB alone. If RT added to SLNB the lymphedema rate was getting higher than SLNB alone. In all patients lymphedema rate was decreased one year after the surgery and further decreased at median 64 months follow-up time period.

A comparison of surgical and radiotherapy breast cancer therapy utilization in Canada (British Columbia), Scotland (Dundee), and Australia (Western Australia) with models of “optimal” therapy - Corrected Proof

2012-03-19

Abstract: Background: Different jurisdictions report different breast cancer treatment rates. Evidence-based utilization models may be specific to derived populations. We compared predicted optimal with actual radiotherapy utilization in British Columbia, Canada; Dundee, Scotland; and Perth, Western Australia.Design: Data were analyzed for differences in demography, tumor, and treatment. Epidemiological data were fitted to published Australian optimal radiotherapy utilization trees and region-specific optimal treatment rates were calculated. Optimal and actual surgery/radiotherapy rates from 2 population-based and 1 institution-based registries were compared for patients diagnosed with breast cancer between 2000 and 2004, and 2002 for British Columbia.Results: Mastectomy rates differed between British Columbia (40%), Western Australia (44%), and Dundee (47%, p<0.01). Radiotherapy rates differed between British Columbia (60%), Western Australia (52%), and Dundee (49%, p<0.01). Actual radiotherapy utilization rates were lower than optimal estimates.Region-specific optimal utilization rates at diagnosis varied from 57% to 71% for radiotherapy and 62% to 64% when taking into account patient preference. Variation was attributed to local differences in demography and tumor stage.Conclusions: Actual treatment rates varied, and were associated with patterns of care and guideline differences. Actual radiotherapy rates were lower than optimal rates. Differences between optimal and actual utilization may be due to access shortfalls, and patient preference.

1st International consensus guidelines for advanced breast cancer (ABC 1) - Corrected Proof

2012-03-19

Abstract: The 1st international Consensus Conference for Advanced Breast Cancer (ABC 1) took place on November 2011, in Lisbon. Consensus guidelines for the management of this disease were developed. This manuscript summarizes these international consensus guidelines.

Dose-dense chemotherapy versus conventional chemotherapy for early breast cancer: A systematic review with meta-analysis - Corrected Proof

2012-03-16

Abstract: Background: Despite the widespread acceptance of dose-dense (DD) regimens as adjuvant chemotherapy for early breast cancer (EBC), studies of efficacy offer contradictory findings. This systematic review evaluates the real impact of DD chemotherapy.Methods: Randomized controlled trials comparing conventional adjuvant chemotherapy versus a DD regimen for EBC patients were searched in electronic databases. Dose-dense regimens included the same drugs and total amount as conventional chemotherapy, but applied in shorter intervals. Meta-analyses were performed using a fixed-effects model. Hazard ratios (HRs) or odds ratios (ORs) were expressed with 95% confidence intervals (95% CI). The outcomes were overall survival (OS), disease-free survival (DFS), and toxicities. Analyses were conducted according to tumor hormone receptor expression, plus tests for interaction.Results: Four studies (3418 patients) were included. The meta-analysis demonstrated that DD therapy can improve DFS (3356 patients; HR = 0.83; 95% CI 0.73–0.95; p = 0.005), independent of hormone receptor expression status. There was no OS benefit with DD therapy (3356 patients; HR = 0.86; 95% CI 0.73–1.01; p = 0.06) irrespective of tumor hormone receptor status (OS in hormone-positive stratum HR = 0.94; 95% CI 0.74–1.21; OS in hormone-negative stratum HR = 0.78; 95% CI 0.62–0.99; interaction test p = 0.28). DD regimens caused a small increase in anemia and mucositis, but had no impact on cardiac events, leukemia or myelodysplasia.Conclusions: DD adjuvant chemotherapy can improve DFS of EBC patients with little impact on safety. However there is no clear benefit in OS. Further research may indicate if there is any impact on OS not presently seen due to small sample size, and which patients may derive greater benefit.

Primary chemo-radiotherapy in the treatment of locally advanced and inflammatory breast cancer - Corrected Proof

2012-03-14

Abstract: Background: The best management of large, diffuse or inflammatory breast cancers is uncertain and the place of radiotherapy and/or surgery is not clearly defined.Methods: A cohort of 123 patients with non-metastatic locally advanced or inflammatory breast cancer 3cm or more in diameter or T4, was treated between 1989 and 2006. All patients received primary chemotherapy followed by radiotherapy, 40Gy in 15 fractions with 10Gy boost. Patients with ER positive tumours received Tamoxifen. Assessment was carried out 8 weeks post-treatment and surgery was reserved for residual or recurrent disease.Results: For each stage there were T2/3: 63, T4b: 31 and T4d: 29 patients. 80 had complete clinical response (65%) but 18 patients were never free of inoperable local disease. 25 patients had residual operable disease at assessment and 12 patients who initially had a complete response developed operable local recurrence (LR). 37 Patients (30%) had surgery at a mean of 15 months post diagnosis. At 5 years, overall survival (OS) of the two surgical groups was not significantly different from those 68 patients who had complete remission without surgery, p=0.218, HR 1.46 (0.80–2.55). Surgery as an independent variable to predict survival was not significant on a Cox proportional hazards model (p=0.97). LR in the surgical groups was 13.5% vs 17.5% in the non-surgical patients. The median OS was 64.5 months and disease-free survival (DFS) was 52.5 months. 5-Year OS was 54% and DFS survival 43%.Conclusion: In patients with a complete or partial response to chemo-radiotherapy for locally advanced or inflammatory breast cancer, reserving surgery for those with residual or recurrent local disease did not appear to compromise survival. This finding would support examination of this treatment strategy by a randomised controlled trial.

Inter- and intra-tumoral heterogeneity in DNA damage evaluated by comet assay in early breast cancer patients - Corrected Proof

2012-03-14

Abstract: There are no clinical tools to functionally assess degree of DNA damage in breast cancer. The comet assay is an accepted research tool for assessing DNA damage, however, most cancer studies have assessed lymphocytes as surrogate cells. The aim of this pilot study was to use the comet assay in early breast cancer directly in tumor tissue to compare DNA damage between and within traditionally defined subgroups, and to explore intra-tumoral heterogeneity. Scrapings of tumor and healthy breast tissue were obtained at primary surgery from 104 women. Comet assay was applied to quantitatively assess DNA damage, revealing substantial inter- and intra-subgroup variation. Marked intra-tumoral heterogeneity was evident across all subgroups. The degree of DNA damage for an individual could not be predicted by breast cancer subgroup. Comet assay warrants further study as a potential clinical tool for identification of tumoral DNA damage and ultimately, individualised use of DNA damaging therapy.

The template technique for breast mound planning when using abdominal flaps for breast reconstruction - Corrected Proof

Ashley Tregaskiss, Pieter V. Vermaak, Richard Boulton, Robert J. Morris — 2012-03-14

Abstract: Delayed breast reconstruction with abdominal flaps typically involves a process of ‘trial and error’ when moulding the flap into a satisfactory breast mound. This moulding process is crucial to the final aesthetic result. We present a template technique to preoperatively plan the skin envelope of each reconstruction. Templates are quick and simple to construct, and are tailor-made based on several measurements from the contralateral breast. The technique is versatile and can be adjusted for use with Wise-pattern breast reduction or mastopexy. In our experience, the template technique reliably attains natural shape and good symmetry when compared with unplanned flap moulding.

Factors predicting the non-sentinel lymph node involvement in breast cancer patients with sentinel lymph node metastases - Corrected Proof

D.E. Boler, C. Uras, U. Ince, N. Cabioglu — 2012-03-14

Abstract: Objective: In a significant proportion of patients, the sentinel lymph node (SLN) is the only involved axillary node. The goal of the present study was to identify predictive factors associated with a positive SLN and with a positive non-SLN in patients in whom axillary lymph node dissection (ALND) was performed.Methods: Data was reviewed for patients with T1–2 invasive breast cancer who underwent SLN biopsy with or without axillary dissection in a single institution between July 2000 and May 2010. The SLNs were examined by serial sectioning and H&E staining, and by cytokeratin immunostaining in suspicious cases.Results: Of 332 patients with SLNB, 134 had SLN positivity, and 116 of them further underwent completion axillary dissection. Patients with T2 tumors (OR=3.2; 95% CI, 1.74–5.58), or tumors with lymphovascular invasion (OR=8.0; 95% CI, 4.44–14.27), or invasive ductal cancer (OR=2.92; 95% CI, 1.1–8.0) were more likely to have a positive SLN. In patients with ALND, the non-SLN involvement rates were 10%, 11.5% and 50% in patients with isolated tumor cells (ITC), micrometastasis and macrometastasis, respectively. Finding of ITC or micrometastasis in SLNs (OR=0.28; 95% CI, 0.08–0.99) or presence of extracapsular invasion (ECI) in SLN (OR=0.24; 95% CI, 0.09–0.67) were the predictive factors of not having a non-SLN metastasis in logistic regression analysis.Conclusions: These findings suggest further axillary surgery can be best omitted in patients with micrometastasis while validation of nomograms including factors such as ECI are still needed to be studied in patients with macrometastasis.

Prognosis of breast cancer in patients with peritoneal metastasis - Corrected Proof

2012-03-09

Metastatic involvement of the peritoneum and its related structures in breast cancer patients is rare. Metastasis to the peritoneum-retroperitoneum was shown to be higher in lobular carcinoma, i.e. 3.1% vs 0.6% for lobular and ductal breast cancer, respectively. There are few studies which have collected such cases within the context of an analysis, in order to shed light on the optimal treatment strategies, prognosis and management of this rare presentation. We have searched the database of Hacettepe University Oncology hospital for breast cancer patients with peritoneal metastasis. The demographic information, histological subtype, tumor receptor status, and stage were collected. The CT images of the patients were evaluated by the co-author of this paper. The follow up times data of patients were reviewed with respect to hormone receptor positivity and histological subtype.

Role of core needle biopsy in the treatment of radial scar - Corrected Proof

2012-03-09

Abstract: Invasive tumor or ductal carcinoma in situ occur in radial sclerosing lesions in one third of the cases therefore, surgical excision is mandatory.Forty-five patients with radial scar morphology were examined. Ultrasound guided fine-needle aspiration biopsy (FNAB) and core biopsy (CB) were performed in all cases. The postoperative pathological findings were compared to the results of preoperative biopsies.Sensitivity of preoperative percutaneous biopsies (FNAB and CB) was 17.6% and 70.6%, false-negative rate was 82.4% with FNAB and 29.4% with CB. The negative predictive value was 48.1% and 84.8% respectively. Had we done preoperative cytology only, we would have had to perform a two-step procedure (sentinel lymph node biopsy) in 7 patients (15.6%), while with preoperative core biopsy it has decreased to 2 patients (4.4%).Preoperative CB in small radial stellate lesions is recommended to achieve accurate diagnosis in order to avoid a two-step surgical procedures.

High prevalence of neuroendocrine carcinoma in breast lesions detected by the clinical symptom of bloody nipple discharge - Corrected Proof

2012-03-07

Abstract: Aim: Bloody nipple discharge (BND) is an important clinical symptom in breast disorders, especially cancers. However, the association between this symptom and breast neuroendocrine carcinomas (NECs) has not been sufficiently investigated or well understood.Methods: We clinicopathologically studied 89 cases using biopsy and/or resection in 144 patients who came to the hospital for a thorough examination of symptomatic BND.Results: Of these 89 cases examined histologically, 24 (27%) were neuroendocrine carcinomas (NECs) in which >50% of cells immuno-expressed chromogranin A and/or synaptophysin. Moreover, NECs made up 44% (24/55) of the mammary cancers found because of the BND. The frequency of diagnosing malignancy preoperatively in 24 NECs was 4% by nipple discharge cytology, 40% by fine needle aspiration cytology, 62% by core needle biopsy and 67% by mammotome biopsy. There were neither postoperative recurrences nor metastases in the NEC cases during a mean follow-up of 83.7 months. The 24 NECs were subclassified into neuroendocrine ductal carcinoma in situ (NE-DCIS) (9 cases) and microinvasive (7 cases) and invasive (8 cases) NECs with extensive NE-DCIS components. Most NECs had early-stage and low-grade pathological parameters: pTis or pT1 (96%), pN0 (96%), low nuclear grade (83%), absence of necrosis (88%), immuno-positivity of estrogen and progesterone receptors (100%) and absence of HER2 protein overexpression (100%).Conclusions: NECs predominantly with NE-DCIS lesions, often under-diagnosed preoperatively, accounted for an important share of breast conditions associated with BND. It is, therefore, worth keeping this type of breast cancer in mind when performing medical examinations on patients with BND.

Axillary management in breast cancer: What's new for 2012? - Corrected Proof

Hiram S. Cody, Nehmat Houssami — 2012-03-05

Abstract: Sentinel lymph node (SLN) biopsy has become standard care for management of the axilla in invasive breast cancer, replacing axillary lymph node dissection (ALND) in most subjects, with a progressively diminishing role of ALND. Advances in preoperative imaging have also changed the algorithm for axillary management, and ultrasound-guided needle biopsy has been shown to triage >50% of subjects with node metastases to ALND. However, the past two years have witnessed remarkable and practice-changing advances in our knowledge and approach to management of the axilla, with availability of high-level evidence that demands reappraisal of practice and challenges the role of routine ALND for SLN-positive patients. In particular, for the group of patients defined by eligibility criteria in the Z0011 trial, it appears that ALND has little or no effect on local recurrence and survival, or on the choice of local or systemic therapies. We review the available evidence on staging and management of the axilla in breast cancer, and outline our interpretation of its implications for clinical practice.

Radiofrequency thermoablation in locally advanced breast cancer - Corrected Proof

Giuseppe Santoro, Mario Avossa, Marcello Della Corte — 2012-03-05

Abstract: The authors report their experience of 8 cases of breast cancer in six patients, treated by radiofrequency thermoablation. Two patients had bilateral breast cancer infiltrating the skin. All patients, but one, were alive at two years follow-up. The age range was 54–75 years old (median, 71 years old). We observed complete regression in one patient, regression with residual scar in two patients and partial regression in the remaining three patients.The authors believe that radiofrequency, alone or associated with other treatments, is an easy and useful alternative for the management of breast cancer, in selected patient who cannot undergo surgery or refuse surgical treatment and other treatments.

Putative relationship between hormonal status and serum pyrrolidone carboxypeptidase activity in pre- and post- menopausal women with breast cancer - Corrected Proof

2012-03-02

Abstract: In breast cancer, hormonal changes are rather constant in post-menopausal women since they tend to vary only over long time spans. However, in pre-menopausal women, the development of breast cancer is associated with hormonal physiological variations. The aim of the present work was to analyse the changes in circulating levels of gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in pre- and post-menopausal women that were healthy or with breast cancer, and their connection to serum pyrrolidone carboxypeptidase (Pcp) activity. We observed significant changes in the hormonal profile in post-menopausal women with breast cancer compared to the control group. In pre-menopausal women, we found significant changes in circulating GnRH levels with respect to the healthy group. Our present results support the existence of neuroendocrine misregulation that could be involved in tumour progression, with Pcp being a potentially new pharmacological target in breast cancer treatments.

Alcohol and breast cancer - Corrected Proof

Helmut K. Seitz — 2012-03-01

Ethanol consumption is a major health problem worldwide and is responsible for more than 200 diseases. The World Health Organization (WHO) has calculated that alcohol accounts for approximately 1.8 million deaths per year (3.2% of all deaths) including addiction, liver cirrhosis and cancer. Epidemiology has convincingly shown that chronic alcohol ingestion is a significant risk factor for the development of cancer of the upper alimentary tract (oropharynx, larynx and oesophagus), for the colorectum, the liver and the female breast. Recently, the International Agency for Research on Cancer (IARC) has identified all alcoholic beverages as carcinogenic to humans and acetaldehyde (AA) as a carcinogen. Compared to other organs, the breast seems especially sensitive towards the carcinogenic action of ethanol as breast cancer risk starts already at very low daily ethanol consumption without any threshold. As ethanol use is widespread and breast cancer is the most frequent cancer in women in USA and in Europe, alcohol as a risk factor for breast cancer is of public concern. In contrast to the liver and the upper gastrointestinal tract, mechanisms by which ethanol stimulates mammary carcinogenesis are still unclear, complex and not well understood.

What factors may influence psychological well being at three months and one year post BRCA genetic result disclosure? - Corrected Proof

2012-03-01

Abstract: Genetic testing for breast cancer predisposition has been available in the clinical practice for more than a decade. How the result of genetic testing affects the psychological well-being of the individuals is an under-researched area in many populations. Follow-up analysis of psychological well-being via HADS scale was performed in 364 individuals at 3 months and 1 year after the disclosure of BRCA1/2 genetic result. We analyzed potential predictors for pathological anxiety and variables associated to the variation of HADS scores over time. At pre-test only 16% and 4% of individuals presented symptoms of anxiety and depression, respectively. Having a prior diagnosis of cancer and presenting a pathological HADS-A score at the baseline were associated with clinically significant anxiety scores at one year, but the genetic test result was not. Thus, BRCA genetic testing does not influence short and long term anxiety and depression levels among those identified as mutation carriers. It is our task to demystify the allegedly negative impact of BRCA testing on psychological well being to increase the uptake of genetic testing and benefit those who are at high risk of developing breast, ovarian and prostate cancer.

Socio-demographic factors and reasons associated with delay in breast cancer presentation: A study in Nigerian women - Corrected Proof

N.A. Ibrahim, M.A. Oludara — 2012-03-01

Abstract: We evaluated the effects of selected socio-demographic factors on late presentation and reasons why our breast cancer patients delay reporting for treatment. All female breast cancer patients referred to one of the general surgery out-patient clinics of Lagos State University Teaching Hospital between January 2009 and December 2010 were interviewed. Relevant socio-demographic and clinical data were obtained and reasons for patient delay documented. Univariate and multivariate logistic regression analyses were conducted to calculate odd ratio for delay. A total of 201 patients were enrolled. Mean duration of symptoms was 12.12 months (SD ± 5.18). Delay for more than 3 months before initial medical consultation was observed in 164 patients (81.6%). Increased risk of late presentation was associated with single women (OR = 2.054), primary level of education (OR = 3.059), negative history of benign breast disease (OR = 1.648) and pre-menopause (OR = 1.861). Ignorance of the nature of illness, belief in spiritual healing, fear of mastectomy and belief in herbal treatment were the leading reasons for delay. Women with higher risk of late presentation should be the target group during interventions aimed at raising breast cancer awareness. Reasons for patient delay should also be addressed.

Post-mastectomy pain syndrome: Incidence and risks - Corrected Proof

2012-02-29

Abstract: Background: Post-mastectomy pain syndrome is defined as a chronic pain that persists beyond the normal healing time of 3 months. It is considered a neuropathic condition that arises after surgery for breast cancer.Aim: To evaluate the incidence and risk factors of pain syndromes in patients undergoing surgical treatment of breast cancer in the National Cancer Institute.Methods: This study is a prospective cohort of women undergoing surgical treatment for breast cancer from September 2008 to June 2009, followed up until 6 months postoperatively.Results and conclusions: One hundred seventy-four women were examined. The mean age was 58 years. The incidence of pain syndrome was 52%. Younger women (<40 years) and those who were submitted to axillary lymph node dissection (with more than 15 lymph nodes excised) have shown a significantly increased risk of pain syndrome after surgery for breast cancer (relative risk (RR) = 5.23 95% confidence interval (CI): 1.11–24.64) and (RR = 2.01 95% CI: 1.08–3.75).

7-year follow up of intra-operative radiotherapy for early breast cancer in a developing country - Corrected Proof

K.J. Baatjes, J.P. Apffelstaedt — 2012-02-29

Abstract: Scarce radiation resources and an often poor, rural population make single fraction, definitive intra-operative radiation (IORT) ideal for developing countries. From 2002 to 2005 IORT in breast conservation was administered utilizing existing infrastructure in an extremely resource-restricted environment.After tumor excision an applicator was introduced into the tumor bed. An existing Ir 192 after loader delivered a single fraction (21 Gy).Of thirty nine patients treated with 84 months follow-up, one patient suffered local, four regional and three systemic relapse. One patient died of disease, 2 of unrelated causes for a local control rate of 95% and a disease-specific survival of 95%. Cosmetic outcome was perceived excellent.IORT using existing after loaders and a low cost applicator greatly reduced health care resources. This extends breast conservation to indigent patients who cannot adhere to lengthy EBRT protocols.

Lifestyle factors associated with serum N-3 fatty acid levels in breast cancer patients - Corrected Proof

Zora Djuric, Jianwei Ren, Patrick R. Brown, Jennifer S. Ellsworth, Ananda Sen — 2012-02-29

Abstract: Long chain n3 fatty acids appear to have beneficial effects in several domains of health relevant to breast cancer survivors. This study evaluated inter-individual differences in serum levels of n3 fatty acids in 40 breast cancer patients who were participating in a pilot study for prevention of weight gain. Significant predictors of baseline n3 fatty acid levels in serum were dietary intakes of n3 fatty acids, BMI, serum levels of carotenoids and TV hours watched/day, accounting for 43% of the variance. Counseling for prevention of weight gain also tended to increase n3 fatty acid blood levels over time during chemotherapy.

Lack of association of ADH1C genotype with breast cancer susceptibility in Caucasian population: A pooled analysis of case–control studies - Corrected Proof

Liping Wang, Ying Zhang, Dapeng Ding, Xiaofeng He, Zhenglan Zhu — 2012-02-22

Abstract: Purpose: Recent epidemiological studies demonstrated that alcohol dehydrogenase 1C (ADH1C) alleles that result in acetaldehyde accumulation in the cells can enhance a drinker’s risk of developing alcohol related cancer in a variety of tissues. The published data on the association between ADH1C alleles and breast cancer occurrence in Caucasians have led to in contradictory results. This meta-analysis of literatures was performed to derive a more precise estimation of the relationship.Methods: A total of 12 studies were identified to the meta-analysis, including 6159 cases and 5732 controls from Caucasians. The pooled odds ratio (OR) with 95% confidence interval (CI) for breast cancer risk associated with ADH1C genotype was estimated.Results: Overall, no significantly elevated breast cancer risk was found in all genetic models when all studies were pooled into the meta-analysis (ADH1C1-2 vs. ADH1C2-2: OR 1.07, 95% CI 0.97–1.19; ADH1C1-1 vs. ADH1C2-2: OR 1.16, 95% CI 0.94–1.43; dominant model: OR 1.07, 95% CI 0.97–1.18; recessive model: OR 1.06, 95% CI 0.93–1.20). There was no evidence for the association between ADH1C genotype and breast cancer risk in subgroup analyses based on design of experiment and menopausal status. And for the additive model, individuals carrying the ADH1C*1 allele were not significantly associated with increased risk to breast cancer (OR 1.01, 95% CI 0.97–1.06).Conclusion: This meta-analysis suggests that ADH1C polymorphism may not be associated with breast cancer development in Caucasians. And larger scale primary studies are required to further evaluate the interaction of ADH1C polymorphism and breast cancer risk in specific populations.

Factors associated with long-term functional outcomes and psychological sequelae in women after breast cancer - Corrected Proof

Fary Khan, Bhasker Amatya, Julie F. Pallant, Ishani Rajapaksa — 2012-02-20

Abstract: The objective of this study was to examine factors impacting long-term functional outcomes and psychological sequelae in survivors of breast cancer (BC). A clinical assessment and structured interview assessed the impact of BC on participants’ (n = 85) current activity and restriction in participation, using validated questionnaires: Functional Independence Measure (FIM), Perceived Impact Problem Profile (PIPP) and Depression Anxiety Stress Scale (DASS). Participants showed good functional recovery (median motor FIM score = 78). Three-quarters (74%) reported pain, 32% reported upper limb weakness, 31% pain limiting shoulder movement and 29% lymphoedema. One third (32%) reported greatest impact on psychological wellbeing. A substantial number of participants reported high levels of depression (22%), anxiety and stress (19% each). Factors associated with poorer current level of functioning and wellbeing included: younger participants, recent diagnoses, aggressive tumour types, receiving chemotherapy, shoulder limitation due to pain, and lymphoedema. BC survivors require long-term management of psychological sequelae impacting activity and participation.

Health care utilization one year following the diagnosis benign breast disease or breast cancer - Corrected Proof

2012-02-20

Abstract: Purpose: We analyzed health care utilization (HCU) and its predictors in the first year after the diagnostic process for breast cancer (BC) or benign breast disease (BBD) using questionnaires. The impact of trait anxiety on HCU was examined.Results: In total 591 women were analyzed, 440 with BBD and 151 with BC. In women with BBD and high trait anxiety (HTA) increased HCU was found. In women with BC and HTA only more use of psychosocial care (PS) was found. HCU in BBD was predicted by lower Quality of Life (QoL) and (adjuvant) treatment predicted HCU in BC.Conclusions: The most important factors for higher HCU were HTA and lower QoL, especially in BBD. In women with BC increased PS use was seen in chronically anxious women. Therefore, it is important to identify these women using a psychometric test and to anticipate to their specific (mental) health care needs.

Breast cancer information on the internet: Analysis of accessibility and accuracy - Corrected Proof

2012-02-20

Abstract: Studies show internet sourced information often has poor accuracy. However, it is rapidly becoming a major source of patient information. Our aim was to assess accuracy of breast cancer-related information on the internet.The top five breast cancer-related search terms were identified using the commercial program “Wordtracker”. These terms were searched using the search-engine “Google” and the top 100 webpages per topic analysed for applicability and accuracy of information.Overall 500 webpages were analysed. 42% were inapplicable to the question asked. Applicable accuracy rates were variable amongst the five terms: “breast cancer symptoms” 84%, “breast cancer care” 87%, “breast cancer stage” 88%, “breast cancer survival” 91% and “breast cancer signs” 78%. Educational websites were more likely to be accurate(p < 0.001) and interest group administered websites less likely to be accurate(p = 0.018) than other websites.Finding accurate breast cancer information on the internet is difficult due to large numbers of inapplicable unregulated websites preferentially returned via search engines.

Increased mean corpuscular volume of red blood cells predicts response to metronomic capecitabine and cyclophosphamide in combination with bevacizumab - Corrected Proof

2012-02-17

Abstract: Background: There is an urgent need for the identification of commonly assessable predictive factors in the treatment of patients with metastatic breast cancer.Methods: During the course of a treatment including low dose metronomic oral cyclophosphamide and capecitabine plus i.v. bevacizumab (plus erlotinib in one third of the patients) for metastatic breast cancer, we observed that a relevant number of patients developed repeatedly elevated levels of mean corpuscular volume (MCV) of red blood cells without a significant fall in hemoglobin levels. We conducted a retrospective analysis on these 69 patients to evaluate if the increase in MCV could be associated to tumor response.Results: During the course of treatment 42 out of 69 patients (61%) developed macrocytosis. Using Cox proportional hazards modeling that incorporated macrocytosis (MCV≥100 fl) as a time-dependent covariate, macrocytosis resulted in a halved risk of disease progression (HR 0.45; 95% CI, 0.22–0.92, p-value 0.028). In a landmark analysis limited to patients with no sign of progression after 24 weeks of treatment, median time to progression was 72 weeks (48 weeks after landmark) in patients who had developed macrocytosis, and 43 weeks (19 weeks after landmark) in patients who had not (p = 0.023).Conclusion: Macrocytosis inversely related to risk of disease progression in patients treated with metronomic capecitabine plus cyclophosphamide and bevacizumab for metastatic breast cancer. This finding may be explained through thymidylate synthase inhibition by capecitabine. Whether bevacizumab has a role in determining macrocytosis, similarly to what happens with sunitinib, has to be further investigated. If other studies will confirm our findings, macrocytosis might be used as an early marker of response during metronomic treatment with capecitabine and cyclophosphamide with or without bevacizumab.

Rapid increase in incidence of breast ductal carcinoma in situ in Girona, Spain 1983–2007 - Corrected Proof

2012-02-16

Abstract: Introduction: The aim of this study was to describe breast ductal carcinoma in situ (DCIS) incidence trends in women in the Girona province during a period of 25 years. The influence of age, use of mammography and implementation of the breast cancer screening programs was explored. Incidence of subsequent invasive breast cancers (IBC) and DCIS treatment was also considered.Materials and methods: Cases diagnosed with primary pure DCIS (n = 416) during 1983–2007 were extracted from the population-based Girona Cancer Registry. The estimated annual percent change was estimated using joinpoint analysis.Results: DCIS incidence showed a sharp rise until 1997, followed by a less marked upward trend. Among women aged 50–69 the increase was particularly important between 1992 and in 1996, reflecting the spread in mammography use.Conclusion: The upward trend of DCIS was mainly related to an increase in mammography use either opportunistic or as a result of screening implementation.

Clinical and pharmacokinetic study of sunitinib and docetaxel in women with advanced breast cancer - Corrected Proof

2012-02-15

Abstract: Background: This exploratory study examined the pharmacokinetics, safety, and antitumor activity of sunitinib plus docetaxel in patients with HER-2-negative advanced breast cancer.Patients and methods: Patients with HER-2-negative disease who had received prior adjuvant anthracycline-based therapy received docetaxel (75 mg/m2) on day 1 of each 3-week cycle followed by sunitinib (37.5 mg/day for 2 weeks on Schedule 2/1) starting on day 2 (day 3 on cycle 2).Results: Twenty-two patients were enrolled. No clinically significant drug–drug interactions were observed. The most common non-hematologic AE (any grade) was fatigue/asthenia. Grade 4 neutropenia occurred in 20/22 patients (91%; n = 7 had neutropenic fever). The safety profile was similar to each agent given individually. 14/19 (73.7%) evaluable patients had a PR and 5/19 (26.3%) had SD.Conclusions: Sunitinib plus docetaxel on Schedule 2/1 did not result in any clinically significant drug–drug interactions. This combination was manageable and exhibited antitumor activity.

Efficacy of angiotensin-receptor blockers on demographic and clinico-pathological characteristics of breast cancer - Corrected Proof

2012-02-13

The renin–angiotensin system (RAS) is an important mediator of tumour progression and metastasis. Type 1 and type 2 angiotensin receptors are important regulators of cellular proliferation, angiogenesis and inflammation. A recent meta-analysis of randomised controlled trials reported an increased risk of cancer with angiotensin receptor blockers (ARBs). However, there are limited data about the association of breast cancer with ARBs. Thus, we aimed to investigate the effect of ARB usage on clinico-pathological properties of breast cancer.

Evolving trends in the initial locoregional management of male breast cancer - Corrected Proof

Scott V. Bratman, Daniel S. Kapp, Kathleen C. Horst — 2012-02-10

Abstract: The locoregional management of breast cancer in men has evolved over time. Multimodality treatment regimens currently in use are based primarily on large randomized trials that exclusively enrolled women with breast cancer. We retrospectively reviewed cases of male breast cancer treated with radiotherapy at Stanford University Medical Center with an emphasis on 22 patients treated with surgery and locoregional radiotherapy. We report trends in the surgical techniques as well as in the use of adjuvant radiotherapy, chemotherapy, and hormonal therapy. There were no isolated locoregional failures in this cohort, and 5-year disease-free survival was 65%. The use of contemporary surgical and radiotherapeutic techniques in men is discussed. We conclude that treatment guidelines designed for women should be applied to the locoregional management of breast cancer in men. However, large international prospective registries and inclusion of men in cooperative group randomized trials will be important to confirm the safety and efficacy of modern treatment modalities for male breast cancer.

Outcome analysis of patients with primary breast cancer initially treated at a certified academic breast unit - Corrected Proof

2012-02-10

Abstract: Introduction: Evaluation of oncological outcome and prognostic factors of patients with primary breast cancer treated at a certified academic breast unit.Patients and methods: We prospectively collected data of 3338 patients, diagnosed with primary breast cancer between 01.01.2003 and 31.12.2010 and treated at the Breast Unit Heidelberg, Germany, in order to analyze outcome in clinical practice. We evaluated local control rate (LCR), disease-free survival (DFS), distant disease-free survival (DDFS), observed overall survival (OS) and age-adjusted relative overall survival (ROS). In addition, the impact of known prognostic factors on these outcome variables was examined in univariate and multivariate analyses.Results: Of all patients, 368 (11.0%) had carcinoma in situ (CIS) and 197 (5.9%) had bilateral cancers. For the 2970 patients with invasive cancer, of which 49 patients (1.7%) had metastastic disease at time of diagnosis, DFS, LCR, DDFS, OOS and ROS at 5 years were 79.8%, 84.7%, 81.2%, 86.3%, and 89.8%, respectively. In multivariate analysis age, pT category, nodal status, hormone receptor status and grading were identified as independent prognostic factors for OS.Conclusion: Compared with recent population-based reports from Germany, more favourable patient characteristics and nominally higher survival was found among this large cohort of patients with primary breast cancer treated at a single certified breast unit.

Angiosarcoma of the breast: A difficult surgical challenge - Corrected Proof

Aaron Hui, Michael Henderson, David Speakman, Anita Skandarajah — 2012-02-06

Abstract: Background and objectives: Breast angiosarcoma presents following radiotherapy after breast conserving surgery, in the setting of chronic lymphoedema after axillary dissection or as a primary tumour. The Peter MacCallum Cancer Centre has significant experience due to large breast and sarcoma units and as a primary radiotherapy centre. Our aims were to evaluate the management and locoregional and distant outcomes after breast angiosarcoma.Methods: Retrospective study of all patients from the prospective breast and sarcoma databases with a diagnosis of primary or secondary breast angiosarcoma at Peter MacCallum Cancer Centre was performed between January 2000 and December 2010. Mode of presentation, management, loco-regional recurrence and survival rates were reviewed.Results: Eight women developed angiosarcoma in the setting of breast conservation with a median latency of 7 years post radiotherapy. Six patients had primary breast angiosarcoma. All breast angiosarcomas were managed with total mastectomy with 5 patients requiring autologous tissue transfer. Four patients had adjuvant radiotherapy and three patients had adjuvant paclitaxel. The median follow-up was 2.5 years (6 month-10 years) with 7 episodes of local recurrence in four patients and 7 patients with distal metastases including two deaths from distant disease.Conclusions: Primary angiosarcoma occurs de novo, presenting as a breast mass. Secondary angiosarcoma presents predominantly as a skin lesion, in the setting post-operative radiotherapy for breast conserving therapy. Angiosarcoma remains a rare and difficult management problem with poor loco-regional and distal control. Secondary AS is an iatrogenic condition that warrants close follow-up and judicial use of radiotherapy in breast conserving therapy.