Low muscle attenuation is a prognostic factor for survival in metastatic breast cancer patients treated with first line palliative chemotherapy

BackgroundLow muscle mass (LMM) and low muscle attenuation (LMA) reflect low muscle quantity and low muscle quality, respectively. Both are associated with a poor outcome in several types of solid malignancies. This study determined the association of skeletal muscle measures with overall survival (OS) and time to next treatment (TNT).Patients and methodsA skeletal muscle index (SMI) in cm²/m² and muscle attenuation (MA) in Hounsfield units (HU) were measured using abdominal CT-images of 166 patients before start of first-line chemotherapy for metastatic breast cancer. Low muscle mass (SMI <41 cm²/m²), sarcopenic obesity (LMM and BMI ≥30 kg/m²) and low muscle attenuation (MA <41 HU and BMI <25 kg/m2 or MA <33 HU and BMI ≥25 kg/m2) were related to OS and TNT.ResultsThe prevalence of LMM, sarcopenic obesity and LMA were 66.9%, 7.2% and 59.6% respectively. LMM and sarcopenic obesity showed no significant association with OS and TNT, whereas LMA was associated with both lower OS (HR 2.04, 95% CI 1.34–3.12, p = 0.001) and shorter TNT (HR 1.72, 95% CI 1.14–2.62, p = 0.010). Patients with LMA had a median OS and TNT of 15 and 8 months respectively, compared to 23 and 10 months in patients with normal MA.ConclusionLMA is a prognostic factor for OS and TNT in metastatic breast cancer patients receiving first-line palliative chemotherapy, whereas LMM and sarcopenic obesity are not. Further research is needed to establish what impact LMA should have in daily clinical practice.     

Biological and clinical significance of loss of heterozygosity at the INPP4B gene locus in Japanese breast cancer

PurposeINPP4B is considered to function as a putative tumor suppressor through its inhibitory function of Akt. In various malignant tumors, loss of heterozygosity (LOH) at the chromosomal region containing INPP4B and lower expression of INPP4B has been reported. The purpose of this study was to examine the frequency of the INPP4B LOH and its association with the clinicopathological characteristics and prognosis in breast cancer of Japanese women.MethodsThe allelic alteration at the INPP4B and PTEN gene loci was analyzed in 277 invasive primary breast carcinomas. The relationships between INPP4B LOH and the clinicopathological features were investigated.ResultsAmong the 238 informative cases for the evaluation, LOH at the INPP4B gene locus was observed in 43 tumors (18.1%). INPP4B LOH was significantly correlated with ER and PR negativity (p = 0.0009 and p = 0.0029, respectively), higher nuclear grade (p < 0.0001), higher Ki67 labeling index (p = 0.0006), triple-negative (TN) subtype (p = 0.0005) and PTEN LOH (p < 0.0001). INPP4B LOH was significantly associated with poorer prognosis, in terms of the relapse-free survival (RFS) and overall survival (OS). According to the multivariate analyses, INPP4B LOH was not independently associated with the prognosis.ConclusionThe incidence of INPP4B LOH was significantly higher in the TN subtype and positively correlated with PTEN LOH. INPP4B LOH was associated with more aggressive and proliferative phenotype. INPP4B LOH was also associated with poorer prognosis.     

Intracystic papillary carcinoma of the breast: A SEER database analysis of implications for therapy

BackgroundIntracystic papillary carcinoma (IPC) of the breast is a rare breast malignancy with an indolent course. However, patients can develop metastatic disease. Indications for surgery and radiotherapeutic management have not been well elucidated.MethodsWe identified 2649 female patients with IPC from the Surveillance, Epidemiology, and End Results (SEER) registry. Differences in demographics, clinical features and survival of patients were assessed using the Kaplan–Meier method and Cox regression.ResultsMedian age was 67 years. The majority of patients were white with Stage 0 disease. Most patients had lymph node evaluation and only 34% received radiation therapy. Using a log-rank test, survival was significantly better in Caucasian compared to African-American patients, patients with early stage disease, negative lymph nodes and those who received radiation (all p < 0.0001). In a Cox regression survival model adjusting for age, stage and grade, patients who were African-American (hazard ratio [HR] 2.0, CI 1.4–2.8; p < 0.0001) had a significantly higher risk of death than Caucasians. Patients who received radiation therapy (HR 0.5, CI 0.3–0.7; p = 0.0003) had a lower chance of death than patients that did not undergo radiation.ConclusionOverall, IPC has a good prognosis. Survival is improved in Caucasian patients and in patients who receive radiation therapy. Radiation therapy should be offered to women with IPC who undergo breast conserving surgery.     

Clinical significance of fatty liver disease induced by tamoxifen and toremifene in breast cancer patients

Background and AimThe aim of this study was to identify the effect of selective estrogen receptor modulator (SERM) on non-alcoholic fatty liver disease (NAFLD) in Asian women.MethodsWe retrospectively evaluated fatty liver development and/or serum alanine aminotransferase (ALT) elevation during SERM treatment in 1061 women who were diagnosed and treated with breast cancer in 2005 at Asan Medical Center.Results45 of 618 SERM-treated patients with normal ALT at baseline experienced ALT elevation during SERM treatment. Among the 112 SERM-treated patients who underwent liver imaging test, fatty liver was observed in 47 and both fatty liver and ALT elevation developed in 16 of 102 SERM-treated patients with normal baseline ALT. The cumulative rates of ALT elevation (10.7 vs. 4.3%; P = 0.002), fatty liver (48.5 vs. 20.9%; P < 0.001), and both fatty liver and ALT elevation (17.7 vs. 7.1%; P = 0.02) at 60 months were significantly higher in the SERM group than non-SERM group. By multivariate analysis, SERM treatment increased the risk of ALT elevation (hazard ratio [HR], 2.20; P = 0.01), fatty liver development (HR, 3.59; P < 0.001), and both fatty liver and ALT elevation (HR, 4.98; P = 0.01). After discontinuation of SERM, elevated serum ALT normalized in 39 (92.9%) and there were no instances of liver-related death or progression to liver cirrhosis in patients who experienced fatty liver or ALT elevation.ConclusionsAlthough SERM treatment is significantly associated with NAFLD in Asian women, considering the tolerability and reversibility of NAFLD induced by SERM, it can be continued with liver function monitoring in relevant patients.     

Intraoperative assessment of sentinel lymph node by one-step nucleic acid amplification in breast cancer patients after neoadjuvant treatment reduces the need for a second surgery for axillary lymph node dissection

PurposeSentinel lymph node (SLN) biopsy has been shown to be both accurate and feasible for women who receive neoadjuvant chemotherapy (NAC). Intraoperative assessment of SLN by frozen sections can produce false negative results. The aim of this study was to compare two different techniques of intraoperative assessment of SLN in breast cancer patients treated with NAC: frozen section (FS) and molecular assay (OSNA).MethodsA multicenter cohort of 320 consecutive breast cancer patients treated with NAC between 2010 and 2014 was analyzed. FS was performed intraoperatively in 166 patients (H&E cohort) and OSNA in 154 patients (OSNA cohort).ResultsA mean of 2.15 SLNs by FS and 1.22 SLNs by OSNA was assessed (p = 0.03). SLN metastasis was found in 44 patients (26.5%) by FS and in 48 (31.2%) by OSNA (p = 0.4). There was no statistical significance in rates of macrometastasis (75%), micrometastasis (20.5%) or ITCs (4.5%) when assessed by FS compared to OSNA (52.3%, 36.3% and 11.4%, respectively) (p = 0.06). There were 10 patients in the H&E cohort with positive-SLN in the definitive pathology assessment with negative intraoperative FS. When OSNA and definitive pathology were compared, there were no differences in rates of macrometastasis (61.1%), micrometastasis (33.3%) nor ITCs (5.6%) (p = 0.5). Fifty-four patients in the H&E cohort and 44 in the OSNA cohort had ALND after positive-SLNs. ALND was performed in a second surgery in 10 patients (18.5%) in the H&E cohort for intraoperative FS false negative results, 90% being micrometastasis. 42 out of 44 patients (95.5%) in the OSNA cohort had an ALND in the same surgery (p = 0.03).ConclusionsOSNA assay detects SLNs metastases as accurately as conventional pathology in the NAC setting. Intraoperative definitive assessment of the SLN by OSNA reduces the need for a second surgery for ALND in 18.5% of breast cancer patients with a positive-SLN after NAC.     

Smoking and FGFR2 rs2981582 variant independently modulate male breast cancer survival: A population-based study in Tuscany,Italy

AimMale breast cancer (MBC) is a rare disease and recommendations for its clinical management are often extrapolated from those for female breast cancer, even if breast cancer (BC) has different characteristics in the two sexes. The purpose of this study was to assess the influence of several individual characteristics including clinico-pathological, lifestyle and genetic factors on overall survival (OS) of a relatively large and well characterized population-based series of 166 MBCs enrolled in Tuscany.MethodsWe genotyped MBC cases at BRCA1/2 genes and at 9 candidate BC susceptibility SNPs. Kaplan-Meier method and multivariate Cox regression, adjusted for several individual characteristics were used. To reduce a possible selection bias related to the interval between diagnosis and enrolment of MBC cases into the study, we used the date of blood donation as the date of the start of observation for survival analysis.ResultsOnly smoking habits had a significant effect on OS at 10 years (for current smokers, HR: 3.34; 95% CI 1.45–7.68; p = 0.004), while lymph node status fell short of reaching statistical significance (for pN positive, HR: 2.07; 95% CI 0.93–4.55; p = 0.07). In the same multivariate analysis we found a significantly higher OS in cases with FGFR2 rs2981582 variant in the dominant transmission model (HR: 0.29; 95% CI: 0.13–0.62; p = 0.028). A sensitivity analysis with left truncation showed similar results.ConclusionsOur results may contribute to shed light on factors influencing MBC survival suggesting an important role for cigarette smoking and FGFR2 rs2981582 variant, and provide clues for better patient management.     

Fatigue,anxiety and depression overrule the role of oncological treatment in predicting self-reported health complaints in women with breast cancer compared to healthy controls

BackgroundWomen with breast cancer often attribute their health problems as side effects caused by oncological treatments. The aim of the study was to examine and compare self-reported health complaints (SHC) in postmenopausal patients with breast cancer to healthy controls.MethodWomen with breast cancer (N = 196) filled in 5 questionnaires 1–2 years after surgery; SHC Inventory, Functional Assessment of Cancer Therapy-Endocrine Subscale (FACT-ES), Fatigue – Functional Assessment of Cancer Therapy-Fatigue subscale (FACIT-F), Fatigue Visual Analog Scale (Fatigue VAS), and Hospital Anxiety and Depression Scale (HADS). Controls comprised 101 blood donors who reported on the questionnaires except for HADS. Bonferroni adjustment and p < 0.0017 was considered statistically significant for SHC Inventory, p < 0.05 for the remaining questionnaires.ResultsThe patients, mean age 58.0 (SD 9.5), reported significantly more self-reported health complaints, whereof 6 of 29 complaints were significantly elevated compared to the controls, mean age 57.0 (SD 5.8) (p < 0.001). HADS scores in patients fell into normal range, mean 6.3 (SD 5.7). A subgroup of 48 patients experienced more frequent and severe symptoms in all the questionnaires compared to the remaining 148 patients, and the 101 controls. Among the patients, fatigue, anxiety and depression explained 49% of the total variance in self-reported health complaints (p ≤ 0.001).ConclusionMost women with breast cancer (76%) reported health complaints equal to the healthy controls. Fatigue, anxiety and depression, not oncological treatments, were significant predictors for the complaints.     

Prolonged clinical benefit from the maintenance hormone therapy in patients with metastatic breast cancer

ObjectiveWe investigated the efficacy of maintenance hormone therapy (MHT), which was given to hormone positive metastatic breast cancer (MBC) patients in non-progression status to the previous chemotherapy.MethodsThis study retrospectively analyzed 76 MBC patients who had been treated with MHT from 2006 to 2010 at a single institute.ResultsFor the 76 patients reviewed, the median progression free survival (PFS) to MHT was 14.4 months (95% CI, 11.6–17.3). Prolonged PFS was associated with less previous palliative chemotherapy, fewer metastatic sites, and the absence of visceral metastasis in univariate analysis. Multivariate analysis showed that only the number of previous palliative chemotherapy (HR 1.73, 95% CI, 1.00–2.98; P = 0.04) remained as a significant variable. MHT was generally well tolerated.ConclusionsMHT showed considerable efficacy and tolerability in this study. Further randomized prospective study is warranted.     

Development and validation of a nomogram for predicting survival on the base of modified lymph node ratio in breast cancer patients

BackgroundAxillary lymph node status is one of the most important prognostic factors in breast cancer and previous studies indicated that lymph node ratio (LNR) could better predict the outcome than the counting of positive lymph nodes. In the current study, we evaluated the prognostic effect of modified LNR in breast cancer patients.MethodsA total of 3339 breast cancer patients undergoing axillary lymph nodes dissection were enrolled and respectively analyzed. Seventy five percent of participants were randomly selected as training cohort and the remaining 25% were as validation cohort. Univariate and multivariate analyses were performed and the prognostic impact of mLNR was compared with pN staging. A prognostic nomogram was established and externally validated in the validation cohort.ResultIn multivariate analysis, both the mLNR and pN staging were independent prognostic factors for breast cancer patients, and the mLNR manifested superior discrimination power than the pN stages regardless of the total number of lymph nodes retrieved and the lymph node status. The nomogram was built including the identified independent prognostic factors and the calibration curves indicated optimal agreement between nomogram prediction and actual observation. The Concordance index (C-index) of the nomogram was statistically higher than that of the TNM system (0.747 vs. 0.711 in training cohort, 0.789 vs. 0.760 in validation cohort, both p < 0.05).ConclusionModified LNR is an important prognostic parameter and can predict survival more accurately than pN staging. The novel nomogram could provide individual prediction for breast cancer patients and help clinicians in treatment option making and prognosis evaluation.     

Oncoplastic breast conservation surgery is oncologically safe when compared to wide local excision and mastectomy

BackgroundSupport for the oncological safety of oncoplastic breast conservation surgery (OBCS) is mostly based on evidence comparing recurrence rates after OBCS to wide local excision (WLE). However, OBCS is often indicated for larger cancers and oncological results should also be compared to patients treated with mastectomy. In this study we compared recurrence and survival following OBCS, mastectomy and WLE.MethodsPatients treated with OBCS between 2009 and 2012 were identified from a prospectively maintained database. For comparison, consecutive patients treated with WLE or mastectomy with or without immediate reconstruction (Ms ± IR) over the same time period were identified. Histological variables of patients were compared using Fisher Exact or Chi squared tests, and recurrence and survival were compared using Kaplan-Meier and Cox regression survival analysis.Results980 patients' data were analysed (OBCS: n = 104; WLE: n = 558; Ms ± IR: n = 318). Tumour size, grade, nodal status, ER, and PR expression of patients treated with OBCS were all significantly more adverse compared with patients treated with WLE (p < 0.001). These histological variables were similar in patients treated with Ms ± IR and OBCS. 5-year local recurrence rates were similar in all three groups (WLE: 3.4 per cent, OBCS: 2 per cent, Ms ± IR: 2.6 per cent; log rank = 0.973), while distant recurrence rates were higher after Ms ± IR and OBCS (Ms ± IR:13.1 per cent, OBCS:7.5 per cent, WLE:3.3 per cent; log rank: p < 0.001).ConclusionOBCS is oncologically safe in patients even when histological results are similar to patients treated with Ms ± IR.     

Molecular based subtyping of feline mammary carcinomas and clinicopathological characterization

Molecular classification of feline mammary carcinomas (FMC) from which specific behavioral patterns may be estimated has potential applications in veterinary clinical practice and in comparative oncology. In this perspective, the main goal of this study was to characterize both the clinical and the pathological features of the different molecular phenotypes found in a population of FMC (n = 102), using the broadly accepted IHC-based classification established by St. Gallen International Expert Consensus panel.The luminal B/HER2-negative subtype was the most common (29.4%, 30/102) followed by luminal B/HER2-positive subtype (19.6%, 20/102), triple negative basal-like (16.7%, 17/102), luminal A (14.7%, 15/102), triple negative normal-like (12.7%, 13/102) and finally, HER2-positive subtype (6.9%, 7/102). Luminal A subtype was significantly associated with smaller tumors (p = 0.024) and with well differentiated ones (p < 0.001), contrasting with the triple negative basal-like subtype, that was associated with larger and poorly differentiated tumors (p < 0.001), and with the presence of necrotic areas in the tumoral lesion (p = 0.003). In the survival analysis, cats with Luminal A subtype presented the highest survival time (mean OS = 943.6 days) and animals with triple negative basal-like subtype exhibited the lowest survival time (OS mean = 368.9 days). Moreover, two thirds (64%, 32/50) of the queens with multiple primary tumors showed different molecular subtypes in each carcinoma, revealing that all independent lesions should be analyzed in order to improve the clinical management of animals.Finally, the similarities between the subtypes of feline mammary tumors and human breast cancer, reveal that feline can be a valuable model for comparative studies.     

Detection of disseminated tumor cells in locally advanced breast cancer patients before primary systemic therapy

AimTo assess the prevalence and prognostic power of disseminated tumor cells (DTC) in patients with locally advanced breast cancer (LABC) before primary systemic therapy (PST).Materials and methodsLABC patients attending our Breast Unit were studied between 2002 and 2012, all of them being considered for PST. To determine the presence of DTC, posterior iliac crest aspirates were obtained and marrow samples were processed by gradient separation with Ficoll (Lymphoprep^®) and immunohistochemical staining using the antiCK A45-B/B3 (EPIMET) antibody. Clinicopathologic variables were recorded before and after PST to assess response. Disease-free survival (DFS) and overall survival (OS) were determined after follow-up. The presence of DTC as a predictor of response to PST and as a prognostic tool for OS and DSF was evaluated.ResultsDTC were observed in 26% of 47 patients included in the study. PST consisted of chemotherapy in 94% and hormone therapy in 6%. Breast-conserving therapy was attained in 33%. Mean follow-up was 68 months. Complete clinical response (CR) after PST was seen in 26%, disease recurrence in 38%, and cancer-related death in 8%; tumor size and negative estrogen receptors were significant predictors of CR and mastectomy was associated with DFS. Persistent axillary disease after PST and previous recurrence were predictive of OS. DTC were detected more often in patients who did not achieve CR and those who presented recurrence. DTC detection was a significant prognostic factor for a worse OS (OR = 7.62; CI95%: 1.46–39.61; p = 0.009) and a decreased survival time (62 versus 82 months, p = 0.004).ConclusionPresence of DTC before PST was found in a significant number of patients with LABC. DTC were found to be a significant prognostic factor for cancer-related death. DTC could be a surrogate predictor of response to PST and also of disease recurrence in LABC patients.     

Role of FDG-PET/CT in evaluating surgical outcomes of operable breast cancer – Usefulness for malignant grade of triple-negative breast cancer

BackgroundThe aim of this study was to evaluate the significance of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for speculating the malignant level and prognostic value of operable breast cancers.MethodsOf 578 consecutive patients with primary invasive breast cancer who underwent curative surgery between 2005 and 2010, 311 patients (53.8%) who received FDG-PET/CT before initial therapy were examined.ResultsReceiver operating characteristics (ROC) curve analysis showed the cutoff value of the maximum standardized uptake value (SUV_max) to predict cancer recurrence was 3.8 in all patients and 8.6 in patients with the triple-negative subtype, respectively. In all patients, 3-year DFS rates were 98.8% for patients with a tumor of SUV_max ≤ 3.8 and 91.6% for patients with a tumor of SUV_max > 3.8 (p < 0.001). High value of SUV_max was significantly associated with large tumor size (p < 0.001), lymph node metastasis (p = 0.040), high nuclear grade (p < 0.001), lymphovascular invasion (p = 0.032), negative hormone receptor status (p < 0.001), and positive HER2 status (p = 0.014). Based on the results of multivariate Cox analysis in all patients, high SUV_max (p = 0.001) and negative hormone receptor status (p = 0.005) were significantly associated with poor prognosis. In patients with triple-negative subtype, 3-year DFS rates were 90.9% for patients with a tumor of SUV_max ≤ 8.6 and 42.9% for patients with a tumor of SUV_max > 8.6 (p = 0.002), and high SUV_max was the only significant independent prognostic factor (p = 0.047).ConclusionFDG-PET/CT is useful for predicting malignant behavior and prognosis in patients with operable breast cancer, especially the triple-negative subtype.     

Sickness absence and disability pension following breast cancer – A population-based matched cohort study

PurposeTo compare sickness absence and disability pension in a population-based cohort of women with breast cancer (n = 463) from 1 year pre-diagnosis until 3 years post-diagnosis with a matched control group (n = 2310), and to investigate predictors of sickness absence during the 2nd and 3rd year post-diagnosis.ResultsFollowing breast cancer, the proportion of disease-free women with sickness absence decreased post-diagnosis (1st–3rd year; 78%-31%-19%), but did not reach the pre-diagnostic level (14%; P < 0.05). Post-diagnosis, patients were more likely than controls to be sickness absent (1st–3rd year; P < 0.001). No between-group differences were observed for disability pension post-diagnosis (P > 0.05). Among patients, chemotherapy, baseline fatigue and pre-diagnosis sick days predicted sickness absence during the 2nd, 3rd, and 2nd and 3rd year post-diagnosis, respectively (P < 0.05).ConclusionsBreast cancer is associated with increased sickness absence 3 years post-diagnosis. In a clinical setting, prevention and treatment of side effects are important in reducing long-term consequences.     

Brain natriuretic peptide as a cardiac marker of transient radiotherapy-related damage in left-sided breast cancer patients: A prospective study

PurposeOur study evaluated brain natriuretic peptide (BNP) changes over time after adjuvant radiotherapy (RT) in women with left-sided breast cancer investigating its correlation with heart dosimetric parameters.MethodsForty-three patients underwent clinical cardiac examination, electrocardiogram (ECG), echocardiography and BNP measurement before RT (T0) and 1 (T1), 6 (T6) and 12 months (T12) after. After T12 cardiac assessment was performed annually in each patient. Mean values and standard deviation (SD) of BNP, left ventricular ejection fraction (LVEF), V20, V25, V30, V45 and mean dose were calculated. Normalized BNP (BNPn) was calculated as follows: BNPnT1 = BNPT1/BNPT0, BNPnT6 = BNPT6/BNPT0, BNPnT12 = BNPT12/BNPT0. Absolute BNP and BNPn values were used for data analysis.ResultsMedian follow-up from the end of RT to the last check-up was 87 months (range 37–120 months). Minimum follow-up was 74 months except for two patients, who died at respectively 37 and 47 months after RT. In all patients LVEF did not change significantly (p = 0.22) after RT. BNP increased significantly (p < 0.001), particularly 1 and 6 months after RT. It slightly decreased after 12 months. BNP did not correlate with V20, V25, V30, V45, mean dose and MHD. All BNPn correlated significantly (p < 0.05) with V20, V25, V30, V45, mean dose and MHD. Four patients had a cardiac event; in the only subject who developed myocardial infarction, V20, V25, V30 and V45 were the highest and BNP increased from T1 and persisted high even at T12.ConclusionOur results confirm that BNP could be a useful minimally invasive marker of early RT related cardiac impairment.     

Efficacy and safety of eribulin as first- to third-line treatment in patients with advanced or metastatic breast cancer previously treated with anthracyclines and taxanes

ObjectivesDespite the survival benefit and acceptable tolerability of eribulin for advanced/metastatic breast cancer (MBC) patients pretreated with anthracyclines and taxanes, there is limited evidence of the clinical benefit of early eribulin use. We investigated the efficacy and safety of first- to third-line eribulin use in patients with MBC.Materials and methodsIn this phase II, open-label, single-arm study conducted at 14 sites in Kyushu, Japan, women with histologically confirmed human epidermal growth factor receptor 2–negative MBC were enrolled between December 1, 2011 and November 30, 2013 (Data cut-off: November 30, 2014). Objective response rate (ORR; primary endpoint), disease control rate (DCR), progression-free survival (PFS), duration of response (DOR), overall survival (OS), and safety were evaluated.ResultsOf 53 recruited patients, 47 were enrolled. The ORR was 17.0% (95% confidence interval, 7.6–30.8), DCR was 66.0% (51.2–77.8), median PFS was 4.9 months (3.5–7.0), DOR was 6.6 months (1.9–14.3), and median OS was 17.4 months (10.1–not evaluable). The common grade 3/4 adverse events were neutropenia (25 patients; 53.2%), leucopenia (16 patients; 42.1%) and febrile neutropenia (4 patients; 8.5%). Toxicity did not increase during the long-term treatment. Subgroup analysis indicated that first-line treatment led to higher ORR and prolonged PFS and OS than second-/third-line treatment and that incidence of adverse events in patients of second-/third-line treatment was not higher than that in patients of first-line treatment.ConclusionEribulin exhibited efficacy and manageable tolerability in Japanese women with pretreated MBC in first- to third-line use. (ID: UMIN000007121).     

Prognostic implications of lobular breast cancer histology: New insights from a single hospital cross-sectional study and SEER data

BackgroundInvasive lobular breast cancer (ILC) is generally believed to have an increased risk for late relapse compared to invasive ductal breast cancer (IDC). However, the study most often referred to is a chemotherapy trial that mainly included node positive patients. We hypothesize that nodal status may influence the hazard of relapse since time of diagnosis differently in invasive ductal carcinoma (IDC) and ILC.MethodsPrimary operable breast cancer patients from our institution diagnosed between 2000 and 2009 were studied. Multivariable analysis and subgroup analyses were performed to assess whether ILC carries a different prognosis compared to IDC. SEER data were used for external validation.ResultsIn lymph node negative patients, ILC carries a better prognosis regarding distant metastasis free interval (DMFI) (HR 3.242 (1.380–7.614), p = 0.0069) with a trend towards improved breast cancer specific survival (BCSS), over the entire study frame (UZ Leuven data). In lymph node positive patients, both DMFI (HR 0.466 (0.309–0.703), p = 0.0003) and BCSS (HR 0.441 (0.247–0.788), p = 0.0057) are significantly worse for ILC, especially after longer follow-up (>4–5 years) (UZ Leuven data). Similar results were found in the SEER cohort. Results remained identical when excluding screen detected cases (data not shown).ConclusionThe prognostic impact of lobular histology not only depends on time since diagnosis but also on nodal status. The general believe that ILC have compromised late-term outcome compared to IDC seems untrue for the majority ( = node negative) of ILCs.     

An evaluation of resource utilisation of single stage porcine acellular dermal matrix assisted breast reconstruction: A comparative study

ObjectivesTo evaluate resource utilization of single stage porcine acellular dermal matrix (ADM) assisted breast reconstruction compared with tissue expander (TE), latissimus dorsi flap and implant (LD/I) and latissimus dorsi flap and TE (LD/TE) reconstructive techniques.Materials and methodsClinical data was collected for length of stay, operative time, additional hospitalisations and operative procedures, and outpatient appointments for 101 patients undergoing unilateral implant based breast reconstruction. Resources utilised by ADM (Strattice Reconstructive Tissue Matrix™) patients were analysed and compared to the resource usage of traditional techniques.Results25 patients undergoing single stage ADM (ADM/I) were compared with 27 having TE, 32 having LD/I and 17 having LD/TE reconstructions. Follow up was 24 months. Compared to TE, ADM/I had similar length of stay and operative time, lower rate and number of additional procedures, fewer, shorter re-admissions (p < 0.05) and fewer appointments (p < 0.05). Compared to LD/TE, ADM/I had shorter length of stay and operative time (p < 0.05), lower rate and number of additional procedures, fewer, shorter re-admissions (p < 0.05) and fewer appointments (p < 0.05). Compared to LD/I, ADM/I had shorter length of stay (p < 0.05) and operative time (p < 0.05), fewer appointments, similar rate and number of additional procedures but required more and longer re-admissions.ConclusionIn our experience, unilateral single stage ADM/I was associated with fewer resources utilised in comparison with two staged TE and LD/TE reconstructions in both complication-free and complicated settings over a 24-month period, despite requiring aesthetic revision in 60.9% of patients. Compared to LD/I, resource utilisation was commensurate in complication-free and complicated settings.     

Contralateral prophylactic mastectomy in an Asian population: A single institution review

BackgroundContralateral prophylactic mastectomy (CPM) removes the non-diseased breast in women who have unilateral breast cancer. This reduces the incidence of contralateral breast cancer, and potentially improves survival in high risk patients. Such surgical risk-reduction strategy is increasingly being adopted in the United States, despite a decreasing incidence of contralateral breast cancer. The use of CPM in an Asian population is yet unknown. We present the first Asian report on CPM rates and trends in Singapore, the country with the highest incidence of breast cancer in Asia.MethodsA retrospective review of all patients who had breast cancer surgery from 2001 to 2010 at the largest healthcare system in Singapore was performed. Patient demographics and tumour characteristics were analysed with regards to type of surgery performed. Factors associated with CPM were identified.ResultsFrom 2001 to 2010, a total of 5130 patients underwent oncological breast surgery. A decreasing trend of mastectomies (82.7%–70.8%), an upward trend of breast conserving surgery (BCS) (17.3%–29.2%) and an increasing trend in CPM (0.46%–1.25%) is observed. Patients who opted for CPM are likely to be younger (48.4 ± 9.4 years), married (60%), parous (56.7%), with no family history of breast/ovarian cancer (66.7%), and diagnosed at an earlier stage. The rate of synchronous occult breast malignancy was found to be 10% (n = 30), and these were in patients who were of a low cancer-risk profile.ConclusionsThis retrospective study reflects an increasing incidence of breast cancer in Singapore, with a decrease in mastectomies, and an increase in BCS and CPM rates, similar to Western data. Similar to Western populations, the Asian woman who opts for CPM is likely to be young and have an earlier stage of breast cancer. In contrast, the Asian woman is likely to have no family history of breast or ovarian cancers. Commonly cited reasons for increased CPM rates such as the increased availability of genetic counselling and pre-operative MRI evaluation, along with wide use of reconstruction, do not feature as dominant factors in our population, suggesting that the Asian patients may have different considerations when electing for CPM.     

Prognostic,predictive abilities and concordance of BCL2 and TP53 protein expression in primary breast cancers and axillary lymph-nodes: A retrospective analysis of the Belgian three arm study evaluating anthracycline vs CMF adjuvant chemotherapy

Given recent data on genetic heterogeneity within and individual’s tumor, we investigated if there were differences in the prognostic and predictive abilities of BCL2 and TP53 protein expression in primary breast cancer (TU) and corresponding axillary lymph-nodes (LN). We used patient samples from the adjuvant Belgian three-arm study which randomized between anthracycline containing regimens and traditional CMF. The endpoints analyzed were overall survival (OS), event-free survival (EFS) and interactions between chemotherapy regimens.At a median follow-up of 15.6 years, BCL2 and TP53 (in both TU and LN) were significantly associated with OS but only in the first 5 years. Likewise, BCL2 and TP53 (in both TU and LN) were associated with EFS in the first 2 years after randomization, with no association after 2 years. BCL2 and TP53 remained statistically significant after adjustment for the standard clinical–pathological characteristics in regard to OS and EFS in the respective first years after randomization, (p value < 0.001 for both markers).Furthermore, an interaction was found between high BCL2 expression in the TU (but not in LN) and benefit to CMF over anthracycline-based chemotherapy (interaction p value EFS: 0.042; OS = 0.01). No interaction was found for TP53 expression neither in TU nor in LN.We conclude that BCL2 and TP53 were predictive biomarkers for better and worse survival respectively, but only in the first two to five years after diagnosis. BCL2 expression in the TU but not in the LN was predictive of increased benefit to CMF vs anthracycline-based chemotherapy.