Survival outcomes after breast-conserving therapy compared with mastectomy for patients with early-stage metaplastic breast cancer: a population-based study of 2412 patients

BackgroundPrevious studies revealed that patients with early-stage metaplastic breast cancer (MBC) underwent mastectomy more often than breast-conserving therapy (BCT) mainly due to the larger tumor size. This study was performed to compare the survival outcomes following BCT versus mastectomy for patients with early-stage MBC.MethodsSurveillance, Epidemiology, and End Results (SEER) database was used to identify women diagnosed with early-stage MBC (T1-3N0-3M0) between 2001 and 2016, who were treated with either BCT or mastectomy. We assessed overall survival (OS) and breast cancer-specific survival (BCSS) using the Kaplan-Meier method and hazard ratios using Cox proportional hazards models.ResultsA total of 2412 MBC patients were identified, 881 (36.5%) of whom underwent BCT and 1531(63.5%) underwent mastectomy. The median follow-up time was 73 months. Most of patients had older age (≥50 years old), larger tumor size, higher American Joint Committee on Cancer (AJCC) stage and hormone receptor negativity. After adjustment for confounding variables, patients who underwent BCT had significantly improved OS (5-year OS: 84.3% vs 62.5%; 10-year OS: 73.0% vs 52.1%; adjusted HR = 0.76, 95%CI: 0.59–0.97, p = 0.028) and BCSS (5-year BCSS: 89.1% vs 70.8%; 10-year BCSS: 83.9% vs 67.5%; adjusted HR = 0.72, 95%CI: 0.53–0.96, p = 0.026) than those who underwent mastectomy, and this improvement remained significant for all T and N stages of MBC except for N2-3 stage.ConclusionBCT conferred improved OS and BCSS compared with mastectomy for patients with early-stage MBC, and the improvement persisted in almost all of the subgroups of different T and N stages.     

Contralateral parenchymal enhancement on MRI is associated with tumor proteasome pathway gene expression and overall survival of early ER+/HER2-breast cancer patients

PurposeTo assess whether contralateral parenchymal enhancement (CPE) on MRI is associated with gene expression pathways in ER+/HER2-breast cancer, and if so, whether such pathways are related to survival.MethodsPreoperative breast MRIs were analyzed of early ER+/HER2-breast cancer patients eligible for breast-conserving surgery included in a prospective observational cohort study (MARGINS). The contralateral parenchyma was segmented and CPE was calculated as the average of the top-10% delayed enhancement. Total tumor RNA sequencing was performed and gene set enrichment analysis was used to reveal gene expression pathways associated with CPE (N = 226) and related to overall survival (OS) and invasive disease-free survival (IDFS) in multivariable survival analysis. The latter was also done for the METABRIC cohort (N = 1355).ResultsCPE was most strongly correlated with proteasome pathways (normalized enrichment statistic = 2.04, false discovery rate = .11). Patients with high CPE showed lower tumor proteasome gene expression. Proteasome gene expression had a hazard ratio (HR) of 1.40 (95% CI = 0.89, 2.16; P = .143) for OS in the MARGINS cohort and 1.53 (95% CI = 1.08, 2.14; P = .017) for IDFS, in METABRIC proteasome gene expression had an HR of 1.09 (95% CI = 1.01, 1.18; P = .020) for OS and 1.10 (95% CI = 1.02, 1.18; P = .012) for IDFS.ConclusionCPE was negatively correlated with tumor proteasome gene expression in early ER+/HER2-breast cancer patients. Low tumor proteasome gene expression was associated with improved survival in the METABRIC data.     

Combined breast conservation therapy versus mastectomy for BRCA mutation carriers – A systematic review and meta-analysis

BackgroundThe non-inferiority of combined breast conservation surgery (BCS) and radiotherapy (breast conservation therapy or BCT) compared to mastectomy in sporadic breast cancer cases is well recognised. Uncertainty remains regarding optimal surgical practice in BRCA mutation carriers.AimsTo evaluate the oncological safety of combined BCT versus mastectomy in BRCA mutation carriers following breast cancer diagnosis.MethodsA systematic review was performed as per PRISMA and MOOSE guidelines. Observational studies comparing BCS and mastectomy in BRCA carriers were identified. Dichotomous variables were pooled as odds ratios (OR) using the Mantel–Haenszel method. Log hazard ratios (lnHR) for locoregional recurrence (LRR), contralateral breast cancer, disease-free and overall survival and their standard errors were calculated from Kaplan-Meier or cox-regression analyses and pooled using the inverse variance method.ResultsTwenty three studies of 3807 patients met inclusion criteria; 2200 (57.7%) were BRCA1 and 1212 (31.8%) were BRCA2 carriers. Median age at diagnosis was 41 years with 96 months follow up. BCS was performed on 2157 (56.7%) while 1408 (41.5%) underwent mastectomy. An increased risk of LRR was observed in patients treated with BCS (HR:4.54, 95% Confidence Interval: 2.77–7.42, P < 0.001, heterogeneity (I²) = 0%). However, the risks of contralateral breast cancer (HR:1.51, 95%CI: 0.44–5.11, P = 0.510, I² = 80%), disease recurrence (HR:1.16, 95%CI: 0.78–1.72, P = 0.470, I² = 44%), disease-specific recurrence (HR:1.58, 95%CI: 0.79–3.15, P = 0.200, I² = 38%) and death (HR:1.10, 95%CI: 0.72–1.69, P = 0.660, I² = 38%) were equivalent for combined BCT and mastectomy.ConclusionsSurvival outcomes following combined BCT is comparable to mastectomy in BRCA carriers. However, the risk of LRR is increased. Patient counselling should be tailored to incorporate these findings.     

Incidence,risk factors and survival of patients with brain metastases at initial metastatic breast cancer diagnosis in China

PurposeTo characterize the incidence, risk factors and survival of patients with brain metastases at initial diagnosis of metastatic breast cancer (MBC) in China.MethodsThe China National Cancer Center database was used to identify 2087 MBC patients diagnosed between 2003 and 2015. Clinicopathological features, treatment and survival information were extracted. Multivariable logistic and Cox regression were performed to determine factors predictive of brain metastases at MBC diagnosis and survival, respectively.ResultsBrain metastases occurred in ninety patients (4.3%) at MBC diagnosis, and in 27 patients (2.5%), 42 patients (7.2%) and 21 patients (5.2%) with hormone receptor positive, human epidermal growth factor receptor 2 negative (HR + HER2-), HER2-positive and triple negative breast cancer (TNBC), respectively. HER2-positive subtype (OR = 2.38; 95% CI 1.40–4.04; p < 0.0001), TNBC subtype (OR = 1.89; 95% CI 1.02–3.51; p = 0.005), and metastases to all three sites of bone, liver and lungs (OR = 3.23; 95% CI 1.52–6.87; p = 0.002) were shown to increase the risk of BM at MBC diagnosis. Median survival after BM was 23.7 months. First-line tyrosine kinase inhibitors (TKI) improved survival compared to trastuzumab-based regimen (44.9 vs 35.4 months, p = 0.09). Factors that independently decreased BM death risk were ECOG<2, brain metastases only and multidisciplinary treatment.ConclusionHER2-positive and TNBC subtypes have a higher incidence of BM at initial MBC diagnosis. Brain screening might be considered in patients with HER2-positive disease at MBC diagnosis, and further prospective randomized study is warranted.     

Predictive role of the overexpression for CXCR4, C-Met,and VEGF-C among breast cancer patients: A meta-analysis

BackgroundThe overexpression of CXCR4, C-Met and VEGF-C present widely in breast tumors, they may be markers of resistance to treatment. However, the studies are still controversial. Thus, this meta-analysis aims to research the relationship between the overexpression of CXCR4, C-Met, VEGF-C and clinical prognosis among breast cancer patients.MethodsPubMed and EMBASE databases were searched for eligible literature. The outcomes of interest were progression-free survival (PFS), relapse-free survival (RFS) and overall survival (OS). All tests of statistical significance were two sided.ResultsA total of 7830 patients from 28 eligible studies were assessed. The overexpression of the CXCR4 and C-Met both implied significantly worse PFS compared with normal expression [HR = 2.56, 95% CI = 1.34–4.91, P = 0.005; and HR = 1.63 95% CI = 1.20–2.22, P = 0.002]. Meanwhile, if patients had high expression of CXCR4, they would have worse OS [HR = 2.56 95% CI = 1.52–4.31, P = 0.000]. However, the overexpression of C-Met did not relate to OS for breast cancer patients [HR = 1.16, 95% CI = 0.69–1.95, P = 0.570]. Meanwhile, no statistically significant different was observed with respect to PFS and OS between VEGF-C overexpression and normal expression [HR = 0.99, 95% CI = 0.64–1.52, P = 0.968; and HR = 0.76, 95% CI = 0.43–1.33, P = 0.333].ConclusionsOur meta-analysis showed that CXCR4 and C-Met were efficient prognostic factors for breast cancer. Nevertheless, highly expressing VEGF-C was not related to progression-free survival and overall survival. Due to the small samples and insufficient date, further studies should be conducted to clarify the association between the overexpression of CXCR4 or C-Met or VEGF-C and the prognosis about breast cancer patients.     

Smoking Cessation has no Influence on Quality of Life in Patients with Peripheral Arterial Disease 5 Years Post-vascular Surgery

ObjectivesSmoking is an important modifiable risk factor in patients with peripheral arterial disease (PAD). We investigated differences in quality of life (QoL) between patients who quitted smoking during follow-up and persistent smokers.DesignCohort study.MethodsData of 711 consecutively enrolled patients undergoing vascular surgery were collected in 11 hospitals in the Netherlands. Smoking status was obtained at baseline and at 3-year follow-up. A 5-year follow-up to measure QoL was performed with the EuroQol-5D (EQ-5D) and Peripheral Arterial Questionnaire (PAQ).ResultsAfter adjusting for clinical risk factors, patients, who quit smoking within 3 years after vascular surgery, did not report an impaired QoL (EQ-5D: odds ratio (OR) = 0.63, 95% confidence interval (CI) = 0.28–1.43; PAQ: OR = 0.76, 95% CI = 0.35–1.65; visual analogue scale (VAS): OR = 0.88, 95% CI = 0.42–1.84) compared with patients, who continued smoking. Current smokers were significantly more likely to have an impaired QoL (EQ-5D: OR = 1.86, 95% CI = 1.09–3.17; PAQ: OR = 1.63, 95% CI = 1.00–2.65), although no differences in VAS scores were found (OR = 1.17, 95% CI = 0.72–1.90).ConclusionsThere was no effect of smoking cessation on QoL in PAD patients undergoing vascular surgery. Nevertheless, given the link between smoking, complications and mortality in this patient group, smoking cessation should be a primary target in secondary prevention.     

Metastatic breast cancer subtypes and central nervous system metastases

BackgroundBreast cancer (BC) subtypes have different survival and response to therapy. We studied predictors of central nervous system metastases (CNS-M) and outcome after CNS-M diagnosis according to tumor subtype.Patients and methods488 patients with diagnosis of metastatic BC were retrospectively evaluated. According to the combination of hormone receptors (HR) and HER2 status, tumors were grouped in: Luminal (Lum), Luminal/HER2+, pure HER2-positive (pHER2+) and triple negative (TN). Time to CNS progression, CNS-M free interval and Overall Survival (OS) after CNS-M occurrence were compared by the log-rank test. Cox-proportional hazard models were used to study predictor factors associated with CNS progression, including tumor subtype and all potentially clinical relevant variables.Results115 patients (pts) developed CNS-M with a median time to CNS progression of 31 months. The rate of CNS-M by subtype was: Lum 14%, Lum/HER2+ 35%, pHER2+ 49%, TN 22% (p < 0.001). Compared with Lum tumors, Lum/HER2+ (HR 2.514, p < 0.001), pHER2+ (HR 6.799, p < 0.0001) and TN (HR = 3.179, p < 0.001) subtypes were at higher risk of CNS-M. Median OS in months after CNS-M was: Lum 7.4, Lum/HER2+ 19.2, pHER2+ 7, TN 4.9 (p < 0.002). Belonging to the Lum/HER2+ subtype (HR 0.48, p < 0.037) and having isolated CNS (HR 0.37, p < 0.004) predicted significantly reduced risk of death.ConclusionsAfter CNS-M, the Lum/HER2+ subtype appears associated with the longest OS. Prospective clinical trials would be required for evaluating the potential role of screening for asymptomatic CNS lesions and of more aggressive CNS-M treatment in Lum/HER2+ subtype.     

Loco‐regional Control After Neo‐adjuvant Chemotherapy and Conservative Treatment for Locally Advanced Breast Cancer Patients

Breast‐conserving treatment (BCT) has been validated for breast cancer patients receiving adjuvant chemotherapy. Our objective was to evaluate the difference in loco‐regional recurrence (LRR) rates between BCT and mastectomy in patients receiving radiation therapy after neo‐adjuvant chemotherapy (NCT). A retrospective data base was used to identify all patients with breast cancer undergoing NCT from 2002 to 2007. Patients with initial metastatic disease were excluded from this analysis. LRR was compared between those undergoing BCT and mastectomy. Individual variables associated with LRR were evaluated. Two hundred eighty‐four patients were included, 111 (39%) underwent BCT and 173 (61%) mastectomy. Almost all patients (99%) in both groups received postoperative radiation. Pathologic complete response was seen in 37 patients, of which 28 underwent BCT (p < 0.001). Patients receiving mastectomy had more invasive lobular carcinoma (p = 0.007) and a higher American Joint Committee on Cancer (AJCC) stage (p < 0.001) at diagnosis than those with BCT. At a median follow‐up of 6.3 years, the loco‐regional control rate was 91% (95% CI: 86–94%). The 10‐year LRR rate was similar in the BCT group (9.2% [95% CI: 4.9–16.7%]) and in the mastectomy group (10.7% [95% CI: 5.9–15.2%]; p = 0.8). Ten‐year overall survival (OS) rates (63% [95% CI: 46–79%] in the BCT group; 60% [95% CI: 47–73%] in the mastectomy group, p = 0.8) were not statistically different between the two patient populations. Multivariate analysis showed that AJCC stage ≥ III (HR: 2.6; 95% CI: 1.2–5.8; p = 0.02), negative PR (HR: 6; 95% CI: 1.2–30.6, p = 0.03), and number of positive lymph nodes ≥3 (HR: 2.5; 95% CI: 1.1–5.9; p = 0.03) were independent predictors of LRR. Ten‐year OS was similar in the BCT and in the mastectomy group (p = 0.1). The rate of LRR was low and did not significantly differ between the BCT and the mastectomy group after NCT. Randomized trials assessing whether mastectomy can be safely omitted in selected breast cancer patients (nonstage III tumors or those which do not require adjuvant hormone suppression) which respond to NCT are required.     

Prognostic impact of HER2-low expression in hormone receptor positive early breast cancer

BackgroundRecent data suggest that human epidermal growth factor receptor 2 (HER2)-low breast cancer may represent a distinct entity. We aimed to compare disease characteristics and outcomes between HER2-low and HER2-0 in estrogen receptor (ER) positive, early-stage breast cancer.MethodsA single center retrospective study comprising all women with ER positive, HER2 negative early breast cancer, for whom an Oncotype DX test was performed between 2005 and 2012. Women were grouped to HER2-low (immunohistochemistry +1 or +2 and in situ hybridization not amplified) or HER2-0. Clinico-pathological features and Oncotype recurrence score (RS) were collected. Data on overall-survival (OS), disease-free survival (DFS) and distant disease-free survival (DDFS) were evaluated according to HER2 expression status.Results608 women were included, of which 304 women had HER2-0 and 304 had HER2-low disease. Lobular subtype was significantly more common in HER-0 compared to HER2-low disease (17% vs. 8%, p = 0.005). The prevalence of other clinic-pathological characteristics and long-term prognosis were comparable between both groups. For women with high genomic risk (RS > 25), HER2-low expression was associated with significantly favorable OS (HR = 0.31, 95% CI 0.11–0.78, p = 0.01), DFS (HR = 0.40, 95% CI 0.20–0.82, p = 0.01) and DDFS (HR = 0.26, 95% CI 0.11–0.63, P = 0.002) compared to women with HER2-0. For women with low genomic risk (RS ≤ 25), long-term prognosis was unrelated to HER2 expression.ConclusionThe prognostic impact of HER2-low expression in early-stage luminal disease varies across the genomic risk, with significant favorable outcomes of HER2-low expression compared to HER2-0 in women with high genomic risk.     

Neo‐adjuvant chemotherapy and axillary de‐escalation management for patients with clinically node‐negative breast cancer

This study aimed to explore the optimal time of sentinel lymph node biopsy (SLNB) and neo‐adjuvant chemotherapy (NAC) and to assess the feasibility of selective elimination of axillary surgery after NAC in clinically node‐negative (cN0) patients. From April 2010 to August 2018, 845 patients undergoing surgery after NAC were included in this retrospective study to analyze the correlation between different clinicopathological characteristics of cN0 patients and negative axillary lymph node after NAC (ypN0). Among the 148 cN0 patients, 83.1% (123/148) were ypN0. The rates of ypN0 in patients with hormone receptor positive (HR+)/HER2?, HR+/HER2+, HR?/HER2+, and triple‐negative (TN) breast cancer were 75.4% (46/61), 82.6% (19/23), 85.2% (23/27), and 94.6% (35/37), respectively (P < 0.001). The rates of ypN0 in TN and HER2+ patients were 94.6% and 95.5%, which were significantly higher than that in HR+/HER2? patients (P < 0.05). Molecular subtypes, clinical stage, radiologic complete response, and pathologic complete response (bpCR) of the breast tumor correlated with ypN0 after full‐course NAC (P < 0.05). Molecular subtypes (OR = 2.374, P = 0.033), clinical stage (OR = 0.320, P = 0.029), and bpCR (OR = 0.454, P = 0.012) were independent predictors for ypN0. The optimal time of SLNB and NAC in cN0 patients might be different among different molecular subtypes: it would be preferable to perform SLNB prior to NAC for HR+/HER2? patients, and SLNB after NAC for TN and HER2+ patients to reduce the risk of axillary lymph node dissection. In view of the high ypN0 rate in cN0 patients, axillary surgical staging might be selectively eliminated, especially for HER2+ and TN patients.     

Prognostic factors of brain metastases from breast cancer: Impact of targeted therapies

IntroductionBrain metastases (BM) from breast cancer are associated with poor prognosis. This study was made to determine the prognostic influence of breast cancer biological subtypes, and to define the best therapeutic options in this setting, with a special focus on the HER2-positive population.Patients and methodsBreast cancer patients with known hormone receptors (HR) and HER2 status presenting with BM treated between 1995 and 2010 in our two institutions were considered for this retrospective study.Results250 patients were included. The study population consisted of 25.6% patients categorized as triple-negative (HR?/HER2?), 30.8% as HR+/HER2? and 43.6% as HER2+ breast cancer. Median overall survival (OS) was 8.9 months (95% CI, 6.9–10.3 months). Cerebral progression remained the most frequent cause of death (57.1%). On multivariate analysis, HER2 positivity and the RPA score were the two most important prognostic factors. Local treatment (surgery or stereotactic radiotherapy) and chemotherapy were significantly associated with an increased survival. On multivariate analysis of the RPA1-2 population, local treatment and chemotherapy were independent prognostic factors in addition to biological subtypes, RPA class, liver metastases and clinical signs of intra-cranial hypertension. Anti-HER2 therapies administered after BM diagnosis significantly and independently increased OS. Median OS in patients receiving both trastuzumab and lapatinib after BM diagnosis was significantly better than that the one of patients receiving only one of the 2 targeted therapies (25.7 vs. 9.6 months, p < 0.001).ConclusionsBiological subtypes are independent prognostic determinants. Chemotherapy and targeted therapies positively affect the prognosis after first BM.     

Does Regional Anesthesia Reduce Complications Following Total Hip and Knee Replacement Compared With General Anesthesia? An Analysis From the National Joint Registry for England,Wales, Northern Ireland and the Isle of Man

BackgroundRegional anesthesia is increasingly used in enhanced recovery programs following total hip replacement (THR) and total knee replacement (TKR). However, debate remains about its potential benefit over general anesthesia given that complications following surgery are rare. We assessed the risk of complications in THR and TKR patients receiving regional anesthesia compared with general anesthesia using the world’s largest joint replacement registry.MethodsWe studied the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man linked to English hospital inpatient episodes for 779,491 patients undergoing THR and TKR. Patients received either regional anesthesia (n = 544,620, 70%) or general anesthesia (n = 234,871, 30%). Outcomes assessed at 90 days included length of stay, readmissions, and complications. Regression models were adjusted for patient and surgical factors to determine the effect of anesthesia on outcomes.ResultsLength of stay was reduced with regional anesthesia compared with general anesthesia (THR = −0.49 days, 95% confidence interval [CI] = −0.51 to −0.47 days, P < .001; TKR = −0.47 days, CI = −0.49 to −0.45 days, P < .001). Regional anesthesia also had a reduced risk of readmission (THR odds ratio [OR] = 0.93, CI = 0.90-0.96; TKA OR = 0.91, CI = 0.89-0.93), any complication (THR OR = 0.88, CI = 0.85-0.91; TKA OR = 0.90, CI = 0.87-0.93), urinary tract infection (THR OR = 0.85, CI = 0.77-0.94; TKR OR = 0.87, CI = 0.79-0.96), and surgical site infection (THR OR = 0.87, CI = 0.80-0.95; TKR OR = 0.84, CI = 0.78-0.89). Anesthesia type did not affect the risk of revision surgery or mortality.ConclusionRegional anesthesia was associated with reduced length of stay, readmissions, and complications following THR and TKR when compared with general anesthesia. We recommend regional anesthesia should be considered the reference standard for patients undergoing THR and TKR.     

The St. Gallen surrogate classification for breast cancer subtypes successfully predicts tumor presenting features,nodal involvement,recurrence patterns and disease free survival

AimsTo evaluate how the St. Gallen intrinsic subtype classification for breast cancer surrogates predicts disease features, recurrence patterns and disease free survival.Materials and methodsSubtypes were classified by immunohistochemical staining according to St. Gallen subtypes classification in a 5-tyre system: luminal A, luminal B HER2-neu negative, luminal B HER2-neu positive, HER2-neu non luminal or basal-like. Data were obtained from the records of patients with invasive breast cancer treated at our institution. Recurrence data and site of first recurrence were recorded. The chi(2) test, analysis of variance, and multivariate logistic regression analysis were used to determine associations between surrogates and clinicopathologic variables.ResultsA total of 2.984 tumors were classifiable into surrogate subtypes. Significant differences in age, tumor size, nodal involvement, nuclear grade, multicentric/multifocal disease (MF/MC), lymphovascular invasion, and extensive intraductal component (EIC) were observed among surrogates (p < 0.0001). After adjusting for confounding factors surrogates remained predictive of nodal involvement (luminal B HER2-neu pos. OR = 1.49 p = 0.009, non-luminal HER2-neu pos. OR = 1.61 p = 0.015 and basal-like OR = 0.60, p = 0.002) while HER2-neu positivity remained predictive of EIC (OR = 3.10, p < 0.0001) and MF/MC (OR = 1.45, p = 0.02). Recurrence rates differed among the surrogates and were time-dependent (p = 0.001) and site-specific (p < 0.0001).ConclusionThe St. Gallen 5-tyre surrogate classification for breast cancer subtypes accurately predicts breast cancer presenting features (with emphasis on prediction of nodal involvement), recurrence patterns and disease free survival.     

Differences between Breast Conservation‐Eligible Patients and Unilateral Mastectomy Patients in Choosing Contralateral Prophylactic Mastectomies

There has been an increasing use of bilateral mastectomy (BM) for breast cancer. We sought to examine our trends among breast conservation (BCT) candidates and women recommended for unilateral mastectomy (UM). Our prospective breast cancer database was queried for women with a first‐time, unilateral breast cancer. Patient and histologic factors and surgical treatment, including reconstruction, were evaluated. A detailed chart review was performed among patients from two representative time periods as to the reasons the patient underwent mastectomy. We identified 3,892 women between 2000 and 2012 of whom 60% underwent BCT, 1092 (28%) had UM and 12% underwent BM. BM rose from 4% in 2000 to a high of 19% in 2011, increasing around 2002 for women <40. BCT was less likely with decreasing age (p < 0.0001), lobular histology (p < 0.0001), higher stage (p < 0.0001) and decreasing BMI (p < 0.0001). Among mastectomy patients, contralateral mastectomy was associated with decreasing age (p < 0.0001), Caucasian race (p < 0.0001), and lower stage (p = 0.005). Over time, indications for mastectomy decreased while patients deemed BCT‐eligible opting for UM or BM increased dramatically. Increases in the use of BM are in large part among women who were otherwise BCT‐eligible. Factors associated with BM use are different for BCT‐eligible patients and those recommended for UM. A better understanding of the factors driving individual patient choices is needed.     

Clinical outcome of patients with brain metastases from breast cancer - A population based study over 21 years

BackgroundBrain metastases (BM) are a feared progression of breast cancer (BC) with impact on quality of life and survival. Despite improved treatments, it is believed patients suffering from BM are increasing.AimsTo study potential changes in the number of BM, the possible links between BC subgroup and extent of BM with prognosis. To investigate the interval between primary BC/extra cranial recurrence, and diagnosis of BM in the years 1994–2014.Patients and methodsClinical data from 191 patients with BM diagnosed 1994–2014, was retrieved from charts. Primary tumours where re-evaluated histologically.ResultsThere was an increase of BM in 5 years cohorts (1994-99 (n = 9); 2000-04 (n = 36); 2005-09 (n = 60); 2010-14 (n = 86)). We found no difference in the time interval from primary BC to BM but an insignificant increase in time from extra cranial relapse to development of BM in the time periods 1994–2004 and 2005–2014 of 15.5 and 25.0 months (p = 0.0612). Survival after BM was 7 months (95% CI 6–10) with a statistically significant difference between HER2 positive and TNBC with an inferior outcome for the latter (p = 0.018) whilst no differences were present when Luminal BC were compared with HER2 positive BC (p = 0.073).ConclusionsWe show an increase of BM over time whilst the time span from primary BC to BM is unchanged supports earlier findings that adjuvant treatments have little preventive function. Time from extra cranial recurrence to BM was prolonged with one year. Patients with TNBC or more advance extent of BM had the shortest survival with BM.     

Locoregional Recurrence and Survival Outcomes by Type of Local Therapy and Trastuzumab Use Among Women with Node-Negative,HER2-Positive Breast Cancer

Background

While human epidermal growth factor receptor 2 (HER2) overexpression is an adverse breast cancer prognostic factor, it is unclear whether there are differences in outcomes between types of local treatment in this population. This retrospective study examined locoregional recurrence and survival in women with node-negative, HER2+ breast cancer treated with breast-conserving therapy (BCT) versus mastectomy.

Methods

Subjects were 748 patients with pT1–2, N0, M0 HER2+ breast cancer, treated with BCT (n = 422) or mastectomy (n = 326). Trastuzumab was used in 54 % of subjects. The 5-year Kaplan–Meier locoregional recurrence free survival (LRRFS), breast cancer specific survival (BCSS), and overall survival (OS) were compared between cohorts treated with BCT versus mastectomy. Subgroup analyses of LRR and survival were performed separately among patients treated with BCT or mastectomy to examine the effect of trastuzumab on outcomes in each group.

Results

Median follow-up was 4.4 years. Patients treated with mastectomy had higher proportions of grade 3 histology (69 vs 60 %, p = 0.004) and lower rates of hormone therapy (51 vs 64 %, p < 0.001) and trastuzumab therapy (50 vs 57 %, p = 0.04). The 5-year outcomes in women treated with BCT compared with mastectomy were: LRRFS 98.0 versus 98.3 % (p = 0.88), BCSS 97.2 versus 96.1 % (p = 0.70), and OS 95.5 versus 93.4 % (p = 0.19). Trastuzumab was associated with similar LRRFS and improved OS in both local treatment groups.

Conclusions

BCT is safe in the population of women with pT1–2, N0, HER2+ breast cancer, providing high rates of locoregional control and survival equivalent to mastectomy. Trastuzumab was associated with improved survival in both groups.     

Phyllodes tumors of the breast: Adjuvant radiation therapy revisited

BackgroundPhyllodes tumors (PT) are rare entity and surgical resection is the cornerstone of treatment. No standard of care exists regarding adjuvant treatment especially radiation therapy (RT).Patients and methodsWe analyzed all patients with non-metastatic, resected phyllodes tumors who presented to our institution from January 2005 through December 2019. Primary study endpoints included local recurrence free survival (LRFS) and overall survival (OS).ResultsOne hundred and eight patients were analyzed (patients with incomplete treatment and follow up data were excluded). Fifty patients had benign phyllodes, 26 patients had borderline and 32 patients had malignant phyllodes. In the benign group, no significant difference in LRFS was observed between patients who received adjuvant RT (n = 3) and those who did not (5-year LRFS 100% vs. 85% respectively, p = 0.49). The 5 year OS for patients who received RT was 60% vs. 89% for those who did not (p 0.40). In the borderline/malignant group, adjuvant RT significantly improved five year LRFS (90% in the RT group vs. 42% in the no RT group, p = 0.005). The 5 year LRFS in patients treated with margin negative breast conserving surgery and RT was 100% vs. 34.3% in patients who did not receive RT (p 0.022). Patients treated with mastectomy and RT had a 5 year LRFS of 100% vs. 83% for patients who did not receive RT (p 0.24). On multivariate analysis, radiation therapy was independently associated with decreased hazard of local failure (HR 0.21, CI 0.05–0.89, p = 0.03). No difference in OS was found between the RT and no RT groups (5-year OS was 52% vs. 45% respectively, p 0.54).ConclusionThe results of the current study confirm the excellent prognosis of benign phyllodes tumors; warranting no further adjuvant treatment after margin-negative surgical resection. For patients with borderline/malignant phyllodes tumors, adjuvant radiation therapy significantly improved LRFS after margin negative wide local excision; however, patients treated with mastectomy did not attain the same benefit from adjuvant irradiation.     

Factors associated with nonunion of the posttraumatic subtalar arthrodesis after displaced intra-articular calcaneal fractures

BackgroundThis study investigated the incidence of and risk factors for nonunion in patients with posttraumatic subtalar arthrodesis (SA).MethodsWe retrospectively reviewed 165 posttraumatic SA cases. Nonunion was diagnosed at 6 months after surgery based on the findings of clinical evaluations, plain radiographs, and CT scans. Patient-specific factors and surgeon-specific factors were evaluated as potential risk factors.ResultsThe overall nonunion rate was 13.3 % (22 of 165 cases). In the final multivariate logistic regression analysis, smoking (odds ratio [OR] = 3.64; 95 % confidence interval [CI] = 1.23–10.75), parallel screw configuration (OR = 5.70; 95 % CI = 1.62–20.06), and freeze dried iliac crest (OR = 9.16; 95 % CI = 2.28–36.79) were demonstrated as risk factors for nonunion of posttraumatic SA.ConclusionPatients with a history of smoking, parallel screw configuration fixation, and those who received freeze dried iliac crest as an interpositional graft, had a significantly higher rate of nonunion.     

Lack of association between breast reconstructive surgery and the development of chronic pain after mastectomy: A propensity matched retrospective cohort analysis

ObjectivesTo compare if mastectomy with reconstructive surgery had greater incidence of chronic pain compared to mastectomy surgery alone.Materials and methodsThe study was a retrospective cohort. Patients who underwent mastectomies with and without reconstruction responded to the modified short form Brief Pain Inventory and the short form McGill pain questionnaire to identify and characterize pain at least 6 months after the surgical procedure. Propensity matching analysis was used to control for covariates differences in the study groups.Results310 subjects were included and 132 patients (43%) reported the presence of chronic pain. After propensity score matching to adjust for covariate imbalances, the incidence of chronic pain in the mastectomy group who had additional surgery for breast reconstruction was not different compared to the group who had mastectomy surgery alone, 26 out of 68 (38%) and 27 out of 68 (39%), respectively P = 1.0. Among patients who had chronic pain, breast reconstruction did not increase the intensity of worst pain in the last 24 h, median (IQR) of 2 (1–5) compared to 4 (1–5) in the no reconstruction group, P = 0.41. Type of reconstruction (breast implants vs. flap tissue) did not result in greater incidence and/or intensity of chronic pain.ConclusionsBreast reconstruction after mastectomy does not result in a greater incidence of chronic pain compared to mastectomy alone. Female patients undergoing breast cancer surgery should not incorporate chronic pain in their decision to undergo reconstructive surgery after mastectomy.     

Co-overexpression of HER2/HER3 is a predictor of impaired survival in breast cancer patients

BackgroundRecently, HER3-expression was postulated as independent risk factor for metastatic spread. Therefore, we investigated the role of HER3 expression as prognostic marker in metastatic breast cancer patients.MethodsPatients of different breast cancer subtypes diagnosed with metastatic disease (visceral and/or brain metastases) were identified from a breast cancer database. Tissue samples of the respective primary tumors were retrieved, and immunohistochemical staining for estrogen-receptor, progesterone-receptor, HER2, and HER3 was performed. In HER2 equivocal and selected HER3 positive cases, subsequent fluorescent in situ hybridization (FISH) analysis was performed.ResultsTissue specimens of 110 patients were available for this analysis. 21% had strong, complete, membranous HER3 staining of at least 10% of all tumor cells; HER3 protein expression was not associated with HER3 gene amplification. HER2/HER3 co-overexpression was observed in 12/110 (11%) specimens and HER3-overexpression showed a statistically significant association with HER2-overexpression (p = 0.02). No correlation was observed for HER3-overexpression and overall survival (OS), time to diagnosis of brain metastases, and incidence of brain metastases. Still, in patients with HER3 overexpression, a higher rate of ‘brain only’ metastatic behavior was observed (p = 0.042). In the HER2-positive subgroup, HER3-overexpression was significantly associated with shorter OS from diagnosis of metastatic disease (median 17 vs. 35 months; p = 0.04; log rank test).ConclusionsHER2/HER3 co-overexpression is significantly associated with impaired OS from diagnosis of metastatic disease in patients with HER2-positive metastatic breast cancer. Co-inhibition of HER2 and HER3 or the inhibition of HER2/HER3 hetero-dimerization may improve clinical outcome in this subgroup.