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.     

Impact of Her‐2‐Targeted Therapy on Overall Survival in Patients With Her‐2 Positive Metastatic Breast Cancer

Upon disease progression on trastuzumab‐based therapy, patients with HER‐2 positive metastatic breast cancer (MBC) may switch to lapatinib or continue on trastuzumab. We aimed to assess the impact of both strategies on overall survival (OS) in all patients treated for HER‐2 positive MBC at the Medical University Vienna from 1999 until 2009. A total of 201 patients were identified from a breast cancer data base. Of these 115 (57.2%) received multiple lines of trastuzumab‐based therapy, whereas 58 (28.9%) were treated with a single line. A control group of 28 patients (13.9%) had never received trastuzumab as they were treated before 1999, when trastuzumab was registered. OS from diagnosis of metastatic disease was defined as primary study endpoint. Trastuzumab significantly prolonged OS in HER‐2 positive MBC (41 versus 13 months; p < 0.001). Administration of multiple lines further improved OS; this, however, did not reach statistical significance (47 versus 28 months; p = 0.069). Positive estrogen receptor (ER) status (HR 1.6; 95% CI 1.13–2.27) was associated with better outcome compared to negative estrogen receptor status (p = 0.02). Addition of lapatinib did not improve OS significantly in patients with prior trastuzumab‐based therapy (62 versus 47 months; p = n.s.). Patients receiving lapatinib after diagnosis of BM, however, experienced an improvement of OS (22 versus 5 months; p = 0.022). Trastuzumab improves OS in patients with HER‐2 positive MBC with further nonsignificant improvement when administered in multiple lines. Lapatinib did not further improve OS in the entire population; however, lapatinib might improve OS in patients with BM.     

Prognosis of HER2-positive pregnancy-associated breast cancer: Analysis from the French CALG (Cancer Associé à La Grossesse) network

IntroductionThe prevalence of pregnancy-associated breast cancer is increasing. HER2-positive breast cancers typically have a poor prognosis. The objective of our study was to compare the prognosis of patients with HER2-positive breast cancer diagnosed during pregnancy (HER2-positive BCP) to young women diagnosed with HER2-positive breast cancer outside of pregnancy (HER2 non-BCP).MethodsData of patients managed for invasive breast carcinoma between January 2005 and 2020 were retrospectively collected from the database of Tenon University Hospital (Paris, France), part of the “Cancer lié à la Grossesse” network.ResultsFifty-one patients with HER2-positive BCP were matched on age at diagnosis with 51 HER2-positive non-BCP patients. Locally advanced disease with axillary lymph node involvement were frequent. Tumors were frequently aggressive with high grade (p = 0.57) and high Ki67 (p = 0.15). Among the HER2-positive BCP patients, the mean term at diagnosis was 19.3 week of gestation (WG). Eighty-four percent of the patients continued their pregnancy with a mean term at delivery of 34.2WG. Chemotherapy modalities differed between the two groups: neoadjuvant chemotherapy was more frequent in the HER2-positive BCP group (p = 0.03) and adjuvant chemotherapy more frequent in the HER2 non-BCP group (p = 0.009). The recurrence rate was 10% (n = 5) and 18% (n = 9) in the HER2-positive BCP and HER2 non-BCP groups, respectively, p = 0.25. Breast cancer-free survival was poorer in the HER2-positive BCP group with earlier recurrence, p = 0.008. No difference in type of recurrence was found between the groups (p = 0.58).ConclusionThis matched case-control study implies that patients with HER2-positive BCP still have a poorer prognosis than non-pregnant HER-positive patients.     

Predictive and prognostic values of tumor infiltrating lymphocytes in breast cancers treated with neoadjuvant chemotherapy: A meta-analysis

BackgroundThis meta-analysis assessed the predictive and prognostic value of tumor infiltrating lymphocytes (TILs) in neoadjuvant chemotherapy (NACT) treated breast cancer and an optimal threshold for predicting pathologic complete response (pCR).MethodsA systematic search of PubMed, EMBASE and Web of Science electronic databases was conducted to identify eligible studies published before April 2022. Either a fixed or random effects model was applied to estimate the pooled hazard ratio (HR) and odds ratio (OR) for prognosis and predictive values of TILs in breast cancer patients treated with NACT. The study is registered with PROSPERO (CRD42020221521).ResultsA total of 29 published studies were eligible. Increased levels of TILs predicted response to NACT in HER2 positive breast cancer (OR = 2.54 95%CI, 1.50–4.29) and triple negative breast cancer (TNBC) (OR = 3.67, 95%CI, 1.93–6.97), but not for hormone receptor (HR) positive breast cancer (OR = 1.68, 95 %CI, 0.67–4.25). A threshold of 20% of H & E-stained TILs was associated with prediction of pCR in both HER2 positive breast cancer (P = 0.035) and TNBC (P = 0.001). Moreover, increased levels of TILs (either iTILs or sTILs) were associated with survival benefit in HER2-positive breast cancer and TNBC. However, an increased level of TILs was not a prognostic factor for survival in HR positive breast cancer (pooled HR = 0.64, 95%CI: 0.03–14.1, P = 0.78).ConclusionsIncreased levels of TILs were associated with increased rates of response to NACT and improved prognosis for the molecular subtypes of TNBC and HER2-positive breast cancer, but not for patients with HR positive breast cancer. A threshold of 20% TILs was the most powerful outcome prognosticator of pCR.     

Level of HER2/neu amplification in primary tumours and metastases in HER2-positive breast cancer and survival after trastuzumab therapy

BackgroundThe level of HER2/neu amplification may vary widely in breast cancers with HER2/neu alteration. The clinical significance of this phenomenon is still unclear. This study was aimed to explore the level of HER2/neu amplification in primary tumours and metastases in HER2-positive metastatic breast cancer (MBC) and its potential impact on survival after a trastuzumab-containing therapy.MethodsWe retrospectively identified MBC patients treated with a trastuzumab-containing therapy and performed dual-colour FISH on tumour samples from either primary tumour and/or metastasis in a central laboratory.ResultsWe retrieved 110 tumour samples from 91 patients and included 79 tumour samples (primary = 56; metastasis = 23) from 63 patients in the final analysis. We found higher level of HER2/neu amplification in the metastases than in the primary tumours (median HER2/CEP17 ratio: 10.5 vs 7.0, respectively). In 69% of patients (n = 16) with two tumour samples, the level of HER2/neu amplification was higher in the metastasis than in the paired primary tumour (median HER2/CEP17 ratio: 10.9 vs 8.3, respectively, p = 0.004). The incremental gain in level of HER2/neu amplification was associated with significantly shorter OS after trastuzumab-containing therapy (p = 0.023, HR 1.014, CI95%: 1.002–1.025).ConclusionsThe level of HER2/neu amplification tends to increase from the primary tumour to the paired metastases in a significant proportion of patients with HER2-positive MBC. This phenomenon, although still not completely understood, could lead to a shorter OS after trastuzumab therapy.     

Outcome Following Local‐Regional Recurrence in Women with Early‐Stage Breast Cancer: Impact of Biologic Subtype

Local‐regional recurrence (LRR) after breast‐conserving therapy (BCT) can result in distant metastasis and decreased disease‐free survival (DFS). This study examines factors associated with DFS following LRR. The initial population included 2,233 consecutive women who underwent BCT from 1998 to 2007. Biologic subtype was approximated using a combination of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and tumor grade. Cumulative incidence of DFS after LRR was calculated. The association of clinical, pathologic, and treatment parameters with DFS was evaluated using a Cox regression model. At a median follow‐up of 105 months, 82 patients (3.7%) had a LRR. Of these, 66 (80%) were in‐breast and 16 (20%) involved the ipsilateral lymph nodes. Twenty patients subsequently developed distant metastases. Five‐year DFS after initial recurrence was 69.6% for the overall cohort. On univariate analysis, triple‐negative disease (ER/PR/HER2 negative, TNBC) was associated with reduced DFS (HR = 3.8; 95% CI: 1.8–8.1; p < 0.001). Other factors associated with reduced DFS were larger tumor size (HR = 1.3; 95% CI: 1.03–1.6; p = 0.02), shorter interval from initial diagnosis to LRR (HR = 0.98 per month; 95% CI: 0.97–0.99; p = 0.02), and no salvage surgery (HR = 0.2; 95% CI: 0.09–0.5; p = 0.001). On multivariate analysis, TNBC remained the most significant factor associated with reduced DFS (HR = 4.8; 95% CI: 2.25–10.4; p < 0.001). Compared to women with luminal A disease, those with TNBC had significantly worse DFS (37.5% versus 88.3% at 5 years; p < 0.001). Women with TNBC who developed LRR were at high risk of subsequent recurrence. Efforts should be targeted toward both preventing initial recurrence and decreasing subsequent metastasis.     

Clinical outcomes and treatment practice patterns of patients with HER2-positive metastatic breast cancer in the post-trastuzumab era

BackgroundTrastuzumab is associated with improvements in overall survival (OS) among patients with HER2-positive metastatic breast cancer (MBC); however disease course and patterns of care in individual patients are highly variable.Methods113 HER2-positive patients diagnosed with MBC from 1999 to 2005 who received trastuzumab-based therapy were retrospectively identified to allow for a minimum of 5 years of follow-up time. Median OS and median duration of therapy were determined using Kaplan–Meier methodology and group comparisons were based on the log-rank test. Hazard ratios (HR) were obtained using a Cox proportional hazards model.ResultsMedian OS was 3.5 years (95% CI 3.0–4.4) from time of initiation of first therapy in the metastatic setting. On univariate analysis, central nervous system (CNS) disease at first recurrence was associated with a shorter OS compared with liver and/or lung metastases or other sites (CNS: 1.9 years CI 0.1–5.9, liver/lung: 3.2 years CI 2.5–4.2, other: 4.6 years CI 2.7–8.0; p = 0.05), however, this was not predictive of survival outcome in multivariate analysis. CNS metastases developed in 62 (55%) patients by the time of death or last follow-up. Median duration of therapy was similar up to 6 lines of treatment, and ranged from 5.2 months to 7.2 months.ConclusionsThe natural history of HER2-positive MBC has evolved with trastuzumab-based therapy with median OS now exceeding 3 years. CNS disease is a major problem with continued risk of CNS progression over time. Patients demonstrate clinical benefit to multiple lines of HER2-directed therapy.     

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.     

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.     

Isolated pachymeningeal metastasis from breast cancer: Clinical features and prognostic factors

PurposeTo evaluate the clinical features and prognoses of patients with isolated pachymeningeal metastasis (IPM) from breast cancer.MethodsWe reviewed the medical records of all patients with metastatic breast cancer (MBC) treated from January 2009 to August 2016. Eligibility criteria included diagnosis of pachymeningeal metastasis based on brain magnetic resonance imaging and histologic diagnosis of primary breast cancer. We excluded patients with concomitant parenchymal or leptomeningeal metastases.ResultsThirty-eight patients who matched our inclusion criteria were included in this study. The incidence of IPM in breast cancer was 1.5% of all patients with MBC. The molecular subtype distribution was: triple negative, 29.0%; ER+/HER2−, 44.7%; ER+/HER2+, 18.4%; and ER−/HER2+, 7.9%. All isolated pachymeningeal involvement resulted from the direct extension of skull metastases. The median time to IPM from systemic metastasis was 28.6 (95% CI: 23.6–33.6) months. The median time to IPM from skull metastasis was 5.2 (95% CI: 0–10.9) months. The median overall survival (OS) from IPM was 4.0 (95% CI: 2.5–5.5) months. In patients who received chemotherapy the OS was longer than for those who received radiotherapy or supportive care only [median OS 8.9 (95% CI: 0.0–18.4), 2.8 (95% CI: 0.5–5.0), and 0.8 (95% CI: 0.6–1.1) months, respectively (p = 0.006)]. Multivariate analysis revealed that good performance status and chemotherapy were associated with better survival outcomes.ConclusionStratified evaluation is required for patients with skull metastasis from breast cancer, as pachymeningeal involvement can develop and be associated with unsuspected outcomes.     

Male breast cancer: Looking for better prognostic subgroups

PurposeMale Breast Cancer (MBC) remains a poor understood disease. Prognostic factors are not well established and specific prognostic subgroups are warranted.Patients/methodsRetrospectively revision of 111 cases treated in the same Cancer Center. Blinded-central pathological revision with immunohistochemical (IHQ) analysis for estrogen (ER), progesterone (PR) and androgen (AR) receptors, HER2, ki67 and p53 was done. Cox regression model was used for uni/multivariate survival analysis. Two classifications of Female Breast Cancer (FBC) subgroups (based in ER, PR, HER2, 2000 classification, and in ER, PR, HER2, ki67, 2013 classification) were used to achieve their prognostic value in MBC patients. Hierarchical clustering was performed to define subgroups based on the six-IHQ panel.ResultsAccording to FBC classifications, the majority of tumors were luminal: A (89.2%; 60.0%) and B (7.2%; 35.8%). Triple negative phenotype was infrequent (2.7%; 3.2%) and HER2 enriched, non-luminal, was rare (≤1% in both). In multivariate analysis the poor prognostic factors were: size >2 cm (HR:1.8; 95%CI:1.0–3.4years, p = 0.049), absence of ER (HR:4.9; 95%CI:1.7–14.3years, p = 0.004) and presence of distant metastasis (HR:5.3; 95%CI:2.2–3.1years, p < 0.001). FBC subtypes were independent prognostic factors (p = 0.009, p = 0.046), but when analyzed only luminal groups, prognosis did not differ regardless the classification used (p > 0.20). Clustering defined different subgroups, that have prognostic value in multivariate analysis (p = 0.005), with better survival in ER/PR+, AR-, HER2-and ki67/p53 low group (median: 11.5 years; 95%CI: 6.2–16.8 years) and worst in PR-group (median:4.5 years; 95%CI: 1.6–7.8 years).ConclusionFBC subtypes do not give the same prognostic information in MBC even in luminal groups. Two subgroups with distinct prognosis were identified in a common six-IHQ panel. Future studies must achieve their real prognostic value in these patients.     

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.     

The role of tumor phenotype in the surgical treatment of early-stage breast cancer

BackgroundWe investigated whether tumor phenotype influences surgical decision-making, and how that may impact overall survival (OS) for early-stage breast cancer.MethodsWomen aged 18–69 with cT0-2/cN0/cM0 breast cancer in the National Cancer Database (2010–2017) were included. A generalized logistic model was used to identify factors associated with surgery type. A Kaplan-Meier curve was used to visualize unadjusted OS, and the log-rank test was used to test for differences in OS between surgery types.ResultsOf 597,149 patients, 58% underwent lumpectomy with radiation (BCT), 25% unilateral mastectomy (UM), and 17% bilateral mastectomy (BM). After adjustment, HER2+ and triple-negative (TN) tumors were less likely to undergo UM than BCT, versus hormone receptor-positive tumors (OR = 0.881, 95% CI = 0.860–0.903; OR = 0.485, 95% CI = 0.470–0.501). UM and BM had worse 5-year OS versus BCT (UM: 0.926, vs BM: 0.952, vs BCT: 0.960).ConclusionsBCT is increasingly used to treat HER2+ and TN tumors. More extensive surgery is not associated with better survival outcomes, regardless of tumor phenotype.     

Prognostic significance of germline BRCA mutations in patients with HER2-POSITIVE breast cancer

BackgroundHER2-positive breast cancers are rare amongst BRCA mutation carriers. No data exist regarding clinicopathological characteristics and prognosis of this subgroup of patients.Materials and methodsUsing a retrospective matched cohort design, we collected data from 700 women who were diagnosed with operable invasive breast cancer from January 2006 to December 2016 and were screened for germline BRCA mutations. Clinicopathological features and survival rates were analyzed by BRCA and HER2 status.ResultsOne hundred and fifteen HER2-positive/BRCA mutated cases were evaluated in comparison to the three control groups: HER2-positive/BRCA wild type (n = 129), HER2-negative/BRCA mutated (n = 222), HER2-negative/BRCA wild type (n = 234). HER2-positive breast cancers were more likely to have high histologic grade and high proliferation rate than HER2-negative neoplasms, regardless of BRCA mutation status. An interaction between BRCA mutations and HER2-positive status was found to correlate with worse survival after adjusting for prognostic variables (HR = 3.4; 95% CI: 1.3–16.7).ConclusionsCo-occurrence of BRCA mutations and HER2-positive status is a poor prognostic factor in patients with early or locally advanced breast cancer. This finding may be a proof of concept that a combined pharmacological intervention directed to these targets could be synergistic.     

Immunohistochemical prediction of brain metastases in patients with advanced breast cancer: The role of Rad51

BackgroundThere are no clinically useful biomarkers predictive of brain metastases (BM) in breast cancer. In this study, we investigated the correlation between expression of selected proteins in the primary tumor and the risk of BM in patients with metastatic breast cancer (MBC).MethodsThe study included 198 MBC patients (96 with and 102 without BM). Using tissue microarrays derived from the primary tumor, we assessed by immunohistochemical expression of ER, PR, HER2, Ki-67, CK5/6, EGFR, HER3, CXCR4, Rad51, E-cadherin, and claudin 3 and 4.ResultsKi-67 ≥14% (hazard ratio [HR] 2.76; P < 0.001), cytoplasmic expression of Rad51 (HR 1.87; P = 0.014) and ER-negativity (HR 1.72; P = 0.029) were associated with increased risk of BM in the multivariate analysis. A three-biomarker profile including ER, Ki-67 and Rad51 vs. other subtypes combined yielded an HR of 4.43 (P < 0.001).ConclusionsER-negativity, cytoplasmic expression of Rad51 and high Ki-67 are associated with increased risk of BM.     

Interferon‐Induced Protein with Tetratricopeptide Repeats 1 (IFIT1) as a Prognostic Marker for Local Control in T1‐2 N0 Breast Cancer Treated with Breast‐Conserving Surgery and Radiation Therapy (BCS + RT)

Interferon‐induced protein with tetratricopeptide repeats 1 (IFIT1) expression, involved in the regulation of translation, has been implicated to mediate resistance to chemotherapy and radiation in cancer cells in vitro. The purpose of this study was to evaluate the prognostic significance of IFIT1 protein expression in patients with breast cancer treated with Breast‐Conserving Surgery and Radiation Therapy (BCS + RT). A tissue microarray was constructed with specimens from 282 women with node‐negative, early‐stage (I/II) breast cancer who were treated with BCS + RT. Immunohistochemistry was used to stain for the IFIT1 protein. Cytoplasmic IFIT1 protein expression levels were correlated with clinicopathologic factors, local relapse‐free survival (LRFS), disease‐free survival (DFS), and overall survival (OS). IFIT1 positivity was found in 123 (49%) of cases. The median follow‐up time was 7.3 years. Eighty percent of the patients had T1 disease, 88% were human epidermal growth factor receptor 2 (HER2) negative, and 20% had triple‐negative breast cancer (TNBC). IFIT1 positivity was associated with estrogen receptor negative status (p = 0.002), progesterone receptor negative status (p = 0.02), TNBC (p = 0.01), and HER2‐positive status (p = 0.006). In univariate and multivariate analysis, IFIT1 positivity was associated with improved LRFS (p = 0.055 and p = 0.04, respectively). Using a log‐rank test, IFIT1 positivity was found to be associated with improved LRFS (94% versus 85%, p = 0.046) but not DFS or OS at 10 years. On subset analysis of the TNBC patients, IFIT1 positivity was found to correlate with improved LRFS (100% versus 53%, p = 0.004) and DFS in (87% versus 49%, p = 0.048) at 10 years. Elevated IFIT1 protein expression is associated with improved LRFS. In addition, our data suggest that IFIT1 expression may help risk stratify patients with TNBC who may benefit from more aggressive therapy. As there is limited data on IFIT1 in breast cancer, additional work is needed to ascertain its significance.     

Efficacy of taxanes rechallenge in first-line treatment of early metastatic relapse of patients with HER2-negative breast cancer previously treated with a (neo)adjuvant taxanes regimen: A multicentre retrospective observational study

BackgroundTaxanes are one of the most effective chemotherapies (CT) in breast cancer (BC), but the efficacy of taxanes rechallenge in early metastatic relapse has been poorly studied in patients previously treated by taxanes in the (neo)adjuvant setting. Our study aimed to analyse the efficacy of taxane rechallenge in case of early metastatic relapse in a multicentre retrospective observational study compared with other chemotherapies.MethodsWe analysed the French national ESME metastatic BC (MBC) database and selected HER2- MBC patients who received CT in first-line treatment for a metastatic relapse occurring 3–24 months after previous (neo)adjuvant taxanes treatment.ResultsOf 23,501 female patients with MBC in ESME, 1057 met the selection criteria. 58.4% received a taxane-based regimen (75.4% concomitant bevacizumab) and 41.6% received other CT.In hormone-receptor positive (HR+)/HER2- MBC, multivariate analysis showed no difference in OS between taxanes without bevacizumab compared to other CT (HZR = 1.3 [0.97; 1.74], but taxanes was significantly associated with worse PFS (HZR = 1.48 [1.14; 1.93]).In TNBC, taxanes without bevacizumab and carboplatin/gemcitabine were not superior to other CT for OS (HZR = 1.07 [0.79; 1.44] and HZR = 0.81 [0.58; 1.13], respectively), while for PFS, taxanes was inferior (HZR = 1.33 [1.06–1.67]) and carboplatin plus gemcitabine was superior to other CT (HZR = 0.63 [0.46; 0.87]).For both subtypes, the worse outcome observed with paclitaxel was no longer observed with the addition of bevacizumab.ConclusionsWith the limitation of retrospective design, taxanes rechallenge in early metastatic relapse of BC may result in a worse PFS in TNBC and HR+/HER2- MBC, which was not observed with the addition of bevacizumab.     

Long-term follow-up of patients with metastatic breast cancer treated by trastuzumab: Impact of institutions

PurposeTrastuzumab in Human Epidermal growth Receptor 2-positive (HER2+) metastatic breast cancer (MBC) was established as standard therapy since 2001. The objective of this study was to search for significant prognostic factors in patients with HER2+ MBC treated by trastuzumab taking into account the institution where the treatment was given.Patients & methodsAll patients with HER2+ MBC treated by trastuzumab between 2001 and 2010 in the 8 hospitals of Franche Comte region were analysed. Univariate and multivariate analysis were conducted to search for factors related to overall survival (OS).ResultsAmong 1234 patients with MBC treated by chemotherapy between 2001 and 2010, 217 patients received trastuzumab. In this subset, the median age was 60 years, 8% and 38% had brain and liver metastases at first occurrence of MBC, 36% of, tumours were hormonal receptors positive. Patients were treated in 48% and 52% of cases in specialized and in general hospitals, respectively. The median OS length was 45.2 months (IQR 23.2–89.3 months). In univariate analysis the following factors were significantly related to favourable OS: inclusion in clinical trials, treatment in a specialized hospital, positive hormonal receptors status, age <50. In multivariate analysis remained significant: treatment in specialized hospital (aHR 0.78; 95%CI 0.64–0.94; p = 0.03) and age <50 (aHR 0.76; 95%CI 0.59–0.95; p = 0.02).ConclusionExposure to trastuzumab erases all established prognostic factors at the metastatic setting. The fact that patients treated in specialized hospitals presented a longer survival emphasizes the dramatic impact of this therapy and the relevance to optimize its use.     

Indeterminate pulmonary nodules are not associated with worse overall survival in Ewing Sarcoma

AimLung metastases are a negative prognostic factor in Ewing sarcoma, however, the incidence and significance of sub-centimetre pulmonary nodules at diagnosis is unclear. The aims of this study were to (1): determine the incidence of indeterminate pulmonary nodules (IPNs) in patients diagnosed with Ewing sarcoma (2); establish the impact of IPNs on overall and metastasis-free survival and (3) identify patient, oncological and radiological factors that correlate with poorer prognosis in patients that present with IPNs on their staging chest CT.Materials & methodsBetween 2008 and 2016, 173 patients with a first presentation of Ewing sarcoma of bone were retrospectively identified from an institutional database. Staging and follow-up chest CTs for all patients with IPN were reviewed by a senior radiologist. Clinical and radiologic course were examined to determine overall- and metastasis-free survival for IPN patients and to identify demographic, oncological or nodule-specific features that predict which IPN represent true lung metastases.ResultsFollowing radiologic re-review, IPN were found in 8.7% of patients. Overall survival for IPN patients was comparable to those with a normal staging chest CT (2-year overall survival of 73.3% [95% CI 43.6–89] and 89.4% [95% CI 81.6–94], respectively; p = 0.34) and was significantly better than for patients with clear metastases (46.0% [95% CI 31.9–59]; p < 0.0001). Similarly, there was no difference in metastasis-free survival between ‘No Metastases’ and ‘IPN’ patients (p = 0.16). Lung metastases developed in 40% of IPN patients at a median 9.6 months. Reduction of nodule size on neoadjuvant chemotherapy was associated with worse overall survival in IPN patients (p = 0.0084).ConclusionIPN are not uncommon in patients diagnosed with Ewing sarcoma. In this study, we were unable to detect a difference in overall- or metastasis-free survival between patients with IPN at diagnosis and patients with normal staging chest CTs.