Background: In the phase III IMpassion130 trial, combining atezolizumab with first-line nanoparticle albumin-boundpaclitaxel for advanced triple-negative breast cancer (aTNBC) showed a statistically significant progression-free survival (PFS) benefit in the intention-to-treat (ITT) and programmed death-ligand 1 (PD-L1)-positive populations, and a clinically meaningful overall survival (OS) effect in PD-L1-positive aTNBC. The phase III KEYNOTE-355 trial adding pembrolizumab to chemotherapy for aTNBC showed similar PFS effects. IMpassion131 evaluated first-line atezolizumabepaclitaxel in aTNBC. Patients and methods: Eligible patients [no prior systemic therapy or 12 months since (neo)adjuvant chemotherapy] were randomised 2:1 to atezolizumab 840 mg or placebo (days 1, 15), both with paclitaxel 90 mg/m 2 (days 1, 8, 15), every 28 days until disease progression or unacceptable toxicity. Stratification factors were tumour PD-L1 status, prior taxane, liver metastases and geographical region. The primary endpoint was investigator-assessed PFS, tested hierarchically first in the PD-L1-positive [immune cell expression 1%, VENTANA PD-L1 (SP142) assay] population, and then in the ITT population. OS was a secondary endpoint. Results: Of 651 randomised patients, 45% had PD-L1-positive aTNBC. At the primary PFS analysis, adding atezolizumab to paclitaxel did not improve investigator-assessed PFS in the PD-L1-positive population [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.60-1.12; P ¼ 0.20; median PFS 6.0 months with atezolizumabepaclitaxel versus 5.7 months with placeboepaclitaxel]. In the PD-L1-positive population, atezolizumabepaclitaxel was associated with more favourable unconfirmed best overall response rate (63% versus 55% with placeboepaclitaxel) and median duration of response (7.2 versus 5.5 months, respectively). Final OS results showed no difference between arms (HR 1.11, 95% CI 0.76-1.64; median 22.1 months with atezolizumabepaclitaxel versus 28.3 months with placeboe paclitaxel in the PD-L1-positive population). Results in the ITT population were consistent with the PD-L1-positive population. The safety profile was consistent with known effects of each study drug. Conclusion: Combining atezolizumab with paclitaxel did not improve PFS or OS versus paclitaxel alone. ClinicalTrials.gov: NCT03125902.

This meta-regression analysis of 29 heterogeneous neoadjuvant trials does not support the use of pCR as a surrogate end point for DFS and OS in patients with breast cancer. However, pCR may potentially meet the criteria of surrogacy with specific systemic therapies.

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Key PointsQuestionIs fat body mass associated with the prevalence of vertebral fracture in patients with breast cancer undergoing aromatase inhibitor therapy?FindingsThis cross-sectional study of 556 postmenopausal women with early-stage breast cancer treated with aromatase inhibitors found that high fat body mass was associated with a numerically but not significantly lower proportion of vertebral fractures in aromatase inhibitor–naive women and a significantly higher proportion of vertebral fractures in aromatase inhibitor–treated women. This opposite trend in fracture prevalence was confirmed after propensity-score matching.MeaningFat body mass may be a factor associated with vertebral fractures in postmenopausal women with breast cancer receiving aromatase inhibitors.

A comparison of 692 early invasive breast cancer with, and 1564 without, a family history of breast cancer showed that the former were younger at diagnosis (P ¼ 0.002), had smaller tumours (P ¼ 0.012), were more frequently oestrogen receptor positive (P ¼ 0.006) and diagnosed preclinically (Po0.001). A long recognised risk factor for breast cancer is a family history of the disease, although the majority of affected women do not have an affected close relative, and only 5 -10% do have a true hereditary predisposition (Carter, 2001). The overall risk of developing breast cancer is 1.9-3.9 times higher in women with an affected mother or sister (Collaborative Group on Hormonal Factors in Breast Cancer, 2001), but only a few studies have investigated the characteristics of breast cancer in women with a family history. We analysed the pathological, biological and clinical features of breast cancer in patients with (FH þ ) and without (FHÀ) a family history of breast cancer, the former being further subdivided into those with an affected first-or second-degree relative. MATERIALS AND METHODSA total of 2256 women with early invasive operable breast cancer, who underwent surgery at Verona Hospitals between January 1992 and April 2001, were asked at their first visit whether they had any first-or second-degree relatives who had had breast cancer. Our analysis first compared those reporting at least one affected relative (FH þ ) with those reporting no affected relative (FHÀ); subsequently, the FH þ patients were divided into those with at least one first-degree relative (1st DFH) and those with only second-degree relatives with breast cancer (2nd DFH): only firstand second-degree relatives were considered in order to reduce ascertainment bias. Answers were always checked at the subsequent visit (at the time of the first cycle for the patients receiving chemotherapy, after 3 months for the others).All of the patients were assigned a UICC pathological TNM stage. On the basis of pathologist-defined tumour size, patients were divided into three categories: pT1 (o2 cm), pT2 (2 -5 cm) and pT3 (45 cm); the number of pathologically positive axillary nodes was divided into none, o3, 4 -10 and 410; tumour grading was recorded as G1 (well differentiated), G2 (moderately differentiated) or G3 (undifferentiated).Immunohistochemistry (IHC) defined oestrogen (ER) and progesterone receptor (PgR) status and was considered positive if more than 10% of the cells were stained for either. The replicative cell fraction was IHC stained using the Ki-67 monoclonal antibody (Mab-DAKO-PC); given the lack of an accepted cutoff point, the results were arbitrarily classified as low, medium or high (p10%, 11 -25% or 425% of stained cells). CerbB-2 levels were determined by IHC using the DAKO-PC monoclonal antibody, and considered positive if at least one cell was stained.At their first visit to the Department of Medical Oncology, all patients were asked about their disease presentation and divided into those who underwent mammography and ultrasonogra...

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Objectives: The aim of this study was to investigate efficacy and safety of eribulin in heavily pretreated patients with advanced breast cancer (BC) in a real-life setting. Methods: This retrospective monocentric study included patients with HER-2-negative metastatic BC, pretreated with anthracyclines and taxanes, who were referred to the Oncology Department of Spedali Civili of Brescia from May 2012 to April 2017. Patients received the same dose of eribulin as that used in the EMBRACE trial: 1.4 mg/m² on days 1 and 8 every 21 days. Results: In a total of 53 patients, 32% obtained a partial response, 11% a stable disease, and 43% a clinical benefit (CB). After a median follow-up of 36 months, median progression-free survival (PFS) was 4.7 months and median overall survival (OS) 13.53 months. Median PFS was significantly longer in patients who reported a CB compared to those with no CB, while survival outcomes (PFS and OS) were better in patients who received > 6 cycles of eribulin. Eribulin showed a good tolerability profile with acceptable toxicities, similar to those reported in EMBRACE. Conclusions: Our experience in a real-world setting confirms the activity, efficacy, and good tolerability profile of eribulin in heavily pretreated BC patients.