To identify the incidence, recurrence pattern and prognosis of brain metastases (BM) among women with metastatic triple negative breast cancer (mTNBC) treated consecutively at a single institution during a 7-year period. Patients with histologically confirmed mTNBC were retrospectively identified. The incidence of BM as first site of recurrence and the cumulative BM incidence were computed. We used the Cox proportional hazards model to identify the univariate and multivariate factors associated with survival. Four hundred thirty three patients were included with a median overall survival (OS) of 21.6 months after median follow-up for 48.1 months. BM was found in 29% (127/433) of the patients and about a quarter (32/127) of BM was first recurrence. The cumulative incidence of BM at 1 and 2 years was 17 and 25%, respectively. The median time from the diagnosis of extracranial metastases to BM was 10 months. Median OS following a diagnosis of BM was 7.3 months. The longer median OS from time of first recurrent BM was noted compared with those of subsequent recurrent (17.3 vs 6.3 months, p = 0.008). However, patients with first recurrent BM were associated with shorter OS compared with those without BM (17.3 vs 22.1 months, p = 0.006). The independent factors that increased BM death risk were > 3 brain lesions, no BM-directed treatment, subsequent recurrent BM, symptomatic BM and uncontrolled extracranial metastasis. Patients with mTNBC have a high incidence of early BM with subsequent poor survival. The findings lend support to consideration of screening imaging of the brain for mTNBC patients.

Nanoparticle albumin-bound (nab)-paclitaxel has better efficacy, safety profiles, and no need to use prophylactic steroids compared with solvent-based paclitaxel. We performed a single arm, phase II study to evaluate the efficacy and safety of weekly nab-paclitaxel and gemcitabine combination in patients with metastatic breast cancer (MBC) and explored role of tumor/stromal Caveolin-1 (Cav-1) as a predictive biomarker for the efficacy. Nab-paclitaxel (125 mg/m2) and gemcitabine (800 mg/m2) were administered on days 1, 8, and 15 in a 4-week cycle. The primary end point was objective response rate (ORR). Secondary end points were progression free survival (PFS), overall survival (OS) and safety profile. Exploratory study included immunohistochemical detection of Cav-1. Among 85 patients enrolled in the study, ORR was 52.4%. After a median follow-up of 17.2 months, median PFS was 7.9 months (95%CI, 6.6–9.2) and median OS was 25.8 months (95% CI, 20.4–31.1). The most common toxicities were neutropenia (75.0% for all grades; 45.2% for grade 3 or worse) and the most common non-hematologic toxicity was peripheral neuropathy (50.0% for all grades, 7.14% for grade 3 or worse). Higher tumor Cav-1 level and lower stromal Cav-1 level were significantly associated with longer PFS of nab-paclitaxel and gemcitabine. The regimen had substantial antitumor activity and was well tolerated in MBC patients. Tumor/stromal Cav-1 level may be a good predictor for the efficacy of nab-paclitaxel and gemcitabine. NCT01550848 . Registered 12 March 2012.

Background: This study aimed to evaluate tumor heterogeneity of metastatic breast cancer (MBC) and investigate its impact on the efficacy of pyrotinib in patients with HER2-positive MBC. Methods: MBC patients who underwent ¹⁸F-FDG PET/CT before pyrotinib treatment were included. Temporal and spatial tumor heterogeneity was evaluated by the discordance between primary and metastatic immunohistochemistry (IHC) results and baseline ¹⁸F-FDG uptake heterogeneity (intertumoral and intratumoral heterogeneity indexes: HI-inter and HI-intra), respectively. Progression-free survival (PFS) was estimated by the Kaplan–Meier method and compared by a log-rank test. Results: A total of 572 patients were screened and 51 patients were included. In 36 patients with matched IHC results, 25% of them had HER2 status conversion. Patients with homogenous HER2 positivity had the longest PFS, followed by patients with gained HER2 positivity, while patients with HER2 negative conversion could not benefit from pyrotinib (16.8 vs. 13.7 vs. 3.6 months, p < 0.0001). In terms of spatial heterogeneity, patients with high HI-intra and HI-inter had significantly worse PFS compared to those with low heterogeneity (10.6 vs. 25.3 months, p = 0.023; 11.2 vs. 25.3 months, p = 0.040). Conclusions: Temporal heterogeneity of HER2 status and spatial heterogeneity of ¹⁸F-FDG uptake could predict the treatment outcome of pyrotinib in patients with HER2-positive MBC, which provide practically applicable methods to assess tumor heterogeneity and guidance for treatment decisions.

Fulvestrant (Ful) is an effective and widely used agent for first- and second-line treatment of hormone receptor-positive, human epidermal growth factor receptor-2-negative (HR+/HER2−) metastatic breast cancer (MBC). However, there is no evidence of treatment after progression on Ful. Our study aimed to investigate the profile of daily practice regarding therapy after Ful. A consecutive series of 131 HR+, HER2- MBC patients who failed Ful 500 mg as first-line or second-line therapy from June 2014 to June 2017 in 6 institutions were included and analysed. Among 131 patients who failed Ful with similar baseline characteristics, 31 (23.7%) received endocrine therapy (ET), and 100 (76.3%) were treated with chemotherapy (CT). The most frequently applied CT regimen was capecitabine (32%), and the ET regimen was exemestane + everolimus (35.5%). Multivariate analysis showed that patients with bone-only metastasis were associated with lower CT use (OR = 7.97, 95% CI 1.51–41.84, P = 0.01). Among patients who received CT and ET as subsequent treatments, the median progression-free survival (PFS) was 7.5 months (95% CI 6.2–8.8) and 6.0 months (95% CI 4.1–7.9), respectively (p = 0.03). Among patients who were resistant to Ful (PFS < 6 months), the PFS on CT was significantly longer than that on ET (7.1 months vs 3.9 months, p = 0.024, HR = 0.5, 95% CI 0.26–0.97); however, among patients with a PFS ≥6 months on Ful, the efficacy of CT and ET was similar. Additionally, among patients with an older age, bone-only metastasis and ≥3 metastatic sites, no significant difference was observed between the CT and ET groups. Moreover, ET was much more tolerated than CT in terms of the incidence of grade 3/4 toxicities (9.6% vs 27%, P < 0.05). Median overall survival (OS) was not reached. Thus, our findings reveal the pattern of post-Ful treatment in current clinical practice and provide evidence on the efficacy, safety and choice of these treatments.

Fulvestrant 500 mg and exemestane are widely used agents in first-line therapy for metastatic breast cancer (MBC) of estrogen receptor (ER)-positive (ER+) postmenopausal MBC after failure of adjuvant nonsteroidal aromatase inhibitor (NSAI) treatment. Although fulvestrant 250 mg had similar efficacy compared with exemestane (Evaluation of Faslodex versus Exemestane Clinical Trial study) and fulvestrant 500 mg was superior to fulvestrant 250 mg (Comparison of FASLODEX In Recurrent or Metastatic Breast Cancer study), no direct comparison between fulvestrant 500 mg and exemestane has been conducted. The aim of this study was to compare the efficacy and safety of fulvestrant 500 mg and exemestane in daily practice. We retrospectively evaluated the medical records of all patients with ER+ HER2- MBC who received fulvestrant 500 mg or exemestane 25 mg as first-line therapy for MBC from 2015 to 2017 in 4 institutions. A total of 120 patients were available for analysis. Both agents accounted for 50% (60) patients. The median progression-free survival (PFS) of the fulvestrant group was significantly longer than that in the exemestane group (6.2 months [95% confidence interval (CI), 5.0-7.4] versus 4.8 months [95% CI, 3.0-6.7], P = .024). In subgroup analysis, for patients with visceral metastasis or primary endocrine resistance, no significant difference considering PFS was observed in the 2 groups (P = .563 and .769). No significant difference of Grade 3/4 adverse events was observed in the 2 groups (3 patients, 5% versus 2 patients, 3.3%; P = .648). Fulvestrant 500 mg showed better efficacy than exemestane in first-line therapy for MBC of ER+ postmenopausal women after failure of adjuvant NSAI treatment. For patients with visceral metastasis or primary endocrine resistance, both treatments showed poor outcomes, indicating a need for further alternatives (targeted therapy or chemotherapy). Both agents were well tolerated in terms of toxicities.