This study investigated the value of some clinicopathological parameters and 18 F-fluorodeoxyglucose-positron emission tomography/computed tomography (18FDG-PET/CT) indices, including textural features, to predict event-free survival (EFS) in estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) locally advanced breast cancer (BC) patients. FDG-PET/CT indices and clinicopathological parameters were assessed before neoadjuvant chemotherapy (NAC). After completion of chemotherapy, all patients had breast surgery with axillary lymph node dissection, followed by radiation therapy and endocrine therapy for 5 years. EFS was estimated using the Kaplan-Meier method. A Cox proportional hazard regression model was used for multivariate analysis. One hundred forty-three consecutive patients with stage II–III ER+/HER2- BC and without distant metastases at baseline PET were included. High standardized uptake values (SUVs), were associated with shorter EFS (HR = 3.51, P < 0.01 for SUVmax; HR = 2.76, P = 0.02 for SUVmean; and HR = 4.40 P < 0.01 for SUVpeak). Metabolically active tumor volume (MATV, HR = 3.47, P < 0.01) and total lesion glycolysis (TLG, HR = 3.10, P < 0.01) were also predictive of EFS. Homogeneity was not predictive (HR = 2.27, P = 0.07) and entropy had weak prediction (HR = 2.89, P = 0.02). Among clinicopathological parameters, EFS was shorter in progesterone receptor (PR)-negative tumor (vs. PR-positive tumor; HR = 3.25, P < 0.01); histology was predictive of EFS (lobular vs. ductal invasive carcinoma; HR = 3.74, P = 0.01) but not tumor grade (grade 3 vs. grade 1–2; HR = 1.64, P = 0.32). Pathological complete response after NAC was not correlated to the risk of relapse. Three parameters remained significantly associated with EFS in multivariate analysis. MATV (HR = 1.01, P < 0.01), progesterone receptor expression (HR = 2.90, P = 0.03) and tumor histology (HR = 3.80, P = 0.02). Baseline PET parameters measured before neoadjuvant treatment have prognostic values in ER+/HER2- locally advanced breast cancer patients. After multivariate analysis, metabolically active tumor volume remains significant while textural analysis of PET images is not of added value. Considering histopathological parameters, our study shows that patients with PR-negative or lobular invasive tumor have poorer prognosis than patients with PR-positive or ductal carcinoma, respectively.

To assess the antitumor efficacy and safety profile of the combination of Fluorouracil (5FU) and vinorelbine given as first-line therapy to patients with advanced breast cancer. As defined in the seven consecutive steps of a phase II group sequential design, 63 patients received 5FU 750 mg/m2/d for 5 consecutive days as a continuous infusion and vinorelbine 30 mg/ m2 on days 1 and 5 as a short intravenous (I/V) infusion every 3 weeks. Forty-one of 63 patients achieved an objective response, which allowed us to discontinue the study and reject a response rate less than 50% with a statistical power of 90%. The unbiased estimate of the response rate was 61.6%. Response rate did not differ significantly according to the following: (1) type of prior adjuvant therapy (none, n = 23; without anthracycline, n = 6; with anthracyline, n = 34); (2) site of metastatic disease; and (3) number of metastatic sites. The median time to progression was 8.4 months. The median response duration was 12.3 months, and the median duration of complete response (CR), from the first assessment of CR, was 7.3 months. The median overall survival time was 23 months (28.1 months for patients with a CR). The main toxicities (grades 3 and 4) were neutropenia (90% of patients), infection (12.7%), mucositis (37%), and constipation (9.5%). Nevertheless, treatment could be given on an outpatient basis to the majority of patients, and the median relative dose-intensity was 86%. This phase II study, which used a group-sequential design, shows that the combination of 5FU and vinorelbine is an active and tolerable regimen for the treatment of first metastatic progression of breast cancer. It provides an alternative regimen for patients who have previously received anthracycline-based adjuvant chemotherapy or in whom anthracyclines cannot be used.

Background: Patients with triple-negative breast cancers (TNBC) have a poor prognosis unless a pathological complete response (pCR) is achieved after neoadjuvant chemotherapy (NAC). Few studies have analyzed changes in TIL levels following dose-dense dose-intense (dd-di) NAC. Patients and methods: From 2009 to 2018, 117 patients with TNBC received dd-di NAC at our institution. We aimed to identify factors associated with pre- and post-NAC TIL levels, and oncological outcomes relapse-free survival (RFS), and overall survival (OS). Results: Median pre-NAC and post-NAC TIL levels were 15% and 3%, respectively. Change in TIL levels with treatment was significantly correlated with metabolic response (SUV) and pCR. High post-NAC TIL levels were associated with a weak metabolic response after two cycles of NAC, with the presence of residual disease and nodal involvement at NAC completion. In multivariate analyses, high post-NAC TIL levels independently predicted poor RFS and poor OS (HR = 1.4 per 10% increment, 95%CI (1.1; 1.9) p = 0.014 and HR = 1.8 per 10% increment 95%CI (1.3–2.3), p < 0.0001, respectively). Conclusion: Our results suggest that TNBC patients with TIL enrichment after NAC are at higher risk of relapse. These patients are potential candidates for adjuvant treatment, such as immunotherapy, in clinical trials.

Inflammatory breast cancers are very aggressive, and among them, triple negative breast cancer (TNBC) has the worst prognosis. While many studies have investigated the association between tumor-infiltrating lymphocytes (TIL) before neoadjuvant chemotherapy (NAC) and outcome in TNBC, the impact of post-NAC TIL and TIL variation in triple negative inflammatory breast cancer (TNIBC) outcome is unknown. Between January 2010 to December 2018, all patients with TNIBC seen at the breast disease unit (Saint-Louis Hospital) were treated with dose-dense dose-intense NAC. The main objective of the study was to determine factors associated with event-free survival (EFS), particularly pathological complete response (pCR), pre- and post-NAC TIL, delta TIL and post-NAC lymphovascular invasion (LVI). After univariate analysis, post-NAC LVI (HR 2.06; CI 1.13–3.74; p = 0.02), high post-NAC TIL (HR 1.81; CI 1.07–3.06; p = 0.03) and positive delta TIL (HR 2.20; CI 1.36–3.52; p = 0.001) were significantly associated with impaired EFS. After multivariate analysis, only a positive TIL variation remained negatively associated with EFS (HR 1.88; CI 1.05–3.35; p = 0.01). TNIBC patients treated with intensive NAC who present TIL enrichment after NAC have a high risk of relapse, which could be used as a prognostic marker in TNIBC and could help to choose adjuvant post-NAC treatment.