Clinical outcomes in patients with triple negative or HER2 positive lobular breast cancer: a single institution experience.

PURPOSE: Invasive lobular carcinomas (ILC) are characterised by loss of the cell adhesion molecule E-cadherin. Approximately 15% of ILC are ER negative at the time of breast cancer diagnosis, or at relapse due to loss of ER expression. Less than 5% of classical ILC but up to 35% of pleomorphic ILC are HER2 positive (HER2+). METHODS: Retrospective analysis of clinic-pathological data from patients with Triple negative (TN) or HER2+ ILC diagnosed 2004-2014 at the Royal Marsden Hospital. The primary endpoint was median overall survival (OS) in patients with metastatic disease. Secondary endpoints included response rate to neo-adjuvant chemotherapy (NAC), median disease-free interval (DFI) and OS for patients with early disease. RESULTS: Three of 16 patients with early TN ILC and 7/33 with early HER2+ ILC received NAC with pCR rates of 0/3 and 3/5 patients who underwent surgery, respectively. Median DFI was 28.5 months [95% Confidence interval (95%CI) 15-78.8] for TN ILC and not reached (NR) (111.2-NR) for HER2+ early ILC. Five-year OS was 52% (95%CI 23-74%) and 77% (95%CI 58-88%), respectively. Twenty-three patients with advanced TN ILC and 14 patients with advanced HER2+ ILC were identified. Median OS was 18.3 months (95%CI 13.0-32.8 months) and 30.4 months (95%CI 8.8-NR), respectively. CONCLUSIONS: In our institution we report a high relapse rate after treatment for early TN ILC, but median OS from metastatic disease is similar to that expected from TN IDC. Outcomes for patients with advanced HER2+ ILC were less favourable than those expected for IDC, possibly reflecting incomplete exposure to anti-HER2 therapies. CLINICAL TRIAL REGISTRATION: ROLo (ClinicalTrials.gov Identifier: NCT03620643), ROSALINE (ClinicalTrials.gov Identifier: NCT04551495).

Impact of timing of adjuvant chemothapy for early breast cancer: the Royal Marsden Hospital experience.

BACKGROUND: The optimal time to deliver adjuvant chemotherapy has not been defined. METHODS: A retrospective study of consecutive patients receiving adjuvant anthracycline and/or taxane 1993-2010. Primary endpoint included 5-year disease-free survival (DFS) in patients commencing chemotherapy <31 versus ≥31 days after surgery. Secondary endpoints included 5-year overall survival (OS) and sub-group analysis by receptor status. RESULTS: We identified 2003 eligible patients: 1102 commenced chemotherapy <31 days and 901 ≥31 days after surgery. After a median follow-up of 115 months, there was no difference in 5-year DFS rate with chemotherapy <31 compared to ≥31 days after surgery in the overall population (81 versus 82% hazard ratio (HR) 1.15, 95% confidence interval (95% CI) 0.92-1.43, p = 0.230). The 5-year OS rate was similar in patients who received chemotherapy <31 or ≥31 days after surgery (90 versus 91%, (HR 1.21, 95% CI 0.89-1.64, p = 0.228). For 250 patients with triple-negative breast cancer OS was significantly worse in patients who received chemotherapy ≥31 versus <31 days (HR = 2.18, 95% CI 1.11-4.30, p = 0.02). DISCUSSION: Although adjuvant chemotherapy ≥31 days after surgery did not affect DFS or OS in the whole study population, in TN patients, chemotherapy ≥31 days after surgery significantly reduced 5-year OS; therefore, delays beyond 30 days in this sub-group should be avoided.

Metastatic Soft Tissue Sarcomas in Adolescents and Young Adults: A Specialist Center Experience.

Purpose: Soft tissue sarcomas (STS) account for 8% of all cancers in adolescents and young adults (AYAs). Metastatic STS contribute significantly to disease-related mortality in this age group; however, data are limited due to under-representation in clinical trials. Methods: AYAs aged 18-39 years, diagnosed with metastatic STS between 1990 and 2012, were identified from The Royal Marsden Hospital database. Outcomes of interest were clinical characteristics, treatment patterns, overall survival (OS), and prognostic factors. Results: Overall, 455 patients were included. Median age at diagnosis of metastatic STS was 33 years (interquartile range [IQR] 27-37 years). The most common histological subtypes were leiomyosarcoma (n = 68, 15%), synovial sarcoma (n = 68, 15%), Ewing sarcoma (n = 44, 10%), and rhabdomyosarcoma (n = 35, 8%). Treatments included systemic therapy (n = 395, 87%; median 2 lines [IQR 1-3]; clinical trial n = 93, 22%), radiotherapy (n = 297, 66%), and metastasectomy (n = 191, 43%). Median duration between last chemotherapy regimen and death was 4.6 months (IQR 2-10). Median OS was 19.2 months (95% confidence interval [CI] 15.8-22.2); 5-year OS was 16%. Of common subtypes, patients with rhabdomyosarcoma had the worst OS (8.8 months; 95% CI 7.9-11.4). Adverse prognostic factors included male gender, synchronous metastases, bone or liver metastases, first-line polychemotherapy, and no metastasectomy. Conclusions: Outcomes were variable; patients with supposed chemosensitive subtypes had particularly poor survival. The diverse behavior of STS in AYAs highlights the need for subtype-specific clinical trials.