Background: Oral progestogens, including megestrol acetate (MA) and medroxyprogesterone acetate (MPA), have largely been superseded by aromatase inhibitors, tamoxifen, and selective oestrogen receptor degraders (SERDs) in oestrogen receptor-positive (ER-positive) metastatic breast cancer. However, they remain an option as late-line therapy after failure of standard treatments. Contemporary data are limited, particularly in patients previously treated with CDK4/6 inhibitors. Methods: We conducted a multi-site retrospective analysis of patients with ER-positive metastatic breast cancer treated with MA or MPA between 2014 and 2024 at four hospital sites across London, United Kingdom. Patients were identified using pharmacy dispensing records. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and Cox regression. Subgroup analyses included prior CDK4/6 inhibitor exposure, histology and liver metastases. Results: A total of 116 patients were included. Median PFS was 2.4 months (95% CI 2.2-2.9), and median OS was 3.3 months (95% CI 2.7-4.9). Prior CDK4/6 inhibitor exposure was associated with shorter PFS (1.9 vs. 2.8 months; HR 1.59; 95% CI 1.08-2.35, p = 0.019) and a trend toward shorter OS (3.1 vs. 3.6 months; HR 1.18, 95% CI 0.80-1.75, p = 0.41). Similarly, liver metastases were associated with shorter PFS (2.3 vs. 2.8 months; HR 1.78, 95% CI 1.12-2.85, p = 0.015), with a trend toward worse OS (3.1 vs. 4.9 months; HR 1.45, 95% CI 0.93-2.25, p = 0.103). A subset of patients derived prolonged benefit, with a 6-month PFS rate of 16%. Toxicity was manageable; thromboembolic events and oedema occurred in 9% and 11% of patients respectively. Appetite improvement was reported in 10%. Conclusions: MA and MPA demonstrated modest but clinically relevant late-line activity in heavily pretreated, endocrine-refractory ER-positive metastatic breast cancer. While prior exposure to CDK4/6 inhibitors was associated with shorter PFS, patients without liver metastases appeared to derive the greatest benefit. These findings support a role for oral progestogens in selected patients who have exhausted standard therapeutic options.

BACKGROUND:Abemaciclib plus fulvestrant was approved in Europe following publication of the MONARCH-2 trial and recommended to enter the NICE Cancer Drugs Fund for HR+/HER2- advanced breast cancer. We aimed to assess MONARCH-2 generalisability to England clinical practice using real-world NHS trust data. METHODS:We identified patients receiving abemaciclib plus fulvestrant from April to December 2019 in the NHS England Blueteq and Systemic Anti-Cancer Therapy data, with follow-up to March 2024. We calculated overall survival (OS) from treatment initiation until death, and treatment-free survival (TFS) and chemotherapy-free survival (CFS) from initiation until post-discontinuation treatment or death (restricting CFS to chemotherapy). We measured outcomes using Kaplan-Meier methodology and compared to MONARCH-2. RESULTS:Median OS was 25.9 months [95% CI: 23.7, 28.4] (N = 876), compared to 46.7 months (N = 446) in MONARCH-2. Differences in gender, age and performance status did not explain OS differences. Median TFS was 11.6 months [95% CI: 10.3, 12.5] compared to a median PFS of 16.9 months in MONARCH-2. Median CFS was 15.3 months [95% CI: 13.8, 16.7], compared to 25.5 months in MONARCH-2. DISCUSSION:MONARCH-2 trial data are not generalisable to this real-world cohort, which had notably shorter OS, TFS and CFS that could not be explained by differences in measured patient characteristics.

Background In selected patients with oligometastatic breast cancer liver metastases (BCLM), liver-directed therapies may provide durable local control and may delay escalation of systemic therapy. This study reports a single-centre experience of percutaneous thermal ablation (radiofrequency ablation [RFA] or microwave ablation [MWA]) for BCLM, including conventional oncologic outcomes and therapy-based endpoints. Methods This retrospective cohort included consecutive patients treated with percutaneous ablation for BCLM following multidisciplinary team approval between 2005 and 2025. Outcomes were defined according to Society of Interventional Oncology (SIO and DATECAN consensus terminology). Lesion-level outcomes included primary/secondary technique efficacy and local tumour progression-free survival (LTPFS). Patient-level outcomes included progression-free survival (PFS), overall survival (OS), time to change of systemic therapy (TTCST) and chemotherapy-free survival (CFS). Kaplan-Meier and Cox regression analyses were performed. Results Forty-six patients underwent 58 ablation sessions treating 80 metastases (median tumour size 19 mm, interquartile range [IQR] 13–27 mm). Primary and secondary technique efficacy were 95% (76/80) and 00% respectively (79/80), respectively. Major complications occurred in 2/58 sessions (3%). Local tumour progression occurred in 16/79 tumours (20%) after a median follow-up of 28 months; LTPFS at 1, 3 and 5 years was 84%, 75% and 75% respectively. Median OS was 44 months (1-, 3- and 5-year OS 94%, 58%, 40%), and median PFS was 8.3 months. Median TTCST was 13 months and median CFS 16.4 months. Triple negative disease was associated with worse LTPFS and shorter CFS. Oligopersistent disease was associated with improved PFS compared with oligoprogression. Conclusion In this selected cohort, percutaneous thermal ablation for BCLM achieved high technique efficacy. Durable local control and low major complication rates. Therapy-based endpoints suggest a clinically meaningful interval without systemic therapy escalation in appropriately selected patients, although comparative studies are needed to quantify the incremental benefit.

BACKGROUND:Adenoid cystic carcinoma (ACC) of the breast is a rare triple-negative malignancy with an indolent clinical course distinct from conventional triple-negative breast cancer (TNBC). Optimal management remains undefined due to limited prospective data. This study aimed to characterise the clinicopathological features, treatment patterns, and long-term outcomes of breast ACC at a high-volume specialist centre, contributing real-world evidence to inform management in the absence of prospective trial data. METHODS:A single-institution retrospective cohort study was conducted of 24 patients with histopathologically confirmed breast ACC treated at The Royal Marsden NHS Foundation Trust between 2000 and 2020. Clinicopathological and outcome data were analysed descriptively; overall survival (OS), disease-specific survival (DSS), and relapse-free survival (RFS) were estimated using the Kaplan-Meier method. RESULTS:Median age was 57 years. Nodal involvement was rare (8%). Adjuvant radiotherapy was administered in 88% of patients; only two patients (8%) received chemotherapy for breast ACC. Five patients (21%) experienced disease relapse after a median of 2.3 years (range 1.3-14.0). The estimated 5- and 10-year OS were both 88.4% (95% CI 74.5-100%) and DSS were both 93.3% (95% CI 81.5-100%). CONCLUSIONS:To our knowledge this represents the largest single-institution cohort study of breast ACC reported to date. The clinical behaviour of breast ACC more closely resembles salivary gland ACC than conventional TNBC, supporting a conservative locoregionally focused management approach and questioning the routine use of chemotherapy on the basis of triple-negative receptor status alone. The propensity for late relapse supports long-term surveillance beyond the standard 5-year window.

Background/Objectives: In selected patients with oligometastatic breast cancer liver metastases (BCLM), liver-directed therapies may provide durable local control and may delay escalation of systemic therapy. This study reports a single-center experience of percutaneous thermal ablation (radiofrequency ablation [RFA] or microwave ablation [MWA]) for BCLM, including conventional oncologic outcomes and therapy-based endpoints. Methods: This retrospective cohort included consecutive patients treated with percutaneous ablation for BCLM following multidisciplinary team approval between 2005 and 2025. Outcomes were defined according to the Society of Interventional Oncology (SIO) and DATECAN consensus terminology. Lesion-level outcomes included primary/secondary technique efficacy and local tumor progression-free survival (LTPFS). Patient-level outcomes included progression-free survival (PFS), overall survival (OS), time to change in systemic therapy (TTCST) and chemotherapy-free survival (CFS). Kaplan-Meier and Cox regression analyses were performed. Results: Forty-six patients underwent 58 ablation sessions treating 80 metastases (median tumor size 19 mm, interquartile range [IQR] 13-27 mm). Primary and secondary technique efficacy were 95% (76/80) and 99% (79/80), respectively. Major complications occurred in 2/58 sessions (3%). Local tumor progression occurred in 16/79 tumors (20%) after a median follow-up of 28 months; LTPFS rates at 1, 3 and 5 years were 84%, 75% and 75%, respectively. Median OS was 44 months (1-, 3- and 5-year OS 94%, 58%, and 40%), and median PFS was 8.3 months. Median TTCST was 13 months, and median CFS was 16.4 months. Triple-negative disease was associated with worse LTPFS and shorter CFS. Oligopersistent disease was associated with improved PFS compared with oligoprogression. Conclusions: In this selected cohort, percutaneous thermal ablation for BCLM achieved high technique efficacy, durable local control and low major complication rates. Therapy-based endpoints suggest a clinically meaningful interval without systemic therapy escalation in appropriately selected patients, although comparative studies are needed to quantify the incremental benefit.

Background: Trastuzumab deruxtecan (T-DXd) is a highly effective treatment for human epidermal growth factor receptor 2 (HER2)-positive and HER2-low advanced breast cancer. Following two fatal pneumonitis cases within 6 months of introducing T-DXd, we implemented more intensive monitoring, including pre-treatment and daily home oxygen saturation measurements and 6-weekly chest imaging. We aimed to investigate the incidence of pneumonitis by grade after implementing this change. Materials and Methods: This paper presents a prospective single-institution observational study of all patients receiving at least one cycle of T-DXd at the Royal Marsden between 1 October 2021 and 30 September 2023, recording patients’ characteristics and treatments. Pneumonitis events were correlated with respiratory symptoms, oxygen saturations and chest imaging. Results: Fourteen patients (22%) developed pneumonitis after a median of eight cycles (range 1–20). Pneumonitis was detected in 2/14 upon emergency computed tomography (CT) scans, in 9/14 patients at the additional 6-weekly thorax CT and in 3/14 upon routine 12-weekly response-evaluation imaging. Pneumonitis was grade 1 in 6 patients, grade 2 in 7 patients and grade 5 in 1 patient. Amongst 8 symptomatic patients, 6/8 reported symptoms only when directly questioned. All 8 described either cough (6), dyspnoea (1) or wheeze (1) with or without fatigue (2). All pneumonitis patients had imaging responses (10) or stable disease (4) to T-DXd. Neither exertional oxygen saturations nor home oxygen saturation monitoring contributed to early pneumonitis diagnosis. Conclusions: Pneumonitis was more common in our real-world setting than in phase 3 trials. Despite intensive monitoring, only 6/14 patients with pneumonitis were diagnosed whilst asymptomatic. Careful patient counselling to report symptoms and their early investigation are critical adjuncts to regular CT scans to detect pneumonitis.

INTRODUCTION:Despite significant evidence supporting the benefits of comprehensive oncogeriatric assessment in the management of older patients with cancer, the adoption of specialised geriatric oncology programs in the United Kingdom remains limited. Descriptions of clinic structure and models, patient demographics and baseline characteristics, resource utilisation, and predictors of resource utilisation are lacking in this population, which may complicate or impede the planning, resourcing, and development of further services in this subspecialty on a national and regional basis.MATERIALS AND METHODS:Between November 2021 and April 2023, 244 patients commencing systemic anticancer treatment at the Royal Marsden Hospital, London underwent geriatric screening using the Senior Adult Oncology Programme-3 (SAOP3) screening tool. Baseline clinical factors (sex, age, Charlson Comorbidity Index score, Cumulative Illness Rating Scale-Geriatric [CIRS-G] score, Katz Index score, Barthel Index score, treatment intent, and Eastern Cooperative Oncology Group Performance Status [ECOG-PS]) were assessed as predictors of geriatric impairments and need for multidisciplinary referral and intervention using a negative binomial regression analysis. Referral rates to multidisciplinary teams were assessed against ECOG-PS score using point-biserial correlation, as well as against a historical control using descriptive statistics.RESULTS:The median age of participants was 77; 75.8% were female. Breast cancer was the most prevalent diagnosis (61.9%). Most patients (67.6%) were undergoing treatment in the palliative setting. Two hundred eleven (86.5%) patients were identified as having at least one geriatric impairment. Six hundred forty-nine multidisciplinary referrals were made, of which 583 (86.7%) were accepted by the referred patient. Higher ECOG PS was positively associated with geriatric impairments in physiotherapy, occupational therapy, dietetics, pharmacy, and welfare rights domains, as well as with the overall number of geriatric impairments.DISCUSSION:The Royal Marsden Senior Adult Oncology Programme represents the first geriatric oncology service in a tertiary cancer centre in the United Kingdom. Following implementation of SAOP3 screening, we observed a substantial increase in referrals to all multidisciplinary teams, suggestive of previously underrecognized needs among this population. The need for multidisciplinary intervention was strongly correlated with baseline ECOG-PS score, but not with other measured clinical variables, including comorbidity or functional indices.

INTRODUCTION:Chemotherapy forms the cornerstone of systemic treatment for advanced ovarian cancer, extending overall survival; however, drug-related toxicity can lead to treatment delays, potentially diminishing treatment efficacy. This study evaluated the impact of treatment delays on all-cause mortality of patients with ovarian cancer, to better inform decisions on patient management. METHODS:This retrospective, population-based cohort study included 1517 women with advanced-stage ovarian cancer, receiving first-line adjuvant or neoadjuvant chemotherapy in 2014 and 2015. The frequency of inter-cycle delays >7 days was calculated using drug administration dates. Kaplan-Meier estimates were used to compare 2-year overall survival (OS) between patients who were delayed and those treated to schedule. Cox proportional hazards regression was used to investigate the impact of treatment delay on all-cause mortality. Inverse probability of treatment weighting propensity scores were used to adjust for confounding variables. RESULTS:Delays >7 days occurred in 35.3% of patients. Two-year OS probability was 62.7% in patients who experienced treatment delays >7 days (95% CI, 58.7-66.9) compared to 69.1% in those treated to schedule (95% CI, 66.2-72.0). Delays were not significantly associated with all-cause mortality when adjusted for confounders (HR 1.00 95% CI, 0.83-1.20, P = .9). CONCLUSIONS:Delays to chemotherapy treatment were not significantly associated with worsened survival in patients with advanced-stage ovarian cancer. These results can inform clinical decision making that prioritize toxicity management and quality of life for those treated with chemotherapy.

Background Inter-cycle delays to chemotherapy are often required to manage drug toxicity. The impact of delays on mortality is poorly characterised. This retrospective cohort study examined the association of treatment delay with all-cause mortality in early-stage breast cancer. Methods This real-world analytical study included adult women with stage 2 or 3 breast cancer receiving first-line (neo-)adjuvant chemotherapy between 01/01/2014 and 31/12/2015 in England. Inter-cycle delays >7 days during the treatment period were calculated, and the association of treatment delay with 5-year all-cause mortality was investigated. Survival was compared between patients experiencing treatment delay and those completing treatment to schedule using landmark methodology and Kaplan-Meier (KM) estimator. Cox proportional hazards regression was used to investigate the impact of delay on survival, using inverse probability of treatment weighting to adjust for confounding variables. Results 8,567 patients were included. 17% (1,448) experienced inter-cycle delay >7 days during the treatment period. 1,120 (13%) women had died at the end of the 5-year follow up period. Median follow-up time was 5.5 years. Survival probability was significantly lower in patients experiencing treatment delay by KM estimator analysis (p<0.0001). Cox proportional hazards regression demonstrated a significant positive association between delay and 5-year all-cause mortality (HR 1.33 95% CI 1.12-1.61, p<0.001). Conclusions This is the largest study of its kind demonstrating an association between treatment delay and all-cause mortality. These findings support interventions to improve toxicity management allowing completion of chemotherapy to schedule where patients experience treatment delay due to treatment-related toxicity or hospital capacity pressures.

Pseudocirrhosis is a diffuse nodularity of the liver that radiologically mimics cirrhosis but is a distinct pathological process. It is seen almost exclusively in patients with liver metastases and may represent a response to systemic treatment. Data on the risk factors for pseudocirrhosis and outcomes are limited. In total, 170 patients with a diagnosis of breast cancer and pseudocirrhosis in a 10-year period were identified and retrospectively analysed. Data were collected on baseline patient characteristics, treatments received, and outcomes. Median time between diagnosis of liver metastases and diagnosis of pseudocirrhosis was 17.1 months (range, 0-149 months). In total, 89.4% of patients received chemotherapy between their diagnosis of breast cancer liver metastases and their diagnosis of pseudocirrhosis, most commonly a taxane (74.7%) or capecitabine (67.1%), and the median treatment lines received was 3. Median OS from first diagnosis of pseudocirrhosis was 7.6 months (95% CI: 6.1-9.6 months) and was longer in patients with HER2+ disease at 16.7 months (95% CI: 6.4-32.9 months), which was statistically significant. In our study, pseudocirrhosis occurred in the presence of liver metastases and was associated with a poor prognosis. HER2+ patients with pseudocirrhosis had a better prognosis than other subtypes, but we did not identify other significant predictors of survival. Chemotherapy was not a prerequisite for pseudocirrhosis development, although the majority of patients had received at least one line of chemotherapy before pseudocirrhosis was diagnosed.

PDF file, 71KB, Efficiency of immunomagnetic separation.

PDF file, 66KB, Oncogenes and mutations detected using the OncoCarta Panel v1.0.

PDF file, 63KB, Survival based on signalling output in total population of 88 patients.

PDF file, 80KB, Experiments detailing the validation of immunomagnetic separation and ELISA.

PDF file, 44KB, Probes for PIK3CA, AKT2 and PTEN.