A randomized trial to assess the biological activity of short-term (pre-surgical) fulvestrant 500 mg plus anastrozole versus fulvestrant 500 mg alone or anastrozole alone on primary breast cancer

Introduction: Fulvestrant shows dose-dependent biological activity. Greater estrogen-receptor (ER) blockade may feasibly be achieved by combining fulvestrant with anastrozole. This pre-surgical study compared fulvestrant plus anastrozole versus either agent alone in patients with ER-positive breast cancer. Methods: In this double-blind, multicenter trial, 121 patients received: fulvestrant 500 mg on day 1 plus anastrozole 1 mg/day for 14-21 days (F+A); fulvestrant plus anastrozole placebo (F); or fulvestrant placebo plus anastrozole (A), 2-3 weeks before surgery. ER, progesterone-receptor (PgR), and Ki67 expression were determined from tumor biopsies before treatment and at surgery. Results: 103 paired samples were available (F, n = 35; F+A, n = 31; A, n = 37). All treatments significantly reduced mean ER expression from baseline (F: 41%, P = 0.0001; F+A: 39%, P = 0.0001; A: 13%, P = 0.0034). F and F+A led to greater reductions in ER versus A (both P = 0.0001); F+A did not lead to additional reductions versus F. PgR and Ki67 expression were significantly reduced with all treatments (means were 34% to 45%, and 75% to 85%, respectively; all P = 0.0001), with no differences between groups. Conclusions: In this short-term study, all treatments reduced ER expression, although F and F+A showed greater reductions than A. No significant differences were detected between the treatment groups in terms of PgR and Ki67 expression. No additional reduction in tumor biomarkers with combination treatment was observed, suggesting that F+A is unlikely to have further clinical benefit over F alone. Trial registration: Clinicaltrials.gov NCT00259090

Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown

Bridging pre-surgical endocrine therapy for breast cancer during the COVID-19 pandemic: outcomes from the B-MaP-C study

Purpose: The B-MaP-C study investigated changes to breast cancer care that were necessitated by the COVID-19 pandemic. Here we present a follow-up analysis of those patients commenced on bridging endocrine therapy (BrET), whilst they were awaiting surgery due to reprioritisation of resources. Methods: This multicentre, multinational cohort study recruited 6045 patients from the UK, Spain and Portugal during the peak pandemic period (Feb–July 2020). Patients on BrET were followed up to investigate the duration of, and response to, BrET. This included changes in tumour size to reflect downstaging potential, and changes in cellular proliferation (Ki67), as a marker of prognosis. Results: 1094 patients were prescribed BrET, over a median period of 53 days (IQR 32–81 days). The majority of patients (95.6%) had strong ER expression (Allred score 7–8/8). Very few patients required expedited surgery, due to lack of response (1.2%) or due to lack of tolerance/compliance (0.8%). There were small reductions in median tumour size after 3 months’ treatment duration; median of 4 mm [IQR − 20, 4]. In a small subset of patients ( n = 47), a drop in cellular proliferation (Ki67) occurred in 26 patients (55%), from high (Ki67 ≥ 10%) to low (< 10%), with at least one month’s duration of BrET. Discussion: This study describes real-world usage of pre-operative endocrine therapy as necessitated by the pandemic. BrET was found to be tolerable and safe. The data support short-term (≤ 3 months) usage of pre-operative endocrine therapy. Longer-term use should be investigated in future trials

Mammographic surveillance in women younger than 50 years who have a family history of breast cancer: tumour characteristics and projected effect on mortality in the prospective, single-arm, FH01 study.

BACKGROUND: Evidence supports a reduction in mortality from breast cancer with mammographic screening in the general population of women aged 40-49 years, but the effect of family history is not clear. We aimed to establish whether screening affects the disease stage and projected mortality of women younger than 50 years who have a clinically significant family history of breast cancer. METHODS: In the single-arm FH01 study, women at intermediate familial risk who were younger than 50 years were enrolled from 76 centres in the UK, and received yearly mammography. Women with BRCA mutations were not explicitly excluded, but would be rare in this group. To compare the FH01 cohort with women not receiving screening, two external comparison groups were used: the control group of the UK Age Trial (106,971 women aged 40-42 years at recruitment, from the general population [ie, average risk], followed up for 10 years), and a Dutch study of women with a family history of breast cancer (cancer cases aged 25-77 years, diagnosed 1980-2004). Study endpoints were size, node status, and histological grade of invasive tumours, and estimated mortality calculated from the Nottingham prognostic index (NPI) score, and adjusted for differences in underlying risk between the FH01 cohort and the control group of the UK Age Trial. This study is registered with the National Research Register, number N0484114809. FINDINGS: 6710 women were enrolled between Jan 16, 2003, and Feb 28, 2007, and received yearly mammography for a mean of 4 years (SD 2) up until Nov 30, 2009; surveillance and reporting of cancers is still underway. 136 women were diagnosed with breast cancer: 105 (77%) at screening, 28 (21%) symptomatically in the interval between screening events, and three (2%) symptomatically after failing to attend their latest mammogram. Invasive tumours in the FH01 study were significantly smaller (p=0·0094), less likely to be node positive (p=0·0083), and of more favourable grade (p=0·0072) than were those in the control group of the UK Age Trial, and were significantly less likely to be node positive than were tumours in the Dutch study (p=0·012). Mean NPI score was significantly lower in the FH01 cohort than in the control group of the UK Age Trial (p=0·00079) or the Dutch study (p<0·0001). After adjustment for underlying risk, predicted 10-year mortality was significantly lower in the FH01 cohort (1·10%) than in the control group of the UK Age Trial (1·38%), with relative risk of 0·80 (95% CI 0·66-0·96; p=0·022). INTERPRETATION: Yearly mammography in women with a medium familial risk of breast cancer is likely to be effective in prevention of deaths from breast cancer