Miscellaneous Publications

On this page you will find information about and links to miscellaneous publications

 

Summary

This national practice questionnaire (NPQ) was designed to establish the current practice of UK breast multidisciplinary teams (MDTs) regarding breast cancer locoregional recurrence (LRR) management. Scenario-based questions were used to elicit preference in pre-operative staging investigations, surgical management, and adjuvant therapy. In total, 822 MDT members across 42 breast units participated in the NPQ (Feb-Aug 2021). Most units (95%) routinely performed staging CT scan, but bone scan was selectively performed (31%). For patients treated with BCS and radiotherapy, few units (7%) always/usually offered repeat BCS. In the absence of radiotherapy, most units (90%) always/usually offered repeat BCS. For patients presenting with local recurrence following previous BCS and SLNB, most units (95%) advocated repeat SLNB. Where SLNs could not be identified, 86% proceeded to a four-node axillary sampling procedure. For ER+HER2- node negative LRR, 10% of units always/usually offered chemotherapy. For ER+HER2- node positive LRR, this recommendation increased to 64%. For triple negative LRR, 90% of units always/usually offered chemotherapy. Further research is required to determine how these management patterns influence patient outcomes, which will refine optimal treatment pathways.

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Summary

This cohort study aimed to determine the outcomes of women who had no surgery for screen-detected DCIS. English breast screening databases were utilised to identify patients diagnosed with DCIS without invasive cancer at screening with no record of surgery within 6 months of diagnosis. Data was available for 311 patients (median age 62 years). 60 patients subsequently developed invasive cancer (56 ipsilateral and 4 contralateral). The ipsilateral invasive cancer risk increased linearly with time. The 10-year cumulative risk of ipsilateral invasive breast cancer was 9%, 39%, and 36% for low, intermediate, and high grade DCIS respectively. Other associated factors that increased this cumulative risk included younger age, larger DCIS lesions, and associated microinvasion. Most subsequent invasive cancers that developed were grade 2 or 3. Therefore, active surveillance may be reasonable alternative to surgery in patients with low grade DCIS. However, patients with intermediate or high grade DCIS should be offered surgery. The study highlights the importance of reproducible DCIS grading to guide patient management.

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This IDEAL stage 2a/2b platform cohort study examined the effectiveness localisation and removal of the index lesion using wires vs. magnetic seeds. From 35 units, 2300 patients were recruited (Aug 2018-Aug 2020). Index lesion identification rate was 99.8% for magnetic seeds (n=946) and 99.1% for wires (n=1170). For patients undergoing breast conserving surgery for lesions <50mm (n=1746), there were no differences in median closest margin (2mm vs. 2mm), re-excision rate (12% vs. 13%), and specimen weight in relation to lesion size (0.15g/mm2 vs. 0.14g/mm2). Therefore, magnetic seed localisation demonstrated similar safety and effectiveness when compared to wire localisation.

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Summary

This randomised controlled trial (n=307) investigated the use of prophylactic compression sleeves to prevent arm swelling post-axillary lymph node dissection. The compression sleeves were used until 3 months after completing adjuvant treatments. Arm swelling was measured using bioimpedance spectroscopy (BIS) and relative arm volume increase (RAVI). Hazard ratio for developing arm swelling in the compression group relative to the control group was 0.61 (p=0.004) using BIS and 0.56 (p=0.034) using RAVI. The estimated cumulative incidence of arm swelling was lower in the compression group using BIS (42% vs. 52%) and RAVI (14% vs. 25%) measurements. Therefore, prophylactic compression sleeves reduced arm swelling in women at high risk of lymphodema in the first year after breast cancer surgery.

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Summary

This prospective cohort study categorised the patient’s presenting symptoms to a breast clinic (over 12 months) to 4 distinct clinical groups in order to investigate cancer incidence. Of 10830 women, 19% were referred with breast pain, 62% with lumps, 4% with nipple symptoms, and 15% with ‘other’ symptoms. Mammograms, performed in 56.4% of women with breast pain, identified breast cancer in 0.7%. Overall breast cancer incidence was 0.4% for patients who present with breast pain. However, breast cancer incidence was 5% in each of the other 3 clinical groups. Compared with reassurance in primary care, referral was more costly (net cost £262) without additional health benefits (net QALY loss -0.012). This study demonstrates that alternative management pathways for breast pain are required to improve capacity and reduce financial burden.

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This EBCTCG meta-analysis investigated whether pre-menopausal women treated with ovarian suppression benefited from aromatase inhibitors (AIs). Meta-analysis was performed from individual patient data from RCTs (ABCSG XII, SOFT, TEXT, and HOBOE trials) comparing AIs vs. tamoxifen in pre-menopausal women with ER+ breast cancer receiving ovarian suppression. Data analysis was performed for 7030 women with ER+ breast cancer enrolled between 1999 to 2015 (median follow up of 8 years). Breast cancer recurrence rate was lower for women allocated to AI as opposed to tamoxifen (RR 0.79; p=0.0005). The main benefit was seen in years 0-4 (RR 0.68; p<0.0001), with a 3.2% absolute reduction in 5 year recurrence risk (6.9% vs. 10.1%). No further benefit was seen in years 5-9 or beyond year 10. Distant recurrence was reduced with AIs (RR 0.83; p=0.018). No significant differences were observed for breast cancer mortality (RR 1.01; p=0.94), death without recurrence (1.3; p=0.34), or all-cause mortality (RR 1.04; p=0.68). More bone fractures were observed with AIs when compared to tamoxifen (6.4% vs. 5.1%; p=0.017). Endometrial cancer was rare (0.2% AI group vs. 0.3% tamoxifen group; p=0.14). This meta-analysis shows that using AIs rather than tamoxifen in pre-menopausal women receiving ovarian suppression reduces breast cancer recurrence risks. Longer term follow-up is required to assess any impact on survival outcomes.    

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Summary

This prospective randomised trial assigned postmenopausal women with HR-positive breast cancer who had received 5 years of adjuvant endocrine therapy (n=3484) to receive either additional 2 or 5 years of anastrozole. After a median follow-up of 118 months, disease progression or death occurred in 335 women in each treatment group with no differences in disease free survival (HR, 0.99; 95% CI; 0.85 to 1.15; p=0.9). No between-group differences occurred in secondary endpoints including overall survival, contralateral breast cancer, and second primary breast cancer. However, the risk of clinical bone fracture was higher in the 5-year group (HR, 1.35; 95% CI; 1.00 to 1.84).

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This study aimed to identify characteristics that are associated with negative pathological node (ypN0) in patients with clinically node-negative (cN0) breast cancer treated with NACT. This cohort study included patients with cT1-3 cN0 breast cancer treated with NACT (2013 to 2018). Overall, 85.5% (259/303 patients) achieved ypN0, with high rates among those with a radiologically complete response (rCR) on breast MRI (95.5%). Some 82% of patients with HR+ breast cancer, 98% of patients with TNBC, and all patients with HER2+ breast cancer who had rCR achieved ypN0. Multivariate analysis showed that HER+ (OR 5.77; 95% CI 1.91 to 23.13) and TNBC subtype (OR 11.65; 95% CI 2.86 to 106.89) were associated with ypN0 status.

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Summary

This pooled analysis of 2310 patients from four neoadjuvant clinical trials examined survival and treatment response in patients with HER2-low-positive (immunohistochemistry 1+ or 2+/in-situ hybridisation negative; n=1098) versus HER2-zero (immunohistochemistry0; n=1212) breast cancer. HER2-low-positive tumours had significantly lower pathological complete response (29.2% vs. 39%; p=0.0002). This was also seen in the hormone receptor positive subgroup (17.5% vs. 23.6%; p=0.024), but not in the hormone receptor negative subgroup (50.1% vs. 48%; p=0.21). Patients with HER2-low-positive tumours had significantly longer survival (3 year DFS 83.4% vs. 76.1%; p=0.0084). This was seen in hormone receptor negative tumours (3 year DFS 84.5% vs. 74.4%; p=0.0076), but not in hormone receptor positive tumours (3 year DFS 82.8% vs. 79.3%; p=0.39).  

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Summary

This meta-analysis, including 14 studies (n=19819), evaluates the safety of breast conserving surgery (BCS) in triple negative breast cancer. 9828 patients underwent BCS (49.6%) and 9991 patients (50.4%) underwent mastectomy. The pooled odds ratio (OR) for locoregional recurrence was 0.64 (0.48 to 0.85; p=0.002) indicating lower odds for LRR for women who had BCS as opposed to mastectomy.  The pooled OR for distant metastasis was 0.7 (0.53 to 0.94; p=0.02) indicating lower odds of distant metastasis for women who underwent BCS. This difference diminished with follow up time. Pooled hazard ratio of 0.78 (0.69 to 0.89; p<0.001) showed lower hazard ratio for all-cause mortality among women treated with BCS.

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Summary

This cohort study used prospectively collected national data and included women diagnosed with primary invasive T1-2 N0-2 breast cancer. Patients underwent breast surgery in Sweden (2008-2017; n=48986 with median follow up of 6.28 years). Patients received BCS and radiotherapy (n=29367; 59.9%), mastectomy without radiotherapy (n=12413; 25.3%), or mastectomy with radiotherapy (n=7206; 14.7%). 5 year OS was 91.1% and BCSS was 96.3%. OS and BCSS were significantly worse after mastectomy without radiotherapy (HR 1.79 and HR 1.66 respectively) and mastectomy with radiotherapy (HR 1.24 and HR 1.26 respectively) than after BCS and radiotherapy. 

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Summary

Poly(adenosine diphosphate–ribose) polymerase inhibitors target cancers with defects in homologous recombination. This study was a phase 3, double-blind, RCT involving patients with HER2–negative early breast cancer with BRCA1 or BRCA2 or likely pathogenic variants who had received local treatment and neoadjuvant or adjuvant chemotherapy. Patients were randomly assigned (in a 1:1 ratio) to 1 year of oral olaparib or placebo.

The primary end point was invasive disease–free survival. A total of 1836 patients underwent randomization.       The 3-year distant disease–free survival was 87.5% in the olaparib group and 80.4% in the placebo group (difference, 7.1 percentage points; 95% CI, 3.0 to 11.1; hazard ratio for distant disease or death, 0.57; 99.5% CI, 0.39 to 0.83; P<0.001). Olaparib was associated with fewer deaths than placebo (59 and 86, respectively) (hazard ratio, 0.68; 99% CI, 0.44 to 1.05; P=0.02); however, the between-group difference was not significant at an interim-analysis boundary of a P value of less than 0.01. Safety data were consistent with known side effects of olaparib, with no excess serious adverse events or adverse events of special interest.

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Summary

This was a multicentre, prospective, observational cohort study of surgery or primary endocrine therapy in women aged over 70 years with operable breast cancer (n=3416 with 56 UK breast units who participated). Adverse effects on quality-of-life outcomes were seen in the first few months after surgery, which largely resolved by 24 months.

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This manuscript was produced on behalf of the academic section of the Association of Breast Surgery and submitted to the Royal College of Surgeons working group on the ‘Future of Surgery’. The article summarises the impact of innovations in science and technology on the future management of breast cancer. The article focuses on genomic advances, de-escalation of surgery, optimisation of breast conserving surgery, neoadjuvant therapy, technologies to improve breast cancer staging, innovations in reconstructive breast surgery, patient follow up and survivorship, and breast cancer surgical research.

Summary

The B-Map-C investigated alterations to breast cancer management during the peak transmission period of the UK COVID-19 pandemic (March to May 2020). 64 UK breast units participated (n=3776) with 59% determined to have had ‘COVID-altered’ management. However, the majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer outcomes are unlikely to be negatively impacted.

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Summary

Significant concerns have been raised about the impact of COVID-19 on the delivery of NHS cancer service. This report compares breast cancer service referral and treatment activity in 2020 and 2021, compared to those in 2019 (pre-pandemic). Data were extracted from the Cancer Waiting Times data set and the COVID-19 Cancer Equity Data Packs. Compared to 2019, there was 33% fewer urgent and 40% fewer routine referrals in the first half of 2020. Urgent referral activity had returned to usual level s by August 2020 and by the first half of 2021, the volume of urgent referral was 10% higher when compared to 2019. The volume of routine referrals remained 16% fewer however. Compared to 2019, there were 16% fewer first treatments for breast cancer in the first half of 2020. There were 19% fewer treatments in the second half of 2020, and only 3% fewer treatments in the first half of 2021. The monthly number of first treatments recovered by December 2020, with the slowest recovery seen in patients aged 50-69 years (population-based screening age group). This reduction in the number of first treatments suggest that there may be approximately 9500 ‘missing’ breast cancer diagnoses since the start of 2020 due to the pandemic. Half of these are likely to be due to reduced screening activity (March to September 2020), and remainder due to the reduction in the number of referral.

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Roszkowski N, Lam SS, Copson E, Cutress RI, Oeppen R. Expanded criteria for pretreatment staging CT in breast cancer. BJS Open. 2021 Mar 5;5(2):zraa006. doi: 10.1093/bjsopen/zraa006. PMID: 33715004; PMCID: PMC7955978.

 

Summary

This study sought to identify factors predictive of distant metastatic disease at presentation to enable appropriate selection of patients for pretreatment CT. A total of 1377 patients with newly diagnosed breast cancer were identified, of whom 1025 had complete data; 323 staging CT examinations were performed. Distant metastases were identified at presentation in 47 (4.6 per cent).Some 30 of 47 patients with metastatic disease met established criteria for staging (T4, recurrence, symptoms of possible distant metastases), leaving 17 patients with metastatic disease potentially missed by use of these criteria alone. Multivariable analysis showed that tumour size at least 3 cm combined with sonographically abnormal axillary lymph nodes predicted a high probability of distant metastatic disease at pre- sentation (positive predictive value 18.8 per cent, odds ratio 4.83, P < 0.001).

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Summary

This study aimed to examine the planned long-term recurrence and survival outcomes from the ELIOT trial. Eligible women, aged 48-75 years with a clinical diagnosis of a unicentric breast carcinoma with an ultrasound diameter not exceeding 25 mm, clinically negative axillary lymph nodes, and who were suitable for breast-conserving surgery, were randomly assigned (1:1) via a web-based system, with a random permuted block design (block size of 16) and stratified by clinical tumour size, to receive post-operative whole breast irradiation (WBI) with conventional fractionation (50 Gy given as 25 fractions of 2 Gy, plus a 10 Gy boost), or 21 Gy intraoperative radiotherapy with electrons (ELIOT) in a single dose to the tumour bed during surgery. The trial was open label and no-one was masked to treatment group assignment. The primary endpoint was the occurrence of IBTR. After a median follow-up of 12·4 years (IQR 9·7-14·7), 86 (7%) patients developed IBTR, with 70 (11%) cases in the ELIOT group and 16 (2%) in the WBI group, corresponding to an absolute excess of 54 IBTRs in the ELIOT group (HR 4·62, 95% CI 2·68-7·95, p<0·0001). At final follow-up on March 11, 2019, 193 (15%) women had died from any cause, with no difference between the two groups (98 deaths in the ELIOT group vs 95 in the WBI group; HR 1·03, 95% CI 0·77-1·36, p=0·85.

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British Journal of Surgery: Feb 2020 

This study examines whether biological subtype in patients diagnosed with inflammatory breast cancer (IBC) influences their outcome using a national cancer database. Amongst 4068 patients diagnosed with IBC, 38.7% were ER+HER2-, 32.5% HER2+, and 28.8% were ER-HER2-. 84% were clinically node positive at presentation. Total pCR rates were 6.2% (ER+HER2-), 38.8% (HER2+), and 19.1% (ER-/HER2-). The 5 year overall survival was rates were 64.9% (ER+HER2-), 74% (HER2+), and 44% (ER-/HER2-). Multivariate analysis showed that ER-/HER2- subtype and the absence of pCR predicted for worse survival. The study findings support the concept that IBC is not a distinct biological entity with uniformly poor outcomes and highlights the recent improved outcomes in HER2+ IBC. However, future studies are needed to improve outcome for patients with ER-/HER2- IBC. 

Medication to Reduce Risk of Breast Cancer: USPS Task Force Recommendation

Journal: JAMA

Young patients with breast cancer and BRCA mutation have similar survival to sporadic breast cancer patients (POSH trial)

Journal: Lancet Oncol

TEAM study

Therapeutic mammaplasty is a safe and effective alternative to mastectomy or standard breast-conserving surgery

Journal: Brit J Surg

RCT Lymphoedema rates reduced with reverse mapping

Journal: Ann Surg Oncol

S-LYMPHA (simplified LYMPHA) may reduce rates of lymphoedema after axillary clearance

Journal: Annals of Surgery

BRASS  Jenny Banks

Breast Angiosarcoma Surveillance Study (BRASS) – A National Audit of Management and Outcomes of Angiosarcoma of the Breast and Chest Wall

The BRASS study is a collaborative project led by practising breast and plastic surgeons in the UK and ROI.