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PurposeTo investigate the frequency of germline pathogenic variants (PVs) in women with bilateral breast cancer.MethodsWe undertookBRCA1/2andCHEK2c.1100delC molecular analysis in 764 samples and a multigene panel in 156. Detection rates were assessed by age at first primary, Manchester Score, and breast pathology. Oestrogen receptor (ER) status of the contralateral versus first breast cancer was compared on 1081 patients with breast cancer withBRCA1/BRCA2PVs.Results764 women with bilateral breast cancer have undergone testing ofBRCA1/2andCHEK2; 407 were also tested forPALB2and 177 forATM. Detection rates wereBRCA111.6%,BRCA214.0%,CHEK22.4%,PALB21.0%,ATM1.1% and, for a subset of mainly very early onset tumours,TP534.6% (9 of 195). The highest PV detection rates were for triple negative cancers forBRCA1(26.4%), grade 3 ER+HER2 forBRCA2(27.9%) and HER2+ forCHEK2(8.9%). ER status of the first primary inBRCA1andBRCA2PV heterozygotes was strongly predictive of the ER status of the second contralateral tumour since ~90% of second tumours were ER− inBRCA1heterozygotes, and 50% were ER− inBRCA2heterozygotes if the first was ER−.ConclusionWe have shown a high rate of detection ofBRCA1andBRCA2PVs in triple negative and grade 3 ER+HER2− first primary diagnoses, respectively. High rates of HER2+ were associated withCHEK2PVs, and women ≤30 years were associated withTP53PVs. First primary ER status inBRCA1/2strongly predicts the second tumour will be the same ER status even if unusual for PVs in that gene.

BackgroundWomen with breast pain constitute >20% of breast clinic attendees.AimTo investigate breast cancer incidence in women presenting with breast pain and establish the health economics of referring women with breast pain to secondary care.Design and settingA prospective cohort study of all consecutive women referred to a breast diagnostic clinic over 12 months.MethodWomen were categorised by presentation into four distinct clinical groups and cancer incidence investigated.ResultsOf 10 830 women, 1972 (18%) were referred with breast pain, 6708 (62%) with lumps, 480 (4%) with nipple symptoms, 1670 (15%) with ‘other’ symptoms. Mammography, performed in 1112 women with breast pain, identified cancer in eight (0.7%). Of the 1972 women with breast pain, breast cancer incidence was 0.4% compared with ∼5% in each of the three other clinical groups. Using ‘breast lump’ as reference, the odds ratio (OR) of women referred with breast pain having breast cancer was 0.05 (95% confidence interval = 0.02 to 0.09, PConclusionThis study shows that referring women with breast pain to a breast diagnostic clinic is an inefficient use of limited resources. Alternative management pathways could improve capacity and reduce financial burden.

Background Bilateral-Risk-Reducing-Mastectomy-(BRRM) is well described in BRCA1/2 pathogenic variant carriers. However, little is known about the relative uptake, time trends or factors influencing uptake in those at increased breast cancer risk not known to be carriers. The aim of this study is to assess these factors in both groups. Methods BRRM uptake was assessed from entry to the Manchester Family History Clinic or from date of personal BRCA1/2 test. Follow up was censored at BRRM, breast cancer diagnosis, death or January 01, 2020. Cumulative incidence and cause specific and competing risk regression analyses were used to assess the significance of factors associated with BRRM. Results Of 7195 women at ≥25% lifetime breast cancer risk followed for up to 32 years, 451 (6.2%) underwent pre-symptomatic BRRM. Of those eligible in different risk groups the 20-year uptake of BRRM was 47.7%-(95%CI = 42.4–53.2%) in 479 BRCA1/2 carriers; 9.0% (95%CI = 7.26–11.24%) in 1261 women at ≥40% lifetime risk (non-BRCA), 4.8%-(95%CI = 3.98–5.73%) in 3561 women at 30–39% risk and 2.9%-(95%CI = 2.09–4.09%) in 1783 women at 25–29% lifetime risk. In cause-specific Cox regression analysis death of a sister with breast cancer50; OR = 0.26,95%CI = 0.17–0.41). Uptake continued to rise to 20 years from initial risk assessment. Conclusion We have identified several additional factors that correlate with BRRM uptake and demonstrate continued increases over time. These factors will help to tailor counselling and support for women., Highlights • BRRM continues even 20 years post original breast cancer risk assessment. • Potential triggers include death of mother/sister, children and a breast biopsy. • Uptake is clearly informed by lifetime risk of BC and higher in younger the women.

PurposeTo investigate frequency of germline pathogenic variants (PVs) in women with ductal carcinoma in situ (DCIS) and grade 1 invasive breast cancer (G1BC).MethodsWe undertookBRCA1/2analysis in 311 women with DCIS and 392 with G1BC and extended panel testing (non-BRCA1/2) in 176/311 with DCIS and 156/392 with G1BC. We investigated PV detection by age at diagnosis, Manchester Score (MS), DCIS grade and receptor status.Results30/311 (9.6%) with DCIS and 16/392 with G1BC (4.1%) had aBRCA1/2PV (p=0.003), and 24/176-(13.6%) and 7/156-(4.5%), respectively, a non-BRCA1/2PV (p=0.004). Increasing MS was associated with increased likelihood ofBRCA1/2PV in both DCIS and G1BC, although the 10% threshold was not predictive for G1GB. 13/32 (40.6%) DCIS and 0/17 with G1BC BRCA1/2) and 9/90 (non-BRCA1/2), and 8/47 (BRCA1/2) and 8/45 (non-BRCA1/2), respectively. 6/9BRCA1and 3/26BRCA2-associated DCIS were oestrogen receptor negative-(p=0.003). G1BC population testing showed no increased PV rate (OR=1.16, 95% CI 0.28 to 4.80).ConclusionDCIS is more likely to be associated with bothBRCA1/2and non-BRCA1/2PVs than G1BC. Extended panel testing ought to be offered in young-onset DCIS where PV detection rates are highest.

BackgroundGermline genetic testing affords multiple opportunities for women with breast cancer, however, current UK NHS models for delivery of germline genetic testing are clinician-intensive and only a minority of breast cancer cases access testing.MethodsWe designed a rapid, digital pathway, supported by a genetics specialist hotline, for delivery of germline testing ofBRCA1/BRCA2/PALB2(BRCA-testing), integrated into routine UK NHS breast cancer care. We piloted the pathway, as part of the larger BRCA-DIRECT study, in 130 unselected patients with breast cancer and gathered preliminary data from a randomised comparison of delivery of pretest information digitally (fully digital pathway) or via telephone consultation with a genetics professional (partially digital pathway).ResultsUptake of genetic testing was 98.4%, with good satisfaction reported for both the fully and partially digital pathways. Similar outcomes were observed in both arms regarding patient knowledge score and anxiety, with ConclusionPilot data indicate preliminary demonstration of feasibility and acceptability of a fully digital pathway for BRCA-testing and support proceeding to a full powered study for evaluation of non-inferiority of the fully digital pathway, detailed quantitative assessment of outcomes and operational economic analyses.Trial registration numberISRCTN87845055.

Women with breast cancer-related genetic pathogenic variants (e.g., BRCA1 , BRCA2 ) or with a strong family history carry lifetime risks of developing breast cancer of up to 80 to 90 percent. A significant proportion of these women proceed to bilateral risk-reducing mastectomy. The authors aimed to document the surgical morbidity of risk-reducing mastectomy and establish whether a diagnosis of breast cancer at the time of surgery impacted outcomes.Clinical details of 445 women identified as having a greater than 25 percent lifetime risk of developing breast cancer who underwent risk-reducing mastectomy and breast reconstruction were interrogated for surgical outcomes such as planned, unplanned, and emergency procedures; complication rates; length of stay; and longevity of breast reconstruction. These outcome measures were recorded in women diagnosed with breast cancer perioperatively (cancer group) and those without malignancy (benign group).Median follow-up was similar in both groups (benign group, 70 months; cancer group, 73 months). Patients were older in the cancer group than in the benign group (43 years versus 39 years; p0.001). Women in the cancer group required more planned procedures to complete reconstruction than those in the benign group (four versus two; p = 0.002). Emergency procedures, unplanned surgical interventions (e.g., capsulectomy), and postreconstruction complication rates were similar between groups. One in five women overall required revision surgery. Patients with autologous reconstructions had a revision rate of 1.24 per 1000 person-years compared with 2.52 per 1000 person-years in the implant reconstruction group.Women contemplating risk-reducing mastectomy can be reassured that this is a safe and effective procedure but will likely take multiple interventions. This knowledge should be integral to obtaining informed consent.Risk, II.

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.

BackgroundWomen testing positive for BRCA1/2 pathogenic variants have high lifetime risks of breast cancer (BC) and ovarian cancer. The effectiveness of risk reducing surgery (RRS) has been demonstrated in numerous previous studies. We evaluated long-term uptake, timing and effectiveness of risk reducing mastectomy (RRM) and bilateral salpingo-oophorectomy (RRSO) in healthy BRCA1/2 carriers.MethodsWomen were prospectively followed up from positive genetic test (GT) result to censor date. χ² testing compared categorical variables; Cox regression model estimated HRs and 95% CI for BC/ovarian cancer cases associated with RRS, and impact on all-cause mortality; Kaplan-Meier curves estimated cumulative RRS uptake. The annual cancer incidence was estimated by women-years at risk.ResultsIn total, 887 women were included in this analysis. Mean follow-up was 6.26 years (range=0.01–24.3; total=4685.4 women-years). RRS was performed in 512 women, 73 before GT. Overall RRM uptake was 57.9% and RRSO uptake was 78.6%. The median time from GT to RRM was 18.4 months, and from GT to RRSO–10.0 months. Annual BC incidence in the study population was 1.28%. Relative BC risk reduction (RRM versus non-RRM) was 94%. Risk reduction of ovarian cancer (RRSO versus non-RRSO) was 100%.ConclusionOver a 24-year period, we observed an increasing number of women opting for RRS. We showed that the timing of RRS remains suboptimal, especially in women undergoing RRSO. Both RRM and RRSO showed a significant effect on relevant cancer risk reduction. However, there was no statistically significant RRSO protective effect on BC.

Introduction Men with gynaecomastia are routinely referred to breast clinics, yet most do not require breast surgical intervention. The aim of this study was to assess the impact of a novel point-of-care gynaecomastia decision infographic in primary care on the assessment, management and referral practices to tertiary breast surgical services. Methods A study was carried out of male patient referrals from primary care in Greater Manchester to a tertiary breast centre between January and March in 2018–2020. Referral patterns were compared before and after the infographic went live in general practices in Greater Manchester in January 2020. Data were collected for gynaecomastia referrals, including aetiology, investigation and management. Results In total, 394 men were referred to a tertiary breast centre from 163 general practices, of which 271 (68.8%) had a diagnosis of gynaecomastia. Use of the decision infographic by primary healthcare providers was associated with a decrease in male breast referrals with gynaecomastia (79.6% to 62.0%). Fewer gynaecomastia patients were referred with a benign physiological or drug-related cause after implementation of the infographic (52.2% vs 41.8%). Only 10 (3.7%) patients with gynaecomastia underwent breast surgery during the study period. Conclusion Implementation of a gynaecomastia infographic in primary care in Manchester was associated with a reduction in gynaecomastia referrals to secondary care. We hypothesise that implementation of the infographic into primary care nationally may potentially translate to hundreds of patients receiving more specialty-appropriate referrals, improving overall management of gynaecomastia. Further study is warranted to test this hypothesis.

Introduction: Approximately 55,000 women in the United Kingdom are diagnosed with new breast cancer annually. Since emerging in December 2019, SARS-CoV-2 (coronavirus disease 2019, COVID-19) has become a global pandemic, affecting healthcare delivery worldwide. In response to the pandemic, multiple guidelines were issued to assist with rationalising breast cancer care. The primary aim of the B-MaP-C study is to audit and describe breast cancer management of patients newly diagnosed with breast cancer during the COVID-19 pandemic against pre-COVID-19 management practice in the UK. The implications of changes to management will be determined and the impact of a COVID-19 diagnosis on the patient's breast cancer management will be determined. Methods and analysis: This is a multi-centre collaborative audit of consecutive breast cancer patients undergoing treatment decisions during the acute and recovery phases of the COVID-19 pandemic. All patients with newly diagnosed primary breast cancer, whose treatment was decided in a multidisciplinary meeting from the 16th March 2020, are eligible for inclusion. Ethics and dissemination: As this is an audit ethical approval is not required. Each participating centre is required to register the study locally and obtain local governance approvals prior to commencement of data collection. Local audit data will be available to individual participating units for governance purposes. The results of the data analysis will be submitted for publication, as well as disseminated via the ABS newsletter and a webinar. All data will be presented at national and international conferences, circumstances permitting. Registration details: Each participating centre received local governance audit registration.

Oncoplastic Breast Surgery has become standard of care in the management of Breast Cancer patients. These guidelines written by an Expert Advisory Group; convened by the Association of Breast Surgery (ABS) and the British Association of Plastic, Reconstructive and Aesthetic Surgeons (BAPRAS), are designed to provide all members of the breast cancer multidisciplinary team (MDT) with guidance on the best breast surgical oncoplastic and reconstructive practice at each stage of a patient's journey, based on current evidence. It is hoped they will also be of benefit to the wide range of professionals and service commissioners who are involved in this area of clinical practice.

These guidelines have been produced with the involvement of the Association of Breast Surgery and the British Association of Plastic, Reconstructive and Aesthetic Surgeons. Recommendations have been derived after a review of published data regarding the use of acellular dermal matrix (ADM), biological and synthetic mesh in breast reconstruction. The guidelines represent a consensus opinion on the optimal management of patients having biological or synthetic mesh assisted breast reconstruction informed by peer-review publications. The Guidelines should be used to inform clinical decision making. Ultimately, members of the MDT remain responsible for the treatment of patients under their care.

Purpose Women at increased familial breast cancer risk have been offered screening starting at an earlier age and increased frequency than national Screening Programmes for over 30 years. There are limited data on longer-term largescale implementation of this approach on cancer diagnosis. Methods Women at our institution at ≥ 17% lifetime breast cancer risk have been offered enhanced screening with annual mammography starting at age 35 or 5-years younger than youngest affected relative, with upper age limit 50 for moderate and 60 for high-risk. Breast cancer pathology, stage and receptor status were assessed as well as survival from cancer diagnosis by Kaplan–Meier analysis. Results Overall 14,311 women were seen and assessed for breast cancer risk, with 649 breast cancers occurring in 129,119 years follow up (post-prevalent annual incidence = 4.55/1000). Of 323/394 invasive breast cancers occurring whilst on enhanced screening, most were lymph-node negative (72.9%), T1 (≤ 20 mm, 73.2%) and stage-1 (61.4%), 126/394 stage2–4 (32%). 10-year breast cancer specific survival was 91.3% (95% CI 87.4–94.0) better than the 75.9% (95% CI 74.9–77.0) published for England in 2013–2017. As expected, survival was significantly better for women with screen detected cancers (p n = 75; 95% CI 84.2–97.6). Women with lobular breast cancers had worse 10-year survival at 85.9% (95% CI 66.7–94.5). Breast cancer specific survival was good for 119 BRCA1/2 carriers with 20-year survival in BRCA1:91.2% (95% CI 77.8–96.6) and 83.8% (62.6–93.5) for BRCA2. Conclusions Targeted breast screening in women aged 30–60 years at increased familial risk is associated with good long-term survival that is substantially better than expected from population data.

Contralateral risk-reducing mastectomy (CRRM) rates have tripled over the last 2 decades. Reasons for this are multi-factorial, with those harbouring a pathogenic variant in the BRCA1/2 gene having the greatest survival benefit. On May 14th, 2013, Angelina Jolie shared the news of her bilateral risk-reducing mastectomy (BRRM), on the basis of her BRCA1 pathogenic variant status. We evaluated the impact of this news on rates of CRRM in women with increased risk for developing breast cancer after being diagnosed with unilateral breast cancer. The prospective cohort study included all women with at least a moderate lifetime risk of developing breast cancer who attended our family history clinic (1987–2019) and were subsequently diagnosed with unilateral breast cancer. Rates of CRRM were then compared between patients diagnosed with breast cancer before and after Angelina Jolie’s announcement (pre- vs. post-AJ). Of 386 breast cancer patients, with a mean age at diagnosis of 48 ± 8 years, 268 (69.4%) were diagnosed in the pre-AJ period, and 118 (30.6%) in the post-AJ period. Of these, 123 (31.9%) underwent CRRM, a median 42 (interquartile range: 11–54) days after the index cancer surgery. Rates of CRRM doubled following AJ’s news, from 23.9% pre-AJ to 50.0% post AJ (p p p = 0.040), and to increase with the estimated lifetime risk of breast cancer (p p = 0.015) on univariable analysis. After adjusting for these factors, the step-change increase in CRRM rates post-AJ remained significant (odds ratio: 9.61, p

Gynaecomastia is the commonest male breast complaint. Most cases are benign but the condition may signify a serious underlying illness. The challenge in primary care is to identify which patients with gynaecomastia are at greatest risk of pathological aetiology, so that they may be offered prompt specialty-appropriate referral and treatment. This article offers guidance on the assessment and management of patients with gynaecomastia, including when and why to refer to secondary care. Gynaecomastia refers to the enlargement of male glandular breast tissue. The condition develops because of an imbalance in the male oestrogen:testosterone ratio from a relative oestrogen excess or testosterone deficiency. Pseudo-gynaecomastia is caused by an excess of adipose tissue and does not warrant investigation or treatment. Gynaecomastia is frequently observed in general practice. Prevalence is between 35%–65% in males aged 50–69 years in the UK.1 Patients typically describe a soft swelling in one or usually both breasts. Tenderness, social embarrassment, or worry about cancer are typical reasons for presentation to primary care. Other men are asymptomatic and gynaecomastia may be noted incidentally on physical examination of the chest. Physiological gynaecomastia is common in newborns, adolescence, and senility. Most do not require investigation or referral. Neonatal gynaecomastia arises from the placental transfer of oestrogen. Over half of all adolescent boys will experience transient gynaecomastia during puberty due to a lag in testosterone secretion, with median age of onset at 14 years.2 Physiological gynaecomastia is common among males aged >50 years as testosterone levels fall with increasing age. Adult gynaecomastia is most commonly idiopathic (Figure 1). Male …

Women testing positive forWomen were prospectively followed up from positive genetic test (GT) result to censor date. χ² testing compared categorical variables; Cox regression model estimated HRs and 95% CI for BC/ovarian cancer cases associated with RRS, and impact on all-cause mortality; Kaplan-Meier curves estimated cumulative RRS uptake. The annual cancer incidence was estimated by women-years at risk.In total, 887 women were included in this analysis. Mean follow-up was 6.26 years (range=0.01-24.3; total=4685.4 women-years). RRS was performed in 512 women, 73 before GT. Overall RRM uptake was 57.9% and RRSO uptake was 78.6%. The median time from GT to RRM was 18.4 months, and from GT to RRSO-10.0 months. Annual BC incidence in the study population was 1.28%. Relative BC risk reduction (RRM versus non-RRM) was 94%. Risk reduction of ovarian cancer (RRSO versus non-RRSO) was 100%.Over a 24-year period, we observed an increasing number of women opting for RRS. We showed that the timing of RRS remains suboptimal, especially in women undergoing RRSO. Both RRM and RRSO showed a significant effect on relevant cancer risk reduction. However, there was no statistically significant RRSO protective effect on BC.

Summary Background Many women with increased lifetime risk of developing breast cancer, due to pathogenic gene variants or family history, choose to undergo bilateral risk reducing mastectomies (BRRM). Patient reported outcome measures (PROMS) are an increasingly important part of informed consent but are little studied in women undergoing BRRM. Methods We used a validated PROMS tool for breast reconstruction (BREAST-Q) in 297 women who had BRRM and breast reconstruction, 81% of whom had no malignancy (Benign Group, BG) and 19% in whom a perioperative breast cancer was diagnosed (Cancer Group, CG). 128 women also completed a Hospital Anxiety & Depression Score (HADS) questionnaire to test if preoperative HADS score could predict PROMS outcomes. Results Women in the CG had lower PROMS scores for satisfaction with their breasts, nipple reconstruction and sexual wellbeing. Both groups reported equal satisfaction with BRRM outcome and psychosocial well-being. Physical well-being PROMS of the abdomen and chest were high in women in both groups as were scores for satisfaction with the care they received. The CG group reported suboptimal quality of patient information. A higher presurgical HADS anxiety score predicted less favourable postoperative psychosocial well-being despite similar levels of satisfaction with aesthetic outcome. Conclusion We show a high degree of patient reported satisfaction by woman undergoing BRRM and reconstruction. There was a negative association with a cancer diagnosis on quality of life PROMS and higher preoperative anxiety levels negatively affected postoperative psychosocial well-being. These important findings should be part of the informed consent process during preoperative counselling.

Background Women with screen-detected invasive breast cancer who have macrometastatic disease on axillary sentinel lymph node biopsy (SLNB) are usually offered either surgical axillary node clearance (ANC) or axillary radiotherapy. These treatments can lead to significant complications for patients. The aim of this study was to identify a group of patients who may not require completion ANC. Methods Data from the NHS Breast Screening Programme between 1 April 2012 and 31 March 2017 were interrogated to identify women with invasive breast carcinoma and a single sentinel lymph node (SLN) with macrometastatic disease who subsequently proceeded to completion ANC. Univariable and multivariable analyses were performed to identify patients with a single positive SLN who had no further lymph node metastasis on ANC. Results Of the 2401 women included in the cohort, the presence of non-sentinel node disease was significantly affected by: the number of nodes obtained at SLNB (odds ratio (OR) 0.49 for retrieval of more than 1 node), invasive size of tumour (OR 1.63 for size greater than 20 mm), surgical treatment (OR 1.34 for mastectomy), human epidermal growth factor receptor (HER) 2 status (OR 0.71 for HER2 positivity), and patient age (OR 1.10 for age less than 50 years; OR 1.46 for age greater than 70 years). Patients aged less than 70 years, with tumour size smaller than 2 cm, more than one node retrieved on SLNB, and who had breast-conserving surgery had a lower chance of positive non-sentinel nodes on completion ANC compared with other patients. Conclusion This study, of a purely screen-detected breast cancer cohort, identified a subset of patients who may be spared completion ANC in the event of a single axillary SLN with macrometastasis.

Therapeutic mammaplasty (TM) may be an alternative to mastectomy, but few well designed studies have evaluated the success of this approach or compared the short-term outcomes of TM with mastectomy with or without immediate breast reconstruction (IBR). Data from the national iBRA-2 and TeaM studies were combined to compare the safety and short-term outcomes of TM and mastectomy with or without IBR.The subgroup of patients in the TeaM study who underwent TM to avoid mastectomy were identified, and data on demographics, complications, oncology and adjuvant treatment were compared with those of patients undergoing mastectomy with or without IBR in the iBRA-2 study. The primary outcome was the percentage of successful breast-conserving procedures in the TM group. Secondary outcomes included postoperative complications and time to adjuvant therapy.A total of 2916 patients (TM 376; mastectomy 1532; mastectomy and IBR 1008) were included in the analysis. Patients undergoing TM were more likely to be obese and to have undergone bilateral surgery than those having IBR. However, patients undergoing mastectomy with or without IBR were more likely to experience complications than the TM group (TM: 79, 21·0 per cent; mastectomy: 570, 37·2 per cent; mastectomy and IBR: 359, 35·6 per cent; P 0·001). Breast conservation was possible in 87·0 per cent of patients who had TM, and TM did not delay adjuvant treatment.TM may allow high-risk patients who would not be candidates for IBR to avoid mastectomy safely. Further work is needed to explore the comparative patient-reported and cosmetic outcomes of the different approaches, and to establish long-term oncological safety.La mamoplastia terapéutica (therapeutic mammaplasty, TM) puede ser una alternativa a la mastectomía, pero hay pocos estudios bien diseñados que hayan evaluado el éxito de esta estrategia o hayan comparado los resultados a corto plazo de la TM con la mastectomía con o sin (+/-) reconstrucción mamaria inmediata (immediate breast reconstruction, IBR). Para comparar la seguridad y los resultados a corto plazo de la TM y la mastectomía +/- IBR se combinaron los datos de los estudios nacionales iBRA-2 y TeaM. MÉTODOS: En el estudio TeaM se identificó el subgrupo de pacientes al que se realizó una TM para evitar la mastectomía y se compararon los datos demográficos, las complicaciones, los resultados oncológicos y el tratamiento adyuvante con las pacientes sometidas a mastectomía +/- IBR del estudio iBRA-2. La variable principal fue el porcentaje de éxito de la cirugía conservadora de mama en el grupo TM. Las variables secundarias fueron las complicaciones postoperatorias y el intervalo de tiempo hasta el inicio del tratamiento adyuvante.Se incluyeron en el análisis 2.916 pacientes (TM n = 376; mastectomía n = 1.532; IBR n = 1.008). La TM era más frecuente en pacientes obesas o en las sometidas a cirugía bilateral en comparación con las pacientes con IBR. Sin embargo, las pacientes sometidas a una mastectomía +/- IBR tenían más probabilidades de desarrollar complicaciones que las del grupo TM (TM n = 79, 21,0%; mastectomía n = 570, 37,2%; mastectomía y IBR n = 359, 35,6%; P 0,001). La conservación de la mama fue posible en el 87% de las pacientes con TM y el procedimiento no retrasó el inicio del tratamiento adyuvante. CONCLUSIÓN: La TM puede permitir que pacientes de alto riesgo que no serían candidatas a IBR eviten la mastectomía de una forma segura. Se necesitan más trabajos para comparar los resultados percibidos por las pacientes y los estéticos de las diferentes estrategias terapéuticas y establecer la seguridad oncológica a largo plazo.

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.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.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.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.

AIMS: These multidisciplinary guidelines aim to provide clinically helpful, evidence-based recommendations on the surgical management of the axilla in patients who have received neo-adjuvant chemotherapy for early breast cancer.MATERIALS & METHODS: Following a review of published evidence, a writing group representing all disciplines quorate within a breast cancer multidisciplinary meeting prepared the guidelines.KEY RECOMMENDATIONS: In patients presenting with clinically node negative axillae, sentinel node biopsy (SNB) may be performed prior to or on completion of neo-adjuvant chemotherapy (NACT). In patients presenting with clinically node positive axillae, SNB may be safely considered following completion of NACT. Four nodes should be removed with dual mapping. If evidence of complete pathological response of previous metastases is seen, axillary radiotherapy may be offered. If residual cancer (isolated tumour cells, micro- or macrometastes) is seen within the SNB, offer axillary node dissection.

Aim In breast cancer patients, post chemotherapy weight gain is linked with increased risk of cancer recurrence. We prospectively studied a cohort of premenopausal women receiving contemporary chemotherapy following a diagnosis of breast cancer to examine factors predicting weight increase. Methods Between May 2005 and January 2008, 523 patients enrolled into the Prospective Outcomes in Sporadic versus Hereditary breast cancer study entered this sub-study comparing weight prior to chemotherapy and weight and waist/hip measurements 12-months following chemotherapy. Results Data from 380 patients were available. Mean (standard deviation [SD]) pre-treatment body mass index (BMI) was 26.3 [5.6] kg/m2; 30% women gained > 5% body weight during the study period. Lower BMI at diagnosis predicted greater subsequent post treatment weight gain (4.3% relative weight gain for those in the 1st quartile of BMI compared to 0.8% for those in the 4th quartile; r=-0.22; p88cm). Conclusions Almost a third of premenopausal patients receiving adjuvant chemotherapy for breast cancer will gain clinically significant weight and over 40% will have central obesity 12-months following diagnosis. A greater weight gain is predicted by lower pretreatment BMI.

Summary Background In 2015, Artia™ (LifeCell, NJ), a new porcine acellular dermal matrix (ADM), was introduced at our unit. As there is lack of clinical studies on its use in breast reconstruction, the purpose of this prospective study was to assess outcome data for patients who underwent Artia™-assisted breast reconstruction. We compared these data with those of other studies of non-human ADMs in widespread use from the literature. Methods All consecutive patients who underwent Artia™-assisted breast reconstruction between July 2016 and February 2018 were identified. A prospective database was maintained, including data of patient demographics, type of reconstruction, type of implant, oncological data if applicable, complication rates and adjuvant treatment delays. Results Fifty-one patients undergoing 83 implant-based breast reconstructions with Artia™ were included in the study. Of the 83 reconstructions, 62% were performed following risk-reducing mastectomy, 28% following therapeutic mastectomy and 10% for revision procedures. After a mean 276-day follow-up period, the overall complication rate was 10.8%, including 6 breasts (7.2%) developing seromas requiring aspiration, 1 breast developing a haematoma (1.2%) and 2 implant losses (2.4%) in a single patient following neo-adjuvant chemotherapy. There were no cases of wound dehiscence or erythema/red breast syndrome. Conclusion This is one of the first studies demonstrating that Artia™-assisted implant-based breast reconstruction is associated with low and acceptable early complication rates. The results are promising and are comparable to our experience using established ADMs, with an implant loss rate of 4.9% across 500 ADM-assisted implant reconstructions.

Clinics for women concerned about their family history of breast cancer are widely established. A Family History Clinic was set-up in Manchester, UK, in 1987 in a Breast Unit serving a population of 1.8 million. In this review, we report the outcome of risk assessment, screening and prevention strategies in the clinic and propose future approaches. Between 1987&ndash, 2020, 14,311 women were referred, of whom 6.4% were from known gene families, 38.2% were at high risk (&ge, 30% lifetime risk), 37.7% at moderate risk (17&ndash, 29%), and 17.7% at an average/population risk who were discharged. A total of 4168 (29.1%) women were eligible for genetic testing and 736 carried pathogenic variants, predominantly in BRCA1 and BRCA2 but also other genes (5.1% of direct referrals). All women at high or moderate risk were offered annual mammographic screening between ages 30 and 40 years old: 646 cancers were detected in women at high and moderate risk (5.5%) with a detection rate of 5 per 1000 screens. Incident breast cancers were largely of good prognosis and resulted in a predicted survival advantage. All high/moderate-risk women were offered lifestyle prevention advice and 14&ndash, 27% entered various lifestyle studies. From 1992&ndash, 2003, women were offered entry into IBIS-I (tamoxifen) and IBIS-II (anastrozole) trials (12.5% of invitees joined). The NICE guidelines ratified the use of tamoxifen and raloxifene (2013) and subsequently anastrozole (2017) for prevention, 10.8% women took up the offer of such treatment between 2013&ndash, 2020. Since 1994, 7164 eligible women at &ge, 25% lifetime risk of breast cancer were offered a discussion of risk-reducing breast surgery and 451 (6.2%) had surgery. New approaches in all aspects of the service are needed to build on these results.

Recommended treatment for thyroid cancers10 mm is single stage total thyroidectomy (SST). Cancers diagnosed by diagnostic lobectomy may need completion surgery resulting in two stage thyroidectomies (TST). We noticed significant variation in numbers of SST and TST between hospitals within our cancer network and explored reasons for this using a prospective database containing all cases from 2004 to 2011 (n = 1030). We therefore conducted a survey of thyroid cytology provision across the network during 2010-2011.A central university hospital with the largest caseload (21.5% of total) was chosen as "benchmark". Of 14 remaining hospitals 3 were excluded from analysis due to low thyroid operation numbers and the remaining compared with benchmark. We used individual chi-squared tests with Bonferroni correction to explore variation in expected and observed numbers of SST/TST. Analysis of variance (ANOVA) was used to examine reasons for observed differences.Significant variance in SST/TST was seen between hospitals (p0.00001). Three hospitals had frequencies of SST statistically similar to reference hospital; each reported 201-300 thyroid cytology cases during the survey period. The remaining 8 had lower rates of SST, the 2 lowest performing hospitals having SST rates of 11% (p = 0.0004) and 9% (p0.0001). These eight hospitals reported fewer than 200 cytology cases each, shared amongst 4-7 pathologists per site. Differences were unrelated to patient age, gender, tumour histology or stage (ANOVA). Only the reference hospital had specialist cytopathologists.Variation in thyroid cytology provision may increase TST rates. Thyroid cytology should be concentrated in high volume centres with specialist thyroid cytopathologists.

Decision-making for women requiring reconstruction and post-mastectomy radiotherapy (PMRT) includes oncological safety, cosmesis, patient choice, potential delay/interference with adjuvant treatment and surgeon/oncologist preference. This study aimed to quantitatively assess surgeons' attitudes and perceptions about reconstructive options in this setting, and to ascertain if surgical volume influenced advice given. A questionnaire was sent to surgical members of the UK Association of Breast Surgery (ABS) in March-June 2014. The questionnaire elicited information on surgeon volume, reconstructive practice and drivers influencing decision-making. Response rate was 42% (148/355), representing 71% of UK breast units. Delayed breast reconstruction (DBR) was offered more commonly than immediate implant, delayed-immediate or immediate autologous reconstruction (p0.05). Cosmesis was thought to be equivalent between IBR and DBR by 15% of surgeons, and 26% believe IBR and DBR offer similar Health-related Quality of Life (HRQoL). Surgeon volume had no effect on reconstruction choice. Common decision-making drivers included negative effects of radiotherapy upon reconstructive and cosmetic outcome. The majority of surgeons (77%) believe the current evidence base is insufficient to guide decision-making. Despite surgeons believing that cosmesis and quality of life are not equivalent between IBR and DBR, DBR remains the commonest approach to this difficult clinical scenario. Surgeons perceive they are using a variety of newer techniques such as Delayed-Immediate Reconstruction and Acellular Dermal Matrices to try to ameliorate the effects of PMRT. This survey demonstrates that there is wide variation in reported surgical practice in this difficult setting. There is widespread acknowledgement of the lack of evidence to guide decision-making.

Introduction: Breast cancers exhibit cellular heterogeneity, containing both stem-like and more differentiated cells. The activity of cancer stem cells (CSC) is likely to be dependent on the microenvironment or niche. Using 158 patient tumour samples, correlations between niche-independent breast CSC activity and clinical and tumour characteristics were tested. Methods: 104 early breast cancer surgical samples and 54 unrelated metastatic samples from pleural or ascitic fluid were harvested. To test CSC activity, isolated cells were grown in both primary (formation) and secondary (self-renewal) mammosphere (MS) culture. Tumour initiating activity was also tested by transplanting breast cancer fragments or cells into the sub-cutaneous flanks of NSG mice (n=84 early and n=10 metastatic). Results: No correlation was found between MS growth, MS formation (%), MS self-renewal (%) or in vivo tumour initiation and breast cancer sub-type, grade, node status or Nottingham prognostic index. 33% of the samples that formed MS in vitro initiated tumours in vivo while only 9% that failed to form MS initiated tumour growth. Metastatic compared to early BC samples grew MS more frequently (53/54 compared to 81/104), and had a higher primary MS formation efficiency (1% vs 0.6%; P Conclusions: In summary, niche-independent breast CSC activity measured in vitro by MS assay and in vivo by xenograft growth is not directly correlated with standard clinical parameters. However, both in vitro and in vivo CSC activity are increased in metastatic samples. These results suggest that breast CSC activity is independent of other prognostic indicators but may predict for poor outcome tumours. Relapse free survival data are maturing and will be presented with analysis of primary tumour ALDH1 expression. Citation Format: Sacha J Howell, Denis Alferez, Katherine Spence, Rachel Eyre, Fran Shaw, Bruno Simoes, Angelica Santiago-Gomez, Maria Bramley, Mohamed Absar, Zahida Saad, Sumohan Chatterjee, Cliona Kirwan, Ashu Gandhi, Anne C Armstrong, Andrew M Wardley, Gillian Farnie, Robert B Clarke. Breast cancer stem-like cell activity correlates with tumour progression to metastasis but not with clinical or tumour characteristics [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-06-02.

Approximately 30-40% of women are not offered immediate breast reconstruction because the possibility of post-mastectomy radiotherapy (PMRT) is unknown at the time of mastectomy. Breast reconstruction may be delayed until final pathology is available and need for radiotherapy established. Surgical literature is replete with studies of varying quality, reporting complication rates for a range of reconstructive procedures, highlighting the need for surgical trials of reconstructive techniques in women at risk of PMRT. Decisions for these patients are complex, involving multiple clinicians including surgeons and oncologists. To inform a surgical trial design, we aimed to determine current UK surgical practice and gain an understanding of the drivers behind decision-making. Methods: A questionnaire, validated in a pilot population, was posted to Consultant members of the Association of Breast Surgery (UK). We collected data on current practice in conducting Delayed, Immediate and Delayed-immediate reconstructive surgery. We collated data on type and volume of procedure performed and factors affecting decision-making including delay to adjuvant treatment, risk of complications, perception of patients’ quality of life (QoL) and aesthetic satisfaction. Results: Of 355 surgeons, 130(37%) responded. Of these, 77% felt the current evidence base was not adequate to guide surgical decisions and 80% felt a need for further trials to guide best treatment. Despite a lack of scientific evidence demonstrating a difference in cosmesis or QoL between Immediate and Delayed reconstruction, 85% felt there is not equivalent cosmesis and 71% felt there is not equivalent QoL between the two groups. There is considerable heterogeneity in reconstructive approach to patients at risk of PMRT (Table 1). Delayed reconstruction remains the most popular option, being regularly used by 94% of surgeons despite only 34% of surgeons believing the majority of patients are satisfied with the approach. Significantly fewer surgeons perform Immediate implant based reconstruction (with or without ADM) than Delayed (p Table 1 No. of responses NeverSometimesOftenAlwaysDelayed5505119Immediate implant584181Immediate ADM+Implant45491452-stage (delayed-immediate) Expander to permanent reconstruction2855335Immediate Autologous2959227 The three most important drivers in making a reconstructive choice were 1. Effect of PMRT on the cosmetic result 2. Minimising risk of complications and avoiding delay to adjuvant treatment 3. Pre-operative uncertainty over the need for PMRT. Conclusions: Surgeons employ a variety of approaches to reconstruction in the face of PMRT, the most common approach being delayed reconstruction. Decision-making is based upon individual surgeon’s perception of risks including likely delay to adjuvant therapy and effect of PMRT on the reconstruction. Drivers appeared to be more surgeon-centred rather than patient-based. There is awareness of a lack of evidence to support decision-making and the need for high quality studies. Randomised clinical trials are needed to provide an evidence base for outcomes. Citation Format: James R Harvey, Nigel J Bundred, Cliona C Kirwan, Ashu Gandhi, Paula J Duxbury. Variation in UK reconstructive practice in the face of post-mastectomy radiotherapy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-14-09.

Aims Increasing use of 18F-Fluorodeoxy glucose (FDG) Positron Emission Tomography Computed Tomography (PET CT) has resulted in an increased frequency of incidentally discovered areas of focally increased FDG uptake within the thyroid gland – thyroid incidentalomas. We aimed to compare radiological characteristics of thyroid incidentalomas with cytology, histology and ultrasound findings. Materials and methods We examined all FDG PET CT scan reports for all patients undergoing this investigation over a 6 year period in a single tertiary cancer centre. All PET CT scans followed an agreed proforma allowing reports mentioning “thyroid” to be identified. Reports commenting on a positive finding within the thyroid gland were investigated further manually. Incidental mentions of thyroid with no underlying abnormality were discounted from analysis. Results In the study period, 7221 patients underwent FDG PET CT scanning in our unit. Within this group 75 (1%) showed diffuse FDG uptake and 81 (1.1%) showed focal uptake (thyroid incidentalomas). Only 30 patients (37%) with incidentalomas had further investigation and malignancy rate was 23% (7/30). Median Standardised Uptake Values (SUV) in malignant lesions was 9.9 (range 3.5–17.8) whilst in benign lesions and diffuse lesions it was 5.4 (2.8–32) and 4.2 (2.1–25.6) respectively ( p = 0.0013, Kruskal Wallis). Conclusion There remains a need to develop a standardised approach to the investigation and management of thyroid incidentalomas discovered on FDG PET CT scanning. Up to 1 in 4 of these patients will harbour thyroid malignancy.

The aim of this multicenter, prospective, longitudinal phase IV study was to establish the optimal duration of neoadjuvant letrozole that would allow breast conservation surgery (BCS) in patients with early breast cancer who were initially unsuitable. Primary, invasive, estrogen-receptor- and/or progesterone-receptor-positive breast cancer patients, with large tumors (≥T2 i.e., >20 mm) not initially suitable for BCS, received 2.5 mg letrozole p.o. daily. Patients continued treatment until they became eligible for BCS, progressed, failed to meet criteria for BCS and withdrew for scheduled mastectomy, withdrew for other reasons, or completed 12 months of letrozole treatment without a BCS decision being made. A total of 146 patients were enrolled; seven patients who did not have a valid postbaseline tumor assessment were excluded from the final efficacy analysis. At study closure, 69 % of patients (96 of 139) were eligible for BCS. The median time to achieve a tumor response sufficient to allow BCS with neoadjuvant letrozole was 7.5 months (95 % CI 6.3–8.5 months). Letrozole was well tolerated, and most adverse events were mild-to-moderate (grade 1–2). The results from this trial suggest that extended letrozole therapy in the neoadjuvant setting (7.5 months), as opposed to conventional treatment of 4 months, is optimal to achieve maximum reduction in tumor volume sufficient for BCS.

Summary Aims This study aimed to investigate whether breast volume measured preoperatively using a Kinect 3D sensor could be used to determine the most appropriate implant size for reconstruction. Methods Ten patients underwent 3D imaging before and after unilateral implant-based reconstruction. Imaging used seven configurations, varying patient pose and Kinect location, which were compared regarding suitability for volume measurement. Four methods of defining the breast boundary for automated volume calculation were compared, and repeatability assessed over five repetitions. Results The most repeatable breast boundary annotation used an ellipse to track the inframammary fold and a plane describing the chest wall (coefficient of repeatability: 70 ml). The most reproducible imaging position comparing pre- and postoperative volume measurement of the healthy breast was achieved for the sitting patient with elevated arms and Kinect centrally positioned (coefficient of repeatability: 141 ml). Optimal implant volume was calculated by correcting used implant volume by the observed postoperative asymmetry. It was possible to predict implant size using a linear model derived from preoperative volume measurement of the healthy breast (coefficient of determination R 2 = 0.78, standard error of prediction 120 ml). Mastectomy specimen weight and experienced surgeons' choice showed similar predictive ability (both: R 2 = 0.74, standard error: 141/142 ml). A leave one-out validation showed that in 61% of cases, 3D imaging could predict implant volume to within 10%; however for 17% of cases it was >30%. Conclusion This technology has the potential to facilitate reconstruction surgery planning and implant procurement to maximise symmetry after unilateral reconstruction.

Tissue expansion with delayed insertion of a definitive prosthesis is the most common form of immediate breast reconstruction performed in the United Kingdom. However, achieving total muscle coverage of the implant and natural ptosis is a key technical challenge. The use of acellular dermal matrices (ADM) to supplement the pectoralis major muscle at the lower and lateral aspects of the breast has been widely adopted in the UK, potentially allowing for a single stage procedure. There is however little published data on the clinical and quality criteria for its use, and no long term follow-up. The guidelines have been jointly produced by the Association of Breast Surgery and the British Association of Plastic, Reconstructive and Aesthetic Surgeons and their aims are: to inform those wishing to undertake ADM assisted breast reconstruction and, to identify clinical standards and quality indicators for audit purposes. The guidelines are based on expert opinion of a multi-disciplinary working group, who are experienced in the technique, and a review of the published data.