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Purpose Changes occur in the expression of oestrogen-regulated and proliferation-associated genes in oestrogen receptor (ER)-positive breast tumours during the menstrual cycle. We investigated if Oncotype® DX recurrence score (RS), Prosigna® (ROR) and EndoPredict® (EP/EPclin) prognostic tests, which include some of these genes, vary according to the time in the menstrual cycle when they are measured. Methods Pairs of test scores were derived from 30 ER-positive/human epidermal growth factor receptor-2-negative tumours sampled at two different points of the menstrual cycle. Menstrual cycle windows were prospectively defined as either W1 (days 1–6 and 27–35; low oestrogen and low progesterone) or W2 (days 7–26; high oestrogen and high or low progesterone). Results The invasion module score of RS was lower (− 10.9%; p = 0.098), whereas the ER (+ 16.6%; p = 0.046) and proliferation (+ 7.3%; p = 0.13) module scores were higher in W2. PGR expression was significantly increased in W2 (+ 81.4%; p = 0.0029). Despite this, mean scores were not significantly different between W1 and W2 for any of the tests and the two measurements showed high correlation (r = 0.72–0.93). However, variability between the two measurements led to tumours being assigned to different risk categories in the following proportion of cases: RS 22.7%, ROR 27.3%, EP 13.6% and EPclin 13.6%. Conclusion There are significant changes during the menstrual cycle in the expression of some of the genes and gene module scores comprising the RS, ROR and EP/EPclin scores. These did not affect any of the prognostic scores in a systematic fashion, but there was substantial variability in paired measurements.

Background The TARGIT-A trial reported risk-adapted targeted intraoperative radiotherapy (TARGIT-IORT) during lumpectomy for breast cancer to be as effective as whole-breast external beam radiotherapy (EBRT). Here, we present further detailed analyses. Methods In total, 2298 women (≥45 years, invasive ductal carcinoma ≤3.5 cm, cN0–N1) were randomised. We investigated the impact of tumour size, grade, ER, PgR, HER2 and lymph node status on local recurrence-free survival, and of local recurrence on distant relapse and mortality. We analysed the predictive factors for recommending supplemental EBRT after TARGIT-IORT as part of the risk-adapted approach, using regression modelling. Non-breast cancer mortality was compared between TARGIT-IORT plus EBRT vs. EBRT. Results Local recurrence-free survival was no different between TARGIT-IORT and EBRT, in every tumour subgroup. Unlike in the EBRT arm, local recurrence in the TARGIT-IORT arm was not a predictor of a higher risk of distant relapse or death. Our new predictive tool for recommending supplemental EBRT after TARGIT-IORT is at https://targit.org.uk/addrt. Non-breast cancer mortality was significantly lower in the TARGIT-IORT arm, even when patients received supplemental EBRT, HR 0.38 (95% CI 0.17–0.88) P = 0.0091. Conclusion TARGIT-IORT is as effective as EBRT in all subgroups. Local recurrence after TARGIT-IORT, unlike after EBRT, has a good prognosis. TARGIT-IORT might have a beneficial abscopal effect. Trial registration ISRCTN34086741 (21/7/2004), NCT00983684 (24/9/2009).

Background: oestrogen receptor positive/ human epidermal growth factor receptor positive (ER+/HER2+) breast cancers (BCs) are less responsive to endocrine therapy than ER+/HER2- tumours. Mechanisms underpinning the differential behaviour of ER+HER2+ tumours are poorly characterised. Our aim was to identify biomarkers of response to 2 weeks’ presurgical AI treatment in ER+/HER2+ BCs. Methods: all available ER+/HER2+ BC baseline tumours (n=342) in the POETIC trial were gene expression profiled using BC360™ (NanoString) covering intrinsic subtypes and 46 key biological signatures. Early response to AI was assessed by changes in Ki67 expression and residual Ki67 at 2 weeks (Ki67 2wk). Time-To-Recurrence (TTR) was estimated using Kaplan-Meier methods and Cox models adjusted for standard clinicopathological variables. New molecular subgroups (MS) were identified using consensus clustering. Findings: HER2-enriched (HER2-E) subtype BCs (44.7% of the total) showed poorer Ki67 response and higher Ki67 2wk (p2wk. Five new MS that were associated with differential response to AI were identified. HER2-E had significantly poorer TTR compared to Luminal BCs (HR 2.55, 95% CI 1.14–5.69; p=0.0222). The new MS were independent predictors of TTR, adding significant value beyond intrinsic subtypes. Interpretation: our results show HER2-E as a standardised biomarker associated with poor response to AI and worse outcome in ER+/HER2+. HRD, TP53 mutational score and immune-tumour tolerance are predictive biomarkers for poor response to AI. Lastly, novel MS identify additional non-HER2-E tumours not responding to AI with an increased risk of relapse. Funding: Cancer Research UK (CRUK/07/015).

Sentinel lymph node biopsy (SLNB) is an accurate and reliable method for staging the axilla in early breast cancer. The gold standard technique for localizing the sentinel lymph node (SLN) is the use of radioisotope with or without blue dye. However, this technique has its limitations. Various alternatives have been explored to overcome the disadvantages of the standard SLNB technique and superparamagnetic iron oxide mapping agents have garnered significant attention. The SMART study aims to compare the magnetic technique using the superparamagnetic iron oxide particles (SPIO, Sienna+®) to the radioisotope technique (Tc99) +/- blue dye, for SLN identification in patients with early breast cancer.A prospective, multicenter study was done that recruited 109 clinically node-negative early-stage breast cancer patients from five centres in the United Kingdom (UK). The patients received radioisotope ± blue dye injections, followed by intraoperative injection of magnetic tracer prior to SLNB. The sentinel node identification rate was compared between the magnetic and standard techniques to evaluate detection rate (per patient and per node), non-inferiority and concordance.Data was analysed for 107 patients. The per patient detection rate was 98.13% (105/107) when using the magnetic tracer and 92.26% (103/107) when using the standard technique. The nodal detection rate was 93.07% (188/202 nodes) when using the magnetic tracer and 96.53% (195/202) when using the standard technique. Of the 31 patients with positive sentinel lymph nodes (SLNs), all 31 (100%) were detected by both techniques.Our study demonstrates that the magnetic technique is a feasible method for SLNB, with an identification rate that is not inferior to the standard technique. The magnetic technique offers a suitable alternative to the standard technique thereby avoiding the need for the complexities of nuclear medicine, the hazards of radiation and the anaphylaxis risk of blue dye.

Objective: Oncoplastic breast surgery is well-established but has a higher risk of wound complications. This may result in a delay in receiving adjuvant therapy, increased hospital visits with associated financial implications, and sub-optimal cosmetic outcomes. Negative pressure wound therapy (NPWT) has emerged as an additional tool to reduce wound complication rates, but further evaluation is required to evaluate its efficacy. This study investigated the prophylactic use of PICO® NPWT in patients undergoing oncoplastic breast surgery. We determined the rate of wound-related complications, including dehiscence, necrosis, implant loss, and infection. We compared our findings with data from the National Mastectomy and Breast Reconstruction Audit 2011 (NMBRA) and implant-based Breast Reconstruction Audit (iBRA). Methods: This was a prospective multi-centre national audit. The participating UK breast units routinely used NPWT for oncoplastic breast surgical procedures. Data collection included rates of wound dehiscence, wound necrosis, wound infection, and implant loss. The study findings were compared against the NMBRA and the iBRA studies. Results: Data from 267 patients were included in the study from 7 centres. The mean duration of PICO use was 6.6 [SD 1.9 days]. In all, 36 patients (13.5%) developed post-operative wound complications; 16 patients (6%) developed skin flap necrosis; wound dehiscence occurred in 13 patients (4.9%); and 15 patients (5.6%) developed post-operative wound infection. Of the whole cohort, 11 patients (4.1%) required further surgery due to wound complications, and 8 patients (3%) had a delay in the receipt of adjuvant therapy. A total of 158 patients underwent mastectomy with immediate implant-based breast reconstruction. The post-operative wound complication rate was comparable in this subgroup (n=22; 13.9%). Skin flap necrosis was seen in 10 patients (6.3%), wound dehiscence was seen in 7 patients (4.4%), and 8 patients (5.1%) developed wound infection. The implant loss rate was 3.8%. The estimated total cost savings were ￡84,613 and ￡316.90 per patient. Conclusion: This study suggests that prophylactic use of NPWT in oncoplastic breast surgery results in a low rate of wound-related complications with associated healthcare cost benefits. A prospective randomised controlled trial is required to further evaluate the prophylactic use of NPWT in oncoplastic breast surgery.

Objectives Extreme oncoplastic breast conserving surgery (eOPBCS) allows breast conservation for tumours ≥ 50 mm, but long-term outcomes are unclear. We investigated early complications and the longer-term clinical and oncological outcomes following eOPBCS to assess the clinical utility and safety of this technique. Materials and methods A prospectively collected database of all eOPBCS procedures (1993–2016) using LD miniflaps (LDm) and therapeutic mammoplasties (TM) was interrogated and cross-checked with hospital records to establish length of follow up (FU), clinical outcomes (complications, revisions), local recurrence (LR) and survival. Results Ninety eOPBCS procedures (62 LDm, 28 TM) performed for large tumours (mean 67 [50–177] mm) were identified, overall FU 80 (10–308) months (LDm 91 [13–308], TM 54 [10–120] months). Forty two per cent were node positive, and 2 were benign (benign cases excluded from LR and FU analysis). Eleven patients required surgery for involved excision margins (LDm 3 re-excisions and 2 mastectomies, TM 6 mastectomies). Surgery for complications and subsequent revision was required in 6% and 37% of LDm and 18% and 7% of TM patients, respectively. Seven patients developed LR (LDm 5 versus TM 2) giving a predicted 5 and 10 year LR rate of 1.1% and 16%. Conclusion Long-term FU of this unique series has confirmed that eOPBCS is a safe procedure for patients with bulky tumours normally treated by mastectomy, without risking local control. TM patients experienced more early complications but LDm patients required more revisions over a more prolonged period of FU.

The major changes in hormone levels that occur through the menstrual cycle have been postulated to affect the expression of hormone-regulated and proliferation-associated genes (PAGs) in premenopausal ER+ breast cancer. Whilst previous studies have demonstrated differences in gene expression, here, we investigated if there are within patient changes in the expression of oestrogen- and progesterone-regulated genes (ERGs and PRGs) and PAGs in ER+ breast cancer during the menstrual cycle. Samples from 96 patients in two independent prospective studies of the effect of menstrual cycle on ER+ breast cancer were used. Plasma hormone measurements were used to assign tumours to one of three pre-defined menstrual cycle windows: W1 (days 27–35 and 1–6; low oestradiol and low progesterone), W2 (days 7–16; high oestradiol and low progesterone) and W3 (days 17–26; intermediate oestradiol and high progesterone). RNA expression of 50 genes, including 27 ERGs, 11 putative PRGs and seven PAGs was measured. The AvERG (geomean of PGR, GREB1, TFF1 and PDZK1) was used as a composite measure of ERG expression and showed significant changes between the three windows of the menstrual cycle increasing over 2.2-fold between W1 and W2 and decreasing between W2 and W3 and between W3 and W1. Proliferation gene expression also varied significantly, following the same pattern of changes as ERG expression, but the changes were of lower magnitude (1.4-fold increase between W1 and W2). Significant changes in the expression of eight individual ERGs, including GREB1, PGR and TFF1, and two PAGs were observed between W1 and either W2 or W3 with all genes showing higher levels in W2 or W3 (1.3–2.4-fold; FDR 0.016–0.05). The AvProg, a composite measure of PRG expression, increased significantly (1.5-fold) in W3 compared to W1 or W2 but no significant changes were observed for individual PRGs. In conclusion, we observed significant changes in ERG, PRG and PAG expression in ER+ breast tumours during the menstrual cycle that may affect the assessment and interpretation of prominent biomarkers (e.g. PgR) and commonly used multigene prognostic signatures in premenopausal ER+ breast cancer.

Key Points Question For early breast cancer, is 5-year local control with delayed second-procedure targeted intraoperative radiotherapy (TARGIT-IORT) noninferior to whole-breast postoperative external beam radiotherapy (EBRT), and how do long-term outcomes compare? Findings In this randomized clinical trial including 1153 participants, delayed second-procedure TARGIT-IORT was not noninferior to EBRT at 5-year complete follow-up; however, long-term (median 9 years) mastectomy-free survival, distant disease-free survival, and overall survival were not different. Meaning For early breast cancer, delayed second-procedure single-dose TARGIT-IORT given by reopening the lumpectomy wound had similar long-term mastectomy-free and overall survival compared with EBRT despite higher local recurrence., This secondary analysis of the TARGIT-A randomized clinical trial compares the effect of delayed second-procedure targeted intraoperative radiotherapy (TARGIT-IORT) with whole-breast external beam radiotherapy (ERBT) on local recurrence at 5 years and long-term survival outcomes among women with early breast cancer., Importance Conventional adjuvant radiotherapy for breast cancer given daily for several weeks is onerous and expensive. Some patients may be obliged to choose a mastectomy instead, and some may forgo radiotherapy altogether. We proposed a clinical trial to test whether radiotherapy could be safely limited to the tumor bed. Objective To determine whether delayed second-procedure targeted intraoperative radiotherapy (TARGIT-IORT) is noninferior to whole-breast external beam radiotherapy (EBRT) in terms of local control. Design, Setting, and Participants In this prospective, randomized (1:1 ratio) noninferiority trial, 1153 patients aged 45 years or older with invasive ductal breast carcinoma smaller than 3.5 cm treated with breast conservation were enrolled from 28 centers in 9 countries. Data were locked in on July 3, 2019. Interventions The TARGIT-A trial was started in March 2000; patients were randomized after needle biopsy to receive TARGIT-IORT immediately after lumpectomy under the same anesthetic vs EBRT and results have been shown to be noninferior. A parallel study, described in this article, was initiated in 2004; patients who had their cancer excised were randomly allocated using separate randomization tables to receive EBRT or delayed TARGIT-IORT given as a second procedure by reopening the lumpectomy wound. Main Outcomes and Measures A noninferiority margin for local recurrence rate of 2.5% at 5 years, and long-term survival outcomes. Results Overall, 581 women (mean [SD] age, 63 [7] years) were randomized to delayed TARGIT-IORT and 572 patients (mean [SD] age, 63 [8] years) were randomized to EBRT. Sixty patients (5%) had tumors larger than 2 cm, or had positive nodes and only 32 (2.7%) were younger than 50 years. Delayed TARGIT-IORT was not noninferior to EBRT. The local recurrence rates at 5-year complete follow-up were: delayed TARGIT-IORT vs EBRT (23/581 [3.96%] vs 6/572 [1.05%], respectively; difference, 2.91%; upper 90% CI, 4.4%). With long-term follow-up (median [IQR], 9.0 [7.5-10.5] years), there was no statistically significant difference in local recurrence-free survival (HR, 0.75; 95% CI, 0.57-1.003; P = .052), mastectomy-free survival (HR, 0.88; 95% CI, 0.65-1.18; P = .38), distant disease-free survival (HR, 1.00; 95% CI, 0.72-1.39; P = .98), or overall survival (HR, 0.96; 95% CI, 0.68-1.35; P = .80). Conclusions and Relevance These long-term data show that despite an increase in the number of local recurrences with delayed TARGIT-IORT, there was no statistically significant decrease in mastectomy-free survival, distant disease-free survival, or overall survival. Trial Registration ISRCTN34086741, ClinicalTrials.gov Identifier: NCT00983684

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.

Recommendations for mastectomy by multidisciplinary teams (MDTs) may contribute to variation in mastectomy rates. The primary aim of this multicentre prospective observational study was to describe current practice in MDT decision-making for recommending mastectomy. A secondary aim was to determine factors contributing to variation in mastectomy rates.Consecutive patients undergoing mastectomy between 1 June 2015 and 29 February 2016 at participating units across the UK were recruited. Details of neoadjuvant systemic treatment (NST), operative and oncological data, and rationale for recommending mastectomy by MDTs were collected.Overall, 1776 women with breast cancer underwent 1823 mastectomies at 68 units. Mastectomy was advised by MDTs for 1402 (76·9 per cent) of these lesions. The most common reasons for advising mastectomy were large tumour to breast size ratio (530 women, 29·1 per cent) and multicentric disease (372, 20·4 per cent). In total, 202 postmenopausal women with oestrogen receptor-positive (ER+) unifocal tumours were advised mastectomy and not offered NST, owing to large tumour to breast size ratio in 173 women (85·6 per cent). Seventy-five women aged less than 70 years with human epidermal growth factor receptor 2-positive (HER2+) tumours were advised mastectomy and not offered NST, owing to large tumour to breast size ratio in 45 women (60 per cent).Most mastectomies are advised for large tumour to breast size ratio, but there is an inconsistency in the use of NST to downsize tumours in patients with large ER+ or HER2+ cancers. The application of standardized recommendations for NST could reduce the number of mastectomies advised by MDTs.Las recomendaciones para la mastectomía por equipos multidisciplinarios (multidisciplinary teams, MDTs) podrían contribuir a explicar la diferencia en las tasas de mastectomía. El objetivo primario de este estudio observacional prospectivo y multicéntrico fue describir la práctica actual en la toma de decisiones de los MDT para recomendar la mastectomía. El objetivo secundario fue determinar factores que contribuyen a la variación en las tasas de mastectomía. MÉTODOS: Se reclutaron pacientes consecutivas sometidas a mastectomía entre el 1 de junio de 2015 y el 29 de febrero de 2016 en las unidades participantes de todo el Reino Unido. Se recogieron datos del preoperatorio, tratamiento neoadyuvante sistémico (neoadjuvant systemic treatment, NST), quirúrgicos y oncológicos, así como la justificación de los MDT para recomendar la mastectomía.Un total de 1.776 pacientes fueron sometidas a 1.823 mastectomías en 68 unidades. La mastectomía fue recomendada por los MDTs en 1.402 (76,9%) de estas mujeres. Las razones más frecuentes para recomendar la mastectomía fueron la elevada proporción entre el tamaño del tumor y el de la mama (530; 29,1%) y la enfermedad multicéntrica (372; 20,4%). En total, a 202 mujeres postmenopáusicas con tumores unifocales positivos para receptores de estrógenos (ER+) se les recomendó la mastectomía y no se les ofreció NST; debido a una elevada proporción entre el tamaño del tumor y de la mama en 173 (86%) pacientes. A 75 mujeres de70 años con tumores positivos para el human epidermal growth factor receptor 2 (HER2+) se les recomendó la mastectomía y no se les ofreció NST; debido a una elevada proporción entre el tamaño del tumor y de la mama en 45 (60%) mujeres. CONCLUSIÓN: La mayoría de las mastectomías se recomendaron en casos con una elevada proporción entre el tamaño del tumor y el de la mama, pero existe una inconsistencia en la utilización de la NST para reducir el tamaño del tumor en pacientes con grandes cánceres ER+ o HER2+. La aplicación de recomendaciones estandarizadas para la NST podría reducir el número de mastectomía recomendadas por los MDT.

Aim Risk-reducing mastectomy (RRM) is on the increase, now frequently combined with breast reconstruction (BR). However, the resource implications associated with bilateral mastectomy and reconstruction are unknown. This study assessed the overall cost of performing risk-reducing surgery. Methods All cases of RRM and BR performed between 1991 and 2011 at this hospital were identified from a prospectively collected database. All patients undergoing bilateral mastectomy were included, when at least one mastectomy was risk-reducing. Overall treatment costs for all surgical procedures, complications, revisional procedures and outpatient attendances were calculated and compared to the National Tariff allowed. Mann–Whitney U and Fischer's exact tests were used to calculate levels of significance. Results Fifty patients underwent bilateral mastectomy and BR (median follow up 20 [range 1–106] months), 72 were Latissimus Dorsi reconstructions (LDR) and 28 were Subpectoral reconstructions (SPR). LDR took longer than SPR (p = 0.001), with a greater length of stay (p = 0.024). Nine percent of patients returned to theatre for early complications, but the type of BR did not influence the early complication rate (LDR versus SPR, p = 0.345) or the need for additional unplanned procedures (LDR versus SPR, p = 0.671). The overall mean cost for bilateral RRM and BR was £14,797 per patient. The inpatient cost for bilateral RRM and LDR was £10,082 compared with £5,905 SPR. Both procedures exceeded the £5,697 tariff allowed in the UK. Conclusion Bilateral RRM and BR is a safe procedure, but the resource implications are considerable and exceed the tariff allowed, particularly when performing more complex techniques.

Supplemental Digital Content is available in the text., Background: Oncoplastic breast-conserving surgery (OBCS) avoids mastectomy for larger tumors, but patient-reported outcomes are unknown. Methods: The BREAST-Q questionnaire was distributed to 333 women following therapeutic mammaplasty or latissimus dorsi (LD) miniflap since 1991 [tumor diameter, 32.5 (5–100) mm). QScore software generated scores/100 for breast appearance, physical, emotional, and sexual wellbeing. Outcomes following therapeutic mammaplasty and LD miniflap were compared and qualitative data analyzed to identify common themes relating to satisfaction. Results: One hundred fifty (45%) women responded [mammaplasty versus LD miniflap, 52% versus 42%; age, 52 (30–83) years; follow-up, 84 (4–281) months). Eighty-nine percent rated OBCS better than mastectomy, > 80% recommending it to others. Mean outcome scores for breast appearance, physical, and emotional wellbeing were high and persisted beyond 15 years. Therapeutic mammaplasty patients were significantly more satisfied than those undergoing LD miniflap with the shape (P < 0.05), the size (P < 0.005), and the natural feel of the treated breast (P = 0.01). They demonstrated similar scores for physical and emotional wellbeing and a lower score for sexual wellbeing than LD miniflap patients. More LD miniflap patients reported back/shoulder symptoms and were more likely to report upper back pain (P < 0.05), but very few (< 5%) were concerned about donor-site appearance. Overall satisfaction with surgical outcomes was high in both OBCS groups (82% “excellent/very good”) but greatest after therapeutic mammaplasty (P < 0.005). Conclusions: Patients report long-lasting satisfaction after OBCS and outcomes that compare very favorably with those reported following mastectomy and immediate autologous reconstruction.

Summary Introduction Latissimus dorsi miniflap is a breast-conserving volume replacement technique for the reconstruction of large breast defects. While mammographic features of miniflap reconstruction have been described, little is known about the incidence, mode of presentation and size of local recurrence after this procedure. This study aimed to investigate the impact of latissimus dorsi miniflap reconstruction on the frequency, presentation and detection of local recurrence. Methods Clinical, radiological and pathological data were reviewed in 261 patients. Complete records were available for 11 patients developing local recurrence, including mode, time of presentation and size of the recurrent tumours. All mammograms before and after local recurrence were assessed in relation to a range of specific characteristics including parenchymal density, flap visibility, architectural distortion, mass, calcifications, fat necrosis, skin thickening and breast oedema. Results Twenty-one patients developed local recurrence at 10.4 years following reconstruction (mean age 49 years, resection weight 182 g and tumour size 33 mm). Following radiotherapy, 0.5% of patients developed local recurrence each year, which increased five-fold when radiotherapy was omitted (HR 4.99). Local recurrences were diagnosed in five patients by mammography alone, in three by mammography and palpable lump, and in three by palpable lump alone. They were detected when small (15 mm) and were associated with new mammographic abnormalities in 10 patients. Conclusions Long follow-up demonstrates that latissimus dorsi miniflap reconstruction allows oncologically safe breast conservation when combined with postoperative radiotherapy. Local recurrences are detected early, either by mammography, clinical examination or both, and detection is not compromised by the presence of a flap.

Background In 2006 Nolvadex was discontinued and replaced by a variety of alternative generic tamoxifen brands for the adjuvant treatment of breast cancer. Anecdotally, patients are switching brands and taking alternative medications to reduce treatment related symptoms. Nevertheless, more severe side effects may equate to better relapse prevention. This study evaluates generic tamoxifen adherence and its correlation with side effects and brand switch. Methods Consecutive disease free ER positive patients (stage I–III) were invited to respond to a questionnaire. 165 of 327 questionnaires were returned (50% response). Pearson's Chi Square test was used for data analysis. Results 63 patients (38%) reported a switch between generic tamoxifen. 59% of all patients experienced side effects associated with tamoxifen treatment of which 53% were severe. Patients experiencing differential symptoms dependent on tamoxifen brand reported more severe side effects ( p = 0.02). Non-prescribed supplements were taken by 42% of all patients with no significant improvement in climacteric symptoms ( p = 0.05). The concomitant use of SSRIs appeared to have no effect on symptoms. A significant number of patients considered discontinuing tamoxifen because of the side effects ( p = 0.001), yet this did not translate into discontinuation or non-adherence ( p = 0.8 and 0.08 respectively). Conclusion Severe tamoxifen side effects are commonly experienced by breast cancer patients and can be significantly altered by change in tamoxifen brand. Most patients will continue to take tamoxifen, despite side effects to avoid cancer relapse. Supplementation and antidepressants did not improve tamoxifen related side effects in our cohort.

Increasing breast specialization triggered a review of our surgical activity. All 10,000 elective inpatient and day case procedures between 1998 and 2008 were grouped into six categories: oncological, primary, secondary and revisional oncoplastic, and other breast and nonbreast procedures. Overall, surgical activity increased, with a rise in breast and a fall in nonbreast procedures, as a result of a changing caseload in each category (chi-squared for linear trend = 55.24: p

Background: Tumor-positive sentinel lymph node (SLN) biopsy results in a risk of non sentinel node metastases in micro-and macro-metastases ranging from 20 to 50%, respectively. Therefore, most patients underwent unnecessary axillary lymph node dissections. We have previously developed a mathematical model for predicting patient-specific risk of non sentinel node (NSN) metastases based on 2460 patients. The study reports the results of the validation phase where a total of 1945 patients were enrolled, aimed at identifying a tool that gives the possibility to the surgeon to choose intraoperatively whether to perform or not axillary lymph node dissection (ALND). Methods: The following parameters were recorded: Clinical: hospital, age, medical record number; Bio pathological: Tumor (T) size stratified in quartiles, grading (G), histologic type, lymphatic/vascular invasion (LVI), ER-PR status, Ki 67, molecular classification (Luminal A, Luminal B, HER-2 Like, Triple negative); Sentinel and non-sentinel node related: Number of NSNs removed, number of positive NSNs, cytokeratin 19 (CK19) mRNA copy number of positive sentinel nodes stratified in quartiles. A total of 1945 patients were included in the database. All patient data were provided by the authors of this paper. Results: The discrimination of the model quantified with the area under the receiver operating characteristics (ROC) curve (AUC), was 0.65 and 0.71 in the validation and retrospective phase, respectively. The calibration determines the distance between predicted outcome and actual outcome. The mean difference between predicted/observed was 2.3 and 6.3% in the retrospective and in the validation phase, respectively. The two values are quite similar and as a result we can conclude that the nomogram effectiveness was validated. Moreover, the ROC curve identified in the risk category of 31% of positive NSNs, the best compromise between false negative and positive rates i.e. when ALND is unnecessary (< 31%) or recommended (> 31%). Conclusions: The results of the study confirm that OSNA nomogram may help surgeons make an intraoperative decision on whether to perform ALND or not in case of positive sentinel nodes, and the patient to accept this decision based on a reliable estimation on the true percentage of NSN involvement. The use of this nomogram achieves two main gools: 1) the choice of the right treatment during the operation, 2) to avoid for the patient a second surgery procedure.

Two large randomised controlled trials of intraoperative radiotherapy (IORT) in breast-conserving surgery (TARGIT-A and ELIOT) have been published 14 years after their launch. Neither the TARGIT-A trial nor the ELIOT trial results have changed the current clinical practice for the use of IORT. The in-breast local recurrence rate (LRR) after IORT met the pre-specified non-inferiority margins in both trials and was 3.3% in TARGIT-A and 4.4% in the ELIOT trial. In both trials, the pre-specified estimates for local recurrence (LR) with external beam radiation therapy (EBRT) significantly overestimated actual LRR. In the TARGIT-A trial, LR with EBRT was estimated at the outset to be 6%, and in the ELIOT trial, it was estimated to be 3%. Surprisingly, LRR in the EBRT groups has been found to be significantly lower, 1.3% in the EBRT arm of the TARGIT-A and 0.4% in the EBRT arm of the ELIOT trial, respectively. Median follow-up was 2.4 years for the TARGIT-A trial and 5.8 years for the ELIOT trial. However, the initial cohort of patients in the TARGIT-A trial (reported in 2010) now have a median follow-up of 3.8 years and data on LR were available at 5 years follow-up on 35% of patients (18% who received IORT). Although further follow-up will increase confidence with the data, it will also further delay clinical implementation. By carefully weighing the risks and benefits of a single-fraction radiation treatment with patients, IORT should be offered within agreed and strict protocols. Patients deemed at low risk of LR or those deemed suitable for partial breast irradiation, according to the GEC-ESTRO and ASTRO recommendations, could be considered as candidates for IORT. These guidelines apply to all partial breast irradiation techniques, and more specific guidelines for IORT would assist clinicians.

Background Breast reconstruction (BR) is considered to be adversely affected by radiotherapy (RT), particularly when an implant is used. The aim of this study was to compare clinical and patient-reported outcomes after expander-assisted latissimus dorsi breast reconstruction depending on the timing of RT. Methods Patients undergoing BR over a 10-year period (follow-up mean, 56 [14-134] months) were divided into 3 groups. Group 1, RT after mastectomy and BR, Group 2, RT before mastectomy and BR, and Group 3, RT after mastectomy but before BR. The primary endpoints were early and late surgical interventions. Validated questionnaires were circulated to all study patients and matched controls. Results Three hundred thirteen patients underwent 389 BRs. One hundred eighteen patients received RT, of which 65 had undergone expander-assisted latissimus dorsi breast reconstruction. Both use and timing of RT influenced clinical outcomes. Overall, use of RT resulted in a 3-fold increase in complications (P = 0.003). Postreconstruction RT resulted in more than double the number of complications compared with prereconstruction RT (P = 0.008) and delaying BR until after mastectomy and RT reduced complications to levels observed in control patients (P = nonsignificant). Complications were halved in patients undergoing autologous LD reconstruction (P = 0.0001). Patient-reported outcomes were similar for emotional well-being, satisfaction, and shoulder symptoms, although a nonsignificant increase in chronic breast symptoms was reported by the RT group. Conclusion The timing and type of LD reconstruction chosen by patients receiving RT has a significant impact on the risk of subsequent complications and unplanned interventions but has little impact on longer term patient well-being or satisfaction.

Increasing breast specialization triggered a review of our surgical activity. All 10,000 elective inpatient and day case procedures between 1998 and 2008 were grouped into six categories: oncological, primary, secondary and revisional oncoplastic, and other breast and nonbreast procedures. Overall, surgical activity increased, with a rise in breast and a fall in nonbreast procedures, as a result of a changing caseload in each category (chi-squared for linear trend = 55.24: p0.00001). These included increases in oncological procedures, secondary oncoplastic, and revisional oncoplastic procedures. Increased oncoplastic activity was associated with a reduction in other breast procedures (chi-squared for linear trend = 04.94: p0.00001). The impact of breast specialization reported in the 1990's has accelerated with the introduction of oncoplastic surgery. This has major short-term and long-term implications when planning a modern breast service.

Background Latissimus dorsi (LD) miniflap volume replacement is used for immediate reconstruction after partial mastectomy. This prospectively collected series was analyzed to evaluate the accuracy of intraoperative frozen sections. Methods After partial mastectomy, “bed biopsies” were submitted for intraoperative frozen-section analysis. If disease free, volume replacement was undertaken; if involved, targeted re-excisions were taken. Demographic, pathological, and outcome data were recorded. The proportion of breast excised was calculated. Local recurrences were recorded. Results One hundred ten partial mastectomies with LD miniflap volume replacement were completed. The median proportion of breast excised was 28% (maximum 72%); median weight 207 g. Frozen sections were positive in 33% of patients with a sensitivity of 83% and accuracy of 96% when compared with paraffin sections. Local recurrence occurred in one case. The median follow-up was 41.4 months. Conclusions LD miniflap volume replacement extends the role of breast-conserving surgery. Frozen-section analysis of bed biopsies facilitates a single-stage procedure.