Surgery For Early Breast Cancer Research Articles

Sentinel lymph node biopsy vs no axillary surgery in early breast cancer clinically and ultrasonographically node negative: A prospective randomized controlled trial-VENUS trial.

Sentinel lymph node biopsy vs no axillary surgery in early breast cancer clinically and ultrasonographically node negative: A prospective randomized controlled trial-VENUS trial.

Assessment of Breast Cancer Mortality Trends Associated With Mammographic Screening and Adjuvant Therapy From 1986 to 2013 in the State of Victoria, Australia

Diagnosis of early breast cancer (EBC) in women by mammographic screening and postsurgical adjuvant endocrine therapy and chemotherapy (termed adjuvant therapy) began simultaneously in many countries in the 1990s. Subsequent breast cancer mortality declines were variously attributed to mammographic screening and/or adjuvant therapy. To determine the relative mortality reductions associated with these 2 interventions in women with EBC who had been exposed to both. This secondary analysis of cross-sectional studies assessed groups of women with invasive breast cancer in the State of Victoria, Australia, from January 1, 1982, to December 31, 2013, who were included in the Victorian Cancer Registry (VCR). The population consisted of participants in population-based studies of female breast cancer from 1986 to 2013 using data from 4 VCR population-based surveys of breast cancer treatment from 1986 to 1999; VCR data on breast cancer incidence, mortality, and TNM stage at diagnosis from 1986 to 2013; and Victorian mammographic screening program (BreastScreen Victoria) data from 1992 to 2007. Breast cancer incidence and mortality data were analyzed for all 76 630 women registered with invasive breast cancer with the VCR from January 1, 1982, to December 31, 2013, and breast cancer treatment and screening data were analyzed additionally for the groups of surveyed women as described above. Participation in BreastScreen Victoria and receipt of adjuvant therapy after surgery for EBC. Data were analyzed for associations between crude breast cancer mortality trends and uptake of adjuvant therapy and downstaging by mammographic screening. Of all 76 630 women registered with breast cancer with the VCR from January 1, 1982, to December 31, 2013. Joinpoint analyses of the time trend in crude mortality showed an increase from 31.6 per 100 000 women in 1982 to 34.3 per 100 000 women in 1994, with a single joinpoint at 1994, followed by a significant declining trend to 23.9 per 100 000 women in 2013 (annual percentage change, -1.3%; 95% CI, -1.6% to -0.9%). By 1999, 74% of all Victorian women with EBC (737 of 1001) had commenced adjuvant endocrine therapy, and 72% (187 of 260) of premenopausal and 29% (215 of 741) of postmenopausal women with EBC had commenced adjuvant chemotherapy. Crude incidence of advanced-stage breast cancer almost doubled from 12.2 per 100 000 women in 1986 to 23.9 per 100 000 women in 2013. This study found that mammographic screening did not downstage breast cancer in Victoria from advanced to early, so population mortality benefit is lacking. Adjuvant therapy uptake was associated with all of the decline in Victorian breast cancer mortality since 1994. Given these findings, monitoring the relative contributions of mammographic screening and adjuvant therapy for EBC to breast cancer mortality reductions in populations of women exposed to both should be mandatory.

Omitting surgery for early breast cancer showing clinical complete response to primary systemic therapy

Breast cancer is highly sensitive to systemic therapy. High probability of pathological complete response suggests a clinical question that omitting surgery is an effective alternative to surgery in breast cancer showing clinical complete response to primary systemic therapy. However, the validity of omitting surgery for early breast cancer after primary systemic therapy has not been sufficiently established; thus, even if pathological complete response is expected in patients showing clinical complete response, excision of the primary tumor site remains the standard treatment of breast cancer. Inappropriate omitting surgery increases the incidence of local recurrence, which can be the risk of a subsequent distant metastasis and reduced overall survival. To achieve acceptable local control rate, omitting surgery should be investigated in patients with early breast cancer where a high percentage of pathological complete response, a high concordance rate between clinical complete response and pathological complete response and an acceptable local control rate are expected. This review presents concept and ongoing clinical trials for omitting surgery for patients with breast cancer showing clinical complete response to primary systemic therapy.

Optimization of Wire-guided Technique With Bracketing Reduces Resection Volumes in Breast-conserving Surgery for Early Breast Cancer

BackgroundWire-guided localization (WGL) of early breast cancer can be facilitated using multiple wires, which is called bracketing wire-guided localization (BWL). The primary aim of this study is to compare BWL and conventional WGL regarding minimization of resection volumes without compromising margin status. Secondly, BWL is evaluated as an alternative method for intraoperative ultrasound (US) guidance in poorly definable breast tumors on US. Patients and MethodsIn this retrospective cohort study, patients with preoperatively diagnosed breast cancer undergoing wide local excision between January 2016 and December 2018 were analyzed. Patients with multifocal disease or neoadjuvant treatment were excluded from this study. Optimal resection with minimal healthy breast tissue removal was assessed using the calculated resection ratio (CRR). ResultsBWL was performed in 17 (9%) patients, WGL in 44 (22%), and US in 139 (70%). The rate of negative margins was comparable in all 3 groups. The CRR was significantly smaller for BWL (0.6) than WGL (1.3) in tumors larger than 1.5 cm. Additionally, BWL (0.8) led to smaller CRRs than US (1.7). This could be explained by the high number of small tumors (≤ 1.5 cm) in the US group for which greater CRRs are obtained than for large tumors (> 1.5 cm) (1.9 vs. 1.4; P = .005). ConclusionFor breast tumors larger than 1.5 cm, BWL achieves more optimal resection volumes without compromising margin status compared with WGL. Moreover, BWL seems a suitable alternative to US in patients with poorly ultrasound-visible breast tumors and patients with a small tumor in a (large) breast.

Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-Forward): 5-year efficacy and late normal tissue effects results from a multicentre, non-inferiority, randomised, phase 3 trial

SummaryBackgroundWe aimed to identify a five-fraction schedule of adjuvant radiotherapy (radiation therapy) delivered in 1 week that is non-inferior in terms of local cancer control and is as safe as an international standard 15-fraction regimen after primary surgery for early breast cancer. Here, we present 5-year results of the FAST-Forward trial.MethodsFAST-Forward is a multicentre, phase 3, randomised, non-inferiority trial done at 97 hospitals (47 radiotherapy centres and 50 referring hospitals) in the UK. Patients aged at least 18 years with invasive carcinoma of the breast (pT1–3, pN0–1, M0) after breast conservation surgery or mastectomy were eligible. We randomly allocated patients to either 40 Gy in 15 fractions (over 3 weeks), 27 Gy in five fractions (over 1 week), or 26 Gy in five fractions (over 1 week) to the whole breast or chest wall. Allocation was not masked because of the nature of the intervention. The primary endpoint was ipsilateral breast tumour relapse; assuming a 2% 5-year incidence for 40 Gy, non-inferiority was predefined as ≤1·6% excess for five-fraction schedules (critical hazard ratio [HR] of 1·81). Normal tissue effects were assessed by clinicians, patients, and from photographs. This trial is registered at isrctn.com, ISRCTN19906132.FindingsBetween Nov 24, 2011, and June 19, 2014, we recruited and obtained consent from 4096 patients from 97 UK centres, of whom 1361 were assigned to the 40 Gy schedule, 1367 to the 27 Gy schedule, and 1368 to the 26 Gy schedule. At a median follow-up of 71·5 months (IQR 71·3 to 71·7), the primary endpoint event occurred in 79 patients (31 in the 40 Gy group, 27 in the 27 Gy group, and 21 in the 26 Gy group); HRs versus 40 Gy in 15 fractions were 0·86 (95% CI 0·51 to 1·44) for 27 Gy in five fractions and 0·67 (0·38 to 1·16) for 26 Gy in five fractions. 5-year incidence of ipsilateral breast tumour relapse after 40 Gy was 2·1% (1·4 to 3·1); estimated absolute differences versus 40 Gy in 15 fractions were −0·3% (−1·0 to 0·9) for 27 Gy in five fractions (probability of incorrectly accepting an inferior five-fraction schedule: p=0·0022 vs 40 Gy in 15 fractions) and −0·7% (−1·3 to 0·3) for 26 Gy in five fractions (p=0·00019 vs 40 Gy in 15 fractions). At 5 years, any moderate or marked clinician-assessed normal tissue effects in the breast or chest wall was reported for 98 of 986 (9·9%) 40 Gy patients, 155 (15·4%) of 1005 27 Gy patients, and 121 of 1020 (11·9%) 26 Gy patients. Across all clinician assessments from 1–5 years, odds ratios versus 40 Gy in 15 fractions were 1·55 (95% CI 1·32 to 1·83, p<0·0001) for 27 Gy in five fractions and 1·12 (0·94 to 1·34, p=0·20) for 26 Gy in five fractions. Patient and photographic assessments showed higher normal tissue effect risk for 27 Gy versus 40 Gy but not for 26 Gy versus 40 Gy.Interpretation26 Gy in five fractions over 1 week is non-inferior to the standard of 40 Gy in 15 fractions over 3 weeks for local tumour control, and is as safe in terms of normal tissue effects up to 5 years for patients prescribed adjuvant local radiotherapy after primary surgery for early-stage breast cancer.FundingNational Institute for Health Research Health Technology Assessment Programme.

The Efficacy of Software to Help Patients Understand Drug for Adjuvant Treatment for Breast Cancer: A Pilot Randomized Controlled Trial.

We assessed the usefulness of ChemoCalc, a software package for calculating drug costs, in helping patients understand these costs. We randomly assigned, in a 1 : 1 ratio, 20 women who had undergone surgery for early breast cancer to a group that discussed adjuvant treatment with their physicians using the ChemoCalc software (ChemoCalc group) or a group that discussed adjuvant treatment without ChemoCalc (Usual Explanation group). The participants completed a five-grade evaluation questionnaire after these discussions. The primary endpoint was the intergroup comparison of the questionnaire scores regarding participants' understanding of their treatment-associated drug costs. Median age was not significantly different between the ChemoCalc group and Usual Explanation group (57 vs. 50, respectively; p=0.27). Patients in the ChemoCalc group had a significantly higher perceived level of understanding of the drug cost than those in the Usual Explanation group (5 [4-5] vs. 2.5 [1-5], respectively; p=0.002). Scores related to the patients' perception that understanding drug costs is an important part of breast cancer treatment were also higher in the ChemoCalc group than the Usual Explanation group (5 [2-5] vs. 3 [1-5], respectively; p=0.049). ChemoCalc was found to be useful for understanding drug costs.

Hypofractionated Whole Breast Radiotherapy with Simultaneous Integrated Boost Following Breast Conservative Surgery for Early Breast Cancer

Background: Hypofractionated whole breast radiotherapy (HFWBRT) showed comparable efficacy and safety to conventional fractionated radiotherapy. Dose and fractionation of the tumor bed boost to be integrated during HF-WBRT schedules is still to be determined. Aim: to investigate the clinical feasibility of HF-WBRT with simultaneous integrated boost (SIB), in early breast cancer patients who underwent breast conserving surgery (BCS). Methods: This single arm prospective study included 40 female patients with pathologically proven stage I-II breast cancer following BCS with high risk factors. Patients received 3D conformal radiotherapy (3DCRT) with field in field (FIF) technique. The whole breast received a dose of 40 gray (Gy) over 15 fractions for 3 weeks with an additional SIB dose of 8 Gy over 15 fractions to be give daily during WBRT. Radiation toxicities were graded using the common terminology criteria for adverse events (NCI-CTCAE) scale version 4.03. Cosmetic outcome was assessed using Harvard cosmetic score. Kaplan Meier method was used to estimate the 3- year disease free (DFS) and overall survival (OS). Results: The median age at presentation was 48 years (range 33-68). No reported grade 3 or 4 toxicities. Grade 1 and 2 radiation dermatitis affected 80% of the patients, breast pain was observed in 62.5% of the patients while 25% had radiation pneumonitis. Most of the patients (95%) had excellent and good cosmetic outcomes. At 3 years the estimated DFS was 95% and OS was 97.5 %. Conclusion: WBRT-SIB using 3DCRT with FIF technique is clinically feasible for early stage breast cancer patients.

FAST-Forward Phase III Randomised Controlled Trial of 1-Week Hypofractionated Breast Radiotherapy: 5-Year Results for Efficacy and Late Normal Tissue Effects

Background: FAST-Forward aims to identify a 5-fraction (Fr) schedule of adjuvant radiotherapy (radiation therapy) delivered in 1 week which is non-inferior for local cancer control and as safe as an international standard 15Fr regimen after primary surgery for early breast cancer. Five-year results are presented. Methods: FAST-Forward (ISRCTN19906132) randomised (1:1:1) patients with invasive carcinoma of the breast (pT1-3 pN0-1 M0) after breast conservation surgery or mastectomy to 40Gy in 15Fr (3 weeks), 27Gy or 26Gy in 5Fr (1 week) to whole breast/chest wall. Primary endpoint was ipsilateral breast tumour relapse (IBTR); assuming 2% 5-year incidence for 40Gy, non-inferiority was pre-defined as < 1.6% excess for 5Fr schedules (critical hazard ratio HR=1.81). Normal tissue effects (NTE) were assessed by clinicians, patients and photographs. Findings: 4096 consenting patients (1361 40Gy, 1367 27Gy, 1368 26Gy) were recruited November 2011-June 2014 from 97 UK centres. At 71 months median follow-up, 79 IBTR events were reported (40Gy: 31, 27Gy: 27, 26Gy: 21); HRs (95%CI) versus 40Gy/15Fr were 27Gy/5Fr: 0.86 (0.51,1.44), 26Gy/5Fr: 0.67 (0.38,1.16). Five-year incidence of IBTR after 40Gy was 2.1% (1.4,3.1); estimated absolute differences versus 40Gy/15Fr were -0.3% (-1.0,0.9) for 27Gy/5Fr (p=0.0022 for non-inferiority) and -0.7% (-1.3,0.3) for 26Gy/5Fr (p=0.00019). 5-year prevalence of any clinician-assessed moderate/marked breast NTE after 40Gy: 98/986 (9.9%), 27Gy: 155/1005 (15.4%), 26Gy: 121/1020 (11.9%). Across all clinician assessments from 1-5 years, odds ratios versus 40Gy/15Fr were 1.55 (1.32,1.83, p<0.0001) for 27Gy/5Fr and 1.12 (0.94,1.34, p=0.20) for 26Gy/5Fr. Patient and photographic assessments showed higher NTE risk for 27Gy versus 40Gy but not for 26Gy. Interpretation: 5-year local tumour incidence and NTE prevalence show 26Gy/5Fr in 1 week to be an effective and safe alternative to 40Gy/15Fr in 3 weeks for patients prescribed adjuvant local radiotherapy after primary surgery for early stage breast cancer. Trial Registration: ISRCTN19906132. Funding Statement: The FAST-Forward trial is funded by the National Institute for Health Research (NIHR) Health Technology Assessment Programme - HTA (UK) (09/01/47), with programme grants from Cancer Research UK to support the work of ICRCTSU (C1491/A15955; C1491/A25351). We acknowledge NHS funding to the NIHR Biomedical Research Centre at the Royal Marsden NHS Foundation Trust and The Institute of Cancer Research (London, UK). Declaration of Interests: JMB reports grants from NIHR HTA and grants from Cancer Research UK during the conduct of the study, and grants and non-financial support from Novartis (previously GSK), grants and non-financial support from Astra Zeneca, grants and non-financial support from Clovis Oncology, grants and non-financial support from Janssen-Cilag, grants and non-financial support from Merck Sharpe & Dohme, grants and non-financial support from Puma Biotechnology, grants and non-financial support from Pfizer, grants and non-financial support from Roche, grants from Medivation, outside the submitted work. DAW reports travel grants from Roche Pharmaceuticals, outside the submitted work. JSH, MAS and LS report grants from NIHR HTA and grants from Cancer Research UK, during the conduct of the study. CCK reports personal fees from Roche Pharmaceutical, outside the submitted work. AA, AMB, DJB, CC, CEC, MC, AG, PH, CM, ZN, NS, IS, JRY declare no competing interests. Ethics Approval Statement: FAST-Forward was approved by the national South East Coast Kent Research Ethics Committee (11/LO/0958) and local Research and Development offices of all participating centres.

Cytoplasmic Cyclin E Is an Independent Marker of Aggressive Tumor Biology and Breast Cancer-Specific Mortality in Women over 70 Years of Age.

Multi-cohort analysis demonstrated that cytoplasmic cyclin E expression in primary breast tumors predicts aggressive disease. However, compared to their younger counterparts, older patients have favorable tumor biology and are less likely to die of breast cancer. Biomarkers therefore require interpretation in this specific context. Here, we assess data on cytoplasmic cyclin E from a UK cohort of older women alongside a panel of >20 biomarkers. Between 1973 and 2010, 813 women ≥70 years of age underwent initial surgery for early breast cancer, from which a tissue microarray was constructed (n = 517). Biomarker expression was assessed by immunohistochemistry. Multivariate analysis of breast cancer-specific survival was performed using Cox’s proportional hazards. We found that cytoplasmic cyclin E was the only biological factor independently predictive of breast cancer-specific survival in this cohort of older women (hazard ratio (HR) = 6.23, 95% confidence interval (CI) = 1.93–20.14; p = 0.002). At ten years, 42% of older patients with cytoplasmic cyclin E-positive tumors had died of breast cancer versus 8% of negative cases (p < 0.0005). We conclude that cytoplasmic cyclin E is an exquisite marker of aggressive tumor biology in older women. Patients with cytoplasmic cyclin E-negative tumors are unlikely to die of breast cancer. These data have the potential to influence treatment strategy in older patients.

Abstract P1-20-05: Surgical margin involvement (&amp;lt;2mm) increases local and distant cancer recurrence

Abstract Background: Leaving involved margins after surgery for early breast cancer is associated with an increased risk of local recurrence but the effect on distant recurrence is controversial. ASCO and ASTRO endorsed a policy that negative margins of no ink on tumour represented sufficient margin for local control and that the routine practice of obtaining a more widely negative margin was not indicated. We aimed to assess margin status (&amp;lt;1mm, 1-2mm and clear margins &amp;gt;2mm) on local and distant control of breast cancer in a consecutive UK patient audit of Breast Cancer Units. Methods: Patients (n = 2795) undergoing surgery for early breast cancer (Tis, T1-3) in 3 Greater Manchester Breast Units had margin status prospectively recorded (reported by micrometer according to NHSBSP pathology guidelines) and local and distant recurrence recorded. All patients received adjuvant therapy according to local guidelines. Statistical analysis using cox proportional hazard regression was used to identify clinicopathological factors predicting recurrence in the multivariate analysis. Results: Overall 575 women (19.3%) had involved (≤1mm clearance) and 235 (8.5%) close (≤2mm clearance) and 1895 clear surgical margins. 1652 patients underwent breast conserving surgery and 1143 mastectomy. Median follow-up is 63.7 months. Overall local recurrence rate was 3.8% and distant recurrence 4.9% by a median of 5 years follow-up. Local and distant recurrence was higher after mastectomy at 7% and 7.8%, respectively. Margin &amp;lt;1mm was associated with increased local and distant recurrence compared to a clear margin &amp;gt;2mm. In multivariate analysis, two factors: molecular phenotype (other phenotypes versus Luminal A HR 1.79) and close / involved margins less than 2mm clearance (versus clear &amp;gt;2mm) [HR 1.76 (95% confidence intervals 1.06 - 2.92)], predicted local recurrence and the same factors together with mastectomy (compared to breast conservation), T and N stage predicted distant recurrence (see table 1). Table 1. Multivariate analysis of factors predicting cancer recurrenceLocal Recurrence (HR)Distant Recurrence (HR)Margin categorical &amp;lt;1mm vs &amp;gt;2mm1.84 (1.05 - 3.22, p=0.031)1.82 (1.1 – 3.02, p= 0.019)Margin &amp;lt;2mm (vs clear &amp;gt;2mm)1.76 (1.06-2.92, p=0.027)1.86 (1.16-2.27, p=0.009)T Stage 2 vs 11.55 (0.88 – 2.73, p=0.129)4.35 (2.07 – 9.14, p&amp;lt;0.001)T Stage 3 vs 11.66 (0.63 – 4.37, p=0.296)4.66 (1.85 – 11.72, p=0.001)N Stage 1 vs 01.74 (0.98 – 3.06, p=0.054)1.161 (0.97 – 2.87, p=0.06)N Stage 2 vs 01.69 (0.75 – 3.8, p=0.201)2.11 (1.07 - 4.17, p=0.03)N Stage 3 vs 02.07 (0.9 – 5.61, p=0.148)6.22 (3.32 – 11.68, p&amp;lt;0.001)Mastectomy vs WLE1.57 (0.91 – 2.72, p=0.103)2.51 (1.41 – 4.17, p=0.002)Luminal A vs Basal-Like0.25 (0.13 – 0.49, p&amp;lt;0.001)0.18 (0.09 – 0.37, p&amp;lt;0.001)Luminal B vs Basal-Like0.37 (0.2 – 0.68, p=0.001)0.33 (0.18 – 0.59, p&amp;lt;0.001)HER-2 vs Basal-Like0.1 (0.01 – 0.75, p=0.024)0.46 (0.19 – 1.15, p=0.095) Conclusion: Clearing surgical margins improves recurrence free survival (both local and distant). Leaving margins ≤2mm increases distant cancer recurrence and clearance of margins should be essential surgical management, particularly in oestrogen receptor (ER) negative breast cancer. Current guidelines accepting margins ≤1mm will increase distant recurrence and deaths from breast cancer. Citation Format: Sarah Michael, Sarah Bowers, Jane Ooi, Mo Absar, James Bundred, Nigel Bundred. Surgical margin involvement (&amp;lt;2mm) increases local and distant cancer recurrence [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-20-05.

Optimization of Wire-Guided Technique with Bracketing Reduces Resection Volumes in Breast-Conserving Surgery for Early Breast Cancer

Background: When a breast tumor is not visible on ultrasound, wire-guided-localization (WGL) is the preferred method for wide local excision (WLE). WGL with a single wire can be enhanced by three dimensional tumor demarcation using multiple wires and wire lengths, which is called bracketing wire-guided localization (BWL). The primary aim of this study is to evaluate whether BWL leads to more optimal resection volumes without compromising margins status compared to normal WGL. Secondly, this study investigated BWL as alternative method for intra-operative ultrasound (US) guidance in poorly definable breast tumors on ultrasound.

Focus issues of breast-conserving surgery in early breast cancer

Breast-conserving surgery (BCS) has become a standard surgical method for early breast cancer. However, with the standardization of BCS, there are still many core issues in clinical practice. First of all, although the indications for BCS generally reach a consensus, the effects of age and tumor size on BCS are still worthy of attention; in addition, how to ensure the negative margin and repair tissue defect that achieve better breast shape are the key to the success of BCS; what′s more, the improvement of margin evaluating methods and the application of oncoplastic technic, neoadjuvant chemotherapy, axillary sentinel lymph node biopsy, mastoscopic technique in the BCS, new artificial materials and 3D printing technology, all for the development of BCS provides a better future. This article will summarize the above-mentioned focus issues on early breast cancer. Key words: Early diagnosis; Breast neoplasms; Surgical procedures, operative; Breast-conserving surgery; Focus issues

Oncoplastic Breast Surgery in Early Breast Cancer

Oncoplastic medical procedure consolidates plastic careful systems with sound careful oncologicstandards. The objective is to totally extract the malignant growth, with wide careful edges whilekeeping up or improving cosmesis. For huge, inadequately characterized, or ominously arrangedtumors, standard lumpectomies may prompt unsuitable restorative outcomes notwithstandingclose or included resection edges. Comparable issues may happen for littler tumors in littlebosoms. Joining of the two careful orders evades or limits poor restorative outcomes after wideextraction. It builds the quantity of ladies who can be treated with breast‐conserving medicalprocedure by permitting bigger bosom extractions with progressively satisfactory correctiveoutcomes. Oncoplastic medical procedure requires a multidisciplinary approach and exhaustivepreoperative arranging. It is totally important to enroll the participation and coordination ofcareful oncology, plastic medical procedure, radiology, pathology, restorative oncology, andradiation oncology. Oncoplastic medical procedure requires a way of thinking that the presenceof the bosom after tumor extraction is significant.

Cytoplasmic cyclin E independently predicts recurrence in older patients with primary breast cancer.

3128 Background: Primary breast cancer in the older ( &gt; 70 years) population has distinct biological characteristics associated with favourable outcome, such as higher rate of estrogen receptor (ER) positivity. Due to comorbidities, older patients with primary breast cancer are more likely to die of non-breast cancer-related causes compared to their younger counterparts. Biomarkers that may influence treatment strategy therefore require interpretation in the specific biological and clinical context of older women. Cyclin E regulates cell cycle transition from G1 to S phase, and its deregulation is implicated in breast cancer pathogenesis. Tumour-specific isoforms of cyclin E localise to the cytoplasm. Expression of cytoplasmic cyclin E (c-cyclin E) is linked with poor clinical outcome. We now present multivariate analysis of breast cancer-specific survival (BCSS) by c-cyclin E and clinical markers of disease biology from a cohort of older women. The primary outcome, BCSS, excludes deaths from competing causes and is used as a surrogate for tumour biology. Methods: Between 1973 and 2010, 813 older women underwent initial surgery for early breast cancer and were followed up in a dedicated clinic in Nottingham. Excised tumours from 517 of these patients were successfully incorporated into a tissue microarray (TMA). Expression of c-cyclin E was assessed by IHC using an assay developed at MDACC, along with a panel of 24 biomarkers. Of these, ER, progesterone receptor (PR), human epidermal growth factor 2 (HER2) and Ki67 are in current clinical use and are analysed alongside c-cyclin E. Grade was assessed from the primary tumour. Multivariate analysis of BCSS was performed by Cox proportional hazard test. Results: In multivariate analysis alongside markers of disease biology currently used in the clinic (ER, PR, HER2, Ki67 and grade), c-cyclin E is the only factor that independently predicts BCSS in this cohort of older women (HR 5.0, 95% CI 2.1 – 12.0; p&lt; 0.001). Conclusions: In the older population with primary breast cancer, c-cyclin E expression is the only independent biological marker of BCSS. Patients with low c-cyclin E expression are unlikely to die of breast cancer. These data have potential to influence treatment strategy in older patients. For example, patients with ER+, c-cyclin E negative disease plus multiple co-morbidities may be suitable for primary endocrine therapy. This hypothesis warrants prospective clinical evaluation.

140P - Evaluation of intraoperative frozen section with final histopathology results for sentinel lymph node biopsy in breast cancer

Background Intraoperative assessment of sentinel lymph nodes for patients undergoing surgery for early breast cancer has the potential to reduce the need for delayed axillary lymph node dissection (ALND), significantly reducing patient morbidity, expediting adjuvant therapy, reducing length of hospital stay and cost of hospitalisation. This study aims to evaluate intraoperative frozen section in identifying cancerous involvement of sentinel lymph nodes in early breast cancer.

Abstract P3-12-22: Targeted intraoperative radiotherapy (TARGIT IORT) during breast conserving surgery for early stage breast cancer in patients with breast augmentation with implants

Abstract Background: Targeted intraoperative radiotherapy (TARGIT) has become a standard option during breast conserving surgery for selected cases of early breast cancer and over 20,000 patients have been treated in over 300 centers around the world. Although a growing number of patients are presenting with implant breast augmentation, no data has been published regarding the safety of TARGIT with implants in situ. TARGIT IORT as a replacement for whole breast irradiation is an important issue in this context because of the high rates of capsular fibrosis following EBRT in such patients. Methods: We are reporting a case series of 12 patients who received TARGIT during breast conserving surgery for early breast cancer, had undergone breast augmentation with implants before and wanted their implants to stay in situ. Patients were informed that no published data existed and decided on this approach on an individual basis. 3 patients received additional EBRT after TARGIT IORT because of the presence of EIC or LVI. TARGIT IORT was performed using Intrabeam - 50 kV – X-rays delivering 20 Gy prescribed at the surface of the tumor bed during the initial lumpectomy procedure. Results:Patient characteristics are given in table 1. Follow-up varied from 78 months to 3 months. 11 patients presented with invasive breast cancer, 1 patient with DCIS. There were no procedure related complications and none of the patients have needed their implant removed. 1/12 patients (ID 7) was diagnosed with a local recurrence in a distant quadrant after 36 months of follow-up. In 11/12 patients no breast-cancer-related events occurred. Patient characteristicsIDER/PR/HER2GradeSentinel NodesTumor Size (mm)Distance Implant to Tumor (mm)EBRT after IORTFollow up time (months)1pos/pos/neg2pN1mi (sn)95No622pos/neg/neg2pN0 (sn)1913Yes543pos/pos/neg3pN0 (sn)0.85Yes324pos/pos/neg2pN0 (sn)611No155pos/pos/neg3pN0 (sn)71Yes146pos/pos/neg1pN0 (sn)515No117pos/pos/neg2pN0 (sn)7not reportedNo378pos/pos/na1 (DCIS)N/A8not reportedNo789pos/pos/neg2pN0 (sn)15not reportedNo1510pos/neg/neg1pN0 (sn)144No4411pos/pos/neg2pN0 (sn)91No1112pos/pos/neg2pN0 (sn)75No3Table 1 Conclusion: This series of patients with TARGIT during breast conserving surgery for early breast cancer after breast augmentation with implants in situ revealed no safety concerns. Our case series gives some confidence in discussing this option with suitable patients. To expand this series, we are gathering details about other cases from the whole TARGIT group worldwide. Citation Format: Kolberg H-C, Uhl V, Massarut S, Holmes D, Liedtke C, Whineray Kelly E, Lövey G, Vaidya JS. Targeted intraoperative radiotherapy (TARGIT IORT) during breast conserving surgery for early stage breast cancer in patients with breast augmentation with implants [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-12-22.

Abstract GS4-05: Dose escalated simultaneous integrated boost radiotherapy for women treated by breast conservation surgery for early breast cancer: 3-year adverse effects in the IMPORT HIGH trial (CRUK/06/003)

Abstract Background IMPORT HIGH is a randomised, multi-centre phase III trial testing dose escalated simultaneous integrated boost (SIB) against sequential boost each delivered by intensity modulated radiotherapy (IMRT) for early stage breast cancer with higher risk of local relapse. The primary endpoint was initially breast induration at 3 years, requiring 840 patients; accrual was extended (target 2568) with the new primary endpoint of local relapse. We report adverse effects (AE) at 3 years. Methods Women age ≥18 after breast conservation surgery for pT1-3 pN0-pN3a M0 invasive carcinoma were eligible. Randomisation was 1:1:1 between 40Gy/15F to whole breast (WB) + 16Gy/8F sequential photon boost to tumour bed (40+16Gy), 36Gy/15F to WB, 40Gy to partial breast + 48Gy (48Gy) or + 53Gy (53Gy) in 15F SIB to tumour bed. AEs were assessed annually by clinicians in all patients and in a planned sub-set (840) of patients by photographs at 3 years and by patients at 6 months, 1 and 3 years. AE scores were dichotomised as none/mild vs marked for photographs and none/mild vs moderate/marked for patients and clinicians. Fisher's exact tests compared groups; principal comparison (protocol-specified) between 53Gy and 48Gy (p&amp;lt;0.01 defined as statistical significance). Results 2617 women consented between 03/2009 and 09/2015 from 39 UK radiotherapy centres. Median follow-up was 49.1 (IQR 36.8-63.2) months. Median age was 49 (IQR 44-56); 9%, 38% &amp; 53% were tumour grade 1, 2 &amp; 3 respectively; 30% were node positive. 66% received chemotherapy and 73% endocrine therapy. 3-year AE data were available for 2017 clinician assessments, 641 photographs and 842 patient assessments. Proportions of patients with marked AEs were low overall. Rates of moderate/marked AEs at 3 years were broadly similar between the randomised groups; with a suggestion of a slightly increased risk for breast induration in 53Gy compared with control (borderline significance). AE at 3 years 40+16Gy n(%)48Gy n(%)53Gy n(%)ClinicianBreast induration;N656668654None451 (69)483 (72)445 (68)Mild167 (25)141 (21)146 (22)Moderate32 (5)42 (6)56 (9)Marked6 (1)2 (1)7 (1)P-value 0.57010.0102 0.0443Breast shrinkage;N655669654None442 (68)472 (71)448 (69)Mild167 (26)161 (24)166 (25)Moderate40 (6)33 (5)35 (5)Marked6 (1)3 (1)5 (1)P-value 0.25410.5772 0.6373Breast distortion;N656669654None451 (69)464 (69)442 (68)Mild169 (26)170 (25)170 (26)Moderate33 (5)32 (5)38 (6)Marked3 (1)3 (1)4 (1)P-value 0.90310.4862 0.4113PatientChange in breast appearance;N287264285None38 (13)50 (19)58 (20)Mild164 (57)151 (57)142 (50)Moderate57 (20)45 (17)54 (19)Marked28 (10)18 (7)31 (11)P-value 0.14910.9992 0.1243PhotographChange in breast appearance;N218210213None183 (84)185 (88)177 (83)Mild25 (11)23 (11)32 (15)Marked10 (5)2 (1)4 (2)P-value 0.03610.1732 0.6853148Gy v 40+16Gy; 253Gy v 40+16Gy; 353Gy v 48Gy Conclusions These results represent the largest and most mature reported AE outcomes of breast SIB within a clinical trial. At 3 years, rates of moderate/marked AEs were similar between SIB IMRT and WB + sequential boost IMRT delivered over 3 and 4.5 weeks respectively. Citation Format: Coles CE, Griffin CL, Kirby AM, Haviland JS, Titley JC, Benstead K, Brunt AM, Chan C, Ciurlionis L, Din OS, Donovan EM, Eaton DJ, Harnett AN, Hopwood P, Jefford ML, Jenkins PJ, Lee CE, McCormack M, Sherwin L, Syndikus I, Tsang Y, Twyman NI, Ventikaraman R, Wickers S, Wilcox MH, Bliss JM, Yarnold JR. Dose escalated simultaneous integrated boost radiotherapy for women treated by breast conservation surgery for early breast cancer: 3-year adverse effects in the IMPORT HIGH trial (CRUK/06/003) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS4-05.

Comparative study of modified radical mastectomy and breast conservative surgery in early breast cancer

The purpose of this study is to compare the outcome in term of post operative complication, recurrence, psychiatric outcome of the two methods, Modified Radical Mastectomy and breast conserving surgery in early breast cancer. This study includes 30 cases of MRM and BCS (15-15 from each group) done for early breast cancer. Every woman with operable breast cancer should be offered option of breast conservation if there are no standard contraindications with explanation of role of radiation in these cases. Acceptability of BCS depends apart from the patient's educational and economic background, also on the treating surgeon's training. Patient that had undergone BCS have significantly better health status with regard to physical functioning, health perception & vitality, social functioning & role, emotional and mental health and self-esteem. Study Design: Observational Study

Possibility of avoiding axillary lymph node dissection by immune microenvironment monitoring in preoperative chemotherapy for breast cancer

BackgroundThe diagnosis of metastasis by sentinel lymph node biopsy (SLNB) in early breast cancer surgery provides an accurate view of the state of metastases to the axillary lymph nodes, and it has now become the standard procedure. In the present study, whether omission of axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC) is possible by evaluation of tumor-infiltrating lymphocytes (TILs) before NAC in cases without metastasis on diagnostic imaging, but with metastasis on SLNB, was retrospectively investigated.MethodsA total of 91 patients with resectable, early-stage breast cancer, diagnosed as cT1–2, N0, M0, underwent SLNB and were treated with NAC. A semi-quantitative evaluation of lymphocytes infiltrating the peritumoral stroma as TILs in biopsy specimens of primary tumors prior to treatment was conducted.ResultsIn cases with a low number of TILs, estrogen receptor expression was significantly higher (p = 0.044), and human epidermal growth factor receptor 2 (HER2) expression was significantly lower than in other cases (p = 0.019). The number of TILs was significantly lower in cases in which the intrinsic subtype was hormone receptor-positive breast cancer (HRBC) (p = 0.044). Metastasis to axillary lymph nodes was significantly more common in HER2-negative cases and cases with a low number of TILs (p = 0.019, p = 0.005, respectively).ConclusionsEven if macrometastases are found on SLNB in cN0 patients, it appears that ALND could be avoided after NAC in cases with a good immune tumor microenvironment of the primary tumor.

Controversial issues in radiotherapy after breast-conserving surgery for early breast cancer in older patients: a systematic review.

Breast cancer is the most common malignant disease among older women, and the number of new older patients per year is increasing year by year. Radiotherapy has been confirmed as an important treatment after breast conservation for the reduction of local recurrence and mortality for all patients, including node-positive cases. However, there are fewer clinical trials evaluating the toxicity and benefits of radiotherapy for older patients. Whether radiotherapy can provide substantial benefit for older patients after breast-conserving surgery is controversial. This systematic review will focus on the key aspects of this controversial issue.