Node-negative Invasive Breast Cancer Research Articles

O71: Sentinel Lymph Node Biopsy in Elderly Patients with Early ER+ Breast Cancer: A Systematic Review of the Literature

Abstract Purpose In 2016, the Choosing Wisely guidelines recommended that women over 70 years of age with Oestrogen Receptor positive (ER+), HER2-negative (HER2-), early-stage (T1, T2), clinically node-negative (cN0) invasive breast cancer (BC) should not routinely undergo sentinel lymph node biopsy (SLNB). The aim of this systematic review is to analyse subsequent literature on the influence of SLNB on management and outcomes. Methods An electronic search of Medline (OVID), EMBASE and Cochrane Reviews was conducted Studies comparing SLNB vs. no SLNB were included. 4 studies were eligible for final inclusion. Overall survival (OS), breast cancer-specific survival (BCSS) and influence on adjuvant therapy decisions were analysed. Results Chagpar et al. found SLNB was independently associated with significantly better OS (HR=0.633) in 157,584 patients and better BCSS (HR=0.452) in a subset of 116,059 patients compared to no SLNB. In 24,995 patients, Xu et al. found better OS in those who received SLNB (HR= 0.585) and better BCSS (HR=0.864) vs. those who did not. Castelo et al. performed 2 studies: the first included 126,047 patients, worse BCSS was observed in the no-SLNB group (sub-distribution HR=1.17); the second included 6,286 patients, both worse OS (adjusted HR=1.22), and BCSS (adjusted HR=1.08) were also associated with not receiving SLNB. Conclusion Better OS and BCSS were seen in patients who received SLNB vs. no SLNB despite adjusting for confounders across these studies. While some selection bias may have influenced results, clinicians should remain cautious in omitting SLNB in this cohort.

Preoperative Dynamic Contrast-Enhanced and Diffusion-Weighted Breast Magnetic Resonance Imaging Findings for Prediction of Lymphovascular Invasion of the Lesions in Node-Negative Invasive Breast Cancer.

Purpose: Our single-centre retrospective study aimed to investigate the relationship between preoperative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) findings and apparent diffusion coefficient (ADC) values and lymphovascular invasion (LVI) status of the lesions in patients with clinically-radiologically lymph node-negative invasive breast cancer. Methods: A total of 250 breast lesions diagnosed in preoperative magnetic resonance imaging were identified. All patients were divided into 2 subgroups: LVI-negative and LVI-positive according to the pathological findings of surgical specimens. The 2 groups' DCE-MRI findings, ADC values, and histopathological results of lesions were compared. Results: LVI was detected in 100 of 250 lesions. Younger age than 45 years and larger lesion size than 20 mm were found to be associated with the presence of LVI (P < .001). High histological and nuclear grade (P = .001), HER2-enriched molecular subtype (P = .001), and Ki-67 positivity (P = .016) were significantly associated with LVI. The LVI positivity rate was significantly higher in the lesions with medium-rapid initial phase kinetic curve and washout delayed phase kinetic curve (P = .001). The presence of LVI was significantly associated with the presence of peritumoural edema, sentinel lymph node metastasis, adjacent vessel sign, and increased whole breast vascularity (P < .001). When diffusion-weighted imaging findings were evaluated, it was determined that tumoural ADC values lower than 1068 × 10-6 mm2/second (P = .002) and peritumoural-tumoural ADC ratios higher than 1.5 (P = .001) statistically increased the probability of LVI. Conclusion: The patient's age, various histopathological and DCE-MRI findings, tumoural ADC value, and peritumoural-tumoural ADC ratio may be useful in the preoperative prediction of LVI status in breast cancer lesions.

Accelerated versus standard epirubicin followed by cyclophosphamide, methotrexate, and fluorouracil or capecitabine as adjuvant therapy for breast cancer (UK TACT2; CRUK/05/19): quality of life results from a multicentre, phase 3, open-label, randomised, controlled trial

Adjuvant chemotherapy for patients with early breast cancer improves outcomes but its toxicity affects patients' quality of life (QOL). The UK TACT2 trial investigated whether accelerated epirubicin improves time to recurrence and if oral capecitabine is non-inferior to cyclophosphamide, methotrexate, and fluorouracil (CMF) for efficacy with less toxicity. Results showed no benefit for accelerated epirubicin and capecitabine was non-inferior. As part of the QOL substudy, we aimed to assess the effect of chemotherapies on psychological distress, physical symptoms, and functional domains. TACT2 was a multicentre, phase 3, open-label, parallel-group, randomised, controlled trial done in 129 UK centres. Participants were aged 18 years or older with histologically confirmed node-positive or high-risk node-negative invasive primary breast cancer, who had undergone complete excision, and due to receive adjuvant chemotherapy. Patients were randomly assigned (1:1:1:1) to four cycles of 100 mg/m2 epirubicin either every 3 weeks (standard epirubicin) or every 2 weeks with 6 mg pegfilgrastim on day 2 of each cycle (accelerated epirubicin), followed by four 4-week cycles of either CMF (600 mg/m2 cyclophosphamide intravenously on days 1 and 8 or 100 mg/m2 orally on days 1-14; 40 mg/m2 methotrexate intravenously on days 1 and 8; and 600 mg/m2 fluorouracil intravenously on days 1 and 8 of each cycle) or four 3-week cycles of 2500 mg/m2 capecitabine (1250 mg/m2 given twice daily on days 1-14 of each cycle). The randomisation schedule was computer generated in random permuted blocks, stratified by centre, number of nodes involved (none vs 1-3 vs ≥4), age (≤50 years vs >50 years), and planned endocrine treatment (yes vs no). QOL was one of the secondary outcomes and is reported here. All patients from a subset of 44 centres were invited to complete QOL questionnaires (Hospital Anxiety and Depression Scale [HADS] and European Organisation for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire 30-item core module [QLQ-C30] and Quality of Life Questionnaire breast module [QLQ-BR23]) at baseline, end of standard or accelerated epirubicin, end of CMF or capecitabine, and at 12 and 24 months after randomisation. The QOL substudy prespecified two coprimary QOL outcomes assessed in the intention-to-treat population: overall QOL (reported elsewhere) and HADS total score. Prespecified secondary QOL outcomes were EORTC QLQ-C30 subscales of physical function, role function, and fatigue and EORTC QLQ-BR23 subscales of sexual function and systemic therapy side-effects. This trial is registered with ISRCTN, ISRCTN68068041, and ClinicalTrials.gov, NCT00301925. From Dec 16, 2005, to Dec 5, 2008, 4391 patients (20 [0·5%] of whom were male) were enrolled in TACT2; 1281 (85·8%) of 1493 eligible patients were included in the QOL substudy. Eight (0·6%) participants in the QOL substudy were male and 1273 (99·4%) were female. Median follow-up was 85·6 months (IQR 80·6-95·9). Analysis was performed on the complete QOL dataset (as of Sept 15, 2011) when all participants had passed the 24-month timepoint. Prerandomisation questionnaires were completed by 1172 (91·5%) patients and 1179 (92·0%) completed at least one postrandomisation questionnaire. End-of-treatment HADS depression score (p=0·0048) and HADS total change score (p=0·0093) were worse for CMF versus capecitabine. Accelerated epirubicin led to worse physical function (p=0·0065), role function (p<0·0001), fatigue (p=0·0002), and systemic side-effects (p=0·0001), but not sexual function (p=0·36), compared with standard epirubicin during treatment, but the effect did not persist. Worse physical function (p=0·0048), sexual function (p=0·0053), fatigue (p<0·0001), and systemic side-effects (p<0·0001), but not role functioning (p=0·013), were seen for CMF versus capecitabine at end of treatment; these differences persisted at 12 months and 24 months. Accelerated epirubicin was associated with worse QOL than was standard epirubicin but only during treatment. These findings will help patients and clinicians make an informed choice about accelerated chemotherapy. CMF had worse QOL effects than did capecitabine, which were persistent for 24 months. The favourable capecitabine QOL compared with CMF supports its use as an adjuvant option after neoadjuvant chemotherapy in patients with triple-negative breast cancer. Cancer Research UK, Amgen, Pfizer, and Roche.

Computational pathology improves risk stratification of a multi-gene assay for early stage ER+ breast cancer

Prognostic markers currently utilized in clinical practice for estrogen receptor-positive (ER+) and lymph node-negative (LN−) invasive breast cancer (IBC) patients include the Nottingham grading system and Oncotype Dx (ODx). However, these biomarkers are not always optimal and remain subject to inter-/intra-observer variability and high cost. In this study, we evaluated the association between computationally derived image features from H&E images and disease-free survival (DFS) in ER+ and LN− IBC. H&E images from a total of n = 321 patients with ER+ and LN− IBC from three cohorts were employed for this study (Training set: D1 (n = 116), Validation sets: D2 (n = 121) and D3 (n = 84)). A total of 343 features relating to nuclear morphology, mitotic activity, and tubule formation were computationally extracted from each slide image. A Cox regression model (IbRiS) was trained to identify significant predictors of DFS and predict a high/low-risk category using D1 and was validated on independent testing sets D2 and D3 as well as within each ODx risk category. IbRiS was significantly prognostic of DFS with a hazard ratio (HR) of 2.33 (95% confidence interval (95% CI) = 1.02–5.32, p = 0.045) on D2 and a HR of 2.94 (95% CI = 1.18–7.35, p = 0.0208) on D3. In addition, IbRiS yielded significant risk stratification within high ODx risk categories (D1 + D2: HR = 10.35, 95% CI = 1.20–89.18, p = 0.0106; D1: p = 0.0238; D2: p = 0.0389), potentially providing more granular risk stratification than offered by ODx alone.

Validation of the prognosis of patients with ER‑positive, HER2‑negative and node‑negative invasive breast cancer classified as low risk by Curebest™ 95GC Breast in a multi‑institutional registry study.

Curebest™ 95GC breast (95GC) is a multigene classifier we developed for the prognostic prediction of patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative and node-negative (ER+/HER2-/n0) invasive breast cancer treated with adjuvant endocrine therapy alone. The aim of the preset study was to evaluate the clinical utility of 95GC in a multiinstitutional registry study. Patients (n=215) with ER+/HER2-/n0 invasive breast cancer who had undergone the 95GC assay in seven hospitals were consecutively recruited in the registry study at various postoperative times. At recruitment, no patients had disease recurrences and were prospectively followed up for a median of 62 (range, 6-91) postoperative months. Of the 124 patients classified as 95GC low risk, 118 received adjuvant endocrine therapy alone and six received adjuvant chemo-endocrine therapy. Only two patients developed distant recurrences, and the 5-year distant recurrence-free survival (DRFS) was as high as 98.0%. Of the 91 patients classified as 95GC high risk, 81 received adjuvant chemo-endocrine therapy and 10 received adjuvant endocrine therapy alone. A total of four of these patients developed distant recurrences (5-year DRFS=95.5%). Among the 95GC high-risk patients, prognosis was significantly improved for the 81 treated with adjuvant chemo-endocrine therapy compared with for the 77 (historical controls) treated with adjuvant endocrine therapy alone (P=0.0002; hazard ratio, 0.24). Compared with the St. Gallen 2013 guideline, a significant de-escalation from 73.1% (155/212) to 40.6% (86/212) in adjuvant chemotherapy was achieved. The excellent prognosis of patients with ER+/HER2-/n0 invasive breast cancer classified as 95GC low risk could be validated in the present registry study, indicating that 95GC is useful for safe de-escalation of adjuvant chemotherapy in patients with ER+/HER2-/n0 invasive breast cancer.

Development and Validation of a Genomic Profile for the Omission of Local Adjuvant Radiation in Breast Cancer.

Adjuvant radiotherapy (RT) is used for women with early-stage invasive breast cancer treated with breast-conserving surgery. However, some women with low risk of recurrence may safely be spared RT. This study aimed to identify these women using a molecular-based approach. We analyzed two randomized trials of women with node-negative invasive breast cancer to ± RT following breast-conserving surgery: SweBCG91-RT (stage I-II, no adjuvant systemic therapy) and Princess Margaret (age 50 years or older, T1-T2, adjuvant tamoxifen). Transcriptome-wide profiling was performed (Affymetrix Human Exon 1.0 ST microarray). Patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative tumors and with gene expression data were included. The SweBCG91-RT cohort was divided into training (N = 243) and validation (N = 354) cohorts. A 16-gene signature named Profile for the Omission of Local Adjuvant Radiation (POLAR) was trained to predict locoregional recurrence (LRR) using elastic net regression. POLAR was then validated in the SweBCG91-RT validation cohort and the Princess Margaret cohort (N = 132). Patients categorized as POLAR low-risk without RT had a 10-year LRR of 6% (95% CI, 2 to 16) and 7% (0 to 27) in SweBCG91-RT and Princess Margaret cohorts, respectively. There was no significant benefit from RT in POLAR low-risk patients (hazard ratio [HR], 1.1 [0.39 to 3.4], P = .81, and HR, 1.5 [0.14 to 16], P = .74, respectively). Patients categorized as POLAR high-risk had a significant decreased risk of LRR with RT (HR, 0.43 [0.24 to 0.78], P = .0055, and HR, 0.25 [0.07 to 0.92], P = .038, respectively). An exploratory analysis testing for interaction between RT and POLAR in the combined validation cohort was performed (P = .066). The novel POLAR genomic signature on the basis of LRR biology may identify patients with a low risk of LRR despite not receiving RT, and thus may be candidates for RT omission.

Predicting lymphovascular invasion in clinically node-negative breast cancer detected by abbreviated magnetic resonance imaging: Transfer learning vs. radiomics.

ObjectiveTo compare the performance of abbreviated breast magnetic resonance imaging (AB-MRI)-based transfer learning (TL) algorithm and radionics analysis for lymphovascular invasion (LVI) prediction in patients with clinically node-negative invasive breast cancer (IBC).MethodsBetween November 2017 and October 2020, 233 clinically node-negative IBCs detected by AB-MRI were retrospectively enrolled. One hundred thirty IBCs from center 1 (37 LVI-positive and 93 LVI-negative) were assigned as the training cohort and 103 from center 2 (25 LVI-positive and 78 LVI-negative) as the validation cohort. Based on AB-MRI, a TL signature (TLS) and a radiomics signature (RS) were built with the least absolute shrinkage and selection operator (LASSO) logistic regression. Their diagnostic performances were validated and compared using areas under the receiver operating curve (AUCs), net reclassification improvement (NRI), integrated discrimination improvement (IDI), decision curve analysis (DCA), and stratification analysis. A convolutional filter visualization technique was used to map the response areas of LVI on the AB-MRI.ResultsIn the validation cohort, compared with RS, the TLS showed better capability in discriminating LVI-positive from LVI-negative lesions (AUC: 0.852 vs. 0.726, p < 0.001; IDI = 0.092, p < 0.001; NRI = 0.554, p < 0.001). The diagnostic performance of TLS was not affected by the menstrual state, molecular subtype, or contrast agent type (all p > 0.05). Moreover, DCA showed that the TLS added more net benefit than RS for clinical utility.ConclusionsAn AB-MRI-based TLS was superior to RS for preoperative LVI prediction in patients with clinically node-negative IBC.

A nomogram for predicting three or more axillary lymph node involvement before breast cancer surgery

Based on the American College of Surgeons Oncology Group (ACOSOG)-Z0011, a useful nomogram has been constructed to identify patients who do not require intraoperative frozen sections to evaluate sentinel lymph nodes in the previous study. This study investigated the developed nomogram by ultrasonography (US) and positron emission tomography (PET)/computed tomography (CT) as a modality. In the training set, 89/1030 (8.6%) patients had three or more positive nodes. Larger tumor size, higher grade ultrasonographic ALN classification, and findings suspicious of positive ALN on PET/CT were associated in multivariate analysis. The areas under the receiver operating characteristic curve (AUC) of the nomogram were 0.856 [95% CI 0.815–0.897] in the training set. The AUC in the validation set was 0.866 [95% CI 0.799–0.934]. Application of the nomogram to 1067 patients who met the inclusion criteria of ACOSOG-Z0011 showed that 90 (8.4%) patients had scores above the cut-off and a false-negative result was 37 (3.8%) patients. And the specificity was 93.8%, and the negative predictive value was 96.4%. The upgraded nomogram improved the predictive accuracy, using only US and PET/CT. This nomogram is useful for identifying patients who do not require intraoperative analysis of sentinel lymph nodes and considering candidates for identifying neoadjuvant chemotherapy. The patients consisted of clinical T1-2 and node-negative invasive breast cancer. The training and validation set consisted of 1030 and 781 patients, respectively. A nomogram was constructed by analyzing factors related to three or more axillary lymph node metastases. The patients who matched the ACOSOG-Z0011 criteria were selected and applied to the new nomogram.

Validation of a nuclear grading system for resected stage I–IIIA, high-risk, node-negative invasive breast carcinoma in the N·SAS-BC 01 trial

BackgroundThis retrospective observational study validated nuclear grading criteria developed to identify a high-risk group with recurrence rate ≥20–30% and local pathology diagnosis used in a previous multi-institutional randomized N·SAS-BC 01 trial, where the efficacy of adjuvant chemotherapy regimens was evaluated in 733 high-risk node-negative invasive breast cancer patients.MethodsOf 545 patients with long-term follow-up data (median 12.1 years), pathology slides, and local pathology diagnosis, 530 eligible patients were subjected to central pathology review (CPR) for histological type and nuclear grade (NG). Concordance in NGs was compared with local diagnosis. The 10/15-year recurrence-free survival (RFS) and overall survival (OS) rates stratified by NG and histological type were calculated.ResultsLocal diagnoses were invasive ductal carcinoma (IDC)-NG2, IDC-NG3, invasive lobular carcinoma (ILC), and metaplastic carcinoma (MC) in 158/327/38/7 patients, respectively. The 10/15-year RFS rates were 87.2/82.6% for IDC-NG2 and 81.8/75.0% for IDC-NG3 (p = 0.061), and OS rates were 95.0/92.8% for IDC-NG2 and 90.8/85.7% for IDC-NG3 (p = 0.042). CPR graded 485 locally diagnosed IDCs as IDC-NG1/NG2/NG3/unknown in 98/116/267/4 patients, respectively. No significant difference was found among survival curves for the three NG groups. Although the agreement level between local and CPR diagnoses was low (κ = 0.311), both diagnoses identified a patient group with a 15-year recurrence rate ≥ 20%. The 10/15-year RFS rates were 79.4/63.5% for ILC and 68.6%/unknown for MC.ConclusionsThe N·SAS grading system identified a patient group with high-risk node-negative invasive breast cancer, suggesting that local diagnosis was performed efficiently in the N·SAS-BC 01 trial.Trial registration number: UMIN000022571.Date of registration: June 1, 2016.

Definitive results of a phase III adjuvant trial comparing six cycles of FEC-100 to four cycles of AC in women with operable node-negative breast cancer: the NSABP B-36 trial (NRG Oncology).

Results from adjuvant trials evaluating 6 cycles of epirubicin-based chemotherapy regimens suggested these programs may be more effective than 4 cycles of doxorubicin-based chemotherapy. NSABP B-36 was a phase III clinical trial originally designed as a 2 × 2 factorial study comparing 6 cycles of 5-FU, epirubicin, and cyclophosphamide (FEC-100) to 4 cycles of conventional doxorubicin and cyclophosphamide (AC) with celecoxib or placebo. Shortly after activation, concerns regarding increased cardiovascular risks among selective COX-2 inhibitors resulted in a decision to remove the celecoxib/placebo from the trial. Women with histologically node-negative invasive breast cancer who had undergone primary surgery with a lumpectomy or total mastectomy were eligible. Primary endpoint was disease-free survival (DFS). Between May 2004 and July 2008, 2722 patients were enrolled. Administration of FEC-100 did not result in improvement in DFS compared to AC (HR 1.09; 95% CI 0.92-1.29, p value = 0.31). The effect of FEC-100 compared to AC on DFS was significantly different for receptor-positive (HR 1.32, 95% CI 1.05-1.66) compared to receptor-negative patients (HR 0.86, 95% CI 0.66-1.11) (treatment-by-receptor status interaction p value = 0.02). There was no statistically significant difference in the effect of treatment on overall survival (OS) with FEC-100 compared to AC (HR 1.06; 95% CI 0.84-1.35, p value = 0.61). Overall, Grade 3 and 4 adverse events were more frequent in the FEC-100 group. The results of B-36 do not support use of six-cycle anthracycline-based regimens in node-negative breast cancer. Prolongation of anthracycline-based therapy with FEC-100 does not improve DFS or OS, relative to AC for 4 cycles, and was associated with expected increases in toxicity. A statistically significant interaction between treatment and hormone receptor status favoring AC in hormone-receptor-positive breast cancers is consistent with the hypothesis that optimal duration of chemotherapy may be four cycles in these patients. Late cardiac events and deaths prior to recurrence or second cancer were infrequent on both arms, but slightly higher with FEC-100. ClinicalTrials.gov: NCT00087178.

Abstract P1-01-06: Predictor of sentinel node positivity in screen-detected invasive breast cancer

Abstract Introduction: Sentinel lymph node biopsy represents the standard of care for staging axilla in breast cancer patients who are clinically node negative. ACOSOG Z11 trial results questioned the importance of low burden nodal disease. Results from the SOUND trial on omission of axillary surgery in selected patients with early stage breast cancer are still awaited. Breast screening programs aim to detect cancers at an early stage and are expected to have low burden of nodal disease. The aim of our study was to determine predictors of sentinel node biopsy positivity in invasive breast cancers detected on screening mammography. Methods: This retrospective study included patients with node negative invasive breast cancer detected on screening mammogram performed between April 2018 and March 2020 and subsequently underwent curative surgery including sentinel node biopsy at breast care unit of Castle Hill Hospital, Cottingham, U.K. We looked at patient’s clinical, radiological and pre-operative pathological features and correlated them with histological results of sentinel node biopsy. Statistical analysis of the data was performed using SPSS version 22 and p-value of 0.05 was considered significant. Results: We identified 304 patients who met inclusion criteria. The mean age of these patients was 62.71 ± 7.2 years (range 47-78 years). Majority (88%) of women were postmenopausal. Overall, the sentinel node positivity rate was 11.76%. Women over the age of 55 years were less likely to be node positive compared to younger women (9.9% vs 22%, p=0.016). Tumours less than 10mm in size had node positive rate of 5.5% compared to tumour larger than 21mm (25%, p = 0.000). In comparison to grade 2and grade 3 tumours, grade 1 tumours had lower node positivity rate, (5% vs 14.4%) but the difference did not reach statistical significance (p= 0.073). All women with tubular and mucinous histological subtypes (n=13) were node negative. All women with grade 1 tumours less than 10mm in size (n=48) had a negative sentinel node biopsy compared to women with grade 2 tumors more than 20mm (9/32=28% positivity rate) and p-value of 0.000. There was no association between oestrogen, progesterone and HER2 receptor status with sentinel lymph node positivity rate. Conclusion: In selected screen detected patients including those above the age of 55 years, having grade 1 cancer, and less than 10 mm size on pre-treatment imaging, there might be scope for omission of axillary surgery. Citation Format: Raouef Ahmed Bichoo, Mohammed Bilal Elahi, Dorin Dumitru, Naila Bint Ihsan, Eiman Khalifa, Masuma Sarker, Tapan K Mahapatra, Brendan Paul Wooler, Peter Kneeshaw, Kartikae Grover. Predictor of sentinel node positivity in screen-detected invasive breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-01-06.

A systematic review and meta-analysis comparing axillary dissection to axillary observation in clinically node-negative invasive breast cancer and assessing relevance to axillary de-escalation trials

Background: Currently, axillary de-escalation trials aim to determine benefit of axillary intervention (sentinel node biopsy (SNB), axillary node clearance (ANC)), over observation (Obs) in clinically node-negative (CN-) breast cancer. However, meta-analysis of studies pre-dating the SNB era, which compared ANC to Obs in CN- women, can predict the outcomes of de-escalation trials as they selected for low axillary burden by definition.

Impact of Choosing Wisely Recommendations on Sentinel Lymph Node Biopsy and Postoperative Radiation Rates in Women Over Age 70 Years with Hormone-Positive Breast Cancer.

In 2016, the Society of Surgical Oncology released a Choosing Wisely guideline recommending sentinel lymph node biopsy (SLNB) omission in females ≥70years of age with early-stage, hormone-positive, clinically node-negative invasive breast cancer. This study investigated the impact of this guideline on SLNB and radiotherapy rates, in addition to assessing temporal trends of nodal biopsy and factors associated with recurrence. The study involved a retrospective review of women who met the guideline criteria and underwent partial mastectomy at a single institution between 2009 and 2018. Using the same inclusion criteria, the National Cancer Database was queried to obtain a separate dataset. Statistical analyses included univariate comparisons, and multivariate logistic regression modeling to predict radiotherapy delivery. In our institutional series, 487 patients were included, 274 (56.3%) of whom received radiotherapy. There were 414 patients (85.0%) who underwent SLNB, with a nodal positivity rate of 11%. SLNB correlated with higher rates of radiotherapy (63.5% vs. 15.1%, p<0.001). Age <80years was an independent predictor of radiotherapy receipt (odds ratio 3.0, 95% confidence interval 0.22-0.52). SLNB performance decreased after 2016 (88.4% vs. 78.4%, p=0.003). Median follow-up was 4.8 years, with 19 (3.9%) documented recurrences. SLNB performance was not associated with recurrence (2.9% vs. 5.5%, p=0.279), whereas radiotherapy resulted in reduced recurrence (1.1% vs. 6.1%, p=0.002). One (0.2%) disease-related mortality was observed. Recurrence rates and disease-related mortality remain low in this demographic regardless of treatment rendered. Omission of SLNB and radiotherapy should remain a consideration, and efforts in both patient and physician education should continue.

Comparative survival analysis of multiparametric tests\u2014when molecular tests disagree\u2014A TEAM Pathology study

Multiparametric assays for risk stratification are widely used in the management of both node negative and node positive hormone receptor positive invasive breast cancer. Recent data from multiple sources suggests that different tests may provide different risk estimates at the individual patient level. The TEAM pathology study consists of 3284 postmenopausal ER+ve breast cancers treated with endocrine therapy Using genes comprising the following multi-parametric tests OncotypeDx®, Prosigna™ and MammaPrint® signatures were trained to recapitulate true assay results. Patients were then classified into risk groups and survival assessed. Whilst likelihood χ2 ratios suggested limited value for combining tests, Kaplan–Meier and LogRank tests within risk groups suggested combinations of tests provided statistically significant stratification of potential clinical value. Paradoxically whilst Prosigna-trained results stratified Oncotype-trained subgroups across low and intermediate risk categories, only intermediate risk Prosigna-trained cases were further stratified by Oncotype-trained results. Both Oncotype-trained and Prosigna-trained results further stratified MammaPrint-trained low risk cases, and MammaPrint-trained results also stratified Oncotype-trained low and intermediate risk groups but not Prosigna-trained results. Comparisons between existing multiparametric tests are challenging, and evidence on discordance between tests in risk stratification presents further dilemmas. Detailed analysis of the TEAM pathology study suggests a complex inter-relationship between test results in the same patient cohorts which requires careful evaluation regarding test utility. Further prognostic improvement appears both desirable and achievable.

A 95-gene signature stratifies recurrence risk of invasive disease in ER-positive, HER2-negative, node-negative breast cancer with intermediate 21-gene signature recurrence scores.

A subset of patients with intermediate 21-gene signature assay recurrence score may benefit from adjuvant chemoendocrine therapy, but a predictive strategy is needed to identify such patients. The 95-gene signature assay was tested to stratify patients with intermediate RS into high (95GC-H) and low (95GC-L) groups that were associated with invasive recurrence risk. Patients with ER-positive, HER2-negative, node-negative breast cancer and RS 11-25 who underwent definitive surgery and adjuvant endocrine therapy without any cytotoxic agents were included. RNA was extracted from archived formalin-fixed, paraffin-embedded samples, and 95-gene signature was calculated. 206 patients had RS of 11-25 (95GC-L, N = 163; 95GC-H, N = 43). In Cox proportional hazards model, 95GC-H was significantly associated with shorter time to recurrence than was 95GC-L (HR 5.94; 95%CI 1.81-19.53; P = 0.005). The correlation between 95-gene signature and 21-gene signature assay scores was not strong (correlation coefficient r = 0.27), which might suggest that 95-gene signature reflects biological characteristics differing from what 21-gene signature shows. The 95-gene signature stratifies patients with ER-positive, HER2-negative, node-negative invasive breast cancer and intermediate RS of 11-25 into high and low groups that are associated with recurrence risk of invasive disease. Further retrospective analysis in the prospectively accrued TAILORx population is warranted to confirm that 95-gene signature can identify patients who would benefit from adjuvant chemoendocrine therapy.

Adding carbon nanoparticles to dual-tracers for the sentinel node evaluation after neoadjuvant chemotherapy in patients with pretreatment node-positive breast cancers: The TT-SLNB trial.

566 Background: This study measures the feasibility and accuracy of sentinel lymph node biopsy (SLNB) with triple-tracers (TT-SLNB) which combines carbon nanoparticles (CNS) with dual tracers of radioisotope and blue dye, hoping to achieve an optimized method of SLNB after neoadjuvant chemotherapy (NAC) in ycN0 breast cancer patients with pretreatment positive axillary lymph nodes. Methods: Clinically node-negative invasive breast cancer patients with pre-NAC positive axillary lymph nodes who received surgeries from November 2020 to January 2021 were included. CNS was injected at the peritumoral site the day before surgery. Standard dual-tracer (SD)-SLNs were defined as blue-colored and/or hot nodes, and TT-SLNs were defined as lymph nodes detected by any of hot, blue-stained, black-stained, and/or palpated SLNs. All patients received subsequent axillary lymph node dissection. Detection rate (DR), false-negative rate (FNR), negative predictive value (NPV) and accuracy of SLNB were calculated. Results: Seventy-six of 121 (62.8%) breast cancer patients converted to cN0 after NAC and received TT-SLNB. After NAC, 28.95% (22/76) achieved overall (breast and axilla) pCR. The DR was 94.74% (72/76), 88.16% (67/76) and 96.05% (73/76) for SLNB with single-tracer of CNS (CNS-SLNB), SD-SLNB, and TT-SLNB, respectively. The FNR was 22.86% (8/35) for CNS-SLNB and 10% (3/30) for SD-SLNB. The FNR of TT-SLNB was 5.71% (2/35), which was significantly lower than those of CNS-SLNB and SD-SLNB. The NPV and accuracy was 95.0% and 97.3% for TT-SLNB, respectively. Moreover, a significant relation was seen between the pretreatment clinical T classification and the DR of TT-SLNB (Fisher’s exact test, p= 0.010). Conclusions: TT-SLNB revealed ideal performance in post-NAC ycN0 patients with pretreatment node-positive breast cancers. The application of TT-SLNB reached a better balance between more accurate axillary evaluation and less intervention. Clinical trial information: ChiCTR2000039814. [Table: see text]

Dynamic contrast enhanced-MRI and diffusion-weighted image as predictors of lymphovascular invasion in node-negative invasive breast cancer

BackgroundLymphovascular invasion (LVI) is an important risk factor for prognosis of breast cancer and an unfavorable prognostic factor in node-negative invasive breast cancer patients. The purpose of this study was to evaluate the association between LVI and pre-operative features of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI) in node-negative invasive breast cancer.MethodsData were collected retrospectively from 132 cases who had undergone pre-operative MRI and had invasive breast carcinoma confirmed on the last surgical pathology report. MRI and DWI data were analyzed for the size of tumor, mass shape, margin, internal enhancement pattern, kinetic enhancement curve, high intratumoral T2-weighted signal intensity, peritumoral edema, DWI rim sign, and apparent diffusion coefficient (ADC) values. We calculated the relationship between presence of LVI and various prognostic factors and MRI features.ResultsPathologic tumor size, mass margin, internal enhancement pattern, kinetic enhancement curve, DWI rim sign, and the difference between maximum and minimum ADC were significantly correlated with LVI (p < 0.05).ConclusionsWe suggest that DCE-MRI with DWI would assist in predicting LVI status in node-negative invasive breast cancer patients.

Abstract PS1-51: A nomogram for predicting three or more axillary lymph node involvement before breast cancer surgery

Abstract Introduction Focus has moved to de-escalate of axillary surgery in the management of early breast cancer. Based on the American College of Surgeons Oncology Group-Z0011, our team created the nomogram to be useful for identifying patients who do not require intraoperative analysis of the sentinel lymph node. The nomogram could identify as patients likely to three or more positive axillary lymph nodes by preoperative imaging. But the nomogram had several limitations. This study investigated a developed nomogram by excluding the chest computed tomography (CT) and adding 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT as a modality. Material and Methods Patients underwent preoperative ultrasonography (US) and PET/CT. The training set consisted of 1030 patients with clinical T1-2 and node-negative invasive breast cancer. Factors associated with ≥ 3 involved axillary lymph nodes (ALNs) were evaluated by logistic regression analysis. The validation set consisted of 781 independent patients. The nomogram was applied to 1,067 patients who met the selection criteria of the ACOSOG-Z0011. Results Of the 1,030 patients, 89 (8.6%) had ≥ 3 positive nodes. Multivariate analysis according to be used for making a new nomogram to predict the probability of involvement ≥ 3 nodes, there was significantly associated with larger tumor size, higher grade ultrasonographic ALN classification, and findings suspicious of positive ALN on PET/CT. The areas under the receiver operating characteristic curve of the nomogram were 0.856 (95% confidence interval [CI], 0.815 to 0.897) for the training set and 0.866 (95% CI, 0.799 to 0.934) for the validation set. Application of the nomogram to the patients who met the ACOSOG-Z0011 showed that 90/1067 (8.4%) had scores above the cut-off and the false-negative rate was 37/977 (3.8%). And the specificity was 93.8%, and the negative predictive value was 96.4%. Conclusion The upgraded nomogram improved predictive accuracy, and that was possible using only US and PET/CT. It reduced operation time and cost, with a very low re-operation rate. This nomogram is useful for identifying patients who do not require intraoperative analysis of sentinel lymph nodes. Citation Format: Young-Joon Kang. A nomogram for predicting three or more axillary lymph node involvement before breast cancer surgery [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-51.

Correlation of circulating or disseminated tumor cells with the Oncotype DX Recurrence Score.

New biomarkers are emerging to predict recurrence risk in women with early-stage breast cancer. High Oncotype DX Recurrence Score® (RS) is associated with worse disease-free and overall survival. Similarly, circulating tumor cells (CTCs, blood) and disseminated tumor cells (DTCs, bone marrow) have prognostic value in breast cancer. We investigated the association between high RS and CTCs or DTCs. Using a prospective database, we evaluated patients with hormone receptor-positive/HER2-negative, node-negative invasive breast cancer from 1/2005 to 1/2017. RS was classified using TAILORx study cutoff points: low (< 11), intermediate (11-25), and high (> 25). CTCs were assessed using CellSearch® and DTCs using cytospin specimens of bone marrow aspirates. Positive result was defined as one or more CTCs or DTCs identified. Chi-square analyses were utilized to evaluate the relationship between RS and CTCs or DTCs. 233 patients were identified from a prospective database, of which 96 had RS results. Of these patients, 88 had CTC results and 58 had DTC results. CTCs were detected in 17/88 (19%) patients, while DTCs were detected in 20/58 (34%). Patients with high RS were not more likely to have CTCs (18%) compared to patients with low/intermediate RS (20%; p = 0.919). Similarly, high RS was not associated with DTC detection, with DTCs present in 40% of patients with high RS versus 33% with low/intermediate RS (p = 0.687). In the subgroup of patients ≤ 50years, no associations were found between high RS and CTCs (p = 0.383) or DTCs (p = 0.234). High Oncotype DX RS did not correlate with CTCs in blood or DTCs in bone marrow in our study.

Accelerated Hypofractionated Whole Breast Radiotherapy for Early Breast Cancer; ARandomized Phase III Clinical Trial

To compare the cosmetic outcome and acute cutaneous, cardiac, and pulmonary toxicity profile of accelerated hypofractionated and conventional whole breast radiotherapy (WBRT).This was a blocked randomized, clinical trial on women with early-stage node-negative invasive breast cancer after breast conservation surgery (BCS) with clear margins randomly assigned to receive WBRT either at a conventional dose of 50.0 grays (Gy) in 25 fractions (the conventional group) or at a dose of 42.5 Gy in 16 fractions (the hypofractionated group). Boost irradiation was permitted in both groups. Data were analyzed by SPSS V21.0 using Mann–Whitney U, independent-samples t- and Chi-Square/Fisher's exact tests at the level of P≤0.05.The median follows up was 16 months. Forty-one patients in the conventional WBRT arm and 45 patients in the hypofractionated WBRT group were enrolled. No significant difference was observed in terms of left and right ventricle systolic dysfunction and diastolic dysfunction. Pulmonary function tests after 6 and 12 months follow up, were comparable in both groups (P=0.2). Skin toxicity during and after treatment was acceptable in both groups. Breast size change in the conventional and the hypofractionated WBRT groups was 14.3% and 7.1%, respectively (P=0.6). Excellent or good cosmetic outcome was similar in both groups.The results of our study support the use of accelerated hypofractionated WBRT in women with invasive breast cancer less than five cm and node-negative after breast-conserving surgery, which provides a more convenient shorter course of radiotherapy with a comparable cosmetic outcome and cutaneous, cardiac, and pulmonary toxicity profile.