Recurrence In Breast Cancer Patients Research Articles

Abstract P4-06-02: Clinically feasible pharmacokinetic model of dynamic contrast-enhanced MRI is prognostic of recurrence free survival in breast cancer patients treated with neoadjuvant therapy

Abstract Background Dynamic contrast-enhanced (DCE) MRI is commonly used for diagnosis and treatment planning of cancers. Its main use is the identification of tumors in soft tissues, where the tumor progression-induced angiogenic changes result in leaky vasculature which is readily highlighted by contrast enhancement. While allowing tumor morphology assessment, DCE MRI also contains rich information on perfusion and permeability which can be modeled as a pharmacokinetic (PK) process, a subject of extensive investigation in the clinical research setting. Several breast DCE MRI studies have suggested that PK parameters might be indicative of response to therapy and recurrence. However, these studies rely on high temporal resolution DCE MRI for accurate PK modeling, which presents a hurdle to adoption in clinical settings where DCE MRI is acquired with low temporal resolution. Methods We present a novel two-parameter modeling framework which circumvents this temporal limitation, allowing kinetic parameters to be extracted from clinical DCE MRI containing 3-6 timepoints spaced 60-90 seconds apart. We sought to examine whether these kinetic parameters (hereafter KP1 and KP2) binned into "high" and "low" values had prognostic value in determining disease recurrence. KP1 reflects the rate of leakiness from vessels into extravascular space, while KP2 reflects the rate of the reverse process. A study was conducted with a cohort of 458 breast cancer patients treated with neoadjuvant therapy (NAT) in which 117 recurrences occurred. Model parameters were extracted from pre-treatment clinical DCE MRI with low temporal resolution. Univariate and multivariate (Cox Proportional Hazard; CPH) analyses were performed to test the prognostic value of covariates in predicting recurrence free survival (RFS). Results A CPH model was constructed that included age, receptor status, cancer stage, kinetic parameters, and pathologic complete response (pCR) as covariates (Table 1). KP2 and pCR were statistically significantly prognostic markers of RFS (p<0.05). KP1 was not a significant prognostic marker of RFS (p=0.055). Interestingly, KP2 had a hazard ratio (HR) similar to pCR (HR: -1.04 [-1.75, -0.33]; p<0.0039 vs. HR: -0.97 [-1.5, -0.44], p<0.00034). Using univariate analysis, we investigated whether KP2 was prognostic of recurrence. Patients were stratified by therapy type, whether they achieved pCR or had residual disease (RD), and by disease subtype. KP2 was found to be predictive of RFS for patients with RD after treatment with NAT chemotherapy (p<0.0004, n=241, log-rank test), but not for patients treated with anti-HER2 NAT (p=0.84, n=124) or patients that achieved pCR (p=0.68, n=139). KP2 was also found to be prognostic in Hormone Receptor+/HER2- patients with RD (p<0.012, n=151) and Hormone Receptor-/HER2+ patients treated with NAT chemotherapy (p<0.001, n=64). The parameter was not found to be prognostic in patients with triple-negative disease. Conclusions We developed a new prognostic imaging marker for disease recurrence in breast cancer patients treated with NAT that relies on only pre-treatment standard-of-care, low temporal resolution DCE MRI. Since the marker was found to have similar prognostic value in terms of hazard ratio as pCR, but in patients with RD, it could prove to be a powerful tool in patient management after surgery. Table 1.Results of Cox Proportional Hazard model.FactorHazard Ratio95% CIp-valueAge-0.01[-0.02, 0.01]0.51ER+-0.35[-0.85, 0.15]0.17HER2+0.02[-0.38, 0.41]0.93PR+0.05[-0.46, 0.56]0.85Stage II0.54[-0.62, 1.7]0.36Stage III1.08[-0.1, 2.27]0.074KP1-0.68[-1.38, 0.01]0.055KP2-1.04[-1.75, -0.33]0.0039pCR-0.97[-1.5, -0.44]0.00034 Citation Format: Joseph R Peterson, Tyler M. Earnest, Wei Huang, Hiroyuki Abe, John A Cole, Jr. Clinically feasible pharmacokinetic model of dynamic contrast-enhanced MRI is prognostic of recurrence free survival in breast cancer patients treated with neoadjuvant therapy [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 P4-06-02.

Abstract P3-20-03: Breast-conserving surgery improves the outcomes of disease-free survival and overall survival in young women with breast cancer (≤35 years): A retrospective study based on surgical options

Abstract Background:Compared with non-young patients, young women with breast cancer (YWBC) has worse prognosis and higher risk of recurrence. Under the age of 35 is an independent risk factor of local recurrence in breast cancer patients, and the proportion of YWBC in China is higher than that in Western countries. Although surgery is the most important local treatment for YWBC, there still lack prospective studies to compare that three major surgical options for cancer recurrence and patient survival. So we retrospectively compared the outcomes of the three surgical options on disease-free survival(DFS) and overall survival(OS) of YWBC in Fudan University Shanghai Cancer Center(FUSCC).Method:YWBC (age ≤ 35) who underwent surgery in FUSCC from 2008 to 2016 were enrolled in analysis, and divided into three groups according to their surgical options:(1)breast-conserving surgery,(2)mastectomy alone, and (3)mastectomy with reconstruction. The survival outcome differences among the three groups were compared using Kaplan-Meier method and Cox regression model. Propensity score matching was also used to balance the baseline characteristics to eliminate selection bias.Results:A total of 1520 YWBC were enrolled with the median followed up for 5.1 years, including 524 patients (34.5%) who underwent breast-conserving surgery, 676 patients (44.5%) who underwent mastectomy alone, and 320 patients (21.1%) who underwent mastectomy with reconstruction; The 5-year DFS was 96%, 87%, and 93%, respectively; 10-year DFS was 93%, 82%, and 87%, respectively (P < 0.001); The 5-year OS was 98%, 94%, and 97%, respectively; and 10-year OS was 97%, 87%, and 91%, respectively (P = 0.002). The multivariate Cox analysis showed that DFS and OS were significantly improved in patients undergoing breast-conserving surgery compared with those undergoing mastectomy alone, with HR of 0.448, [95% CI 0.276 ~ 0.728] P = 0.001; 0.405, [95% CI 0.206 ~ 0.797] P = 0.009, respectively. After propensity score matching, the DFS and OS were significantly improved in patients undergoing breast-conserving surgery compared with patients undergoing mastectomy alone (DFS P = 0.001, OS P = 0.009); the outcome of patients underwent mastectomy with reconstruction was also improved compared with patients underwent mastectomy alone in terms of DFS and OS, but the difference was not statistically significant (DFS P = 0.164, OS P = 0.130). Conclusion:Surgical options was an independent factor affecting DFS and OS in YWBC, and the DFS and OS were significantly improved in patients who underwent breast-conserving surgery compared with those who underwent mastectomy alone. The reason of this result may be related to the development of systemic therapy that reduce the local recurrence of breast-conserving surgery. Furthermore, complete body image could make those patients return to families and society, and ensure the quality of life. These findings still need further investigation. Taken together, breast conserving surgery are preferred for early YWBC, and mastectomy with reconstruction are the best option for remodeling the image of YWBC who can not receive breast conserving surgery. Citation Format: Pei Li, Lun Li, Jingyan Xue, Jiong Wu. Breast-conserving surgery improves the outcomes of disease-free survival and overall survival in young women with breast cancer (≤35 years): A retrospective study based on surgical options [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 P3-20-03.

On top of that all, now Covid-19, too. A scoping review of specificities and correlates of fear of cancer recurrence in breast cancer patients during COVID-19.

Fear of cancer recurrence (FCR) is a normal response in cancer survivors and one of the most prevalent reactions reported by up to 87% of them. However, elevated levels of FCR impair well-being, quality of life and professional functioning, and lead to anxiety, depression or PTSD. COVID-19 pandemic can exacerbate FCR symptoms, given the restricting access to follow-up investigations and treatment, the isolation restrictions imposed and the possibility of the medical system becoming overworked. This scoping review's objective was to synthesize the literature investigating the factors associated with higher levels of FCR in cancer survivors during the COVID-19 pandemic. The focus was on FCR in breast cancer patients, including most of the studies (5 out of 9) on this topic. However, given the novelty of the subject, the increased interest in it, and the fact that there are few studies in this field, the review included 4 other studies with mixed samples of patients with breast cancer and other oncological pathologies. Following rigorous methodological criteria, 9 studies with quantitative or mixed methodology were included (N = 4831 patients). The results indicate that high levels of FCR are associated with distress and concerns regarding the pandemic impact, with most common concerns of patients being changes in treatment plan (delays and interruptions), dysfunctional communication with medical staff or difficult access to food or medicine. The most common correlates of FCR during the pandemic are marital status, childlessness, low financial status, level of education, type of cancer diagnosis, generalized anxiety and depression.

Prior Local or Systemic Treatment: A Predictive Model Could Guide Clinical Decision-Making for Locoregional Recurrent Breast Cancer.

IntroductionLocoregional recurrent breast cancer indicates poor prognosis. No solid prediction model is available to predict prognosis and guide clinical management. Prior local treatment or systemic treatment remains controversial.MethodsLocoregional recurrent breast cancer patients operated in Fudan University Shanghai Cancer Center were enrolled as a training cohort. An external validation cohort included breast cancer patients after locoregional recurrence from Ruijin Hospital, Shanghai Jiaotong University. A nomogram predicting overall survival after locoregional recurrence was established using multivariable Cox regression analysis while internal and external validation were performed to evaluate its calibration and discrimination.ResultsOverall, 346 and 96 breast cancer patients were included in the training cohort and the validation cohort separately. A nomogram was developed, including age, neoadjuvant chemotherapy, breast surgery, pathology type, tumor size, lymph node status, hormonal receptor and Her-2 status, disease-free interval, and sites of locoregional recurrence. It had modest calibration and discrimination in the training cohort, internal validation and external validation (concordance index: 0.751, 0.734 and 0.722, respectively). The nomogram classified 266 and 80 patients into low and high-risk subgroups with distinctive prognosis. Local treatment after locoregional recurrence was associated with improved overall survival in low-risk group (P = 0.011), while systemic therapies correlated with better outcomes only in high-risk group (P < 0.001).ConclusionA nomogram based on clinicopathological factors can predict prognosis and identify low and high-risk patients. Local treatment is a prior choice for low-risk patients whereas systemic treatment needs to be considered for high-risk patients, warranting further validation and exploration.

The clinical effects of Vinorelbine for advanced and recurrent breast cancer patients

Background: Vinorelbine (VNB) is one of the key drugs for advanced and recurrent breast cancer, but it was often used in the later line because of the advent of eribulin and bevacizumab. We examined the effect of VNB by subtypes and the peripheral blood lymphocyte count (LY) and the ratio of peripheral blood neutrophil and lymphocyte count (NLR).

Post-operative re-irradiation with hyperthermia in locoregional breast cancer recurrence: Temperature matters

PurposeTo investigate the impact of hyperthermia thermal dose (TD) on locoregional control (LRC), overall survival (OS) and toxicity in locoregional recurrent breast cancer patients treated with postoperative re-irradiation and hyperthermia. MethodsIn this retrospective study, 112 women with resected locoregional recurrent breast cancer treated in 2010–2017 with postoperative re-irradiation 8frx4Gy (n = 34) or 23frx2Gy (n = 78), combined with 4–5 weekly hyperthermia sessions guided by invasive thermometry, were subdivided into ‘low’ (n = 56) and ‘high’ TD (n = 56) groups by the best session with highest median cumulative equivalent minutes at 43 °C (Best CEM43T50) < 7.2 min and ≥7.2 min, respectively. Actuarial LRC, OS and late toxicity incidence were analyzed. Backward multivariable Cox regression and inverse probability weighting (IPW) analysis were performed. ResultsTD subgroups showed no significant differences in patient/treatment characteristics. Median follow-up was 43 months (range 1–107 months). High vs. low TD was associated with LRC (p = 0.0013), but not with OS (p = 0.29) or late toxicity (p = 0.58). Three-year LRC was 74.0% vs. 92.3% in the low and high TD group, respectively (p = 0.008). After three years, 25.0% and 0.9% of the patients had late toxicity grade 3 and 4, respectively. Multivariable analysis showed that distant metastasis (HR 17.6; 95%CI 5.2–60.2), lymph node involvement (HR 2.9; 95%CI 1.2–7.2), recurrence site (chest wall vs. breast; HR 4.6; 95%CI 1.8–11.6) and TD (low vs. high; HR 4.1; 95%CI 1.4–11.5) were associated with LRC. TD was associated with LRC in IPW analysis (p = 0.0018). ConclusionsHigh thermal dose (best CEM43T50 ≥ 7.2 min) was associated with significantly higher LRC for patients with locoregional recurrent breast cancer treated with postoperative re-irradiation and hyperthermia, without augmenting toxicity.

Axillary Recurrence in Breast Cancer Patients After Negative Sentinel Lymph Node Biopsy: Retrospective Cohort Study From Riyadh, Saudi Arabia.

Breast cancer (BC) is among the most prevalent cancers globally. For minimally invasive axillary staging in early breast cancer, sentinel lymph node biopsy (SLNB) is commonly regarded as the gold standard. Historically, axillary lymph node dissection (ALND) was used as a staging procedure, but the less morbid SLNB has now replaced it. This retrospective cohort study, undertaken with patients at King Saud University Medical City in Riyadh, Saudi Arabia, evaluates mid-term follow-up data on axillary recurrences and outcomes for breast cancer patients with negative SLNB. The results indicate that the five-year risk of developing regional recurrence following negative SLNB is 0% in breast cancer patients. The low relapse rate further contributes to the evidence base suggesting the efficacy of SLNB and the higher morbidity associated with ALND. Future researchers should conduct a nationwide and long-term follow-up study to offer additional insights into the efficacy of SLNB.

Reverse Abdominoplasty: A Novel Practical Approach Using Oncoplastic Reconstruction in Managing Major Chest Wall Defects for Patients With Loco-Regional Recurrence Following Breast Cancer Surgery.

BackgroundLoco-regional recurrence of breast cancer in patients with large chest wall defects following mastectomy poses significant oncoplastic challenges. Reverse abdominoplasty is most commonly used to treat patients with excess upper abdominal soft tissue and laxity following massive weight loss. Widely employed as a technique for aesthetic contouring of the upper anterior trunk, as well as in augmentation mammoplasty, its use to date for reconstructive purposes is mainly limited to burns and large site surgical tumour ablation.MethodHere we review our experience of using reverse abdominoplasty as a novel approach to filling major anterior chest wall defects in patients with cutaneous manifestations of loco-regional or distant recurrence of breast cancer.ResultsSeven patients with metastatic breast cancer underwent reverse abdominoplasty for disease recurrence following mastectomy, with good patient-reported outcomes, and minimal surgical complications. Moreover, follow-up data in the patients surveyed also showed minimal to no limitations on their activities of daily living following the procedure.ConclusionHere we demonstrate the successful employment of reverse abdominoplasty - a technique not usually reserved in breast oncoplastic surgery - to treat fungating breast lesions and/or other manifestations of loco-regional recurrence in metastatic breast cancer. This may herald a paradigm shift in the way surgeons approach breast cancer recurrence in patients with pre-existing major chest wall defects.

1577 Using CTS5 Calculator to Predict The 5-10-Year Risk of Late Distant Recurrence for Women With ER-Positive Breast Cancer Who Are Recurrence-Free 5 Years After Endocrine Therapy and To Reduce the Number of Patients Needing Discussion for The Extended Endocrine Therapy in The Breast MDTs: A Quality Improvement Project

Abstract Introduction The increasing number of patients has created a pressure on the services provided that aim to ensure the maximum level of care, particularly MDT meetings. Using the CTS5 calculator can readily reduce the number of patients needing discussion for EET. This is will prevent delays in decisions made for patients and more importantly, an evidence-based tool will be used for more accurate results. Method A retrospective data collection was undertaken from the Breast MDT records, initially dating from January to December 2018. Then when the optional use of CTS5 was established, data were retrieved from August to October 2019. As per guidance for the use of the CTS5 calculator; Women were deemed low risk if their 5–10-year risk is less than 5%, intermediate if between 5–10%, and high risk if their 5–10-year risk is more than 10%. Finally, a prospective data collected from January to March 2020 where an agreement was made for all involved Surgeons to use the CTS5 calculator. Results Before Introducing the CTS5 Calculator, in 2018, the number of patients was 1523 from which 66 were for EET 4.3%. When CTS5 Calculator was first introduced, 1st of August - 31st October 2019, the percentage reduced to 4.1% and from January to March 2020, a further reduction 3.9% was noticed. Conclusions The CTS5 calculator is an effective evidence-based tool used to predict the risk of 5-10 years recurrence in breast cancer patients. Implementing it will reduce the number of patients needing discussion in Breast MDTs, sparing meetings’ and patients’ time.

Molecular type and maximal metastasis diameter influence risk of axillary recurrence in breast cancer patients after positive sentinel lymph node biopsy

Breast cancer patients with positive sentinel lymph node biopsy (SLNB) may be spared axillary lymph node dissection (ALND) in favour of irradiation. The aim of the study was to estimate local control probability in the axilla (axLCP).We identified 1832 invasive breast cancer patients who had undergone SLNB at our centre. We measured maximal metastasis diameter (SLDmax) in the sentinel lymph nodes and lymph node metastasis volume (VALN) from ALND in 246 patients with one or two positive SLNs. We calculated axLCP after irradiation and systemic treatment for different molecular types.VALN values are higher for high grade tumours and larger metastases in SLNs (> 5 mm). It is smaller in luminal A tumours. axLCP is high, nearly 100%, in all molecular types in radiation sensitive tumours (SF2 Gy = 0.45), except luminal B. Expected axLCP is relatively low (67%) in luminal B radiation sensitive tumours with no chemotherapy and nearly 100% with chemotherapy.VALN values differ among molecular tumour types. They depend on SLNDmax and tumour grade. New prognostic factors are needed for selected luminal B breast cancer patients (i.e. high grade tumours, large metastases in SLNs) after positive SLNB intended to be spared ALND and chemotherapy.

Anoikis resistance in mammary epithelial cells is mediated by semaphorin 7a

Semaphorin-7a (SEMA7A), best known as a neuroimmune molecule, plays a diverse role in many cellular processes and pathologies. Here, we show that SEMA7A promotes anoikis resistance in cultured mammary epithelial cells through integrins and activation of pro-survival kinase AKT, which led us to investigate a role for SEMA7A during postpartum mammary gland involution—a normal developmental process where cells die by anoikis. Our results reveal that SEMA7A is expressed on live mammary epithelial cells during involution, that SEMA7A expression is primarily observed in α6-integrin expressing cells, and that luminal progenitor cells, specifically, are decreased in mammary glands of SEMA7A−/− mice during involution. We further identify a SEMA7A-α6/β1-integrin dependent mechanism of mammosphere formation and chemoresistance in mammary epithelial cells and suggest that this mechanism is relevant for recurrence in breast cancer patients.

Predictors for Fear of Cancer Recurrence in Breast Cancer Patients Referred to Radiation Therapy During the COVID-19 Pandemic: A Multi-Center Cross-Section Survey.

ObjectiveThe outbreak of COVID-19 pandemic has greatly impacted on radiotherapy (RT) strategy for breast cancer patients, which might lead to increased distressing psychological symptoms. We performed a multi-center cross-section survey to investigate prevalence of fear of cancer recurrence (FCR) and predictors for FCR in patients referred to RT during pandemic.Methods542 patients were consecutively enrolled from three regions in China including Yangtze Delta River Region, Guangdong and Shanxi province. Patients’ characteristics were collected using an information sheet, Fear of progression questionnaire-short form, Hospital Anxiety/Depression Scale and EORTC QLQ-C30. The hierarchical multiple regression models were performed.Results488 patients with complete data were eligible. The RT strategy was affected in 265 (54.3%) patients, including 143 with delayed RT initiation, 66 believing to have delayed RT initiation but actually not, 24 with RT interruptions, 19 shifting to local hospitals for RT and the remaining 13 influenced on both RT schedule and hospital level. The model explained 59.7% of observed variances in FCR (p<0.001) and showed that influence of RT strategy had significantly impacted on FCR (△R2 = 0.01, △F=2.966, p=0.019). Hospitals in Shanxi province (β=-0.117, p=0.001), emotional function (β=-0.19, p<0.001), social function (β=-0.111, p=0.006), anxiety (β=0.434, p<0.001) and RT interruption (β=0.071, p=0.035) were independent predictors.ConclusionsRT strategy for breast cancer patients was greatly influenced during pandemic. RT interruption is an independent predictor for high FCR. Our findings emphasize the necessity to ensure continuum of RT, and efforts should be taken to alleviate FCR through psychological interventions.

BRENDA-Score, a Highly Significant, Internally and Externally Validated Prognostic Marker for Metastatic Recurrence: Analysis of 10,449 Primary Breast Cancer Patients.

Simple SummaryThe BRENDA-Score provides an easy to use tool for clinicians to estimate the risk of recurrence in primary breast cancer. The algorithm has been validated via a second independent database and provides five recurrence risk groups. This grouping helps clinicians to encourage high risk patients to undergo the recommended treatment. Background Current research in breast cancer focuses on individualization of local and systemic therapies with adequate escalation or de-escalation strategies. As a result, about two-thirds of breast cancer patients can be cured, but up to one-third eventually develop metastatic disease, which is considered incurable with currently available treatment options. This underscores the importance to develop a metastatic recurrence score to escalate or de-escalate treatment strategies. Patients and methods Data from 10,499 patients were available from 17 clinical cancer registries (BRENDA-project. In total, 8566 were used to develop the BRENDA-Index. This index was calculated from the regression coefficients of a Cox regression model for metastasis-free survival (MFS). Based on this index, patients were categorized into very high, high, intermediate, low, and very low risk groups forming the BRENDA-Score. Bootstrapping was used for internal validation and an independent dataset of 1883 patients for external validation. The predictive accuracy was checked by Harrell’s c-index. In addition, the BRENDA-Score was analyzed as a marker for overall survival (OS) and compared to the Nottingham prognostic score (NPS). Results: Intrinsic subtypes, tumour size, grading, and nodal status were identified as statistically significant prognostic factors in the multivariate analysis. The five prognostic groups of the BRENDA-Score showed highly significant (p < 0.001) differences regarding MFS:low risk: hazard ratio (HR) = 2.4, 95%CI (1.7–3.3); intermediate risk: HR = 5.0, 95%CI.(3.6–6.9); high risk: HR = 10.3, 95%CI (7.4–14.3) and very high risk: HR = 18.1, 95%CI (13.2–24.9). The external validation showed congruent results. A multivariate Cox regression model for OS with BRENDA-Score and NPS as covariates showed that of these two scores only the BRENDA-Score is significant (BRENDA-Score p < 0.001; NPS p = 0.447). Therefore, the BRENDA-Score is also a good prognostic marker for OS. Conclusion: The BRENDA-Score is an internally and externally validated robust predictive tool for metastatic recurrence in breast cancer patients. It is based on routine parameters easily accessible in daily clinical care. In addition, the BRENDA-Score is a good prognostic marker for overall survival. Highlights: The BRENDA-Score is a highly significant predictive tool for metastatic recurrence of breast cancer patients. The BRENDA-Score is stable for at least the first five years after primary diagnosis, i.e., the sensitivities and specificities of this predicting system is rather similar to the NPI with AUCs between 0.76 and 0.81 the BRENDA-Score is a good prognostic marker for overall survival.

Oncotype Dx score associated to pathological features to better prognosticate the risk of recurrence for breast cancer patients.

e12562 Background: Oncotype Dx (ODX) prognosticates the risk of recurrence and predicts the benefit of adjuvant chemotherapy in estrogen-receptor-positive breast cancer (BC). However, it puts aside important clinical features. Our objective is to develop a model that uses routine clinical parameters associated with Oncotype Dx score to estimate the recurrence rate in our population. Methods: We retrospectively reviewed ODX and pathology reports from 371 early BC patients diagnosticated between 2014 and 2016 in a specialized cancer center, with a 5 year follow up. Variables were selected first with a univariate cox regression, then the statistically significant variables underwent a multivariate cox regression. The β coefficients from selected variables were used to create the prediction formula. Results: Among the tested variables, ki67, estrogen receptor (ER) and ODx score were significantly associated with Recurrence. The linear predictor is: (0.1331 x Ki67) + (0.4232 x ER)+(0.2112xODx score). The threshold score for this equation was set on 33 (median value) to discriminate low and high estimated risks for recurrence. The correct classification rate (CCR) for the training and validation sets was 76% and 68%, respectively. Conclusions: It is possible to optimize the Oncotype Dx to better determine a recurrence score with selected pathological features.

Presentation and management of patients with brain metastases of primary melanoma, non-small cell lung cancer, and breast cancer origin.

2033 Background: As systemic therapy improves; the prevalence of brain metastases is increasing. Screening brain MRIs are currently recommended for all stage ≥ II non-small cell lung cancer (NSCLC) and stage IIIB–IV melanoma patients, but only when neurologic symptoms arise in stage IV or recurrent breast cancer (BC) patients. This study assessed the presentation and institutional outcomes treating brain metastases (BM) of BC, NSCLC, and melanoma origin. Methods: Patients with BM treated between 2014 and 2019 with primary melanoma, NSCLC, and BC were identified. Characteristics of initial BM diagnoses were retrieved from clinical chart review. Kruskal-Wallis and Pearson’s chi-square tests were used to test differences between groups. Overall survival (OS) was calculated from dates of initial BM diagnosis using the Kaplan–Meier method. Results: A total of 959 patients were identified (BC 18%, NSCLC 51%, melanoma 31%). BC patients were younger at initial presentation (BC median age: 57, NSCLC 65, melanoma 62, p&lt; 0.0001). At BM diagnosis, BC patients were more likely to have concurrent systemic metastasis (BC 77%, NSCLC 42%, melanoma 69%, p&lt; 0.0001), at least 5 BM (BC 27%, NSCLC 14%, melanoma 13%, p= 0.0004), and leptomeningeal disease (BC 23%, NSCLC 6%, melanoma 6%, p&lt; 0.0001). Patients with BC were significantly more likely to receive whole brain radiation therapy (WBRT) (BC 58%, NSCLC 37%, melanoma 22%, p&lt; 0.0001) and less likely to receive stereotactic radiation (BC 26%, NSCLC 48%, melanoma 58%, p&lt; 0.0001) following initial BM diagnosis. There were no significant differences in surgical resection between cancer types (BC 24%, NSCLC 24%, melanoma 29%, p =0.166). Median OS was shorter for BC (BC 9.9 months, NSCLC 10.3 months, melanoma 13.7 months, p= 0.0006) following BM diagnosis. Conclusions: Our institutional analysis found BC patients were more likely to be younger, present with more advanced brain disease, require WBRT, and have poorer OS than NSCLC and melanoma patients following initial brain metastasis diagnosis. This may be due in part to a lack of brain MRI screening recommendations in BC. Further investigation is needed to determine which BC patients are at sufficient risk to warrant brain MRI screening.

Effect of surgical complications on outcomes in breast cancer patients treated with mastectomy and immediate reconstruction.

Operative complications affect recurrence in non-breast malignancies. Rising rates of mastectomy with immediate reconstruction and their increased post-operative complications fuel concerns for poorer outcome in breast cancer (BC). We sought to determine the effect of complications on recurrence in BC patients. A single-institution retrospective review was conducted of incident BC treated with mastectomy and immediate reconstruction. Overall survival and recurrence were compared between patients with complications to those without. Of 201 patients (350 mastectomies, 86 nipple-sparing), 62 (30.8%) had a surgical complication. Patients with complications were older, but groups were similar for type of reconstruction, tobacco use, hormone receptor status, HER2, lymphovascular invasion, and pathologic stage (all p > 0.05). Twenty-two complications (10.9%) were infection, 5 (2.5%) dehiscence, 14 flap necrosis (7%), 21 hematomas (10.4%), and 8 nipple necroses (9%). Recurrence occurred in 18 (8.9%) patients: 4 local, 2 regional, and 12 distant. After 8.9years of median follow-up, patients with complications trended towards higher recurrence (hazard ratio (HR) 2.23, log-rank p = 0.08, Cox regression p = 0.05), particularly with nipple necrosis (HR 3.28, log-rank p = 0.09, regression p = 0.06). Patients with other complications had similar recurrence-free survival to those without (all p > 0.05). Higher stage (HR 13.66, log-rank p = 0.03) and adjuvant radiation (HR 2.78, log-rank p = 0.04) cases were more likely to recur. Patients with complications had similar overall survival to those without (log-rank p > 0.05). BC patients with surgical complications do not have lower overall survival. This finding may be due to the improved prognosis compared to non-breast malignancies.

65P Patient follow-up of NEOVATTL study

Sentinel lymph node biopsy has gained attention due to its potential for less invasive management of the axilla and the increasing number of early-stage breast cancer patients treated with neoadjuvant systemic therapy prior to surgery. One-Step Nucleic Acid Amplification (OSNA) assay is an accurate and reliable option for intraoperative molecular analysis of SLN status. NEOVATTL study demonstrates its predictive and prognostic value for non-SLN involvement and disease recurrence in breast cancer patients who had received NST. Therefore, the aim of the study was to show the follow-up of those patients that were recruited in NEOVATTL study and to corroborate the favorable prognosis of the patients with low axillary tumour load. This is a multicentric and retrospective study in which the patients underwent intraoperative SLN biopsy after NST. The data was obtained from a Spanish Sentinel Lymph Node database. TTL was defined as the total sum of CK19 mRNA copies in all positive SLNs. A total of 314 patients were included; 75.0% were cN0 prior to NST. 91.7% received chemotherapy with or without biologic therapy, and 81 patients had a pathologic complete response. TTL was predictive of non-SLN involvement at a cut-off of 15,000 copies/μL had a negative predictive value of 90.5%. TTL was prognostic of disease recurrence and DFS at a cut-off of 25,000 copies/μL. TTL >15,000 mRNA copies/μL was predictive of non-SLN involvement and TTL >25,000 mRNA copies/μL was associated with a higher risk of disease recurrence in breast cancer patients who had received NST. Follow up between five to ten years have demonstrated a favourable prognosis of patients with low TTL (<15,000mRNA).

ALG3 contributes to stemness and radioresistance through regulating glycosylation of TGF-\u03b2 receptor II in breast cancer

BackgroundRadiotherapy is a conventional and effective local treatment for breast cancer. However, residual or recurrent tumors appears frequently because of radioresistance. Novel predictive marker and the potential therapeutic targets of breast cancer radioresistance needs to be investigated.MethodsIn this study, we screened all 10 asparagine-linked glycosylation (ALG) members in breast cancer patients’ samples by RT-PCR. Cell viability after irradiation (IR) was determined by CCK-8 assay and flow cytometry. The radiosensitivity of cell lines with different ALG3 expression was determined with the colony formation assay by fitting the multi-target single hit model to the surviving fractions. Cancer stem-like traits were assessed by RT-PCR, Western blot, and flow cytometry. The mechanisms of ALG3 influencing radiosensitivity was detected by Western blot and immunoprecipitation. And the effect of ALG3 on tumor growth after IR was verified in an orthotopic xenograft tumor models. The association of ALG3 with prognosis of breast cancer patients was confirmed by immunohistochemistry.ResultsALG3 was the most significantly overexpressing gene among ALG family in radioresistant breast cancer tissue. Overexpression of ALG3 predicted poor clinicopathological characteristics and overall survival (OS), and early local recurrence-free survival (LRFS) in breast cancer patients. Upregulating ALG3 enhanced radioresistance and cancer stemness in vitro and in vivo. Conversely, silencing ALG3 increased the radiosensitivity and repressed cancer stemness in vitro, and more importantly inhibition of ALG3 effectively increased the radiosensitivity of breast cancer cells in vivo. Mechanistically, our results further revealed ALG3 promoted radioresistance and cancer stemness by inducing glycosylation of TGF-β receptor II (TGFBR2). Importantly, both attenuation of glycosylation using tunicamycin and inhibition of TGFBR2 using LY2109761 differentially abrogated the stimulatory effect of ALG3 overexpression on cancer stemness and radioresistance. Finally, our findings showed that radiation played an important role in preventing early recurrence in breast cancer patients with low ALG3 levels, but it had limited efficacy in ALG3-overexpressing breast cancer patients.ConclusionOur results suggest that ALG3 may serve as a potential radiosensitive marker, and an effective target to decrease radioresistance by regulating glycosylation of TGFBR2 in breast cancer. For patients with low ALG3 levels, radiation remains an effective mainstay therapy to prevent early recurrence in breast cancer.

Lost clips after targeted lymph node biopsy in breast cancer patients: Follow-up of the CLIP-study

IntroductionClipping and selective removal of axillary lymph nodes in breast cancer patients presenting with initially node-positive disease and achieving a nodal downstaging after primary systemic therapy is a less invasive method for axillary staging. An imaging guided localization and successful extirpation of these clipped lymph nodes is not possible in all patients. To date no follow-up data regarding patients with lost clips are available. Material and methodsThe oncological outcome of all participants of the CLIP-study and the results of postoperative axillary imaging in those patients with unproven clip resection are presented. ResultsA total of thirty patients were included into the pilot study. In ten of these patients (33%) the removal of the clipped axillary lymph node could not be verified by intraoperative radiograph. Postoperative imaging did not find lost clips in eight of these ten patients (80%). The lost clip was detected in two patients after surgery (20%), by mammography in one patient during routine follow-up and by computed tomography scan in one patient before radiotherapy. After a median follow-up of 40 months, 26 (87%) patients were still alive. Seven patients (23%) developed distant recurrent disease. No local or axillary recurrences were observed. ConclusionLost clips were detected by postoperative imaging only in a minority of patients. The impact of lost clips on axillary recurrences in breast cancer patients is still unclear and should be further clarified in larger, multicentric trials.

Role of F-18 FDG PET/CT in Patients with Suspected Recurrent Breast Cancer: Additional Value over Conventional Imaging Modalities

Background: The aim of the present study was to investigate the added value of F-18 fludeoxyglucose (FDG) positron-emission tomography (PET)/computed tomography (CT) compared with conventional imaging modalities for the evaluation of locoregional and distant sites of recurrence in breast cancer patients. Methods: From May 2013 to September 2016, 109 patients with suspected recurrent breast cancer who underwent conventional imaging and F-18 FDG PET/CT with an interval of 6 weeks were consecutively enrolled (mean age: 52.66 years; range: 29?79). Histopathologic results and clinical follow up based on the gold-standard imaging modality or serial imaging were considered as the reference for verification of F-18 FDG PET/CT findings. Results: Of 109 patients, 81 were found to have at least one site of recurrence (74.31%). Local recurrence was correctly identified in 32/32 patients following PET/CT, which was higher than that on conventional imaging (20/32, 62.5%). PET/CT detected 27 additional nodal metastases compared with conventional imaging (59 vs. 32, 45.76%), most frequently in the hilar/mediastinal region (n=27), followed by the supraclavicular lymph nodes (n=20, 62.5%), internal mammary lymph nodes (n=6, 18.77%), and axillary basin (n=6, 18.77%). Additional sites of distant metastasis were identified in 41 patients (37.61%) following F-18 FDG PET/CT imaging, 48.78% of which were localized in the skeletal system (n=20), 21.95% in the liver (n=9), 12.19% in the lungs (n=5), 12.19% in the brain (n=5), and 4.87% in the adrenal glands (n=2). Conclusion: F-18 FDG PET/CT serves as a useful supplement to conventional imaging techniques by identifying additional sites of disease recurrence in patients with breast cancer, which may change the preferred treatment strategy, particularly in regions that are not routinely evaluated by conventional imaging.