Significant Predictors Of Locoregional Recurrence Research Articles

A nomogram with Nottingham prognostic index for predicting locoregional recurrence in breast cancer patients.

The Nottingham prognostic index (NPI) has been shown to negatively impact survival in breast cancer (BC). However, its ability to predict the locoregional recurrence (LRR) of BC remains still unclear. This study aims to determine whether a higher NPI serves as a significant predictor of LRR in BC. In total, 238 patients with BC were included in this analysis, and relevant clinicopathological features were collected. Correlation analysis was performed between NPI scores and clinicopathological characteristics. The optimal nomogram model was determined by Akaike information criterion. The accuracy of the model's predictions was evaluated using receiver operating characteristic curves (ROC curves), calibration curves and goodness of fit tests. The clinical application value was assessed through decision curve analysis. Six significant variables were identified, including age, body mass index (BMI), TNM stage, NPI, vascular invasion, perineural invasion (P<0.05). Two prediction models, namely a TNM-stage-based model and an NPI-based model, were constructed. The area under the curve (AUC) for the TNM-stage- and NPI-based models were 0.843 (0.785,0.901) and 0.830 (0.766,0.893) in training set and 0.649 (0.520,0.778) and 0.728 (0.610,0.846) in validation set, respectively. Both models exhibited good calibration and goodness of fit. The F-measures were 0.761vs 0.756 and 0.556 vs 0.696, respectively. Clinical decision curve analysis showed that both models provided clinical benefits in evaluating risk judgments based on the nomogram model. a higher NPI is an independent risk factor for predicting LRR in BC. The nomogram model based on NPI demonstrates good discrimination and calibration, offering potential clinical benefits. Therefore, it merits widespread adoption and application.

Pattern of LRR in Endometrial Cancer and Identification of Predictive Factors

Background: Tailored adjuvant treatment is key to managing endometrial cancer effectively. Understanding prognostic factors of loco-regional failure and the impact of adjuvant treatment can help in treatment de-escalation without compromising survival outcomes. The aim of this study was to assess the pattern of failure in endometrial cancer patients and to determine predicting Loco-Regional Recurrence (LRR) factors. Patients and methods: Data were collected from 214 patients treated for endometrial cancer between 2005 and 2012 in Salah Azaiez Institute in Tunisia. All patients underwent upfront surgery followed by adjuvant brachytherapy with or without external beam radiation. The median follow-up period was 44 months. Univariate and multivariate analyses were performed to identify prognostic factors for LRR. Results: The 5-year overall survival rate was 78.1%, and the 5-year progression-free survival rate was 80.1%. LRR occurred in 25 patients (11.6%), with a median recurrence time of 29 months (range 4 months - 46 months). Pelvic relapse was the most common site, occurring in 10 patients. Vaginal relapses were observed in 9 patients, and retro-peritoneal relapses were observed in 6 cases. FIGO stage, tumor grade, histologic type, Lympho-Vascular Space Invasion (LVSI), and delays in adjuvant treatment were significant predictors of LRR. Conclusion: Identifying prognostic factors for LRR in endometrial cancer is crucial for optimizing adjuvant treatment strategies. Higher FIGO stages and the presence of LVSI were independent predictive factors for LRR. Tailored adjuvant treatment, taking these prognostic factors into account, is essential to improve patient outcomes and minimize unnecessary treatment-related toxicity.

Patterns of failure for recurrent head and neck squamous cell carcinoma treated with salvage surgery and postoperative IMRT reirradiation

Purpose/ObjectivesThe purpose of this study was to evaluate patterns of locoregional recurrence (LRR) after surgical salvage and adjuvant reirradiation with IMRT for recurrent head and neck squamous cell cancer (HNSCC). Materials/MethodsPatterns of LRR for 61 patients treated consecutively between 2003 and 2014 who received post-operative IMRT reirradiation to ≥ 60 Gy for recurrent HNSCC were determined by 2 methods: 1) physician classification via visual comparison of post-radiotherapy imaging to reirradiation plans; and 2) using deformable image registration (DIR). Those without evaluable CT planning image data were excluded. All recurrences were verified by biopsy or radiological progression. Failures were defined as in-field, marginal, or out-of-field. Logistic regression analyses were performed to identify predictors for LRR. ResultsA total of 55 patients were eligible for analysis and 23 (42 %) had documented LRR after reirradiation. Location of recurrent disease prior to salvage surgery (lymphatic vs. mucosal) was the most significant predictor of LRR after post-operative reirradiation with salvage rate of 67 % for lymphatic vs. 33 % for mucosal sites (p = 0.037). Physician classification of LRR yielded 14 (61 %) in-field failures, 3 (13 %) marginal failures, and 6 (26 %) out-of-field failures, while DIR yielded 10 (44 %) in-field failures, 4 (17 %) marginal failures, and 9 (39 %) out-of-field failures. Most failures (57 %) occurred within the original site of recurrence or first echelon lymphatic drainage. Of patients who had a free flap placed during salvage surgery, 56 % of failures occurred within 1 cm of the surgical flap. ConclusionOur study highlights the role of DIR in enhancing the accuracy and consistency of POF analysis. Compared to traditional visual inspection, DIR reduces interobserver variability and provides more nuanced insights into dose-specific and spatial parameters of locoregional recurrences. Additionally, the study identifies the location of the initial recurrence as a key predictor of subsequent locoregional recurrence after salvage surgery and re-IMRT.

Predictors of recurrence in oral cavity cancer with clear surgical margins

Introduction: Oral cancers recur in a significant proportion of patients, in spite of aggressive treatment strategies. The presence of a clear surgical margin is an important predictor of recurrent disease, among others. Since oral cancers often recur in the absence of compromised margins, there is a need to study the factors affecting recurrence and overall survival outcomes where clear surgical margins have been achieved during upfront surgery. This study attempts to identify the significant predictors of locoregional recurrence in oral squamous cell carcinoma (OSCC) with pathologically clear surgical margins. Methodology: This retrospective study was done to study the clinicopathological parameters associated with recurrence of oral cavity squamous cell carcinoma (SCC) in patients with clear surgical margins operated in our unit between January 2010 and December 2015. A total of 526 cases of oral cavity SCC were analyzed and records of 160 cases with clear surgical margins were reviewed for clinical details, histopathological data, and follow-up status. Age, gender, subsite, T–N clinical and pathological staging, tumor depth of invasion, grade of differentiation, lymphovascular invasion, perineural spread, adjuvant therapy, and recurrence details were analyzed. Results: Lymphovascular Invasion was found to be a significant predictor for local recurrence in OSCC in both univariate and multivariate analysis. Median recurrence-free survival was 53.6 months. Conclusion: Despite the best efforts of the surgeon in obtaining adequate tumor-free margins and the most comprehensive adjuvant treatment, recurrence patterns in oral cancers continue to defy accurate prediction. Lymphovascular invasion could be an important predictor of recurrence for oral cavity cancers in patients with clear surgical margins that require aggressive management.

Positive bag lavage cytology during thoracoscopic surgery for lung cancer is a significant predictor of locoregional recurrence.

Advances in thoracoscopic surgery have made skin incisions smaller, but there are concerns about cancer cell contamination during sample extraction. We performed retrieval bag lavage cytology (BLC) during thoracoscopic surgery to evaluate the risk of cancer dissemination and the prognostic influence of BLC status. BLC was investigated in 893 patients who underwent thoracoscopic lobectomy or segmentectomy for lung cancer between 2013 and 2018. The clinicopathological features and prognosis were compared between the BLC-positive and BLC-negative groups. Forty-nine patients (5.5%) were positive for BLC. BLC correlated with pleural invasion (49.0% vs. 12.9%, P < 0.001); however, BLC was positive in 3.3% of cases without pleural invasion. Multivariate analysis revealed that tumor size, lymph node metastasis, lymphatic and pleural invasion were predictive factors for positive BLC. Prognosis was poorer in the BLC-positive group than in the BLC-negative group (5-year overall survival, 73.6% vs. 90.2%, P < 0.001); nevertheless, positive BLC was not an independent prognostic factor. The locoregional recurrence rate was higher among BLC-positive patients than among BLC-negative patients, whereas there was no significant difference in the distant recurrence rate. Positive BLC was associated with locoregional recurrence (hazard ratio 1.87, P = 0.044) and the correlation was stronger in stage I lung cancer. There were no cases of extraction bag breakage or port-site recurrence. BLC positivity was correlated with the risk of locoregional recurrence in patients with surgically resected lung cancer, although it was not an independent prognostic factor. Careful manipulation is essential for extracting specimens from the thoracic cavity.

Breast Conservation among Older, Early Stage Breast Cancer Patients: Locoregional Recurrence Following Adjuvant Radiation or Hormone Therapy

Following breast-conserving surgery (BCS), both radiation therapy (RT) and hormone therapy (HT) reduce the risk of locoregional recurrence (LRR) among favorable subgroups of breast cancer. Several studies have evaluated HT +/- RT, though local outcomes of HT versus RT monotherapy remain unclear. Indeed, many patients do not complete the full multi-year course of HT, yet little is known about LRR rates in absence of HT. Here, we evaluate rates of adjuvant HT and RT use in a cohort of favorable-risk patients over 65 years of age, and report LRR in the setting of adjuvant RT alone, HT alone, neither, or both. We analyzed a cohort of breast cancer patients ≥65 years of age with estrogen receptor positive (ER+), HER2/neu negative (HER2-) T1N0 breast cancer diagnosed between 2010 and 2015 and treated with BCS. Clinicopathologic features were collected including type of axillary surgery, RT modality, use of RT boost, duration of HT, chemotherapy, and OncotypeDx Recurrence Scores (RS). Cox regression analysis was conducted using time to LRR as the primary endpoint. A total of 1,016 women were included with a median age of 70 (IQR 67-75) and median follow-up of 4.9 years (range 0.4-7.7). Overall, 36 (4%) LRR events were observed and 16 (2%) patients had a distant recurrence. The 5-year overall survival rate for the cohort was 96%. A total of 624 (61%) patients received RT. While 894 (88%) were started on HT, 725 (72%) completed a full course or remain adherent at last follow-up. Evaluated by treatment group (with HT defined as fully compliant to date), 481 (48%) patients received both HT and RT (5-year LRR 2%, 95%CI 1-4%), 244 (24%) received HT alone (5-year LRR 4%, 95% CI 2-8%), 143 (14%) received RT alone (5-year LRR 5%, 95%CI 2-11%), and 142 (14%) received neither HT nor RT (LRR 11%, 95%CI 6-19%). LRR rates were significantly different between these four treatment groups (Log rank p<0.001). On Cox regression, accounting for clinicopathologic variables, lymphovascular invasion (HR 6.37, 95%CI 2.17-18.7; p<0.001) and adjuvant treatment group were significant predictors of LRR. Compared to neither HT nor RT, combination HT and RT was significantly associated with the greatest reduction in LRR (HR 0.11, 95%CI 0.04-0.29; p<0.001). HT or RT monotherapy each yielded similar reductions in LRR: HT alone (HR 0.28, 95%CI 0.11-0.71; p = 0.008) and RT alone (HR 0.29, 95%CI 0.10-0.84; p = 0.023). The risk of LRR following BCS is low among women ≥65 years of age with T1N0, ER+/HER2- breast cancer. RT and HT monotherapy each significantly reduce this risk to a similar extent. While the combination of RT and HT further reduces the risk of LRR in a statistically significant manner, the absolute benefit of this dual-approach is modest. Further study will elucidate whether appropriate patients may feasibly receive RT monotherapy rather than the current standards of HT monotherapy or dual RT and HT therapy.

Predictors of Locoregional Recurrence After Failure to Achieve Pathologic Complete Response to Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer.

This study evaluated factors predictive of locoregional recurrence (LRR) in women with triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy who do not experience pathologic complete response (pCR). This is a single-institution retrospective review of women with TNBC treated with neoadjuvant chemotherapy, surgery, and radiation therapy in 2000 through 2013. LRR was estimated between patients with and without pCR using the Kaplan-Meier method. Patient-, tumor-, and treatment-specific factors in patients without pCR were analyzed using the Cox proportional hazards method to evaluate factors predictive of LRR. Log-rank statistics were then used to compare LRR among these risk factors. A total of 153 patients with a median follow-up of 48.6 months were included. The 4-year overall survival and LRR were 70% and 15%, respectively, and the 4-year LRR in patients with pCR was 0% versus 22.0% in those without (P<.001). In patients without pCR, lymphovascular space invasion (LVSI; hazard ratio, 3.92; 95% CI, 1.64-9.38; P=.002) and extranodal extension (ENE; hazard ratio, 3.32; 95% CI, 1.35-8.15; P=.009) were significant predictors of LRR in multivariable analysis. In these patients, the 4-year LRR with LVSI was 39.8% versus 15.0% without (P<.001). Similarly, the 4-year LRR was 48.1% with ENE versus 16.1% without (P=.002). In patients without pCR, the presence of both LVSI and ENE were associated with an even further increased risk of LRR compared with patients with either LVSI or ENE alone and those with neither LVSI nor ENE in the residual tumor (P<.001). In patients without pCR, the presence of LVSI and ENE increases the risk of LRR in TNBC. The risk of LRR is compounded when both LVSI and ENE are present in the same patient. Future clinical trials are warranted to lower the risk of LRR in these high-risk patients.

Predictors of locoregional recurrence in early stage buccal cancer with pathologically clear surgical margins and negative neck

ObjectiveTo identify the significant predictors of locoregional recurrence in early stage squamous cell carcinoma (SCC) of buccal mucosa with pathologically clear surgical margins and negative neck. MethodSeventy-three patients who underwent per oral wide excision and supraomohyoid neck dissection for early stage buccal SCC with clear surgical margins (>5mm margins each) and negative neck (N0) were included. None of the patients received postoperative radiotherapy or chemotherapy. Univariate and multivariate analyses were used to identify independent predictors of locoregional recurrence. ResultsRecurrence was observed in 22 of 73 (30%) cases. Twelve had local, seven had regional and three developed locoregional recurrences. Both univariate and multivariate analyses demonstrated that lymphovascular invasion (LVI) and non-T4 muscular invasion (non-T4MI) were independent predictors affecting locoregional control. ConclusionLymphovascular invasion (LVI) and non-T4 muscular invasion (non-T4MI) significantly increased the locoregional recurrence rate in early stage buccal SCC with clear surgical margins and negative nodal status. Adjuvant treatment with either radiation or chemoradiation should be considered when one or both of these factors present.

Predictors of locoregional recurrence in early stage buccal cancer with pathologically clear surgical margins and negative neck

ObjectiveTo identify the significant predictors of locoregional recurrence in early stage squamous cell carcinoma (SCC) of buccal mucosa with pathologically clear surgical margins and negative neck. MethodSeventy-three patients who underwent per oral wide excision and supraomohyoid neck dissection for early stage buccal SCC with clear surgical margins (>5mm margins each) and negative neck (N0) were included. None of the patients received postoperative radiotherapy or chemotherapy. Univariate and multivariate analyses were used to identify independent predictors of locoregional recurrence. ResultsRecurrence was observed in 22 of 73 (30%) cases. Twelve had local, seven had regional and three developed locoregional recurrences. Both univariate and multivariate analyses demonstrated that lymphovascular invasion (LVI) and non-T4 muscular invasion (non-T4MI) were independent predictors affecting locoregional control. ConclusionLymphovascular invasion (LVI) and non-T4 muscular invasion (non-T4MI) significantly increased the locoregional recurrence rate in early stage buccal SCC with clear surgical margins and negative nodal status. Adjuvant treatment with either radiation or chemoradiation should be considered when one or both of these factors present.

The impact of elevated C-reactive protein level on the prognosis for oro-hypopharynx cancer patients treated with radiotherapy

The purpose of this study was to investigate an association between the prognosis for oro-hypopharynx squamous cell carcinoma treated with radiation therapy and the pre-therapeutic level of C-reactive protein (CRP). Patient with oro-hypopharyngeal squamous cell carcinoma who underwent definitive radiotherapy in our institution from January 2002 to August 2016 were enrolled. The patient were divided into elevated CRP (over 0.3 mg/dl) group and normal CRP groups, according to pre-treatment serum levels. There were 276 evaluable patients, and the median follow up was 41 months, ranging from 2 to 171 months. The 3-year OS and CSS for all enrolled patients were 67.0% and 72.8%, respectively. The OS and CSS rates were significantly worse in the elevated CRP group than in the normal CRP group, according to Kaplan-Meier survival curves analysed by a Log-rank test (p = 0.005 and p < 0.001, respectively). Multivariate analyses indicated that serum CRP levels remained independent predictors for both OS (HR: 1.588, p = 0.022) and CSS (HR: 1.989, p = 0.005). The pre-treatment CRP level is an independent predictor of treatment prognosis in patients with oro-hypopharyngeal cancer who underwent definitive radiotherapy. Especially, it is curious that an elevated CRP serum level is a significant predictor of loco-regional recurrence.

Factors predictive of locoregional recurrence following neoadjuvant chemotherapy in patients with large operable or locally advanced breast cancer: An analysis of the EORTC 10994/BIG 1-00 study

PurposeIdentification of clinicopathological factors predicting for a locoregional recurrence (LRR) after neoadjuvant chemotherapy (NAC) could help to decide on the optimal locoregional radiotherapy. The objective of this trial is to identify those factors in the context of a phase III trial (European Organisation for Research and Treatment of Cancer 10994). MethodsPatients received NAC followed by surgery with or without radiotherapy. Radiotherapy was administered according to pre-specified guidelines. Patients with hormone receptor positive tumours received adjuvant hormonal therapy. A proportion of patients with human epidermal growth factor receptor 2 (HER2) positive cancer received adjuvant trastuzumab. The predictive factors for LRR were identified by multivariate analysis with time to LRR as first event as the primary end-point. ResultsThe median follow-up was 4.4 years. In 1553 eligible patients, there were 76 LRRs with a 5-year cumulative incidence of 4.9% (95% confidence interval, CI [3.76–6.04]). In multivariate analysis, breast cancer subtype was a significant predictor of LRR (p < 0.0001): hazard ratio (HR) 6.44 (95% CI [2.83–14.69]) for triple negative, 6.26 (95% CI [2.81–13.93]) for HER2+ without trastuzumab (T) and 3.37 (95% CI [1.10–10.34]) for HER2+ with T cancers, all compared to luminal A patients. Lack of pathological response was also associated with significantly higher LRR risk in case of ≥4 pathologically positive nodes, HR 2.43 (95% CI [1.34–4.40], p < 0.0001). ConclusionBreast cancer subtype and lack of pathological response are predictive factors for high LRR after NAC.

Prediction of central lymph node metastasis in patientswith thyroid papillary microcarcinoma

Background/aim: The purpose of this study was to analyze the clinicopathological characteristics of patients with papillary thyroid carcinoma (PTC) and papillary thyroid microcarcinoma (PTMC) and predictive factors for central lymph node metastasis (CLNM).Materials and methods: Patients diagnosed as having PTC and PTMC were evaluated. Clinical and laboratory parameters were recorded.Results: The mean age at diagnosis was 47.3 +- 11.9 years. Of all 223 patients, 91 (40.8%) had lymph nodes removed, 29 of whom had lymph node metastasis and 24 of whom had only CLNM. Univariate analysis revealed that central lymph node metastasis was associated with male sex, presence of bilaterality, presence of extrathyroidal extension, and tumor size (P = 0.033, P = 0.027, P < 0.001, P < 0.001, respectively). However, multivariate logistic regression analysis showed that sex, age, tumor size, multifocality, bilaterality, extrathyroidal extension, clinical suspicion, and chronic lymphocytic thyroiditis were not significantly correlated with an increased risk for CLNM.Conclusion: Lymph node metastasis is known to be a significant predictor of locoregional recurrence in patients with PTC and PTMC. Further prospective studies are needed to identify the extent of surgery such as central lymph node dissection in patients with PTC or PTMC.

Pattern of invasion and lymphovascular invasion in squamous cell carcinoma of the floor of the mouth: an interobserver variability study.

Lymphovascular invasion (LVI) and the histological pattern of invasion (POI) at the invasive tumour front have been reported as adverse prognosticators in oral squamous cell carcinoma (SCC). However, assessment of these parameters is hampered by variation in the criteria used for their evaluation. Our objective was to evaluate interobserver variability in the assessment of the POI and LVI in SCC of the floor of the mouth (FOM), and to study the impact of the POI on clinical outcomes by using varying quantitative cut-offs. Fifty-eight cases of FOM SCC were independently evaluated for the POI and LVI by three pathologists. Interobserver variability was analysed by the use of Fleiss kappa statistics. Interobserver agreement was substantial for the assessment of LVI [κ=0.64, 95% confidence interval (CI) 0.60-0.68]. Interobserver agreement was moderate for evaluation of the POI with a 50% cut-off (κ=0.58, 95% CI 0.54-0.62), a 20% cut-off (κ=0.58, 95% CI 0.54-0.62) cut-off, and worst POI (κ=0.43, 95% CI 0.39-0.46). A consensus diagnosis of the POI was a significant predictor of locoregional recurrence (LRR), disease-specific survival (DSS) and overall survival (OS) on univariate analysis when a 50% cut-off was used (LRR, P=0.01; DSS, P=0.01; OS, P=0.01) and when a 20% cut-off was used (LRR, P=0.02; DSS, P=0.02; OS, P=0.03), but was not significant when worst POI was used (LRR, P=0.18; DSS, P=0.16; OS, P=0.17). Interobserver agreement in the diagnosis of LVI was substantial. The POI at the 50% and 20% cut-offs is moderately reproducible, and has prognostic value in FOM SCC. Further studies are necessary to establish the optimum quantitative cut-off for the POI.

Predictors of Locoregional Outcome in HER2-Overexpressing Breast Cancer Treated With Neoadjuvant Chemotherapy

We identified prognostic factors for locoregional recurrence (LRR) in a cohort of patients with HER2-overexpressing breast cancer treated with neoadjuvant chemotherapy (NACT). We reviewed records of 157 patients with HER-overexpressing tumors who received NACT between May 1999 and December 2009 and collected demographics, disease/treatment characteristics, and clinical outcome. We estimated rate of LRR by the method of cumulative incidence. Presentation was 33% stage II and 67% stage III; 29.9% were clinically node positive. All patients received NACT, 94% trastuzumab containing. 90.4% had mastectomy and 6.4% breast-conserving surgery; 3.2% had no surgery. Among surgical patients, 48% were pathologically N0, 28.8% had 1 to 3 positive nodes, and 23.7% had ≥4 positive nodes. 79.6% received radiation therapy (RT) to the breast/chest wall±supraclavicular field. Median follow-up was 43 months. Three-year cumulative incidence of LRR was 8.2%; 50% of LRR had a regional component. Predictors for LRR included use of RT (HR=4.70, P=0.006), lymph node positivity (≥4 vs. 0 HR=19.99, P=0.008; 1 to 3 vs. 0 HR=10.8, P=0.031), and ER status (negative vs. positive HR=6.02, P=0.006). The only risk factor for regional failure specifically was residual nodal disease (≥4 HR=6.5, 1 to 3 HR=5.1, P=0.031). In a cohort with stage II to III HER2-overexpressing breast cancer treated predominantly with trastuzumab-containing NACT followed by mastectomy±RT, we identified omission of RT, negative ER status, and residual positive lymph nodes as significant predictors of LRR, with 50% of LRR having a regional component.

Locoregional and Distant Recurrence Patterns in Young versus Elderly Women Treated for Breast Cancer.

Objective. This study examined recurrence patterns in breast cancer patients younger than age of 40 and older than age of 75, two groups that are underrepresented in clinical trials and not routinely screened by mammography. Methods. The records of 230 breast cancer patients (n = 125 less than 40 and n = 105 greater than 75) who presented to the Emory University Department of Radiation Oncology for curative treatment between 1997 and 2010 were reviewed. Data recorded included disease presentation, treatment, and areas of locoregional recurrence. Results. Women less than 40 years of age had higher rates of locoregional recurrence (20% versus 7%, P = 0.004) and distant recurrence (18% versus 5%, P = 0.003) than patients above 75 years of age. On multivariate analysis, patient age less than 40 was the only significant predictor of locoregional recurrence (P = 0.018). In a univariate analysis of each age group, receptor status and postlumpectomy radiation were significant predictors of locoregional recurrence-free survival in younger women while mammography screening predicted for distant recurrence-free survival in older patients. Conclusion. The factors identified in our age-stratified analysis highlight patients who are at high risk of locoregional and distant recurrence. Future studies aimed at enhancing therapies in young patients are warranted.

The effect of margin status and molecular subtype on women with invasive breast cancer treated with breast-conservation therapy.

83 Background: A consensus statement was recently published by SSO/ASTRO on margins for stage I and II invasive breast cancer treated with breast conserving surgery (BCS). We examined patients with invasive breast cancer who underwent BCS to determine if margin status and molecular subtype influence outcomes. Methods: We the reviewed charts of 754 Stage I-III breast cancer patients treated with BCS from 2003-2010. Margin status was defined as negative ≥ 2mm, close &lt; 2mm and positive as tumor on ink. Conventional receptor analyses were used as markers for molecular subtype classification (luminal A, luminal B, Her2 positive, and basal). Clinicopathologic variables were tested using the Fisher’s exact, Chi-square, ANOVA F-test, and Kruskal-Wallis tests. A Cox proportional - Hazards model was used to measure the impact of these variables on locoregional recurrence (LRR), breast cancer-specific (BCSS) and overall survival (OS). Results: The median age of the cohort was 58 (range 27-89 years). Most were white (88%), had T1 tumors (76%), luminal A tumors (66%), invasive ductal histology (80%), and were node negative (76%). Of the 754 patients, 26% had close margins, 2% positive margins, and 9% unknown margins. With a median follow-up of 5.2 years, OS was 92%. Twenty eight patients had a LRR with a median time to recurrence of 5.1 years. On multivariate analysis, molecular subtype, pathologic grade (p=0.01), and use of radiation (p&lt;0.0001) were the only significant predictors of LRR. Unknown subtype, compared to Luminal A, was less likely to have a LRR (p=0.04). Basal (p=0.0002), Her2+ (p=0.03), Luminal B (p=0.002) and unknown subtype (p=0.04) had worse BCSS compared to Luminal A tumors. Margins had no impact on LRR or BCSS but those with close margins and unknown margins had worse OS compared to negative margins (p=0.01, p=0.007). Variables predictive of OS were margins, age, race, node status, chemotherapy, anti-endocrine therapy, and radiation. Conclusions: In this cohort treated with BCS, molecular subtype was a predictor of LRR and BCSS but not OS. Margin status did not impact LRR and BCSS. Although margin status was a predictor of OS, tumor biology remains the significant determinant of outcome.

The significance of margin status in patients with DCIS undergoing breast-conserving surgery.

98 Background: Recently, SSO/ASTRO published a consensus statement on margins for stage I and II invasive breast cancer treated with breast conserving surgery (BCS). We examined patients with ductal carcinoma in situ (DCIS) who underwent BCS to determine the effect of clinicopathologic and treatment factors including margin status, on locoregional recurrence (LRR), breast cancer-specific (BCSS) and overall survival (OS). Methods: From 2003-2010, we conducted a retrospective chart review of 253 consecutively diagnosed patients who underwent BCS for DCIS. Clincopathologic and treatment data were extracted. Margin status was defined by pathology reports with a negative margin as ≥ 2mm, close margin &lt; 2mm and positive margin as tumor on ink. Clinicopathologic variables were tested using the Fisher’s exact test, Chi-square test, ANOVA F-test, and Kruskal-Wallis test. A Cox proportional - Hazards model was used to calculate the impact of these factors on LRR, BCSS and OS. Results: The median age of the cohort was 57 (range 21-89) and the majority were white (79%), ER+ (78%) and underwent radiation therapy (67%). Forty six percent took anti-endocrine therapy. Of 252 patients, 29% had close margins, 63% had negative margins and 7% had unknown margins. One patient had a positive margin and was alive without disease at last follow-up. At a median follow-up of 5 years, OS was 96%. Thirteen patients experienced a LRR with a median time to recurrence of 4.9 years (5 with close margins, 7 with negative, 1 unknown). On multivariate analysis, age and PR status were significant predictors of LRR. Patients with age &gt;70 were more likely to recur than those age 50-69 (HR 6.7 95% CI (1.7-25.4) p= 0.005) as were patients with PR negative tumors (HR 5.7 95% CI (1.7-19.5) p= 0.005). Those patients who did not receive radiation therapy had a worse OS than those who did (HR 4.3 95%CI (1.5-12.6) p = 0.007). No variables were significant for BCSS. Conclusions: In this cohort of patients with DCIS treated with BCS, age and PR status were the only predictors of LRR. OS was only impacted by receipt of radiotherapy. Margin status was not predictive of LRR, BCSS or OS. This data suggests that routine re-excision for close margins may not be warranted.

Molecular Predictors of Locoregional Recurrence

Molecular Predictors of Locoregional Recurrence

Abstract S1-10: Association between the 21-gene recurrence score (RS) and benefit from adjuvant paclitaxel (Pac) in node-positive (N+), ER-positive breast cancer patients (pts): Results from NSABP B-28

Abstract Background: The RS result predicts outcome in N- and N+, ER+ pts treated with adjuvant endocrine therapy. RS also predicts benefit from adjuvant chemotherapy (CT) and pts with a high RS result receive most of the benefit. We evaluated the association between RS and paclitaxel (Pac) benefit in N+, ER+ pts from NSABP B-28. Methods: B-28 compared 4 cycles of doxorubicin/cyclophosphamide (AC) vs. AC followed by Pac × 4 (AC→Pac). Pts ≥50 yrs and those&amp;lt;50 yrs with ER+ and/or PR+ tumors also received 5 yrs of tamoxifen starting with CT. From 8/95 to 5/98 3060 pts were accrued. The present study includes 1065 pts, ER+ by central tissue microarray IHC assay, tamoxifen-treated, and with a RS result from the Oncotype DX 21-gene assay by standard processes. Sub-distribution analyses were used for loco-regional recurrence (LRR) to account for competing risks, including distant recurrence (DR), second primary cancers, and death. Kaplan-Meier estimates and Cox models were used for other clinical outcomes. Results: Median follow-up time was 11.2 yrs. Of the 1065 pts, 386 (36%) had low RS (&amp;lt;18); 364 (34%) intermediate RS (18–30); and 315 (30%) high RS (≥31). RS was a significant predictor of LRR, DFS event, DR, and death in univariate analyses both in pts treated with AC and in those treated with AC→Pac (Table). Pts with low RS had similar outcomes at 10 yrs when treated with AC→Pac vs. AC (Table). The majority of Pac benefit was observed in pts with intermediate/high RS (Table). Interaction tests between RS and Pac benefit were not statistically significant (LRR: p = 0.75, DFS: p = 0.65, DR: p = 0.93, death: p = 0.30). Conclusions: RS significantly predicts risk for LRR, DR, DFS event, and death in N+, ER+ pts treated with AC or AC→Pac adjuvant CT. Pts with a low RS value have similar outcomes whether treated with AC or with AC→Pac and most of Pac benefit is evident in pts with intermediate/high RS. Although there was no significant interaction between RS and Pac benefit, these results support previous findings of lack of CT benefit in pts with a low RS result. Supported by: NCI grants U10-CA-12027, -69651, -37377, -69974, U24-CA-114732, and CA-75362; Susan G. Komen for the Cure® grants; and Bristol-Myers Squibb Pharmaceutical Research Institute Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr S1-10.

Prognostic Factors Affecting Postmastectomy Locoregional Recurrence in Patients with Early Breast Cancer: Are Intrinsic Subtypes Effective?

Many studies have investigated the association between the molecular subtypes of breast cancer and survival. The aim of this study was to identify the effects of intrinsic subtypes of breast cancer and the other clinicopathological factors on postmastectomy locoregional recurrence (LRR) in patients with early breast cancer. The records of 1,195 consecutive early breast cancer patients treated with modified radical mastectomy between 2004 and 2008 were retrospectively evaluated. The effects of intrinsic subtypes of the tumor (luminal A, luminal B, HER2-overexpressing, and triple-negative) and classical clinicopathological factors on LRR were identified by univariate and multivariate statistical analyses. The median follow-up time was 44 months, and 16 (1.3%) patients experienced a LRR during this period. In univariate analysis, the intrinsic subtypes of breast cancer had a significant effect on LRR (p = 0.002). In multivariate analysis, only extranodal invasion and estrogen receptor (ER) status were significant predictors of LRR (p = 0.003 and 0.0001, respectively), whereas intrinsic subtypes did not reveal a significant relationship with LRR (p = 0.57; hazard ratio, 2.9; 95% confidence interval, 0.2-4.7). The results of this study suggest that the extranodal invasion and negative ER status should potentially be considered when evaluating the risk of LRR. The predictive power of intrinsic subtypes for LRR is less than that of classical pathological indicators. This information may be useful in planning management of LRR in early breast cancer patients treated with mastectomy.