Higher Residual Cancer Burden Research Articles

Association of antibiotic exposure with residual cancer burden in HER2-negative early stage breast cancer

Antibiotic exposure during immunotherapy (IO) has been shown to negatively affect clinical outcomes in various cancer types. The aim of this study was to evaluate whether antibiotic exposure in patients with high-risk early-stage HER2-negative breast cancer (BC) undergoing treatment with neoadjuvant pembrolizumab impacted residual cancer burden (RCB) and pathologic complete response (pCR) in the pembrolizumab-4 arm of the ISPY-2 clinical trial. Patients received pembrolizumab for four cycles concurrently with weekly paclitaxel for 12 weeks, followed by four cycles of doxorubicin plus cyclophosphamide every 2 or 3 weeks. Patients who received at least one dose of systemic antibiotics concurrently at the time of immunotherapy (IO) were included in the antibiotic exposure group (ATB+). All other participants were included in the control group (ATB-). RCB index and PCR rates were compared between the ATB+ and ATB- groups using t-tests and Chi-squared tests, and linear and logistic regression models, respectively. Sixty-six patients were included in the analysis. 18/66 (27%) patients were in the ATB+ group. Antibiotic use during IO was associated with a higher mean RCB index (1.80 ± 1.43 versus 1.08 ± 1.41) and a lower pCR rate (27.8% versus 52.1%). The association between antibiotic use and the RCB index remained significant in multivariable linear regression analysis (RCB index-coefficient 0.86, 95% CI 0.20–1.53, P = 0.01). Our findings suggest that concurrent antibiotic exposure during neoadjuvant pembrolizumab in HER2-negative early-stage BC is associated with higher RCB. Further validation in larger cohorts is needed to confirm these findings.

ARNEO: A Randomized Phase II Trial of Neoadjuvant Degarelix with or Without Apalutamide Prior to Radical Prostatectomy for High-risk Prostate Cancer

BackgroundHigh-risk prostate cancer (PCa) patients have a high risk of biochemical recurrence and metastatic progression following radical prostatectomy (RP). ObjectiveTo determine the efficacy of neoadjuvant degarelix plus apalutamide before RP compared with degarelix with a matching placebo. Design, setting, and participantsARNEO was a randomized, placebo-controlled, phase II neoadjuvant trial before RP performed between March 2019 and April 2021. Eligible patients had high-risk PCa and were amenable to RP. InterventionPatients were randomly assigned at a 1:1 ratio to degarelix (240–80–80 mg) + apalutamide (240 mg/d) versus degarelix + matching placebo for 3 mo followed by RP. Prior to and following neoadjuvant treatment, pelvic 18F-PSMA-1007 positron emission tomography (PET)/magnetic resonance imaging (MRI) was performed. Outcome measurements and statistical analysisThe primary endpoint was the difference in proportions of patients with minimal residual disease (MRD; = residual cancer burden (RCB) ≤0.25 cm3 at final pathology). Secondary endpoints included differences in prostate-specific antigen responses, pathological staging, and change in TNM stage on prostate-specific membrane antigen (PSMA) PET/MRI following hormonal treatment. Biomarkers (immunohistochemical staining on prostate biopsy [PTEN, ERG, Ki67, P53, GR, and PSMA] and PSMA PET/MRI-derived characteristics) associated with pathological response (MRD and RCB) were explored. Results and limitationsPatients were randomized to neoadjuvant degarelix + apalutamide (n = 45) or degarelix + matching placebo (n = 44) for 12 wk and underwent RP. Patients in the degarelix + apalutamide arm achieved a significantly higher rate of MRD than those in the control arm (38% vs 9.1%; relative risk [95% confidence interval] = 4.2 [1.5–11], p = 0.002). Patients with PTEN loss in baseline prostate biopsy attained significantly less MRD (11% vs 43%, p = 0.002) and had a higher RCB at final pathology (1.6 vs 0.40 cm3, p < 0.0001) than patients without PTEN loss. Following neoadjuvant hormonal therapy, PSMA PET–estimated tumor volumes (1.2 vs 2.5 ml, p = 0.01) and maximum standardized uptake value (SUVmax; 4.3 vs 5.7, p = 0.007) were lower in patients with MRD than in patients without MRD. PSMA PET–estimated volume and PSMA PET SUVmax following neoadjuvant treatment correlated significantly with RCB at final pathology (both p < 0.001). ConclusionsIn high-risk PCa patients, neoadjuvant degarelix plus apalutamide prior to RP results in a significantly improved pathological response (MRD and RCB) compared with degarelix alone. Our trial results provide a solid hypothesis-generating basis for neoadjuvant phase 3 trials, which are powered to detect differences in long-term oncological outcome following neoadjuvant androgen receptor signaling inhibitor therapy. Patient summaryIn this study, we looked at the difference in pathological responses in high-risk prostate cancer patients treated with degarelix plus apalutamide or degarelix plus matching placebo prior to radical prostatectomy. We demonstrated that patients treated with degarelix plus apalutamide achieved a significantly better tumor response than patients treated with degarelix plus matching placebo. Long-term follow-up is required to determine whether improved pathological outcome translates into better oncological outcomes.

Abstract P2-01-05: Impact of post-treatment ctDNA and residual cancer burden (RCB) on outcomes in patients with triple-negative breast cancer (TNBC) and residual disease

Abstract Introduction: Residual disease (RD) after neoadjuvant chemotherapy (NACT) is associated with high risk of recurrence in TNBC. RCB classification is prognostic in patients with RD. Recent studies show that post-NACT circulating cell-free tumor DNA (ctDNA) also provides prognostic information in patients with RD. Most TNBC patients with RD receive adjuvant therapy after surgery (chemotherapy and/or radiation), thus ctDNA status at completion of all adjuvant therapy (end of treatment, EOT) may be a better indicator of long-term prognosis. Furthermore, the impact of EOT ctDNA status on prognosis in context of RCB is of interest. Utilizing data from a prospective registry, the objective of this study was to investigate the impact of EOT ctDNA status and RCB class on outcomes in TNBC patients with RD. We hypothesized that RCB and EOT ctDNA status may provide complementary prognostic information. Methods: Study population included TNBC patients with RD post-NACT and available EOT plasma samples who were enrolled in an IRB-approved multisite prospective registry between 2011 and 2018. EOT samples were collected after completion (1-6 months) of all curative treatment (local and systemic). ctDNA was isolated and subjected to next generation sequencing (QIAseq 275-gene Human Comprehensive Cancer Panel on an Illumina NextSeq 550). Samples demonstrating pathogenic/likely pathogenic variant(s) with 3-40% allelic frequencies were considered ctDNA positive. Variants with allelic frequencies ≥40% were included in ctDNA positive status only if not present in ClinVar8/dbSNP9 as a known germline variant. The impact of EOT ctDNA status and RCB on event-free survival (EFS) and overall survival (OS) were estimated according to the Kaplan-Meier method and compared among groups by log-rank test, followed by Cox regression analysis. Results: For 47 TNBC patients with RD and available EOT plasma sample, the median age was 47 years, and 43% had node-positive disease at diagnosis. RCB class distribution was as follows: RCB I=28%, RCB II=49%, RCB III=15%, RCB unknown=8%. 45% of patients received adjuvant chemotherapy (59% with RCB II-III received adjuvant chemotherapy), and 68% received adjuvant radiation. EOT ctDNA was positive in 34% (16/47) of patients and was associated with higher T stage (p=0.012), TNM stage (p=0.033) and trend toward higher RCB class (p=0.078). ctDNA positivity rates in RCB I, II and III classes were 23%, 30% and 71%, respectively. Among all patients, 3-year EFS and OS were 71% and 73%, respectively. Table 1 provides 3-year EFS and OS by ctDNA status in all patients and by RCB class. ctDNA positive status was associated with inferior EFS and OS. Conclusion: EOT ctDNA positivity was noted in one-third of TNBC patients with residual disease and was highly prognostic, with almost half of patients with ctDNA positivity suffering an EFS event by 3 years. Patients with RCB III had very poor outcome (3-year EFS ≤20%) regardless of ctDNA status. However, in RCB classes I/II, ctDNA provided further prognostic utility, as ctDNA negative patients with RCB I/II had excellent outcomes (3-year EFS &amp;gt;90%). These findings should be confirmed in other studies and provide insights into the role of ctDNA for patient stratification/selection in residual disease adjuvant therapy intensification trials for TNBC. 3-year EFS3-year OSAll patients: ctDNA positive vs ctDNA negative56% vs 78%, HR 3.02 (95% CI: 1.01-9.01), p=0.03856% vs 82%, HR 3.05 (95% CI: 1.02-9.13), p=0.037RCB I/II: ctDNA positive vs ctDNA negative73% vs 92%, HR 4.38, p=0.07873% vs 92%, HR 3.03, p=0.159RCB III: ctDNA positive vs ctDNA negative0% vs 20%, HR 1.67, p=0.5610% vs 20%, HR 1.30, p=0.765 Citation Format: Priyanka Sharma, Shane R Stecklein, Bruce F Kimler, Rachel Yoder, Kelsey Schwensen, Joshua M Staley, Qamar J Khan, Anne P O'Dea, Lauren E Nye, Manana Elia, Jaimie Heldstab, Trisha Home, Stephen Hyter, Kamilla Isakova, Harsh B Pathak, Andrew K Godwin. Impact of post-treatment ctDNA and residual cancer burden (RCB) on outcomes in patients with triple-negative breast cancer (TNBC) and residual disease [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 P2-01-05.

Persistence of ctDNA in Patients with Breast Cancer During Neoadjuvant Treatment Is a Significant Predictor of Poor Tumor Response.

Accurate response assessment during neoadjuvant systemic treatment (NST) poses a clinical challenge. Therefore, a minimally invasive assessment of tumor response based on cell-free circulating tumor DNA (ctDNA) may be beneficial to guide treatment decisions. We profiled 93 genes in tissue from 193 patients with early breast cancer. Patient-specific assays were designed for 145 patients to track ctDNA during NST in plasma. ctDNA presence and levels were correlated with complete pathological response (pCR) and residual cancer burden (RCB) as well as clinicopathologic characteristics of the tumor to identify potential proxies for ctDNA release. At baseline, ctDNA could be detected in 63/145 (43.4%) patients and persisted in 25/63 (39.7%) patients at mid-therapy (MT) and 15/63 (23.8%) patients at the end of treatment. ctDNA detection at MT was significantly associated with higher RCB (OR = 0.062; 95% CI, 0.01-0.48; P = 0.0077). Of 31 patients with detectable ctDNA at MT, 30 patients (96.8%) were nonresponders (RCB II, n = 8; RCB III, n = 22) and only one patient responded to the treatment (RCB I). Considering all 145 patients with baseline (BL) plasma, none of the patients with RCB 0 and only 6.7% of patients with RCB I had ctDNA detectable at MT, whereas 30.6% and 29.6% of patients with RCB II/III, respectively, had a positive ctDNA result. Overall, our results demonstrate that the detection and persistence of ctDNA at MT may have the potential to negatively predict response to neoadjuvant treatment and identify patients who will not achieve pCR or be classified with RCB II/III.

Prognostic factors in triple-negative breast cancer: a retrospective cohort.

Triple-negative breast cancer (TNBC) is characterized by lack of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) expression and accounts for 15-20% of all breast cancers. This study aims to analyze prognostic factors related to a reduction in overall survival (OS), disease-free survival (DFS), and risk of mortality and recurrence in TNBC. This is a retrospective observational cohort study. Medical records of 532 patients with breast cancer diagnosed from 2007 to 2020 were analyzed. Of these patients, 93 (17%) were women with TNBC. Ten medical records were excluded, and the final sample was composed of 83 women with TNBC. OS and DFS were estimated by the Kaplan-Meier model. Univariate analysis (log-rank test) and multivariate analysis (Cox regression) were used to examine prognostic factors related to a statistically significant reduction (p<0.05) in OS and DFS and increased risk of mortality and tumor recurrence. Smoking, advanced clinical stage, larger tumor size, angiolymphatic invasion, positive sentinel lymph node, axillary node involvement, higher cancer burden, surgical treatment with mastectomy, and recurrence were related to a significant decrease in OS and/or DFS and increased risk of mortality and/or recurrence in TNBC. The 10-year OS and DFS was around 61 and 65%, respectively. Advanced clinical stage, positive sentinel lymph node, axillary node involvement, surgical treatment with mastectomy, and higher residual cancer burden were related to a significant reduction in OS and DFS and increased risk of mortality and recurrence in TNBC.

PD-L1 Expression after Neoadjuvant Chemotherapy in Triple-Negative Breast Cancers Is Associated with Aggressive Residual Disease, Suggesting a Potential for Immunotherapy

Simple SummaryImmune checkpoint inhibitors (ICI) are now part of the therapeutical arsenal for cancers at several sites and in several settings. PD-L1 expression is assessed to predict treatment response. We used immunohistochemistry (E1L3N clone) to assess PD-L1 expression on tumor and immune cells from a cohort of 89 surgical specimens of T1-T3NxM0 triple-negative breast cancers (TNBC) from patients treated with neoadjuvant chemotherapy (NAC) with residual disease. PD-L1 expression levels were low in tumor and immune cells from post-NAC surgical specimens. PD-L1 positivity in tumor cells was significantly associated with aggressive post-NAC tumor characteristics. A small subset of TNBC patients displaying PD-L1 expression in the context of a more extensive post-NAC tumor burden could benefit from ICI treatment after NAC.The consequences of neoadjuvant chemotherapy (NAC) for PD-L1 activity in triple-negative breast cancers (TNBC) are not well-understood. This is an important issue as PD-LI might act as a biomarker for immune checkpoint inhibitors’ (ICI) efficacy, at a time where ICI are undergoing rapid development and could be beneficial in patients who do not achieve a pathological complete response. We used immunohistochemistry to assess PD-L1 expression in surgical specimens (E1L3N clone, cutoff for positivity: ≥1%) on both tumor (PD-L1-TC) and immune cells (PD-L1-IC) from a cohort of T1-T3NxM0 TNBCs treated with NAC. PD-L1-TC was detected in 17 cases (19.1%) and PD-L1-IC in 14 cases (15.7%). None of the baseline characteristics of the tumor or the patient were associated with PD-L1 positivity, except for pre-NAC stromal TIL levels, which were higher in post-NAC PD-L1-TC-positive than in negative tumors. PD-L1-TC were significantly associated with a higher residual cancer burden (p = 0.035) and aggressive post-NAC tumor characteristics, whereas PD-L1-IC were not. PD-L1 expression was not associated with relapse-free survival (RFS) (PD-L1-TC, p = 0.25, and PD-L1-IC, p = 0.95) or overall survival (OS) (PD-L1-TC, p = 0.48, and PD-L1-IC, p = 0.58), but high Ki67 levels after NAC were strongly associated with a poor prognosis (RFS, p = 0.0014, and OS, p = 0.001). A small subset of TNBC patients displaying PD-L1 expression in the context of an extensive post-NAC tumor burden could benefit from ICI treatment after standard NAC.

Impact of antibiotics on residual cancer burden and pathologic response rates during neoadjuvant pembrolizumab in breast cancer (BC).

e12622 Background: Antibiotic exposure during immunotherapy has been shown to negatively affect clinical outcomes in metastatic melanoma and non-small cell lung cancer. We tested whether antibiotics exposure during neoadjuvant pembrolizumab (NA-P) affects residual cancer burden (RCB) and pathologic complete response rate (pCR) in the pembrolizumab-4 arm of the ISPY-2 trial. Methods: I-SPY2 is an adaptively-randomized, ph-II trial in patients with high-risk, stage II/III breast cancer (BC). In pembrolizumab-4 arm patients with HER2-negative BC received NA-P 200mg every 3 weeks for four cycles concurrently with 80mg/m2 paclitaxel weekly for 12 weeks, followed by four cycles of 60mg/m2 doxorubicin plus 600mg/m2 cyclophosphamide every 2 weeks. Data on antibiotic use during NA-P was reviewed. Patients who received at least one dose of systemic antibiotics were included in the antibiotic exposure group (ATB+). All other patients were included in the no exposure group (ATB-). RCB index was used to evaluate RCB as a continuous variable. A higher RCB index indicated higher RCB. RCB index and pCR rates were compared between ATB+ and ATB- groups. Association of antibiotic use with RCB and pCR rates was evaluated using linear regression and logistic regression respectively. Clinical variables for adjustment were age, stage and hormone receptor (HR) status. Results: 69 patients received NA-P with chemotherapy. All patients had HER2-negative BC. One patient was excluded due to missing data on antibiotics. 68 patients were included in the final analysis. 19/68 (28%) patients were in the ATB+ group. Antibiotic use in HR+ and HR- patients were 9/19 (47%) and 31/49 (63%) respectively ( P=0.23). Compared to ATB- group, patients in the ATB+ group had higher mean RCB index (1.05 vs 1.80, P=0.04) and lower pCR rate (53.1% vs 26.3%, P=0.05). Antibiotic use was associated with higher probability of RCB in univariate analysis (Coefficient estimate CE: 0.75, 95% CI 0.01-1.48, P=0.04) and multivariable analysis (CE: 0.89, 95% CI 0.11-1.65, P=0.02). HR positivity was independently associated with higher probability of RCB (CE: 1.07, 95% CI 0.38-1.77 P=0.002). Antibiotic use was associated with higher probability of not having pCR (Odds ratio 3.17, 95% CI 0.99-10.15, P=0.05). Conclusions: Patients with antibiotic exposure during NA-P in HER2-negative early stage BC were associated with higher RCB and lower pCR rates. Further validation in a larger independent cohort is needed to confirm these findings.

Abstract P2-14-01: The impact of local therapy on locoregional recurrence in women with high risk breast cancer in the neoadjuvant I-SPY2 TRIAL

Abstract Background: In women with breast cancer receiving neoadjuvant chemotherapy, residual cancer burden (RCB) predicts distant recurrence and survival. In those with high risk tumors, locoregional recurrence (LRR) remains a concern, and has been associated with type of local therapy received. We evaluated the impact of local therapy on LRR in the ISPY-2 TRIAL. Methods: Data were analyzed in Stata 14.2, using Chi2 test, log rank test, and a Cox proportional hazards model. RCB was considered a categorical variable (0/1 versus 2/3), as described in prior publications. Breast surgery categories were lumpectomy +/- radiotherapy, or mastectomy +/- radiotherapy. Axillary surgery was defined as sentinel lymph node (SLN) surgery (≤6 nodes removed) or axillary dissection (&amp;gt;6 nodes). Results: Follow up data from the I-SPY2 TRIAL were available for 630 patients (median follow up 2.76 yrs, range 0.4-7.2). Type of local therapy was significantly associated with clinical stage at presentation, with stage III patients most frequently undergoing mastectomy + radiation (p&amp;lt;0.001). Women with higher RCB were more likely to undergo mastectomy than those with lower RCB (61.3% vs 48.8% mastectomy rate, p=0.002), and more likely to receive adjuvant radiotherapy (62.0% vs 53.9%, p=0.048). There was no association between clinical stage, type of surgery, or radiotherapy and LRR (Table). Higher RCB was significantly associated with LRR, with 3 year locoregional recurrence free rate of 95.1% in RCB 0/1 versus 89.9% in RCB 2/3 (p=0.003). In a Cox model adjusting for clinical stage, tumor subtype, surgical therapy, RCB status, nodal radiation, and age, significant predictors for LRR were tumor subtype and RCB status. Hazard ratio (HR) for LRR in those with RCB 0/1 was 0.39 compared to those with RCB 2/3 (95% CI 0.17-0.87, p=0.021). There was no difference in LRR between breast conservation and mastectomy; within the breast conservation group, those who had lumpectomy alone had higher hazard of LRR compared to those having lumpectomy + radiation (HR 3.1, 95% CI 1.1-9.2, p=0.043). Conclusions: Extent of surgical therapy was not associated with local tumor control, regardless of advanced tumor stage at presentation. Rather, tumor biology and response to therapy were the best predictors of LRR. These data highlight the opportunity to minimize the morbidity of extensive surgical therapy for patients with excellent response to systemic therapy. LRR rates by clinical features and treatment status FrequencyLRR RateP valueClinical Stage 0.5I240 (47.5%)5.8% II185 (36.6%)8.7% III80 (15.8%)6.3% Tumor Subtype 0.014ER+PR+Her2-161 (26.4%)3.1% ER+PR-Her2-56 (9.2%)3.6% Her2+176 (28.9%)6.3% Triple negative216 (35.5%)11.1% Local therapy 0.169Lumpectomy85 (13.5%)11.8% Lumpectomy with radiation198 (31.4%)5.6% Mastectomy173 (27.5%)5.2% Mastectomy with radiation174 (27.6%)8.6% Axillary surgery 0.23None5 (0.8%)20% SLN329 (52.2%)5.8% ALND296 (47%)8.5% Axillary radiation 0.535Yes42 (6.7%)9.5% No588 (93.3%)7.0% Axillary management 0.2No surgery or radiation5 (0.8%)20.0% SLN312 (50%)5.3% SLN+Axillary radiation17 (2.7%)8.3% ALND271 (43%)10.3% ALND+Axillary radiation25 (4%)5.4% RCB 0.0020/1293 (50.1%)3.8% 2/3292 (49.9%)10.3% Citation Format: Silverstein J, Suleiman L, Yau C, Price ER, Singhrao R, Yee D, DeMichele A, Isaacs C, Albain KS, Chien AJ, Forero-Torres A, Wallace AM, Pusztai L, Ellis ED, Elias AD, Lang JE, Lu J, Han HS, Clark AS, Korde L, Nanda R, Northfelt DW, Khan QJ, Viscusi RK, Euhus DM, Edmiston KK, Chui SY, Kemmer K, Wood WC, Park JW, Liu MC, Olopade O, Leyland-Jones B, Tripathy D, Moulder SL, Rugo HS, Schwab R, Lo S, Helsten T, Beckwith H, I-SPY 2 TRIAL Consortium, Berry DA, Asare SM, Esserman LJ, Boughey JC, Mukhtar RA. The impact of local therapy on locoregional recurrence in women with high risk breast cancer in the neoadjuvant I-SPY2 TRIAL [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-14-01.

Study of the PD-L1 status in breast cancer, by using the SP142 monoclonal antibody, and the prospects for determining treatment policy

To investigate the expression of programmed death ligand 1 (PD-L1) in triple-negative and luminal B, HER2-negative breast cancer, by using the SP142 antibody and to assess the association of the PD-L1 status with prognosis for patients. The study was conducted using surgical materials (full sections) obtained from 72 patients. The sections were stained with the SP142 PD-L1 antibody. Differences were found in the detection rates of the PD-L1-positive status in the primary tumor and regional metastasis (primary tumor in 26 (36.1%) cases and metastasis in 18 (47.4%) of the 38 cases). By and large, the PD-L1-positive status was less common in the patients receiving neoadjuvant chemotherapy (25.8% versus 53.7%); however, it should be noted that the PD-L1-positive status was more often detected in those who had a higher residual cancer burden (RCB) (RCB-III versus RCB-II). Considering the findings, it is necessary to clarify the status of not only a primary focus, but also clinically significant metastases, especially if the primary tumor has yielded a negative result. The patients with disease progression who receive standard therapy regimens may have a chance for a good result when using PD-1/PD-L1 blockers. At the same time, the association of the PD-L1 status with RCB may affect the choice of adjuvant treatment policy.

Residual cancer burden (RCB) is practical and may be more informative than pathological response following neoadjuvant chemotherapy (NC) for locally advanced breast cancer (LABC)

21103 Background: Complete pathological response (pCR) has been considered a reliable endpoint to assess the benefit of NC. However, different pathological responses ranging from near complete response to resistance would likely indicate different prognostic groups. Method: We studied patients with locally advanced breast cancer (LABC) who received NC between 2001–2006 at the University of Cincinnati. Pathological response to therapy was evaluated. In addition, RCB was quantified according to MD Anderson RCB Calculator index that combines pathologic measurements of primary tumor (size and cellularity) and nodal metastases (number and size). We examined the correlation between pCR, RCB, event-free survival (EFS) and over all survival (OS) by Cox regression analyses. Result: Pathological slides of 32 patients were analyzed. Median age 52, 38% white and 62% African American. Stage IIB 12% , Stage IIIA 19%, Stage IIIB 53% and Stage IIIC 16% . 72% invasive ducal, 6% invasive lobular and 22% inflammatory cancer. Forty seven percent of tumors were ER +/or PR+ , 53% ER-/PR-, 28% HER-2 /neu + ( IHC 3+ or FISH HER2 gene to chromosome 17 ration &gt; 2.2). Tumor response was as follows: 22% (n=7) achieved pCR , RCB scores ranged between 0- 4.87. By univariate Cox regression analysis, RCB correlated with EFS {Hazard ratio (HR) 1.57 (95% CI 1.04–2.38), p-value 0.018}, and with OS {HR 1.74 (95% CI 0.91 -3.32), p value-0.09}. However, pCR did not seem to correlate with EFS {HR 0 .24 (95%CI 0.03 -1.86–2.38), p-value .172} or OS {HR 0.03 (95% CI 0–89),p value-0.40}. By multivariate Cox regression analysis, RCB was noted to be an independent predictive variable for EFS {HR 1.59 (95% CI 1.04–2.43), p value-0.033} while pCR was not {HR 0.90 (95% CI 0.52–1.57), p value-0.7. Conclusion: RCB was easily quantifiable and appears to be a better predictor of outcome following neoadjuvant chemotherapy in LABC compared to pCR. Higher RCB scores were associated with higher EFS and lower rate of OS. Prospective trials are needed to further evaluate the role of RCB as an endpoint following NC. No significant financial relationships to disclose.