Axillary Pathologic Complete Response Research Articles

Axillary Pathologic Complete Response After Neoadjuvant Systemic Therapy by Breast Cancer Subtype in Patients With Initially Clinically Node-Positive Disease

An overview of rates of axillary pathologic complete response (pCR) for all breast cancer subtypes, both for patients with and without pathologically proven clinically node-positive disease, is lacking.To provide pooled data of all studies in the neoadjuvant setting on axillary pCR rates for different breast cancer subtypes in patients with initially clinically node-positive disease.The electronic databases Embase and PubMed were used to conduct a systematic literature search on July 16, 2020. The references of the included studies were manually checked to identify other eligible studies.Studies in the neoadjuvant therapy setting were identified regarding axillary pCR for different breast cancer subtypes in patients with initially clinically node-positive disease (ie, defined as node-positive before the initiation of neoadjuvant systemic therapy).Two reviewers independently selected eligible studies according to the inclusion criteria and extracted all data. All discrepant results were resolved during a consensus meeting. To identify the different subtypes, the subtype definitions as reported by the included articles were used. The random-effects model was used to calculate the overall pooled estimate of axillary pCR for each breast cancer subtype.The main outcome of this study was the rate of axillary pCR and residual axillary lymph node disease after neoadjuvant systemic therapy for different breast cancer subtypes, differentiating studies with and without patients with pathologically proven clinically node-positive disease.This pooled analysis included 33 unique studies with 57 531 unique patients and showed the following axillary pCR rates for each of the 7 reported subtypes in decreasing order: 60% for hormone receptor (HR)-negative/ERBB2 (formerly HER2)-positive, 59% for ERBB2-positive (HR-negative or HR-positive), 48% for triple-negative, 45% for HR-positive/ERBB2-positive, 35% for luminal B, 18% for HR-positive/ERBB2-negative, and 13% for luminal A breast cancer. No major differences were found in the axillary pCR rates per subtype by analyzing separately the studies of patients with and without pathologically proven clinically node-positive disease before neoadjuvant systemic therapy.The HR-negative/ERBB2-positive subtype was associated with the highest axillary pCR rate. These data may help estimate axillary treatment response in the neoadjuvant setting and thus select patients for more or less invasive axillary procedures.

Sentinel lymph node BIOPSY after neoadjuvant therapy in breast cancer patients with lymph node involvement at diagnosis. Could wire localization of clipped node improve our results?

IntroductionSentinel lymph node biopsy (SLNB) after neoadjuvant therapy (NAT) in node-positive (N+) breast cancer patients at diagnosis remains a controversial issue, with no consensus on implementation or safety. ObjectivesWe sought to assess the accuracy of SLNB after NAT in biopsy-proven N+ cases at diagnosis and the efficacy and accuracy of wire localization of the clipped node to improve results. Material and methodsA cross-sectional diagnostic technique validation study in N+ patients following NAT was performed. The biopsy-proven affected lymph node was clipped at diagnosis. SLNB and axillary lymph node dissection (ALND) were performed in cases of clinical-radiological lymph node response after NAT. For the purposes of our study we added wire localization of the clipped node. Results103 patients were included (mean age, 54.4 years [± 12.7]). Wire marking was performed in 28 cases. The overall identification rate (IR) of SLN was 81.6%. The median number of nodes removed was 2 (range 2). The overall false negative rate (FNR) was 6.1%. Sensitivity and overall accuracy were 93.9% and 95.2%, respectively (area under curve 0.97). In the double-marked (clip and wire) group the FNR decreased to 0% and accuracy was 100%. Axillary pathologic complete response was observed in 24.3% of cases. ConclusionsSLNB is useful in node-positive patients at diagnosis who respond to NAT. Combining this with preoperative wire localization of the biopsied lymph node reduces the FNR without increasing the number of complications.

Abstract PS13-19: Achieving a pathologically negative axilla after neoadjuvant chemotherapy for breast cancer is associated with presenting tumor size and subtype

Abstract Introduction: Axillary pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) confers higher overall and recurrence-free survival, compared to residual axillary disease. Recent findings suggest that pCR in the breast (ypT0) post-NAC is associated with a pathologically negative axilla (ypN0) in patients (pts) presenting with lower stage HER2+ and triple negative breast cancer (TNBC). Additional studies are needed to understand how clinical T (cT) and N (cN) staging are associated with ypN0 in other tumor subtypes, including hormone-receptor (HR) positive tumors. The ability to reliably predict axillary pathologic response post-NAC may allow identification of a subset of pts for whom axillary staging may be safely omitted. We hypothesize that tumor subtype and lower clinical stage at presentation are associated with ypN0. Methods: A single institution cancer registry was retrospectively reviewed for pts receiving NAC followed by surgery from January 2010-June 2018. Fisher’s exact tests were used to compared proportion of breast and axillary pCR by tumor subtype (TNBC, HR+/HER2-, HR+/HER2+ and HR-/HER2+). Univariable logistic regression determined factors associated with ypN0. Multivariable logistic regression determined the association between ypN0 and tumor subtype adjusting for factors that retained significance on univariable analysis. Sensitivity analyses determined how cN status affected ypN status by tumor subtype. Results: Of the 1348 pts who received NAC followed by surgery, median age was 54 (IQR 44-63); 59% (n=738) were postmenopausal. Proportion of tumor subtypes were: 15% (n=197) TNBC, 12% (n=155) HR+/HER2-, 48% (n=653) HR+/HER2+, and 25% (n=343) HR-/HER2+. Tumor size at diagnosis was: 1% (n=18) T0, 20% (n=272) T1, 53% (n=713) T2, 17% (n=230) T3 and 9% (n=111) T4. Clinical nodal staging at diagnosis was: 52% cN0 (n=695), 41% cN1 (n=550), 5% cN2 (n=61), and 3% cN3 (n=43). TNBC and HER2+ subtypes were associated with the highest rate of breast pCR and ypN0. On univariable analyses of the cN positive pts, younger age at diagnosis, non-postmenopausal status, oral contraceptive use, alcohol consumption, cT stage, cN stage and tumor subtype were significantly associated with ypN0 (Table1A). In the adjusted model, postmenopausal status, cT, and tumor subtype were associated with ypN0. Lower cT and HR- subtypes had significantly higher odds of ypN0 (Table 1B). In sensitivity analyses, cN2/cN3 was associated with lower odds of ypN0 compared to cN0/cN1 disease in TNBC (OR0.11 95%CI 0.03,0.40, p=0.001), HR-/HER2+ disease (OR0.42, 95%CI 0.22,0.77, p=0.005), and HR+/HER2+ (OR0.26 95%CI 0.11,0.61 p=0.002), but not in HR+/HER2- disease (OR1.17, 95%CI 0.25,5.57, p=0.838). Conclusion: HR- and low cT stage at diagnosis are associated with ypN0 in this large cohort. Younger age, pre-menopausal status and cN stage may be important considerations in future investigations aimed at defining the subset of patients most likely to achieve ypN0 and ultimately to be considered for de-escalation of axillary staging post NAC. A.Univariable logistic regression analysisVariableOdds Ratio95% Confidence Intervalp valueAge at diagnosis0.990.98, 0.99<0.001RaceWhite1.060.70, 1.600.777Black0.600.17, 2.080.421Asian1.200.36, 4.000.768Postmenopausal0.760.60, 0.960.023BMI1.000.99. 1.000.424Oral contraceptive use1.250.95, 1.630.114Alcohol consumption1.601.05, 2.440.027 Tobacco use1.130.99, 1.290.064Family history of cancer1.250.92, 1.680.148Grade12.170.75, 6.250.15320.950.45, 2.010.89131.700.81, 3.590.163HistologyIDC1.451.10, 1.890.007ILC0.370.23, 0.60<0.001Mixed0.950.68, 1.320.764Other0.440.18, 1.080.073Clinical T stage11.370.47, 3.980.56920.760.27, 2.160.60530.350.12, 1.020.05540.150.05, 0.450.001Clinical N stage10.140.11, 0.18<0.00120.130.07, 0.23<0.00130.110.06, 0.21<0.001Tumor subtypeTNBC1.591.00, 2.530.049HR+/ HER2 -0.550.35, 0.870.010HR+/ HER2+0.690.47, 1.000.049HR-/ HER2 +1.641.09, 2.460.019B.Multivariable logistic regression analysisAge at diagnosis0.980.97, 0.99<0.001Alcohol use1.190.74, 1.930.476HistologyIDC1.150.82, 1.610.414ILC0.570.32, 1.010.053Mixed1.080.71, 1.630.721Other0.790.28, 2.220.660Clinical T stage11.190.39, 3.580.76120.740.25, 2.160.58530.510.17, 1.540.23540.290.09, 0.910.034Clinical N stage10.130.10, 0.18<0.00120.140.08, 0.26<0.00130.100.05, 0.20<0.001Tumor subtypeTNBC1.440.84, 2.470.181HR+/ HER2 -0.540.31, 0.940.028HR+/ HER2+0.600.39, 0.930.024HR-/ HER2 +1.701.05, 2.730.030 Citation Format: Sara P Myers, Gillian M Ahrendt, Joanna S Lee, Jennifer G Steiman, Atilla Soran, Ronald R Johnson, Priscilla F McAuliffe, Emilia J Diego. Achieving a pathologically negative axilla after neoadjuvant chemotherapy for breast cancer is associated with presenting tumor size and subtype [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS13-19.

Abstract PS1-29: Predicting axillary pathologic response to neoadjuvant chemotherapy for node-positive breast cancer: Clinical predictive model by using MRI and ultrasound

Abstract Purpose: Neoadjuvant chemotherapy (NAC) has been shown to eradicate axillary lymph node metastasis in approximately 40% of patients. Sentinel lymph node biopsy (SLNB) could be an alternative surgical approach for these patients to avoid morbidity from axillary lymph node dissection (ALND). However, high false-negative rates of SLNB for initially node-positive patients were reported in previous trials. The aim of this study was to evaluate clinicopathological factors and imaging characteristics by MRI and ultrasound (US) as predictors of axillary pathologic complete response (ypN0) after NAC, which enable to identify candidates for SLNB in patients with clinically node-positive disease. Patients and methods: We identified 153 patients with clinically node-positive breast cancer who received NAC from May 2009 to December 2019. Clinicopathological data including age, clinical T/N status, nuclear grade, hormone receptor (HR) and HER2 status were collected. All patients underwent MRI and US before and after NAC. Patients were judged to be node-positive when they have cytologically-proven nodal disease by fine-needle aspiration (FNA) or suspicious lymph nodes by diagnostic imaging. Lymph nodes with cortical thickness (>3.5mm), loss of fatty hilum or round shape (short-axis/long-axis ratio > 0.5) were defined as suspicious lymph nodes. All imaging data were evaluated at baseline and after NAC. To develop a predictive model for ypN0, the association between ypN0 status and clinicopathological and imaging characteristics were assessed by multivariate logistic regression analysis. The area under the receiver operating characteristic (ROC) curve was used to evaluate discrimination by the model. Results: The median age was 55.0 (range: 22-79) years and the mean tumor size was 3.86 ± 2.04 cm. Pretherapeutic lymph node status was assessed by FNA in 88 (57.5%) patients. Of 153 patients, 80 (52.3%) patients had luminal, 39 (25.5%) had HER2-positive, and 34 (22.2%) had triple negative disease. Sequential anthracycline and taxane were administered for 138 (90.2%) patients, and 37 (94.9%) patients with HER2-positive-disease received concomitant anti-HER2 agents preoperatively. Overall, 62 (40.5%) patients achieved ypN0. Independent predictors of ypN0 status were breast complete response by MRI (odds ratio [OR]: 9.01, p<0.001), clinical stage N1 (OR: 6.64 vs. cN2-3, p=0.009), absence of lymphadenopathy after NAC (OR: 6.09, p<0.001), HR negativity (OR: 3.10, p=0.02) and HER2 positivity (OR: 2.87, p=0.04). In a model using these predictors, the area under the ROC curve was 0.870 (95% confidence interval: 0.814-0.925, p<0.001). Sensitivity, specificity, positive predictive value and negative predictive value of the model were 72.6%, 86.8%, 78.9% and 82.3%, respectively. After a median follow-up of 49.7 months, 5-year disease-free survival (DFS) was significantly higher in patients who achieved ypN0 than patients with residual axillary disease (88.7% vs. 76.9%, p=0.046). Among 62 patients who achieved ypN0 after NAC, ALND was omitted in 24 (38.7%) patients and irradiation to regional lymph nodes was performed in 8 (33.3%) out of 24 patients. Five-year DFS was comparable between patients with or without ALND (86.8% vs. 91.7%, p=0.815). Conclusions: Our predictive model based on imaging characteristics by MRI and US could help to identify good candidates for omission of ALND after NAC in patients with initially node-positive breast cancer. Citation Format: Akiko Matsumoto, Miki Yamada, Daisuke Tsukahara, Yasuko Umemoto, Hiromitsu Jinno. Predicting axillary pathologic response to neoadjuvant chemotherapy for node-positive breast cancer: Clinical predictive model by using MRI and ultrasound [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-29.

Diagnostic performance of noninvasive imaging for assessment of axillary pathologic complete response after neoadjuvant systemic therapy in clinically node-positive breast cancer: a meta-analysis

Background: Neoadjuvant systemic therapy (NST) can lead to downstaging of axillary lymph node disease. Imaging can potentially provide information about the axillary response to NST and, consequently, tailor the surgical management. The purpose of this study was to perform a systematic review and meta-analysis to determine the diagnostic performance of current noninvasive imaging modalities for assessment of axillary response after NST in clinically node-positive breast cancer patients.

Impact of Breast Cancer Pretreatment Nodal Burden and Disease Subtype on Axillary Surgical Management

BackgroundThe management of clinically node-positive breast cancer after neoadjuvant chemotherapy (NAC) has progressed with the potential to avoid the morbidity of axillary lymph node dissection in patients with complete response to therapy. This study addresses the impact of pretreatment nodal burden and tumor subtype on axillary pathologic complete response (AXpCR) in patients treated with NAC to better inform axillary surgical management. MethodsA prospective database was reviewed to identify clinically node-positive patients who underwent NAC followed by axillary lymph node dissection. Patients were stratified in accordance with abnormal nodal burden on pretreatment axillary imaging defined as low (1-2 nodes) or high (≥3 nodes), and biologic subtype defined by hormone receptor (HR+, HR-) and HER2 (human epidermal growth factor receptor 2) status. The primary outcome was AXpCR. ResultsAXpCR was 43% in the study population. There was no difference in AXpCR between low and high nodal burden groups (44% versus 42%, P = 0.87). Subtype correlated to AXpCR (P < 0.001) with the highest rate (78%) in the HR−/HER2+ group. Overall, HER2+ patients had a significantly higher AXpCR than HER2- subtypes (66% versus 28% P < 0.001). HR and HER2 status were also predictive of AXpCR when comparing patient, tumor, and treatment variables. ConclusionsBiologic subtype better correlated with rates of AXpCR than nodal burden alone with the highest rates of AXpCR in HER2+ patients. Consideration of tumor biology is more informative than nodal burden when evaluating options for axillary management after NAC.

The Role of Oncotype DX® Recurrence Score in Predicting Axillary Response After Neoadjuvant Chemotherapy in Breast Cancer.

Oncotype DX® recurrence score (RS) is well-recognized for guiding decision making in adjuvant chemotherapy; however, the predictive capability of this genomic assay in determining axillary response to neoadjuvant chemotherapy (NCT) has not been established. Using the National Cancer Data Base (NCDB), we identified patients diagnosed with T1-T2, clinically N1/N2, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER +/HER2 -) invasive ductal carcinoma of the breast between 2010 and 2015. Patients with an Oncotype DX® RS who received NCT were included. RS was defined as low (< 18), intermediate (18-30), or high (> 30). Unadjusted and adjusted analyses were performed to determine the association between axillary pathologic complete response (pCR) and RS. This study included a total of 158 women. RS was low in 56 (35.4%) patients, intermediate in 62 (39.2%) patients, and high in 40 (25.3%) patients. The majority of patients presented with clinical N1 disease (89.2%). Axillary pCR was achieved in 23 (14.6%) patients. When stratifying patients with axillary pCR by RS, 11 (47.8%) patients had a high RS, 6 (26.1%) patients had an intermediate RS, and 6 (26.1%) patients had a low RS. Comparing cohorts by RS, 27.5% of patients with high RS tumors had an axillary pCR, compared with only 9.7% in the intermediate RS group, and 10.7% in the low RS group (p = 0.0268). Our findings demonstrate that Oncotype DX® RS is an independent predictor of axillary pCR in patients with ER +/HER2 - breast cancers receiving NCT. A greater proportion of patients with a high RS achieved axillary pCR. These results support Oncotype DX® as a tool to improve clinical decision making in axillary management.

Sentinel Lymph Node Biopsy in Breast Cancer Patients With Pathological Complete Response in the Axillary Lymph Node After Neoadjuvant Chemotherapy

PurposeSentinel lymph node biopsy (SLNB) alone following neoadjuvant chemotherapy (NAC) remains controversial in patients with breast cancer who are initially lymph node-positive. The present study aimed to evaluate the impact of SLNB and axillary lymph node dissection (ALND) on breast cancer recurrence and survival in patients who converted from lymph node-positive to pathological node-negative (ypN0) after NAC.MethodsThis single-center retrospective study included 223 patients who converted to axillary lymph node-negative status after NAC and underwent breast and axillary surgery between January 2006 and December 2015. This study compared the overall survival (OS), disease-free survival (DFS), ipsilateral axillary lymph node recurrence rates and incidence of postoperative complications, especially, arm lymphedema and shoulder stiffness between SLNB and ALND.ResultsThis study included 223 patients with axillary pathological complete response (pCR) after NAC and surgery. The SLNB and ALND groups included 94 and 129 patients, respectively. The median follow-up time was 57 (range, 6–155) in the SLNB group and 99 (range 2–159) months in the ALND group. The corresponding 5-year OS and DFS rates were 96.3% and 94.2% (p = 0.392), and 89.2% and 86.4% (p = 0.671), respectively. Four patients (4.3%) in the SLNB group and nine (7.0%) in the ALND group developed locoregional recurrences. Ipsilateral axillary lymph node recurrence and distant metastasis were observed in one (1.1%) and three (2.3%) patients, and in 10 (10.6%) and 11 (8.5%) patients, respectively. Patients in the ALND group were more likely than their SLNB counterparts to experience complications, such as shoulder stiffness (9 [7.0%] vs. 4 [4.3%] patients, p = 0.57). The rate of lymphedema in the ALND group was three times that in the SLNB group (35 [27.1%] vs. 8 [8.5%] patients, p < 0.001).ConclusionAs an alternative to ALND, SLNB has oncological safety in patients with axillary pathological complete response after NAC.

Discrepancy of Breast and Axillary Pathologic Complete Response and Outcomes in Different Subtypes of Node-positive Breast Cancer after Neoadjuvant Chemotherapy.

Few studies have analyzed the discrepancy between breast pathologic complete response (B-pCR) and axillary node pCR (N-pCR) rates and their impact on survival outcomes in different intrinsic subtypes of early breast cancer after neoadjuvant chemotherapy (NAC). We retrospectively reviewed B-pCR, N-pCR, and total (breast and axillary node) pCR (T-pCR) after NAC to assess the discrepancy and outcomes between 2005 and 2017. A total of 968 patients diagnosed with cT1-4c, N1-2, and M0 breast cancer were enrolled in the study. The median age was 49 years and the median follow-up time was 45 months. Of these patients, 213 achieved T-pCR, 31 achieved B-pCR with axillary node pathologic non-complete response (N-non pCR), 245 achieved N-pCR with breast pathologic non-complete response (B-non pCR), and 479 achieved total (breast and axillary node) pathologic non-complete response (T-non pCR) after NAC. The highest B-pCR and N-pCR rates were found in the hormone receptor-negative, human epidermal growth factor receptor 2-positive HR(-)HER2(+) subtype, while the lowest B-pCR rate was found in the HR(+)HER2(-) subtype. The N-pCR rate was correlated to the B-pCR rate (P<0.001), but was higher than the B-pCR rate in all subtypes. The 5-year overall survival (OS) rates for patients with T-pCR, B-pCR, and N-pCR were 91.2%, 91.7%, and 91.9%, respectively. For non-pCR, non-pCR, and non-pCR, the 5-year OS rates were 73.6%, 78.9%, and 74.7%, respectively (P<0.0001). B-non pCR patients had a lower risk of recurrence than T-non pCR or N-non-pCR patients, although there were no differences in OS among them. In conclusion, the N-pCR rate was higher than the B-pCR rate after NAC in all intrinsic subtypes, and N-non pCR or T-non pCR patients had the worst outcomes.

A study of neutrophil to lymphocyte ratio for the prediction of axillary pathological complete response after neoadjuvant therapy in breast cancer

A study of neutrophil to lymphocyte ratio for the prediction of axillary pathological complete response after neoadjuvant therapy in breast cancer

Diagnostic Performance of Noninvasive Imaging for Assessment of Axillary Response After Neoadjuvant Systemic Therapy in Clinically Node-positive Breast Cancer: A Systematic Review and Meta-analysis.

The purpose of this study was to perform a systematic review and meta-analysis to determine the diagnostic performance of current noninvasive imaging modalities for assessment of axillary response after neoadjuvant systemic therapy (NST) in clinically node-positive breast cancer patients. NST can lead to downstaging of axillary lymph node disease. Imaging can potentially provide information about the axillary response to NST and, consequently, tailor the surgical management. PubMed and Embase were searched for studies that compared noninvasive imaging after NST with axillary surgery outcome to identify axillary response in patients with initial pathologically proven axillary lymph node metastasis. Two reviewers independently screened the studies and extracted the data. A meta-analysis was performed by computing the pooled sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Thirteen studies describing 2380 patients were included for final analysis. Of these patients, 1322 had undergone axillary ultrasound, 849 breast MRI, and 209 whole-body 18F-FDG PET-CT. The overall axillary pathologic complete response rate was 39.5% (941/2380). For axillary ultrasound, the pooled sensitivity, specificity, PPV, and NPV were 65%, 69%, 77%, 50%, respectively. For breast MRI, the pooled sensitivity, specificity, PPV, and NPV were 60%, 76%, 78%, 58%, respectively. For whole-body 18F-FDG PET-CT, the pooled sensitivity, specificity, PPV, and NPV were 38%, 86%, 78%, 49%, respectively. The diagnostic performance of current noninvasive imaging modalities is limited to accurately assess axillary response after NST in clinically node-positive breast cancer patients.

Tumor-infiltrating lymphocytes benefit prediction of axillary pathologic response and prognostication of event-free survival in HER2-positive and biopsy-proven node-positive breast cancer treated with neoadjuvant therapy.

The present study evaluated tumor-infiltrating lymphocytes (TILs) based on standardized scoring method and investigated its predictive value for axillary pathologic complete response (apCR) and prognostic significance for event-free survival (EFS) in neoadjuvant-treated HER2-positive breast cancer with initially biopsy-proven nodal metastasis. We assessed TILs in a total of 187 pretherapeutic core biopsies of primary tumors. Receiver operating characteristic curve analysis was conducted to calculate the optimal cut-off point of TILs in discriminating axillary pathologic response. The associations of TILs with apCR or EFS were investigated by univariate and multivariate analyses. Receiver operating characteristic curve analysis identified a 10% cut-off point of TILs that optimally discriminated apCR from non-apCR (P < 0.001). High TILs were determined as TILs ≥ 10%, and tumor with TILs < 10% was defined as lymphocyte-depleted breast cancer (LDBC). The apCR rate of the entire cohort was 66.3% (124/187). Tumors with high TILs had a significantly higher apCR rate compared with LDBC (78.5% vs. 43.9%; P < 0.001). High TILs (P < 0.001), breast pathologic complete response (P = 0.006), and negative status of hormone receptor (P = 0.021) were independent predictors for apCR. High TILs were a markedly powerful predictor with an odds ratio of 4.01 (P < 0.001). EFS was significantly better among patients with high TILs than among those with LDBC (P < 0.001). Univariate and multivariate analyses indicated that high TILs (P = 0.019) and apCR (P = 0.013) were independent predictors for favorable EFS. TILs have predictive value for apCR and prognostic significance for EFS in initially node-positive and HER2-positive breast cancer treated with neoadjuvant therapy. LDBC (TILs < 10%) has a significantly unfavorable impact on apCR rate and EFS.

Heterogeneity in Outcomes among Women with Clinically Node-positive Breast Cancer and Axillary Pathologic Complete Response: An Analysis of NSABP B18, B27, B40, and B41

Heterogeneity in Outcomes among Women with Clinically Node-positive Breast Cancer and Axillary Pathologic Complete Response: An Analysis of NSABP B18, B27, B40, and B41

Can we avoid axillary lymph node dissection in N2 breast cancer patients with chemo-sensitive tumours such as HER2 and TNBC?

To find a group of cN2 patients or patients with high axillary burden who become ypN0 after neoadjuvant chemotherapy (NACT) and who may benefit from avoiding a lymphadenectomy. A retrospective observational cohort study was conducted with 221 clinically staged N2 patients or patients with at least 3 suspicious lymph nodes found by ultrasound at diagnosis. The predictive factors for ypN0 analysed were age, MRI-determined tumour size, histological subtype, the Nottingham histologic grade, surrogate molecular subtype, ki-67 and vascular invasion when present. Clinical and radiological responses after NACT were also evaluated. Univariate and multivariate analyses by logistic regression were performed. Distant disease-free survival (DDFS) was calculated in relation to the status of the axillary lymph nodes after NACT. After NACT, 89 patients (40.3%) had axillary pathologic complete response (pCR) (ypN0) and 132 (59.7%) had residual axillary disease (ypN+). Molecular surrogate subtype, Ki-67 expression, and the clinical and radiological responses to NACT were the only independent factors associated with ypN0. Axillary pCR was observed more often in HER2-positive and triple-negative tumours than in luminal ones (OR 7.5 and 3.6, respectively). DDFS was 88.7% (95% CI 80.7-96.7%) for ypN0 and 56.2% (95% CI 32.1-80.3%) for ypN+ (p = 0.09). In HER2-positive and triple-negative breast cancer patients staged as cN2 or with high axillary burden before NACT, a sentinel lymph node biopsy after NACT could be recommended if there is a clinical and radiological response.

Predictive value of tumor-infiltrating lymphocytes for pathological response to neoadjuvant chemotherapy in breast cancer patients with axillary lymph node metastasis

We investigated the role of tumor-infiltrating lymphocytes (TILs) in pretreatment primary breast cancer to predict pathological response to neoadjuvant chemotherapy (NAC) in patients with clinical node-positive disease (cN +). The subjects of this study were 60 patients with cN + , who received NAC followed by breast surgery with axillary lymph node dissection (ALND). We conducted a semi-quantitative assessment of TILs in pretreatment primary tumors and their association with clinicopathological factors and axillary lymph node metastasis. We observed a higher number of TILs in tumors with negative hormone receptors, positive human epidermal growth factor receptor 2, or high Ki67. TILs were associated with a favorable response to NAC in primary tumors. The rate of axillary pathologic complete response (Ax-pCR) was significantly higher in patients with a high number of TILs than in patients with a low number of TILs (72.0% versus 17.1%, p < 0.001). In multivariable analysis, a high number of TILs was a significant predictor of Ax-pCR as well as of pCR of the primary tumor after NAC. Importantly, all patients with HER2-positive tumors in the high TILs group showed Ax-pCR on ALND. TILs in pretreatment primary breast cancer had the potential to predict therapeutic efficacy of NAC in patients with clinical node-positive disease.

245 Poster - Diagnostic performance of noninvasive imaging for assessment of axillary pathologic complete response after neoadjuvant systemic therapy in clinically node-positive breast cancer: A systematic review and meta-analysis

245 Poster - Diagnostic performance of noninvasive imaging for assessment of axillary pathologic complete response after neoadjuvant systemic therapy in clinically node-positive breast cancer: A systematic review and meta-analysis

Survival in Cytologically Proven Node-Positive Breast Cancer Patients with Nodal Pathological Complete Response after Neoadjuvant Chemotherapy.

Simple SummaryIt is unknown whether patients with cytologically proven axillary node-positive breast cancer, who achieve axillary pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) have a comparable prognosis to patients with axillary pathological node-negative disease (pN-) without NAC. The aim of this retrospective study was to clarify the clinical impact of axillary pCR after NAC on survival and to compare survival outcomes between breast cancer patients with axillary pCR, and those with axillary pN- without NAC, using propensity score matching to adjust for baseline characteristics other than nodal status. Axillary pCR after NAC was associated with improved prognosis in patients with axillary node-positive disease, and patients with axillary pCR and matched pairs with axillary pN- without NAC had comparable outcomes.Background: It is unknown whether patients with cytologically proven axillary node-positive breast cancer who achieve axillary pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) have comparable prognosis to patients with axillary pathological node-negative disease (pN-) without NAC. Methods: We retrospectively reviewed the data of patients with cytologically proven axillary node-positive disease who received NAC and those with axillary pN- without NAC for control between January 2007 and December 2012. We compared outcomes according to response in the axilla to NAC and between patients with axillary pCR and matched pairs with axillary pN- without NAC using propensity scores. Results: We included 596 patients with node-positive breast cancer who received NAC. The median follow-up period was 64 months. Patients with axillary pCR showed significantly better distant disease-free survival (DDFS) and overall survival (OS) than patients with residual axillary disease (both p < 0.01). There was no significant difference in DDFS and OS between patients with axillary pCR and matched pairs with axillary pN- without NAC. Conclusion: Axillary pCR was associated with improved prognosis. Patients with axillary pCR and matched pairs with axillary pN- without NAC had comparable outcomes. This information will be useful when considering the intensity of follow-up and adjuvant therapy.

Association of higher axillary pathologic complete response rate with breast pathologic complete response after neoadjuvant chemotherapy.

BackgroundTo investigate the association of axillary pathologic complete response (pCR) rate among breast cancer patients with pCR after neoadjuvant chemotherapy (NCT).MethodsThe retrospective clinical data of 1,903 patients who were treated with NCT between March, 2010 and December, 2018, were collected from one Chinese database and analyzed. The correlations between clinicopathological characteristics and breast pCR with axillary pCR were calculated by χ2 test. Binary logistic regression analysis was used for multivariate analysis. The relative risk of positive axillary nodes after NCT in patients with and without breast pCR was analyzed using a Cochran-Mantel-Haenszel (CMH) test stratified by initial N stage and tumor subtype.ResultsThe rate of axillary pCR was increased in the cases with initial cN0, Ki67 high expression, HR+HER2+/HR-HER2+/TN subtypes, and breast pCR. After NCT, the relative risk of nodal disease burden was 4.81 in patients without breast pCR compared with patients with breast pCR. The relative risk of positive nodal status in patients with cN0, cN1, cN2, and cN3 disease without vs. with breast pCR was 6.45, 4.88, 5.69 and 6.24, respectively. The relative risk of positive nodal status in patients with HR+HER2−, HR+HER2+, HR−HER2+, and TN disease was 4.02, 4.50, 3.82 and 4.18, respectively. Of cN0 patients with breast pCR, only 4 out of 44 (9%) with HER2-positive disease had 1 or 2 axillary lymph node metastases at final surgical pathology compared to 30 out of 98 (31%) of those without breast pCR. There was no evidence of positive nodal residue among all 21 patients (100%) with TN disease compared to 65% (36 of 55) of patients without breast pCR.ConclusionsNodal status is strongly correlated with breast pCR after NCT. Patients with initial cN0/1 TN/HER2 positive disease who achieve breast pCR at surgery have a low risk of nodal metastasis. These results suggest that the failure rate of missing positive lymph nodes among those patients was very low and that it is safe for such patients to undergo sentinel lymph node biopsy (SLNB) after NCT. This study also provides a theoretical basis for clinical trials focused on the avoidance of axillary surgery in selected patients.

A nomogram for predicting axillary pathologic complete response in hormone receptor–positive breast cancer with cytologically proven axillary lymph node metastases

The objective of this study was to determine an axillary pathologic complete response (pCR) and its influencing factors in patients with hormone receptor (HR)-positive breast cancer and cytologically proven axillary lymph node metastases. A prediction nomogram was established to provide information for the de-escalation of axillary management in these patients after neoadjuvant chemotherapy. The authors retrospectively enrolled all patients with HR-positive breast cancer in the neoadjuvant chemotherapy data set of Fudan University Shanghai Cancer Center. All data were prospectively collected. From 2007 to 2016, 533 consecutive patients were included. Multivariate logistic regression analysis was performed, after which a nomogram was constructed and validated. An axillary pCR was achieved in 168 patients (31.5%), the which was much higher than the proportion of those who achieved a breast pCR (103 patients; 19.3%). Patients who had human epidermal growth factor receptor 2-positive disease (P=.004), a better primary tumor response (P=.001), earlier clinical stage (P=.045), and lower estrogen receptor expression (P<.001) were more likely to achieve a lymph node pCR. The nomogram indicated an area under the receiver operating characteristic curve (AUC) of 0.84 (95% CI, 0.78-0.89) in the training set. The validation set showed good discrimination with an AUC of 0.75 (95% CI, 0.69-0.81). The C-index was 0.834 and 0.756 in the training and validation cohort, respectively. The nomogram was well calibrated. The authors developed and validated a nomogram for predicting axillary pCR in patients with HR-positive disease accurately by using clinicopathologic factors available before surgery. The model will facilitate logical clinical decision making and clinical trial design.

Abstract P4-02-07: Validity of omission of axillary lymph node dissection after neoadjuvant chemotherapy for node-positive primary breast cancer

Abstract Background: Anthracycline and taxane-based neoadjuvant chemotherapy (NAC) has been shown to downstage axillary lymph nodes in approximately 40% of patients. However, the feasibility of sentinel lymph node biopsy (SLNB) following NAC for initially node-positive patients is unclear because of high false-negative rates reported in previous trials. The aim of this study was to evaluate whether axillary lymph node dissection (ALND) could be safely omitted for patients with clinically node-positive breast cancer treated with NAC. Patients and methods: We identified 128 patients with clinically node-positive breast cancer who received NAC from March 2006 to March 2017. A correlation between axillary pathologic response and clinicopathological factors was analyzed. Preoperative clinical assessment of lymph-node status was performed by palpation and diagnostic imaging such as ultrasound and MRI. Lymphatic mapping was performed using a combined method of blue dye and radioisotope. Results: The median age was 56.5 (range: 29-79) years and the mean tumor size was 3.6 ± 2.37cm. Of 128 patients, 72 (56.2%) patients had luminal, 32 (31.3%) had HER2-positive, and 24 (18.8%) had triple-negative disease. Sequential anthracycline and taxane were administered for 115 (89.8%) patients, and 25 (78.1%) patients with HER2-positive disease received concomitant trastuzumab preoperatively. Overall, 53 (41.4%) patients achieved axillary pathologic complete response (ypN0). The ypN0 status was significantly correlated with clinical complete response (cCR) in breast (67.9%, p=0.004), ER-negative disease (59.5%, p=0.004) and HER2-positive disease (56.3%, p=0.049). Multivariate analysis demonstrated that cCR in breast (p=0.015) and ER negativity (p=0.006) were significant predictive factors for ypN0. In 14 ER-negative patients achieving cCR in breast, ypN0 was found in 12 (85.7%) patients. Among 85 patients who converted to clinically node-negative, ALND was omitted in 16 patients (18.8%) after SLNB. Of these 16 patients, irradiation to whole-breast and axilla was performed in 14 (87.5%) and 5 (31.3%) patients, respectively. After a median follow-up of 53.2 months, no axillary recurrence was observed in entire patients and 5-year disease-free survival was not significantly different between patients with or without ALND (85.5% vs. 87.5%, p=0.965). Conclusions: As ER-negativity and cCR were correlated with high eradication rate of initially positive lymph nodes, these patients might be good candidates of omission of ALND after NAC. Citation Format: Akiko Matsumoto, Yasuko Umemoto, Daisuke Tsukahara, Hiromitsu Jinno. Validity of omission of axillary lymph node dissection after neoadjuvant chemotherapy for node-positive primary breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-02-07.