Axillary Node-positive Breast Research Articles

Abstract PO2-23-06: Clinical study of stained region lymph node biopsy (SrLNB) in axillary surgery after neoadjuvant systemic therapy in patients with axillary lymph node positive breast cancer

Abstract Background The probability of axillary lymph node converting from positive to negative after neoadjuvant systemic therapy (NST) for breast cancer patients is approximately 40%. A variety of axillary lymph node biopsy surgeries based on sentinel lymph node biopsy (SLNB) can help to omit axillary lymph node dissection (ALND). The common disadvantages, however, are mainly the restrictions, such as the need for strict regulation of the use of radiotracers, the high number of retrieved lymph nodes required, and the need to purchase ancillary equipment. The more restrictions there are, the more they limit the spread and availability of the technique and, more importantly, reduce the number of patients who will benefit. In fact, for patients with metastatic lymph nodes, the sentinel lymph nodes must be included in the lymph nodes that have metastasized. If these metastatic lymph nodes can be accurately marked and precisely retrieved after NST, it is possible to assess whether the axillary lymph nodes are converted from positive to negative without the need for SLNB. Materials and methods Breast cancer patients with pathologically confirmed axillary lymph node metastases who were receiving NST were recruited for this study. Before NST, carbon nanoparticles suspension injections were injected into the cortex of the pathologically confirmed metastatic lymph node to stain the region where the metastatic lymph node was located. The lymph nodes in the stained region were retrieved by stained region lymph node biopsy (SrLNB) during the axillary surgery, followed by ALND, without the use of SLNB. Finally, the identification rate and false-negative rate (FNR) of SrLNB were statistically analyzed according to pathology data. Results A total of 159 patients were successfully enrolled in this study between September 24, 2020 and December 2, 2022, with an axillary pCR rate of 40.9% (65/159). The identification rate of SrLNB was 100% (159/159), with an overall FNR of 5.3% (5/94). Subgroup analysis revealed that in the subgroups of 1, 2, 3 and ≥4 SrLN, the FNR was 0%, 0%, 0% and 8.9% (5/56), respectively, whereas in the cN1, cN2 and cN3 subgroups the FNR was 7.7% (3/39), 2.6% (1/38) and 5.9% (1/17), respectively. The FNR indexes were within the safety threshold of 10% in all subgroups. Conclusion SrLNB has a high identification rate and a low FNR and is useful for screening patients with positive to negative axillary lymph nodes for omitting ALND. srLNB requires only the use of an affordable and radiation-free carbon nanoparticles suspension injection for marking, making the whole technique simpler and easier to disseminate. The data from this study also suggest that SLNB may not be mandatory for axillary biopsy in patients with positive axillary lymph nodes undergoing NST. Table 1. General characteristics of enrolled patients. Table 2. Analysis of factors affecting axillary pCR rates. Table 3. Analysis for the FNR of SrLNB. Citation Format: Jue Wang, Rui Chen, Cuiying Li, Hailing Zha, Qiannan Zhu, Lifeng Huang, Xiaoming Zha. Clinical study of stained region lymph node biopsy (SrLNB) in axillary surgery after neoadjuvant systemic therapy in patients with axillary lymph node positive breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-23-06.

Noninvasive prediction of node-positive breast cancer response to presurgical neoadjuvant chemotherapy therapy based on machine learning of axillary lymph node ultrasound

ObjectivesTo explore an optimal model to predict the response of patients with axillary lymph node (ALN) positive breast cancer to neoadjuvant chemotherapy (NAC) with machine learning using clinical and ultrasound-based radiomic features.MethodsIn this study, 1014 patients with ALN-positive breast cancer confirmed by histological examination and received preoperative NAC in the Affiliated Hospital of Qingdao University (QUH) and Qingdao Municipal Hospital (QMH) were included. Finally, 444 participants from QUH were divided into the training cohort (n = 310) and validation cohort (n = 134) based on the date of ultrasound examination. 81 participants from QMH were used to evaluate the external generalizability of our prediction models. A total of 1032 radiomic features of each ALN ultrasound image were extracted and used to establish the prediction models. The clinical model, radiomics model, and radiomics nomogram with clinical factors (RNWCF) were built. The performance of the models was assessed with respect to discrimination and clinical usefulness.ResultsAlthough the radiomics model did not show better predictive efficacy than the clinical model, the RNWCF showed favorable predictive efficacy in the training cohort (AUC, 0.855; 95% CI 0.817–0.893), the validation cohort (AUC, 0.882; 95% CI 0.834–0.928), and the external test cohort (AUC, 0.858; 95% CI 0.782–0.921) compared with the clinical factor model and radiomics model.ConclusionsThe RNWCF, a noninvasive, preoperative prediction tool that incorporates a combination of clinical and radiomics features, showed favorable predictive efficacy for the response of node-positive breast cancer to NAC. Therefore, the RNWCF could serve as a potential noninvasive approach to assist personalized treatment strategies, guide ALN management, avoiding unnecessary ALND.

Abemaciclib: The First FDA-Approved CDK4/6 Inhibitor for the Adjuvant Treatment of HR+ HER2- Early Breast Cancer.

To review the new indication of cyclin-dependent kinase (CDK4/6) inhibitor abemaciclib for the adjuvant treatment of hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), axillary lymph node (LN) positive early breast cancer (EBC) at high risk of recurrence and a Ki-67 ≥20%. A literature search was performed through PubMed, ClinicalTrials.gov, and Food and Drug Administration (FDA) website (February 1, 2018, to December 23, 2021) to identify relevant information. Human and animal studies related to pharmacology, pharmacokinetics, efficacy, and safety of abemaciclib were identified. Addition of abemaciclib to standard of care endocrine therapy (ET) for patients with high-risk clinicopathologic features and Ki-67 ≥20% demonstrated 30% reduction in the risk of developing invasive disease and distant recurrence. At 15.5 months, abemaciclib + ET demonstrated a significant improvement in invasive disease-free survival (IDFS) vs ET alone (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.60-0.93, P = 0.01). At 27 months, IDFS benefit was maintained (HR, 0.70; 95% CI, 0.59-0.82, P < 0.0001). Diarrhea occurred in more than 80% of patients in the abemaciclib arm. This review describes the clinical applicability of adjuvant abemaciclib for patients with HR+, HER2- EBC at high risk for recurrence. Adjuvant abemaciclib significantly reduces the risk for early development of invasive disease and distant recurrence in patients with HR+, HER2- node positive EBC. Longer follow-up is needed to determine the impact of adjuvant abemaciclib on late disease recurrence and survival outcomes.

El papel pronóstico del SUVmáx basal y cambio del SUVmáx en la PET/TC con18F-FDG en pacientes con cáncer de mama con ganglios positivos que reciben quimioterapia neoadyuvante

ObjectiveThis study aimed to determine the prognostic role of baseline maximum standardized uptake value (SUVmax) obtained by pretreatment PET/CT and the change in SUVmax (ΔSUVmax [%]) in patients with axillary lymph node–positive breast cancer receiving neoadjuvant chemotherapy (NAC). MethodsOne hundred and eighty patients with baseline SUVmax and 121 patients with SUVmax measurement after treatment were evaluated in the study. The baseline SUVmax value of the breast (SUVmaxBI) and axilla (SUVmaxAI) and the change in the SUVmax of the breast (ΔSUVmaxB) and axilla (ΔSUVmaxA) were measured. The optimal cut-off value of SUVmax and ΔSUVmax were determined by ROC curve analysis. Disease-free survival (DFS) and overall survival (OS) were calculated using Kaplan–Meier curves. ResultsΔSUVmaxB, pCRB, pCRA, and pCR parameters were found to be associated with relapse (p < 0.001, p = 0.033, p = 0.016, and p = 0.013, respectively). ΔSUVmaxB and SUVmaxAI were associated with mortality (p = 0.001 and p = 0.006, respectively). Multiple Cox regression analyses revealed that ΔSUVmaxB value was an independent prognostic factor for relapse and mortality (p = 0.013 and p = 0.010, respectively). ConclusionThe results showed that ΔSUVmaxB was an independent prognostic factor for relapse and mortality in patients with axillary lymph node–positive breast cancer who received NAC.

The prognostic role of baseline 18F-FDG PET/CT SUVmax and SUVmax change in patients with node-positive breast cancer receiving neoadjuvant chemotherapy

ObjectiveThis study aimed to determine the prognostic role of baseline maximum standardized uptake value (SUVmax) obtained by pretreatment PET/CT and the change in SUVmax (ΔSUVmax [%]) in patients with axillary lymph node–positive breast cancer receiving neoadjuvant chemotherapy (NAC). MethodsOne hundred and eighty patients with baseline SUVmax and 121 patients with SUVmax measurement after treatment were evaluated in the study. The baseline SUVmax value of the breast (SUVmaxBI) and axilla (SUVmaxAI) and the change in the SUVmax of the breast (ΔSUVmaxB) and axilla (ΔSUVmaxA) were measured. The optimal cut-off value of SUVmax and ΔSUVmax were determined by ROC curve analysis. Disease-free survival (DFS) and overall survival (OS) were calculated using Kaplan–Meier curves. ResultsΔSUVmaxB, pCRB, pCRA, and pCR parameters were found to be associated with relapse (P < .001, P = .033, P = .016, and P = .013, respectively). ΔSUVmaxB and SUVmaxAI were associated with mortality (P = .001 and P = .006, respectively). Multiple Cox regression analyses revealed that ΔSUVmaxB value was an independent prognostic factor for relapse and mortality (P = .013 and P = .010, respectively). ConclusionThe results showed that ΔSUVmaxB was an independent prognostic factor for relapse and mortality in patients with axillary lymph node–positive breast cancer who received NAC.

Intensity-Modulated Radiation Therapy versus 3D Conformal Radiation Therapy in Patients Undergoing Regional Nodal Irradiation/Postmastectomy Radiation Therapy for Breast Cancer: Looking Beyond Dosimetric Outcomes

Prospective data and meta-analyses support the use of adjuvant regional nodal irradiation (RNI)/postmastectomy radiation therapy (PMRT) for the majority of women with axillary lymph node positive breast cancer. However, RNI increases dose to the heart and lung compared resulting in increased toxicity. Inverse-planned intensity modulated radiation therapy (IMRT) has the ability to reduce high dose to the heart/lung compared to traditional 3D conformal radiation therapy (3DCRT). Early concerns with IMRT were that it may be too conformal resulting in increased risk of local-regional failures (LRF). To date, clinical outcomes with IMRT have not been well studied in patients receiving RNI/PMRT. We have used planning target volume (PTV)-based, dose-volume analysis driven RNI/PMRT planning since 2013 using primarily 3DCRT but IMRT as needed to meet heart/lung planning objectives. We hypothesize that toxicity and LRF rates are similar between patients treated with IMRT and 3DCRT. We identified patients that received RNI/PMRT from 2013-2016. Patients received conventional fractionation (200 cGy/day) to the breast/chestwall, axillary, supraclavicular (SCV), and internal mammary chain (IMC) PTVs. We divided the cohort into 2 groups (IMRT vs. 3DCRT). We collected patient and disease characteristics, acute toxicity, LRF, and distant metastases (DM) events. Differences in characteristics were evaluated with the t-test or Chi-square test. The primary endpoint was the cumulative incidence of LRF as a first failure. We also evaluated the cumulative incidence of DM. We included 241 patients (69 IMRT, 172 3DCRT): 60% had stage III disease; 60% (ER+ or PR+)/HER2-; 20% triple-negative; 20% HER2+. IMRT group had higher rates of left-sided (65% vs. 47%, p=0.009) and grade 3 (58% vs. 43%, p=0.04) disease. The IMCs were irradiated in 97%. Treatment was well tolerated: grade 3 dermatitis 6% in each group with no other grade 3 toxicities. Grade 2 pneumonitis occurred in 2 (0.83%), both 3DCRT. Median follow-up is 3.5 years. There were 5 LRF events (2 IMRT, 3 3DCRT): 2 patients with isolated LRF (iLRF) and 3 patients with simultaneous LRF+DM resulting in 4-year LRF=2.1% (4.1% IMRT vs. 1.4% 3DCRT, p=0.55) and 4-yr iLRF=1.1% (1.5% vs. 0.8%, p=0.43). The iLRF (1 IMRT, 1 3DCRT) both occurred in the SCV region. The other LRF+DM event in the IMRT group was a chestwall/axillary/IMC recurrence post-mastectomy. The additional 2 LRF+DM events in the 3DCRT group included: ipsilateral SCV and level V nodes post-lumpectomy; and a lumpectomy bed recurrence. Most failures were DM: 4-year rate=15% (21.0% IMRT vs. 13.2% 3DCRT, p=0.58). In this modern cohort of patients receiving RNI/PMRT with a PTV-based approach, we saw rare high-grade toxicity, and we found no difference in LRF and DM rates between IMRT and 3DCRT patients. These data should provide reassurance that IMRT does not compromise disease outcomes and that IMRT can safely be used when needed to meet normal tissue constraints.

Topoisomerase II alpha and microtubule-associated protein-tau as a predictive marker in axillary lymph node positive breast cancer.

The aims of this study were to investigate the correlation between topoisomerase II alpha (TOP2A), microtubule-associated protein-tau (MAP-tau) and other prognostic factors in breast cancer and to evaluate the predictive value of TOP2A and MAP-tau in breast cancer patients who received anthracycline and taxane-containing adjuvant chemotherapy. Seventy patients with axillary lymph node positive breast cancer who underwent curative surgery between January 2000 and December 2005 were evaluated retrospectively. The levels of protein expression of TOP2A and MAP-tau were assessed using immunohistochemistry. Among the 70 patients, 43 (61.4%) showed TOP2A overexpression and 30 (42.9%) showed MAP-tau positivity. TOP2A overexpression was associated with p53 positivity and high histological grade. MAP-tau positivity was associated with a lower positive lymph node ratio, lower proliferative activity, and hormone receptor positivity. Based on the TOP2A and MAP-tau expression, there was no significant difference in disease-free survival in the breast cancer patients who received anthracycline and taxane-containing adjuvant chemotherapy. We conclude that immunohistochemical analysis of TOP2A and MAP-tau protein expression may not predict the benefits of adjuvant anthracycline and taxane chemotherapy in axillary node positive breast cancer.

Nomogram for prediction of level 2 axillary lymph node metastasis in proven level 1 node-positive breast cancer patients.

BackgroundThe current management of the axilla in level 1 node-positive breast cancer patients is axillary lymph node dissection regardless of the status of the level 2 axillary lymph nodes. The goal of this study was to develop a nomogram predicting the probability of level 2 axillary lymph node metastasis (L-2-ALNM) in patients with level 1 axillary node-positive breast cancer.Materials and MethodsWe reviewed the records of 974 patients with pathology-confirmed level 1 node-positive breast cancer between 2010 and 2014 at the Liaoning Cancer Hospital and Institute. The patients were randomized 1:1 and divided into a modeling group and a validation group. Clinical and pathological features of the patients were assessed with uni- and multivariate logistic regression. A nomogram based on independent predictors for the L-2-ALNM identified by multivariate logistic regression was constructed.ResultsIndependent predictors of L-2-ALNM by the multivariate logistic regression analysis included tumor size, Ki-67 status, histological grade, and number of positive level 1 axillary lymph nodes. The areas under the receiver operating characteristic curve of the modeling set and the validation set were 0.828 and 0.816, respectively. The false-negative rates of the L-2-ALNM nomogram were 1.82% and 7.41% for the predicted probability cut-off points of < 6% and < 10%, respectively, when applied to the validation group.ConclusionsOur nomogram could help predict L-2-ALNM in patients with level 1 axillary lymph node metastasis. Patients with a low probability of L-2-ALNM could be spared level 2 axillary lymph node dissection, thereby reducing postoperative morbidity.

Predictive factors of pathologic complete response in HER2-positive and axillary lymph node positive breast cancer after neoadjuvant paclitaxel, carboplatin plus with trastuzumab.

ObjectiveThis study was performed to investigate the proportion as well as the predictive factors of pathologic complete response in HER2-positive and axillary lymph node positive breast cancer after neoadjuvant paclitaxel, carboplatin plus with trastuzumab (PCH).ResultsThe pCR rate in the breast, axilla and both was 44.3% (39/88), 47.7% (42/88) and 34.1% (30/88), respectively. Patients with and without pCR were similar in term of age, BMI, menstrual status, family history, treatment cycles and tumor characteristics (laterality and size of tumor). Multivariate logistic regression demonstrated that pCR was significantly associated with HR negativity (HR = 5.587, 95% CI 2.25−3.889, p < 0.001), high Ki67 index (HR = 4.130, 95% CI 1.607−10.610, p = 0.003). Further investigation found that patients with HR-negative/high Ki67 index had higher pCR rate, compared to other patients (HR = 7.583, 95% CI 2.503−22.974, p < 0.001).Materials and Methods88 consecutive Chinese HER2-positive/axillary lymph node-positive breast cancer patients with neodjuvant therapy regimen containing paclitaxel, carboplatin and trastuzumab were divided into two groups: pathological complete response (pCR) or non-pCR group. Clinico-pathological characteristics were compared and analyzed, and univariate and multivariate analyses were performed to detect the predictive factors of pCR.ConclusionsPreoperative PCH regimen was an effective neoadjuvant therapy in HER2 positive and axillary lymph node positive patients, and patients coexisting with HR-negative and high Ki67 index may benefit more from this regimen.

Abstract P2-05-15: The lymph node ratio as an independent prognostic factor for node-positive triple-negative breast cancer

Abstract Purpose: To evaluate the prognostic value of the lymph node ratio (LNR) in patients with axillary lymph node-positive triple-negative breast cancer (TNBC). Patients and methods: Based on X-tile plots, we classified women into low-, medium-, and high-risk LNR groups. Univariate and multivariate Cox proportional hazards regression analyses for overall survival (OS), breast cancer-specific survival (BCSS) and disease-free survival (DFS) were performed. The prognostic efficacy of the LNR was investigated in the first cohort from the Surveillance, Epidemiology, and End Results (SEER) database (n=4114) and was further validated in an independent cohort from Fudan University Shanghai Cancer Center (n=417). Results: The patients were classified into low- (≤0.30), medium- (0.30 to 0.70) and high-risk (&amp;gt;0.70) LNR groups. Multivariate analysis revealed that the LNR was an independent predictor of OS (hazard ratio (HR) for high-risk LNR: 3.24; 95% confidence interval (CI): 2.56 to 4.09) and BCSS (HR for high-risk LNR: 3.57; 95% CI: 2.76 to 4.62) in the SEER population and also for DFS (HR for high-risk LNR: 4.29; 95% CI: 2.24-8.21) in the validation population. Subgroup analysis revealed that patient classification according to the LNR could discriminate among groups of patients with different survival rates based on pN staging. Effect of Lymph Node Ratio and pN Classification on Survival Among Patients from SEERVariableOSBCSS HR a(95% CI)PHR a(95% CI)PLymph node ratio Low,≤0.301-1-Medium, &amp;gt;0.30 and ≤0.702.05(1.63-2.59)&amp;lt;0.0012.26(1.75-2.92)&amp;lt;0.001High,&amp;gt;0.703.24(2.56-4.09)&amp;lt;0.0013.57(2.76-4.62)&amp;lt;0.001pN N11-1-N21.53(1.21-1.93)&amp;lt;0.0011.63(1.27-2.10)0.001N32.72(2.14-3.46)&amp;lt;0.0012.97(2.29-3.85)&amp;lt;0.001a Cox proportional hazards model. Hazard ratios are adjusted for age, race, histologic grade, tumor size, surgery type and radiotherapy. Conclusion: The LNR shows potential for use as an additional prognostic factor for TNBC patients with positive lymph node involvement. Considering the heterogeneity of TNBC, use of the LNR might allow for optimization of the pN staging system, and this ratio should be considered when making treatment decisions. Citation Format: He M, Jiang Y-Z, Tang L-C, Chen Y-L, Shao Z-M, Di G-H. The lymph node ratio as an independent prognostic factor for node-positive triple-negative breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-05-15.

Abstract P3-09-01: A multicenter randomized study comparing the dose dense G-CSF-supported sequential administration of FEC followed by docetaxel versus docetaxel plus cyclophosphamide as adjuvant chemotherapy in women with HER2-negative, axillary lymph node-positive breast

Abstract Background: The dose dense sequential administration of anthracycline and taxane is very effective as adjuvant therapy in node-positive early breast cancer. The non-anthracycline regimen docetaxel plus cyclophosphamide (TC regimen) was better than four cycles of doxorubicin/cyclophosphamide as adjuvant therapy. This study compared the dose dense sequential regimen versus the TC regimen as adjuvant therapy. Methods: Women with axillary node-positive, HER2-negative early breast cancer were randomized following surgery to receive either dose dense G-CSF-supported FEC (5FU 500mg/m2, epirubicin 75mg/m2, cyclophosphamide 500mg/m2 every 14 days for 4 cycles) followed by Docetaxel (75mg/m2 every 14 days for 4 cycles) (arm A) or 6 cycles of Docetaxel 75mg/m2 plus Cyclophospamide 600mg/m2 every 3 weeks (arm B). The primary endpoint of the study was the 3-year disease-free survival (DFS). Results: Six hundred fifty patients were randomized; 326 on arm A and 324 on arm B. Of them 109 (33%) and 90 (28%) were premenopausal, 196 (60%) and 218 (67%) had 1-3 positive nodes, 284 (87%) and 288 (89%) were hormone receptor positive in arm A and B, respectively. Chemotherapy was completed in 97% and 93% of patients in arm A and B, respectively. After a median follow up of 46 and 47 months, there were 37 (11.3%) and 33 (10.1%) disease relapses and the median DFS has not yet been reached (p=0.5) while the 3-year DFS rate was 89.5% and 91.1% for arm A and B, respectively. Neutropenia grade III-IV was more common in arm B and anemia, nausea, vomiting and fatigue grade II-III in arm A. No toxic deaths occurred. Conclusions: The 3-year DFS rate was similar between the dose dense sequential FEC/docetaxel combination and the TC regimen in women with node-positive HER2-negative early breast cancer. Citation Format: Dimitrios Mavroudis, Nikolaos Malamos, Pavlos Papakotoulas, Stylianos Kakolyris, Ioannis Boukovinas, Elias Athanasiadis, Nikolaos Kentepozidis, Nikolaos Ziras, Kostas Kalbakis, Charalambos Christophyllakis, Vassilis Georgoulias. A multicenter randomized study comparing the dose dense G-CSF-supported sequential administration of FEC followed by docetaxel versus docetaxel plus cyclophosphamide as adjuvant chemotherapy in women with HER2-negative, axillary lymph node-positive breast [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-09-01.

Abstract S3-03: Ten year update of E1199: Phase III study of doxorubicin-cyclophosphamide followed by paclitaxel or docetaxel given every 3 weeks or weekly in patients with axillary node-positive or high-risk node-negative breast cancer

Abstract Background: We had previously reported after a median followup of 5.3 years that disease free survival (DFS) was improved with either adjuvant weekly paclitaxel (hazard ratio [HR] 0.73, p=0.0006) or every 3 week docetaxel (HR 0.77, p=0.02) compared with every 3 week paclitaxel (N Eng J Med 2008; 358; 1663), and that obesity and black race were independently associated with inferior outcomes in estrogen receptor (ER)-positive disease after a longer followup (Cancer 2012: 118: 5937 &amp; JNCI 2012; 104: 406). We now report updated results after a median followup of 12.1 years. Methods: Eligibility included axillary lymph node positive or high-risk (tumor at least 2 cm) node-negative breast cancer. All patients received 4 cycles of AC (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2) every 3 weeks, followed by either: (1) paclitaxel 175 mg/m2 every 3 weeks x 4 (P3), (2) paclitaxel 80 mg/m2 weekly x 12 (P1), (3) docetaxel 100 mg/m2 every 3 weeks x 4 (D3), or (4) docetaxel 35 mg/m2 weekly x 12 (D1). Patients with ER-positive breast cancer also received endocrine therapy for at least 5 years, including either tamoxifen and/or an aromatase inhibitor. The primary comparisons included taxane (P vs. D) and schedule (every 3 weeks vs. weekly), and the primary endpoint was DFS, defined as local, regional, and/or distant relapse, second primary breast cancer, or death without recurrence. Results: A total of 4954 eligible patients were accrued between October 1999 and January 2002. At the time of this analysis, 90% of surviving patients were followed for at least 10 years, and there were substantially more DFS events (1639 vs. 1048) and deaths (1283 vs. 686) than the original report. For the primary comparison, there remains no significant difference in DFS by taxane (p=0.33) or schedule (p=0.88), although there was a significant interaction between taxane and schedule (p&amp;lt;0.007). When comparing the standard arm (P3) to the other arms (with a hazard ratio [HR] &amp;lt; 1 favoring the experimental arms using a stratified Cox model), the HRs for DFS were 0.84 (p = 0.011) for arm P1 and 0.79 (p=0.001) for arm D3 arm, and for overall survival (OS) were 0.87 (p=0.09) and 0.86 (p=0.054), respectively. When evaluated by subtypes in exploratory analyses, the P1 arm (but not the D3 arm) was associated with improved DFS (HR 0.69, p=0.01) and OS (HR 0.69, p=0.019) in the 1025 patients with triple negative breast cancer (TNBC), and the D3 arm (but not P1 arm) was associated with improved DFS (HR 0.76, p=0.004) but not OS (HR 0.87, p=0.20) in the 2785 patients with ER-positive, HER2-negative/unknown breast cancer (ERBC). In ERBC but not other subtypes, black race (HR 1.60, p=0.002) and obesity (HR 1.23, p=0.009) were associated with inferior OS, and obesity was associated with a higher recurrence risk between 3-8 years after diagnosis. Conclusions: Improvements in DFS observed at 10 years for the P1 and D3 arms compared with the P3 arm are qualitatively similar but quantitatively less than at 5 years, and the effects on OS are marginal in the overall population. The relative effectiveness of weekly paclitaxel and every 3 week docetaxel may vary by subtype. Citation Format: Joseph A Sparano, Fengmin Zhao, Silvana Martino, Jennifer Ligibel, Thomas Saphner, Antonio C Wolff, George W Sledge Jr, Edith A Perez, William C Wood, Nancy E Davidson. Ten year update of E1199: Phase III study of doxorubicin-cyclophosphamide followed by paclitaxel or docetaxel given every 3 weeks or weekly in patients with axillary node-positive or high-risk node-negative breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr S3-03.

P341 Use of fibrin glue in the prevention of seroma formation after axillary lymphadenectomy

Goals: The ACOSOG Z0011 trial showed that an axillary lymph node dissection (ALND) may be safely omitted in selected patients with a positive sentinel lymph node biopsy (SNB). One of these eligible criteria has non palpable lymphadenopathy. However, the eligibility for patients with a suspicious Ultrasonography (US) is controversial. The purpose of this study was to evaluate the validity of the SNB for patients with suspicious lymph node (sN+) compared to clinical node negative patients (cN0). Methods: Patients with suspicious axillary lymph node positive breast cancer by preoperative assessed US or CT were performed fine needle aspiration (FNA) cytology between 2004 and 2014. Patients with a negative axillary US (cN0 group) or negative FNAC (sN+ group) result underwent SNB. All SNB positive patients underwent completion ALND. The number of positive nodes after ALND was compared cN0 group with sLN group. Results: 530/2683 patients (19.7%) had positive SNB. Ultrasoundaxilla was 49% sensitive and 84% specific in predicting SNB metastases. The positive (PPV) and negative predictive value (NPV) was 53% and 81% respectively. For suspicious group, this was 68.4% sensitive and 99.7% specific in detecting SNB metastases. PPV and NPV were 99.6% and 74.2% respectively. The number of metastasis lymph nodes is 1 (48%), 2 (19%), 3 (9%), more than 4 (54%) and N1mic (17%) in the cN0 group, and 1 (37%), 2 (14%), 3 (7%), more than 4 (10%) and N1mic (28%) in the cN1 suspicious group. Conclusion: These results suggest that patients with suspicious axillary metastases on ultrasound-guided biopsy have less involved nodes than SNB-positive patients with clinical negative node. Therefore, we conclude that SNB can be safely performed in patients with clinically suspicious lymph node on ultrasonography. Disclosure of Interest: No significant relationships.

The efficacy of adjuvant trastuzumab in HER-2 positive breast cancer with axillary lymph node metastases according to the treatment duration

Introduction:Trastuzumab is the first anti-HER-2 humanized monoclonal antibody. The benefit of adjuvant trastuzumab has been shown in randomized phase III trials. Despite trastuzumab being recommended for 52 weeks in the adjuvant treatment of HER-2 positive breast cancer according to the current breast cancer guidelines, there is still no consensus on the optimal duration of adjuvant trastuzumab. The aim of our study is to investigate the efficacy and safety of adjuvant trastuzumab for 9 weeks and 52 weeks in axillary lymph node positive HER-2 positive breast cancer patients.Patients and methods:A total of 271 HER-2 and axillary node positive breast cancer patients who received trastuzumab in adjuvant treatment between the years 2005 and 2013 were retrospectively analyzed. Patients with axillary node positive HER-2 positive breast cancer who were non-metastatic were enrolled to the study. Patients were allocated to the 9 week trastuzumab group (n = 155) or the 52 week trastuzumab group (n = 116). Kaplan–Meier survival analysis was carried out for disease free survival (DFS) and overall survival (OS). Two-sided p values of <0.05 were considered statistically significant. The most important limitation of our manuscript is the retrospective design.Results:The median follow-up time for this analysis was 34 (4–95) months. Patients’ clinical and pathological characteristics were well balanced between the two treatment arms. In the 9 week trastuzumab treatment group, the DFS rate was 96.7%, 84.8% and 74.9% in the first, third and fifth years respectively, whereas in the 52 week trastuzumab treatment group it was 94.3%, 80.0% and 80.0% (P = 0.76). In the 9 week trastuzumab treatment group, the OS rate was 99.3%, 92.2% and 88.3% in the first, third and fifth years respectively, whereas in the 52 week trastuzumab treatment group it was 99.0%, 94.7% and 78.6% (P = 0.99). In both groups, symptomatic heart failure was not reported but asymptomatic left ventricular ejection fraction (LVEF) decline was observed 3 (1.9%) and 18 (15.5%) patients in the 9 week and 52 week trastuzumab treatment groups, respectively (P < 0.001).Conclusion:In our study, the efficacy of trastuzumab for 52 weeks and 9 weeks was similar in node-positive HER-2 positive breast cancer. Cardiotoxicity was significantly increased in the 52 week trastuzumab arm compared to the 9 week trastuzumab arm.

The study of associations between circulating tumor cells and clinicopathologic characteristics in axillary lymph node positive primary breast cancer

To investigate the correlations between circulating tumor cell (CTC) and clinicopathologic characteristics of tumors obtained by core needle biopsy in axillary lymph node positive primary breast cancer patients. The peripheral venous blood samples were collected from 126 patients with axillary lymph node positive primary breast cancer and were detected to found CTCs using the CellSearch automatic detection system. The associations between CTCs and clinicopathologic characteristics of tumors were analyzed in axillary lymph node positive primary breast cancer patients. All patients were female, age ranging from 27 to 65 years (median, 49 years). One or more CTCs were detected from the peripheral blood in 25.4% (32/126) patients. The positive rate of CTCs was 36.2% (17/47) in the human epidermal growth factor receptor 2 (HER-2) (+) patients, 19.0% (15/79) in the HER-2 (-) patients. In univariate analysis, there were significant differences about the positive rate of CTCs between the two groups (χ² = 4.592, P < 0.05). In multivariate analysis, the risk of circulating tumor cells positive in HER-2 (+) patients was 2.712 times higher than in HER-2 (-) patients (OR = 2.712, 95% CI: 1.117-6.584, P = 0.027), whereas the positive rate of CTCs in axillary lymph node positive primary breast cancer patients showed no significant differences among the different subgroups with regards to age, menopausal status, the T staging of the tumor, histological type, histological grade, hormone receptor status and Ki-67 expression level (P > 0.05). There are significant correlations between the presence of CTCs and the HER-2 status of the tumor in axillary lymph node positive primary breast cancer patients. No significant correlations are found between the presence of CTCs and the age, menopausal status, T staging of the tumor, histological type, histological grade, hormone receptor status and Ki-67 expression level.

Topoisomerase II Alpha and Microtubule-associated Protein-tau as a Predictive Marker in Axillary Lymph Node Positive Breast Cancer

Topoisomerase II Alpha and Microtubule-associated Protein-tau as a Predictive Marker in Axillary Lymph Node Positive Breast Cancer

Abstract P1-13-09: A multicenter randomized study comparing the dose dense G-CSF-supported sequential administration of FEC followed by docetaxel versus paclitaxel as adjuvant chemotherapy in women with axillary lymph node positive breast cancer.

Abstract Purpose: To compare the efficacy of dose dense docetaxel versus paclitaxel following FEC as adjuvant chemotherapy in node positive early breast cancer. Patients and treatment: Women 18–75 years old with histologically confirmed HER2-negative invasive breast carcinoma surgically resected with at least one infiltrated axillary lymph node and absence of metastatic disease were randomized to receive 4 cycles of fluorouracil (700mg/m2), epirubicin (75mg/m2), cyclophosphamide (700mg/m2) followed by 4 cycles of either docetaxel (75mg/m2) or paclitaxel (175mg/m2). All chemotherapy cycles were administered every 14 days with G-CSF support. Stratification was based on menopausal status, number of involved nodes and hormone receptor expression. The primary endpoint of the study was to compare the disease-free survival (DFS) at 3 years and 239 patients were scheduled to enroll on each arm. Results: Between 2004–2007, 481 women were randomized and received FEC followed by docetaxel (arm A; n=240) or paclitaxel (arm B; n=241). The median age was 55 years in both arms, premenopausal status 31.3% versus 32.8%, more than 10 involved axillary nodes in 12.9% versus 12.4%, histological grade 3 tumor in 36.3% versus 35.3% and hormone receptor negative disease in 14.6% versus 12% of patients in arms A and B, respectively. After a median follow up of 56.3 and 55.6 months (p = 0.3) for arms A and B, respectively, there were 42 (17.5%) versus 47 (19.5%) disease relapses (p = 0.5) and 20 (8.3%) versus 22 (9.1%) disease-related deaths (p = 0.7), respectively. The 3-year DFS rates were 88.1% versus 87.3% for arms A and B, respectively. Toxicity included grade 2–4 neutropenia in 31% versus 21% (p = 0.01), thrombocytopenia 3.5% versus 0.8% (p = 0.06), febrile neutropenia 2.1% versus 1.2% (p = 0.5), diarrhea 3.7% versus 2.5% (p = 0.4), neurotoxicity 2.9% versus 4.6% (p = 0.3) of patients in arms A and B, respectively. There were no toxic deaths. Conclusion: The dose dense administration with G-CSF support of FEC followed by either docetaxel or paclitaxel as adjuvant chemotherapy in women with node positive early breast cancer is well tolerated and results in a similar 3-year DFS rate. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-13-09.

Abstract P1-13-01: A randomized trial of CEF versus dose dense EC followed by paclitaxel versus AC followed by paclitaxel in women with node positive or high risk node negative breast cancer, NCIC CTG MA.21: Results of the final relapse free survival analysis.

Abstract Background: In 2000, cyclophosphamide(C), epirubicin(E) and fluorouracil (F) (CEF) and doxorubicin (A) and C followed by paclitaxel (T) (AC/T) given every three weeks were commonly used regimens in Canada and the USA to treat women with node positive or high risk node negative operable breast cancer. In a previous trial in women with locally advanced breast cancer, 3 months of dose-dense EC was equivalent to six months of CEF. We hypothesized that the addition of 3 months of a taxane following dose-dense EC would be superior to CEF alone or AC/T. In a randomized trial in women with early breast cancer we compared CEF, dose dense EC/T and AC/T. An interim analysis (JCO, 2010) conducted when 50% of the events for the relapse-free-survival (RFS) analysis were observed, demonstrated that AC/T administered every 3 weeks was significantly inferior to CEF or EC/T. The results of the final RFS including CEF versus EC/T will be presented. Methods: Women, 60 years or younger, with operable axillary node positive or high risk node negative breast cancer were randomized to adjuvant CEF, EC/T or AC/T. CEF was given for 6 cycles and consisted of: C 75 mg/m2 orally on Days 1–14, and E 60 mg/m2 and F 500 mg/m2, IV on Days 1 and 8. CEF patients received concurrent antibiotic prophylaxis. EC/T consisted of 6 cycles of EC every 14 days; E 120 mg/m2 and C 830 mg/m2, both IV on Day 1 with filgrastim 5 [ug]/kg/day subcutaneous from Days 2–13 and epoetin alpha 40,000 units subcutaneous once weekly. After completion of EC, 4 cycles of T 175 mg/m2 every 21 days with filgrastim and epoetin alpha were given. The AC/T regimen consisted of A 60 mg/m2 and C 600 mg/m2 IV every 21 days for 4 cycles. This was followed by T 175 mg/m2 every 21 days for 4 cycles. The final analysis for RFS was planned when 453 events were observed permitting the detection of a hazard ratio (HR) of 1.43 between CEF and AC/T and a HR of 1.43 between EC/T and the best of the other two arms. Quality of Life data using the EORTC C-30 and the Breast Cancer Chemotherapy questionnaires were collected throughout the study. The results will be available at the time of the presentation. Results: A total of 2104 women were enrolled between December 2000 and April 2005. The required 453 events for the RFS analysis were observed by the clinical cut-off date of March 30, 2012. At this point 369 deaths had been observed. The median follow-up is 87.5 months. Outstanding data and queries are currently being collected and reviewed with an expected database lock and final analysis mid August, 2012. Febrile neutropenia remains higher on the CEF and EC/T arms while more neuropathy was seen in the taxane containing regimens. Conclusions: Although the two regimens considered a standard of care at the time the study was initiated are no longer widely used, the trial results will enhance our understanding of the magnitude of benefit of taxane following an anthracycline, the significance of cumulative anthracycline dose, and the role of dose density/ intensity as backbone of conventional chemo regimens. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-13-01.

Relationship between taxane-induced neuropathy and clinical outcomes after adjuvant chemotherapy.

270 Background: Neuropathy is a common and potentially enduring and disabling complication of adjuvant taxane therapy. Recent studies have identified candidate host single nucleotide polymorphisms (SNPs) associated with taxane-induced neuropathy (Schneider et al. ASCO 2011, abstr. 1000). We therefore sought to determine whether neuropathy was associated with breast cancer recurrence. Methods: This study included 4,950 eligible women with axillary lymph node positive or high-risk node-negative breast cancer who received up to 4 cycles of AC (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2) every 3 weeks, followed by either: (1) paclitaxel 175 mg/m2 every 3 weeks x 4 (P3), (2) paclitaxel 80 mg/m2 weekly x 12 (P1), (3) docetaxel 100 mg/m2 every 3 weeks x 4 (D3), or (4) docetaxel 35 mg/m2 weekly x 12 (D1). Chemotherapy doses were based on actual body weight. Cox proportional hazards model were used to determine the relationship between neuropathy and disease free survival (DFS) and overall survival (OS) treating neuropathy status as a time dependent covariate and using a landmark analysis. Results: Of 4,702 patients who received at least 1 taxane dose, grade 2-4 neuropathy developed in 20%, 27%, 16%, and 16% in the P3, P1, D3, and D1 arms, respectively. In a model including age, tumor size, nodal status, treatment arm, neuropathy, and the neuropathy- treatment interaction, there was no relationship between neuropathy and DFS and OS in the entire population, for any of the individual treatment arms, or for any breast cancer subtypes, whether analyzed as a time-dependent covariate or using a landmark analysis. Baseline covariates associated with an increase rate of neuropathy included black race (25% vs. 19% grade 2-4, p=0.02) and obesity (21% vs. 19%, p=0.04), but not age. Conclusions: There was no association between taxane-induced neuropathy and DFS or OS in patients treated with contemporary AC-taxane therapy, including weekly paclitaxel. These findings show that taxane-induced neuropathy is not associated with outcome, thus suggesting that validation of SNPs predictive of neuropathy may be useful in identifying patients at higher risk for neuropathy but not taxane benefit and thereby improve therapeutic individualization.

The Prognostic Significance of the Lymph Node Ratio in Axillary Lymph Node Positive Breast Cancer

PurposeThis study evaluated the prognostic impact of the lymph node ratio (LNR; i.e., the ratio of positive to dissected lymph nodes) on recurrence and survival in breast cancer patients with positive axillary lymph nodes (LNs).MethodsThe study cohort was comprised of 330 breast cancer patients with positive axillary nodes who received postoperative radiotherapy between 1987 and 2004. Ten-year Kaplan-Meier locoregional failure, distant metastasis, disease-free survival (DFS) and disease-specific survival (DSS) rates were compared using Kaplan-Meier curves. The prognostic significance of the LNR was evaluated by multivariate analysis.ResultsMedian follow-up was 7.5 years. By minimum p-value approach, 0.25 and 0.55 were the cutoff values of LNR at which most significant difference in DFS and DSS was observed. The DFS and DSS rates correlated significantly with tumor size, pN classification, LNR, histologic grade, lymphovascular invasion, the status of estrogen receptor and progesterone receptor. The LNR based classification yielded a statistically larger separation of the DFS curves than pN classification. In multivariate analysis, histologic grade and pN classification were significant prognostic factors for DFS and DSS. However, when the LNR was included as a covariate in the model, the LNR was highly significant (p<0.0001), and pN classification was not statistically significant (p>0.05).ConclusionThe LNR predicts recurrence and survival more accurately than pN classification in our study. The pN classification and LNR should be considered together in risk estimates for axillary LNs positive breast cancer patients.