Residual Axillary Burden After Neoadjuvant Chemotherapy (NACT) in Early Breast Cancer in Patients with a priori Clinically Occult Nodal Metastases – a transSENTINA Analysis

Abstract

Background Among patients with breast cancer undergoing neoadjuvant chemotherapy (NACT), the association between pathological complete remission (pCR) in the breast and clinical/pathological parameters is well established, whereas the association between these parameters and residual axillary involvement after NACT remains unclear.

Methods Patients with clinically occult nodal metastases (i.e. negative by clinical assessment but positive by SLNB prior to NACT, i.e. Arm B of the SENTINA trial) were included in the presented analysis. All patients received a second sentinel lymph node biopsy (SLNB) and axillary dissection after NACT. Univariate and multivariate analyses were carried out to evaluate the association between clinical/pathological parameters and axillary involvement after NACT.

Results Arm B of the SENTINA study contained 360 patients, 318 of which were evaluable for this analysis. After NACT, 71/318 (22.3%) patients had involved SLNs or non-SLNs after NACT. Overall, 71/318 (22.3%) patients achieved a pCR in the breast. Associations of extranodal spread, lack of multifocality and pCR in the breast with residual axillary burden were statistically significant. In a descriptive analysis including all patients with clinically negative axilla before NACT in the SENTINA trial 1.2% of triple negative (TN) patients and 0.5% of HER/2 positive patients had residual axillary disease in case of a breast pCR.

Conclusions Patients in the SENTINA trial with clinically negative axilla and involved SLNs still carried a significant risk of nodal metastases after NACT. However, the risk of residual axillary burden was particularly low in TN and HER/2 positive tumors in case of a breast pCR.

Zusammenfassung

Hintergrund Der Zusammenhang zwischen pathologischer Komplettremission (pCR) der Brust und klinischen/pathologischen Parametern ist bei Brustkrebspatientinnen, die sich einer neoadjuvanten Chemotherapie (NAC) unterziehen, bekannt. Noch nicht geklärt ist aber der Zusammenhang zwischen diesen Parametern und der residualen axillären Lymphknotenlast nach NAC.

Methoden In dieser Studie wurden Patientinnen mit klinisch-okkulten Lymphknotenmetastasen (d. h. klinisch-negativ, aber SLN-positiv vor NAC; d. h. aus dem Arm B der SENTINA-Studie) aufgenommen. Bei allen Patientinnen wurde eine zweite Sentinel-Lymphknoten-Biopsie (SLNB) sowie eine axilläre Lymphknotendissektion nach der NAC durchgeführt. Es wurden univariate und multivariate Analysen durchgeführt, um den Zusammenhang zwischen klinischen/pathologischen Parametern und axillärem Lymphknotenbefall nach NAC zu bestimmen.

Ergebnisse Es wurden 360 Patientinnen aus dem Arm B der SENTINA-Studie in diese Studie aufgenommen, die Daten von 318 dieser Patientinnen wurden analysiert. Nach der NAC wurde bei 71/318 (22,3%) Patientinnen ein Befall der SLN oder Non-SLN festgestellt. Bei insgesamt 71/318 (22,3%) Patientinnen konnte eine pCR der Brust erreicht werden. Der Zusammemhang zwischen extranodaler Ausbreitung, fehlender Multifokalität sowie pCR der Brust und der residualen axillären Lymphknotenlast war statistisch signifikant. Bei der deskriptiven Analyse aller Patientinnen mit klinisch-negativen axillären Lymphknoten vor NAC in der SENTINA-Studie hatten 1,2% der triple-negativen (TN) Patientinnen und 0,5% der HER/2-positiven Patientinnen eine residuale axilläre Tumorlast trotz pCR der Brust.

Schlussfolgerungen Patientinnen der SENTINA-Studie mit klinisch-negativen axillären Lymphknoten und Sentinel-Lymphknoten-Befall haben ein signifikantes Risiko für nodale Metastasen nach NAC. Allerdings ist das Risiko einer residualen axillären Tumorlast besonders gering bei Frauen mit pathologischer Komplettremission der Brust und triple-negativen oder HER/2-positiven Tumoren.

Key words

prediction of lymph node status - primary systemic therapy - SENTINA trial - sentinel lymph node biopsy

Schlüsselwörter

prädiktiver Wert des Lymphknotenstatus - primäre Systemtherapie - SENTINA-Studie - Sentinel-Lymphknoten-Biopsie

Publication History

Received: 20 August 2020

Accepted after revision: 30 October 2020

Article published online:
03 December 2020

• References

• 1 Fisher B, Bauer M, Wickerham DL. et al. Relation of number of positive axillary nodes to the prognosis of patients with primary breast cancer. An NSABP update. Cancer 1983; 52: 1551-1557
• 2 Curigliano G, Burstein HJ, Winer EP. et al. De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann Oncol 2018; 29: 2153 doi:10.1093/annonc/mdx806
• 3 Reimer T, Engel J, Schmidt M. et al. Is Axillary Sentinel Lymph Node Biopsy Required in Patients Who Undergo Primary Breast Surgery?. Breast Care (Basel) 2018; 13: 324-330 doi:10.1159/000491703
• 4 Engel J, Emeny RT, Hölzel D. Positive lymph nodes do not metastasize. Cancer Metastasis Rev 2012; 31: 235-246
• 5 Sparano JA, Gray RJ, Makower DF. et al. Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer. N Engl J Med 2018; 379: 111-121 doi:10.1056/NEJMoa1804710
• 6 Cardoso F, vanʼt Veer LJ, Bogaerts J. et al. MINDACT Investigators. 70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer. N Engl J Med 2016; 375: 717-729 doi:10.1056/NEJMoa1602253
• 7 Albain KS, Barlow WE, Shak S. et al. Breast Cancer Intergroup of North America. Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial. Lancet Oncol 2010; 11: 55-65 doi:10.1016/S1470-2045(09)70314-6
• 8 Giuliano AE, Hunt KK, Ballman KV. et al. Axillary dissection vs. no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA 2011; 305: 569-575
• 9 Reimer T, Stachs A, Nekljudova V. et al. Restricted Axillary Staging in Clinically and Sonographically Node-Negative Early Invasive Breast Cancer (c/iT1–2) in the Context of Breast Conserving Therapy: First Results Following Commencement of the Intergroup-Sentinel-Mamma (INSEMA) Trial. Geburtshilfe Frauenheilkd 2017; 77: 149-157 doi:10.1055/s-0042-122853
• 10 Kuehn T, Bauerfeind I, Fehm T. et al. Sentinel-lymph-node biopsy in patients with breast cancer before and after neoadjuvant chemotherapy (SENTINA): a prospective, multicentre cohort study. Lancet Oncol 2013; 14: 609-618
• 11 Boughey JC, Suman VJ, Mittendorf EA. et al. Alliance for Clinical Trials in Oncology. Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 (Alliance) clinical trial. JAMA 2013; 310: 1455-1461 doi:10.1001/jama.2013.278932
• 12 Classe JM, Loaec C, Gimbergues P. et al. Sentinel lymph node biopsy without axillary lymphadenectomy after neoadjuvant chemotherapy is accurate and safe for selected patients: the GANEA 2 study. Breast Cancer Res Treat 2019; 173: 343-352 doi:10.1007/s10549-018-5004-7
• 13 Rao R, Euhus D, Mayo HG. et al. Axillary node interventions in breast cancer: a systematic review. JAMA 2013; 310: 1385-1394
• 14 Cortazar P, Zhang L, Untch M. et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 2014; 384: 164-172 doi:10.1016/S0140-6736(13)62422-8
• 15 Shi ZQ, Qiu PF, Liu YB. et al. Neo-adjuvant chemotherapy and axillary de-escalation management for patients with clinically node-negative breast cancer. Breast J 2019; 25: 1154-1159 doi:10.1111/tbj.13422
• 16 Liedtke C, Kolberg HC, Kerschke L. et al. Systematic analysis of parameters predicting pathological axillary status (ypN0 vs. ypN+) in patients with breast cancer converting from cN+ to ycN0 through primary systemic therapy (PST). Clin Exp Metastasis 2018; 35: 777-783
• 17 Samiei S, van Nijnatten TJA, de Munck L. et al. Correlation Between Pathologic Complete Response in the Breast and Absence of Axillary Lymph Node Metastases After Neoadjuvant Systemic Therapy. Ann Surg 2020; 271: 574-580 doi:10.1097/SLA.0000000000003126
• 18 R Core Team. R: A language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2019. Accessed February 02, 2019 at: https://www.R-project.org/
• 19 Ditsch N, Untch M, Thill M. et al. AGO Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2019. Breast Care (Basel) 2019; 14: 224-245 doi:10.1159/000501000
• 20 Classe JM, Bordes V, Campion L. et al. Sentinel lymph node biopsy after neoadjuvant chemotherapy for advanced breast cancer: results of Ganglion Sentinelle et Chimiotherapie Neoadjuvante, a French prospective multicentric study. J Clin Oncol 2009; 27: 726-732 doi:10.1200/JCO.2008.18.3228
• 21 von Minckwitz G, Untch M, Blohmer JU. et al. Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol 2012; 30: 1796-1804 doi:10.1200/JCO.2011.38.8595
• 22 Marmor S, Hui JYC, Huang JL. et al. Relative effectiveness of adjuvant chemotherapy for invasive lobular compared with invasive ductal carcinoma of the breast. Cancer 2017; 123: 3015-3021 doi:10.1002/cncr.30699
• 23 Kantor O, Sipsy LM, Yao K. et al. A Predictive Model for Axillary Node Pathologic Complete Response after Neoadjuvant Chemotherapy for Breast Cancer. Ann Surg Oncol 2018; 25: 1304-1311 doi:10.1245/s10434-018-6345-5