Preoperative factors that predict pathologic nodal involvement in early-stage HER2+ breast cancer: selecting cT1cN0 patients for treatment with neoadjuvant chemotherapy versus upfront surgery.
Axillary lymph nodes
Breast neoplasms
HER2
Neoadjuvant chemotherapy
Journal
Breast cancer research and treatment
ISSN: 1573-7217
Titre abrégé: Breast Cancer Res Treat
Pays: Netherlands
ID NLM: 8111104
Informations de publication
Date de publication:
21 Feb 2024
21 Feb 2024
Historique:
received:
28
08
2023
accepted:
05
01
2024
medline:
21
2
2024
pubmed:
21
2
2024
entrez:
21
2
2024
Statut:
aheadofprint
Résumé
The goal of this study was to identify the preoperative predictors of pathologic nodal metastases (pN+) in cT1cN0 HER2+ breast cancer undergoing upfront surgery. We retrospectively reviewed data from women with cT1-T2N0 HER2+ breast cancer treated with neoadjuvant therapy (NAC) or upfront surgery at our institution between 2012 and 2023. Factors associated with management strategy were evaluated, and in those undergoing upfront surgery, univariate analyses were performed to identify the clinicopathologic factors associated with nodal metastases. Overall, 255 women with cT1-T2N0 HER2+ breast cancer met inclusion criteria, including 170 (68.6%) upfront surgery patients and 85 (31.4%) who underwent NAC. The median age at diagnosis was 59 years (range, 27-90 years). Younger age, larger clinical tumor size, high-grade disease, ER-PR-HER2+ subtype, and year of diagnosis after 2019 were significantly associated with receipt of NAC (p < 0.05). In those undergoing upfront surgery, 25.3% were pN+ , including 32.5% of cT1cN0 tumors. Factors associated with nodal involvement included age under 50, larger clinical tumor size, lymphovascular invasion (LVI), multifocality/multicentricity, and abnormal lymph nodes on axillary ultrasound (p < 0.05). In subset analysis of cT1cN0 HER2+ cases, LVI remained the strongest predictor of pN + disease (73.3% vs. 22.6%, p < 0.001). Patients with cT1cN0 HER2+ breast cancer under 50 years had a 47.1% likelihood of pN+ disease. Patients with cT1cN0 breast cancer have a 32.5% likelihood of nodal metastases, with higher incidence with younger age, LVI, multifocality/multicentricity, and abnormal axillary ultrasound. The presence of these factors may identify the patients who would benefit from treatment with neoadjuvant chemotherapy.
Identifiants
pubmed: 38381275
doi: 10.1007/s10549-024-07251-8
pii: 10.1007/s10549-024-07251-8
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Fonds de Recherche du Québec - Santé
ID : 309854
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Références
Howlader N, Altekruse SF, Li CI, Chen VW, Clarke CA, Ries LA, Cronin KA (2014) US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status. J Natl Cancer Inst. https://doi.org/10.1093/jnci/dju055
doi: 10.1093/jnci/dju055
pubmed: 24777111
pmcid: 4580552
Tolaney SM, Barry WT, Dang CT, Yardley DA, Moy B, Marcom PK, Albain KS, Rugo HS, Ellis M, Shapira I et al (2015) Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer. N Engl J Med 372(2):134–141
doi: 10.1056/NEJMoa1406281
pubmed: 25564897
pmcid: 4313867
Tolaney SM, Guo H, Pernas S, Barry WT, Dillon DA, Ritterhouse L, Schneider BP, Shen F, Fuhrman K, Baltay M et al (2019) Seven-year follow-up analysis of adjuvant paclitaxel and trastuzumab trial for node-negative, human epidermal growth factor receptor 2-positive breast cancer. J Clin Oncol 37(22):1868–1875
doi: 10.1200/JCO.19.00066
pubmed: 30939096
pmcid: 7587424
Tolaney SM, Tarantino P, Graham N, Tayob N, Pare L, Villacampa G, Dang CT, Yardley DA, Moy B, Marcom PK et al (2023) Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer: final 10-year analysis of the open-label, single-arm, phase 2 APT trial. Lancet Oncol 24(3):273–285
doi: 10.1016/S1470-2045(23)00051-7
pubmed: 36858723
von Minckwitz G, Huang CS, Mano MS, Loibl S, Mamounas EP, Untch M, Wolmark N, Rastogi P, Schneeweiss A, Redondo A et al (2019) Trastuzumab emtansine for residual invasive HER2-positive breast cancer. N Engl J Med 380(7):617–628
doi: 10.1056/NEJMoa1814017
Mamounas EP, Untch M, Mano MS, Huang CS, Geyer CE Jr, von Minckwitz G, Wolmark N, Pivot X, Kuemmel S, DiGiovanna MP et al (2021) Adjuvant T-DM1 versus trastuzumab in patients with residual invasive disease after neoadjuvant therapy for HER2-positive breast cancer: subgroup analyses from KATHERINE. Ann Oncol 32(8):1005–1014
doi: 10.1016/j.annonc.2021.04.011
pubmed: 33932503
Balic M, Thomssen C, Gnant M, Harbeck N (2023) St. Gallen/Vienna 2023: optimization of treatment for patients with primary breast cancer - A brief summary of the consensus discussion. Breast Care (Basel) 18(3):213–222
doi: 10.1159/000530584
pubmed: 37383954
Waks AG, Tolaney SM (2015) The evolving understanding of small HER2-positive breast cancers: matching management to outcomes. Future Oncol 11(24):3261–3271
doi: 10.2217/fon.15.240
pubmed: 26634944
Dominici LS, Negron Gonzalez VM, Buzdar AU, Lucci A, Mittendorf EA, Le-Petross HT, Babiera GV, Meric-Bernstam F, Hunt KK, Kuerer HM (2010) Cytologically proven axillary lymph node metastases are eradicated in patients receiving preoperative chemotherapy with concurrent trastuzumab for HER2-positive breast cancer. Cancer 116(12):2884–2889
doi: 10.1002/cncr.25152
pubmed: 20564395
Hunt KK, Yi M, Mittendorf EA, Guerrero C, Babiera GV, Bedrosian I, Hwang RF, Kuerer HM, Ross MI, Meric-Bernstam F (2009) Sentinel lymph node surgery after neoadjuvant chemotherapy is accurate and reduces the need for axillary dissection in breast cancer patients. Ann Surg 250(4):558–566
doi: 10.1097/SLA.0b013e3181b8fd5e
pubmed: 19730235
Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, Tausch C, Seo JH, Tsai YF, Ratnayake J et al (2013) Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol 24(9):2278–2284
doi: 10.1093/annonc/mdt182
pubmed: 23704196
Untch M, Jackisch C, Schneeweiss A, Conrad B, Aktas B, Denkert C, Eidtmann H, Wiebringhaus H, Kummel S, Hilfrich J et al (2016) Nab-paclitaxel versus solvent-based paclitaxel in neoadjuvant chemotherapy for early breast cancer (GeparSepto-GBG 69): a randomised, phase 3 trial. Lancet Oncol 17(3):345–356
doi: 10.1016/S1470-2045(15)00542-2
pubmed: 26869049
van Ramshorst MS, van der Voort A, van Werkhoven ED, Mandjes IA, Kemper I, Dezentje VO, Oving IM, Honkoop AH, Tick LW, van de Wouw AJ et al (2018) Neoadjuvant chemotherapy with or without anthracyclines in the presence of dual HER2 blockade for HER2-positive breast cancer (TRAIN-2): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol 19(12):1630–1640
doi: 10.1016/S1470-2045(18)30570-9
pubmed: 30413379
Kuemmel S, Heil J, Rueland A, Seiberling C, Harrach H, Schindowski D, Lubitz J, Hellerhoff K, Ankel C, Grasshoff ST et al (2022) A prospective, multicenter registry study to evaluate the clinical feasibility of targeted axillary dissection (TAD) in node-positive breast cancer patients. Ann Surg 276(5):e553–e562
doi: 10.1097/SLA.0000000000004572
pubmed: 33156057
Mamtani A, Barrio AV, King TA, Van Zee KJ, Plitas G, Pilewskie M, El-Tamer M, Gemignani ML, Heerdt AS, Sclafani LM et al (2016) How Often Does neoadjuvant chemotherapy avoid axillary dissection in patients with histologically confirmed nodal metastases? Results of a prospective study. Ann Surg Oncol 23(11):3467–3474
doi: 10.1245/s10434-016-5246-8
pubmed: 27160528
pmcid: 5070651
Simons JM, van Nijnatten TJA, van der Pol CC, van Diest PJ, Jager A, van Klaveren D, Kam BLR, Lobbes MBI, de Boer M, Verhoef C et al (2022) Diagnostic accuracy of radioactive iodine seed placement in the axilla with sentinel lymph node biopsy after neoadjuvant chemotherapy in node-positive breast cancer. JAMA Surg 157(11):991–999
doi: 10.1001/jamasurg.2022.3907
pubmed: 36069889
pmcid: 9453629
Al-Hilli Z, Hoskin TL, Day CN, Habermann EB, Boughey JC (2018) Impact of neoadjuvant chemotherapy on nodal disease and nodal surgery by tumor subtype. Ann Surg Oncol 25(2):482–493
doi: 10.1245/s10434-017-6263-y
pubmed: 29181679
Thompson JL, Wrubel E, Davis AT, Koehler T, Chung MH, Wright GP (2020) Impact of neoadjuvant versus adjuvant chemotherapy on the extent of axillary surgery for clinically node-negative breast cancers of triple-negative and HER2-Overexpressing phenotypes. Clin Breast Cancer 20(5):390–394
doi: 10.1016/j.clbc.2020.04.007
pubmed: 32444317
Englander K, Chintapally N, Gallagher J, Elleson K, Sun W, Whiting J, Laronga C, Lee MC (2023) Factors influencing lymph node positivity in HER2/neu+ breast cancer patients. Curr Oncol 30(3):2825–2833
doi: 10.3390/curroncol30030215
pubmed: 36975428
pmcid: 10047436
McCaffrey RL, Thompson JL, Oudsema RH, Sciallis AP, Cobain EF, Sabel MS, Jeruss JS (2022) Management of early stage HER2 positive breast cancer and increased implementation of axillary imaging to improve identification of nodal metastasis. J Surg Oncol 125(8):1218–1223
doi: 10.1002/jso.26840
pubmed: 35230701
Weiss A, Martinez-Saez O, Waks AG, Laws A, McGrath M, Tarantino P, Portnow L, Winer E, Rey M, Tapia M et al (2023) Nodal positivity and systemic therapy among patients with clinical T1–T2N0 human epidermal growth factor receptor-positive breast cancer: Results from two international cohorts. Cancer 129(12):1836–1845
doi: 10.1002/cncr.34750
pubmed: 36951169
Faleh S, Prakash I, Eisenberg E, Basik M, Boileau JF, Tejera D, Panet F, Buhlaiga N, Meterissian S, Wong SM (2023) Predictors of nodal metastases in early stage HER2+ breast cancer: deciding on treatment approach with neoadjuvant chemotherapy vs. upfront surgery. Eur J Surg Oncol. https://doi.org/10.1016/j.ejso.2023.03.226
doi: 10.1016/j.ejso.2023.03.226
pubmed: 37031045
Capdet J, Martel P, Charitansky H, Lim YK, Ferron G, Battle L, Landier A, Mery E, Zerdoub S, Roche H et al (2009) Factors predicting the sentinel node metastases in T1 breast cancer tumor: an analysis of 1416 cases. Eur J Surg Oncol 35(12):1245–1249
doi: 10.1016/j.ejso.2009.06.002
pubmed: 19574018
Viale G, Zurrida S, Maiorano E, Mazzarol G, Pruneri G, Paganelli G, Maisonneuve P, Veronesi U (2005) Predicting the status of axillary sentinel lymph nodes in 4351 patients with invasive breast carcinoma treated in a single institution. Cancer 103(3):492–500
doi: 10.1002/cncr.20809
pubmed: 15612028
Prakash I, Neely NB, Thomas SM, Sammons S, Blitzblau RC, DiLalla GA, Hyslop T, Menendez CS, Plichta JK, Rosenberger LH et al (2022) Utilization of neoadjuvant chemotherapy in high-risk, node-negative early breast cancer. Cancer Med 11(4):1099–1108
doi: 10.1002/cam4.4517
pubmed: 34989142
pmcid: 8855910
Debien V (2022) DECRESCENDO: De-escalation of adjuvant chemotherapy in patients with HER2+/HR-/node-negative early breast cancer who achieve pCR after neoadjuvant taxane and subcutaneous dual anti-HER2 blockade. J Clin Oncol 40(16):621–621
doi: 10.1200/JCO.2022.40.16_suppl.TPS621
Waks AG, Desai NV, Li T, Poorvu PD, Partridge AH, Sinclair N, Spring LM, Faggen M, Constantine M, Metzger O et al (2022) A prospective trial of treatment de-escalation following neoadjuvant paclitaxel/trastuzumab/pertuzumab in HER2-positive breast cancer. NPJ Breast Cancer 8(1):63
doi: 10.1038/s41523-022-00429-7
pubmed: 35538105
pmcid: 9091255
Nitz UA, Gluz O, Christgen M, Grischke EM, Augustin D, Kuemmel S, Braun M, Potenberg J, Kohls A, Krauss K et al (2017) De-escalation strategies in HER2-positive early breast cancer (EBC): final analysis of the WSG-ADAPT HER2+/HR- phase II trial: efficacy, safety, and predictive markers for 12 weeks of neoadjuvant dual blockade with trastuzumab and pertuzumab +/- weekly paclitaxel. Ann Oncol 28(11):2768–2772
doi: 10.1093/annonc/mdx494
pubmed: 28945833