Comparison of Axillary Sentinel Lymph Node Biopsy Versus no Axillary Surgery

Although there is no doubt that the presence of lymph node metastases worsens prognosis of a patient, unambiguous evidence to support lymph node dissection is still lacking. For many solid tumors, the role of lymph node dissection is yet controversial, and may depend on the tumor type and the stage of patient presentation for diagnosis. Axillary surgery for breast cancer is now considered as staging procedure that does not seem to influence breast cancer mortality. Women with breast cancer have benefitted greatly from a series of carefully performed randomized controlled trial focusing on axillary surgery. The objective of INSEMA is to show that less axillary surgery is better, in that oncological outcomes are the same and less surgical intervention will result in fewer surgical complications.

Sex

Female

Minimum age

18 Years

Inclusion Criteria:

* Written informed consent prior to beginning breast-conserving surgery, including expected cooperation of the patients for follow-up, must be obtained and documented according to the local regulatory requirements
* Histologically confirmed unilateral primary invasive carcinoma of the breast (core biopsy or open biopsy). Multifocal or multicentric tumors are allowed if breast-conserving surgery is planned
* Age at diagnosis at least 18 years
* Preoperative imaging techniques with estimated tumor size of \<5 cm (iT1/iT2 irrespective of hormone sensitivity or HER2 status)
* Clinically and sonographically tumor-free axilla prior to core biopsy (cN0/iN0)
* In cases with cN0 and iN+, a negative core biopsy or fine needle aspiration (FNA) biopsy of the sonographically suspected lymph node is required before randomization
* No clinical evidence for distant metastasis (M0)
* Planned breast-conserving surgery (R0 resection) with postoperative external whole-breast irradiation (conventional fractionation or hypofractionation)

Exclusion Criteria:

* History of malignancy within last 5 years, except curatively treated basalioma of the skin and carcinoma in situ of the cervix
* Time since core biopsy \>3 months (optimal \<1 month)
* Previous and already (neoadjuvant) treated invasive breast carcinoma
* Histologically non-invasive breast carcinoma
* cT3/T4 or iT3/T4 tumors
* pregnant or lactating patients
* Planned total mastectomy (e.g. multicentric tumors )
* Planned intraoperative radiotherapy (e.g. Intrabeam) or postoperative partial breast irradiation (e.g. multicatheter technique) alone; both procedures are allowed as boost techniques
* Male patients

• RESULTReimer T, Stachs A, Nekljudova V, Loibl S, Hartmann S, Wolter K, Hildebrandt G, Gerber B. 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 Feb;77(2):149-157. doi: 10.1055/s-0042-122853. PMID 28331237
• RESULTHildebrandt G, Stachs A, Gerber B, Potenberg J, Krug D, Wolter K, Kuhn T, Zierhut D, Sedlmayer F, Kaiser J, Reitsamer R, Heil J, Nekljudova V, Bekes I, Loibl S, Reimer T. Central Review of Radiation Therapy Planning Among Patients with Breast-Conserving Surgery: Results from a Quality Assurance Process Integrated into the INSEMA Trial. Int J Radiat Oncol Biol Phys. 2020 Jul 15;107(4):683-693. doi: 10.1016/j.ijrobp.2020.04.042. Epub 2020 May 11. PMID 32437921
• RESULTReimer T, Stachs A, Veselinovic K, Polata S, Muller T, Kuhn T, Heil J, Ataseven B, Reitsamer R, Hildebrandt G, Knauer M, Golatta M, Stefek A, Zahm DM, Thill M, Nekljudova V, Krug D, Loibl S, Gerber B; INSEMA investigators. Patient-reported outcomes for the Intergroup Sentinel Mamma study (INSEMA): A randomised trial with persistent impact of axillary surgery on arm and breast symptoms in patients with early breast cancer. EClinicalMedicine. 2022 Nov 25;55:101756. doi: 10.1016/j.eclinm.2022.101756. eCollection 2023 Jan. PMID 36457648
• RESULTMarme F, Krieghoff-Henning E, Gerber B, Schmitt M, Zahm DM, Bauerschlag D, Forstbauer H, Hildebrandt G, Ataseven B, Brodkorb T, Denkert C, Stachs A, Krug D, Heil J, Golatta M, Kuhn T, Nekljudova V, Gaiser T, Schonmehl R, Brochhausen C, Loibl S, Reimer T, Brinker TJ. Deep learning to predict breast cancer sentinel lymph node status on INSEMA histological images. Eur J Cancer. 2023 Dec;195:113390. doi: 10.1016/j.ejca.2023.113390. Epub 2023 Oct 18. PMID 37890350
• RESULTReimer T, Stachs A, Veselinovic K, Kuhn T, Heil J, Polata S, Marme F, Muller T, Hildebrandt G, Krug D, Ataseven B, Reitsamer R, Ruth S, Denkert C, Bekes I, Zahm DM, Thill M, Golatta M, Holtschmidt J, Knauer M, Nekljudova V, Loibl S, Gerber B. Axillary Surgery in Breast Cancer - Primary Results of the INSEMA Trial. N Engl J Med. 2025 Mar 13;392(11):1051-1064. doi: 10.1056/NEJMoa2412063. Epub 2024 Dec 12.