ADVANCES IN BREAST CANCER DIAGNOSIS AND TREATMENT: ESSENTIALS

Advances in breast cancer diagnosis and treatment Essentials_kapak

MANAGEMENT OF DCIS AND EARLY STAGE BREAST CANCER

Burak Çelik

Koç University, Faculty of Medicine, Department of General Surgery, İstanbul, Türkiye

Çelik B. Management of DCIS and Early Stage Breast Cancer. In: Citgez B editor. Advances in Breast Cancer Diagnosis and Treatment Essentials. 1st ed. Ankara: Türkiye Klinikleri; 2025. p.119-136.

ABSTRACT

Ductal carcinoma in situ is a premalignant neoplasm without basement membrane invasion. According to the American Joint Committee on Cancer, it is classified as stage 0 cancer. DCIS accounts for 18% to 25% of all breast cancer diagnoses in the United States. With the widespread adoption of mammography as a screening tool, the detection rate has increased over the years. Approximately 80% of DCIS cases present as asymptomatic calcifications. The management and treatment of DCIS, like other types of breast cancer, should be carried out through a multidisciplinary approach, such as surgery, radiation oncology, and medical oncology, tailored to the individual patient’s diagnosis, risk factors, and personal treatment preferences. Initial treatment typically involves surgery, followed by radiotherapy if breast-conserving surgery is performed to improve local control. In addition, endocrine therapy in hormone receptor-positive DCIS has been proven to reduce the relative risk of developing invasive breast cancer. Recently, studies have begun to explore patient-specific treatment algorithms that may allow for the omission of surgery or radiotherapy in selected cases. Early-stage breast cancer includes tumors that are confined to the breast tissue and have not spread to more than three lymph nodes in the axilla. According to this definition, these tumors are classified as stage I or II based on the American Joint Committee on Cancer staging system. Surgery is generally considered the initial treatment for early-stage breast cancer. Accurate clinical staging, including identification of the tumor subtype, is essential for determining the appropriate treatment approach in patients diagnosed with breast cancer. It guides whether the patient should begin with surgery or proceed with upfront systemic therapy. However, neoadjuvant systemic therapy is preferred for patients with triple-negative or HER2-positive tumors that are two cms or larger or when axillary LNs are clinically involved (cN1). Over the past 15 years, studies have led to practice-changing developments in axillary management, significantly reducing axillary dissection among patients with limited positive lymph nodes. Ongoing research investigates the feasibility of applying similar approaches in patients who have received.

Keywords: Breast cancer; Ductal carcinoma in situ; Early stage; Sentinel lymph node biopsy; Breast surgery; Axilla; Radiotherapy

Referanslar

  1. Hortobagyi GN, Connolly JL, D'Orsi CJ, Edge SB, Mittendorf EA, et al. Breast. In: Amin MB, Edge S, Greene F, et al., editors. AJCC cancer staging manual. 8th ed. New York: Springer; 2017.
  2. Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;731:17-48. [Crossref]  [PubMed]
  3. Virnig BA, Tuttle TM, Shamliyan T, Kane RL. Ductal carcinoma in situ of the breast: a systematic review of incidence, treatment, and outcomes. J Natl Cancer Inst. 2010;1023:170-8. [Crossref]  [PubMed]
  4. Lynge E, Ponti A, James T, Májek O, von Euler-Chelpin M, Anttila A, et al. Variation in detection of ductal carcinoma in situ during screening mammography: a survey within the International Cancer Screening Network. Eur J Cancer. 2014;501:185-92. [Crossref]  [PubMed]  [PMC]
  5. DeSantis CE, Ma J, Gaudet MM, Newman LA, Miller KD, Goding Sauer A, et al. Breast cancer statistics, 2019. CA Cancer J Clin. 2019; 69:438-51. [Crossref]  [PubMed]
  6. Narod SA, Iqbal J, Giannakeas V, Sopik V, Sun P. Breast cancer mortality after a diagnosis of ductal carcinoma in situ. JAMA Oncol. 2015;17:888-96. [Crossref]  [PubMed]
  7. Bombonati A, Sgroi DC. The molecular pathology of breast cancer progression. J Pathol. 2011;2232:307-17. [Crossref]  [PubMed]  [PMC]
  8. Allred DC. Ductal carcinoma in situ: terminology, classification, and natural history. J Natl Cancer Inst Monogr. 2010;201041:134-8. [Crossref]  [PubMed]  [PMC]
  9. Lagios MD, Margolin FR, Westdahl PR, Rose MR. Mammographically detected duct carcinoma in situ: frequency of local recurrence following tylectomy and prognostic effect of nuclear grade on local recurrence. Cancer. 1989;634:618-24. [Crossref]  [PubMed]
  10. Guth AA, Mercado C, Roses DF, Darvishian F, Singh B, Cangiarella JF. Microinvasive breast cancer and the role of sentinel node biopsy: an institutional experience and review of the literature. Breast J. 2008;144:335-9. [Crossref]  [PubMed]
  11. McAuliffe P. Ductal carcinoma in situ. In: Aydiner A, Igci A, Soran A, eds. Breast Diseases: Diagnosis and Pathology. Vol.1. 2nd ed. Cham: Springer Nature Switzerland AG; 2019. p.115-24.
  12. Grimm LJ, Rahbar H, Abdelmalak M, Hall AH, Ryser MD. Ductal carcinoma in situ: state-of-the-art review. Radiology. 2021;3022:246-55. [Crossref]  [PubMed]  [PMC]
  13. Li JK, Wang HF, He Y, Huang Y, Liu G, Wang ZL. Ultrasonographic features of ductal carcinoma in situ: analysis of 219 lesions. Gland Surg. 2020;96:1945-54. [Crossref]  [PubMed]  [PMC]
  14. Obdeijn IMA, Loo CE, Rijnsburger AJ, Wasser MNJM, Bergers E, Kok T, et al. Assessment of false-negative cases of breast MR imaging in women with a familial or genetic predisposition. Breast Cancer Res Treat. 2010;1192:399-407. [Crossref]  [PubMed]
  15. Wurdinger S, Kamprath S, Eschrich D, Schneider A, Kaiser WA. False-negative findings of malignant breast lesions on preoperative magnetic resonance mammography. Breast. 2001; 10:131-9. [Crossref]  [PubMed]
  16. Greenwood HI, Maldonado Rodas CK, Freimanis RI, et al. Magnetic resonance imaging insights from active surveillance of women with ductal carcinoma in situ. NPJ Breast Cancer. 2024; 10:71. [Crossref]  [PubMed]  [PMC]
  17. Lehman CD, Gatsonis C, Kuhl CK, Hendrick RE, Pisano ED, Hanna L, et al. MRI evaluation of the contralateral breast in women with recently diagnosed breast cancer. N Engl J Med. 2007;35613:1295-303. [Crossref]  [PubMed]
  18. Li L, Roth R, Germaine P, Ren S, Lee M, Hunter K, et al. Contrast-enhanced spectral mammography CESM versus breast magnetic resonance imaging MRI: a retrospective comparison in 66 breast lesions. Diagn Interv Imaging. 2017;982:113-23. [Crossref]  [PubMed]
  19. Sensakovic WF, Carnahan MB, Czaplicki CD, Fahrenholtz S, Panda A, Zhou Y, et al. Contrast-enhanced mammography: how does it work? Radiographics. 2021;413:829-39. [Crossref]  [PubMed]
  20. Wapnir IL, Dignam JJ, Fisher B, Mamounas EP, Anderson SJ, Julian TB, et al. Long-term outcomes of invasive ipsilateral breast tumor recurrences after lumpectomy in NSABP B-17 and B-24 randomized clinical trials for DCIS. J Natl Cancer Inst. 2011;1036:478-88. [Crossref]  [PubMed]  [PMC]
  21. Tomlinson-Hansen SE, Khan M, Cassaro S. Breast ductal carcinoma in situ. In: StatPearls [Internet]. Treasure Island FL: StatPearls Publishing; 2025 Jan-.
  22. Boyages J, Delaney G, Taylor R. Predictors of local recurrence after treatment of ductal carcinoma in situ: a meta-analysis. Cancer. 1999;853:616-28. [Crossref]
  23. Wagner JL, Fearmonti R, Hunt KK, Hwang RF, Meric-Bernstam F, Kuerer HM, et al. Prospective evaluation of the nipple-areola complex sparing mastectomy for risk reduction and for early-stage breast cancer. Ann Surg Oncol. 2012;194:1137-44. [Crossref]  [PubMed]  [PMC]
  24. Papassotiropoulos B, Güth U, Chiesa F, et al. Prospective evaluation of residual breast tissue after skinor nipple-sparing mastectomy: results of the SKINI-trial. Ann Surg Oncol. 2019; 26:1254-62. [Crossref]  [PubMed]
  25. Fitzsullivan E, Lari SA, Smith B, Caudle AS, Krishnamurthy S, Lucci A, et al. Incidence and consequence of close margins in patients with ductal carcinoma in situ treated with mastectomy: is further therapy warranted? Ann Surg Oncol. 2013;2013:4103-12. [Crossref]  [PubMed]  [PMC]
  26. Marinovich ML, Azizi L, Macaskill P, Irwig L, Morrow M, Solin LJ, et al. The association of surgical margins and local recurrence in women with ductal carcinoma in situ treated with breast-conserving therapy: a meta-analysis. Ann Surg Oncol. 2016;23:3811-21. [Crossref]  [PubMed]  [PMC]
  27. Moran MS, Schnitt SJ, Giuliano AE, Harris JR, Khan SA, Horton J, et al. Society of Surgical Oncology-American Society for Radiation Oncology consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in stages I and II invasive breast cancer. Ann Surg Oncol. 2014;21:704-16. [Crossref]  [PubMed]
  28. Morrow M, Van Zee KJ, Solin LJ, Houssami N, Chavez-MacGregor M, Harris JR, et al. Society of Surgical Oncology-American Society for Radiation Oncology-American Society of Clinical Oncology consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in ductal carcinoma in situ. Ann Surg Oncol. 2016; 23:3801-10. [Crossref]  [PubMed]  [PMC]
  29. Kuerer HM, Smith BD, Chavez-MacGregor M, Albarracin C, Barcenas CH, Santiago L, et al. DCIS margins and breast conservation: MD Anderson Cancer Center multidisciplinary practice guidelines and outcomes. J Cancer. 2017;814:2653-62. [Crossref]  [PubMed]  [PMC]
  30. Shin YD, Lee HM, Choi YJ. Necessity of sentinel lymph node biopsy in ductal carcinoma in situ patients: a retrospective analysis. BMC Surg. 2021; 21:159. [Crossref]  [PubMed]  [PMC]
  31. Lee SK, Yang JH, Woo SY, Lee JE, Nam SJ. Nomogram for predicting invasion in patients with a preoperative diagnosis of ductal carcinoma in situ of the breast. Br J Surg. 2013;10013:1756-63. [Crossref]  [PubMed]
  32. Boler DE, Cabioglu N, Ince U, Esen G, Uras C. Sentinel lymph node biopsy in pure DCIS: is it necessary? ISRN Surg. 2012; 2012:394095. [Crossref]  [PubMed]  [PMC]
  33. Hwang ES, Hyslop T, Lynch T, Ryser MD, Weiss A, Wolf A, et al. Active monitoring with or without endocrine therapy for low-risk ductal carcinoma in situ: the COMET randomized clinical trial. JAMA. 2025;33311:972-80. [Crossref]  [PubMed]  [PMC]
  34. Francis A, Bartlett JMS, Billingham LJ, Bowden SJ, Brookes CL, Dodwell DJ, et al. The LORIS trial: a multicenter, randomized phase III trial of standard surgery versus active monitoring in women with newly diagnosed low-risk ductal carcinoma in situ. Cancer Res. 2013;73Suppl: OT2-3-1. [Crossref]
  35. Elshof LE, Tryfonidis K, Slaets L, van Leeuwen-Stok AE, Skinner VP, Dif N, et al. Feasibility of a prospective, randomised, open-label, international multicentre, phase III, non-inferiority trial to assess the safety of active surveillance for low-risk ductal carcinoma in situ: the LORD study. Eur J Cancer. 2015;5112:1497-510. [Crossref]  [PubMed]
  36. Kanbayashi C, Thompson AM, Hwang SS, Partridge AH, Rea DW, Wesseling J, et al. The international collaboration of active surveillance trials for low-risk DCIS LORIS, LORD, COMET, LORETTA. J Clin Oncol. 2019. [Crossref]
  37. Fisher B, Land S, Mamounas E, Dignam J, Fisher ER, Wolmark N. Prevention of invasive breast cancer in women with ductal carcinoma in situ: an update of the National Surgical Adjuvant Breast and Bowel Project experience. Semin Oncol. 2001;284:400-18. [Crossref]
  38. Julien JP, Bijker N, Fentiman IS, Peterse JL, Delledonne V, Rouanet P, et al. Radiotherapy in breast-conserving treatment for ductal carcinoma in situ: first results of the EORTC randomised phase III trial 10853. Lancet. 2000;3559203:528-33. [Crossref]  [PubMed]
  39. Houghton J, George WD, Cuzick J, Duggan C, Fentiman IS, Spittle M, et al. Radiotherapy and tamoxifen in women with completely excised ductal carcinoma in situ of the breast in the UK, Australia, and New Zealand: randomised controlled trial. Lancet. 2003;3629378:95-102. [Crossref]  [PubMed]
  40. Moran MS, Zhao Y, Ma S, et al. Association of radiotherapy boost for ductal carcinoma in situ with local control after whole-breast radiotherapy. JAMA Oncol. 2017;38:1060- 1068 [Crossref]  [PubMed]  [PMC]
  41. McCormick B, Winter KA, Woodward W, Kuerer HM, Sneige N, Rakovitch E, et al. Randomized phase III trial evaluating radiation following surgical excision for goodrisk ductal carcinoma in situ: long-term report from NRG Oncology/RTOG 9804. J Clin Oncol. 2021;3932:3574-82. [Crossref]  [PubMed]  [PMC]
  42. Bremer T, Whitworth PW, Patel R, Savala J, Barry T, Lyle S, et al. A biological signature for breast ductal carcinoma in situ to predict radiotherapy benefit and assess recurrence risk. Clin Cancer Res. 2018;2423:5895-901. [Crossref]  [PubMed]
  43. Fisher B, Dignam J, Wolmark N, Wickerham DL, Fisher ER, Mamounas E, et al. Tamoxifen in treatment of intraductal breast cancer: National Surgical Adjuvant Breast and Bowel Project B-24 randomised controlled trial. Lancet. 1999;3539169:1993-2000. [Crossref]  [PubMed]
  44. Cuzick J, Sestak I, Forbes JF, Dowsett M, Cawthorn S, Mansel RE, et al. Use of anastrozole for breast cancer prevention IBIS-II: long-term results of a randomised controlled trial. Lancet. 2020;39510218:117-22. [Crossref]  [PubMed]
  45. Margolese RG, Cecchini RS, Julian TB, Ganz PA, Costantino JP, Vallow LA, et al. Anastrozole versus tamoxifen in postmenopausal women with ductal carcinoma in situ undergoing lumpectomy plus radiotherapy NSABP B-35: a randomised, double-blind, phase 3 clinical trial. Lancet. 2016;38710021:849-56. [Crossref]  [PubMed]
  46. National Comprehensive Cancer Network [Internet]. NCCN Clinical Practice Guidelines in Oncology: Breast Cancer. Version 5.2024. Plymouth Meeting PA: National Comprehensive Cancer Network; ©2024 [Accessed: May 3, 2025].
  47. Lazzeroni M, Puntoni M, Guerrieri-Gonzaga A, Serrano D, Boni L, Buttiron Webber T, et al. Randomized placebo-controlled trial of low-dose tamoxifen to prevent recurrence in breast noninvasive neoplasia: a 10-year follow-up of TAM01 study. J Clin Oncol. 2023;4117:3116-21. [Crossref]  [PubMed]
  48. Byng D, Thomas SM, Rushing CN, Lynch T, McCarthy A, Francescatti AB, et al. Surveillance imaging after primary diagnosis of ductal carcinoma in situ. Radiology. 2023;3071 [Crossref]  [PubMed]  [PMC]
  49. Bastos MCS, Almeida AP, Bagnoli F, Oliveira VM. Early breast cancer: concept and therapeutic review. Rev Assoc Med Bras 1992. 2023;69Suppl 1:e2023S114. [Crossref]  [PubMed]  [PMC]
  50. Chang JM, Leung JWT, Moy L, Ha SM, Moon WK. Axillary nodal evaluation in breast cancer: state of the art. Radiology. 2020;2953:500-15. [Crossref]  [PubMed]
  51. Ganguly A, Giles TE, Smith PA, White FE, Nixon PP. The benefits of on-site cytology with ultrasound-guided fine needle aspiration in a one-stop neck lump clinic. Ann R Coll Surg Engl. 2010;928:660-664. [Crossref]  [PubMed]
  52. Surveillance, Epidemiology, and End Results SEER Program [Internet]. SEER cancer stat facts: female breast cancer. National Cancer Institute. [Accessed April 15, 2025].
  53. Groheux D, Vaz SC, Poortmans P, Mann RM, Ulaner GA, Cook GJR, et al. Role of [18F] FDG PET/CT in patients with invasive breast carcinoma of no special type: literature review and comparison between guidelines. Breast. 2024;78:103806. [Crossref]  [PubMed]  [PMC]
  54. Rubio IT, Sobrido C. Neoadjuvant approach in patients with early breast cancer: patient assessment, staging, and planning. Breast. 2022;62Suppl 1: S17-24. [Crossref]  [PubMed]  [PMC]
  55. Gianni L, Pienkowski T, Im YH, Tseng LM, Liu MC, Lluch A, et al. 5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer NeoSphere: a multicentre, open-label, phase 2 randomised trial. Lancet Oncol. 2016;176:791-800. [Crossref]  [PubMed]
  56. Boughey JC, McCall LM, Ballman KV, Mittendorf EA, Ahrendt GM, Wilke LG, et al. Tumor biology correlates with rates of breast-conserving surgery and pathologic complete response after neoadjuvant chemotherapy for breast cancer: findings from the ACOSOG Z1071 Alliance prospective multicenter clinical trial. Ann Surg. 2014;2604:608-14. [Crossref]  [PubMed]  [PMC]
  57. Loibl S, André F, Bachelot T, Barrios CH, Bergh J, Burstein HJ, et al. Early breast cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol. 2024;352:159-82. [Crossref]  [PubMed]
  58. Fisher B, Anderson S. Conservative surgery for the management of invasive and noninvasive carcinoma of the breast: NSABP trials. World J surg.1994;181:63-9. [Crossref]  [PubMed]
  59. Veronesi U, Zucali R, Luini A. Local control and survival in early breast cancer: The Milan Trial. Int J Radiat Oncol Biol Phys. 1986;125:717-20. [Crossref]  [PubMed]
  60. Moran MS, Schnitt SJ, Giuliano AE, Harris JR, Khan SA, Horton J, et al. Society of Surgical Oncology-American Society for Radiation Oncology consensus guideline on margins for breast-conserving surgery with whole-breast irradiation in stages I and II invasive breast cancer. J Clin Oncol. 2014;3214:1507-15. [Crossref]  [PubMed]
  61. Houssami N, Macaskill P, Marinovich ML, Morrow M. The association of surgical margins and local recurrence in women with early-stage invasive breast cancer treated with breast-conserving therapy: a meta-analysis. Ann Surg Oncol. 2014;213:717-30. [Crossref]  [PubMed]  [PMC]
  62. Audretsch W, Rezai M, Kolotas C. Oncoplastic surgery: "target" volume reduction BCT-mastopexy, lumpectomy, reconstruction BCT-reconstruction, and flap-supported operability in breast cancer. In: Proceedings of the Second European Congress on Senology, Breast Diseases; 1994:139-57.
  63. Tian R, Zheng Y, Liu R, Jiang C, Zheng H. Efficacy and safety of oncoplastic breast-conserving surgery versus conventional breast-conserving surgery: an updated meta-analysis. Breast. 2024; 77:103784. [Crossref]  [PubMed]  [PMC]
  64. Weber WP, Haug M, Kurzeder C, Bjelic-Radisic V, Koller R, Reitsamer R, et al. Oncoplastic Breast Consortium consensus conference on nipple-sparing mastectomy. Breast Cancer Res Treat. 2018;1723:523-37. [Crossref]  [PubMed]  [PMC]
  65. Orzalesi L, Casella D, Santi C, Cecconi L, Murgo R, Rinaldi S, et al. Nipple sparing mastectomy: surgical and oncological outcomes from a national multicentric registry with 913 patients 1006 cases over a six-year period. Breast. 2016; 25:75- [Crossref]  [PubMed]
  66. Krag DN, Julian TB, Harlow SP, Weaver DL, Ashikaga T, Bryant J, et al. NSABP-32: phase III randomized trial comparing axillary resection with sentinel lymph node dissection: a description of the trial. Ann Surg Oncol. 2004;113 Suppl:208S-10S. [Crossref]  [PubMed]
  67. Giuliano AE, Ballman KV, McCall L, et al. Effect of axillary dissection vs no axillary dissection on 10-year overall survival among women with invasive breast cancer and sentinel node metastasis: the ACOSOG Z0011 Alliance randomized clinical trial. JAMA. 2017;31810:918-26. [Crossref]  [PubMed]  [PMC]
  68. Rutgers EJ, Donker M, Straver ME, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer EORTC 10981-22023 AMAROS: a randomised, multicentre, open-label, phase 3 non-inferiority trial. Lancet Oncol. 2014;1512:1303-10.
  69. Galimberti V, Cole BF, Zurrida S, et al. Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases IBCSG 23-01: a phase 3 randomised controlled trial. Lancet Oncol. 2013;144:297-305. [Crossref]  [PubMed]
  70. de Boniface J, Tvedskov TF, Rydén L, Szulkin R, Reimer T, Kühn T, et al. Omitting axillary dissection in breast cancer with sentinel-node metastases. N Engl J Med. 2024; 390:1163-75. [Crossref]  [PubMed]
  71. Boughey JC, Suman VJ, Mittendorf EA, Ahrendt GM, Wilke LG, Taback B, et al. Sentinel lymph node surgery after neoadjuvant chemotherapy in patients with node-positive breast cancer: the ACOSOG Z1071 Alliance clinical trial. JAMA. 2013;31014:1455-61. [Crossref]  [PubMed]  [PMC]
  72. Kuehn T, Bauerfeind I, Fehm T, Fleige B, Hausschild M, Helms G, 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;147:609-18. [Crossref]  [PubMed]
  73. Boileau JF, Poirier B, Basik M, Holloway CMB, Gaboury L, Sideris L, et al. Sentinel node biopsy after neoadjuvant chemotherapy in biopsy-proven node-positive breast cancer: the SN FNAC study. J Clin Oncol. 2015;333:258-64. [Crossref]  [PubMed]
  74. Caudle AS, Yang WT, Krishnamurthy S, Mittendorf EA, Black DM, Gilcrease MZ, et al. Improved axillary evaluation following neoadjuvant therapy for patients with node-positive breast cancer using selective evaluation of clipped nodes: implementation of targeted axillary dissection. J Clin Oncol. 2016;3410:1072-8. [Crossref]  [PubMed]  [PMC]
  75. van Hemert AKE, van Loevezijn AA, Baas MPD, Stokkel MPM, Groen EJ, van der Noort V, et al. Omitting axillary lymph node dissection in breast cancer patients with extensive nodal disease and excellent response to primary systemic therapy using the MARI protocol. Breast. 2025;80:104411. [Crossref]  [PubMed]  [PMC]
  76. Muslumanoglu M, Cabioglu N, Igci A, Karanlik H, Kocer HB, Senol K, et al. Combined analysis of the MF18-02/ MF18-03 NEOSENTITURK studies: ypN-positive disease does not necessitate axillary lymph node dissection in patients with breast cancer with a good response to neoadjuvant chemotherapy as long as radiotherapy is provided. Cancer. 2025;1311:e35610. [Crossref]  [PubMed]  [PMC]
  77. Banys-Paluchowski M, Gasparri ML, de Boniface J, Gentilini O, Stickeler E, Hartmann S, et al. Surgical management of the axilla in clinically node-positive breast cancer patients converting to clinical node negativity through neoadjuvant chemotherapy: current status, knowledge gaps, and rationale for the EUBREAST-03 AXSANA study. Cancers Basel. 2021;136:1345. [Crossref]  [PubMed]  [PMC]
  78. Heidinger M, Knauer M, Tausch C, Weber WP. Tailored axillary surgery - a novel concept for clinically node-positive breast cancer. Breast. 2023;69:281-289. [Crossref]  [PubMed]  [PMC]
  79. Gentilini OD, Botteri E, Sangalli C, Galimberti V, Porpiglia M, Agresti R, et al. Sentinel lymph node biopsy vs no axillary surgery in patients with small breast cancer and negative results on ultrasonography of axillary lymph nodes: The SOUND randomized clinical trial. JAMA Oncol. 2023;911:1557-1564. [Crossref]  [PubMed]  [PMC]
  80. Reimer T, Stachs A, Veselinovic K, Kühn T, Heil J, Polata S, et al. Axillary surgery in breast cancer primary results of the INSEMA trial. N Engl J Med. 2025;39211:1051-1064. [Crossref]  [PubMed]
  81. Montagna G, Laws A, Ferrucci M, Mrdutt MM, Sun SX, Bademler S, et al. Nodal burden and oncologic outcomes in patients with residual isolated tumor cells after neoadjuvant chemotherapy ypN0i+: the OPBC-05/ICARO study. J Clin Oncol. 2025;437:810-820. [Crossref]  [PubMed]  [PMC]