Neoadjuvant Chemoradiotherapy Compared to Neoadjuvant Chemotherapy for Luminal-Type Locally Advanced Breast Cancer: A Clinical Study

Overview

This study focuses on preoperative treatment modalities for luminal-type locally advanced breast cancer. Based on modern precision radiotherapy technologies such as MRI-Linac, CyberKnife, and VMAT, it aims to compare the pCR rate, breast conserving surgery (BCS) rate, progression-free survival (PFS), and treatment-related side effects between preoperative neoadjuvant chemotherapy and preoperative neoadjuvant SBRT combined with chemotherapy in patients with this type of breast cancer. The goal is to provide new strategic options for the preoperative treatment of luminal-type locally advanced breast cancer.

Detailed description

Breast cancer is a tumor with high tumor heterogeneity, and treatment outcomes vary significantly across different molecular subtypes. In recent years, the emergence of novel treatment methods has significantly improved the overall survival and progression-free survival of patients with early-stage, especially metastatic tumors. However, a portion of patients with locally advanced breast cancer (LABC) still have poor prognoses. As early as the 1970s, preoperative radiotherapy was applied to locally advanced breast cancer to increase resectability, but due to limitations in radiotherapy techniques and other factors, preoperative radiotherapy increased the incidence of acute toxic reactions and postoperative complications. Compared to traditional postoperative radiotherapy, neoadjuvant radiotherapy has several theoretical advantages, such as more precise tumor target localization, optimization of breast reconstruction radiotherapy strategies, increased tumor downstaging to improve breast-conserving surgery opportunities, and improved pathological complete response rates, potentially eliminating the need for breast surgery. With the advent of the era of precision radiotherapy, modern radiotherapy technologies have provided solutions to reduce the acute toxic reactions associated with preoperative radiotherapy. This study focuses on preoperative treatment modalities for luminal-type locally advanced breast cancer. It aims to compare the pCR rate, breast-conserving surgery (BCS) rate, progression-free survival (PFS), and treatment-related side effects between preoperative neoadjuvant chemotherapy and preoperative neoadjuvant SBRT combined with chemotherapy in these patients. The goal is to provide new strategic options for the preoperative treatment of luminal-type locally advanced breast cancer.

Interventions

• Radiation Preoperative SBRT for the Primary Lesion of Breast Cancer
  SBRT for Primary Lesion of Breast Cancer, Radiation Dose: Primary Lesion ≤3 cm, GTV 24Gy/3F; Primary Lesion \>3 cm, GTV 30Gy/5F.

Primary outcome measures

• pCR [Time frame: From enrollment to one month after surgery]

Secondary outcome measures (3)

• Breast Conserving Surgery Rate [Time frame: From enrollment to the completion of surgery]
• PFS [Time frame: From enrollment to the completion of the 3-year follow-up period]
• Adverse Event Incidence Rate [Time frame: From enrollment to the completion of the 3-year follow-up period]

Eligibility criteria

Inclusion criteria

• Pathologically confirmed invasive breast cancer ;
• Breast MRI showing stages IIB to IIIC (2017 AJCC 8th edition staging);
• Clinical staging confirmed by chest MRI and/or axillary ultrasound, as well as CT scans of the neck, abdomen, and pelvis, and bone scintigraphy, including T and N staging and assessment of distant metastasis;
• Karnofsky performance score ≥80 or ECOG performance status of 0-1;
• No history of allergies to doxorubicin, cyclophosphamide, paclitaxel/docetaxel;
• No prior exposure to radiotherapy, chemotherapy, endocrine therapy, targeted therapy, or immunotherapy.

Exclusion criteria

• History of malignancy at other sites, excluding curable non-melanoma skin cancer and carcinoma in situ of the cervix;
• Inability to complete MRI;
• Inflammatory breast cancer;
• Bilateral or multifocal primary tumors;
• Active infection currently present; clinically evident heart disease; myocardial infarction or cerebrovascular accident within 6 months prior to enrollment.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Sichuan Cancer Hospital — Chengdu

Publications

• Vasmel JE, Charaghvandi RK, Houweling AC, Philippens MEP, van Asselen B, Vreuls CPH, van Diest PJ, van Leeuwen AMG, van Gorp J, Witkamp AJ, Koelemij R, Doeksen A, Sier MF, van Dalen T, van der Wall E, van Dam I, Veldhuis WB, Kirby AM, Verkooijen HM, van den Bongard HJGD. Tumor Response After Neoadjuvant Magnetic Resonance Guided Single Ablative Dose Partial Breast Irradiation. Int J Radiat Oncol B PMID 31812720
• Nichols E, Kesmodel SB, Bellavance E, Drogula C, Tkaczuk K, Cohen RJ, Citron W, Morgan M, Staats P, Feigenberg S, Regine WF. Preoperative Accelerated Partial Breast Irradiation for Early-Stage Breast Cancer: Preliminary Results of a Prospective, Phase 2 Trial. Int J Radiat Oncol Biol Phys. 2017 Mar 15;97(4):747-753. doi: 10.1016/j.ijrobp.2016.11.030. Epub 2016 Nov 27. PMID 28244410
• Semiglazov VF, Topuzov EE, Bavli JL, Moiseyenko VM, Ivanova OA, Seleznev IK, Orlov AA, Barash NY, Golubeva OM, Chepic OF. Primary (neoadjuvant) chemotherapy and radiotherapy compared with primary radiotherapy alone in stage IIb-IIIa breast cancer. Ann Oncol. 1994 Sep;5(7):591-5. doi: 10.1093/oxfordjournals.annonc.a058929. PMID 7993833
• Ishitobi M, Suzuki O, Komoike Y, Ohsumi S, Nakahara S, Yagi T, Yoshinami T, Tomita Y, Inaji H. Phase II study of neoadjuvant anastrozole and concurrent radiotherapy for postmenopausal breast cancer patients. Breast Cancer. 2014 Sep;21(5):550-6. doi: 10.1007/s12282-012-0426-2. Epub 2012 Nov 2. PMID 23117619
• Bollet MA, Kirova YM, Antoni G, Pierga JY, Sigal-Zafrani B, Laki F, Campana F, Dendale R, Salmon R, Cottu P, Fourquet A. Responses to concurrent radiotherapy and hormone-therapy and outcome for large breast cancers in post-menopausal women. Radiother Oncol. 2007 Dec;85(3):336-45. doi: 10.1016/j.radonc.2007.10.003. Epub 2007 Oct 29. PMID 17967495
• Spring LM, Gupta A, Reynolds KL, Gadd MA, Ellisen LW, Isakoff SJ, Moy B, Bardia A. Neoadjuvant Endocrine Therapy for Estrogen Receptor-Positive Breast Cancer: A Systematic Review and Meta-analysis. JAMA Oncol. 2016 Nov 1;2(11):1477-1486. doi: 10.1001/jamaoncol.2016.1897. PMID 27367583
• Brackstone M, Palma D, Tuck AB, Scott L, Potvin K, Vandenberg T, Perera F, D'Souza D, Taves D, Kornecki A, Muscedere G, Chambers AF. Concurrent Neoadjuvant Chemotherapy and Radiation Therapy in Locally Advanced Breast Cancer. Int J Radiat Oncol Biol Phys. 2017 Nov 15;99(4):769-776. doi: 10.1016/j.ijrobp.2017.06.005. Epub 2017 Jun 20. PMID 28870785
• Roth SL, Audretsch W, Bojar H, Lang I, Willers R, Budach W. Retrospective study of neoadjuvant versus adjuvant radiochemotherapy in locally advanced noninflammatory breast cancer : survival advantage in cT2 category by neoadjuvant radiochemotherapy. Strahlenther Onkol. 2010 Jun;186(6):299-306. doi: 10.1007/s00066-010-2143-0. Epub 2010 May 21. PMID 20495968

Identifiers

NCT: NCT06697938 · SCCSMC-01-2024-034

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗