Safety of Breast-Conserving Surgery for Multifocal or Multicentric Breast Cancer

Official title

Safety Evaluation of Breast-Conserving Surgery for Multifocal or Multicentric Breast Cancer: A Prospective Cohort Study

Overview

The objective of this observational study is to evaluate the oncological safety of breast-conserving surgery combined with standard postoperative radiotherapy in adult female patients diagnosed with multifocal or multicentric breast cancer. The main questions it aims to answer are: What is the local recurrence rate and the time distribution of local recurrence after breast-conserving therapy in patients with multifocal or multicentric breast cancer? What independent risk factors are associated with postoperative local recurrence among these patients? There is no separate comparison group in this single-arm prospective cohort study. Participants will: Receive standardized breast-conserving surgery plus routine postoperative radiotherapy and individualized adjuvant therapy in accordance with clinical guidelines; Complete regular clinical follow-up visits, telephone and WeChat follow-ups for at least 3 years after surgery to collect data on surgical complications, tumor recurrence, metastasis and survival status; Fill out standardized questionnaires including Breast-Q, SDS, SAS and EORTC QLQ-C30 to assess postoperative breast satisfaction, psychological status and quality of life.

Detailed description

This single-center, single-arm prospective observational cohort study enrolls female patients aged ≥18 years with unilateral multifocal or multicentric breast cancer treated at the Department of Breast Surgery, the First Affiliated Hospital of Nanjing Medical University. Subjects are screened in strict accordance with unified inclusion and exclusion criteria. All enrolled patients receive breast-conserving surgery followed by standardized postoperative radiotherapy and individualized adjuvant therapy without trial-specific interventions, and all treatment regimens are formulated in line with domestic guidelines for breast cancer diagnosis and treatment. All participants sign written informed consent prior to enrollment.

Uniform baseline data including demographic characteristics, menstrual and reproductive history, family history of malignancy, imaging findings, pathological profiles, molecular subtypes, and surgical information are collected. Postoperative 30-day surgical complications are documented to evaluate short-term surgical safety. Standardized long-term follow-up lasting no less than 3 years is conducted after surgery via outpatient visits, telephone calls and WeChat communication to continuously track oncological endpoints such as ipsilateral breast tumor local recurrence, regional lymph node recurrence, contralateral breast malignancy and distant metastasis, as well as data on disease-free survival and overall survival. Validated standardized questionnaires including Breast-Q, SDS, SAS and EORTC QLQ-C30 are administered at scheduled follow-up time points to assess patients' satisfaction with breast appearance, anxiety and depression status, and overall quality of life.

All data are double-entered, subjected to regular quality control and anonymized for privacy protection. Statistical analyses consist of descriptive statistics, univariate analyses, multivariate Logistic regression, Cox proportional hazards regression, and Kaplan-Meier survival analysis. Subgroup analyses stratified by molecular subtype, lesion distribution pattern and axillary lymph node status are performed, and a nomogram predicting the risk of postoperative local recurrence is constructed to facilitate individualized clinical risk assessment.

Patients with inflammatory breast cancer, extensive lesions precluding negative surgical margins, severe vital organ dysfunction, pregnancy or lactation incompatible with radiotherapy, or inability to complete long-term follow-up are excluded from the study. Lost-to-follow-up cases are treated as censored data in survival analyses, and baseline characteristics are compared between lost and fully followed patients to mitigate attrition bias. This study receives no external funding. All study procedures strictly comply with the Declaration of Helsinki and institutional ethical review requirements. The study aims to clarify the oncological safety of comprehensive breast-conserving therapy for multifocal or multicentric breast cancer, identify independent risk factors for postoperative local recurrence, and provide native evidence-based references for individualized surgical management of such patients in China.

Interventions

• Other Breast-conserving surgery, postoperative radiotherapy and individualized adjuvant systemic therapy
  All patients receive routine standard clinical treatment rather than investigational interventions, including breast-conserving surgery, axillary staging surgery, postoperative adjuvant radiotherapy, and guideline-concordant chemotherapy, endocrine therapy or anti-HER2 targeted therapy according to pathological and molecular characteristics.

Primary outcome measures

• Local recurrence rate of ipsilateral breast [Time frame: 3 years after surgery]

Secondary outcome measures (10)

• Incidence of postoperative surgical complications [Time frame: Within 3 years after surgery]
• Disease-free survival (DFS) [Time frame: 3 years after surgery]
• Overall survival (OS) [Time frame: At least 3 years after surgery]
• Regional lymph node recurrence rate [Time frame: 3 years after surgery]
• Contralateral breast malignancy rate [Time frame: 3 years after surgery]
• Distant metastasis rate [Time frame: 3 years after surgery]
• Breast-Q patient-reported outcome [Time frame: Baseline, 1 year, 2 years and 3 years after surgery]
• Self-rating anxiety scale (SAS) score [Time frame: Baseline, 1 year, 2 years and 3 years after surgery]
• Self-rating depression scale (SDS) score [Time frame: Baseline, 1 year, 2 years and 3 years after surgery]
• EORTC QLQ-C30 global quality of life score [Time frame: Baseline, 1 year, 2 years and 3 years after surgery]

Eligibility criteria

Inclusion criteria

• Female patients aged ≥18 years with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
• Pathologically confirmed invasive breast carcinoma or ductal carcinoma in situ (DCIS);
• Radiologically confirmed unilateral multifocal or multicentric breast cancer;
• No systemic distant metastasis detected on preoperative imaging;
• Comprehensive clinical evaluation predicts all tumor lesions can be completely resected by breast-conserving surgery (BCS) to obtain negative surgical margins, and patients are suitable for standardized adjuvant whole-breast radiotherapy postoperatively;
• Adequate function of vital organs (cardiac, hepatic, renal and hematopoietic systems) to tolerate surgery, subsequent adjuvant radiotherapy and chemotherapy;
• Voluntarily agree to participate in the study after fully understanding the study purpose, procedures, potential risks and benefits, and provide written informed consent.

Exclusion criteria

• Inflammatory breast cancer;
• Extensive tumor burden that prevents complete resection via breast-conserving surgery or attainment of negative surgical margins;
• Severe dysfunction or failure of vital organs (heart, liver, kidney, lung) making patients unable to tolerate surgery, radiotherapy or chemotherapy;
• Pregnant or lactating women who are ineligible for postoperative radiotherapy;
• Patients who are unwilling or unable to complete long-term postoperative follow-up and data collection.

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

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Poenaru MO, Amza M, Toma CV, Augustin FE, Pacu I, Zampieri G, Ples L, Sima RM, Diaconescu AS. Multicentric and Multifocal Breast Tumors-Narrative Literature Review. Cancers (Basel). 2025 Oct 20;17(20):3380. doi: 10.3390/cancers17203380. PMID 41154435
• Sun Y, Gao L, Zhou X, Wang Z, Li Y, Sun Q. Local Recurrence and Survival Outcomes of Multifocal/Multicentric Breast Cancer After Breast Conserving Therapy: A systematic Review and Meta-Analysis. Clin Breast Cancer. 2025 Apr;25(3):e229-e239.e9. doi: 10.1016/j.clbc.2024.10.009. Epub 2024 Oct 18. PMID 39542811
• Masannat YA, Rocco N, Garreffa E, Gulluoglu BM, Kothari A, Maglia A, Nava MB, Omar OS, Potter S, Catanuto G. Global variations in the definition and management of multifocal and multicentric breast cancer: the MINIM international survey. Br J Surg. 2022 Jul 15;109(8):656-659. doi: 10.1093/bjs/znac080. No abstract available. PMID 35352093
• De Lorenzi F, Borelli F, Pagan E, Bagnardi V, Peradze N, Jereczek-Fossa BA, Leonardi C, Mazzarol G, Favia G, Corso G, Montagna E, Rietjens M, Veronesi P. Oncoplastic Breast-Conserving Surgery for Synchronous Multicentric and Multifocal Tumors: Is It Oncologically Safe? A Retrospective Matched-Cohort Analysis. Ann Surg Oncol. 2022 Jan;29(1):427-436. doi: 10.1245/s10434-021-10800-w. Epub 2021 Oct 6. PMID 34613536
• Koppiker C, Joshi S, Mishra R, Kelkar DA, Chigurupati P, Joshi A, John J, Kadu S, Bagdia A, Thakkar D, Deshmukh C, Allampati H, Sharan G, Dhar U, Nare S, Nagarkar S, Busheri L, Varghese B, Pai M. Therapeutic mammoplasty: a "wise" oncoplastic choice-lessons from the largest single-center cohort from Asia. Front Oncol. 2023 Apr 14;13:1131951. doi: 10.3389/fonc.2023.1131951. eCollection 2023. PMID 37124516
• Zhang J, Fang H, Zhao Z, Guo Y, Li Y, Wang Y, Guo X, Ning Z, Wang H. Clinicopathological characteristics and prognostic analysis of multifocal/multicentric breast cancer. Sci Rep. 2025 Dec 29;15(1):44869. doi: 10.1038/s41598-025-28687-y. PMID 41462542
• Tong Y, Sun F, Zhang C, Yang S, Yu Z, Zhao Y. Multifocal/multicentric breast cancer: Does each focus matter? Cancer Med. 2023 Apr;12(7):8815-8824. doi: 10.1002/cam4.5626. Epub 2023 Feb 3. PMID 36734288
• Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023 Jan;73(1):17-48. doi: 10.3322/caac.21763. PMID 36633525

Identifiers

NCT: NCT07677956 · NJMU-BC14

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗