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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Other: Breast-conserving surgery, postoperative radiotherapy and individualized adjuvant systemic therapy

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.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: WenBin Zhou, Ph.D; Phone Number: 025-68308161; Email: Zhouwenbin@njmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This single-center prospective cohort enrolls women aged ≥18 years with an ECOG performance status of 0-1 and pathologically confirmed unilateral multifocal/multicentric breast cancer without distant metastasis. Eligible candidates are suitable for breast-conserving surgery with negative margins and postoperative adjuvant radiotherapy. Patients with inflammatory breast cancer, extensive unresectable lesions, severe vital organ dysfunction, pregnancy or lactation, or poor follow-up compliance will be excluded. All participants provide written informed consent and receive standard routine treatment, with long-term follow-up conducted to observe oncological outcomes, surgical complications and patient-reported quality of life.

Description

Inclusion Criteria:

1. Female patients aged ≥18 years with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
2. Pathologically confirmed invasive breast carcinoma or ductal carcinoma in situ (DCIS);
3. Radiologically confirmed unilateral multifocal or multicentric breast cancer;
4. No systemic distant metastasis detected on preoperative imaging;
5. 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;
6. Adequate function of vital organs (cardiac, hepatic, renal and hematopoietic systems) to tolerate surgery, subsequent adjuvant radiotherapy and chemotherapy;
7. 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:

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Multifocal or Multicentric Breast Cancer Patients Undergoing Breast-Conserving Surgery; This cohort consists of female patients aged ≥18 years with pathologically confirmed unilateral multifocal or multicentric breast cancer who meet all inclusion and exclusion criteria. All participants receive standardized breast-conserving surgery combined with sentinel lymph node biopsy or axillary lymph node dissection as clinically indicated. Postoperatively, all subjects undergo standard adjuvant radiotherapy followed by individualized systemic adjuvant therapy (chemotherapy, endocrine therapy, anti-HER2 targeted therapy) formulated in accordance with national breast cancer clinical guidelines. No investigational interventions are administered, all treatments are routine standard clinical care. Participants will complete long-term follow-up for at least 3 years and finish validated patient-reported outcome (PRO) questionnaires at scheduled visits.

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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Local recurrence rate of ipsilateral breast	Ipsilateral breast local recurrence rate within 3 years after breast-conserving surgery	3 years after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of postoperative surgical complications	Incidence of short-term complications after surgery, short-term complications (hemorrhage, wound infection, skin flap necrosis) occurring within 30 days after surgery. Long-term upper extremity lymphedema will be monitored for up to 3 years.	Within 3 years after surgery
Disease-free survival (DFS)	DFS is defined as the time interval from surgery to the first event of tumor recurrence, distant metastasis, or breast cancer-related death.	3 years after surgery
Overall survival (OS)	OS is defined as the time from surgery to all-cause death	At least 3 years after surgery
Regional lymph node recurrence rate	Incidence of ipsilateral axillary regional lymph node recurrence during follow-up	3 years after surgery
Contralateral breast malignancy rate	Incidence of new malignant lesions in the contralateral breast	3 years after surgery
Distant metastasis rate	Incidence of systemic distant metastasis at any site during follow-up	3 years after surgery
Breast-Q patient-reported outcome	Patient-reported breast satisfaction and cosmetic outcomes assessed via the validated Breast-Q questionnaire.	Baseline, 1 year, 2 years and 3 years after surgery
Self-rating anxiety scale (SAS) score	Anxiety status measured by the validated Self-Rating Anxiety Scale (SAS).	Baseline, 1 year, 2 years and 3 years after surgery
Self-rating depression scale (SDS) score	Depressive symptoms assessed using the validated Self-Rating Depression Scale (SDS).	Baseline, 1 year, 2 years and 3 years after surgery
EORTC QLQ-C30 global quality of life score	Overall cancer-related quality of life evaluated with the validated EORTC QLQ-C30 questionnaire.	Baseline, 1 year, 2 years and 3 years after surgery

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital with Nanjing Medical University

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Estimated): July 15, 2026
• Primary Completion (Estimated): December 30, 2031
• Study Completion (Estimated): December 30, 2036

Study Registration Dates

• First Submitted: June 22, 2026
• First Submitted That Met QC Criteria: June 30, 2026
• First Posted (Actual): July 1, 2026

Study Record Updates

• Last Update Posted (Actual): July 1, 2026
• Last Update Submitted That Met QC Criteria: June 30, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Breast-conserving surgery; Local recurrence; Multifocal or multicentric breast cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Surgical Procedures, Operative; Mastectomy; Mastectomy, Segmental
• Other Study ID Numbers: NJMU-BC14

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The individual participant data involves sensitive personal clinical information of patients, and there is no established data sharing protocol approved by the ethics committee for external researchers at present. Therefore, IPD will not be shared after the study is finished.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No