Study design and patients
We conducted this retrospective matched cohort study at the Harbin Medical University Cancer Hospital (HMUCH, Heilongjiang, China). Patients were selected from a standardized institutional database if they (1) had histologically or pathologically confirmed invasive breast cancer without distant metastasis or local relapses; (2) had surgical pathological specimens of the primary tumor available for review. Cancer stages were identified according to the American Joint Committee on Cancer [AJCC] TNM staging system (16). All patients were scheduled with IR. Exclusion criteria included in situ carcinoma, bilateral or multicentric breast cancer, recurrent cancer, metastatic breast cancer at presentation, a history of invasive breast cancer, other previous tumors and pregnancy. Patients who received neoadjuvant chemotherapy and intraoperative electron beam radiotherapy for cancer treatment were also excluded. Patients with T > 3cm lesions were not included either if they undertook neoadjuvant chemotherapy before BCS. The study protocol was reviewed and approved by the Ethical Committee of HMUCH. We obtained written informed consent from all patients.
Procedures
We established two different study cohorts according to the tumor (T) size of breast cancer. Cases in the T ≤ 3 cm group were invasive ductal carcinomas patients who underwent IR. Controls were patients who underwent either BCS or TM, matching with cases for age, pathological tumor size (pT) and pathologic nodal status (pN) in a 1:1:1 ratio during the same study period. In the T > 3cm group, we included patients who underwent IR as cases. Patients underwent TM were selected as controls, matching for age, pT and pN in a 1:1 ratio.
We collected patients’ demographic data, clinicopathological data, and immunohistochemistry (IHC) results regarding estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her2), P53, Ki67, and prognosis information.
The analytical results of breast cancer subtypes have been described elsewhere (17). Subtypes in this study included luminal A (ER positive [+] and/or PR + and Her2- and Ki67 < 14%), luminal B (ER + and/or PR + and Her2- and Ki67 > 14%; ER + and/or PR + and Her2 + and Ki67 anyway), Her2 overexpression (ER negative [-], PR-, and Her2+) and triple-negative breast carcinoma (TNBC [ER-, PR-, and Her2-]). However, cases of Her2 with IHC (2+) and FISH (+) were excluded from the TNBC group. IHC was scored by two independent pathologists who were blinded to patient clinicopathological characteristics and outcomes. To eliminate nonspecific staining, a negative control was performed using Phate Buffered Saline (PBS).
All cases were evaluated by key stakeholders from a multidisciplinary consultation board with full adherence to updated international guidelines (18). The follow-up period for each patient was estimated from the date of diagnosis of cancer to January, 2020 (the end of the study). Patients in each cohort followed the same clinical follow-up protocols, which were scheduled every six months.
Recurrences include local recurrence (chest wall) and regional recurrence (the lymphatic region of the breast). Distant metastases of breast cancer occur most in bone, lung, liver and brain. Patients underwent BCS and IR received bilateral ultrasound and mammogram each year. Monolateral mammogram was scheduled annually for patients who underwent TM. Radiological examination plans would be adjusted accordingly in cases of any clinical suspicion. A radiological examination of the lung was routinely performed every six months. Liver function, bone and biological markers were checked every year.
Outcomes
The primary endpoint was 5-year disease-free survival (DFS), which was defined from the date of surgery until relapse or the date patients were last known to be alive. The secondary outcome was patient satisfaction and quality of life, which were evaluated with study-specific and health-related questionnaires administered during clinical follow-up. The study-specific questionnaire was concerned about the satisfaction with the choice of procedure and aesthetic result of the operation (19). Necrosis is a clinical manifestation of tissue death, most commonly due to alteration of cutaneous blood flow. Infection is a category of diseases caused by specific pathogens. Some pathogens cause local infections with symptoms confined to the skin. Hematoma/Seroma is the phenomenon of blood/fluid accumulation in the cavity or under the skin. Prolonged wound healing is primary healing cannot be achieved. Such wounds heal by secondary intention and prolonged and complicated healing process.
Statistical analysis
We constructed Kaplan-Meier curves to estimate the 5-year DFS. The log-rank test was used to assess differences between groups. χ2 test was used to compare clinicopathological characteristics between two groups. Statistical analyses were performed using SPSS version 17.0 (IBM Corporation, Armonk, NY, USA) for Windows (Microsoft Corporation, Redmond, WA, USA). A P value less than 0.05 was considered statistically significant.