Breast-conserving therapy versus mastectomy for breast cancer: a ten-year follow-up single-center real-world study

Introduction

From Halsted’s mastectomy in 1880s to modified mastectomy in 1970s, breast cancer treatment first revolved around local treatment but gradually progressed towards systematic treatment as doctors experimenting with less drastic approaches saw similar prognosis (1). Breast-conserving therapy (BCT) was eventually established as the standard treatment for early-stage breast cancer. Randomized trials with long-term follow-up have provided sufficient and high-level evidence that BCT can achieve similar prognosis compared with mastectomy (MT) (2-5). However, a few recent observational studies have arrived at the conclusion that BCT displayed better survival outcomes than MT (6-9). This discrepancy may derive from the difference in patient composition, development of systematic treatment and involvement of other socioeconomic factors. Some studies have proposed that the improvement in overall survival with BCT is associated to early stage, negative lymph node stage, luminal and triple-negative subtype (10,11). The role of other impacting factors such as tumor biology, systematic treatment, surgery type on prognosis is also the center of debate since it concerns patient selection on BCT (12).

Consistent with the general trends in breast cancer treatment, breast-conserving surgery (BCS) adopted a less invasive approach with the goal of minimizing resection volume (RV) in order to achieve better aesthetic outcome (13). To guarantee a clean margin and total resection of the tumor, intraoperative margin assessment (IMA) rose in response (14,15). However, due to the short amount of time and varied quality of IMA, its efficacy remains controversial (16). Likewise, axillary lymph node dissection (ALND) is no longer routinely performed since ALND and sentinel lymph node biopsy (SLNB) was confirmed to yield similar survival with patients undergoing SLNB suffering from less adverse reactions such as lymphedema. New evidence has surfaced that patients within limited range of lymph node metastasis are also potential candidates for SLNB (17-20).

By comparing prognosis in BCT with MT in patient subgroups, we aim to clarify the influence of surgery type on different individuals. Patients with ductal carcinoma in situ (DCIS) components undergoing BCS is attached with special emphasis. In addition, we also place a special interest on whether having higher RV, conducting an IMA, and ALND is necessary for better local control. It is noteworthy that the aforementioned randomized trials were mostly targeted at early-stage breast cancer and options for systematic treatment were rather limited at time of study. This is the first long-term follow-up real-world study with large cohort of breast cancer patients conducted in China in recent years. We intend to match treatment options with a specific group of patients who will most likely become its beneficiary which can help clinicians reach wise and informative clinical decisions. We present the following article in accordance with the STROBE reporting checklist (available at https://gs.amegroups.com/article/view/10.21037/gs-22-142/rc).

Methods

The nature of this study is retrospective and data were retrospectively collected. This study collected cases of BCT and MT for breast cancer from October 1, 2005 to September 31, 2010 in the breast cancer database of Chinese PLA General Hospital. In the first 2 years after surgery, patient was seen for follow-up every three months. After that, patient was followed every six months. Follow-up was done in the form of phone call or outpatient clinic visit. A total of 971 patients were enrolled in this study who were divided into the BCS and the MT group. Level 2 BCS was standard treatment at our hospital. The exclusion criteria were as follows: (I) patients receiving neo-adjuvant chemotherapy; (II) patients with synchronic bilateral breast cancers; (III) male patients with breast cancer; (IV) patients who have undergone lumpectomy in other hospitals; (V) cases lost to follow-up; (VI) patients with incomplete pathological data. For patients with asynchronous bilateral breast cancer, they were grouped and analyzed according to the surgical treatment of the breast cancer that occurred earlier. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Ethics Committee of Chinese PLA General Hospital (No. S2022-147-01) and individual consent for this retrospective analysis was waived. The following information of the patients was recorded: age at diagnosis; pathological classification [invasive breast carcinoma (IBC) or DCIS] of tumors; histological grade of IBC; extent of invasive carcinoma; lymph node status; the expression status of hormone receptors of IBC; Ki67 index of IBC; HER-2 status of IBC; axillary nodal surgery methods; location of the tumor; IMA methods including frozen section (FS) method and gross examination (GE) by surgeons in the BCS group; the duration for pathological FS analysis of surgical margins; three-dimensional size (length, width, and height) of breast tissue removed during BCS; maximum tumor diameter (MTD) including the largest diameter of the infiltrating component and DCIS component in the BCS group; pathological classification (DCIS or IBC) of ipsilateral breast tumor recurrence (IBTR) and regional recurrence in the BCS group; the treatment of patients including chemotherapy, endocrine therapy, and radiotherapy; the patients’ follow-up time and survival status.

Endpoints were defined referring to the STEEP System. BCSS was defined as the time period between surgery and death from breast cancer. DFS was defined as the minimum time period between surgery and local recurrence/regional recurrence/distant metastasis (21). Pathological stages of IBC were evaluated according to the eighth edition of Cancer Staging Manual of the American Joint Committee on Cancer (AJCC) (22). For cases in the two groups that did not undergo ALND or SLNB, and imaging examinations showed no lymph node metastasis, they were staged as pathological classification N0. Histological grading of IBC was performed according to Nottingham modification of the SBR grading system (23). The positivity of HER-2, ER, and PR was defined referring to recommendations of the American Society of Clinical Oncology/College of American Pathologists HER2, ER and PR testing guideline (24,25). According to 2013 St Gallen International Expert Consensus (26), the molecular subtypes of IBC were defined as follows: luminal A-like type: ER+, HER2−, Ki67 <20%, PR ≥20%; luminal B-like type: ER+, and/or HER2+, and/or Ki67 ≥20%, PR <20%; HER2 overexpression type: ER−, PR−, HER2+; Basal-like type: ER−, PR−, HER2−. RV of breast tissue including the tumor in the BCS group was calculated by one half of each of the three dimensions and the formula 4/3π (1/2 length × 1/2 width × 1/2 height) for an ellipsoid specimen volume (27).

Statistical analysis

The clinicopathological characteristics of patients from the BCS and the MT group were compared by chi-square test or Fisher’s exact test. One-way analysis of variance (ANOVA) was used to compare the RV in the BCS group. Correlation analysis (Pearson) was used to compare the relationship between MTD and RV of breast tissue. Breast cancer specific survival (BCSS), disease-free survival (DFS), local recurrence-free survival (LRFS), loco-regional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) were calculated and compared by Kaplan-Meier survival analysis and log-rank test firstly. And then Cox Proportional-Hazards model was used for multivariate analysis of BCSS, DFS, LRFS, LRRFS, and DMFS. Statistical significance was defined as P<0.05. All statistical analyses were performed using IBM Statistical Package for SPSS version 22.0.

Results

Baseline characteristics

In this study, there were 296 patients in the BCS group, including 267 patients with IBC and 29 patients with DCIS, and 675 patients in the MT group, including 638 patients with IBC and 37 patients with DCIS. There 971 patients in the entire cohort and all of them were female. Table 1 described the demographic characteristics, clinicopathological characteristics, and follow-up of patients with IBC in the BCS and MT group. Compared with the MT group, the proportion of patients <40 years old (P<0.001), the proportion of IBC with histological grade 1 (P=0.003), the proportion of patients of stage I-II (P<0.001), the proportion of patients undergoing SLNB (P<0.001) and radiotherapy (P<0.001) were higher in the BCS group. There was no significant difference in the distribution of molecular subtypes and the proportion of patients receiving chemotherapy and endocrine therapy between the two groups of patients.

Table 2 described the demographic characteristics, clinicopathological characteristics, and follow-up of patients with DCIS in the BCS and MT group. Compared with the MT group, patients in the BCS group had a lower percentage of patients receiving axillary nodal surgery (P=0.010), and a higher percentage of patients receiving radiotherapy (P<0.001). The overall local recurrence rate (25.0% vs. 0%, P=0.002) and the overall local-regional recurrence rate (25.0% vs. 2.7%, P=0.017) in the BCS group were higher than those in the MT group. And there were no deaths or distant metastases in the patients with DCIS of the two groups. In the BCS group, a total of 7 patients with DCIS had IBTR, 3 cases of recurring tumors were DCIS, and 4 cases were IBC. In the MT group, 1 case of DCIS had regional recurrence, and metastatic carcinoma appeared in the left supraclavicular lymph node.

According to whether the tumor contained DCIS component, the patients in the BCS group were divided into cases with and without DCIS component. Table 3 described the demographic, clinicopathological characteristics and follow-up of breast cancer patients with and without DCIS component in the BCS group. There were no significant differences in the age distribution, N stages, IMA methods, axillary nodal surgery methods, and endocrine therapy options for the two types of lesions. A higher proportion of breast cancer patients with DCIS component received radiotherapy. Table 4 described the tumor location in patients undergoing ALND, SLNB and none nodal surgery in the BCS group. The proportion of tumor located in the upper-lateral quadrant in the ALND group was higher that of the SLNB group, though the difference was statistically insignificant (55.0% vs. 44.6%, P=0.304). There was no correlation between MTD and RV of breast tissue in the BCS group (Table 5, P=0.132). A total of 29 cases in the BCS group performed IMA through pathological evaluation of FS, and the average duration required for FS analysis was 34–99 (average 61) minutes.

Surgery type and BCSS in the entire cohort

Patients with invasive breast cancer in the entire cohort were followed up for 2–192 (average 118.1) months. Kaplan-Meier survival analysis showed that the 10-year BCSS rate (96.6% vs. 88.3%, P<0.001) of patients with IBC in the BCS group was significantly higher than that in the MT group (Table 1). The stratification of IBC by staging showed that for IBC of stage I-II, the 10-year BCSS rate (96.8% vs. 92.3%, P=0.025) of the BCS group was significantly higher than that of the MT group (Table 1). For IBC of stage III-IV, the 10-year BCSS rate (91.7% vs. 70.3%, P=0.207) of the BCS group was higher than that of the MT group, but there was no statistical difference (Table 1). Univariate Cox regression shows that 4 factors were adversely correlated with BCSS of IBC in the entire cohort：molecular subtypes (HR for luminal B-like type =3.601, P<0.001 and HR for HER2 overexpression type =2.828, P=0.025); pathological stage III-IV (HR =5.434, P<0.001); increasing N stages (HR for N1=2.478, P=0.003, HR for N2=5.701, P<0.001; HR for N3=11.102, P<0.001); MT (HR =3.194, P=0.001) (Table 6). Multivariate Cox regression showed that Luminal B-like type (HR=15.101, P=0.009) and N stages (HR for N1=4.545, P=0.017, HR for N2=11.842, P=0.001; HR for N3=9.167, P=0.014) were independently associated with BCSS, and surgery type was not an independent factor associated with BCSS of IBC in the entire cohort (Table 6).

Surgery type and DFS/LRFS in the entire cohort

Kaplan-Meier survival analysis showed that there was no significant difference in the 10-year DFS rate of IBC (87.6% vs. 83.8%, P=0.146) between the BCS and MT group (Table 1). The 10-year LRFS rate of IBC (93.1% vs. 96.1%, P=0.023) in the BCS group was significantly lower than that in the MT group (Table 1). For IBC of stage I-II, the 10-year LRFS rate of patients with BCS was lower than that of those with MT (93.6% vs. 96.0%, P=0.064), but there was no statistical difference (Table 1). For IBC of stage III-IV, the 10-year LRFS rate of the BCS group was significantly lower than that of the MT group (83.9% vs. 96.4%, P=0.041) (Table 1). Multivariate Cox regression showed that surgery type was not an independent factor associated with DFS (P=0.202) and LRFS (P=0.223) of IBC in the entire cohort (Tables 6,7). The age of 40–59 (HR =0.412, P=0.003), Stage N2 (HR =2.435, P=0.047), and ALND (HR =0.470, P=0.038) were independent prognostic factors for DFS (Table 6). Only the age of 40–59 (HR =0.236, P=0.003) was an independent factor for LRFS of IBC in the entire cohort (Table 7).

DCIS component and BCSS/DFS in the BCS group

Kaplan-Meier survival analysis showed there was no significant difference between the 10-year BCSS rate (95.8% vs. 97.8%, P=0.605) of breast cancer patients with DCIS component and that of breast cancer patients without DCIS component in the BCS group (Table 3). The 10-year DFS rate (80.3% vs. 90.7%, P=0.011) of breast cancer patients with DCIS component was significantly lower than that without DCIS component in the BCS group (Table 3). Univariate (HR =6.416, P=0.021) and Multivariate (HR =35.611, P=0.008) Cox regression both showed only stage N2 was a prognostic factor for BCSS in the BCS group (Table 8). Univariate Cox regression showed breast cancer with DCIS component, MTD, RV, stage N2, N3, and endocrine therapy were adversely associated with DFS in the BCS group (Table 8). Multivariate Cox regression showed MTD (HR =1.349, P=0.049), RV (HR =1.005, P=0.039), stage N3 (HR =14.610, P=0.021), and ALND (HR =0.289, P=0.021) were independent prognostic factors for DFS in the BCS group, while BC with DCIS component, stage N2, IMA, radiotherapy, and endocrine therapy were not (Table 8).

DCIS component and LRFS/LRRFS/ DMFS in the BCS group

Kaplan-Meier survival analysis showed that the 10-year LRFS rate (86.3% vs. 94.4%, P=0.024) and the 10-year LRRFS rate (85.4% vs. 94.4%, P=0.009) of breast cancer patients with DCIS component were significantly lower than that of breast cancer patients without DCIS component in the BCS group (Table 3). And there was no significant difference between the 10-year DMFS rate (93.0% vs. 95.5%, P=0.278) of breast cancer patients with DCIS component and that without DCIS component in the BCS group (Table 3). Multivariate Cox regression showed MTD (HR =1.449, P=0.044) and RV (HR =1.009, P=0.004) were independent risk factor for local recurrence in the BCS group (Table 9). MTD (HR =1.465, P=0.035), RV (HR =1.010, P=0.002), and stage N3 (HR =29.001, P=0.007) were adversely associated with LRRFS in the BCS group (Table 9). And breast cancer with DCIS component, IMA, were not independent prognostic factors for LRFS and LRRFS in the BCS group (Table 9). ALND was a protective prognostic factor for local recurrence (HR =0.265, P=0.036) and local-regional recurrence (HR =0.262, P=0.034) in the BCS group (Table 9). Only N stages (HR for N1 =7.763, P=0.030, HR for N2 =27.044, P=0.007; HR for N3 =43.841, P=0.009) were independent factors for DMFS in the BCS group (Table 9).

Discussion

This study showed that the 10-year BCSS rate of patients with IBC in the BCS group was significantly higher than that of the MT group (96.6% vs. 88.3%, P<0.001). However, after stratification by staging, only the 10-year BCSS rate of patients in the BCS group at stage I-II was significantly higher than that of the MT group (96.8% vs. 92.3%, P=0.025), and there was no difference in the 10-year BCSS rate of patients at stage III-IV between the two groups (P=0.207). After controlling for other confounders including age, histological grade, molecular classification, T/N staging, axillary nodal surgery methods, and systemic treatment by multivariate survival analysis, BCSS (HR =1.057, P=0.925), DFS (HR =1.572, P=0.202), and LRFS (HR =2.132, P=0.223) had no significant difference between the two surgical methods. This is consistent with the results of several randomized clinical trials published from 1980 to 2008 that showed no significant difference in OS (2,28-37) and DFS (2,28,34,36) between stage I-II (T1-2, N0-1) IBC patients who underwent BCS plus radiation and radical or modified radical mastectomy at 5-20 years of follow-up. Similar to the results of this study, a meta-analysis including 25 Chinese Case-Control Studies from 2004 to 2010 showed that there was no significant difference between 3-year and 5-year OS of IBC patients with early stage in the BCS group and the MT group (38). We believe that large randomized clinical trials can better eliminate confounders and compare the impact of the two surgical methods on the survival more objectively. It may be because our multivariate survival analysis included more comprehensive prognostic factors, which led to BCSS and DFS being consistent with conclusions of the clinical trials. Different from the results of this study, several large retrospective studies in recent years had shown that the prognosis of IBC patients of early stage with BCS plus radiotherapy after long-term follow-up was better than that of patients with MT (6,7,39). We consider two possible reasons leading to this conclusion. First, although the survival analysis of these studies has included as many prognostic factors as possible, including socioeconomic/demographic, clinicopathological characteristics and systemic treatments, there will still be unmeasured confounders. For example, the retrospective study of the Netherlands Cancer Registry did not take the prognostic effects of Herceptin targeted therapy into account (39). In the population-based study for Danish breast cancer patients and Louisiana women with early stage breast cancer, lymph node management was not included as a prognostic risk factor (6,7,39). Second, early clinical randomized trials were carried out more than 30 years ago. At the time when recent observational studies were conducted, breast imaging methods, systemic treatment, radiotherapy methods, and evaluation methods of margin have advanced rapidly, which may improve the survival of patients with BCS. The cases enrolled in our study were patients from 2005 to 2010, when BCS was first initiated in our hospital. In our next step, we intend to investigate the impact of changes in breast imaging examination methods, treatment methods, and pathological assessment methods on the survival of patients by conducting observational studies on recent cases, and further compare the survival between patients treated with BCS and MT.

Moreover, multivariate analysis in this study showed that N stage (HR for N1 =4.545, P=0.017, HR for N2 =11.842, P=0.001; HR for N3 =9,167, P=0.014) and luminal B-like subtype (HR =15.101, P=0.009) were independent prognostic factors for the BCSS of IBC in the entire cohort (Table 6). And stage N2 (HR =35.611, P=0.008) in the BCS group was the only independent risk factor for BCSS. This is consistent with previous studies (40,41), suggesting that regardless of the surgical method, early or advanced stage, IBC or DCIS, lymph node staging is the main factor affecting OS.

In our study, patients undergoing breast conserving surgery had both IBC and DCIS, both early and advanced cancer, including 253 cases of IBC of stage I-II, 14 cases of IBC of stage III-IV, and 29 cases of DCIS. We propose to analyze the survival and recurrence of these patients in the real world, as well as the prognostic factors, especially the factors affecting the loco-regional recurrence. Several randomized controlled trials and meta-analyses revealed local recurrence risk factors after BCS for IBC may include tumor size, histologic grade, margin status, lymph node metastasis, systemic therapy, and radiotherapy (42,43). A few nomograms predicting the risk of local recurrence after BCS for DCIS suggested that age, margin status, number of excisions, endocrine therapy, adjuvant RT, and treatment time period had a greater impact on local recurrence (44-46). With reference to the above reports, our study included age, MTD, RV of breast tissue, N stage, axillary lymph node surgery, methods of IMA, endocrine therapy, and radiotherapy as possible prognostic variables of loco-regional recurrence in the BCS group. However, a nomogram predicting IBTR suggested the presence of DCIS being one of major risk factors for recurrence of early breast cancer (47). So in our study design, we further divided patients in the BCS group into two subgroups according to whether DCIS component was present in the tumor. The 10-year LRFS rate (86.3% vs. 94.4%, P=0.024) and the 10-year LRRFS rate (85.4% vs. 94.4%, P=0.009) of breast cancer with DCIS component were significantly lower than that of breast cancer without DCIS component in the BCS group (Table 3). But multivariate Cox regression showed the presence of DCIS component was not an independent factor for local recurrence (HR =0.441, P=0.169) and local-regional recurrence (HR =0.423, P=0.137) in the BCS group (Table 9). Consistent with the reports above, stage N3 is an independent risk factor for local-regional recurrence (HR =29.001, P=0.007) of patients with BCS (Table 9).

Another end of our study was to assess whether MTD and RV of breast tissue were related to local and loco-regional recurrence. As was reported in the literature (48), MTD was an independent risk factor for local-recurrence (HR =1.449, P=0.044) and local-regional recurrence (HR =1.465, P=0.035) in the BCS group of our study. A few studies suggested that the volume of breast tissue removed during BCS was inversely correlated with local recurrence. Data from Vicini et al. showed that a smaller resection volume of breast tissue (<60 cm³) was an independent risk factor for local recurrence after BCS in patients with DCIS (49). Mazeh et al. found that the specimen-to-tumor-volume ratio was significantly negatively correlated with local recurrence for breast cancer patients with BCS (50). Contrary to existing research results, RV in the BCS group of our study was an independent risk factor for local recurrence (HR =1.009, P=0.004) and local-regional recurrence (HR =1.010, P=0.002). It has been reported that the inflammatory response caused by surgery may provoke angiogenesis, proliferation of dormant cancer cells, and local micro-metastasis, which may be a likely explanation for early postoperative recurrence (51,52). We speculate that the increase in the resection volume breast tissue may trigger a wider area of inflammatory response, which is more conducive to the proliferation and metastasis of dormant cancer cells, thereby increasing the risk of local recurrence.

In our study, only 29 cases (10%) of the margins in the BCS group were determined by the FS method during the operation, and the rest were determined by the surgeon using the GE method. Interestingly, the multivariate analysis of this group showed that whether or not FS was performed was not related to LRFS (P=0.335) and LRRFS (P=0.349), but the FS analysis took an average of 61 minutes. Similar to our study, Nowikiewicz et al. compared the methods of IMA during BCS at their center, and the results indicated that the positive rate of margins and the percentage of reoperations of FS and GE method were not significantly different, but the use of FS method has dramatically increased the operation time (53). A few theories arise which can account for the similar judgment effects between macroscopic and microscopic inspection. They were listed as follows: (I) the FS method for margin evaluation is susceptible to subjectivity and uncertainty. The influencing factors include pathologists’ skillfulness in FS and histologic diagnosis, the sampling method, the number of cut edges, and the controversial definition for positive margin (54); (II) the experience and techniques of the surgeon can improve the accuracy of IMA (55). In recent years, with the development of new techniques and methods for IMA, in addition to traditional pathology and imaging methods, research on non-traditional imaging methods and biological dye methods continued to emerge (56-60). The search for methods that can improve the accuracy of IMA while shorten the duration of operation time is always a problem that urgently needs to be addressed by surgeons and pathologists.

Our hospital started SLNB in early 2007, which gave us the opportunity to observe the impact of SLNB and ALND on the survival and loco-regional recurrence of patients undergoing BCS in the same period (2005–2010) in the real world. Multivariate survival analysis showed that ALND in the BCS group was not an independent prognostic factor for BCSS (HR =0.113, P=0.135), but ALND was an independent protective factor for local-regional recurrence (HR =0.262, P=0.034). In support of our conclusion, there have been many observational studies, clinical trials, and meta-analyses suggesting that patients undergoing BCS showed no difference in survival between SLNB and ALND, but ALND can reduce axillary regional recurrence by 1–3% (61). The multivariate survival analysis of our study showed that ALND is an independent protective factor for local recurrence (HR =0.265, P=0.036) in the BCS group. Only a few studies found that there was no significant difference in the IBTR rate of BCS patients after SLNB and ALND in univariate analysis (62). An intriguing correlation between the quadrant of the breast tumor and whether or not the ALND was performed has caught our attention. This phenomenon could partially account for the protective function of ALND against recurrence. Our study has shown that more patients in the BCS group presenting with breast cancer located in the upper-lateral quadrant has had ALND compared with SLNB. Considering that tumor located in that specific region is susceptible to lymph node metastasis in the axilla, surgeons are prone to take a more drastic approach so as to prevent recurrence. In addition, speaking from a technical point of view, the vicinity of upper-lateral breast tumor and axillary breast cancer sometimes makes it inoperable to perform SLNB.

It should be noted that our results may be biased due to limited cases enrolled, influencing factors which we did not take into consideration such as socioeconomic status, comorbidity, detailed plan of chemotherapy, radiotherapy and endocrine therapy.

Conclusions

This study suggests that there is no significant difference in BCSS between breast cancer patients undergoing BCS and MT after adjusting for confounding factors. Lymph node staging is the major risk factor affecting patients’ survival. Therefore, patients might have a wider range of choices of surgical methods based on their subjective wishes. In this case, choosing patients with smaller tumor size, avoiding patients with stage N3, and removing a smaller volume of breast tissue including tumors while ensuring negative margins may reduce the patient's risk of local recurrence and loco-regional recurrence.

Acknowledgments

Funding: None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://gs.amegroups.com/article/view/10.21037/gs-22-142/rc

Data Sharing Statement: Available at https://gs.amegroups.com/article/view/10.21037/gs-22-142/dss

Peer Review File: Available at https://gs.amegroups.com/article/view/10.21037/gs-22-142/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-22-142/coif). XL serves as an Editor-in-Chief of Gland Surgery from May 2022 to April 2024. The other authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Ethics Committee of Chinese PLA General Hospital (No. S2022-147-01) and individual consent for this retrospective analysis was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Zurrida S, Veronesi U. Milestones in breast cancer treatment. Breast J 2015;21:3-12. [Crossref] [PubMed]
2. Fisher B, Anderson S, Bryant J, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 2002;347:1233-41. [Crossref] [PubMed]
3. Litière S, Werutsky G, Fentiman IS, et al. Breast conserving therapy versus mastectomy for stage I-II breast cancer: 20 year follow-up of the EORTC 10801 phase 3 randomised trial. Lancet Oncol 2012;13:412-9. [Crossref] [PubMed]
4. Simone NL, Dan T, Shih J, et al. Twenty-five year results of the national cancer institute randomized breast conservation trial. Breast Cancer Res Treat 2012;132:197-203. [Crossref] [PubMed]
5. Veronesi U, Cascinelli N, Mariani L, et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med 2002;347:1227-32. [Crossref] [PubMed]
6. Christiansen P, Carstensen SL, Ejlertsen B, et al. Breast conserving surgery versus mastectomy: overall and relative survival-a population based study by the Danish Breast Cancer Cooperative Group (DBCG). Acta Oncol 2018;57:19-25. [Crossref] [PubMed]
7. Chu QD, Hsieh MC, Lyons JM, et al. 10-Year Survival after Breast-Conserving Surgery Compared with Mastectomy in Louisiana Women with Early-Stage Breast Cancer: A Population-Based Study. J Am Coll Surg 2021;232:607-21. [Crossref] [PubMed]
8. Hartmann-Johnsen OJ, Kåresen R, Schlichting E, et al. Survival is Better After Breast Conserving Therapy than Mastectomy for Early Stage Breast Cancer: A Registry-Based Follow-up Study of Norwegian Women Primary Operated Between 1998 and 2008. Ann Surg Oncol 2015;22:3836-45. [Crossref] [PubMed]
9. de Boniface J, Szulkin R, Johansson ALV. Survival After Breast Conservation vs Mastectomy Adjusted for Comorbidity and Socioeconomic Status: A Swedish National 6-Year Follow-up of 48 986 Women. JAMA Surg 2021;156:628-37. [Crossref] [PubMed]
10. Almahariq MF, Quinn TJ, Siddiqui Z, et al. Breast conserving therapy is associated with improved overall survival compared to mastectomy in early-stage, lymph node-negative breast cancer. Radiother Oncol 2020;142:186-94. [Crossref] [PubMed]
11. Yu P, Tang H, Zou Y, et al. Breast-Conserving Therapy Versus Mastectomy in Young Breast Cancer Patients Concerning Molecular Subtypes: A SEER Population-Based Study. Cancer Control 2020;27:1073274820976667. [Crossref] [PubMed]
12. Hwang ES. Breast conservation: is the survival better for mastectomy? J Surg Oncol 2014;110:58-61. [Crossref] [PubMed]
13. Chan SW, Cheung PS, Lam SH. Cosmetic outcome and percentage of breast volume excision in oncoplastic breast conserving surgery. World J Surg 2010;34:1447-52. [Crossref] [PubMed]
14. Pradipta AR, Tanei T, Morimoto K, et al. Emerging Technologies for Real-Time Intraoperative Margin Assessment in Future Breast-Conserving Surgery. Adv Sci (Weinh) 2020;7:1901519. [Crossref] [PubMed]
15. Schwarz J, Schmidt H. Technology for Intraoperative Margin Assessment in Breast Cancer. Ann Surg Oncol 2020;27:2278-87. [Crossref] [PubMed]
16. Thill M, Baumann K, Barinoff J. Intraoperative assessment of margins in breast conservative surgery--still in use? J Surg Oncol 2014;110:15-20. [Crossref] [PubMed]
17. Galimberti V, Cole BF, Viale G, et al. Axillary dissection versus no axillary dissection in patients with breast cancer and sentinel-node micrometastases (IBCSG 23-01): 10-year follow-up of a randomised, controlled phase 3 trial. Lancet Oncol 2018;19:1385-93. [Crossref] [PubMed]
18. 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;318:918-26. [Crossref] [PubMed]
19. Qiu SQ, Zhang GJ, Jansen L, et al. Evolution in sentinel lymph node biopsy in breast cancer. Crit Rev Oncol Hematol 2018;123:83-94. [Crossref] [PubMed]
20. Veronesi P, Corso G. Standard and controversies in sentinel node in breast cancer patients. Breast 2019;48:S53-6. [Crossref] [PubMed]
21. Hudis CA, Barlow WE, Costantino JP, et al. Proposal for standardized definitions for efficacy end points in adjuvant breast cancer trials: the STEEP system. J Clin Oncol 2007;25:2127-32. [Crossref] [PubMed]
22. Hortobagyi GN, Connolly JL, D'Orsi CJ, et al. Breast. In: Amin MB, Edge S, Greene F, et al., eds; American Joint Committee on Cancer. AJCC cancer staging manual, 8th ed. Springer, 2017:589-636.
23. Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 1991;19:403-10. [Crossref] [PubMed]
24. Wolff AC, Hammond ME, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. Arch Pathol Lab Med 2007;131:18-43. [Crossref] [PubMed]
25. Allison KH, Hammond MEH, Dowsett M, et al. Estrogen and Progesterone Receptor Testing in Breast Cancer: ASCO/CAP Guideline Update. J Clin Oncol 2020;38:1346-66. [Crossref] [PubMed]
26. Goldhirsch A, Winer EP, Coates AS, et al. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol 2013;24:2206-23. [Crossref] [PubMed]
27. Krekel NM, Zonderhuis BM, Stockmann HB, et al. A comparison of three methods for nonpalpable breast cancer excision. Eur J Surg Oncol 2011;37:109-15. [Crossref] [PubMed]
28. Veronesi U, Saccozzi R, Del Vecchio M, et al. Comparing radical mastectomy with quadrantectomy, axillary dissection, and radiotherapy in patients with small cancers of the breast. N Engl J Med 1981;305:6-11. [Crossref] [PubMed]
29. Sarrazin D, Lê M, Rouëssé J, et al. Conservative treatment versus mastectomy in breast cancer tumors with macroscopic diameter of 20 millimeters or less. The experience of the Institut Gustave-Roussy. Cancer 1984;53:1209-13. [Crossref] [PubMed]
30. Fisher B, Redmond C, Poisson R, et al. Eight-year results of a randomized clinical trial comparing total mastectomy and lumpectomy with or without irradiation in the treatment of breast cancer. N Engl J Med 1989;320:822-8. [Crossref] [PubMed]
31. Veronesi U, Banfi A, Salvadori B, et al. Breast conservation is the treatment of choice in small breast cancer: long-term results of a randomized trial. Eur J Cancer 1990;26:668-70. [Crossref] [PubMed]
32. Blichert-Toft M, Rose C, Andersen JA, et al. Danish randomized trial comparing breast conservation therapy with mastectomy: six years of life-table analysis. Danish Breast Cancer Cooperative Group. J Natl Cancer Inst Monogr 1992;19-25. [PubMed]
33. van Dongen JA, Bartelink H, Fentiman IS, et al. Randomized clinical trial to assess the value of breast-conserving therapy in stage I and II breast cancer, EORTC 10801 trial. J Natl Cancer Inst Monogr 1992;15-8. [PubMed]
34. Straus K, Lichter A, Lippman M, et al. Results of the National Cancer Institute early breast cancer trial. J Natl Cancer Inst Monogr 1992;27-32. [PubMed]
35. van Dongen JA, Voogd AC, Fentiman IS, et al. Long-term results of a randomized trial comparing breast-conserving therapy with mastectomy: European Organization for Research and Treatment of Cancer 10801 trial. J Natl Cancer Inst 2000;92:1143-50. [Crossref] [PubMed]
36. Poggi MM, Danforth DN, Sciuto LC, et al. Eighteen-year results in the treatment of early breast carcinoma with mastectomy versus breast conservation therapy: the National Cancer Institute Randomized Trial. Cancer 2003;98:697-702. [Crossref] [PubMed]
37. Blichert-Toft M, Nielsen M, Düring M, et al. Long-term results of breast conserving surgery vs. mastectomy for early stage invasive breast cancer: 20-year follow-up of the Danish randomized DBCG-82TM protocol. Acta Oncol 2008;47:672-81. [Crossref] [PubMed]
38. Cai X, Liu X, Yu H, et al. Breast-conserving therapy for early-stage breast cancer in Chinese women: a meta-analysis of case-control studies. Onkologie 2012;35:133-9. [Crossref] [PubMed]
39. Lagendijk M, van Maaren MC, Saadatmand S, et al. Breast conserving therapy and mastectomy revisited: Breast cancer-specific survival and the influence of prognostic factors in 129,692 patients. Int J Cancer 2018;142:165-75. [Crossref] [PubMed]
40. Beenken SW, Urist MM, Zhang Y, et al. Axillary lymph node status, but not tumor size, predicts locoregional recurrence and overall survival after mastectomy for breast cancer. Ann Surg 2003;237:732-8; discussion 738-9. [Crossref] [PubMed]
41. Saadatmand S, Bretveld R, Siesling S, et al. Influence of tumour stage at breast cancer detection on survival in modern times: population based study in 173,797 patients. Ned Tijdschr Geneeskd 2016;160:A9800. [PubMed]
42. Polo A, Polgár C, Hannoun-Levi JM, et al. Risk factors and state-of-the-art indications for boost irradiation in invasive breast carcinoma. Brachytherapy 2017;16:552-64. [Crossref] [PubMed]
43. Skandarajah AR, Bruce Mann G. Selective use of whole breast radiotherapy after breast conserving surgery for invasive breast cancer and DCIS. Surgeon 2013;11:278-85. [Crossref] [PubMed]
44. Rudloff U, Jacks LM, Goldberg JI, et al. Nomogram for predicting the risk of local recurrence after breast-conserving surgery for ductal carcinoma in situ. J Clin Oncol 2010;28:3762-9. [Crossref] [PubMed]
45. Sweldens C, Peeters S, van Limbergen E, et al. Local relapse after breast-conserving therapy for ductal carcinoma in situ: a European single-center experience and external validation of the Memorial Sloan-Kettering Cancer Center DCIS nomogram. Cancer J 2014;20:1-7. [Crossref] [PubMed]
46. Collins LC, Achacoso N, Haque R, et al. Risk Prediction for Local Breast Cancer Recurrence Among Women with DCIS Treated in a Community Practice: A Nested, Case-Control Study. Ann Surg Oncol 2015;22:S502-8. [Crossref] [PubMed]
47. van Werkhoven E, Hart G. Nomogram to predict ipsilateral breast relapse based on pathology review from the EORTC 22881-10882 boost versus no boost trial. Radiother Oncol 2011;100:101-7. [Crossref] [PubMed]
48. Kantor O, Winchester DJ. Breast conserving therapy for DCIS--does size matter? J Surg Oncol 2014;110:75-81. [Crossref] [PubMed]
49. Vicini FA, Kestin LL, Goldstein NS, et al. Relationship between excision volume, margin status, and tumor size with the development of local recurrence in patients with ductal carcinoma-in-situ treated with breast-conserving therapy. J Surg Oncol 2001;76:245-54. [Crossref] [PubMed]
50. Mazeh H, Sagiv I, Katz D, et al. Association between patient age, volume of breast tissue excised, and local recurrence. J Surg Res 2013;181:187-92. [Crossref] [PubMed]
51. Demicheli R, Retsky MW, Hrushesky WJ, et al. The effects of surgery on tumor growth: a century of investigations. Ann Oncol 2008;19:1821-8. [Crossref] [PubMed]
52. Retsky M, Demicheli R, Hrushesky WJ, et al. Reduction of breast cancer relapses with perioperative non-steroidal anti-inflammatory drugs: new findings and a review. Curr Med Chem 2013;20:4163-76. [Crossref] [PubMed]
53. Nowikiewicz T, Śrutek E, Głowacka-Mrotek I, et al. Clinical outcomes of an intraoperative surgical margin assessment using the fresh frozen section method in patients with invasive breast cancer undergoing breast-conserving surgery - a single center analysis. Sci Rep 2019;9:13441. [Crossref] [PubMed]
54. Guidi AJ, Tworek JA, Mais DD, et al. Breast Specimen Processing and Reporting With an Emphasis on Margin Evaluation: A College of American Pathologists Survey of 866 Laboratories. Arch Pathol Lab Med 2018;142:496-506. [Crossref] [PubMed]
55. Cleffken B, Postelmans J, Olde Damink S, et al. Breast-conserving therapy for palpable and nonpalpable breast cancer: can surgical residents do the job irrespective of experience? World J Surg 2007;31:1731-6. [Crossref] [PubMed]
56. Ha R, Friedlander LC, Hibshoosh H, et al. Optical Coherence Tomography: A Novel Imaging Method for Post-lumpectomy Breast Margin Assessment-A Multi-reader Study. Acad Radiol 2018;25:279-87. [Crossref] [PubMed]
57. Tang R, Saksena M, Coopey SB, et al. Intraoperative micro-computed tomography (micro-CT): a novel method for determination of primary tumour dimensions in breast cancer specimens. Br J Radiol 2016;89:20150581. [Crossref] [PubMed]
58. Kho E, Dashtbozorg B, de Boer LL, et al. Broadband hyperspectral imaging for breast tumor detection using spectral and spatial information. Biomed Opt Express 2019;10:4496-515. [Crossref] [PubMed]
59. Ueo H, Shinden Y, Tobo T, et al. Rapid intraoperative visualization of breast lesions with gamma-glutamyl hydroxymethyl rhodamine green. Sci Rep 2015;5:12080. [Crossref] [PubMed]
60. Maeda A, Bu J, Chen J, et al. Dual in vivo photoacoustic and fluorescence imaging of HER2 expression in breast tumors for diagnosis, margin assessment, and surgical guidance. Mol Imaging 2014; [Crossref] [PubMed]
61. Rao R, Euhus D, Mayo HG, et al. Axillary node interventions in breast cancer: a systematic review. JAMA 2013;310:1385-94. [Crossref] [PubMed]
62. Wernicke AG, Goodman RL, Turner BC, et al. A 10-year follow-up of treatment outcomes in patients with early stage breast cancer and clinically negative axillary nodes treated with tangential breast irradiation following sentinel lymph node dissection or axillary clearance. Breast Cancer Res Treat 2011;125:893-902. [Crossref] [PubMed]