
==== Front
J Breast Cancer
J Breast Cancer
JBC
Journal of Breast Cancer
1738-6756
2092-9900
Korean Breast Cancer Society

39228155
10.4048/jbc.2023.0234
Original Article
Intensive Surveillance for Women With Breast Cancer: A Multicenter Retrospective Study in Korea
https://orcid.org/0000-0003-1162-4639
Park Sungmin 1
https://orcid.org/0000-0002-9981-0286
Moon Hyeong-Gon 2
https://orcid.org/0000-0001-7875-1603
Lee Jong Won 3
https://orcid.org/0000-0003-2710-112X
Kim Ku Sang 4
https://orcid.org/0000-0002-1413-2800
Kim Zisun 5
https://orcid.org/0000-0002-4508-4522
Jung So-Youn 6
https://orcid.org/0000-0003-0041-8717
Lee Jihyoun 7
https://orcid.org/0000-0003-1630-1783
Lee Se Kyung 8
https://orcid.org/0000-0003-1564-0978
Chae Byung Joo 8
https://orcid.org/0000-0002-0131-8593
Jung Sung Ui 4
https://orcid.org/0000-0001-6438-5526
Chun Jung Whan 9
https://orcid.org/0000-0001-9986-5597
Cheun Jong-Ho 10
https://orcid.org/0000-0002-2407-8537
Youn Hyun Jo 11
1 Department of Surgery, Chungbuk National University Hospital, College of Medicine, Chungbuk National University, Cheongju, Korea.
2 Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
3 Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
4 Department of Surgery, Kosin University Gospel Hospital, Busan, Korea.
5 Department of Surgery, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
6 Department of Surgery, National Cancer Center, Goyang, Korea.
7 Department of Surgery, Soonchunhyang University Seoul Hospital, Seoul, Korea.
8 Department of Surgery, Samsung Seoul Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
9 Department of Surgery, Korea University Anam Hospital, Seoul, Korea.
10 Department of Surgery, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul, Korea.
11 Department of Surgery, Research Institute of Clinical Medicine of Jeonbuk National University, Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Korea.
Correspondence to Hyun Jo Youn. Department of Surgery, Research Institute of Clinical Medicine of Jeonbuk National University, Biomedical Research Institute of Jeonbuk National University Hospital, 20 Geonji-ro, Deokjin-gu, Jeonju 54907, Korea. yhj0903@jbnu.ac.kr
8 2024
09 8 2024
27 4 235247
25 10 2023
20 4 2024
04 8 2024
© 2024 Korean Breast Cancer Society
2024
Korean Breast Cancer Society
https://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Purpose

This study evaluated the effectiveness of different surveillance intensities on morbidity and mortality in women with breast cancer.

Methods

This retrospective study included patients who had undergone breast cancer surgery in the Republic of Korea between 2009 and 2011. The patients were divided into two groups based on the intensity of their postsurgical surveillance: intensive surveillance group (ISG) and less-intensive surveillance group. Surveillance intensity was measured based on the frequency and type of follow-up diagnostic tests conducted, including mammography, ultrasonography, computed tomography, magnetic resonance imaging, bone scans, and positron emission tomography scans.

Results

We included 1,356 patients with a median follow-up period of 121.2 months (range, 12.8–168.0 months). The analysis revealed no significant difference in the overall survival (OS) between the two groups within five years of surgery. However, patients with ISG exhibited significantly better breast cancer-specific survival (BCSS) and distant metastasis-free survival (DMFS) within the same period. Five years after surgery, the differences in survival outcomes between the groups were not statistically significant.

Conclusion

Intensive surveillance did not demonstrate a significant improvement in OS for patients with breast cancer beyond five years postoperatively. However, within the first five years, intensive surveillance was associated with better BCSS and DMFS. These findings suggest that personalized surveillance strategies may benefit specific patient subsets, particularly in the early years after treatment. Further nationwide randomized studies are warranted to refine surveillance guidelines and optimize outcomes in patients with breast cancer.

Breast Neoplasms
Prognosis
Recurrence
Korea Breast Cancer Foundation https://doi.org/10.13039/100020379 Chungbuk National University Hospital
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pmcINTRODUCTION

Breast cancer is the most common cancer (11.7%, 2,261,419) worldwide and ranks fifth among all cancer types, accounting for 6.9% (6,84,996) of all cancer deaths [1]. Breast cancer is common in Koreans, and the number of patients with breast cancer is increasing constantly [2]. However, the effectiveness of treatments is also improving [3]. The number of breast cancer survivors has increased with decreasing mortality rates and these patients require long-term surveillance [4]. Despite improved survival, several breast cancer patients develop distant metastases after primary treatment [5]. Several imaging techniques have advanced significantly, leading to an improved diagnostic accuracy. Therefore, the clinical significance of intensive surveillance needs to be reviewed from a different perspective [6].

Women with breast cancer require surveillance to monitor their response to treatment and detect recurrence or newly diagnosed contralateral breast cancer. Surveillance intensity can be defined according to the number of visiting physicians and/or physical examinations, and surveillance practices vary across hospitals [7]. Despite ambiguity regarding the benefits of intensive surveillance care for the survival of these patients, it is relatively common in real practice [8]. Therapeutic options have progressed as we continue to understand the biology of breast cancer and develop improved diagnostic tools. Therefore, new personalized surveillance approaches are required [9]. Therefore, we evaluated the effectiveness of different surveillance intensities on the morbidity and mortality in women with breast cancer.

METHODS

Study population

We retrospectively studied patients who underwent breast cancer surgery between 2009 and 2011. We reviewed their clinical data, including sex, age, surgical method, and cancer stage, according to the American Joint Committee on Cancer (AJCC) classification; histological types and status of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2); type of adjuvant treatment; and date and cause of death. We reviewed several imaging modalities including chest radiography, mammography, ultrasonography (USG), computed tomography (CT), magnetic resonance imaging (MRI), bone scans, and 18F-fludeoxyglucose positron emission tomography (18F-FDG PET). Medical records were obtained from eight hospitals in South Korea. Patients with distant metastasis at the initial work-up and those who had received follow-up care for less than five years were excluded. Patients with in-situ carcinoma lesions were excluded.

The participants were categorized into four groups based on the status of hormone receptor (HR) and HER2: 1) HR-positive (HR+), HER2-negative (HER2−); 2) HR+, HER2-positive (HER2+); 3) triple-negative breast cancer (TNBC); and 4) HR-negative (HR−), HER2+.

Intensity of surveillance

Local recurrence was defined as recurrence in the breast or regional lymph nodes. Distant metastasis was defined as metastasis to the bones, liver, lungs, or brain. The total number of examinations performed between the time of surgery and the time of confirmed local recurrence or distant metastasis was counted. Surveillance was assessed using two categories (intensive surveillance group [ISG] and less-intensive surveillance group [LSG]). Next, we divided the patients into groups based on the follow-up time intervals. In 2005, the National Health Insurance Service (a) for patients with cancer regarding the reimbursement of treatment payments. These patients were identified using specialized claims code V193. In South Korea’s cancer care system, a dedicated insurance claims code (V193) is assigned to medical claims data specific to cancer treatment. Beneficiaries of National Health Insurance (NHI) cover only 5% of medical expenses related to cancer care. For medical services other than cancer care, a co-payment of 20% to 30% is typically applied under the NHI scheme [10]. The follow-up methods and schedules differed within and after five years of breast cancer diagnosis. Therefore, we assessed the intensity of follow-up in two categories: 1) distant metastasis within five years postoperatively and 2) distant metastasis five years postoperatively.

These protocols were differentiated based on the frequency and types of diagnostic modalities employed during two distinct post-operative periods: within five years post-surgery and after five years post-surgery (Supplementary Table 1).

Within five years post-surgery

The ISG underwent a surveillance regimen that included routine clinical visits complemented by at least two of the following diagnostic modalities: bone scan, chest CT, abdominal CT, abdominal USG, or 18F-FDG PET. These modalities are used annually to detect distant metastases. Surveillance in the LSG was less frequent, involved routine clinical visits, and used the same diagnostic modalities as the ISG less than once annually.

After five years post-surgery

Surveillance for the ISG included routine clinical visits and at least two of the following diagnostic tests conducted once or more annually: chest radiography, bone scintigraphy, chest CT, abdominal CT, abdominal USG, or 18F-FDG PET. The LSG underwent the same diagnostic tests as the ISG less than once annually.

The follow-up examinations performed at each center are shown in Supplementary Table 2.

Statistical analyses

χ2 and Fisher’s exact tests were used to compare clinicopathological factors between groups. Overall survival (OS) and breast-cancer-specific survival (BCSS) were based on the period between the date of initial diagnosis and death. Local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) were defined as the period between the date of initial diagnosis and the date of the first clinical diagnosis of local recurrence or distant metastasis, respectively. The dates of death were obtained from the Statistics Korea database (www.kostat.go.kr). We used a 1:1 propensity score-matching analysis for the ISG and LSG to reduce the effects of bias on outcomes [11]. For propensity score matching (PSM), we adjusted for the age at breast cancer diagnosis, stage, subtype, histological grade, lymphovascular invasion (LVI), adjuvant endocrine therapy, chemotherapy, anti-HER2 therapy, and radiotherapy. We used the Kaplan–Meier method for survival analyses and the log-rank test to compare survival curves. We employed the Cox proportional hazards model to analyze time-to-event data. Censoring in our study occurred because of factors such as participants being lost to follow-up or patients being transferred to alternative medical facilities. Patients who did not experience a specific event such as death or recurrence during the study period were right censored at the time of their most recent follow-up assessment. The Cox proportional hazards model was adjusted for age, stage, subtype, histological grade, LVI, chemotherapy, endocrine therapy, radiotherapy, and surveillance intensity. We calculated hazard ratios and 95% confidence intervals (CIs) to quantify the association between specific risk factors and time-to-event. SPSS version 26 (IBM Corp., Armonk, USA) was used for all the analyses. Statistical significance was set at p < 0.05 as significant.

Ethical statement

This study was approved by the Institutional Review Board of all institutions including Jeonbuk National University Hospital (approval number: CUH 2021-08-020). The processes involving human participants adhered to the ethical standards of the institutional and/or national research committee. All procedures were performed in accordance with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. The requirement for informed consent was waived because of the retrospective nature of the study, and because the analysis used anonymous clinical data.

RESULTS

Patients’ characteristics

We identified 1,356 patients with breast cancer; the mean age at the time of initial treatment was 49.1 ± 9.7 years. The median age was 48 years (range: 19–79 years), and the median follow-up period was 121.2 months (range: 12.8–168.0 months). More than half of the patients (56.9%) were premenopausal, and 84.7% had stage I or II cancer. Nearly two-thirds of patients underwent breast-conserving surgery. The baseline patient characteristics are shown in Table 1.

Table 1 Demographic characteristics of patients

Characteristics	Total (n = 1,356)	
Age (yr)		
	Mean ± standard deviation	49.1 ± 9.7	
	Median (range)	48 (19–79)	
Follow-up time (mo)		
	Mean ± standard deviation	118.4 ± 22.5	
	Median (range)	121.2 (12.8–168.0)	
Menopause		
	Premenopause	730 (56.9)	
	Menopause	554 (43.1)	
	Unknown	72	
Family history		
	Yes	126 (9.3)	
	No	1,230 (90.7)	
Stage		
	1	525 (38.7)	
	2	624 (46.0)	
	3	207 (15.3)	
T stage		
	1	703 (51.8)	
	2	567 (41.8)	
	3	66 (4.9)	
	4	20 (1.5)	
N stage		
	0	826 (60.9)	
	1	360 (26.5)	
	2	118 (8.7)	
	3	52 (3.8)	
ER/PR		
	Negative	341 (25.1)	
	Positive	1,015 (74.9)	
HER2		
	Negative	1,051 (77.5)	
	Positive	298 (22.1)	
	Unknown	7	
Ki-67		
	< 20%	804 (63.7)	
	≥ 20%	459 (36.3)	
	Unknown	93	
Subtype		
	HR+, HER2−	850 (62.7)	
	HR+, HER2+	158 (11.7)	
	TNBC	201 (14.8)	
	HR−, HER2+	140 (10.3)	
	Unknown	7	
Histologic grade		
	1	168 (13.0)	
	2	672 (52.1)	
	3	450 (34.9)	
	Unknown	66	
LVI		
	Negative	869 (69.1)	
	Positive	389 (30.9)	
	Unknown	98	
Surgery		
	Breast conserving surgery	863 (63.6)	
	Mastectomy	493 (36.4)	
Chemotherapy		
	No	284 (22.8)	
	Neoadjuvant	147 (11.8)	
	Adjuvant	817 (65.5)	
	Unknown	108	
Endocrine therapy		
	No	329 (24.7)	
	Tamoxifen	549 (44.0)	
	Aromatase inhibitor	300 (24.0)	
	Others (switch)	91 (7.3)	
	Unknown	107	
Radiotherapy		
	No	326 (26.2)	
	Yes	919 (73.8)	
	Unknown	111	
Anti-HER2 therapy		
	No	1,060 (85.0)	
	Yes	187 (15.0)	
	Unknown	109	
Data shown are number (%) not otherwise specified.

ER = estrogen receptor; PR = progesterone receptor; HER2 = human epidermal growth factor receptor 2; HR+ = hormone receptor-positive; HER2− = human epidermal growth factor receptor 2-negative; HER2+ = human epidermal growth factor receptor 2-positive; TNBC = triple-negative breast cancer; HR− = hormone receptor-negative; LVI = lymphovascular invasion.

The characteristics of the study population after PSM are presented in Tables 2 and 3. After matching, the results demonstrated no significant differences between the ISG and LSG for breast cancer regarding age at diagnosis, stage, subtype, histologic grade, LVI, adjuvant endocrine therapy, chemotherapy, anti-HER2 therapy, and radiotherapy.

Table 2 Clinical characteristics of patients of less-intensive surveillance and intensive surveillance groups (surveillance of distant metastasis within five years post-surgery)

Characteristics	Before PSM	p *	After PSM	p †	
LSG (n = 1,018)	ISG (n = 338)	LSG (n = 250)	ISG (n = 250)	
Age (yr)	48.9 ± 9.7	48.9 ± 9.5	0.671	48.9 ± 10.1	49.0 ± 9.9	0.95	
Stage			< 0.001		0.648	
	1	430 (42.2)	95 (28.1)	79 (31.6)	70 (28.0)	
	2	446 (43.8)	178 (52.7)	121 (48.4)	130 (52.0)	
	3	142 (13.9)	65 (19.2)	50 (20.0)	50 (20.0)	
Subtype			0.78			0.919	
	HR+, HER2−	640 (62.9)	210 (62.1)	153 (61.2)	152 (60.8)	
	HR+, HER2+	122 (12.0)	36 (10.7)	32 (12.8)	29 (11.6)	
	TNBC	145 (14.2)	56 (16.6)	35 (14.0)	40 (16.0)	
	HR−, HER2+	105 (10.3)	35 (10.4)	30 (12.0)	29 (11.6)	
Histologic grade			0.045			0.117	
	1	138 (13.6)	30 (8.9)	32 (12.8)	25 (10.0)	
	2	491 (48.2)	181 (53.6)	120 (48.0)	143 (57.2)	
	3	344 (33.8)	106 (31.4)	98 (39.2)	82 (32.8)	
LVI			< 0.001			0.649	
	No	686 (67.4)	183 (54.1)	151 (60.4)	145 (58.0)	
	Yes	267 (26.2)	122 (36.1)	99 (39.6)	105 (42.0)	
Chemotherapy			< 0.001			0.056	
	No	252 (24.8)	32 (9.5)	26 (10.4)	27 (10.8)	
	Neoadjuvant	100 (9.8)	47 (13.9)	21 (8.4)	38 (15.2)	
	Adjuvant	596 (58.5)	221 (65.4)	203 (81.2)	185 (74.0)	
Endocrine therapy			0.016			0.514	
	No	232 (22.8)	77 (22.8)	56 (22.4)	65 (26.0)	
	Tamoxifen	431 (42.3)	118 (34.9)	116 (46.4)	100 (40.0)	
	Aromatase inhibitor	224 (22.0)	76 (22.5)	58 (23.2)	61 (24.4)	
	Others (switch)	62 (6.1)	29 (8.6)	20 (8.0)	24 (9.6)	
Radiotherapy			0.028			0.418	
	No	239 (23.5)	87 (25.7)	62 (24.8)	71 (28.4)	
	Yes	706 (69.4)	213 (63.0)	188 (75.2)	179 (71.6)	
Anti-HER2 therapy			0.029			0.908	
	No	810 (79.6)	250 (74.0)	203 (81.2)	205 (82.0)	
	Yes	137 (13.5)	50 (14.8)	47 (18.8)	45 (18.0)	
Values are presented as mean ± standard deviation or number (%).

PSM = propensity score matching; LSG = less-intensive surveillance group; ISG = intensive surveillance group; HR+ = hormone receptor-positive; HER2− = human epidermal growth factor receptor 2-negative; HER2+ = human epidermal growth factor receptor 2-positive; TNBC = triple-negative breast cancer; HR− = hormone receptor-negative; LVI = lymphovascular invasion; HER2 = human epidermal growth factor receptor 2.

*p-value by χ2 test and Student’s t-test; †p-value by conditional logistic regression.

Table 3 Clinical characteristics of patients of less-intensive surveillance and intensive surveillance groups (surveillance of distant metastasis after five years post-surgery)

Characteristics	Before PSM	p *	After PSM	p †	
LSG (n = 970)	ISG (n = 386)	LSG (n = 303)	ISG (n = 303)	
Age (yr)	49.3 ± 9.8	48.4 ± 9.5	0.196	48.4 ± 9.6	49.1 ± 10.0	0.394	
Stage			< 0.001		0.870	
	1	420 (43.0)	103 (27.6)	84 (27.7)	87 (28.7)	
	2	430 (44.0)	191 (51.2)	158 (52.1)	160 (52.8)	
	3	127 (13.0)	79 (21.2)	61 (20.1)	56 (18.5)	
Subtype			< 0.001			0.468	
	HR+, HER2−	612 (63.1)	238 (61.7)	183 (60.4)	181 (59.7)	
	HR+, HER2+	112 (11.5)	46 (11.9)	44 (14.5)	36 (11.9)	
	TNBC	141 (14.5)	60 (15.5)	37 (12.2)	49 (16.2)	
	HR−, HER2+	98 (10.1)	42 (10.9)	39 (12.9)	37 (12.2)	
Histologic grade			0.835			0.873	
	1	126 (12.9)	41 (11.0)	41 (13.5)	38 (12.5)	
	2	488 (49.9)	182 (48.8)	155 (51.2)	161 (53.1)	
	3	317 (32.4)	130 (34.9)	107 (35.3)	104 (34.3)	
LVI			0.008			0.399	
	No	632 (64.7)	232 (62.2)	187 (61.7)	198 (65.3)	
	Yes	258 (26.4)	130 (34.9)	116 (38.3)	105 (34.7)	
Chemotherapy			< 0.001			0.346	
	No	251 (25.7)	31 (8.3)	36 (11.9)	34 (11.2)	
	Neoadjuvant	91 (9.3)	55 (14.7)	33 (10.9)	45 (14.9)	
	Adjuvant	570 (58.3)	244 (65.4)	234 (77.2)	224 (73.9)	
Endocrine therapy			< 0.001			0.185	
	No	230 (23.5)	77 (20.6)	64 (21.1)	78 (25.7)	
	Tamoxifen	420 (43.0)	127 (34.0)	138 (45.5)	116 (38.3)	
	Aromatase inhibitor	217 (22.2)	81 (21.7)	79 (26.1)	78 (25.7)	
	Others (switch)	45 (4.6)	46 (12.3)	22 (7.3)	31 (10.2)	
Radiotherapy			0.021			0.713	
	No	233 (23.8)	90 (24.1)	78 (25.7)	83 (27.4)	
	Yes	677 (69.3)	239 (64.1)	225 (74.3)	220 (72.6)	
Anti-HER2 therapy			0.003			0.537	
	No	787 (80.6)	267 (71.6)	248 (81.8)	241 (79.5)	
	Yes	125 (12.8)	62 (16.6)	55 (18.2)	62 (20.5)	
Values are presented as mean ± standard deviation or number (%).

PSM = propensity score matching; LSG = less-intensive surveillance group; ISG = intensive surveillance group; HR+ = hormone receptor-positive; HER2− = human epidermal growth factor receptor 2-negative; HER2+ = human epidermal growth factor receptor 2-positive; TNBC = triple-negative breast cancer; HR− = hormone receptor-negative; LVI = lymphovascular invasion; HER2 = human epidermal growth factor receptor 2.

*p-value by χ2 test and Student’s t-test; †p-value by conditional logistic regression.

Recurrence outcome

A total of 129 patients experienced recurrence (local or distant metastasis). Thirty-three patients experienced contralateral breast cancer. Local recurrence was observed in 43 patients (33.3%), with a mean LRFS of 56.2 ± 5.3 months. Symptoms (palpable tumors) were reported in 20 individuals. Distant metastasis occurred in 105 patients, with a mean DMFS of 56.4 ± 3.5 months. Nineteen patients with distant metastases experienced locoregional recurrences. This subset was further analyzed based on metastasis sites, which included the bone (24 patients); visceral organs such as the lungs, liver, and brain (41 patients); lymph nodes (12 patients); and multiple sites (28 patients). Thirty-six patients with distant metastasis reported the presence of symptoms including cough, back pain, bone pain, or headaches (Supplementary Table 3).

We evaluated the incidences of local recurrence and distant metastasis in the two surveillance groups within 5-year period after surgery. The local recurrence rates were slightly higher in the ISG (2.8%) than in the LSG (2.0%); however, this difference was not statistically significant (p = 0.770). The majority of local recurrences occurred within the first five years in both groups. Distant metastasis was significantly more frequent in the LSG (11.2%) than in the ISG (4.8%) over five years (p = 0.013). Within the first five years, 64.3% of the LSG patients experienced distant metastasis compared to 33.3% of the ISG patients (p = 0.145; Supplementary Table 4).

After stratification based on the intensity of post-treatment surveillance in the initial five years following surgery, the prevalence of local recurrence slightly increased in both groups. However, the rate remained higher in the ISG (2.9%) than in the LSG (1.0%). This difference was not statistically significant (p = 0.071). The distant metastasis rates at the 10-year follow-up were identical in both groups (6.6%), with no significant differences observed (p = 0.638). Half of these metastases occurred within the first five years in both groups (Supplementary Table 5).

Survival outcomes

In the survival analysis of the surveillance data of patients with distant metastasis within five years post-surgery, subsequent to PSM, no significant difference was observed in OS between the ISG and LSG (p = 0.101; Figure 1A). However, the ISG had better BCSS and DMFS (BCSS, p = 0.005 and DMFS, p = 0.005; Figure 1B and C). In the survival analysis of surveillance for distant metastasis five years post-surgery, no difference was noted in OS, BCSS, or DMFS between the two groups (Figure 2).

Figure 1 Survival analysis for the surveillance of distant metastasis within five years post-surgery.

(A) OS, (B) BCSS, and (C) DMFS for the surveillance of distant metastasis (after propensity score matching).

OS = overall survival; BCSS = breast cancer-specific survival; DMFS = distant metastasis-free survival; LSG = less-intensive surveillance group; ISG = intensive surveillance group.

Figure 2 Survival analysis for the surveillance of distant metastasis after five years post-surgery.

(A) OS, (B) BCSS, and (C) DMFS for the surveillance of distant metastasis (after propensity score matching).

OS = overall survival; BCSS = breast cancer-specific survival; DMFS = distant metastasis-free survival; LSG = less-intensive surveillance group; ISG = intensive surveillance group.

In the context of multivariate Cox regression analysis following PSM, the ISG exhibited a more favorable prognosis than the LSG with respect to both OS and DMFS within five years postoperatively (OS: hazard ratio, 0.367; 95% CI, 0.136–0.987; p = 0.047 and DMFS: hazard ratio, 0.0371; 95% CI, 0.183–0.751; p = 0.006) (Tables 4 and 5). However, no significant was noted in the difference in OS and DMFS between the two groups for surveillance of distant metastasis at five years post-surgery (Supplementary Tables 6 and 7).

Table 4 Multivariate analysis of overall survival for breast cancer patients (surveillance of distant metastasis within five years post-surgery)

Variables	B	Standard error	Wald	p	Hazard ratio	95% CI	
Lower	Upper	
LVI								
	No						(ref)	
	Yes	0.956	0.479	3.983	0.046	2.602	1.017	6.656	
Chemotherapy								
	No			6.318	0.079		(ref)	
	Yes	0.178	1.057	0.028	0.867	1.194	0.151	9.476	
Endocrine therapy								
	No			3.721	0.053		(ref)	
	Tamoxifen	−1.009	0.595	2.876	0.090	0.365	0.114	1.170	
	Aromatase inhibitor	0.005	0.545	0.000	0.992	1.005	0.345	2.927	
Surveillance of distant metastasis within 5 years post-surgery								
	LSG						(ref)	
	ISG	−1.003	0.505	3.945	0.047	0.367	0.136	0.987	
CI = confidence interval; LVI = lymphovascular invasion; LSG = less-intensive surveillance group; ISG = intensive surveillance group.

Table 5 Multivariate analysis of distant metastasis-free survival for breast cancer patients (surveillance of distant metastasis within five years post-surgery)

Variables	B	Standard error	Wald	p	Hazard ratio	95% CI	
Lower	Upper	
LVI								
	No						(ref)	
	Yes	0.035	0.349	0.010	0.921	1.035	0.522	2.052	
Endocrine therapy								
	No			3.243	0.356		(ref)	
	Tamoxifen	−0.221	0.568	0.152	0.697	0.802	0.263	2.441	
	Aromatase inhibitor	0.292	0.632	0.214	0.644	1.340	0.388	4.626	
Radiotherapy								
	No						(ref)	
	Yes	0.552	0.469	1.385	0.239	1.736	0.693	4.353	
Anti-HER2 therapy								
	No						(ref)	
	Yes	−0.321	0.483	0.443	0.506	0.725	0.281	1.868	
Surveillance of distant metastasis within 5 years post-surgery								
	LSG						(ref)	
	ISG	−0.992	0.360	7.605	0.006	0.371	0.183	0.751	
CI = confidence interval; LVI = lymphovascular invasion; HER2 = human epidermal growth factor receptor 2; LSG = less-intensive surveillance group; ISG = intensive surveillance group.

DISCUSSION

This study demonstrated that ISG had a better prognosis than LSG in terms of BCSS and DMFS when we categorized the groups based on surveillance of distant metastasis within five years post-surgery. However, no significant differences were observed in OS, BCSS, and DMFS between the two groups based on surveillance of distant metastasis five years post-surgery.

Two randomized controlled trials (RCTs) showed that intensive surveillance for distant metastases had no survival benefits. The Interdisciplinary Group for Cancer Care Evaluation (Gruppo Italiano Valutazione Interventi in Oncologia; GIVIO) demonstrated no significant difference in the clinical outcomes and quality of life between intensive and clinical surveillance groups in a randomized study involving 1,320 patients [12]. In the second study involving 1,243 patients randomized into a clinical group (physical examination and mammography every six months) and an intensive group (additional chest radiography and bone scan every six months), recurrence-free survival was higher in the clinical group. However, no difference was noted in OS at five and 10 years of follow-up [1314]. Based on this evidence, current guidelines recommend minimal surveillance of patients with early breast cancer patients [15161718]. However, these guidelines are not applied in real practice, and experts prefer more intensive surveillance than that recommended in the current guidelines [19]. In Korea, it is recommended that surgically treated patients who have undergone breast-conserving surgery and radiation therapy undergo a breast imaging procedure every six months post-surgery. Subsequent follow-up examinations should be scheduled at intervals of six months-to-one year for two to five years. To confirm distant metastasis, tests such as liver function tests, chest radiography, chest CT scan, bone scan, abdominal ultrasound, abdominal CT scan, 18F-FDG PET/CT, and tumor marker tests may not be routinely conducted as part of regular surveillance in asymptomatic patients with stage I or II early breast cancer. However, it is only performed if symptoms are present or deemed necessary [20]. Nevertheless, follow-up examinations are performed more frequently than suggested by existing guidelines, and the follow-up approach can differ among several institutions [21]. Systemic metastases were evaluated using at least two examinations: chest radiography, chest CT, abdominal CT, abdominal USG, bone scan, and 18F-FDG PET. A more sophisticated surveillance strategy could detect recurrence earlier and offer a better prognosis for the intensive care group. More effective diagnostic examinations may be helpful in detecting distant metastases earlier, and this strategy can be applied to new treatments [2223].

A recent systematic review showed that intensive surveillance, including diagnostic tests or visits to physicians, has no beneficial effect on 5- or 10-year overall mortality and recurrence compared with less intensive surveillance [7]. Another RCT assessed the OS and recurrence-free period in 672 patients, and only the role of chest radiography in the diagnosis of recurrence was evaluated [24]. However, given advances in breast cancer treatment, the results of previous studies should be reconsidered. Targeted therapies have remarkably improved the clinical outcomes of patients with HER2+ breast cancer and the survival rate of patients with metastatic HER2+ breast cancer [32526]. Furthermore, no ongoing clinical trials are available assessing the effectiveness of surveillance plans for early or locally advanced breast cancer, although research on cancer treatment is actively developing [27]. We included patients who were newly diagnosed with breast cancer between 2009 and 2011 with a follow-up duration of > 10 years (121.2 months). More than 1,300 patients treated over a similar timeline reflected the same treatment trend, and a longer follow-up duration may have enhanced the power of this study.

In our study, the recurrence rate was 9.51%, which was lower than that reported in a previous study. Another study reported that among 1,169 patients with no recurrence, 88% were followed up for at least 10 years [5]. In this study, among all the patients, 84.7% of the patients were diagnosed with early-stage breast cancer (including stages I and II). The lower recurrence rate in this study could be attributed to the relatively high percentage of patients with early-stage breast cancer. However, similar cohorts could be used to evaluate the effect of surveillance intensity on the majority of early-stage breast cancer survivors, and we could consider updating the current guideline recommendations for the surveillance of these patients.

In this study, the ISG had a better prognosis than the LSG for both OS and DMFS when the groups were categorized based on surveillance of distant metastases within five years post-surgery. However, no significant difference was observed in OS and DMFS between the two groups in the surveillance of distant metastasis at five years post-surgery. This is consistent with the results of a previous study in patients with lung metastasis, wherein the detection of distant metastasis in advance did not offer any additional benefit to clinical outcomes [6]. However, a recent study determined that intensive postoperative bone scan screening for patients with breast cancer with bone metastasis was an independent prognostic factor that improved survival outcomes; intensive postoperative bone scan screening prolonged survival in patients with breast cancer with bone metastasis, especially for those with high risks (younger than 50 years, stage II, histology grade G3, and TNBC subtype) [28]. In this study, the classification of LSG and ISG was approached distinctively within five years and within five years following the surgical procedure, primarily because of the unique characteristics of Korea, where individuals who receive medical care for cancer treatments are beneficiaries of the NHI. Discrepancies in standard protocols and less frequent utilization of diagnostic modalities could have influenced the lack of significant differentiation between LSG and ISG at five years postoperatively.

A limitation of our study is that it was retrospective, and there was a possibility of selection bias. Patients with high-risk features or more advanced cancers have a shorter disease-free survival durations and tend to undergo intensive surveillance. This may have obscured the effects of intensive surveillance. To avoid selection bias, we employed 1:1 PSM. Second, we could not adjust for the exact chemotherapeutic regimens for palliative treatment of recurrent/distant metastases, which might have impacted survival outcomes. The lack of detailed data on patient responses to specific chemotherapy regimens limits our ability to fully assess their impact on the study outcomes. The intensity of surveillance after breast cancer treatment is still debated and can influence patient outcomes.

In conclusion, this study demonstrated that the ISG had a better prognosis than the LSG when patients were categorized according to distant metastasis surveillance within five years of surgery. However, intensive surveillance was not related to a better prognosis for distant metastasis surveillance at five years post-surgery. Nevertheless, intensive surveillance and early treatment may have potential benefits for specific patient subsets such as those with bone metastasis, and tailored surveillance strategies may enhance survival outcomes. Further research using nationwide randomized studies is required.

SUPPLEMENTARY MATERIALS

Supplementary Table 1

Definition of intensity surveillance and less-intensive surveillance groups

Supplementary Table 2

Follow-up protocols in each center

Supplementary Table 3

Clinical outcome of patients with recurrence (n = 129)

Supplementary Table 4

Comparative analysis of local recurrence and distant metastasis rates in patients under less intensive versus intensive surveillance within five years after surgery

Supplementary Table 5

Comparative analysis of local recurrence and distant metastasis rates in patients under less intensive versus intensive surveillance at five years post-surgery

Supplementary Table 6

Multivariate analysis of overall survival in patients with breast cancer (surveillance of distant metastasis five years post-surgery)

Supplementary Table 7

Multivariate analysis of distant metastasis-free survival in patients with breast cancer (surveillance of distant metastasis at five years post-surgery)

Funding: This study was supported by the Korea Breast Cancer Foundation 2020 and the Chungbuk National University Hospital grants.

Conflict of Interest: The authors declare that they have no competing interests.

Data Availability: In accordance with the ICMJE data sharing policy, the authors have agreed to make the data available upon request.

Author Contributions: Conceptualization: Park S, Moon HG, Lee JW, Kim KS, Kim Z, Jung SY, Lee J, Lee SK, Chae BJ, Jung SU, Chun JW, Cheun JH, Youn HJ.

Data curation: Park S, Moon HG, Lee JW, Kim KS, Kim Z, Jung SY, Lee J, Lee SK, Chae BJ, Jung SU, Chun JW, Cheun JH, Youn HJ.

Formal analysis: Park S.

Funding acquisition: Youn HJ.

Investigation: Park S, Kim KS, Kim Z, Jung SY, Lee J, Lee SK, Chae BJ, Jung SU, Chun JW, Cheun JH, Youn HJ.

Project administration: Park S.

Resources: Park S, Lee JW, Kim KS, Kim Z, Jung SY, Lee J, Lee SK, Chae BJ, Jung SU, Chun JW, Cheun JH, Youn HJ.

Supervision: Moon HG, Lee JW, Kim KS, Kim Z, Jung SY, Lee J, Lee SK, Chae BJ, Youn HJ.

Validation: Park S.

Visualization: Park S.

Writing - original draft: Park S, Youn HJ.

Writing - review & editing: Park S, Youn HJ.
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