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. 2021 Sep 1;10(18):6480–6491. doi: 10.1002/cam4.3873

Clinical impact of follow‐up imaging on mortality in Korean breast cancer patients: A national cohort study

So‐Youn Jung 1,2,[Link], Young Ae Kim 2,3,[Link], Dong‐Eun Lee 4, Jungnam Joo 5, Joung Hwan Back 6, Sun‐Young Kong 2,7,8, Eun Sook Lee 1,2,✉
PMCID: PMC8446413  PMID: 34472221

Abstract

Background

As the incidence of breast cancer has increased and the survival rate has improved, supporting the optimal follow‐up strategy has become an important issue. This study aimed to evaluate follow‐up imaging usage after breast cancer surgery and the implications on mortality in Korea.

Methods

This study included 96,575 breast cancer patients diagnosed during 2002–2010 and registered in the Korea Central Cancer Registry, Statistics Korea, and Korean National Health Insurance Service. We evaluated the frequency of breast imaging (mammography and breast MRI) and systemic imaging for evaluating the presence of distant metastasis (chest CT, bone scan, and PET‐CT), and performed analyses to determine if they had an effect on mortality.

Results

The median follow‐up period was 72.9 months (range: 12.0–133.3) and 7.5% of the patients died. Among all patients, 54.7%, 16.2%, 45.6%, and 8.5% received 3 or more mammograms, chest CTs, bone scans, and PET‐CTs within 3 years after surgery, respectively. Among patients who developed recurrence after 3 or more years, a comparison of overall mortality and breast‐cancer specific mortality according to the frequency of imaging by modality (<3 vs. ≥3) showed that only mammography had significantly reduced mortality (hazard ratio [HR]: 0.72, 95% CI: 0.61–0.84, p < 0.0001; HR: 0.72, 95% CI: 0.61–0.84; p < 0.0001).

Conclusions

This study showed that only frequent mammography reduced mortality and frequent imaging follow‐up with other modalities did not when compared to less frequent imaging. This finding provides supportive evidence that clinicians need to adhere to the current guidelines for surveillance after breast cancer surgery.

Keywords: breast cancer, follow‐up, image, surgery, surveillance, survivors

This study aimed to evaluate follow‐up imaging usage and the clinical implications after breast cancer surgery using Korea national cohort. We found that only frequent mammography reduced mortality and other imaging modalities did not. Therefore, clinicians need to adhere to the current guidelines for surveillance after breast cancer surgery.

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1. INTRODUCTION

As the incidence of breast cancer has increased and the survival rate has improved,1, 2 determining the ideal follow‐up strategy has become an important issue. Follow‐up in breast cancer patients is aimed at the detection of recurrence, metastasis, or new primary cancers; evaluation of treatment‐related long‐term or late effects, adherence to the recommended therapy and screening; and psychosocial and decision‐making support.3, 4

Current guidelines recommend regular follow‐up with history taking, physical examination, and annual mammography to detect new primary cancers, recurrence, and treatment‐related adverse effects.5, 6 In contrast, they do not recommend regular systemic imaging such as chest computed tomography (CT), bone scan, and positron emission tomography (PET)‐CT for the follow‐up of asymptomatic breast cancer patients. These recommendations are based on results from prior studies which established that early diagnosis of distant metastasis provides no additional advantage for survival or health‐related quality of life (QoL).7, 8

Despite these guidelines, the patient fear of recurrence and clinician inclination for early detection of disease recurrence result in frequent usage of systemic imaging.9, 10 In a previous survey of medical and surgical breast oncologists conducted by the Korean Breast Cancer Society, 50% of respondents indicated that they perform follow‐up chest CT more than once a year for the first 5 years and PET‐CT more than once a year for the first 3 years.11

This study aimed to evaluate the recent clinical usage of follow‐up imaging by frequency and modality after curative treatment among Korean breast cancer patients and their implications on mortality. Towards this goal, we analyzed the combined data of the Korea Central Cancer Registry (KCCR), Statistics Korea, and Korean National Health Insurance Service (KNHIS) (Big Data‐Based Guideline for Work‐up and Interval after Surgery in Breast Cancer Patients: BIG‐WISE Study).

2. METHODS

2.1. Study design and population

This BIG‐WISE study was approved by the Institutional Review Board of the National Cancer Center, Korea (NCC 2016‐0209), and the requirement for informed consent was waived because of the use of de‐identified data. The subjects were Korean female breast cancer patients (with International Classification of Diseases, 10th revision [ICD‐10] code12) diagnosed between 2002 and 2010 and registered in the KCCR, Statistics Korea, and KNHIS.

Of the 96,575 breast cancer patients initially identified, we excluded 27,031 patients who were male (n = 480), did not undergo breast cancer surgery (n = 12,390), did not have 3 years of data on imaging in the KNHIS (n = 12,393), had distant metastasis at diagnosis (n = 949), or had less than 12 months of follow‐up (n = 816) (Figure 1). Finally, 69,544 breast cancer patients were included in the analysis. Age at diagnosis was classified as <30, 30–39, 40–49, 50–59, 60–69, and ≥70 years. Comorbidities were evaluated using the Charlson Comorbidity Index (CCI) and categorized as 0, 1, and ≥2. Stage at diagnosis, the data on which became available in the KCCR starting in 2005, was classified as local, regional, and missing/unknown following the Surveillance, Epidemiology, and End Results staging system.13

FIGURE 1.

FIGURE 1

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Study population from National Cohort

2.2. Data sources

For this BIG‐WISE study, we established a merged database from three national cohorts: KCCR, KNHIS, and Statistics Korea. KCCR is a population‐based national cancer registry that includes information on more than 98% of patients with newly diagnosed cancer in Korea.14, 15 The KNHIS is the single insurer of the Korean public health system, and tracks medical information including cancer treatment status (chemotherapy, radiotherapy, and endocrine therapy) and imaging studies.16 Mortality data were obtained from Statistics Korea.17

2.3. Imaging modalities

As follow‐up imaging modalities after surgery, breast imaging (mammography and breast MRI), systemic scans to assess the presence of distant metastasis (chest X‐ray, chest CT, bone scan, and PET‐CT) and treatment‐related imaging (DEXA) were evaluated. We investigated the date at which each follow‐up modality was performed and the number of studies performed for each modality.

To assess the effect of follow‐up imaging on clinical outcomes, patients were divided into two groups according to the number of studies performed for each modality. A cut‐off value of 3 was set based on annual check for 3 years. Univariate and multivariate analyses were performed comparing overall and breast cancer‐related mortality between the divided groups for each imaging modality. An additional analysis was performed in patients with recurrence after 3 or more years to determine whether the frequent follow‐up imaging during 3 years after curative treatment can improve clinical outcomes in recurrent patients.

2.4. Assessment of recurrence and death

Mortality data were obtained from Statistics Korea with the date of the last follow‐up as December 31, 2011.17 The cause of death was recorded and classified according to ICD‐10 code.12 Because KCCR and KNHIS did not have the exact medical information on the date or site of recurrence, we defined recurrence as the presence of new breast cancer surgery, chemotherapy, or radiotherapy, or a change of hormonal therapy, excluding switching and extended therapy, after completion of curative treatments.

2.5. Statistical analysis

Baseline characteristics and imaging modality after surgery were expressed as frequencies in percent. Between‐group comparisons of patient characteristics at diagnosis and treatment status (adjuvant chemotherapy, adjuvant radiotherapy, adjuvant hormonal therapy) were performed using the chi‐squared test or Fisher's exact test, as appropriate. Cox proportional model was used to evaluate the association between patient survival and the frequency of imaging follow‐up for each modality after surgery. Age at diagnosis, treatment status (chemotherapy, radiotherapy, adjuvant hormonal therapy), and CCI without cancer were adjusted for in the multivariable Cox proportional hazard model. All statistical analyses were performed using SAS 9.4 (SAS Institute Inc.), and a p value <0.05 was considered statistically significant.

3. RESULTS

3.1. Patient characteristics

Baseline characteristics for 69,544 breast cancer patients are summarized in Table 1. The most common age at diagnosis was 40–49 years (28,383/69,544; 40.8%), followed by 50–59 years (17,358/69,544; 25.0%). In total, 36.8% (25,583/69,544) and 25.3% (17,617/69,544) of the patients had localized disease and regional metastasis, respectively, and 14.4% patients (10,032/69,544) had a CCI score of ≥3. Overall, 76.3% (53,035/69,544) underwent adjuvant chemotherapy; 61.1% (42,504/69,544), adjuvant radiotherapy; and 69.8% (48,511/69,544), adjuvant hormonal therapy.

TABLE 1.

Baseline patient characteristics

N %
Total 69,544 100.0
Age at diagnosis, years <30 1157 1.7
30–39 10,905 15.7
40–49 28,383 40.8
50–59 17,358 25.0
60–69 8630 12.4
≥70 3111 4.5
Stage at diagnosisa Localized 25,583 36.8
Regional 17,617 25.3
Unknown or missing 26,344 37.9
Year of diagnosis 2002 6237 9.0
2003 6969 10.0
2004 7388 10.6
2005 8049 11.6
2006 9069 13.0
2007 9947 14.3
2008 10,697 15.4
2009 11,188 16.1
Charlson comorbidity indexb 0 22,333 32.1
1 23,892 34.4
2 13,287 19.1
≥3 10,032 14.4
Adjuvant chemotherapy No 16,509 23.7
Yes 53,035 76.3
Adjuvant radiotherapy No 27,040 38.9
Yes 42,504 61.1
Adjuvant hormonal therapy No 21,033 30.2
Yes 48,511 69.8
Recurrence No 57,868 83.2
Yes 11,676 16.8
Death No 64,303 92.5
Yes 5241 7.5
Cause of death Breast cancer 4357 83.1
Other cancer 350 6.7
Other cause 502 9.6
Missing 32 0.6
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a

Stage was evaluated since 2005.

b

Except cancer.

The median follow‐up period was 72.9 months (range: 12.0–133.3), and 11,676 patients (16.8%) experienced recurrence and 5241 (7.5%) died, 83.1% of whom died from breast cancer.

3.2. Imaging follow‐up

After completion of surgery, 93.1% (64,754/69,544) of survivors underwent mammography; 6.8% (4737/69,544), breast MRI; 94.5% (65,713/69,544), chest radiography; 71.3% (49,588/69,544), chest CT; 84.5% (58,746/69,544), bone scan; 67.1% (46,680/69,544), PET‐CT; and 53.8% (37,389/69,544), DEXA. In total, 97.2% (67,587/69,544) underwent CT, bone scan, or PET at least once (Table 2). Within 3 years of breast cancer surgery, ≥1 and ≥3 mammography examinations were performed in 89.6% (62,288/69,544) and 54.7% (27,353/69,544, 39.3%, 3–4; 10,669/69,544, 15.4%, ≥5); chest radiography in 88.6% (61,584/69,544) and 66.5% (46,212/69,544); chest CT in 40.3% (28,007/69,544) and 16.2% (11,274/69,544); bone scan in 78.7% (54,740/69,544) and 45.6% (31,719/69,544); and PET‐CT in 40.3% (28,052/69,544) and 8.5% (5927/69,544).

TABLE 2.

Follow‐up frequency and modality after surgery by time period

Total ≤6 months 6 −12 months 12–24 months 24–36 months >36 months ≤36 months
N % N % N % N % N % N % N %
Local work‐up
Mammography No 4790 6.9 53,995 77.6 30,735 44.2 15,735 22.6 17,181 25.2 14,666 22.4 7256 10.4
Yes All 64,754 93.1 15,549 22.4 38,809 55.8 53,809 77.4 51,093 74.8 50,760 77.6 62,288 89.6
1 or 2 9309 13.4 15,498 22.3 38,491 55.4 50,897 73.2 49,019 71.8 21,608 33.1 24,262 34.9
3 or 4 15,342 22.0 51 0.1 302 0.4 2795 4.0 2001 2.9 15,457 23.6 27,357 39.3
≥5 40,103 57.7 0 0.0 16 0.0 117 0.2 73 0.1 13,695 20.9 10,669 15.4
Breast MRIa No 64,807 93.2 69,082 99.3 68,978 99.2 68,287 98.2 66,945 98.1 62,612 95.7 67,267 96.7
Yes All 4737 6.8 462 0.7 566 0.8 1257 1.8 1329 1.9 2814 4.3 2277 3.3
1 3138 4.5 455 0.7 546 0.8 1121 1.6 1262 1.8 2230 3.4 1578 2.3
2 828 1.2 7 0.0 19 0.0 125 0.2 64 0.1 378 0.6 406 0.6
≥3 771 1.1 0 0.0 1 0.0 11 0.0 3 0 206 0.3 293 0.4
Systemic work‐up
Chest radiography No 3831 5.5 28,146 40.5 24,822 35.7 14,820 21.3 17,231 25.2 15,397 23.5 7960 11.5
Yes All 65,713 94.5 41,398 59.5 44,722 64.3 54,724 78.7 51,043 74.8 50,029 76.5 61,584 88.6
1 or 2 6147 8.8 24,749 35.6 39,345 56.6 45,721 65.8 44,286 64.9 17,838 27.3 15,372 22.1
3 or 4 7718 11.1 6905 9.9 4055 5.8 6332 9.1 4124 6 13,325 20.4 23,720 34.1
≥5 51,848 74.6 9744 14.0 1322 1.9 2671 3.8 2633 3.9 18,866 28.8 22,492 32.4
Chest CT No 19,956 28.7 40,746 58.6 53,316 76.7 51,977 74.7 49,381 72.3 40,485 61.9 41,537 59.7
Yes All 49,588 71.3 28,798 41.4 16,228 23.3 17,567 25.3 18,893 27.7 24,941 38.1 28,007 40.3
1 or 2 25,228 36.3 28,132 40.5 15,605 22.4 15,597 22.4 16,653 24.4 13,582 20.8 16,733 24.1
3 or 4 8199 11.8 652 0.9 606 0.9 1528 2.3 1554 2.3 5412 8.2 7204 10.4
≥5 16,161 23.2 14 0.0 17 0.0 442 0.6 686 1 5947 9.1 4070 5.8
Bone scan No 10,798 15.5 53,335 76.7 36,224 52.1 23,116 33.2 24,089 35.3 20,194 30.9 14,804 21.3
Yes All 58,746 84.5 16,209 23.3 33,320 47.9 46,428 66.8 44,185 64.7 45,232 69.1 54,740 78.7
1 or 2 11,375 16.4 16,174 23.2 33,246 47.8 44,618 64.2 42,633 62.4 21,633 33.0 23,021 33.1
3 or 4 14,116 20.3 35 0.1 74 0.1 1,770 2.5 1,467 2.2 12,430 19.0 22,616 32.5
≥5 33,255 47.8 0 0.0 0 0.0 40 0.1 89 0.1 11,169 17.1 9103 13.1
PET‐CTb No 22,864 32.9 65,598 94.3 60,426 86.9 52,814 75.9 50,103 73.4 31,999 48.9 41,492 59.7
Yes All 46,680 67.1 3946 5.7 9118 13.1 16,730 24.1 18,171 26.6 33,427 51.1 28,052 40.3
1 or 2 28,578 41.1 3809 5.5 9027 13.0 16,146 23.2 17,765 26 28,137 43.0 22,125 31.8
3 or 4 13,076 18.8 129 0.2 87 0.1 546 0.8 359 0.5 3909 6.0 5010 7.2
≥5 5026 7.2 8 0.0 4 0.0 38 0.1 47 0.1 1381 2.1 917 1.3
DEXA No 32,155 46.2 65,725 94.5 61,705 88.7 54,248 78.0 51,315 75.2 38,444 58.8 45,052 64.8
Yes All 37,389 53.8 3819 5.5 7839 11.3 15,296 22.0 16,959 24.8 26,982 41.2 24,492 35.2
1 10,759 15.5 3747 5.4 7718 11.1 14,311 20.6 16,167 23.7 12,589 19.2 11,743 16.9
2 8769 12.6 71 0.1 121 0.2 940 1.3 783 1.1 7380 11.3 9288 13.3
≥3 17,861 25.7 1 0.0 0 0.0 45 0.1 9 0 7013 10.7 3461 5.0
PET‐CT, CT, or bone scan No 1957 2.8 31,300 45.0 26,727 38.4 15,163 21.8 14,504 21.2 11,072 16.9 6765 9.7
Yes All 67,587 97.2 38,244 55.0 42,817 61.6 54,381 78.2 53,770 78.8 54,354 83.1 62,779 90.3
1 or 2 6802 9.8 33,243 47.8 36,183 52.0 36,612 52.7 35,720 52.4 15,614 23.9 14,082 20.2
3 or 4 7473 10.7 4288 6.2 5672 8.2 13,369 19.2 13,532 19.8 11,636 17.8 18,964 27.3
≥5 53,312 76.7 713 1.0 962 1.4 4400 6.3 4518 6.6 27,104 41.4 29,733 42.8
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a

Evaluated since 2005.

b

Since 2006.

Young women aged <30 years underwent less mammography (576/1157, 49.8%, p < 0.001) and more breast MRI (73/1157, 6.3%, p < 0.001, Table 3). Old women aged ≥70 years had less imaging work‐up (mammography: 37.6% (1170/3111), breast MRI: 1.3% (39/3111), chest radiography: 48.5% (1509/3111), chest CT: 11.0% (343/3111), bone scan: 27.5% (856/3111), and PET‐CT: 5.9% (183/3111), Table 3). Patients with local disease underwent more mammography (14,987/25,583, 58.6%) and breast MRI (1281/25,583, 5.0%). Systemic imaging work‐ups were performed in patients with regional disease, those who underwent chemotherapy, and those who underwent radiotherapy (Table 3). Patients who underwent adjuvant hormonal therapy underwent more bone scan (46.9% (22,729/48,511) vs. 42.7% (8990/21,033), p < 0.001) and less chest CT (15.6% (7589/48,511) vs. 17.5% (3685/21,033), p < 0.001) and PET‐CT (7.9% (3826/48,511) vs. 10.0% (2101/21,033), p < 0.001).

TABLE 3.

Comparison of follow‐up imaging frequency and modality within 3 years after treatment based on clinical characteristics

Total Age at diagnosis (years) Stage at diagnosis
<30 30–39 40–49 50–59 60–69 ≥70 p‐value Localized Regional Unstaged or missing p‐value
N % N % N % N % N % N % N % N % N %
Follow‐up imaging 69,544 1157 100 10,905 100 28,383 100 17,358 100 8630 100 3111 100 25,583 100 17,617 100 26,344 100
Mammographya <3 31,518 581 50.2 4930 45.2 12,187 42.9 7705 44.4 4174 48.4 1941 62.4 <0.0001 10,596 41.4 8089 45.9 12,833 48.7 <0.0001
≥3 38,026 576 49.8 5975 54.8 16,196 57.1 9653 55.6 4456 51.6 1170 37.6 14,987 58.6 9528 54.1 13,511 51.3
Breast MRIb No 67,267 1084 93.7 10,483 96.1 27,394 96.5 16,809 96.8 8425 97.6 3072 98.7 <0.0001 24,302 95.0 16,899 95.9 26,066 98.9 <0.0001
Yes 2277 73 6.3 422 3.9 989 3.5 549 3.2 205 2.4 39 1.3 1281 5.0 718 4.1 278 1.1
Chest radiographya <3 23,332 367 31.7 3365 30.9 9090 32.0 5698 32.8 3210 37.2 1602 51.5 <0.0001 9683 37.8 5490 31.2 8159 31.0 <0.0001
≥3 46,212 790 68.3 7540 69.1 19,293 68.0 11,660 67.2 5420 62.8 1509 48.5 15,900 62.2 12,127 68.8 18,185 69.0
Chest CTa <3 58,270 963 83.2 8964 82.2 23,856 84.1 14,488 83.5 7231 83.8 2768 89.0 <0.0001 21,499 84.0 13,107 74.4 23,664 89.8 <0.0001
≥3 11,274 194 16.8 1941 17.8 4527 15.9 2870 16.5 1399 16.2 343 11.0 4084 16.0 4510 25.6 2680 10.2
Bone scana <3 37,825 636 55.0 5755 52.8 15,002 52.9 9317 53.7 4860 56.3 2255 72.5 <0.0001 14,961 58.5 9248 52.5 13,616 51.7 <0.0001
≥3 31,719 521 45.0 5150 47.2 13,381 47.1 8041 46.3 3770 43.7 856 27.5 10,622 41.5 8369 47.5 12,728 48.3
PET‐CTa <3 63,617 1040 89.9 9918 90.9 26,067 91.8 15,756 90.8 7908 91.6 2928 94.1 <0.0001 23,027 90.0 14,961 84.9 25,629 97.3 <0.0001
≥3 5927 117 10.1 987 9.1 2316 8.2 1602 9.2 722 8.4 183 5.9 2556 10.0 2656 15.1 715 2.7
DEXAa Yes 45,052 935 80.8 8314 76.2 18,970 66.8 9874 56.9 4947 57.3 2012 64.7 <0.0001 14,271 55.8 9478 53.8 21,303 80.9 <0.0001
No 24,492 222 19.2 2591 23.8 9413 33.2 7484 43.1 3683 42.7 1099 35.3 11,312 44.2 8139 46.2 5041 19.1
CT or PET‐CT or Bone scana <3 20,847 391 33.8 3243 29.7 8201 28.9 4934 28.4 2584 29.9 1494 48.0 <0.0001 8075 31.6 3555 20.2 9217 35.0 <0.0001
≥3 48,697 766 66.2 7662 70.3 20,182 71.1 12,424 71.6 6046 70.1 1617 52.0 17,508 68.4 14,062 79.8 17,127 65.0
Adjuvant chemotherapy Adjuvant radiotherapy Adjuvant hormonal therapy
No Yes p‐value No Yes p‐value No Yes p‐value
N % N % N % N % N % N %
Follow‐up imaging 16,509 100 53,035 100 27,040 100 42,504 100 21,033 100 48,511 100
Mammographya <3 7548 45.7 23,970 45.2 0.24 13,888 51.4 17,630 41.5 <0.0001 10,600 50.4 20,918 43.1 <0.0001
≥3 8961 54.3 29,065 54.8 13,152 48.6 24,874 58.5 10,433 49.6 27,593 56.9
Breast MRIb No 15,999 96.9 51,268 96.7 0.13 26,680 98.7 40,587 95.5 <0.0001 20,202 96.0 47,065 97.0 <0.0001
Yes 510 3.1 1767 3.3 360 1.3 1917 4.5 831 4.0 1446 3.0
Chest radiographya <3 6597 40.0 16,735 31.6 <0.0001 10,487 38.8 12,845 30.2 <0.0001 7675 36.5 15,657 32.3 <0.0001
≥3 9912 60.0 36,300 68.4 16,553 61.2 29,659 69.8 13,358 63.5 32,854 67.7
Chest CTa <3 15,096 91.4 43,174 81.4 <0.0001 24,127 89.2 34,143 80.3 <0.0001 17,348 82.5 40,922 84.4 <0.0001
≥3 1413 8.6 9861 18.6 2913 10.8 8361 19.7 3685 17.5 7589 15.6
Bone scana <3 11,167 67.6 26,658 50.3 <0.0001 15,805 58.5 22,020 51.8 <0.0001 12,043 57.3 25,782 53.1 <0.0001
≥3 5342 32.4 26,377 49.7 11,235 41.5 20,484 48.2 8990 42.7 22,729 46.9
PET‐CTa <3 15,816 95.8 47,801 90.1 <0.0001 25,307 93.6 38,310 90.1 <0.0001 18,932 90.0 44,685 92.1 <0.0001
≥3 693 4.2 5234 9.9 1733 6.4 4194 9.9 2101 10.0 3826 7.9
DEXAa No 9821 59.5 35,231 66.4 <0.0001 18,822 69.6 26,230 61.7 <0.0001 15,482 73.6 29,570 61.0 <0.0001
Yes 6688 40.5 17,804 33.6 8218 30.4 16,274 38.3 5551 26.4 18,941 39.0
CT or PET‐CT or Bone scana <3 7951 48.2 12,896 24.3 <0.0001 9903 36.6 10,944 25.7 <0.0001 6838 32.5 14,009 28.9 <0.0001
≥3 8558 51.8 40,139 75.7 17,137 63.4 31,560 74.3 14,195 67.5 34,502 71.1
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a

Chi‐squared test.

b

Fisher's exact test

3.3. Survival according to pattern of imaging work‐up

Our analysis of the association between imaging follow‐up and clinical outcomes showed that the patients who underwent more systemic imaging follow‐up had higher rates of recurrence, breast cancer‐related mortality, and overall mortality (Table 4). To determine whether frequent imaging follow‐up resulted in a lower mortality rate, we separately compared the HRs for breast cancer‐related mortality and overall mortality according to the number of imaging studies performed for each modality (<3 vs. ≥3) within 3 years among patients who developed recurrence 3 years after surgery (Table 5). In univariate analyses, patients who underwent mammography ≥3 times showed a lower overall mortality rate (HR: 0.69, 95% CI: 0.59–0.81, p < 0.001) and breast cancer‐related mortality rate (HR: 0.69, 95% CI: 0.58–0.81, p < 0.001) compared to those who underwent mammography <3 times. After adjusting for age at diagnosis, chemotherapy, radiotherapy, adjuvant hormonal therapy, and comorbidities, only frequent mammography significantly influenced overall mortality (HR: 0.72, 95% CI: 0.61–0.84, p < 0.001) and breast cancer‐related mortality (HR: 0.72, 95% CI: 0.61–0.84, p < 0.001). After additionally adjusting for the stage at diagnosis, any breast imaging including mammography and systemic imaging did not influence survivals (Table 5).

TABLE 4.

Univariable and multivariable Cox proportional hazard models for clinical outcomes by type of follow‐up frequency and modality

Total (N = 69,544) Death Breast cancer‐related death Recurrence
Event (N = 5241) HR (95% CI) aHRa (95% CI) aHRb (95% CI) Event (N = 4357) HR (95% CI) aHRa (95% CI) aHRb (95% CI) Event (N = 11,676) HR (95% CI) aHRa (95% CI) aHRb (95% CI)
Mammography <3 31,518 3179 1 1 1 2551 1 1 1 4944 1 1 1
≥3 38,026 2062 0.53 (0.50–0.56) 0.55 (0.52–0.58) 0.53 (0.49–0.58) 1806 0.56 (0.54–0.61) 0.59 (0.55–0.62) 0.59 (0.53–0.65) 6732 1.12 (1.08–1.16) 1.08 (1.04–1.12) 1.14 (1.08–1.21)
Breast MRI No 67,267 5163 1 1 1 4284 1 1 1 11,311 1 1 1
Yes 2277 78 0.60 (0.48–0.75) 0.54 (0.43–0.67) 0.66 (0.51–0.87) 73 0.66 (0.53–0.84) 0.55 (0.44–0.70) 0.71 (0.54–0.93) 365 1.17 (1.06–1.30) 1.06 (0.95–1.18) 1.27 (1.13–1.43)
Chest radiography <3 23,332 1269 1 1 1 905 1 1 1 3001 1 1 1
≥3 46,212 3972 1.54 (1.45–1.64) 1.59 (1.49–1.70) 1.93 (1.74–2.15) 3452 1.89 (1.75–2.03) 1.86 (1.73–2.00) 2.35 (2.07–2.67) 8675 1.49 (1.43–1.56) 1.42 (1.37–1.49) 1.54 (1.45–1.63)
Chest CT <3 58,270 3714 1 1 1 2932 1 1 1 8915 1 1 1
≥3 11,274 1527 2.60 (2.45–2.76) 2.32 (2.18–2.47) 2.39 (2.18–2.61) 1425 3.04 (2.85–3.24) 2.58 (2.42–2.75) 2.75 (2.49–3.03) 2761 1.95 (1.87–2.04) 1.79 (1.71–1.87) 1.98 (1.87–2.09)
Bone scan <3 37,825 2801 1 1 1 2171 1 1 1 5558 1 1 1
≥3 31,719 2440 1.00 (0.95–1.06) 0.97 (0.92–1.03) 0.89 (0.82–0.98) 2186 1.16 (1.09–1.23) 1.08 (1.01–1.15) 1.04 (0.94–1.14) 6118 1.30 (1.26–1.35) 1.22 (1.18–1.27) 1.25 (1.18–1.32)
PET‐CT <3 63,617 4560 1 1 1 3711 1 1 1 9977 1 1 1
≥3 5927 681 2.16 (1.99–2.34) 1.79 (1.65–1.95) 2.49 (2.26–2.75) 646 2.47 (2.27–2.68) 1.96 (1.80–2.13) 2.83 (2.55–3.14) 1699 2.43 (2.31–2.56) 2.19 (2.08–2.31) 2.96 (2.78–3.14)
DEXA No 45,052 4303 1 1 1 3601 1 1 1 8705 1 1 1
Yes 24,492 938 0.47 (0.44–0.50) 0.45 (0.42–0.48) 0.51 (0.46–0.57) 756 0.45 (0.41–0.41) 0.43 (0.40–047) 0.49 (0.44–0.55) 2971 0.64 (0.64–0.69) 0.60 (0.58–0.63) 0.64 (0.60–0.68)
CT, PET‐CT, or bone scan <3 20,847 1361 1 1 1 955 1 1 1 2858 1 1 1
≥3 48,697 3880 1.35 (1.27–1.44) 1.26 (1.18–1.34) 1.40 (1.25–1.57) 3402 1.67 (1.56–1.80) 1.46 (1.36–1.57) 1.87 (1.63–2.16) 8818 1.44 (1.38–1.51) 1.30 (1.24–1.35) 1.51 (1.41–1.62)
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a

Adjusted for age at diagnosis, treatment status (chemotherapy, radiotherapy, adjuvant hormonal therapy), and Charlson comorbidity index.

b

Adjusted for stage, age at diagnosis, treatment status (chemotherapy, radiotherapy, adjuvant hormonal therapy), and Charlson comorbidity index.

TABLE 5.

Univariable and multivariable analyses for clinical outcomes by type of follow‐up frequency and modality in patients who developed recurrence 3 years after surgery

Death (N = 4937) Death Breast Cancer‐related Death
Event (N = 616) HR (95% CI) aHRa (95% CI) aHRb (95% CI) Event (N = 575) HR (95% CI) aHRa (95% CI) aHRb (95% CI)
Mammography <3 2157 327 1 1 1 306 1 1 1
≥3 2780 289 0.69 (0.59–0.81) 0.72 (0.61–0.84) 0.94 (0.65–1.35) 269 0.69 (0.58–0.81) 0.72 (0.61–0.84) 1.00 (0.69–1.45)
Breast MRI No 4858 611 1 1 1 570 1 1 1
Yes 79 5 0.82 (0.34–1.97) 0.61 (0.25–1.48) 0.21 (0.03–1.51) 5 0.87 (0.36–2.10) 0.63 (0.26–1.53) 0.22 (0.03–1.57)
Chest radiography <3 1430 180 1 1 1 168 1 1 1
≥3 3507 436 0.96 (0.81–1.14) 0.96 (0.80–1.14) 1.39 (0.93–2.06) 407 0.96 (0.80–1.15) 0.95 (0.80–1.14) 1.36 (0.91–2.04)
Chest CT <3 4342 546 1 1 1 509 1 1 1
≥3 595 70 1.28 (1.00–1.65) 1.15 (0.90–1.48) 1.00 (0.67–1.67) 66 1.295 (1.00–1.68) 1.14 (0.88–1.49) 1.07 (0.68–1.68)
Bone scan <3 2532 327 1 1 1 304 1 1 1
≥3 2405 289 0.90 (0.77–1.06) 0.88 (0.75–1.03) 1.04 (0.73–1.50) 271 0.91 (0.77–1.07) 0.84 (0.74–1.03) 1.09 (0.76–1.58)
PET‐CT <3 4714 601 1 1 1 560 1 1 1
≥3 223 15 0.96 (0.57–1.60) 0.74 (0.44–1.23) 0.94 (0.53–1.68) 15 1.02 (0.61–1.71) 0.77 (0.46–1.28) 0.98 (0.55–1.76)
DEXA No 3508 486 1 1 1 452 1 1 1
Yes 1429 130 0.83 (0.69–1.01) 0.88 (0.72–1.07) 0.86 (0.59–1.26) 123 0.85 (0.69–1.03) 0.90 (0.74–1.11) 0.88 (0.60–1.30)
CT, PET‐CT, or bone scan <3 1553 218 1 1 1 202 1 1 1
≥3 3384 398 0.92 (0.78–1.09) 0.86 (0.73–1.02) 1.17 (0.75–1.81) 373 0.93 (0.79–1.11) 0.85 (0.71–1.01) 1.21 (0.77–1.91)
Open in a new tab
a

Adjusted for age at diagnosis, treatment status (chemotherapy, radiotherapy, and adjuvant hormonal therapy), and Charlson comorbidity index.

b

Adjusted for stage, age at diagnosis, treatment status (chemotherapy, radiotherapy, adjuvant hormonal therapy), and Charlson comorbidity index.

4. DISCUSSION

This study found that among the imaging modalities used for follow‐up surveillance after curative surgery for breast cancer, only frequent mammography is associated with survival, and frequent use of other imaging modalities did not lower the rates of overall and breast cancer‐related mortality, particularly in patients who developed recurrence after surgery. Further, the pattern of imaging follow‐up differed by age, stage, and type of treatment.

Recent guidelines, such as those from the American Society of Clinical Oncology, National Comprehensive Cancer Network (NCCN), and European Society for Medical Oncology (ESMO) do not recommend other laboratory tests (e.g., tumor markers) or imaging tests (e.g., bone scans, chest or abdominal CT, PET‐CT) in asymptomatic patients because there is no evidence to support their survival benefit.5, 18, 19 However, these tests are being performed in clinical practice because of patient and clinician fear of recurrence or metastasis and the belief that early detection using more intensive imaging work‐ups reduces cancer‐related death. This is supported by the results of the current study, in which 97.2% of the patients underwent a systemic imaging work‐up that included a bone scan, CT, or PET‐CT. In a survey of clinicians on follow‐up after primary treatment of breast cancer conducted by the Korean Breast Cancer Society, most respondents indicated that they conducted more intensive follow‐up imaging work‐ups than recommended in the current guidelines,11 similar to the findings of the current study.

With respect to the patterns of imaging work‐ups, we found that they differed by age, stage, and type of treatment. In young women aged <30, more breast MRIs and fewer mammograms were performed. This could be because of the tendency for dense breast tissue and genetic susceptibility (BRCA1/2 mutation) in these patients.20, 21

Meanwhile, in patients treated with adjuvant hormonal therapy (i.e., those with hormone receptor‐positive breast cancer), more bone scans and fewer chest CTs were performed. This result could be interpreted to mean that clinicians tend to recommend different systemic imaging modalities according to the tumor characteristics, as hormone receptor‐positive tumors develop more bone metastases than visceral metastases.

We also found that systemic imaging work‐ups were more frequently performed in patients with advanced cancer and in patients who receive chemotherapy. However, this did not improve overall survival or breast cancer‐related survival. Previous randomized controlled trials have found that less‐intensive follow‐up strategies did not negatively affect patient outcomes or early detection of recurrence. In addition, more intensive follow‐up was associated with higher costs without differences in early detection of relapses.22, 23 In other systematic review article evaluating the clinical effects of intensive versus less‐intensive follow‐up on disease outcomes, intensive follow‐up with more frequent work‐ups did not reduce mortality and recurrences in breast cancer patients. 24 In addition, there was no survival benefit associated with the early diagnosis of recurrence by intensive follow‐up prior to the occurrence of symptoms, supporting the validity of the current guidelines.9 Moreover, one study reported that the intensity of imaging work‐up did not affect QoL in breast cancer survivors, and 70% of the patients even reported feeling more stressed and anxious when they visited clinics, especially after undergoing tests. 25 Expert panel on breast imaging according to ACR appropriateness criteria comment that there is no role for imaging to screen for distant recurrences in asymptomatic patients with a history of stage I breast cancer that received treatment for curative intent. They recommend that routine surveillance with an annual mammogram is the only imaging test that should be performed to detect an in‐breast recurrence or a new primary breast cancer in women with a history of stage I breast cancer. 26

This study has some limitations. First, the merged data used for the study did not include detailed information on tumor characteristics, such as hormone receptor status. To compensate, we analyzed the outcomes by adjusting for hormonal therapy status. Second, we were not able to take into account the indication for the imaging work‐ups such as cancer‐related symptoms, comorbidity‐related causes, or other medical issues or who prescribed the work‐ups (e.g., oncologists or primary physician) in our analyses. However, we considered the presence of morbid disease and the cause of death in our analysis of the effect of intensive imaging work‐ups on survival. Third, this study was not randomized or a planned prospective study. However, the national health insurance data and statistics which our analyses are based on are highly specific because the KNHIS is the only public health insurer and covers at least 98% of Koreans and is the only representative national database to include cause of death. 27

In conclusion, this study showed that as a follow‐up imaging modality, only frequent mammography and no other imaging modalities reduce overall mortality and breast cancer‐related mortality in Korean female breast cancer patients. These findings provide evidence that frequent systemic imaging work‐ups are not needed despite the fear of recurrence. Therefore, clinicians need to adhere to the current guidelines for surveillance after curative treatment in breast cancer patients.

CONFLICT OF INTEREST

The authors declare no potential conflicts of interest.

Funding information

This work was supported by a grant from the National Cancer Center Grant (NCC‐1911272) and the National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea (1520240).

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon reasonable request with the permission of KCCR, Statistics Korea, and KNHIS.

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Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request with the permission of KCCR, Statistics Korea, and KNHIS.

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