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Abstract

As the efficacy of chemotherapy and adjuvant endocrine therapy for breast cancer increase, the quality-of-life to cancer survivors could be more important issue in strategies of breast cancer treatment. Bone health has become more compelling in care of breast cancer survivor than ever before. This retrospective study was aimed to evaluate factors relating to the change in BMD and to ascertain the correlation between changes in BMD and EMT of women with breast cancer in follow-up. Records of 164 women who underwent surgery for breast cancer were reviewed in this study. The basal characteristics included parity, menopausal state, medication with vitamin D, bisphosphonate, selective estrogen modulator (SERM), aromatase inhibitor (AI), gonadotrophin releasing hormone agonist (GnRHa), chemotherapy, radiotherapy, cancer type including positivity of estrogen receptor, progesterone receptor and HER2, combined the other gynecologic disease or the other origin cancer. At initial and follow-up visit, all subjective were checked with BMD, endometrial thickness (EMT). The mean age was 52.1 ± 8.5 years old and overall interval between initial and follow-up visits were 17.6 ± 7.5 month in this study. The BMDs of L1–4 (1.040 ± 0.166 g/cm² vs 1.070 ± 0.181 g/cm², p < 0.001), femur neck (0.850 ± 0.121 g/cm² vs 0.870 ± 0.136 g/cm², p < 0.001), and femur total (0.902 ± 0.132 g/cm² vs 0.915 ± 0.138 g/cm², p < 0.001) at follow-up visit were significantly lower than those at initial visit. The change in BMDs of L1–4 (ΔBMD_L1–4, r = 0.353, p < 0.001, and r = 0.228, p = 0.003), femur neck (ΔBMD_Neck, r = 0.198, p = 0.011, and r = 0.282, p < 0.001), femur total (ΔBMD_Total, r = 0.294, p < 0.001, and r = 0.327, p < 0.001) had positive correlation with age and the change in EMT (ΔEMT). After age correction, ΔEMT had positive correlation with ΔBMD_Neck (r = 0.245, p = 0.002) and ΔBMD_Total (r = 0.273, p < 0.001). ΔBMD_L1–4 and ΔBMD_Neck differed according to menopausal state (p < 0.001 and p = 0.035), bisphosphonate (p < 0.001 and p < 0.001), and GnRHa (p < 0.001 and p < 0.001). In follow-up of women with history of breast cancer, ΔEMT could be an alternative screening marker for BMD decrease.

Keywords

Bone mineral density endometrial thickness breast cancer

Introduction

According to the Korean national cancer registration database, breast cancer is the leading cancer incidence in Korean women with 347.6 per 100,000 persons, and shows a relatively good prognosis with 92.7% of overall 5-year survival rate.¹ As the efficacy of chemotherapy and adjuvant endocrine therapy for breast cancer increase, the quality-of-life to cancer survivors could be more important issue in strategies of breast cancer treatment. So, follow-up of breast cancer survivors could be involved by multidisciplinary clinical care.^2–4

Breast cancer survivors, women on selective estrogen receptor modulator (SERM) therapies in particular, should be recommended for an annual gynecologic assessment to surveilling the uterine endometrium and screening the other cancer, because long-term SERM therapy of postmenopausal women with breast cancer is associated with uterine pathology.⁴ For screening procedure, ultrasonography is useful in asymptomatic patients selecting cases with increased endometrial thickness for further investigation.⁵ The previous studies reported that increased endometrial thickness (EMT) as assessed by ultrasonography was associated with increased risk of endometrial pathologies including carcinomas, and identification of cancer at an early stage could be possible by the regular endometrial surveillance.^6,7 However, a previous study suggested that frequent surveillance for EMT would not be necessary in the follow-up for this patients because most endometrial changes were not a serious problem even though adjuvant hormonal therapy after breast cancer surgery exhibited changes in the endometrium and ovary.⁸

Bone health has become more compelling in care of breast cancer survivor than ever before.⁹ The estrogen deprivation status after breast cancer treatment including chemotherapy and adjuvant hormone therapy disrupts the skeletal homeostasis, promoting loss of bone mineral density (BMD), and increasing the risk of osteoporosis.^10–12 Osteoporosis is a “silent disease” with rare symptoms in its early stages, and often goes undiagnosed until severe fractures occur.^13,14 Therefore, the multidisciplinary clinical care for breast cancer survivor should include surveillance of BMD change.^15,16

Some previous studies found SERM could increase BMD without significant EMT change in breast cancer survivors.^17,18 However, the correlation between changes in BMD and EMT has been rarely known up-to-date, even though both could be the alternative marker for estrogen status of breast cancer patients. This study was aimed to evaluate factors relating to the change in BMD and to ascertain the correlation between changes in BMD and EMT of women with breast cancer in follow-up.

Materials and methods

Subjective

The patients who had been undergone operative treatment due to breast cancer and visited gynecology clinic were recruited in this retrospective study. Records of a 164 women were reviewed from January 1, 2015 to December 31, 2018. The purpose of visit to gynecology clinic was routine gynecologic examination. All patients visited gynecology clinic twice a year. The first and the following visits were terms as “the initial visit” and “the follow-up visit.”

Clinical variables

The basal characteristics of all subject were checked at the initial visit. The basal clinical variables included age, parity, and menopausal state at breast cancer diagnosis. Cancer type including positivity of estrogen receptor, progesterone receptor and HER2 by pathologic report was checked. The information about receiving chemotherapy and/or radiotherapy after surgery, combined the other origin cancer and/or gynecologic disease was obtained. The current medication with vitamin D, bisphosphonate, selective estrogen modulator (SERM), aromatase inhibitor (AI), and gonadotrophin releasing hormone agonist (GnRHa) at visit were checked. All subjects were undertaken gynecologic ultrasonography for surveillance of EMT, and BMD at initial and follow-up visit.

Statistical analysis

Data were analyzed by Student t test, paired t test, and Pearson correlation test as appropriate. In all tests, significance was accepted for a p value of <0.05. All data were analyzed using Statistical Package for the Social Sciences for Windows (version 25; SPSS, Chicago, IL).

Ethics statement

The present study protocol was reviewed and approved by the Institutional Review Board of Seoul National University College of Medicine (approval No. H-1104-076-359) and Korea University Guro Hospital (approval No. 2018GR0355).

Results

Characteristics of the subject

The basal characteristics are summarized in Tables 1 and 2. The mean age of the subjective was 52.1 ± 8.5 year-old and the mean BMI was 23.3 ± 3.2 kg/m² at initial visit in this study. The overall interval between initial and follow-up visits were 17.6 ± 7.5 month. In the subjective, the nulliparous, the primiparous and the multiparous were 20 (12.2%), 32 (19.5%), and 112 (68.5%). Sixty of women (36.6%) were premenopausal, and 104 of women (63.4%) were postmenopausal at the initial visit. One hundred and forty-one of women (86.0%) had no history of hormone therapy for menopausal symptom before breast cancer diagnosis. According to breast cancer tissue analysis, 159 of women (97.0%) had estrogen receptor, and 128 of women (78.0%) had progesterone receptor. By Her2/neu staining score according to the American Society of Clinical Oncology/College of American Pathologists guidelines,¹⁹ 117 of women (71.3%) were negative (− to 1+), 38 of women (23.2%) were equivocal (2+), and 9 of women (5.5%) were positive (3+). For adjuvant therapy, chemotherapy (n = 44, 26.8%), tamoxifen (n = 122, 74.4%), aromatase inhibitor (n = 43, 26.2%), radiotherapy (n = 103, 62.8%), and GnRHa (n = 36, 22.0%) were conducted. Ninety-five of women (57.9%) took calcium combined with vitamin D, and 31 of women (18.9%) took bisphosphonate. Eighty-five of women (51.8%) had other gynecologic disease, and 15 of women (9.1%) had other cancer.

Table 1.

The basal characteristics of the subject (n = 164).

Characteristics	Minimal value	Maximum value	Mean ± S.D.
Age (years)	30.0	77.0	52.1 ± 8.5
Height (cm)	146.0	172.5	157.2 ± 5.3
Weight (kg)	41.2	84.1	57.6 ± 7.6
BMI (kg/m²)	17.3	36.4	23.3 ± 3.2
Interval of measurements (month)	6.0	46.0	17.6 ± 7.5
BMD_L1–L4 (g/cm²)
Initial visit	0.677	1.592	1.070 ± 0.181
Follow-up visit	0.680	1.573	1.040 ± 0.166
The difference	−0.154	0.101	−0.030 ± 0.052
BMD_Neck (g/cm²)
Initial visit	0.590	1.318	0.870 ± 0.136
Follow-up visit	0.608	1.259	0.850 ± 0.121
The difference	−0.324	0.163	−0.020 ± 0.056
BMD_Total (g/cm²)
Initial visit	0.620	1.397	0.915 ± 0.138
Follow-up visit	0.612	1.376	0.902 ± 0.132
The difference	−0.108	0.064	−0.013 ± 0.031
EMT (mm)
Initial visit	1.4	15.3	4.76 ± 2.57
Follow-up visit	1.5	15.3	4.21 ± 2.25
The difference	−11.8	9.0	−0.56 ± 3.18

BMD: bone mineral density; EMT: endometrial thickness; SD: standard deviation.

Table 2.

The categorical variables of the subject (n = 164).

Variables	n (%)
Parity
0	20 (12.2)
1	32 (19.5)
≥2	112 (68.5)
Menopausal status
premenopausal	60 (36.6)
Postmenopausal	104 (63.4)
History of HRT
No	141 (86.0)
Yes	23 (14.0)
Hormone receptor
Positive estrogen receptor	159 (97.0)
Positive progesterone receptor	128 (78.0)
Her2/neu (IHC)
(−) or 1+	117 (71.3)
2+ (equivocal)	38 (23.2)
3+	9 (5.5)
Adjuvant therapy
Chemotherapy	44 (26.8)
Tamoxifen	122 (74.4)
Aromatase inhibitor	43 (26.2)
Radiotherapy	103 (62.8)
GnRHa	36 (22.0)
Other medications
Calcium + vitamin D	95 (57.9)
bisphosphonate	31 (18.9)
Combined other disease
Gynecology	85 (51.8)
Other cancer	15 (9.1)

Change of BMD and EMT

Change of BMD and EMT were shown in Table 3. BMD_L1–L4 (1.040 ± 0.166 g/cm² vs 1.070 ± 0.181 g/cm², p < 0.001), BMD_Neck (0.850 ± 0.121 g/cm² vs 0.870 ± 0.136 g/cm², p < 0.001), and BMD_Total (0.902 ± 0.132 g/cm² vs 0.915 ± 0.138 g/cm², p < 0.001) decreased significantly at the follow-up visit compared to the initial visit. EMT at the follow-up visit (4.21 ± 2.25 mm) decreased significantly than EMT at the initial visit (4.76 ± 2.57 mm, p = 0.028).

Table 3.

Change of BMD and EMT from initial to follow-up visit.

Characteristics	Minimal value	Maximum value	mean ± S.D.	p Value
BMD_L1–L4 (g/cm²)
Initial visit	0.677	1.592	1.070 ± 0.181	<0.001
Follow-up visit	0.680	1.573	1.040 ± 0.166	<0.001
The difference	−0.154	0.101	−0.030 ± 0.052
BMD_Neck (g/cm²)
Initial visit	0.590	1.318	0.870 ± 0.136	<0.001
Follow-up visit	0.608	1.259	0.850 ± 0.121	<0.001
The difference	−0.324	0.163	−0.020 ± 0.056
BMD_Total (g/cm²)
Initial visit	0.620	1.397	0.915 ± 0.138	<0.001
Follow-up visit	0.612	1.376	0.902 ± 0.132	<0.001
The difference	−0.108	0.064	−0.013 ± 0.031
EMT (mm)
Initial visit	1.4	15.3	4.76 ± 2.57	0.028
Follow-up visit	1.5	15.3	4.21 ± 2.25	0.028
The difference	−11.8	9.0	−0.56 ± 3.18

BMD: bone mineral density; EMT: endometrial thickness; SD: standard deviation.

Correlation between change of BMD and EMT

Analysis on correlation between ΔBMD and ΔEMT were summarized in Tables 4 and 5. ΔBMD_L1–L4 had significant positive correlation with age (r = 0.353, p < 0.001) and ΔEMT (r = 0.228, p = 0.003). ΔBMD_Neck had significant positive correlation with age (r = 0.198, p = 0.011) and ΔEMT (r = 0.282, p < 0.001). ΔBMD_Total had significant positive correlation with age (r = 0.294, p < 0.00111) and ΔEMT (r = 0.327, p < 0.001). By partial correlation analysis with adjusting for age, ΔBMD_Neck (r = 0.245, p = 0.002) and ΔBMD_Total (r = 0.273, p < 0.001) had significant positive correlation with ΔEMT. Figures 1(a) to (c) and 2(a) to (c) show the correlation scatter plots of ΔEMT correlated with ΔBMD_L1–L4, ΔBMD_Neck, and ΔBMD_Total by the linear and the quadratic model, respectively. The squared correlation coefficient (R²) of ΔEMT correlated with ΔBMD_L1–L4, ΔBMD_Neck, and ΔBMD_Total were 0.052, 0.080, and 0.107 by the linear model, and 0.110, 0.108, and 0.155 by the quadratic model, respectively.

Table 4.

Correlation coefficients of ΔBMD with the other continuous variables.

	r with ΔBMD	p Value
ΔBMD_L1–L4
Age	0.353	<0.001
BMI	0.098	0.210
ΔEMT	0.228	0.003
ΔBMD_Neck
Age	0.198	0.011
BMI	−0.026	0.741
ΔEMT	0.282	<0.001
ΔBMD_Total
Age	0.294	<0.001
BMI	0.144	0.066
ΔEMT	0.327	<0.001

Table 5.

Partial correlation coefficients of ΔBMD with ΔEMT adjusting for age.

	r with ΔBMD	p Value
ΔBMD_L1–L4 and ΔEMT	0.151	0.054
ΔBMD_Neck and ΔEMT	0.245	0.002
ΔBMD_Total and ΔEMT	0.273	<0.001

Figure 1.

The correlation scatter plots ΔEMT compared to ΔBMD by the linear model: (a) the correlation scatter plots of ΔEMT compared to ΔBMD_L1–L4, (b) the correlation scatter plots of ΔEMT compared to ΔBMD_Neck, and (c) The correlation scatter plots of ΔEMT compared to ΔBMD_Total.

Figure 2.

The correlation scatter plots of ΔEMT compared to ΔBMD by the quadratic model: (a) the correlation scatter plots of ΔEMT compared to ΔBMD_L1–L4, (b) the correlation scatter plots of ΔEMT compared to ΔBMD_Neck, and (c) the correlation scatter plots of ΔEMT compared to ΔBMD_Total.

Change in BMD and EMT according to the categorical variables

Comparison of change in BMD and EMT according to the categorical variables were summarized in Table 6. ΔBMD_L1–L4 showed significant differences according to menopausal status, Her2/neu and use of GnRH agonist and bisphosphonate. ΔBMD_Neck showed significant differences according to use of GnRH agonist and bisphosphonate. ΔBMD_Total showed significant differences according to menopausal status, use of GnRH agonist and bisphosphonate. ΔEMT showed significant differences according to menopausal status and use of GnRH agonist. There were no significant difference in BMD and EMT according to the other categorical variables.

Table 6.

Comparison of ΔBMD_L1–L4, ΔBMD_Neck, ΔBMD_Total, and ΔEMT according to the categorical variables.

	ΔBMD_L1–L4		ΔBMD_Neck		ΔBMD_Total		ΔEMT
	Mean ± SD	p Value	Mean ± SD	p Value	Mean ± SD	p Value	Mean ± SD	p Value
Parity
0 (n = 20)	−0.043 ± 0.045	0.460	−0.019 ± 0.028	0.662	−0.019 ± 0.026	0.670	−0.03 ± 0.31	0.948
1 (n = 32)	−0.030 ± 0.052		−0.028 ± 0.027		−0.011 ± 0.028		−0.06 ± 0.33
≥2 (n = 112)	−0.028 ± 0.053		−0.018 ± 0.065		−0.013 ± 0.033		−0.06 ± 0.32
Menopausal status
Premenopausal (n = 60)	−0.050 ± 0.052	<0.001	−0.025 ± 0.041	0.382	−0.020 ± 0.030	0.035	−0.15 ± 0.41	0.004
Postmenopausal (n = 104)	−0.018 ± 0.049	<0.001	−0.017 ± 0.063	0.382	−0.009 ± 0.032	0.035	−0.01 ± 0.41	0.004
History of HRT
No (n = 141)	−0.031 ± 0.052	0.372	−0.023 ± 0.058	0.151	−0.015 ± 0.030	0.056	−0.06 ± 0.33	0.797
Yes (n = 23)	−0.021 ± 0.052	0.372	−0.005 ± 0.034	0.151	−0.002 ± 0.035	0.056	−0.04 ± 0.21	0.797
Estrogen receptor
Negative (n = 5)	−0.020 ± 0.051	0.675	−0.041 ± 0.015	0.398	−0.025 ± 0.024	0.408	−0.14 ± 0.18	0.527
Positive (n = 159)	−0.030 ± 0.052	0.675	−0.020 ± 0.056	0.398	−0.013 ± 0.031	0.408	−0.05 ± 0.32	0.527
Progesterone receptor
Negative (n = 36)	−0.030 ± 0.049	0.977	−0.026 ± 0.047	0.459	−0.014 ± 0.029	0.972	−0.01 ± 0.31	0.369
Positive (n = 128)	−0.030 ± 0.053	0.977	−0.019 ± 0.058	0.459	−0.013 ± 0.032	0.972	−0.06 ± 0.32	0.369
Her2/neu (IHC)
(−) or 1+ (n = 117)	−0.037 ± 0.053	0.031	−0.015 ± 0.047	0.167	−0.013 ± 0.031	0.736	−0.07 ± 0.34	0.450
2+ (equivocal) (n = 38)	−0.014 ± 0.045		−0.035 ± 0.074		−0.017 ± 0.027		−0.02 ± 0.27
3+ (n = 9)	−0.010 ± 0.052		−0.021 ± 0.059		−0.010 ± 0.050		0.04 ± 0.24
Chemotherapy
No (n = 120)	−0.032 ± 0.055	0.381	−0.022 ± 0.059	0.534	−0.014 ± 0.031	0.677	−0.07 ± 0.34	0.318
Yes (n = 44)	−0.024 ± 0.043	0.381	−0.016 ± 0.046	0.534	−0.012 ± 0.031	0.677	−0.01 ± 0.24	0.318
Tamoxifen
No (n = 42)	−0.033 ± 0.050	0.691	−0.029 ± 0.055	0.218	−0.016 ± 0.031	0.481	−0.06 ± 0.22	0.924
Yes (n = 122)	−0.029 ± 0.053	0.691	−0.017 ± 0.056	0.218	−0.012 ± 0.032	0.481	−0.05 ± 0.35	0.924
Aromatase inhibitor
No (n = 121)	−0.029 ± 0.053	0.611	−0.018 ± 0.056	0.317	−0.012 ± 0.031	0.291	−0.05 ± 0.35	0.866
Yes (n = 43)	−0.033 ± 0.050	0.611	−0.028 ± 0.055	0.317	−0.018 ± 0.031	0.291	−0.06 ± 0.22	0.866
Radiotherapy
No (n = 61)	−0.028 ± 0.046	0.672	−0.011 ± 0.048	0.089	−0.008 ± 0.033	0.100	−0.01 ± 0.27	0.123
Yes (n = 103)	−0.031 ± 0.056	0.672	−0.026 ± 0.059	0.089	−0.016 ± 0.030	0.100	−0.08 ± 0.34	0.123
GnRHa
No (n = 128)	−0.020 ± 0.050	<0.001	−0.015 ± 0.051	0.014	−0.008 ± 0.030	<0.001	−0.01 ± 0.24	<0.001
Yes (n = 36)	−0.063 ± 0.046		−0.040 ± 0.068		−0.031 ± 0.028		−0.25 ± 0.16	<0.001
Calcium + vitamin D
No (n = 69)	−0.034 ± 0.045	0.344	−0.026 ± 0.054	0.242	−0.017 ± 0.028	0.248	−0.06 ± 0.24	0.974
Yes (n = 95)	−0.027 ± 0.056	0.344	−0.016 ± 0.056	0.242	−0.011 ± 0.034	0.248	−0.05 ± 0.37	0.974
Bisphosphonate
No (n = 133)	−0.039 ± 0.050	<0.001	−0.030 ± 0.055	<0.001	−0.018 ± 0.032	<0.001	−0.08 ± 0.32	0.100
Yes (n = 31)	0.011 ± 0.039	<0.001	0.009 ± 0.047	<0.001	0.005 ± 0.021	<0.001	0.03 ± 0.29	0.100
Combined gynecology disease
No (n = 79)	−0.022 ± 0.052	0.059	−0.013 ± 0.059	0.097	−0.009 ± 0.032	0.092	−0.01 ± 0.25	0.067
Yes (n = 85)	−0.037 ± 0.051	0.059	−0.027 ± 0.051	0.097	−0.017 ± 0.030	0.092	−0.01 ± 0.36	0.067
Combined other cancer
No (n = 135)	−0.028 ± 0.052	0.388	−0.022 ± 0.059	0.337	−0.015 ± 0.032	0.223	−0.06 ± 0.32	0.448
Yes (n = 29)	−0.037 ± 0.054	0.388	−0.011 ± 0.038	0.337	−0.007 ± 0.026	0.223	−0.01 ± 0.32	0.448

Discussion

This study was aimed to evaluate factors relating to the change in BMD of women with history of breast cancer. We found change in EMT could be a screening marker of change in BMD in follow-up for breast cancer patients. Additionally, our results suggest some clinical factors including age, menopausal status, and use of GnRH agonist and bisphosphonate could have effects on the change in BMD.

Our results showed mean BMDs in all checked point decreased at the follow-up visit compared to the initial visit. These results suggest that breast cancer survivors could be at the risk of decrease in BMD during follow-up. Furthermore, ΔBMD had a positive correlation with age and ΔEMT, even though it had no significant correlation with BMI. In the analysis of partial coefficients of ΔBMD with ΔEMT by adjusting for age, ΔEMT still showed positive correlation with ΔBMD. Furthermore, the correlation scatter plots of ΔEMT correlated with ΔBMD by the linear and the quadratic model showed significant correlation. Ultrasonography is a popular screening tool for gynecologic surveillance of breast cancer follow-up, and measurement of EMT by ultrasonography could be an easily accessible screening marker. A few previous study reported that ultrasonographic EMT shows a positive correlation with BMD in postmenopausal women consistent with our results.^20,21 Considering mean age and proportion of postmenopausal status of this present study (52.1 ± 8.5 and 63.4%), this result was consistent with the previous studies with subjects of similar age.^22,23 Unlike these studies which showed this correlation with healthy postmenopausal women, this present study was conducted with breast cancer survivors.

In the comparison of ΔBMD according to the categorical variables, use of GnRH agonist and bisphosphonate showed a significance. Use of GnRH agonist showed more decreased BMD in all points. This finding suggests that the patients with long-term use of GnRH agonist may need more careful check for bone change. The previous studies reported that adjuvant treatment including GnRH agonist could enhance the rate of bone loss in breast cancer patients, consistent with our data.^15,24 Use of bisphosphonate showed a protective effect against bone loss in this cohort study, and it was consistent with the previous studies.^25–27 Menopausal status had a significance in only ΔBMD_L1–L4 in this present study. Premenopausal women showed larger difference in ΔBMD_L1–L4 than postmenopausal women. It implicates cessation of ovarian hormone production could affect homeosis of lumbar bone first rather than femoral bone. Interestingly, consistent with our results, a previous study reported that surgically induced menopause is associated with loss of the lumbar BMD and no significant change of BMD in the femoral neck in 2 years.²⁸

In the comparison of ΔEMT according to the categorical variables, use of GnRH agonist and menopausal status showed a significance. Use of GnRH agonist enhanced change of EMT. A previous randomized controlled clinical trial also showed GnRH agonist had an effect of thinner EMT in breast cancer patients.²⁹ It could be due to GnRH agonist-induced estradiol suppression. There was no significant effect on change of EMT according to use of calcium, vitamin D, and bisphosphonate. Postmenopausal women showed a smaller change of EMT than premenopausal women. We presumed that EMT of postmenopausal status already could have a low capacity to change.

Some questions to be answered remain from our results. First of all, no correlation between BMD and BMI were shown in our study. Many previous data suggested higher BMI could act as a protective factor for decreased BMD.^30–32 However, in contrast with what has been reported above, some recent data suggested that lean body mass could have an impact on BMD rather than BMI in postmenopausal women,³³ and BMI could not be a predictor of fracture risk in obese postmenopausal women.³⁴ Our subjects included 23.7% (40/169) of obese women with BMI over 25.0 kg/m². We inferred that this characteristic could affect these results, due to small sample size of this study. Further study with large sample size should be necessary. The second one could be the low R² of ΔEMT correlated with ΔBMD. Concerning to this in our data, linear model R² showed 0.052 to 0.107, and quadratic model R² showed 0.108 to 0.155. It suggests that our functional correlation model could interpret exactly only 5% to 15% of all cases. However, our results suggested that ΔEMT could be a useful screening marker for warning to a steep BMD decrease, rather than factor for calculating BMD decrease. Considering breast cancer survivors could be at the risk of BMD decrease, easy-accessible and cost-effective ultrasonographic screening could have an advantage.

Conclusions

In conclusion, ΔEMT by ultrasonography between patient’s visits could be an alternative screening marker for BMD decrease in follow-up of women with history of breast cancer. Easy accessibility and cost-effectiveness could be beneficial by using this ultrasonographic screening of gynecology clinics adding values to previously reported efficacy of gynecologic follow-up.^35,36

Footnotes

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by grant from the Ministry of Science and ICT (2020R1A2C1010293) and by the Medical Research Program at Seoul National University College of Medicine.

Ethics approval

Ethical approval for this study was obtained from the Institutional Review Board of Seoul National University College of Medicine (approval No. H-1104-076-359) and Korea University Guro Hospital (approval No. 2018GR0355).

Informed consent

Informed consent was not sought for the present study because of retrospective nature.

ORCID iD

Seung-Yup Ku

Author biographies

Ji Han Lee participated in this study via SNUMC Medical Investigation Program as Young Principal Investigator.

Yong Jin Kim is reproductive endocrinologist, and his research interest includes the development of fertility preservation strategy for aged women.

Sung Woo Kim is clinical expert and serves as executive secretary of KSRM.

Hoon Kim has high expertise in reproductive epidemiology and osteoporosis endocrinology.

Wonshik Han has remarkably contributed to the fields of breast and endocrine surgery and has been collaborating with reproductive endocrinology team in numerous projects.

Seung-Yup Ku, is Professor at Seoul National University, and has published more than 120 papers and his research interests include the basic and clinical aspects of reproductive endocrinology including stem cells and reproductive engineering.

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