Vitamin D Levels Among Breast Cancer Patients in a Tertiary

Hospital in Lampung, Indonesia

Indri Windarti

, Bintang Abadi Siregar

, Rizki Hanriko

, Aditya Kusumaningtyas

and

Bayu Putra Danan Jaya

Department of Anatomical Pathology, Faculty of Medicine, University of Lampung, Lampung, Indonesia

Department of Surgical, Faculty of Medicine, University of Lampung/Dr. H. Abdul Moeloek Hospital, Lampung, Indonesia

Keywords: Breast Cancer, Comorbidity, Vitamin D Level.

Abstract: Introduction: Vitamin D levels can vary among populations due to geographical location and sun exposure,

dietary habits, lifestyle, and genetic factors. People living in Indonesia may have a higher potential for sun

exposure, which can lead to adequate vitamin D synthesis in the skin. Several studies have suggested a

potential protective role of vitamin D against breast cancer. Preclinical studies have shown that vitamin D

may inhibit the growth and spread of breast cancer cells, induce cell death, and inhibit angiogenesis. Some

studies have found an inverse association, suggesting that higher vitamin D levels may be associated with a

reduced risk of breast cancer. This study was conducted to obtain the most recent information about the

vitamin D levels of breast cancer patients of Indonesian women, especially in Lampung. Methods: We

performed an observational analysis in an ongoing prospective cohort study of breast cancer patients at Dr.

H. Abdul Moeloek Hospital, Bandar Lampung, Indonesia. Sixty-eight subjects were collected from the main

study. Information on subjects, sociodemographic characteristics, clinical status, and tumor profile was

assessed. Vitamin D level was measured using ELISA methods. The association between sociodemographic

and clinical profiles with vitamin D levels was tested using Chi-square. Results: Breast cancer patients' mean

vitamin D level was low (19.7 ± 6.4 ng/ml). There was no correlation between sun exposure,

sociodemographic, and clinical status to Vitamin D levels of breast cancer patients. Patients with comorbidity

tend to have a low vitamin D level, primarily type 2 diabetes. Conclusion: Low vitamin D levels are frequently

found in our population. Further information about vitamin D levels and their association with the survival of

breast cancer patients is still challenging to become research questions.

1 INTRODUCTION

Breast cancer continues to evoke fear among the

majority of women. It is one of the prevalent

malignancies affecting women and the primary

contributor to global cancer-related fatalities.

Approximately 2.3 million new cases of breast cancer

are diagnosed each year (Mattiuzzi & Lippi, 2019;

Sung et al., 2021). The current approach to breast

cancer treatment involves surgical procedures,

chemotherapy, radiotherapy, and hormonal therapy.

However, these diverse treatments still have adverse

effects on patients. Optimal treatment with minimal

side effects has yet to be discovered. Particular

natural compounds are purported to enhance

https://orcid.org/0000-0001-8594-7137

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https://orcid.org/0000-0009-5795-0022

treatment efficacy and act as a preventive against

breast cancer (Buja et al., 2020; Choudhury et al.,

2020; Ren et al., 2020). One such compound is

vitamin D (Bernhardt et al., 2021; Grabiec et al.,

2013).

Vitamin D, classified as a fat-soluble vitamin, is

essential in many biological processes. Operating as

a prohormone, it is crucial to managing calcium,

phosphorus, and skeletal muscle metabolism.

Moreover, vitamin D contributes to cardiovascular

and reproductive functions and is involved in various

physiological processes, including cell

differentiation, apoptosis, inflammation, and insulin

sensitivity (Chen & Zhi, 2020; Cosentino et al., 2021;

Janoušek et al., 2022). Interestingly, vitamin D is

130

Windarti, I., Siregar, B. A., Hanriko, R., Kusumaningtyas, A. and Jaya, B. P. D.

Vitamin D Levels Among Breast Cancer Patients in a Tertiary Hospital in Lampung, Indonesia.

DOI: 10.5220/0012901800004564

Paper published under CC license (CC BY-NC-ND 4.0)

In Proceedings of the 5th International Conference on Social Determinants of Health (ICSDH 2023), pages 130-137

ISBN: 978-989-758-727-6; ISSN: 2975-8297

recognized in preventing various cancer types, such

as colorectal, prostate, ovarian, lung, skin, and breast

cancers (Giovannucci, 2009; Kazemi et al., 2022). In

preclinical investigations, vitamin D has

demonstrated its ability to inhibit the proliferation of

cancer cells (Lopes et al., 2012; Zheng et al., 2017),

trigger apoptosis (Vanoirbeek et al., 2011), and

suppress angiogenesis (Susanti et al., 2018).

While vitamin D can be sourced from dietary

consumption, its primary source stems from the

synthesis of 7-dehydrocholesterol by epidermal cells

upon exposure to UV-B rays from the sun (Chen &

Zhi, 2020). Consequently, regions with limited sun

exposure necessitate supplementary vitamin D intake

to address the body's requirements. As a tropical

nation, Indonesia enjoys abundant sunshine

throughout the year, theoretically providing ample

sun exposure for its population and enabling adequate

synthesis of vitamin D in the skin to fulfill bodily

needs. However, several studies have revealed a

pronounced incidence of vitamin D deficiency,

particularly prevalent among the female population in

Indonesia (Green et al., 2008; Setiati, 2008). A recent

study has revealed a surprising prevalence of 63% in

vitamin D deficiency among pregnant women in

Indonesia (Octavius et al., 2023).

Vitamin D deficiency is associated with an

increased risk of developing several health

conditions, including rickets, osteoporosis, type 2

diabetes, cardiovascular disease, and autoimmune

disorders (Forouhi et al., 2012; Giovannucci, 2009).

It is also linked to an increased risk of developing

breast cancer. Women with sufficient vitamin D

levels have a lower risk of developing breast cancer

than women with deficient vitamin D levels (Atoum

& Alzoughool, 2017; Shaukat et al., 2017). This risk

applies to pre- and postmenopausal women (Bidgoli

& Azarshab, 2014; Kim et al., 2014). Interestingly, in

parallel with the prevalence of vitamin D deficiency

among women in Indonesia, breast cancer has

progressively risen, coupled with lower life

expectancies relative to other nations in the regions

(Susanti et al., 2018). This trend suggests a possible

association between vitamin D deficiency and breast

cancer in the Indonesian female population.

Vitamin D levels within the body can vary,

influenced by various factors, including geographic

location, ethnicity, medical conditions, lifestyle, and

genetics (Mazahery & Von Hurst, 2015). Despite

much evidence establishing a connection between

elevated vitamin D levels and a decreased risk of

breast cancer, there has been limited study exploring

the pattern of vitamin D levels among Indonesian

women diagnosed with breast cancer. Therefore, this

study was conducted to acquire current insights into

the vitamin D levels among breast cancer patients

within the female population of Indonesia, with a

particular emphasis on Lampung Province, and to

explore the association between vitamin D levels and

the sociodemographic and clinical characteristics of

the affected individuals.

2 METHODS

This study used an observational analytic approach

within an ongoing prospective cohort study involving

breast cancer patients at RSUD Dr. H. Abdul

Moeloek in Bandar Lampung, Indonesia. The study's

target population comprises breast cancer patients

currently undergoing treatment at Dr. H. Abdul

Moeloek Bandar Lampung who met the

predetermined inclusion and exclusion criteria. The

inclusion criteria encompass patients diagnosed with

breast cancer through histopathological and

mammographic assessments between 2021 and 2022,

possessing comprehensive medical record

data, and demonstrating a willingness to partake by

signing an informed consent. Conversely, exclusion

criteria pertain to breast cancer patients who have

undergone chemotherapy or radiotherapy, are

currently pregnant, or have declined participation in

the study. The final sample size consistent with the

inclusion and exclusion criteria comprised 68 breast

cancer patients. Ethical clearance for this research has

been obtained from the Ethics Committee for Health

Research, Faculty of Medicine, University of

Lampung, with EC number

2762/UN.26.18/PP.05.02.00/2022.

The data collected in this study included

sociodemographic characteristics (age, education,

occupation, and duration of sun exposure), clinical

information (metastases, types of breast cancer, and

comorbidities), and serum vitamin D levels.

Sociodemographic data were collected through direct

interviews employing a structured questionnaire.

Clinical data were collected from medical record

data. Serum 25-OH vitamin D levels were measured

using the CMIA method by the ARCHITECT

i2000SR immunoassay analyzer at the Prodia Clinical

Laboratory, Jakarta. Vitamin D levels are expressed

in units of ng/mL, where patients are classified as

deficient if their levels fall below 20 ng/mL.

The association between sociodemographic and

clinical characteristics of patients with serum vitamin

D levels was assessed through the Chi-Square test.

Differences in mean serum vitamin D levels in

various comorbid groups were assessed using the

Vitamin D Levels Among Breast Cancer Patients in a Tertiary Hospital in Lampung, Indonesia

131

unpaired t-test and one-way analysis of variance

(ANOVA). All statistical tests were conducted at a

significance level of 95%.

3 RESULTS

3.1 Sample Characteristics

This study included 68 breast cancer patients as a

sample. The average age of the participants was 52.04

years, and 73.5% were over 45 years old.

Predominantly, the sample consisted of homemakers

(38.2%) with a high school education level (32.4%).

Exposure to sunlight was infrequent among most

participants (60.3%), and a significant proportion

reported having no comorbidities (77.9%). Among

the 68 participants, 94.1% were diagnosed with

invasive ductal carcinoma (IDC). Lung metastases

were the most frequent distant metastases (7.4%). The

average vitamin D level among breast cancer patients

was notably low, at 19.6 ng/mL, with the majority

exhibiting either vitamin D deficiency or

insufficiency, as illustrated in Table 1.

3.2 Association between

Sociodemography Characteristics

and Vitamin D Levels

This study's sociodemographic characteristics

included age, education level, occupation, and sun

exposure. Age was categorized into two categories,

namely ≤ 45 years and > 45 years. Education level is

categorized into education up to senior high school

(unschooled, elementary, junior, and senior high

school) and higher education (diploma and bachelor).

Occupational variables are categorized into not-

workers and workers, while sun exposure variables

are categorized into high and low exposure. The Chi-

Square test results found no significant relationship

between these four variables and vitamin D levels

(Table 2).

3.3 Association between Clinical

Characteristics and Vitamin D

Levels

In this study, no significant association was found

between the type of breast cancer, the presence of

metastases, and comorbidities with vitamin D levels

in breast cancer patients (p > 0.05) (Table 3).

However, the presence of comorbidities appears to

affect vitamin D levels. Breast cancer patients with

comorbidities tend to have lower vitamin D levels

when compared to breast cancer patients without

comorbidities (Table 4). When examined further,

breast cancer patients with comorbid type 2 DM have

significantly lower vitamin D levels when compared

to breast cancer patients with comorbid hypertension

and no comorbid (Figure 1)

Table 1: Distribution of sociodemographic characteristics, tumor profile, and vitamin D levels.

Variable N %

Age, years (Min-Max) 52,04±8,88 (32-73)

-. ≤ 45 years 18 26,5

-. > 45 years 50 73,5

Education

-. Unschoole

8 11,8

-. Elementary School 9 13,2

-. Junior High School 9 13,2

-. Senior High School 22 32,4

-. Diploma 7 10,3

-. Bachelo

13 19,1

Occupation

-. Civil Servant 4 5,9

-. Private employees 4 5,9

-. Farme

15 22,1

-. Laboure

1 1,5

-. Housewife 26 38,2

-. Others 18 26,5

Sun Exposure

-. High 27 39,7

-. Low 41 60,3

Comorbid

ICSDH 2023 - The International Conference on Social Determinants of Health

132

-. DM 7 10,3

-. Hypertension 8 11,8

-. No Comorbidities 53 77,9

Type

-. IDC 64 94,1

-. Clear Cell Carcinoma 1 1,5

-. ILC 2 2,9

-. Mixe

1 1,5

Distant Metastases

-. Lungs 5 7,4

-. Mammae 1 1,5

-. Subclavicula

1 1,5

-. Brain 1 1,5

-. No Metastases 60 88,2

Vitamin D (ng/mL) 19,7±6,5

-. Deficienc

35 50,7

-. Insufficienc

29 42

-. Sufficienc

4 5,8

4 DISCUSSION

Vitamin D can be employed as an additional

supplement in treating breast cancer. Various studies

have proven the ability of this vitamin to induce

apoptosis, inhibit proliferation and angiogenesis, and

reduce the progression and risk of breast cancer

(Lopes et al., 2012; Vanhevel et al., 2022; Vanoirbeek

et al., 2011). Additional investigations have also

proven that high vitamin D levels can reduce the risk

of developing breast cancer (Estébanez et al., 2018;

Shamsi et al., 2020).

This study found that most newly diagnosed

breast cancer patients had vitamin D

deficiency/insufficiency, with an average vitamin D

level of 19.7 ng/mL. This value is lower when

compared to the established reference value for

sufficient vitamin D levels, set at 30 ng/mL (Amrein

et al., 2020). This result aligns with several previous

studies, which found similar results (Imtiaz &

Siddiqui, 2014; Narvaez et al., 2014; Shaukat et al.,

2017). Vitamin D deficiency in breast cancer patients

is recognized for its involvement in the proliferation

of primary tumors and metastases and cancer

aggressiveness (Al-Azhri et al., 2017; Williams et al.,

2016). This phenomenon can be attributed to the

disruption caused by the deficiency in regulating the

signaling of the vitamin D receptor and the metabolic

enzymes CYP27B1 and CYP24A1. These enzymes

facilitate the conversion of serum vitamin D into a

form capable of binding to vitamin D receptors. The

role of vitamin D receptors in suppressing tumor

growth is established; hence, the presence of these

imbalances can curtail their effectiveness in

restraining tumor progression (Voutsadakis, 2020).

Table 2: Association between Sociodemography Characteristics and Vitamin D Levels.

Sociodemography Characteristics

Vitamin D Levels

Deficienc

Not deficienc

Age

0,197

-. > 45

ears 19

(

38,0%

)

(

62,0%

)

-. ≤ 45

ears 10

(

55,6%

)

(

44,4%

)

Education

0,429 -. Up to senior high school 19 (39,6%) 29 (60,4%)

-. Higher education 10 (50%) 10 (50%)

Occupation

0,583

-. Worke

(

45,2%

)

(

54,8%

)

-. Not-worke

(

38,5%

)

(

61,5%

)

Sun Ex

osure

0,448 -. High 10 (37,0%) 17 (63,0%)

-. Low 19 (46,3%) 22 (53,7%)

Vitamin D Levels Among Breast Cancer Patients in a Tertiary Hospital in Lampung, Indonesia

133

Table 3: Association between Clinical Characteristics and Vitamin D Levels.

Clinical Characteristic

Kadar Vitamin D

Deficiency Not deficiency

Metastases

0,715 -. Yes 4 (50%) 4 (50%)

-. No 25 (41,7%) 35 (58,3%)

Type

0,305 -. IDC 26 (40,6%) 38 (59,4%)

-. Non IDC 3 (75,0% 1 (25,0%)

Comorbid

0,343

-. Yes 8 (53,3%) 7 (46,7%)

-. No 21 (39,6%) 32 (60,4%)

Table 4: Difference in Vitamin D Levels between Comorbid and Non-comorbid.

Comorbid n Mean±SD (ng/mL) p

-. Yes 15 16,68±6,32 0,041*

-. No 53 20,54±6,31

Exp: * there is a significant relationship based on the unpaired t-test at α=5%.

This study also revealed that breast cancer

patients with comorbidities exhibited notably reduced

vitamin D levels compared to those without

comorbidities. Moreover, patients with both breast

cancer and type 2 diabetes mellitus (DM) displayed

particularly deficient vitamin D levels. Vitamin D's

interconnection with type 2 DM and hypertension has

been long recognized. The deficiency of vitamin D is

intricately linked to the onset of type 2 DM (Chagas

et al., 2012; Lim et al., 2013) and hypertension (Qi et

al., 2017; Zhang et al., 2017). Among patients with

type 2 DM, an inadequate supply of vitamin D is

responsible for instigating glucose intolerance and

interfering with insulin secretion. This disruption is

attributed to the activity of the vitamin D receptor, or

indirectly, via calcium hormones and inflammatory

processes (Chagas et al., 2012).

Vitamin D deficiency stems from several factors:

sun exposure duration, lifestyle, genetic

predisposition, age, and dietary vitamin D intake.

Interestingly, this study found no association between

vitamin D levels and duration of sun exposure,

lifestyle (education and occupation), and age. This

fact leads us to hypothesize that vitamin D deficiency

in breast cancer patients is more dominantly caused

by a lack of vitamin D intake from food. This

hypothesis gains empirical validation from the

findings of a pivotal study conducted by Alco et al.

(2014). Their investigation reveals that inadequate

vitamin D intake corresponds to a remarkable 28.7-

fold escalation in the risk of vitamin D deficiency or

insufficiency among breast cancer patients (Alco et

al., 2014).

Several studies have shown that vitamin D

supplementation to breast cancer patients can

increase serum vitamin D levels without inducing

toxic manifestations (Alco et al., 2014). While

animal-based experimental studies have

demonstrated a favorable impact of vitamin D

supplementation on breast cancer, clinical

investigations have not shown similar results (de La

Puente-Yagüe et al., 2018; Linowiecka et al., 2021).

Vitamin D supplementation has not shown significant

benefits in the effective treatment of breast cancer

patients (Zemlin et al., 2023). Nevertheless, the

potential benefits of vitamin D supplementation,

particularly in individuals with concurrent type 2

diabetes mellitus (DM) conditions, warrant careful

consideration, given the diminished vitamin D levels

observed in this subgroup. This deliberation is

motivated by the intent to avert other ailments linked

to vitamin D deficiency, such as rickets and

osteoporosis, which can potentially exacerbate the

health status of breast cancer patients.

ICSDH 2023 - The International Conference on Social Determinants of Health

134

✱

Figure 1: Differences in mean vitamin D levels between comorbid groups.

5 CONCLUSIONS

Vitamin D deficiency is commonly observed among

breast cancer patients, especially those with type 2

DM comorbidities. The presence of vitamin D

deficiency in breast cancer patients does not exhibit

any association with sociodemographic attributes or

clinical status. Further information about vitamin D

levels and their association with the survival of breast

cancer patients is still challenging to become research

questions.

ACKNOWLEDGEMENTS

We thank the Higher Education for Technology and

Innovation Project (HETI Project) Universitas

Lampung for supporting this research through the

Innovation and Collaboration Grant 2022.

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