Profile of Breast Cancer Patients with Radiotherapy in Hasan Sadikin Hospital Bandung
Atikah Larasati
1*, Marhendra Satria Utama
2, Adji Kusumadjati
21 Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia
2 Department of Radiology, Radiation Oncology Sub-Division, Hasan Sadikin General Hospital / Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia
A R T I C L E I N F O
Received : 07 September 2021 Reviewed : 07 October 2021 Accepted : 02 December 2021
Keywords:
breast cancer, profile, radiotherapy
A B S T R A C T
Background: Breast cancer is the most common cancer in women worldwide and in Indonesia.
Most patients arrived at the hospital too late to receive the optimal benefit from breast cancer therapies, in which radiotherapy is one of the essential modalities. Radiotherapy is conducted as a local control by using the principle of ionizing radiation to eradicate the growth of cancer cells, hence reducing the chances of recurrence and enhancing survival rates. Some of the side effects include skin conditions that can manifest as redness and dry skin, fatigue, lymphedema, and chest wall fibrosis. Data and research on the profile of breast cancer patients with radiotherapy were still limited in Indonesia, particularly in West Java. This study aimed to assess the profile of breast cancer patients in Hasan Sadikin Hospital Bandung.
Methods: This study was conducted with the retrospective descriptive quantitative method. The sampling technique was total sampling using 280 medical records of breast cancer patients with radiotherapy from January 1, 2018, until December 31, 2019, which were registered in the Hospital-Based Cancer Registry at the Radiotherapy Department, Hasan Sadikin General Hospital.
Results: Breast cancer patients undergoing radiotherapy were mostly in the 45–54 years age group (36.4%). The most common chief complaint was a lump in the breast (66.4%), particularly in the left breast (45.0%). About 22.5% of all patients arrived at a locally advanced stage and 30.7% at an advanced stage with bone metastasis (10.6%), histopathological subtype Invasive Carcinoma No Special Type (IC-NST) (81.1%), and molecular subtype luminal B (9.6%). The most widely performed therapies were total mastectomy surgery (16.1%), neoadjuvant chemotherapy (62.9%), and complete adjuvant radiotherapy (47.1%) with External Beam Radiotherapy (EBRT) method using LINAC (71.1%).
Conclusions: Breast cancer is a health burden in Hasan Sadikin General Hospital and remains one of the national health priorities. Further evaluation of management and follow-up studies need to be done to improve the implementation of therapies for patients and reduce the incidence rate.
INTRODUCTION
Breast cancer is a neoplasm or malignancy in breast tissue that can originate from ducts or lobules. It is the most common cancer in women and ranks second in cancer with the world’s highest incidence after lung cancer [1]. In Indonesia, breast cancer has the highest incidence rate of all cancers, which is 16.7% of the total 348,809 cases. In addition, breast cancer also has the second-highest mortality rate after lung cancer, which is 11% of the total 207,210 cases of death due
to cancer [2]. More than 80% of patients arrived at the hospital too late to receive the optimal benefit from breast cancer therapies [3]. Delayed early detection to treatment contributed to the high mortality rate.
Hence, breast cancer is among national health priorities.
The link between genetic and environmental factors causes multifactorial breast cancer. Risk factors that are considered to play a significant role are sex, age, and family or genetic history [4]. Other factors are the history of breast disease, history of early or slow menstruation, obesity, alcohol, hormonal contraceptive use, and history
*Corresponding author:
Atikah Larasati
Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia [email protected]
of chest wall radiation. Most breast cancers are invasive, with 70% coming from ducts and 15–20% from lobules [5].
Therapeutic modalities that can be applied are surgery, chemotherapy, hormone therapy, and radiotherapy. One of the essential modalities in the treatment of breast cancer is radiation therapy or radiotherapy. Radiotherapy uses the principle of ionizing radiation to eradicate the growth of cancer cells. Procedures, target determination, and dosage are adjusted according to the stage of cancer.
Indications of radiotherapy in breast cancer patients can be curative or definitive, adjuvant, neoadjuvant, palliative, or emergent. Radiotherapy is carried out as a local control to reduce the chances of recurrence, enhance survival rates, and improve the patient’s quality of life [3]. Some of the side effects include skin conditions that can manifest as redness and dry skin, fatigue, lymphedema, and chest wall fibrosis [6].
Data and research on breast cancer patients’ profiles with radiotherapy were still limited and difficult to find in Indonesia, particularly in West Java, hence the latest research was needed to find out about its recent status.
This research was conducted at Hasan Sadikin General Hospital because it functions as the main referral hospital for tertiary care in West Java. Therefore, the author was interested in conducting research on the profile of breast cancer patients with radiotherapy at Hasan Sadikin General Hospital from 2018 to 2019. This also aimed to help medical professionals manage patients’ data, assess the effectiveness of therapeutic approaches, and help relevant policymakers evaluate breast cancer treatment policies.
METHODS
This study was conducted with a retrospective descriptive quantitative method to assess the profile of breast cancer patients treated with radiotherapy at Hasan Sadikin General Hospital which was conducted from September to December 2020. The sampling technique was total sampling using medical record data of patients with breast cancer based on the Hospital- Based Cancer Registry (HBCR) at Hasan Sadikin General Hospital obtained from January 1, 2018, to December 31, 2019. The inclusion criterion of this study was medical record data of breast cancer patients treated with radiotherapy only and radiotherapy combined with chemotherapy. The number of subjects was 280 patients out of 411 patients with breast cancer and about 20.2%
of the total 1,388 registered patients who received radiotherapy at Hasan Sadikin General Hospital.
Data collection was done by recording patient profiles with age, sex, region, and marital status variables. In addition, there were disease characteristics that included the basis of diagnosis, laterality, chief complaint, clinical
stage, histopathological subtype, molecular subtype, and metastatic status. This study also recorded the management profile in patients, which included type of surgery, type of chemotherapy, an indication of radiotherapy, and method of radiotherapy. Research data was processed by calculating each variable’s frequency using IBM SPSS version 25 statistical software and analyzed descriptively.
RESULTS
The results of the collection of information on patient profiles, disease characteristics, as well as patient management profiles were discussed further. The results of the study were presented in the form of frequency and percentage in Table 1.
Based on West Java Health Profile in 2017 by the West Java Provincial Health Office [7], the age range is divided into eight groups. The median age of breast cancer patients treated with radiotherapy was 47 years.
The most common age group was 45–54 years (36.4%).
The youngest recorded patient was 21 years old, and the oldest one was 90 years old.
Patients often came with a lump in the breast (66.4%), commonly in the left breast (45.0%). There were also patients that came with a wound on the breast (2.9%), lump in the armpit (2.9%), pain in the bone (2.5%), speed of growing with/without pain (1.4%), hardened breasts (1.1%), and other specific complaints as well, such as headache (1.4%), arm edema (0.4%), weakened limbs and arms (0.4%). According to the clinical stage, there were mostly cases of advanced stage and locally advanced stage in total, with stage IV in 86 cases (30.7%), followed by stage IIIB in 27 cases (9.6%). As stated in Table 2, both frequently occurred in the age group of 45-54 years.
About 227 cases (81.1%) were found to be Invasive Carcinoma No Special Type (IC-NST) or Invasive Ductal Carcinoma (IDC) in the histopathological subtype. Luminal B (9.6%) was the most common one in the molecular subtype of 50 known cases. Most of the cases did not metastasize (67.8%), and the cases with advanced stage mostly metastasized to the bone (10.6%). There were multiple metastases (5.4%), with other commonly involved organs including the lung (5.3%) and brain (5.3%).
The most widely performed surgery was total mastectomy (16.1%), followed by modified radical mastectomy (4.6%). In the case of chemotherapy, neoadjuvant chemotherapy (62.9%) was frequently conducted. There were 41 patients (14.6%) that did not undergo chemotherapy. Based on the indication of radiotherapy, most patients underwent complete adjuvant radiotherapy (47.1%). There were 63 cases (22.5%) with incomplete radiotherapy. EBRT with LINAC (67.9%) was the most used method of radiotherapy.
Table 1. Demographic and clinical characteristics of breast cancer patients
Variable Category n %
Age < 15 years old 0 0.0
15-24 years old 4 1.4
25-34 years old 15 5.4
35-44 years old 92 32.9
45-54 years old 102 36.4
55-64 years old 57 20.4
65-74 years old 8 2.9
> 75 years old 2 0.7
Sex Male 0 0.0
Female 280 100
Unknown 3 1.1
Laterality Right 123 43.9
Left 126 45.0
Bilateral 12 4.3
Unknown 19 6.8
Chief
Complaint Lump in the breast 186 66.4
Discharge from the nipple 3 1.1
Skin disorder 1 0.4
Speed of growing with/without
pain 4 1.4
Hardened breast 3 1.1
Lump in the armpit 8 2.9
Wound on the breast 8 2.9
Pain in the breast 2 0.7
Bone pain 7 2.5
Arm edema 1 0.4
Others 21 7.5
Unknown 36 12.9
Clinical
Stage I 3 1.1
IA 2 0.7
IB 1 0.4
II 6 2.1
IIA 7 2.5
IIB 25 8.9
III 11 3.9
IIIA 21 7.5
IIIB 27 9.6
IIIC 4 1.4
IV 86 30.7
Unknown 87 31.1
Histopatho- logical Subtype
Invasive carcinoma-no special
type/Invasive ductal carcinoma 227 81.1 Invasive lobular carcinoma 12 4.3
Medullary carcinoma 1 0.4
Mucinous carcinoma 3 1.1
Variable Category n %
Micropapillary carcinoma 3 1.1 Adenoid cystic carcinoma 11 3.9
Phyllodes tumor 15 5.4
Paget disease 1 0.4
Mixed carcinoma 4 1.4
Solid papillary 1 0.4
Invasive pleomorphic lobular
carcinoma 1 0.4
Neuroendocrine carcinoma 1 0.4 Molecular
Subtype Luminal A 2 0.7
Luminal B 27 9.6
HER2-enriched 8 2.9
Triple-negative 13 4.6
Unknown 230 82.1
Metastatic
Status None 166 67.8
Distant lymph nodes 5 2.0
Bone 26 10.6
Liver 4 1.6
Lung 13 5.3
Brain 13 5.3
Skin 1 0.4
Multiple 15 6.1
Others 2 0.8
Type
of Surgery Breast-conserving surgery 1 0.4 Modified radical mastectomy 13 4.6
Radical mastectomy 7 2.5
Total mastectomy 45 16.1
Excision biopsy 1 0.4
Unknown 213 76.1
Type of Chemo- therapy
Neoadjuvant 176 62.9
Durante radiation 5 1.8
Adjuvant 0 0.0
Not done 41 14.6
Unknown 58 20.7
Indication of Radio- therapy
Complete curative 32 11.4
Incomplete curative 38 13.6
Complete adjuvant 132 47.1
Incomplete adjuvant 25 8.9
Palliative 53 18.9
Method of Radio- therapy
EBRT with 60Co 75 26.8
EBRT with LINAC 199 71.1
EBRT with 60Co and
brachytherapy 4 1.4
EBRT with LINAC and
brachytherapy 2 0.7
*EBRT: External Beam Radiotherapy
Table 2. Distribution of clinical stage by age
group Clinical Stage Age Group
Total 15-24 25-34 35-44 45-54 55-64 65-74 > 75
I 0 0 0 1 1 1 0 3
IA 0 0 0 2 0 0 0 2
IB 0 0 0 0 1 0 0 1
II 0 1 4 1 0 0 0 6
IIA 0 1 1 1 3 1 0 7
IIB 0 1 7 10 6 0 1 25
III 0 0 2 6 3 0 0 11
IIIA 1 0 9 7 3 1 0 21
IIIB 1 3 6 10 5 2 0 27
IIIC 0 0 1 2 1 0 0 4
IV 1 4 30 33 15 3 0 86
Unknown 1 5 32 29 19 0 1 87
Total 4 15 92 102 57 8 2 280
Figure 1. Distribution of age group by molecular subtype
DISCUSSION
One of the important matter to address is the association between age group with molecular subtype and clinical stage of cancer (Figure 1). The finding of this study showed that the most common age group of breast cancer patients was 45–54 years, followed by the age group of 35–44 years. According to the World Health Organization, the women’s reproductive age group was 15–49 years, and the most common age group in this study showed that breast cancer mostly occurred in women in their late reproductive age or perimenopause period. Research in the United States in 2004–2013 by the National Program of Cancer Registries and Surveillance, Epidemiology, and End Results Program reported that
most breast cancer cases were found in women aged 40–44 years and 45–49 years (77.3%) [8].
Research at Surabaya Oncology Hospital mentioned that the highest incidence of breast cancer happened in patients aged 41–50 years and 51–60 years [9]. The same age group was also reported in the research at Cipto Mangunkusumo Hospital in 2010–2014, which was 41–50 years [10]. These findings were in line with the results of this study. One of the suspected factors was the presence of reproductive factors with strong associations with hormonal receptors that play a role in breast cancer, such as estrogen, both endogenous and exogenous [11]. The reproductive factors in question
locally advanced to advanced stages was found, especially in the age groups of 45–54 years and 35–44 years. This was in line with the previous research at Hasan Sadikin General Hospital, where 70–90% of patients came in advanced stages [19].
Other thing to note is the tendencies of laterality.
Breast cancer can occur in the left breast, the right breast, or even bilaterally. The result showed that most cases occurred in the left breast. This was similar to some literature that stated breast cancer was more common in the left breast compared to the right breast [20,21]. One of the other possible factors was genetic factors, where inherited genes could contribute to laterality tendency, before or during gastrulation, which could initiate breast cancer risk factors. In addition to the mechanism of laterality tendencies that remain unknown, this could affect the treatment, especially in the case of patients with comorbidity of heart disease as well as patients who need implantation tools such as pacemakers or defibrillators, related to the process of administering treatments such as radiotherapy [21].
The most common histopathological subtype of breast cancer in this study was the Invasive Carcinoma- No Special Type (IC-NST) subtype or commonly known as Invasive Ductal Carcinoma (IDC). In Iran, a study showed that invasive ductal carcinoma was the most frequent cancer followed by invasive lobular carcinoma [13]. The result of this study was also under some literature stating that the most common subtype of breast cancer was invasive ductal carcinoma, which accounted for 70–80% of all invasive lesions [13,22,23].
Since breast cancer is a compilation of distinct pathologic features, there were also varieties of rare histopathological subtypes, like medullary, mucinous, micropapillary, cystic adenoid, solid papillary, and neuroendocrine. Most invasive breast cancers have no special features and are classified as invasive carcinoma-no special type or previously known as invasive ductal carcinoma [23].
It is also important to note the association between chief complaint and clinical stage. About 66.4% of all patients came to the hospital with a chief complaint which was a lump in the breast. A mass that indicates breast cancer is usually solitary, discrete, hard, and nontender. It can be fixed to the skin or the muscle in some cases. In early-stage breast cancer, it can be asymptomatic, hence the patients often come in a locally advanced stage. A screening approach is needed because in some instances, a tumor can be too small to be felt.
There were also the patients that came with pain in the bone (2.5%) and other specific complaints as well, such as headache (1.4%), weakened limbs and arms (0.4%), convulsions (0.4%), and back pain (0.4%). The symptoms indicated that the patients were already in an advanced stage where the cancer cells have already metastasized.
It showed the problems of the site or organs affected [4].
can be seen as manifestations of the patient’s risk factors, such as early menarche, slow menopause, nulliparity, and the use of hormonal contraceptive pills, due to the increased exposure to estrogen that can increase the risk of breast cancer [3].
The previous statement relates to a large number of breast cancer subtypes with positive hormonal receptors. In this study, it was found that the most common subtype was luminal B with positive estrogen and/or progesterone receptor, negative or positive HER2 receptor, and high Ki-67 protein levels in the 35–44 years age group. About 230 cases were unknown for the molecular subtype, but the possibility of the most common subtype was deemed to be luminal B, considering this was following some literature from previous studies stating that most breast cancers were luminal B subtype with positive hormonal receptors, HER2 negative, and high level of Ki-67 protein [12].
Previous studies in America and Iran stated that the most common subtype was the luminal A subtype with positive hormonal receptors, HER2 negative, low level of Ki-67 protein, with a better prognosis compared to the luminal B subtype [13,14]. Ki-67 is a nuclear antigen expressed by cancer cells that proliferate and is one of the parameters in immunohistochemistry to determine prognosis [15]. Data from Bandung, Indonesia, showed that Ki-67 could also be used as a good predictive marker for assessing neoadjuvant chemotherapy outcomes, which low to the modest expression of Ki-67 was found to be better at predicting the response to neoadjuvant chemotherapy [16]. In this case, the luminal B subtype has a higher proliferation index than luminal A.
In India, more than 70% of breast cancers were detected at an advanced stage with 40% of cases in the reproductive age group and 60% in pre-menopausal or post-menopausal periods [17]. These cases were strongly related to the large population factor and were not balanced with adequate detection and treatment, and the problem was similar to the cause of high cases in Indonesia. In other advanced countries such as the United States, life expectancy has increased along with declining mortality rates due to higher public awareness of breast cancer and the presence of comprehensive early detection, as well as the availability of medical facilities for more advanced therapies [14]. Meanwhile, in Indonesia, the awareness of early detection and knowledge about breast cancer itself was still lacking.
Some of the reasons were that the patient did not feel and recognize the initial symptoms, the patient considered visiting the hospital as the second option, the patient no longer came for control after the first visit, and the patient did not continue treatment due to financial problems and no health insurance, hence many patients came in already severe conditions, either in locally-advanced stage, advanced stage, or relapse [18]. Out of 193 data, a significant number of cases in
One of the factors that cause worsening of the prognosis as well as the difficulty of healing is the metastasis of the tumor itself. It was found that the majority of deaths from breast cancer were caused by distant metastasis to other organs [24]. Cancer cells can metastasize to organs near or far which can contribute to the incurability of cancer [11]. From the results of the study, the four most common metastatic locations included bone, lungs, brain, and liver. This was in line with the research in Singapore which stated that breast cancer cells more often metastasized to the bones and lungs compared to other organs. The expression of a particular gene affected the cell’s preference to mutate, which also involved chemokines and their receptors.
Hiratsuka et al. mentioned tumor cells could induce signals that trigger the expression of MMP9 in endothelium and macrophages to facilitate the invasion of tumor cells into the lungs. Cancer cells also expressed the receptors of CXCR4 chemokines, with its ligands named CXCL12 expressed in lymph nodes, lungs, liver, and bones, and expressed slightly in the small intestine, kidneys, brain, skin, and muscles. Organs with high CXCL12 expressions have a high potential to become metastatic locations [24].
Regarding the therapeutic excellence, it is necessary to comprehend the modalities of breast cancer treatment in advance. The modalities of breast cancer treatment consist of surgery, chemotherapy, radiotherapy, hormonal therapy, and targeted therapy. The implementation of therapy in breast cancer is determined based on the degree of severity, which can be decided by the stage of cancer and its biomolecular expression. The gold standard approach for patients with early-stage breast cancer is breast-conserving therapy which consists of breast-conserving surgery with adjuvant radiotherapy. The results showed that during the early stages, the types of implemented surgery were breast-conserving surgery, modified radical mastectomy, and total mastectomy, with radiotherapy and adjuvant chemotherapy. Common indications to implement mastectomy include multicentricity, inability to obtain clear surgical margins, tumor size concerning breast size, patient preferences, and radiotherapy [25].
Most surgeries were performed in stages IV, IIIB, and IIB, with the types of surgery performed mostly total mastectomy and modified radical mastectomy. About 213 cases were unknown for the surgery, but the possibility of the most common surgery type was deemed to be total mastectomy, considering most patients came to the hospital at locally advanced stage and advanced stage.
In this study, the most widely applied type of chemotherapy was neoadjuvant chemotherapy. This was in line with the procedure in which neoadjuvant chemotherapy is the standard of care for patients with locally advanced breast cancer [3]. This also underlies the possibility of the most common chemotherapy type in 58 unknown cases to be neoadjuvant chemotherapy.
However, out of 222 cases, there were 41 patients (14.6%) that did not undergo chemotherapy.
Radiotherapy is an essential modality in breast cancer because it plays a role in the local control of tumors with less invasive actions. It is known that adjuvant radiotherapy can improve survival rates through local control. In 2018, the number of patients treated in radiotherapy departments was 126 patients, and in 2019 as many as 154 patients. The most widely used method of radiotherapy was using the LINAC method, which has been considered more effective. The study found that the most widely performed radiotherapy was radiotherapy with an indication of complete adjuvant.
There were 63 cases (22.5%) with incomplete radiotherapy.
This could be due to the limitation of health facilities and qualified medical professionals which created the gap between radiotherapy demand and supply, lack of compliance of the patients in completing therapy, fear of the side effects and complications, socioeconomic problems related to medical costs, and other conditions that reinforce the incomplete therapy [26].
CONCLUSIONS
Breast cancer remains one of the national health priorities and a health burden at Hasan Sadikin General Hospital with mostly occurred in 45–54 years age group.
The most common chief complaint was a lump in the breast, particularly in the left breast. About 22.5% of all patients arrived at a locally advanced stage and 30.7%
at an advanced stage with bone metastasis (10.6%).
Invasive Carcinoma No Special Type (IC-NST) is the most frequent histopathological subtype and luminal B is the most common molecular subtype. The most widely performed therapies were total mastectomy surgery, neoadjuvant chemotherapy, and complete adjuvant radiotherapy with EBRT method using LINAC. Further evaluation of management and follow-up studies need to be done to improve the implementation of therapies for patients and reduce the incidence rate.
DECLARATIONS
Ethics ApprovalThis study had been approved by the Research Ethics Committee of Universitas Padjadjaran with number 815/
UN6.KEP/EC/2020 and Hasan Sadikin General Hospital with number LB 02.01/X.2.2.1/20909/2020.
Competing of Interest
The authors declare no competing interest in this study.
Acknowledgment
The authors wish to thank Andri Rezano, dr., M.Kes., Ph.D, and Mas Adi Sunardi, dr., Sp.Onk.Rad as supervisors, the patients whose medical records getting
selected as subjects, the friends who helped in the process and gave a huge contribution to this study, and Hasan Sadikin General Hospital and the staff involved who helped collecting the data for this research.
REFERENCES
1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394–424.
2. World Health Organization. Indonesia - Global Cancer Observatory [Internet]. 2021 [cited 2022 Jan 30].
Available from: https://gco.iarc.fr/today/data/
factsheets/populations/360-indonesia-fact-sheets.pdf 3. Komite Penanggulangan Kanker Nasional (KPKN).
Panduan Penatalaksanaan Kanker Payudara [Internet]. 2015 [cited 2022 Jan 30]. Available from:
h t t p s : / / w w w . p o i j a y a . o r g / w p - c o n t e n t / uploads/2021/03/PPKPayudara.pdf
4. Davidson NE. Breast Cancer and Benign Breast Disorders. In: RCSI Handbook of Clinical Surgery for Finals. Elsevier Inc.; 2020. p. 1319–26.
5. Wild CP, Weiderpass E, Stewart BW. World Cancer Report: Cancer Research for Cancer Prevention [Internet]. Lyon, France: International Agency for Research on Cancer; 2020 [cited 2020 Nov 30].
Available from: http://publications.iarc.fr/586 6. Washington CM, Leaver D. Principles and Practice
of Radiation Therapy. 4th ed. Elsevier Ltd; 2016.
7. Dinas Kesehatan Provinsi Jawa Barat. Profil Kesehatan Jawa Barat 2017. 2018;154.
8. Shoemaker ML, White MC, Wu M, et al. Differences in breast cancer incidence among young women aged 20–49 years by stage and tumor characteristics, age, race, and ethnicity, 2004–2013. Breast Cancer Res Treat. 2018;169(3):595–606.
9. Lumintang L, Susanto A, Gadri R, Djatmiko A. Profil Pasien Kanker Payudara di Rumah Sakit Onkologi Surabaya, 2014. Indones J Cancer. 2015;9(3):105–110.
10. Zuraidah E, Edwar SQ. Oral Contraceptive as a Risk Factor of Breast Cancer in Female Patients at Dr.
Cipto Mangunkusumo National Public Hospital, Jakarta, Indonesia in 2010-2014. International Journal of Innovative Science and Research Technology. 2020;5(5):1778–82.
11. Sun YS, Zhao Z, Yang ZN, et al. Risk factors and preventions of breast cancer. Int J Biol Sci.
2017;13(11):1387–97.
12. Valla M, Vatten LJ, Engstrøm MJ, et al. Molecular subtypes of breast cancer: Long-term incidence trends and prognostic differences. Cancer Epidemiol Biomarkers Prev. 2016;25(12):1625–34.
13. Nafissi N, Khayamzadeh M, Zeinali Z, et al.
Epidemiology and Histopathology of Breast Cancer in Iran vs Other Middle Eastern Countries. Middle East J Cancer. 2018;9(3):243–51.
14. American Cancer Society. Breast Cancer Facts &
Figures 2019-2020 [Internet]. Atlanta: American Cancer Society, Inc; 2019 [cited 2022 Jan 30].
Available from: https://www.cancer.org/content/
dam/cancer-org/research/cancer-facts-and-statistics/
breast-cancer-facts-and-figures/breast-cancer-facts- and-figures-2019-2020.pdf
15. Viale G, Hanlon Newell AE, Walker E, et al. Ki-67 (30-9) scoring and differentiation of Luminal A- and Luminal B-like breast cancer subtypes. Breast Cancer Res Treat. 2019 Nov;178(2):451–458.
16. Rezano A, Pan CE, Istiqomah AA, Zada A. Association of Ki-67 Expression and Response of Neoadjuvant Chemotherapy in Invasive Breast Cancer Patients in Bandung. Int J Integr Heal Sci. 2018;6(2):80–83.
17. Vanamail P. Epidemiological profile of female breast cancer in reproductive age-group and its association with maternal characteristics: -A population-based observational study in India. Oncomedicine.
2019;4:27–34.
18. Badudu F, Suardi D, Ahmad D, et al. Challenges of locally advanced breast cancer in Hasan Sadikin Hospital Bandung Indonesia. The Breast. 2011;20:S52.
19. Sander MA. Profil Penderita Kanker Payudara Stadium Lanjut Baik Lokal Maupun Metastasis Jauh Di Rsup Hasan Sadikin Bandung. Farmasains J Farm dan Ilmu Kesehat. 2012;1(2).
20. Cheng SA, Liang LZ, Liang QL, et al. Breast cancer laterality and molecular subtype likely share a common risk factor. Cancer Manag Res. 2018 Nov 29;10:6549–6554.
21. Amer MH. Genetic factors and breast cancer laterality.
Cancer Manag Res. 2014 Apr 16;6:191–203.
22. Syafri M, Rachmawati M, Istuti RDI. Karakteristik Penderita Kanker Payudara Berdasarkan Gambaran Histopatologi di RSUD Al-Ihsan Bandung Periode 2011-2014. Prosiding Pendidikan Dokter, UNISBA.
2019;1(1):1–5.
23. Kumar V, Abbas AK, Aster JC. Robbins Basic Pathology. 10th ed. Philadephia: Elsevier Inc.; 2018.
24. Tsuji W, Plock JA. Breast Cancer Metastasis. In:
Aamir Ahmad, editor. Introduction to Cancer Metastasis. 1st ed. Elsevier; 2016. p.13–31.
25. Franceschini G, Martin Sanchez A, Di Leone A, et al. New trends in breast cancer surgery: a therapeutic approach increasingly efficacy and respectful of the patient. G Chir. 2015 Jul-Aug;36(4):145–52.
26. Yap ML, Zubizarreta E, Bray F, et al. Global Access to Radiotherapy Services: Have We Made Progress During the Past Decade? J Glob Oncol. 2016 Mar 16;2(4):207–215.
