Luminal B
Luminal B
Luminal B
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Luminal B is the Most Common Intrinsic Molecular Subtypes of Breast Carcinoma
1
Department of Community Medicine, 4Medical Doctor Program,Faculty of Medicine, 2Research Center of MCTrops, Mulawarman
University, 3Department of Pathological Anatomy, Abdul Wahab Sjahranie General County Hospital, Samarinda, East Kalimantan,
Indonesia. *For Correspondence: s.paramita@fk.unmul.ac.id
Asian Pacific Journal of Cancer Prevention, Vol 20 2247
Swandari Paramita et al
size, the best prognosis and the lowest recurrence rate than (Wolff et al., 2013). Then, tumors containing ≥ 14% of
other subtypes. Technically, it is characterized by higher nuclear Ki-67 expression was considered as having a high
levels of ER and lower levels of the proliferation-related Ki-67 rate (Cheang et al., 2009).
genes, including Ki-67. In practices, recommendations
for luminal A are mainly based on endocrine therapy Definition of intrinsic molecular subtypes
(Prat et al., 2013). Furthermore, Luminal B has an According to the 2013 St. Gallen Consensus, samples
aggressive phenotype and worse prognosis compared could be distinguished based on their ER, PgR, HER2,
to luminal A. It is characterized by higher levels of and Ki-67 expressions. Technically speaking, samples
growth factor receptor such as HER2, which activates were stated as luminal A (ER+, PgR+, HER2-, and Ki-67
signaling pathways (Yan et al., 2015). In details, HER2+ low), luminal B (ER+, PgR+, any HER2, and any Ki-67),
subtypes have a poor prognosis, and characterized by HER2+ (ER-, PgR-, and HER2 over-expressed) or triple
high proliferation rates. Therapy for luminal B subtype negative (ER-, PgR-, and HER2-) (Goldhirsch et al., 2013).
includes the uses of anti-HER2 such as Trastuzumab. In
terms of recommended therapies, luminal B delivers its Statistical analysis
best responses to neoadjuvant chemotherapy (Asif et al., In this study, a chi-square test was employed to examine
2016). Moreover, the triple-negative subtype has been the association of breast carcinoma intrinsic molecular
recognized to show the most aggressive behavior with subtypes with clinical and immunohistochemical factors.
the worst outcome. This subtype is not responding well The test applied values of p < 0.05 as considerably
to either endocrine or adjuvant chemotherapy. Requiring significant. All statistical analyses were performed in
a specific-targeted therapy, chemotherapy is hence stated PSPPIRE 1.0.1 software.
as the only choice of treatment. Then, these subtypes
have been actively studied by various researchers (Keam Results
et al., 2011).
In the literature, prior studies on intrinsic molecular Characteristics of patients
subtypes of breast carcinoma in Indonesia have been A total of 92 cases of breast carcinoma were included
focusing on ER, PgR, HER2, and Ki-67 markers. They in this study with the following clinical information. First,
are, however, largely produce different results (Prihantono the mean of patient’s age was 48.29 years old (ranged
et al., 2017a, 2017b; Rahmawati et al., 2018; Widodo et between 23-83 years old), while the mean of tumor
al., 2017, 2014). size was 5 cm (ranged between 1-17 cm). Besides, the
majority of patient’s histological grade was in the third
Materials and Methods group (68.48%). After the immunohistochemical staining
process, the ER, PgR, and HER2 positive expressions were
Patients
A retrospective study was performed at Abdul Wahab Table 1. Clinical and Immunohistochemical
Sjahranie County General Hospital, Samarinda, East Characteristics of Patients
Kalimantan, Indonesia, involving samples from patients Characteristics
between January-December 2016. An ethical clearance Age (years) Mean ± SD 48.29 ± 10.7
was obtained from the Ethical Review Committee of
Min – Max 23 – 83
the Faculty of Medicine, Mulawarman University,
Samarinda, Indonesia (49/KEPK-FK/VI/2017) before Tumor size (cm) Mean ± SD 5.00 ± 3.1
conducting the study. In addition to ER, PgR and HER2 Min – Max 1 – 17
status and Ki67 index, clinical information used in this Histological Grade 1 5 (5.43%)
included ages at diagnosis, tumor sizes, and histological 2 24 (29.09%)
grades. After data gathering, there were 92 cases
3 63 (68.48%)
during the period under investigation. These cases had
Molecular Subtypes Luminal A 7 (7.61%)
formalin-fixed paraffin-embedded blocks available for
immunohistochemical staining. Luminal B 39 (42.39%)
HER2+ 36 (39.13%)
Immunohistochemical Triple negative 10 (10.87%)
In this study, immunohistochemical staining method ER Negative 46 (50%)
was performed on formalin-fixed paraffin-embedded
Positive 46 (50%)
blocks. Technically, a section of blocks was stained with
primary antibodies for ER, PgR, HER2, and Ki-67 (all PgR Negative 47 (51.09%)
from Leica Biosystem, Newcastle, UK). An automated Positive 45 (48.91%)
immunohistochemical staining was conducted and assessed HER2 Negative 39 (42.39%)
in Leica BOND MAX (Leica Biosystem, Newcastle, UK). Positive 53 (57.61%)
Tumors with ≥ 1% positively nuclear-stained cells were
Ki-67 <14 % 15 (16.30%)
considered positive for both ER and PgR expression
(Hammond et al., 2010). Besides, HER2 positive was 14-30 % 18 (19.67%)
scored if the staining occured for > 10% of tumor cells >30 % 59 (64.13%)
discovered to be 50%, 48.91%, and 57.61%, respectively. 5 cm (ranged between 1-17 cm). In fact, similar results
In particular, the majority of Ki-67 expressions were in the were discovered by other studies in Indonesia. It confirmed
high group (64.13%). Among observed samples, luminal B a behavior among breast carcinoma patients in Indonesia,
comprised the most common intrinsic molecular subtypes who, in most cases, reported their health condition when
in the population (42.39%), which was then followed their tumor had already become larger in size (Widodo
by HER2+ (39.13%), luminal A (10.87%), and triple- et al., 2017). On the other hand, the majority of patient’s
negative (7.61%). Table 1 presents the characteristics of histological grade in this research was in the high group
observed patients with breast carcinoma. (68.48%). Different results were revealed by other studies
in Indonesia, in which moderate differentiation was the
Association between clinical and immunohistochemical most common grade compared to high and low group.
factors with intrinsic molecular subtypes In practices, histological grading was the predictive and
Looking at the chi-square test, a significant result prognostic factor of breast carcinoma (Rahmawati et al.,
(p = 0.019) was revealed for the association of between 2018; Widodo et al., 2014).
age with intrinsic molecular subtypes of breast carcinoma. Furthermore, positive ER, PgR, and HER2 expression
In this study, luminal B was discovered as the most were discovered at 50%, 48.91%, and 76.09%, respectively.
commonly occuring subtypes in patients aged ≤ 35 It was parallel with the high frequency of positive HER2
years, while HER2+ was most common subtypes in older expressions (56.6%) found in prior study conducted in
patients. Table 2 exhibits the association between clinical Makassar, Indonesia (Prihantono et al., 2017b). Besides,
and immunohistochemical factors with intrinsic molecular the majority of Ki-67 expressions were in the high group
subtypes of breast carcinoma. (83.7%), which was similar to previous results of the study
in Makassar with Ki-67 positive index at about 54.2%
Discussion (Prihantono et al., 2017a).
Next, this study discovered luminal B to comprise the
This research had evaluated the distribution of most commonly occuring intrinsic molecular subtypes
intrinsic molecular subtypes of breast carcinoma and among observed population (42.39%). After luminal
studied their association and correlation with clinical B, the following ranks were HER2+ (39.13%), luminal
and immunohistochemical factors. In this study, samples A (6.52%), and triple-negative (4.36%). The result was
under investigation included 92 breast carcinoma patients. particularly similar to other studies that focused on cases
The mean age of these samples was 48.29 years old in Southeast Asia regions. Prior research in Vietnam, for
(ranged between 23-83 years old), which was in fact example, revealed a relatively high percentage of luminal B
similar to prior study in Makassar, Indonesia, with 46 subtype (56.5%) (Thang et al., 2015). In another research,
years old as the average age at diagnosis (Prihantono et the mean percentage of luminal B patients discovered in
al., 2017a). Besides, studies in Malaysia and Indonesia Myanmar was 46.2%, which was considerably higher than
indicated breast carcinoma to present at a younger age other subtypes (San et al., 2017). Results in Southeast Asia
for Indonesian women compared to Malaysian women. regions were also similar to studies conducted on breast
Ethnical and genetic differences might highlight these carcinoma cases in other Asia regions. Outside Asia, e.g.
results (Ng et al., 2011). in Morocco, luminal B was also discovered as the most
Furthermore, the mean of tumor size in this study was frequently occuring molecular subtype of breast cancer
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