CHAPTER FOUR
RESULTS PRESENTATION AND DATA ANALYSIS
4.1 Introduction
The chapter provides a comprehensive analysis of the sociodemographic and
clinicopathological parameters of the study population, the prevalence of the various subtypes
of breast cancer. Additionally, it examines the survival outcome, mutational burden and copy
number of variations of the population of study. Data retrieved was analyzed and reported,
the results are presented using frequency tables, pie charts, and bar graphs. This was followed
by a brief interpretation and a discussion on research findings. Data analysis was based and
guided by the research objectives.
Understanding the sociodemographic and clinicopathological parameters of the study
population is paramount. It not only provides insight into the diverse characteristics of the
patient cohort but also serves as a foundational step in correlating these parameters with
genomic alterations and clinical outcomes. Given the heterogeneity of breast cancer and its
subtypes, these parameters can offer pivotal insights into patient prognosis, potential
therapeutic strategies, and broader trends in disease presentation and progression within
diverse populations
4.2 Sociodemographic characteristics of the study population (n=5511)
The table below reveals that the surveyed population consisted of both males and females.
Among the study population, 23(0.4%) were identified as males, while the majority,
5448(99.6%) were females.
The data on age at diagnosis showed that the highest percentage of respondents fell within
NA group, 1937(35.2%). This showed that information on age at diagnosis was not given for
these participants. The 61-70 age range represented 990(18.0%) of the sample.
The data on the race of category of the study population showed that majority, 4517(82.0%)
were not categorized, while 751(13.6%) of the White race were involved. This was followed
by the Black or African American race, 182(3.3%). The subsequent races, namely American
or Indian or Alaska Native had 60(1.1%) and 1(0%) respectively.
The survival status of the patients showed that, 1717(31.2%) of the study population died out
of the disease, while the majority 3266(59.3%) were still alive. 528(9.6%) were not specified,
whether dead or alive.
Table 4.1 Sociodemographic Characteristics of the Study Population
Frequency (n) Percentage (%)
Sex Male 23 0.4
Female 5448 99.6
Age at Diagnosis <30 30 0.5
31-40 235 4.3
41-50 635 11.5
51-60 862 15.6
61-70 990 18.0
71-80 630 11.4
81-90 186 3.4
>90 6 0.1
NA 1937 35.2
Race Category White 751 13.6
Black or African American 182 3.3
Asian 60 1.1
American Indian or Alaska Native 1 .0
NA 4355 82.0
Overall Survival Living 3266 59.3
Status Deceased 1717 31.2
NA 528 9.6
4.3 Clinicopathological Parameters of the Study Population
Table 4.2 portrays key clinical features of breast cancer patients in the dataset. The stage at
diagnosis varied, with a noticeable proportion, 3723 (67.6%), not being staged. Among those
staged, Stage IA was more common with 524 cases (9.7%), while Stage IB was the least
frequent, with 32 cases (0.5%). In terms of treatment modalities, while 412 (7.7%) patients
underwent chemotherapy, a vast majority, 3369 (63.3%), had no data available for both
chemotherapy and hormone therapy. For the latter, 1216 (22.7%) patients received it. Tumor
size distribution was skewed, with a significant 1483 cases (26.9%) having a size between 0-
25 units, while sizes between 101-125 and 151-175 were rarest, each with just 1 case
(0.02%). The evaluation of lymph nodes revealed that 2138 (38.80%) samples had 0-10
nodes examined positive. On assessing the histologic grade of the neoplasm, Grade 3 was
predominant with 1198 cases (21.74%), though a significant number, 3123 (56.67%),
remained ungraded.
Table 4.2 Clinicopathological Characteristics of the Study Population
Variable Overall N %
Stage at Diagnosis
IA 524 9.7
IB 32 0.5
IIA 348 6.5
IIB 215 4.0
IIIA 206 3.8
IIIB 51 0.9
IIIC 133 2.4
IV 395 7.3
Unk 14 64.4
Chemotherapy
YES 412 7.7
NO 1568 29.3
NA 3369 63.3
Hormone Therapy
Yes 1216 22.7
No 764 14.2
NA 3369 63.3
Tumor Size
0 - 25 1483 26.91
26 - 50 751 13.63
51 - 75 92 1.67
76 - 100 24 .44
101 - 125 1 .02
126 - 150 4 .07
151-175 1 .02
176 - 200 2 .04
NA 3153 57.21
Lymph nodes examined
positive
0 - 10 2138 38.80
11 - 20 86 1.56
21 - 30 15 .27
31 - 40 2 .04
41 - 50 2 .04
NA 3123 56.67
Neoplasm Histologic Grade
1 214 3.88
2 976 17.71
3 1198 21.74
NA 3123 56.67
After reviewing various parameters like age at diagnosis, race category, chemotherapy,
hormone therapy, tumor size, lymph nodes examined positive, and neoplasm histologic grade,
it's observed that a significant portion of the data is uncategorized or marked as 'Not
Available'. This extensive lack of categorization may largely be attributed to the nature of
global datasets in cBioPortal. Many entries might lack specific details due to diverse origins
where certain attributes aren't uniformly recorded, potential privacy considerations, or
instances of incomplete clinical data submissions. A deeper dive into these gaps might be
warranted in the study's limitations.
4.4 Molecular subtypes of breast cancer
Table 4.1 provides a comprehensive breakdown of the breast cancer samples categorized into
four primary subtypes: Luminal A, Luminal B, HER2, and Triple-Negative Breast Cancer
(TNBC). For each subtype, the frequency and percentage of occurrence in the dataset are
detailed. Furthermore, the table delineates the presence (Yes) or absence (No) of three key
receptors—Estrogen Receptor (ER), Progesterone Receptor (PR), and Human Epidermal
Growth Factor Receptor (HER2)—for each subtype. Notably, each subtype displays distinct
receptor profiles. Breast cancer encompasses a range of molecular subtypes, each
characterized by specific receptor profiles. These profiles, specifically the presence or
absence of Estrogen Receptor (ER), Progesterone Receptor (PR), and Human Epidermal
Growth Factor Receptor (HER2), play a pivotal role in the classification of breast cancer
cases.
Table 4.1 offers a detailed classification of the breast cancer samples from the dataset into
four primary subtypes: Luminal A, Luminal B, HER2, and Triple-Negative Breast Cancer
(TNBC). The table presents the frequency and percentage of occurrence for each subtype and
highlights the receptor profiles and the most frequently mutated genes associated with each
subtype. The table concludes with a list of the most frequently mutated genes for each
subtype, with TP53 being predominant in Luminal B, HER2, and TNBC, while PIK3CA is
the most mutated for Luminal A.
Luminal A Luminal B HER2 TNBC
Frequency 1472 244 212 491
(%)
ER Yes Yes No No
PR Yes Yes No No
HER No Yes Yes No
Most PIK3CA TP53 TP53 TP53
Mutated
Gene
Table 4.3: Subtype Classification and Key Characteristics of Breast Cancer Samples
4.5 Histological subtypes of breast cancer
The highest percentage of histological subtypes (78%) were from Invasive Ductal Carcinoma
and the least percentage of histological subtypes (2%) were from Invasive Breast Carcinoma.
The percentages of histological subtypes from Invasive Lobular Carcinoma and Mixed
Ductal and Lobular Carcinoma were 13% and 7% respectively as shown in the figure below
7% 3%
13%
78%
Invasive Ductal Carcinoma Invasive Lobular Carcinoma
Mixed Ductal and Lobular Carcinoma Invasive Breast Carcinoma
Figure 4.1 Percentage of Histological Subtypes of Breast Cancer
4.6 Survival outcomes across Breast Cancer Subtypes
The bar graph provides a comparative visualization of survival outcomes—categorized as
'Alive' and 'Deceased'—for four prominent breast cancer subtypes: Luminal A, Luminal B,
HER2+ Enriched, and Triple-Negative Breast Cancer (TNBC). Each subtype is represented
by a pair of adjacent bars, with the left bar indicating the number of individuals alive and the
right bar representing the deceased.
For the Luminal A subtype, the graph depicts a larger number of individuals still alive (863)
compared to those who are deceased (609). A similar pattern emerges for Luminal B, with
185 individuals alive and 59 deceased. The HER2+ Enriched category presents a closer ratio,
with 115 alive and 97 deceased, suggesting a relatively higher mortality rate when compared
to the Luminal subtypes. Lastly, TNBC demonstrates 301 individuals alive, contrasting with a
significant count of 190 deceased, further underscoring the aggressive nature of this subtype
Survival outcome based on Molecu-
lar subtypes
1000
900 863
800
700 609
600
500
400 301
300 190
185
200 115 97
100 59
0
Luminal A Luminal B Her2+ enriched Basal like/Triple
negative
Series1 Series2
Figure 4.2 Bar graph showing the frequency of survival outcome of the various subtypes of
breast cancer
TOP 10 MUTATED GENES
40.00%
35.00%
30.00%
25.00%
20.00%
15.00%
10.00%
5.00%
0.00%
PIK3CA TP53 MUC16 GATA3 CDH1 AHNAK2 SYNE1 KMT2C MAP3K1 PTEN
Figure 4.3: Bar graph illustrating the top 10 most frequently mutated genes in breast cancer
(From Left to Right)
4.7 Mutational Burden of the Subtypes of Breast Cancer
Among the 5,511 breast cancer samples analyzed, the genomic landscape was categorized
into the four subtypes: Luminal A, Luminal B, HER2 Positive, and Triple-Negative Breast
Cancer (TNBC). The analysis revealed distinctive mutational patterns for each subtype.
In the Luminal A subtype, PIK3CA mutations were predominant, observed in 50.9% of the
cases. It's worth noting that amplifications, notably in the PROX1-AS1 gene, were evident in
28.4% of the samples. Interestingly, a significant majority (790 samples) had a Tumor
Mutational Burden (TMB) within the range of 0-4.
Luminal B demonstrated a different pattern with TP53 mutations being significant, marked in
41.6% of the samples. PCAT2 gene amplifications were conspicuous in this subtype, with
36.2% of the samples reflecting this alteration. Here, a considerable proportion (189 samples)
showed a TMB range of 0-4.
For the HER2 Positive subtype, a striking 76.6% harbored TP53 mutations. The amplification
pattern prominently highlighted PGAP3, observed in a commanding 85.8% of samples. In
terms of TMB, 87 samples were clustered in the 0-4 range.
Lastly, TNBC was characterized by an overwhelming 83.2% of samples with TP53
mutations. MYC gene amplifications stood out, prevalent in 35.2% of these samples. A
significant count of the samples (242) fell within the TMB range of 0-4.
The table that follows provides a detailed breakdown of the top mutated genes, CNA genes,
and TMB distribution for each subtype. It's imperative to understand these patterns as they
offer insights into potential therapeutic targets and prognosis markers.
Luminal A Luminal B
Mutated Genes Percentage Mutated Genes Percentage
(Top 5) % (Top 5) %
PIK3CA 50.9% TP53 41.6%
GATA3 16.4% PIK3CA 31.3%
MAP3K1 14.8% TTN 20.3%
CDH1 14.3% GATA3 17.3%
TTN 14.0% KMT2C 11.5%
CNA Genes Alteration CNA Genes Alteration
Type Type
PROX1-AS1 28.4% AMP PCAT2 36.2% AMP
SPATA17-AS1 28.1% AMP CASC11 36.2% AMP
DISC1-IT1 27.9% AMP SPATA17-AS1 36.2% AMP
RGS2-AS1 26.8% AMP CASC19 36.2% AMP
LINC01031 26.7% AMP PROX1-AS1 34.0% AMP
TMB N TMB N
0-4 790 0-4 189
4-8 387 4-8 35
8-12 192 >8 20
12-16 65
>16 38
HER2 TNBC
POSITIVE
Mutated Genes Percentage Mutated Genes Percentage
(Top 5) % (Top 5) %
TP53 76.6% TP53 83.2%
PIK3CA 35.1% TTN 24.0%
TTN 28.2% MUC16 16.0%
MUC16 22.9% SYME1 14.3%
AHNAK2 18.5% PIK3CA 13.8%
CNA Genes Alteration CNA Genes Alteration
Type Type
PGAP3 85.8% AMP MYC 35.2% AMP
ERBB2 85.4% AMP CASC11 35.0% AMP
TCAP 84.4% AMP POU5F1B 34.8% AMP
MIEN1 84.4% AMP CASC8 34.6% AMP
PNMT 84.4% AMP CCAT2 33.9% AMP
TMB N TMB N
0-4 87 0-4 242
4-8 61 4-8 145
8-12 38 8-12 63
12-16 17 12-16 21
>16 9 >16 20
Table 4.4 Mutational Burden of the Subtypes of Breast Cancer