Clinicopathologic characteristics of the breast cancer samples
The characteristics of the samples are summarized in Table 1. A total of 104 (50.2%) samples were obtained from the right breast, while 103 (49.8%) samples were obtained from the left breast. The mean age of the patients was 56 years old. Histopathological types included 4 (1.9%) samples of grade I Invasive Breast Carcinoma of No Special Type (IBC-NST), 81 (39.1%) samples of grade II IBC-NST, 84 (40.6%) samples of grade III IBC-NST, 34 (16.4%) samples of Invasive Lobular Carcinoma, 1 (0.5%) sample of Invasive Papillary Carcinoma, and 3 (1.4%) samples of Mucinous Carcinoma. Molecular Subtypes, as determined by Immunohistochemistry Evaluation, comprised 102 (49.3%) samples of Luminal A, 37 (17.9%) samples of Luminal B HER-2 (negative), 21 (10.1%) samples of Luminal B HER-2 (positive), 20 (9.7%) samples of HER-2 Enriched, and 27 (13%) samples of triple-negative breast cancer (TNBC).
Table 1. Clinicopathology characteristics of the study samples
Characteristic
|
N (%)
|
|
|
Age
|
|
|
≤ 50 years old
|
75 (36.2%)
|
|
> 50 years old
|
132 (63.8%)
|
|
Location
|
|
|
Right Breast
|
104 (50.2%)
|
|
Left Breast
|
103 (49.8%)
|
|
Histopathology Diagnosis
|
|
|
Invasive Breast Carcinoma of NST, Grade I
|
4 (1.9%)
|
|
Invasive Breast Carcinoma of NST, Grade II
|
81 (39.1%)
|
|
Invasive Breast Carcinoma of NST, Grade III
|
84 (40.6%)
|
|
Invasive Lobular Carcinoma of the Breast
|
34 (16.4%)
|
|
Invasive Papillary Carcinoma of the Breast
|
1 (0.5%)
|
|
Mucinous Carcinoma of the Breast
|
3 (1.4%)
|
|
Molecular Subtypes (IHC Evaluation)
|
|
|
Luminal A
|
102 (49.3%)
|
|
Luminal B HER-2 (negative)
|
37 (17.9%)
|
|
Luminal B HER-2 (positive)
|
21 (10.1%)
|
|
HER-2 Enriched
|
20 (9.7%)
|
|
TNBC
|
27 (13%)
|
|
Abbreviations: NST = No Special Type, IHC = Immunohistochemistry, HER-2 = Human Epidermal Growth Factor-2, TNBC = Triple Negative Breast Cancer.
PIK3CA Mutation Status in Breast Cancer Samples
A total of 75 (36.2%) samples showed positive PIK3CA mutation (Table 2).
Table 2. Frequency of the PIK3CA mutations in breast cancer samples
Characteristic
|
N (%)
|
|
|
PIK3CA mutation status
|
|
|
Positive (Mutated)
Negative (Wild type)
|
75 (36.2%)
132 (63.8%)
|
|
Table 3 illustrates the correlation between clinicopathological features and the PIK3CA mutation status. Notably, a substantial proportion of samples from patients aged over 50 years (34.1%) exhibited PIK3CA mutation; however, no significant association between mutation status and patient age was observed (p > 0.05). Similarly, no discernible correlation was found between mutation status and tumor location, whether in the right or left breast (p > 0.05). Regarding Invasive Breast Carcinoma (IBC) grades, mutations were more prevalent in higher grades (Grade I: 25%; Grade II: 35.8%; Grade III: 42.9%). Nonetheless, no definitive association between histopathology diagnosis and PIK3CA mutation status was established. These findings suggest that mutation status does not significantly correlate with age, tumor location, or histopathology diagnosis in breast cancer cases; rather, these variables appear to be independent based on the dataset analyzed. However, a noteworthy discovery in this study was the significant association between PIK3CA mutation status and molecular subtypes as determined by immunohistochemistry evaluation (p=0.01; p<0.05). Specifically, PIK3CA mutations were more prevalent in Luminal A breast cancer samples (mutation rate: 46.1%) and Luminal B HER-2 (negative) breast cancer samples (mutation rate: 40.5%), compared to Luminal B HER-2 (positive), HER-2 enriched, and triple-negative breast cancer (TNBC) subtypes (mutation frequencies: 19%, 20%, 18.5%, respectively), which exhibited lower mutation frequencies than the overall mutation frequency of 36.2% (refer to Table 2).
Table 3. Association between the Clinicopathology Characteristics and PIK3CA mutation status in breast cancer samples
Characteristic
|
PIK3CA Mutation Status
|
p-value
|
|
|
Negative (Wildtype), N (%)
|
Positive (Mutated), N (%)
|
|
Age
|
|
|
0.453
|
|
≤ 50 years old
|
45 (60%)
|
30 (40%)
|
|
|
> 50 years old
|
87 (65.9%)
|
45 (34.1%)
|
|
|
Location
|
|
|
0.472
|
|
Right Breast
|
69 (66.3%)
|
35 (33.7%)
|
|
|
Left Breast
|
63 (61.2%)
|
40 (38.8%)
|
|
|
Histopathology Diagnosis
|
|
|
0.169
|
|
Invasive Breast Carcinoma of NST, Grade I
|
3 (75%)
|
1 (25%)
|
|
|
Invasive Breast Carcinoma of NST, Grade II
|
52 (64.2%)
|
29 (35.8%)
|
|
|
Invasive Breast Carcinoma of NST, Grade III
|
48 (57.1%)
|
36 (42.9%)
|
|
|
Invasive Lobular Carcinoma of the Breast
|
26 (76.5%)
|
8 (23.5%)
|
|
|
Invasive Papillary Carcinoma of the Breast
|
0 (0%)
|
1 (100%)
|
|
|
Mucinous Carcinoma of the Breast
|
3 (100%)
|
0 (0%)
|
|
|
Molecular Subtypes (IHC Evaluation)
|
|
|
0.01*
|
|
Luminal A
|
55 (53.9%)
|
47 (46.1%)
|
|
|
Luminal B HER-2 (negative)
|
22 (59.5%)
|
15 (40.5%)
|
|
|
Luminal B HER-2 (positive)
|
17 (81%)
|
4 (19%)
|
|
|
HER-2 Enriched
|
16 (80%)
|
4 (20%)
|
|
|
TNBC
|
22 (81.5%)
|
5 (18.5%)
|
|
|
*Fisher's exact test p<0.05. Abbreviations: NST = No Special Type, IHC = Immunohistochemistry, HER-2 = Human Epidermal Growth Factor-2, TNBC = Triple Negative Breast Cancer.
Table 4 showed that findings of the study indicate a strong correlation between histopathology diagnosis and molecular subtypes of breast cancer (p=0.007; p<0.01). Notably, Luminal A BC is most commonly observed in IBC of NST compared to all other molecular subtypes. On the other hand, Luminal B HER-2 (positive), HER-2 Enriched, Luminal B HER-2 (negative) BC, and TNBC are frequently observed in IBC of NST, with proportions of 90.5%, 75%, 67.6%, and 66.7% respectively.
Table 4. Association between Clinicopathology Characteristics in breast cancer samples (IHC vs Histopathology Diagnosis)
Characteristic
|
Histopathology Diagnosis
|
p-value
|
|
|
Invasive Breast Carcinoma of NST
|
Invasive Lobular Carcinoma of the Breast
|
Invasive Papillary Carcinoma of the Breast
|
Mucinous Carcinoma of the Breast
|
|
Molecular Subtypes (IHC)
|
|
|
|
|
0.007*
|
|
Luminal A
|
92 (90.2%)
|
8 (7.8%)
|
0 (0%)
|
2 (2%)
|
|
|
Luminal B HER-2 (negative)
|
25 (67.6%)
|
10 (27%)
|
1 (2.7%)
|
1 (2.7%)
|
|
|
Luminal B HER-2 (positive)
|
19 (90.5%)
|
2 (9.5%)
|
0 (0%)
|
0 (0%)
|
|
|
HER-2 Enriched
|
15 (75%)
|
5 (25%)
|
0 (0%)
|
0 (0%)
|
|
|
TNBC
|
18 (66.7%)
|
9 (33.3%)
|
0 (0.0%)
|
0 (0.0%)
|
|
|
*Fisher's exact test p<0.05. Abbreviations: NST = No Special Type, IHC = Immunohistochemistry, HER-2 = Human Epidermal Growth Factor-2, TNBC = Triple Negative Breast Cancer.
Table 5 showed that there is no significant association between PIK3CA mutation status and different luminal molecular subtypes (p>0.05). However, we found that the Luminal B HER-2 (positive) subtype has a lower mutation frequency of 19% compared to the 46.1% and 40.5% of Luminal A and Luminal B HER-2 (negative) BC respectively. Within the Luminal Mutated PIK3CA tumors, only 4 of 66 samples (6%) are Luminal B HER-2 (positive).
Table 5. Association between the Luminal Hormonal Receptor Positive Molecular Subtypes and PIK3CA mutation status in breast cancer samples
Characteristic
|
PIK3CA Mutation Status
|
p-value
|
|
|
Negative (Wildtype), N (%)
|
Positive (Mutated), N (%)
|
|
Molecular Subtypes (IHC Evaluation)
|
|
|
0.07
|
|
Luminal A
|
55 (51.6%)
|
47 (46.1%)
|
|
|
Luminal B HER-2 (negative)
|
22 (61.1%)
|
15 (40.5.%)
|
|
|
Luminal B HER-2 (positive)
|
17 (81%)
|
4 (19%)
|
|
|
*Fisher's exact test p<0.05. Abbreviations: IHC = Immunohistochemistry, HER-2 = Human Epidermal Growth Factor-2.
Table 6 showed that there is no significant association between PIK3CA mutation status with the TNBC and HER-2 enriched molecular subtypes. Similarly, both HER-2 enriched and TNBC showed lower mutation frequency compared to overall PIK3CA mutation frequency.
Table 6. Association between the TNBC and HER-2 Molecular Subtypes and PIK3CA mutation status in breast cancer samples
Characteristic
|
PIK3CA Mutation Status
|
p-value
|
|
|
Negative (Wildtype), N (%)
|
Positive (Mutated), N (%)
|
|
Molecular Subtypes (IHC Evaluation)
|
|
|
1.000
|
|
HER-2 Enriched
|
16 (80.0%)
|
4 (20.0%)
|
|
|
TNBC
|
22 (81.5%)
|
5 (18.5%)
|
|
|
*Fisher's exact test p<0.05. Abbreviations: IHC = Immunohistochemistry, HER-2 = Human Epidermal Growth Factor-2, TNBC = Triple Negative Breast Cancer.
Upon a more comprehensive analysis as presented in Table 7, it was observed that there is no statistically significant association between age groups and molecular subtypes in PIK3CA positive (mutated) samples. Nevertheless, it is evident that there is a higher prevalence (68.1%) of older (>50 years old) patients in Luminal A with PIK3CA positive (mutated) samples. When comparing between molecular subtypes in those who are >50 years old , it is also evident that Luminal A is the most prevalent molecular subtype (71%).
Table 7. Association between each molecular subtypes and age in PIK3CA positive (mutated) breast cancer samples
Characteristic
|
Age
|
p-value
|
|
|
≤ 50 years old
|
> 50 years old
|
|
Molecular Subtypes (IHC Evaluation) in PIK3CA Positive (Mutated) Samples
|
|
|
0.298
|
|
Luminal A
|
15 (31.9%)
|
32 (68.1%)
|
|
|
Luminal B HER-2 (negative)
|
8 (53.3%)
|
7 (46.7%)
|
|
|
Luminal B HER-2 (positive)
|
3 (75%)
|
1 (25%)
|
|
|
HER-2 Enriched
|
2 (50%)
|
2 (50%)
|
|
|
TNBC
|
2 (40%)
|
3 (60%)
|
|
|
*Fisher's exact test p<0.05. Abbreviations: IHC = Immunohistochemistry, HER-2 = Human Epidermal Growth Factor-2, TNBC = Triple Negative Breast Cancer.