Triple-negative breast cancer in India: Exploring age distribution and laterality patterns

Data collection

In the present study, a retrospective analysis of patients with equivocal HER2/Neu IHC status was included where their HER2 status was confirmed using the fluorescent in situ hybridization (FISH) technique by the cytogenetics department at SN Gene Laboratory Pvt. Ltd. FISH score of <2 was considered negative and more than 2 as positive. In total we received 488 samples of breast cancer between January 23 and November 23 from these 149 patients, which are included in this study, were TNBC cases. We analyzed the data for these patients. The clinical characteristics of the patients included were age of patients when received the samples, status for ER, PR, and Ki67, laterality, and histologic grade. Data on ER, PR, and Ki67 expression status were retrieved from the medical records of patients, which were assessed using IHC.

Informed consent was taken from patients.

Statistical analysis

The distribution of various factors was compared using the Chi-square test to determine the difference between left and right breast cancers concerning each factor. The ratio of left breast cancer to right breast cancer (left-to-right ratio [LRR]) was analyzed. The number and ratio of left- to right-sided were calculated according to different factors. All statistical analyses were performed using the R language. P < 0.05 was considered statistically significant.

Prevalence of TNBC

TNBC accounts for 30.53% out of 488 breast cancer cases observed between January and November 2023, which is consistent with reported Indian studies (11.8% to 31.9%).^[5,7,8]

Age distribution

The median age of TNBC patients was 55 years, aligning with findings from Western studies reporting a median age of 53 years.^[7] Patients aged 45-55 formed the largest subgroup (30.20%), showing a significant correlation with TNBC incidence (P value <0.001). A sharp decline in cases was seen after the age of 75 (4.69%) [Table 1]. These age-related findings are in line with previous literature by Chowdhary et al.^[9]

Laterality

There was a significant left-sided predominance in TNBC cases, with 69.12% occurring on the left side and 30.87% on the right (P value <0.001) [Table 1]. The observed left-sided dominance aligns with previous studies reporting variations in breast cancer laterality.^{[7, 10]}

Ki-67 expression

A high Ki-67 expression (>20%) was found in 96.24% of TNBC cases, indicating increased proliferative activity associated with TNBC (P value <0.001) [Table 1].

Tumor grade

There was no statistically significant difference in tumor grade distribution between left and right-sided TNBC cases (P value = 0.0943561) [Table 2].

Left vs. Right-sided TNBC

The comparison of key parameters between left and right-sided TNBC revealed no significant differences in age distribution, with the Left-to-Right Ratio (LRR) ranging from 1.50 to 6.00 across age groups (P value > 0.05). Both sides exhibited similarly high Ki-67 expression (>20%) (P value =0.9674364), underscoring the consistent aggressive nature of TNBC regardless of laterality [Table 2].

Data limitations

Missing data (3 entries for tumor grade and 16 for Ki-67 expression) may have influenced the overall results. Limited patient information was also a constraint in this study.

Age and TNBC

The age-related susceptibility of TNBC, with a peak incidence between 45-55 years and a decline after 75, is consistent with global findings and indicates a critical window for intervention in middle-aged women. This age distribution emphasizes the importance of early screening in at-risk populations.

Laterality

The observed left-sided predominance in TNBC cases may have clinical implications, particularly in understanding the biological mechanisms driving asymmetrical disease distribution. Future studies should investigate how laterality might affect treatment strategies and patient outcomes. This finding reinforces the need for vigilance in the diagnosis and management of left-sided breast cancer.

Tumor grade and Ki-67 expression

The high prevalence of grade III tumors and the elevated Ki-67 proliferation index (>20%) in TNBC reflect its aggressive nature. These findings emphasize the importance of personalized therapeutic approaches for TNBC patients, particularly those with higher tumor grades and high Ki-67 levels.

Laterality and Ki-67 expression

Despite the left-sided dominance of TNBC, no significant differences were observed between left and right-sided cases in terms of Ki-67 expression and age distribution, indicating that these factors do not appear to drive laterality differences.

Clinical implications

The study's findings underscore the need for personalized treatment strategies, especially for patients with high Ki-67 expression and advanced tumor grade. The left-sided predominance of TNBC also warrants further research to explore the underlying biological mechanisms and their potential impact on treatment responses.