Prognostic significance of body mass index in patients with triple negative breast cancer: A retrospective observational study

INTRODUCTION

Breast cancer remains one of the most prevalent malignancies worldwide, according to Global Cancer Observatory (GLOBOCAN) 2022. Breast cancer is the most common cancer in India, accounting for 13.8% incidence, with a heterogeneous spectrum of subtypes displaying distinct biological behaviors and clinical outcomes. Triple negative breast cancer (TNBC), characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression, represents a particularly aggressive subtype. It constitutes approximately 10-20% of all breast cancer cases.^[1,2]

TNBC exhibits a higher propensity for early metastasis, increased rates of recurrence, and poorer overall prognosis compared to other breast cancer subtypes.^[3] The absence of therapeutic targets such as hormone receptors and HER2 amplification limits treatment options, restricting patients to conventional chemotherapy regimens, which often yield variable responses and limited survival benefits.^[4] Immunotherapy is playing an increasingly important role in the treatment of TNBC, especially in locally advanced & metastatic disease.

Obesity, defined by a higher body mass index (BMI), has emerged as a significant public health concern globally, with escalating prevalence rates observed across diverse demographic profiles.^[5] Mounting evidence suggests that obesity not only predisposes individuals to various chronic diseases but also influences cancer development, progression, and treatment outcomes.^[6] In breast cancer, obesity has been implicated in promoting tumor initiation, enhancing tumor growth through adipose tissue-derived signaling molecules, fostering inflammation, and modulating hormonal pathways, thereby contributing to tumor aggressiveness and therapy resistance.^[7,8]

The association between obesity and breast cancer risk, particularly among postmenopausal women, has been extensively investigated, but its impact on the clinical course and outcomes of TNBC remains less elucidated, especially in regional contexts with distinct epidemiological and socio-cultural profiles, such as Eastern India.

Therefore, this retrospective observational study aims to address this critical knowledge gap by evaluating the prognostic significance of BMI in TNBC patients treated in Eastern India. Specifically, we seek to investigate whether higher BMI is associated with reduced survival outcomes in TNBC patients, providing insights into the impact of obesity on the clinical management and prognostication of this aggressive breast cancer subtype.

MATERIAL AND METHODS

A retrospective observational study was conducted involving 742 patients diagnosed with primary invasive breast cancer at the Institute of Post Graduate Medical Education & Research, Kolkata, India, from January 2016 to December 2020. Data were retrieved from medical records, encompassing socio-demographic variables, clinicopathological characteristics, and pertinent clinical information. Inclusion criteria were all stages except stage IV cancer, ER, PR, or HER2 negative, and left, right, or both-sided breast cancers. Exclusion criteria were male breast cancer, stage IV metastatic disease, ER, PR, or HER2 positive, or inadequate immunohistochemical information.

Patients with incomplete information on ER, PR, and HER2 status (n=28) and male breast cancer patients (n=2) within the triple-negative breast cancer subgroup were excluded, resulting in a final cohort of 242 female triple-negative breast cancer patients. Follow-up extended until December 2023, with censoring for individuals alive after the last follow-up date.

BMI was calculated as weight in kilograms divided by height in meters squared (kg/m²), categorized according to World Health Organization (WHO) definitions: overweight (BMI 25-29.9 kg/m²), healthy weight (BMI 18.5-24.9 kg/m²), obesity (BMI ≥30 kg/m²), and underweight (BMI <18.5 kg/m²).^[9]

Descriptive statistics summarized baseline characteristics, and the Chi-square test compared clinicopathologic characteristics across BMI groups. Survival endpoints [Overall Survival (OS)- time from diagnosis or treatment start to death from any cause), Disease-Free Survival (DFS)- time after treatment during which the patient remains free of disease), Metastasis-Free Survival (MFS)- time from treatment start to detection of metastasis)] were assessed using the Kaplan-Meier method with log-rank tests for group comparisons.^[10] Cox’s proportional hazards regression conducted univariate and multivariate analyses to determine hazard ratios (HR) with 95% confidence intervals (CI).^[11]

Statistical analyses were performed using the DATA tab platform with a significance level set at P < 0.05.

RESULTS

The median age of breast cancer patients is 45 years, range (24 to 83 years).

The onset of menarche was within normal range in 98.76% of cases. Additionally, 54.55% of all were pre-menopausal and 45.45% post-menopausal; 89.67% patients had a history of breastfeeding [Table 1]. Socio-economically, 10.33% reported an addiction to tobacco or alcohol, and 23.97% had comorbidities. Family history (only first-degree relatives included) was positive in 7.02% of patients. The average BMI was 23.95, with a range from 14.2 to 37.56 (95% CI 23.49; 24.4), indicating a normal weight for the majority (62.81%), though overweight and obesity were also present [Figure 1].

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Figure 1:

Distribution of body mass index (BMI) categories. 62.8% constitutes a healthy weight, 28.5% overweight, 4.55% underweight, and 4.13% obesity.

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Clinically, nearly equal distribution was between the right (52.48%) and left (47.52%) breasts, with major symptoms being lump and pain (97.93%), typically lasting 6-12 months. Most patients underwent Modified Radical Mastectomy, with 67.8% Grade 2 tumors. Lymphovascular invasion (LVI) was present in less than half of the cases, and PNI in 13.2% patients [Table 2].

The study’s survival curve over 35 months shows that individuals with underweight have the highest Metastasis Free Survival (MFS) rates (90.91%), with a noticeable decline across all categories at 10 months, and obese individuals have the lowest rate (70%) by the end.

The Chi-Square value of 3.11 and a p-value of 0.376 suggest no statistically significant difference in MFS across BMI categories, failing to reject the null hypothesis [Figure 2].

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Figure 2:

Kaplan-Meier curve analysis of metastasis-free survival (MFS) across BMI categories: p value 0.376.

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Conversely, the survival curves for DFS over 25 months indicate a significant difference across BMI categories, with a Chi-Square value of 30.29 and a p-value less than 0.001, leading to the rejection of the null hypothesis and suggesting BMI’s influence on DFS [Figure 3].

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Figure 3:

Kaplan-Meier Curve Analysis of Disease-Free Survival (DFS) Across BMI Categories: p value <0.001.

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Lastly, the OS rates curve for 40 months shows no significant difference across BMI categories [Figure 4], with a Chi-Square value corresponding to a non-significant p-value of 0.444, indicating that BMI may not significantly affect OS rates [Table 3].

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Figure 4:

Kaplan-Meier Curve Analysis of Overall Survival (OS) Across BMI Categories: p value 0.444.

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DISCUSSION

The retrospective observational study conducted in Eastern India provides a nuanced view of the prognostic significance of BMI in patients with triple-negative breast cancer (TNBC). The findings suggest a complex relationship between BMI and survival outcomes in TNBC patients.

The demographic profile of the study indicates a median age of 45 years for breast cancer patients, which is consistent with global epidemiological data showing a higher incidence of breast cancer in middle-aged women.^[12] The high rate of breastfeeding history (89.67%) among the participants aligns with previous research.^[13]

The clinical distribution of breast cancer between the right and left breasts does not show a significant preference, which is in accordance with the literature, breast cancer can occur in either breast without predilection.^[12] The predominance of symptoms such as lumps and pain, and the commonality of Modified Radical Mastectomy, reflect standard clinical presentations and treatment approaches for TNBC.^[12]

The study’s survival analysis over 35 months reveals that individuals with a healthy BMI have high MFS rates. This observation is intriguing, as it suggests that a normal BMI may confer a survival advantage in TNBC. However, the lack of statistical significance in MFS across BMI categories (Chi-Square = 3.11, p-value = .376) indicates that BMI alone may not be a strong independent prognostic factor for MFS in this population.

In contrast, the significant difference in DFS across BMI categories (Chi-Square = 30.29, p-value < .001) suggests that BMI may influence DFS in TNBC patients. This is supported by a systematic review and meta-analysis, which found that overweight was associated with shorter DFS in TNBC patients.^[14] The current study’s findings add to this body of evidence, indicating that higher BMI may be associated with reduced DFS.

Lastly, the OS rates over 40 months showed no significant difference across BMI categories (Chi-Square value corresponding to a non-significant p-value of 0.444). This aligns with other studies that have reported mixed results regarding the impact of BMI on OS in breast cancer patients.^[15,16] It suggests that while BMI may influence DFS, its impact on OS is less clear and may be confounded by other factors such as treatment response, comorbidities, and socioeconomic status.

CONCLUSION

The study conducted in Eastern India on the prognostic significance of BMI in TNBC patients reveals that higher BMI is associated with reduced DFS, but it does not significantly affect MFS or OS. The lack of statistical significance in MFS and OS suggests that factors other than BMI may play a more critical role in the long-term prognosis of TNBC. The significant impact of BMI on DFS underscores the need for a nuanced understanding of how obesity influences cancer progression and patient outcomes. This study contributes to the body of evidence that supports the inclusion of BMI in the clinical management and prognostication of TNBC. Further research is warranted to explore the complex interplay between BMI and TNBC outcomes, considering various confounding factors.