Elsevier

The Breast

Volume 37, February 2018, Pages 142-147
The Breast

Original article
Impact of body mass index on the clinical outcomes of patients with HER2-positive metastatic breast cancer

https://doi.org/10.1016/j.breast.2017.11.004Get rights and content

Highlights

  • Body mass index (BMI) is a weight-for-height ratio used to assess a person's relative body fatness.

  • Limited data are available on the impact of obesity in HER2-positive metastatic breast cancer (MBC).

  • No difference in progression-free survival to first-line trastuzumab was observed according to BMI.

  • There was no overall survival difference between normal/underweight and overweight/obese patients.

Abstract

Background

Overweight and obesity are associated with an increased risk of developing many types of cancer, including breast cancer. Moreover, increased body mass index (BMI) seems to be associated with a worse prognosis in patients with HER2-positive early breast cancer. However, little is known about the impact of BMI on the clinical outcomes of HER2-positive metastatic breast cancer (MBC).

Methods

This was a multicenter retrospective cohort study including 329 consecutive patients with HER2-positive MBC treated with first-line trastuzumab-based regimens. BMI at the time of MBC diagnosis was collected. World Health Organization BMI categories were used: underweight <18.5, normal 18.5–24.9 Kg/m2, overweight 25–29.9 Kg/m2, and obese ≥30 Kg/m2. The analyses were conducted using two categories: BMI < 25.0 (normal/underweight) and BMI ≥ 25 (overweight/obese). Progression-free survival (PFS) and overall survival (OS) rates were estimated using Kaplan-Meier method. Univariate and multivariate survival analyses were performed using the Cox's proportional hazards model. Disease response to therapy was analyzed using univariate and multivariate logistic regression.

Results

Overall, 176 (53.5%) patients were normal/underweight and 153 (46.5%) overweight/obese. Median PFS was 14.8 months in BMI < 25 group and 15.7 months in BMI ≥ 25 group (adjusted-HR 0.88; 95% CI 0.66–1.17; p = 0.387). Median OS was 58.6 months in BMI < 25 group and 52.6 in BMI ≥ 25 group (adjusted-HR 0.88; 95% CI 0.59–1.31; p = 0.525). Overall response rate was 71.7% and 65.9% (p = 0.296) and clinical benefit rate was 82.1% and 83.3% (p = 0.781) in BMI < 25 and BMI ≥ 25 groups, respectively.

Conclusions

BMI does not seem to be associated with clinical outcomes in HER2-positive MBC patients.

Introduction

Body mass index (BMI) is a weight-for-height ratio that has been used for decades by the World Health Organization (WHO) to assess quantitatively a person's relative body fatness [1]. It categorizes individuals into four groups: underweight (<18.5), normal weight (18.5–24.9), overweight (25.0–29.9) and obese (≥30.0). Despite its limitations, this standardized measure is now commonly used worldwide. Epidemiological studies including more than 68.5 million participants in 195 countries showed that the prevalence of obesity is 12.0% among adults worldwide [2]. Projections are alarming as it is estimated that by 2025 the prevalence of obesity will reach 18% and 21% in men and women respectively [3]. Obesity has been associated with an increased risk of developing many types of cancer including breast cancer [4]. In addition, pre- and postmenopausal breast cancer survivors appear to have an increased mortality risk if they are obese at time of diagnosis [5]. The limited data available in the metastatic setting suggest no impact of BMI on the outcome of patients treated with first line chemotherapy in unselected breast cancer patients [6].

Breast cancer is a heterogeneous disease composed of different subtypes [7]. Among them, HER2-positive tumors account for 15–20% of all breast cancers [8]. The prognostic impact of BMI in HER2-positive tumors is uncertain as limited and conflicting results have been reported so far. In the adjuvant setting, the NSABP B-31 trial did not show a significant difference in OS and in breast cancer recurrence for overweight or obese patients compared to normal weight patients [9]. In contrast, the N9831 trial showed that obese patients had a significantly worse disease-free survival (DFS) in comparison to normal BMI patients, but no statistical difference in breast cancer-specific survival was noted [10]. More recently, the impact of baseline BMI on outcomes in the HERA trial revealed that baseline BMI did not significantly impact on breast cancer-free interval, disease specific-survival and OS [11].

Data on the impact of BMI on outcomes in HER2-positive metastatic setting are considerably lacking. To our knowledge, only one retrospective study analyzed the impact of BMI on outcomes in patients with HER2-positive MBC treated with trastuzumab-based regimens. This study showed that a higher BMI was associated with worse outcomes [12]. To help in better counseling patients diagnosed with HER2-positive disease in the metastatic setting on this crucial issue, we conducted the present study aiming to compare the effectiveness and response to first-line trastuzumab-based therapy according to BMI status in patients with HER2-positive MBC.

Section snippets

Study design

The Gruppo Italiano Mammella (GIM) conducted a multicenter retrospective cohort study across 14 affiliated Italian centers. Between January 2000 and December 2013, patients diagnosed with recurrent HER2-positive MBC and treated with first-line trastuzumab-based therapy were consecutively identified and analyzed to determine their clinical outcomes. Further details of the study were previously reported [13], [14]. The present analysis was conducted within the same dataset and aimed to evaluate

Results

Between January 2000 and December 2013, 329 (79.1%) consecutive women diagnosed with recurrent HER2-positive MBC and treated with first-line trastuzumab-based therapy were included from the initial data set of 416 patients. Among included patients, 176 (59.5%) had a BMI < 25 and 153 (46.5%) had a BMI ≥ 25. Median follow up was 3.0 years (IQR 2.1–5.4).

There was no significant difference in baseline demographic characteristics between the two BMI cohorts (Table 1). A total of 86 (26.5%) patients

Discussion

To our knowledge, this is the largest study that evaluated the impact of BMI on clinical outcomes of patients with HER2-positive MBC. In our analysis, BMI was not associated with PFS, OS and response rate (ORR and CBR). These results are in contrast with the findings of Parolin and colleagues [12]. This retrospective study evaluated the impact of BMI on outcomes in 155 patients with HER2-positive breast cancer patients treated with trastuzumab and chemotherapy in different settings of the

Conclusion

In conclusion, our study did not demonstrate that BMI at the time of diagnosis of metastatic disease is negatively associated with clinical outcomes of HER2-positive MBC patients. Our study gives further insights on the complex relationship between BMI and tumor biology and reinforces the need to better understand how they may be intertwined in different settings of the same disease. Additional data are needed to clarify the uncertainties surrounding the impact of BMI for HER2-positive MBC in

Funding

This work did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Disclosure

Matteo Lambertini served as a consultant for Teva and received a travel grant from Astellas outside the submitted work. Filippo Montemurro received honoraria from Roche–Genentech, Novartis and Astra Zeneca and travel grants and accommodation from Roche–Genentech and Astra Zeneca outside the submitted work. Lucia Del Mastro received personal fees from Novartis Pharma AG, Roche–Genentech, Ipsen, Astrazeneca, Takeda, Eli Lilly outside the submitted work. All the other authors declare that they

Acknowledgements

We thank all of the investigators affiliated with the Gruppo Italiano Mammella (GIM) study group who contributed to the study.

Dr. Samuel Martel acknowledges the support from the Société des Médecins de l'Université de Sherbrooke (SMUS) for a Fellowship at the Institut Jules Bordet in Brussels (Belgium). Dr. Matteo Lambertini acknowledges the support from the European Society for Medical Oncology (ESMO) for a Translational Research Fellowship at the Institut Jules Bordet in Brussels (Belgium).

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