Elsevier

The Breast

Volume 22, Issue 5, October 2013, Pages 691-697
The Breast

Original article
FDG PET/CT during neoadjuvant chemotherapy may predict response in ER-positive/HER2-negative and triple negative, but not in HER2-positive breast cancer

https://doi.org/10.1016/j.breast.2012.12.020Get rights and content

Abstract

Background

Response monitoring with MRI during neoadjuvant chemotherapy (NAC) in breast cancer is promising, but knowledge of breast cancer subtype is essential. The aim of the present study was to evaluate the relevance of breast cancer subtypes for monitoring of therapy response during NAC with 18F-FDG PET/CT.

Methods

Evaluation included 98 women with stages II and III breast cancer. PET/CTs were performed before and after six or eight weeks of NAC. FDG uptake was quantified using maximum standardized uptake values (SUVmax). Tumors were divided into three subtypes: HER2-positive, ER-positive/HER2-negative, and triple negative. Tumor response at surgery was assessed dichotomously (presence or absence of residual disease) and ordinally (breast response index, representing relative change in tumor stage). Multivariate regression and receiver operating characteristic (ROC) analyses were employed to determine associations with pathological response.

Results

A (near) complete pathological response was seen in 19 (76%) of 25 HER2-positive, 7 (16%) of 45 ER-positive/HER2-negative, and 20 (71%) of 28 triple negative tumors. Multivariate regression of pathological response indicated a significant interaction between change in FDG uptake and breast cancer subtype. The area under the ROC curve was 0.35 (0.12–0.64) for HER2-positive, 0.90 (0.76–1.00) for ER-positive/HER2-negative, and 0.96 (0.86–1.00) for triple negative tumors. We found no association between age, stage, histology, or baseline SUVmax and pathological response.

Conclusion

Response monitoring with PET/CT during NAC in breast cancer seems feasible, but is dependent on the breast cancer subtype. PET/CT may predict response in ER-positive/HER2-negative and triple negative tumors, but seems less accurate in HER2-positive tumors.

Introduction

Neoadjuvant chemotherapy (NAC) is the standard of care in locally advanced breast cancer and is increasingly applied in larger operable breast cancer or in node-positive disease.1 As compared with adjuvant chemotherapy, the administration of NAC results in similar disease-free and overall survival and in comparable local control.2, 3 However, by reducing tumor load in the majority of patients, it results in a higher proportion of breast-conserving treatment and may allow surgery in patients who are deemed to be inoperable.2, 4

Breast cancer is a heterogeneous disease comprising various subtypes with different prognoses. NAC offers an excellent platform for translational research in this context, since the molecular characteristics of the individual tumors can be directly related to sensitivity and resistance for NAC. Based on immunohistochemistry, three different subtypes can be distinguished: human epidermal growth factor receptor 2 (HER2)-positive, estrogen receptor (ER)-positive/HER2-negative, and triple negative. These subtypes exhibit different behavior regarding response to chemotherapy5 and prognosis.6, 7 The presence of tumor cells in the surgery specimen following NAC has been associated with an unfavorable prognosis, thereby emphasizing the need for individualized chemotherapy and achieving a complete pathological response (pCR) of the primary tumor.8, 9

NAC provides an opportunity to monitor treatment response as well. In case of an unfavorable response, there is the possibility to switch the chemotherapeutic regimen or perform early surgery. This could prevent patients from experiencing unnecessary further drug toxicity. Further, randomized controlled trials, performing response assessment with clinical examination and ultrasound, have shown potential benefit of modifying therapy in both responders and non-responders regarding pCR and survival.10, 11, 12 These findings substantiate the need for accurate response prediction during NAC.

A recent review by Marinovich et al. concluded that response monitoring with magnetic resonance imaging (MRI) during NAC is promising, although there is lack of standardization.13 If response during NAC is monitored with MRI, knowledge of the breast cancer subtype is important; MRI response monitoring during NAC seemed accurate in HER2-positive and triple negative disease, but was less accurate in ER-positive/HER2-negative breast cancer.14

The value of positron emission tomography with integrated computed tomography (PET/CT) using 18F-fluorodeoxyglucose (FDG) in breast cancer has been studied extensively in recent years. Several studies have reported diverse behavior of different types of breast cancer regarding visualization and quantification of FDG uptake, with a higher degree of FDG uptake in tumors with an unfavorable prognosis.15, 16 Studies regarding the use of PET/CT during NAC to monitor response have shown promising results,17, 18, 19, 20, 21 but up till now only one paper differentiates between clinical subtypes.22 The aim of the present study was to evaluate the relevance of breast cancer subtype on PET/CT markers for monitoring of therapy response during NAC.

Section snippets

Patients

Patients with primary invasive breast cancer >3 cm and/or at least one tumor-positive node receive NAC according to one of several prospective trials studying chemotherapeutic regimens.14 The N08-RMB trial, running since September 2008, is an additional imaging study that evaluates the value of FDG PET/CT for response monitoring during NAC. Patients with two PET/CT examinations, one before and a second during NAC (after 6 weeks or, in case of HER2-positivity, 8 weeks), quantifiable tumor FDG

Results

Since September 2008 a total of 185 breast cancer patients underwent baseline PET/CT before treatment with NAC. Due to insufficient FDG uptake PET/CT response monitoring was impossible in ten (5%) of them. Of the remaining 175 patients, 58 did not give informed consent for PET/CT response monitoring. Of 117 patients, the second PET/CT was not performed in 16 of them, whereas in 3 patients it was performed at a different time-point during NAC.

We included a total of 98 patients in this study.

Discussion

This study demonstrates that the association between the change in FDG uptake during NAC and pathological response is dependent on the breast cancer subtype. Changes in FDG uptake during NAC correlated well with pathological response for ER-positive/HER2-negative and triple negative tumors, but not for HER2-positive tumors.

Numerous studies have shown that breast cancer is a heterogeneous disease. Classification according to the clinical subtype (HER2-positive, ER-positive/HER2-negative, and

Conflict of interest

None declared.

Acknowledgements

This study was performed within the framework of CTMM, the Center for Translational and Molecular Medicine (www.ctmm.nl), project Breast CARE (grant 03O-104).

We gratefully thank Marjo Holtkamp, Margaret Schot, and Jacqueline van Zyll de Jong for their active participation and guidance of patients throughout this study.

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