Trastuzumab and Hypofractionated Whole Breast Radiotherapy: A Victorious Combination?

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Abstract

Micro-Abstract

Radiotherapy (RT) and trastuzumab are usually administered concurrently in patients with human epidermal growth factor receptor-2-positive breast cancer. Adjuvant hypofractionated RT, delivered in 15 or 16 fractions, has been accepted as a valid alternative to standard fractionation. We examined the feasibility of associating hypofractionated RT with trastuzumab, finding a safe profile in terms of acute skin and cardiac toxicity.

Introduction:

The purpose of this study was to examine the impact of trastuzumab on acute skin and cardiac toxicity in patients with breast cancer treated with chemotherapy with or without trastuzumab and adjuvant whole breast hypofractionated radiotherapy (hypo-RT).

Materials and Methods:

The study was conducted on 727 patients treated from April 2009 to October 2016. Patients received 42.4 Gy in 16 daily fractions (2.65 Gy per fraction). A boost was only administered in cases with grade (G) 3 primary tumor and close or positive margins. Acute and late toxicity was assessed prospectively during and after hypo-RT, based on the Radiation Therapy Oncology Group scale. Multivariable logistic regression models were used to examine the onset of acute skin toxicity (≥ G2) in the whole study population, and the impact of trastuzumab on the onset of acute skin (≥ G2) or cardiac toxicity in the subgroup of 176 patients given chemotherapy.

Results:

A total of 176 patients received chemotherapy with anthracycline and taxane, and 51 (29%) of them were also treated with trastuzumab. Acute G1, G2, and G3 skin toxicity occurred, respectively, in 56.8%, 27.3%, and 1.1% of the patients given chemotherapy alone, and in 64.7%, 19.6%, and 0% of those given trastuzumab as well. Among the patients given chemotherapy, left ventricular ejection fraction (LVEF) toxicity developed with a severity of G1 (LVEF < 60%-50%) in 12 (6.8%) patients, G2 (LVEF < 50%-40%) in 2 (1.1%) patients, and G3 (LVEF < 40%) in 1 (0.6%) patient. Among the patients also given trastuzumab, 7 (13.7%) patients had G1 LVEF toxicity, and 1 (2%) patient had G2 LVEF toxicity. We found that patients given trastuzumab were at higher risk of cardiac toxicity ≥ G1 (odds ratio, 4.3; P = .01), and at lower risk of acute skin toxicity ≥ G2 (odds ratio, 0.4; P = .03) than patients given chemotherapy alone.

Conclusions:

This analysis showed that trastuzumab with adjuvant hypo-RT for patients with breast cancer was generally well-tolerated in routine clinical practice. A longer follow-up will be necessary to assess late cardiac toxicity.

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