Patient-Reported Outcomes From Phase III Neoadjuvant Systemic Trial Comparing Neoadjuvant Chemotherapy With Neoadjuvant Endocrine Therapy in Pre-Menopausal Patients With Estrogen Receptor-Positive and HER2-Negative, Lymph Node-Positive Breast Cancer

Abstract

We aimed to evaluate the patient-reported outcomes (PROs) in a prospective phase III clinical trial, comparing neoadjuvant endocrine therapy (NET) with conventional neoadjuvant chemotherapy (NCT) in patients with hormone status positive, lymph node-positive premenopausal breast cancer (NCT01622361). The patients were randomized prospectively to either 24 weeks of NCT with adriamycin plus cyclophosphamide followed by taxane or NET with gonadotropin-releasing hormone agonist and tamoxifen. The patients were examined at the surgery unit of a large tertiary care hospital with a comprehensive cancer center. PROs were assessed on the first day of the trial (day 1, baseline) and at the end of treatment, using the breast cancer module of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 23 (EORTC QLQ BR23). One hundred and eighty-seven patients were randomly assigned to chemotherapy (n=95) or endocrine therapy (n=92), and 174 patients completed 24 weeks of the neoadjuvant treatment period (n=87, in each group). Baseline scores were similar between the groups. After treatment, there were no statistically significant differences in the function scales, including body image, sexual functioning, and sexual enjoyment between the groups, although the endocrine treatment group showed a significant improvement in the future perspective (hazard ratio, 8.3; 95% confidence interval, 1.72-18.38; P = 0.021). Similarly, there were no statistically significant differences in the symptom scales between the groups, including adverse effects of systemic therapy, breast symptoms, arm symptoms, and upset about hair loss. In conclusion, overall PROs were similar in both treatment groups, except for "future perspective," which was significantly better in the NET group than in the NCT group.

Clinical trial registration: ClinicalTrials.Gov, identifier NCT01622361.

Keywords: HER2-negative; Neoadjuvant stusdy of chemotherapy versus Endocrine therapy in premenopausal patient with hormone responsive; lymph node-positive breaST cancer (NEST); neoadjuvant chemotherapy; neoadjuvant endocrine therapy; patient-reported outcomes; quality of life.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Gwark, Ahn, Noh, Lee, Jung, Kim, Han, Nam, Gong, Kim and Kim.

Figures

Figure 1

Flowchart and CONSORT Diagram. ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; NCT, neoadjuvant chemotherapy; NET, neoadjuvant endocrine therapy. (A) Flowchart outlining recruitment to NEST trial, (B) CONSORT diagram of participant randomization.

Figure 2

Forest plot model of estimated difference (NET: ETx vs. NCT: CTx) in overall change from baseline (repeated-measures mixed-effect model) in PRO-evaluable population. CTx, chemotherapy; EORTC, European Organisation for Research and Treatment of Cancer; ETx, endocrine therapy; NCT, neoadjuvant chemotherapy; NET, neoadjuvant endocrine therapy; PRO, patient-reported outcome; QLQ-BR23, Quality of Life Questionnaire Breast Cancer Module; QoL, quality of life. (A) EORTC QLQ-BR23: functional scales, (B) EORTC QLQBR23 symptom scales. aThe sample sizes for the "sexual enjoyment" functional scale were smaller than other functional scales because patients were asked to respond question that they were sexually active. bThe sample sizes for the "upset by hair loss" symptom scale were smaller than other symptom scales because patients were asked to respond to this question only if they responded in a previous question that they were experiencing hair loss.

Figure 3

Estimated overall change from baseline in PRO-evaluable population. CI, confidence interval; CTx, chemotherapy; EORTC, European Organisation for Research and Treatment of Cancer, ETx, endocrine therapy; NCT, neoadjuvant chemotherapy; NET, neoadjuvant endocrine therapy; PRO, patient-reported outcome; QLQ-BR23, Quality of Life Questionnaire breast cancer module; QoL, quality of life. (A) EORTC QLQ-BR23: functional scales, (B) EORTC QLQ-BR23: symptom scales. aArrow denotes direction of improved outcome. bThe sample sizes for the "sexual enjoyment" functional scale was smaller than other functional scales because patients were asked to respond to this question only if they responded in a previous question that they were sexually active. cThe sample sizes for the ‘upset by hair loss’ symptom scale was smaller than other symptom scales because patients were asked to respond to this question only if they responded in a previous question that they were experiencing hair loss.

Figure 4

Estimated overall change from baseline in 6 patients who refuse to undergo surgery after treatment (all received NET). CI, confidence interval; EORTC, European Organisation for Research and Treatment of Cancer; NET, neoadjuvant endocrine therapy; PRO, patient-reported outcome; QLQ-BR23, Quality of Life Questionnaiure Breast Cancer Module; QoL, quality of life. (A) EORTC QLQ-BR23; functional scales, (B) EORTC QLQ-BR23: symptom scales. aArrow denotes direction of improved outcome. bThe sample sizes for the "sexual enjoyment" functional scale was smaller than other fuctional scales because patients were asked to respond to this question only if they responded in a previous question that they were sexually active. cThe sample sizes for the "upset by hair loss" symptom scale was smaller than other symptom scales because patients were asked to respond to this question only if they responded in a previous question that they were experiencing hair loss.