The impact of age and clinical factors on quality of life in early breast cancer: An analysis of 2208 women recruited to the UK START Trial (Standardisation of Breast Radiotherapy Trial)

Summary

Quality of life (QOL) assessments of women entering a UK randomised trial of adjuvant radiotherapy (START) were investigated to estimate the independent effects on QOL of age, time since surgery, type of breast surgery, chemotherapy and endocrine therapy. QOL was evaluated using the EORTC general cancer QOL scale (EORTC QLQ-C30), breast cancer module (BR23), the Body Image Scale (BIS) and the Hospital Anxiety and Depression Scale (HADS). Independent effects of age and clinical factors were tested using multiple regression analysis.

A total of 2208 (mean age 56.9 years, range 26–87) consented to the QOL study prior to radiotherapy; 17.1% had undergone mastectomy (Mx) and the remainder had undergone a wide local excision (WLE). 33.3% had received adjuvant chemotherapy (CT) and 56.7% were taking endocrine therapy (ET). Age had significant effects on QOL with older and younger subgroups predicting poorer QOL for different domains. CT affected most QOL domains and resulted in worse body image, sexual functioning, breast and arm symptoms (<0.001). Mx was associated with greater body image concerns (p<0.001), and WLE with more arm symptoms (p=0.01). There were no effects of ET on QOL. Women <50 years (proxy pre-menopausal) had worse QOL in respect of anxiety, body image and breast symptoms but age and clinical factors had no effect on depression.

Overall, QOL and mental health were favourable for most women about to start RT, but younger age and receiving CT were significant risk factors for poorer QOL, and so patients in these subgroups warrant further monitoring. Surgery had a limited impact and ET had no effect on QOL.

Introduction

Women with primary breast cancer usually undergo breast surgery plus adjuvant systemic treatments in order to reduce the risks of local and distant disease recurrence, but with the potential for multiple effects on quality of life (QOL). The overall psychosocial impact of these modern treatments has been reported.1, 2, 3, 4, 5, 6, 7, 8 Younger patients are more likely to suffer adverse effects because of induction of an early menopause and possible infertility. Other reported problems have included poor sexual functioning, altered body image, fatigue and difficulty with shoulder and arm movements. These effects may have an impact on QOL in the longer term. Radiotherapy is known to have late effects on normal tissues which could contribute adversely to body image and related QOL parameters but it is often impossible to attribute QOL effects, such as breast symptoms, to a specific adjuvant strategy in multimodal therapy.9, 10, 11, 12, 13, 14, 15 Ganz and colleagues commented that women are generally well prepared for the acute toxicities of breast cancer treatments but that clinicians have limited information on the physical and psychosocial sequelae of primary treatments, or the pattern of recovery. This highlights the need for more precise data on individual treatment effects and interactions.¹⁶

The QOL protocol in the Standardisation of Breast Radiotherapy Trial (START) trial will help address these deficiencies, through its prospective design and long term follow-up, by using patient assessed measures of body image and QOL, and by identifying the effects of individual treatments in multimodal therapy. The trial includes women of all ages allowing the effect of age on QOL to be explored. The purpose of the trial is to test the effects of radiotherapy fractions >2.0 Gy on local tumour control and late normal tissue response in the breast area after tumour excision. The trial comprises two randomised comparisons, namely Trial A, which tests three fractionation schedules; 50 Gy in 25 fractions (F) over 5 weeks versus two dose levels of a test schedule giving 41.6 Gy or 39 Gy in 13 F over 5 weeks, and Trial B, which tests the standard therapy (50 Gy in 25 F) against a dose level of 40 Gy in 15 F over 3 weeks.¹⁷ Long-term follow-up is now being completed and QOL will form part of the outcome assessment of the randomised comparison. Over 2000 women (>50% of trial participants) have been accrued to the QOL study, making this the largest such investigation in the UK. Prior to breaking the randomisation code, we have undertaken this analysis to describe QOL in the overall cohort of patients and to investigate the effects on QOL of age and other primary treatments, prior to starting radiotherapy, in order to gauge the extent to which key domains such as body image may be affected by other primary treatments. The size of the database allows us to explore the individual impact of type of surgery, endocrine therapy (ET), chemotherapy (CT), as well as examining age effects, whilst controlling for time since surgery, on all QOL domains.

To describe all aspects of QOL at baseline, i.e. prior to undergoing radiation therapy.

To determine the impact on QOL of age, type of breast surgery (Mx vs WLE), adjuvant CT and ET whilst controlling for time elapsed since surgery. These factors were selected to accurately determine the impact of primary breast cancer treatment on QOL before radiotherapy, whilst taking account of the fact that patients undergoing CT would have a longer time between breast surgery and radiotherapy compared with those proceeding directly to radiotherapy. Age was included because it is known to influence some aspects of QOL.

To compare women under 50 years with those aged ⩾50 in terms of QOL. These age-groups were chosen to provide subgroups representing proxy pre- and post-menopausal status in the analysis at baseline.