Abstract Background: There is growing interest in treatment optimization in early breast cancer (EBC). PROSPECT (ANZ-1002) provided compelling evidence that a combination of pre-operative MRI and pathological features could identify a substantial group of patients with localised EBC in whom radiotherapy (RT) could be safely omitted. The patient experience of de-escalation or its association with health-related quality of life (HRQoL) and fear of cancer recurrence (FCR), was not examined in PROSPECT but is a key consideration of treatment decision-making. We conducted a retrospective, mixed methods, cross-sectional study to explore this association. Methods: Psychometrically validated measures including the Fear of Cancer Recurrence Inventory Short-Form, Depression Anxiety Stress Scale, Breast Cancer Treatment Outcomes Scale, EORTC QLQ-C30 and its breast-specific module, the BR23, and the Decision Regret Scale were completed by three groups of women with early EBC: Women in the PROSPECT clinical trial who underwent pre-surgical MRI and omitted RT (A), women who underwent pre-surgical MRI and received RT (B); and women who received usual care (no MRI, received RT; C). Between group differences were analysed with ANOVA or equivalent non-parametric tests. A subset from each group participated in a semi-structured interview. These data (n=44) were analysed with directed content analysis. Results: Data from 400 women were analysed. Median age was 65 years, and median time since diagnosis was 4.4 years. There were no group differences in neuroticism, mental health, age, medical comorbidities, parity, or time since diagnosis. Significantly lower FCR was observed in Group A (n=125) than in Group B (n=102; p=.002) or Group C (n=173; p=.001), and when participants were categorized by RT status (omitted RT vs received RT; p< .001). The proportion of women with normal FCR was significantly (p < .05) larger in Group A (62%) than in Group B (35%) or Group C (40%). There were no differences between groups on depression and anxiety. Women in Group A had fewer breast symptoms than in Group B (p=.003) and Group C (p= < .001), fewer arm symptoms than in Group B (p=.004) and Group C (p=.011), and better body image than Group C (p=.041). Compared to Groups B and C, Group A performed better on cosmetic (both p< .001), functional (A vs C: p=.011) and breast-specific pain measures (both p< .001). Pre-operative MRI and omission of RT were highly acceptable and decision regret was low. A secondary analysis was conducted to eliminate any potential impact of disease severity on the analysis. All cases (n=126) with any positive nodes, a Grade 3 tumour and tumour size >20mm were removed. The remaining sample comprised 274 women. The results were similar to the primary analysis. Qualitative analysis showed that women who omitted RT viewed this as appropriate treatment, not undertreatment. Women considered RT toxic but endured it as a necessity, if prescribed. Few women experienced ongoing negative effects from RT but there was a tendency to minimize RT treatment burden. Women managed their FCR by having trust in their treatment and faith in the medical advice they received. Conclusions: In the setting of the PROSPECT trial, treatment de-escalation via omitting RT was associated with less FCR, better HRQoL and functional and cosmetic outcomes and was highly acceptable. Clinicians should consider the potential for preserved HRQoL associated with omission of RT in treatment decision-making. Positive perceptions about tailored care, lower treatment burden, and trust in clinicians appear to be protective against FCR. Future studies should include prospective collection of FCR and HRQoL measures. Citation Format: Bruce Mann, Michelle Sinclair, Phyllis Butow, Janemary Hughes, Allan Park, Leslie Gilham, Allison Rose, Lesley Stafford. Is de-escalation of treatment by omission of radiotherapy associated with fear of cancer recurrence and health-related quality of life in women with early breast cancer? An exploratory study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS02-03.
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