Abstract P4-11-02: Endocrine-related symptoms during neoadjuvant endocrine therapy for breast cancer: Agreement between patient and physician reporting in a prospective clinical trial
Authors: Fujisawa T , Iwata H , Sakai T , Nakamura R , Hasegawa Y , Ohtani S , Kashiwaba M , Taira N , Toyama T , Masuda N , Yamamoto Y , Kihara K , Shimozuma K , Ohashi Y , Mukai H 
Published: May 2016

Abstract
Background: There is a high risk of under-reporting subjective toxicities by physicians, even when collected prospectively in clinical trials. It has been recommended to include patient reported measures regarding symptoms in prospective clinical comparative effectiveness trials. However, there have been few reports of agreement in endocrine related symptoms between patient and physician reporting.
Patients and Method: The National Surgical Adjuvant Study of Breast Cancer 06 (N-SAS BC 06) is a multicenter, randomized clinical trial of postmenopausal, hormone receptor-positive breast cancer patients, with a two-stage (preoperative and postoperative) enrollment, and intervention. The primary aim was to evaluate the need for adjuvant chemotherapy in the treatment of postmenopausal breast cancer patients who responded to neoadjuvant treatment with Letrozole (LET) for 24-28 weeks. After surgery, responders were randomized into two arms receiving either chemotherapy plus LET, or LET alone. The primary endpoint was disease-free survival, and the secondary endpoints included adverse events, quality of life and health economic evaluation. This study enrolled 497 subjects from the N-SAS BC 06 who were evaluated by Patient Reported Outcomes (PROs). The concordance rate between Clinician Reported Outcomes (CROs) and PROs in their endocrine symptoms during neoadjuvant endocrine therapy was examined. Symptoms were collected prospectively by physicians using the Common Toxicity Criteria for Adverse Events at enrollment, i.e., baseline, and 4 and 16 weeks after starting neoadjuvant LET. Patients also completed the FACT-G (General), B (Breast), ES (Endocrine Symptoms), and HADS. The endocrine symptoms according to the PROs, included nausea, hot flushes, cold sweats, headaches, and HADS-Depression score. In FACT, "Not at all" was used to express the absence of the symptoms, and "A little bit", "Some-what", "Quite a bit", and "Very much" were used to express the presence of symptoms. The HADS-Depression score threshold was 10/11. According to the CROs, grade 0 was defined as the absence of symptoms and grade 1 or more was defined as the presence of symptoms. Cohen's kappa was used to determine the concordance between CROs and PROs. The sensitivity of CROs was also calculated.
Results: The calculated point estimates of Cohen's kappa at Weeks 4 and 16 after starting neoadjuvant LET were 0.12 and 0.01 for nausea, 0.16 and 0.18 for hot flushes, 0.12 and 0.09 for cold sweats, 0.03 and 0.02 for headaches, and 0.11 and 0.11 for dysthymia/depression, respectively; the concordance was quite low. The sensitivity of CROs at Weeks 4 and 16 after starting neoadjuvant LET was 0.07 and 0.03 for nausea, 0.16 and 0.17 for hot flushes, 0.1 and 0.08 for cold sweats, 0.03 and 0.03 for headaches, and 0.11 and 0.1 for dysthymia/depression, respectively; the sensitivity was quite low.
Conclusion: This study showed that there were big differences between CROs and PROs in endocrine symptoms associated with endocrine therapy for breast cancer and that physicians could not obtain sufficient information on the endocrine symptoms. It is recommended that PROs be used to evaluate adverse events caused by endocrine therapy.
Citation Format: Fujisawa T, Iwata H, Sakai T, Nakamura R, Hasegawa Y, Ohtani S, Kashiwaba M, Taira N, Toyama T, Masuda N, Yamamoto Y, Kihara K, Shimozuma K, Ohashi Y, Mukai H. Endocrine-related symptoms during neoadjuvant endocrine therapy for breast cancer: Agreement between patient and physician reporting in a prospective clinical trial. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-11-02.