Adjuvant Tamoxifen Plus Ovarian Function Suppression Versus Tamoxifen Alone in Premenopausal Women With Early Breast Cancer: Patient-Reported Outcomes in the Suppression of Ovarian Function Trial.

PURPOSE The Suppression of Ovarian Function trial showed improved disease control for tamoxifen plus ovarian function suppression (OFS) compared with tamoxifen alone for the cohort of premenopausal patients who received prior chemotherapy. We present the patient-reported outcomes. PATIENTS AND METHODS The quality-of-life (QoL) analysis includes 1,722 of 2,045 premenopausal patients with hormone receptor-positive breast cancer randomly assigned to receive adjuvant treatment with 5 years of tamoxifen plus OFS or tamoxifen alone. Chemotherapy use before enrollment was optional. Patients completed a QoL form consisting of global and symptom indicators at baseline, every 6 months for 24 months, and annually during years 3 to 6. Differences in the change of QoL from baseline between the two treatments were tested at 6, 24, and 60 months with mixed models for repeated measures with and without chemotherapy and overall. RESULTS Patients on tamoxifen plus OFS were more affected than patients on tamoxifen alone by hot flushes at 6 and 24 months, by loss of sexual interest and sleep disturbance at 6 months, and by vaginal dryness up to 60 months. Without prior chemotherapy, patients on tamoxifen alone reported more vaginal discharge over the 5 years than patients on tamoxifen plus OFS. Symptom-specific treatment differences at 6 months were less pronounced in patients with prior chemotherapy. Changes in global QoL indicators from baseline were small and similar between treatments over the whole treatment period. CONCLUSION Overall, OFS added to tamoxifen resulted in worse endocrine symptoms and sexual functioning during the first 2 years of treatment, with variable magnitudes of treatment differences. Short-term differences in symptom-specific QoL, treatment burden, and coping effort between treatment groups were less pronounced for patients with prior chemotherapy, the cohort that benefited most from OFS in terms of disease control.

[1]  R. Gelber,et al.  Patient-reported outcomes with adjuvant exemestane versus tamoxifen in premenopausal women with early breast cancer undergoing ovarian suppression (TEXT and SOFT): a combined analysis of two phase 3 randomised trials. , 2015, The Lancet. Oncology.

[2]  R. Gelber,et al.  Tailoring therapies—improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015 , 2015, Annals of oncology : official journal of the European Society for Medical Oncology.

[3]  A. Giobbie-Hurder,et al.  Adjuvant ovarian suppression in premenopausal breast cancer. , 2015, The New England journal of medicine.

[4]  Dawn L Hershman,et al.  Perfecting breast-cancer treatment--incremental gains and musculoskeletal pains. , 2015, The New England journal of medicine.

[5]  T. Bevers,et al.  Quality of life in MAP.3 (mammary prevention 3): A randomized, placebo-controlled trial evaluating exemestane for prevention of breast cancer , 2015 .

[6]  N. Davidson,et al.  Should we embrace or ablate our urge to (ovarian) suppress? , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  S. Martino,et al.  Phase III comparison of tamoxifen versus tamoxifen plus ovarian function suppression in premenopausal women with node-negative, hormone receptor-positive breast cancer (E-3193, INT-0142): a trial of the Eastern Cooperative Oncology Group. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[8]  A. Giobbie-Hurder,et al.  Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. , 2014, The New England journal of medicine.

[9]  R. Gelber,et al.  Adjuvant treatment of premenopausal women with endocrine-responsive early breast cancer: design of the TEXT and SOFT trials. , 2013, Breast.

[10]  E. Perez,et al.  Randomized phase II study of lonaprisan as second-line therapy for progesterone receptor-positive breast cancer , 2013 .

[11]  V. Varela,et al.  Sexuality in adult cancer survivors: challenges and intervention. , 2012, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  T. Ruhstaller,et al.  Cervical and vaginal cancer in a woman with chronic graft‐versus‐host disease , 2011, International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.

[13]  T. Ruhstaller,et al.  Cetuximab in combination with chemoradiotherapy before surgery in patients with resectable, locally advanced esophageal carcinoma: a prospective, multicenter phase IB/II Trial (SAKK 75/06). , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[14]  R. Herrmann,et al.  Combination of bevacizumab and 2-weekly pegylated liposomal doxorubicin as first-line therapy for locally recurrent or metastatic breast cancer. A multicenter, single-arm phase II trial (SAKK 24/06). , 2011, Annals of oncology : official journal of the European Society for Medical Oncology.

[15]  T. Ruhstaller,et al.  Heated (37°C) oxaliplatin infusion in combination with capecitabine for metastatic colorectal carcinoma: can it reduce neuropathy? , 2010, Supportive Care in Cancer.

[16]  T. Ruhstaller,et al.  Limited Predictive Value of FDG-PET for Response Assessment in the Preoperative Treatment of Esophageal Cancer: Results of a Prospective Multi-Center Trial (SAKK 75/02) , 2009, Oncology Research and Treatment.

[17]  K. Rufibach,et al.  Breast Cancer Patients on Endocrine Therapy Reveal More Symptoms when Self-Reporting than in Pivotal Trials: An Outcome Research Study , 2009, Oncology.

[18]  T. Ruhstaller,et al.  Is a change in patient-reported dysphagia after induction chemotherapy in locally advanced esophageal cancer a predictive factor for pathological response to neoadjuvant chemoradiation? , 2009, Supportive Care in Cancer.

[19]  T. Ruhstaller,et al.  Bevacizumab-associated osteonecrosis of the jaw. , 2008, Annals of oncology : official journal of the European Society for Medical Oncology.

[20]  T. Ruhstaller,et al.  Fatal Herpes Simplex Virus Hepatitis in a Patient with Esophageal Cancer under Radiochemotherapy , 2008, Oncology Research and Treatment.

[21]  W. Scheithauer,et al.  Clinical benefit and quality of life in patients with advanced pancreatic cancer receiving gemcitabine plus capecitabine versus gemcitabine alone: a randomized multicenter phase III clinical trial--SAKK 44/00-CECOG/PAN.1.3.001. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  L. Schover Premature ovarian failure and its consequences: vasomotor symptoms, sexuality, and fertility. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[23]  T. Ruhstaller,et al.  Is surgery still part of local therapy in patients with locally advanced esophageal carcinoma? , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[24]  D. Bowen,et al.  Psychometric properties of a tool for measuring hormone‐related symptoms in breast cancer survivors , 2006, Psycho-oncology.

[25]  B. Thürlimann,et al.  The multidisciplinary meeting: An indispensable aid to communication between different specialities. , 2006, European journal of cancer.

[26]  F. Strasser,et al.  Comparison of orally administered cannabis extract and delta-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: a multicenter, phase III, randomized, double-blind, placebo-controlled clinical trial from the Cannabis-In-Cachexia-Study-Group. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[27]  B. Thürlimann,et al.  Fatigue and menopausal symptoms in women with breast cancer undergoing hormonal cancer treatment. , 2006, Annals of oncology : official journal of the European Society for Medical Oncology.

[28]  M. Stockler,et al.  Patients' preferences for adjuvant endocrine therapy in early breast cancer: what makes it worthwhile? , 2005, British Journal of Cancer.

[29]  A. Mueller,et al.  Is there really enough evidence to abandon surgery after radiation chemotherapy in esophageal cancer? , 2005, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[30]  J. Sloan,et al.  Issues for Statisticians in Conducting Analyses and Translating Results for Quality of Life End Points in Clinical Trials , 2004, Journal of biopharmaceutical statistics.

[31]  T. Ruhstaller,et al.  Resection of Skin Metastases from Gastric Carcinoma with Long–Term Follow–Up: An Unusual Clinical Presentation , 2004, Oncology Research and Treatment.

[32]  A. Goldhirsch,et al.  The Perceived Adjustment to Chronic Illness Scale (PACIS): a global indicator of coping for operable breast cancer patients in clinical trials , 1993, Supportive Care in Cancer.

[33]  L. Rutqvist,et al.  Side effects of adjuvant endocrine treatment in premenopausal breast cancer patients: a prospective randomized study. , 2003, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[34]  Ross Camidge,et al.  The European Organisation for Research and Treatment of Cancer , 2002 .

[35]  J. Bernhard,et al.  Patients' estimation of overall treatment burden: why not ask the obvious? , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[36]  M. Stockler,et al.  Patients' preferences for adjuvant chemotherapy in early breast cancer: a review of what makes it worthwhile. , 2001, The Lancet. Oncology.

[37]  P. Sjödén,et al.  Effect of endocrine treatment on sexuality in premenopausal breast cancer patients: a prospective randomized study. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[38]  M Sullivan,et al.  Clinical relevance of single item quality of life indicators in cancer clinical trials , 2001, British Journal of Cancer.

[39]  J. Cuzick,et al.  Tamoxifen for the prevention of breast cancer: psychosocial impact on women participating in two randomized controlled trials. , 2001, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[40]  T. Ruhstaller,et al.  Rituximab: active treatment of central nervous system involvement by non-Hodgkin's lymphoma? , 2000, Annals of oncology : official journal of the European Society for Medical Oncology.

[41]  J. Costantino,et al.  Health-related quality of life and tamoxifen in breast cancer prevention: a report from the National Surgical Adjuvant Breast and Bowel Project P-1 Study. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[42]  Susan R. Johnson,et al.  Symptom Relief and Side Effects of Postmenopausal Hormones: Results From the Postmenopausal Estrogen/Progestin Interventions Trial , 1998, Obstetrics and gynecology.

[43]  C. Hürny,et al.  Subjective health estimations (SHE) in patients with advanced breast cancer: an adapted utility concept for clinical trials. , 1998, British Journal of Cancer.

[44]  R. Gelber,et al.  Quality of life assessment in patients receiving adjuvant therapy for breast cancer: The IBCSG approach , 1998 .

[45]  R. Gelber,et al.  Responsiveness of a single-item indicator versus a multi-item scale: assessment of emotional well-being in an international adjuvant breast cancer trial. , 1996, Medical care.

[46]  C. Loprinzi North Central Cancer Treatment Group (NCCTG). , 1996, Journal of the National Cancer Institute. Monographs.

[47]  C. Redmond,et al.  Base-line quality-of-life assessment in the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial. , 1995, Journal of the National Cancer Institute.

[48]  P. Butow,et al.  On the receiving end. IV: Validation of quality of life indicators. , 1991, Annals of oncology : official journal of the European Society for Medical Oncology.