Olivia Pagani

557 Background: Little is known about endocrine symptoms, QoL and sexual function in premenopausal women with BC receiving adjuvant endocrine therapy. TEXT and SOFT are the first trials providing patient-reported data in this population. Methods: From Nov 2003 to Apr 2011, 4096 premenopausal patients (pts) with HR+ BC were enrolled and included in the QoL analysis of the randomized phase III trials, TEXT and SOFT, to receive adjuvant treatment with 5 yrs E+OFS or T+OFS. Chemotherapy (chemo) was optional in both trials; received concurrently with OFS after randomization in TEXT and prior to randomization in SOFT, with women eligible if they remained premenopausal after completing chemo. Pts completed a questionnaire consisting of global and symptom-specific indicators at baseline, every 6 months for the first 24 months, and annually yrs 3 to 6. Differences in change of QoL from baseline between the two treatments were tested at short-, mid-, and long-term (6, 24 and 60 months post-randomization, respectively) for 3 global QoL and 5 symptom indicators using mixed models with repeated measures. Results: Pts on T+OFS were significantly more affected by hot flushes than E+OFS, with treatment difference persisting over time (each p<.05). The change of hot flushes from baseline improved over time for both treatments. Throughout treatment, pts on E+OFS reported more vaginal dryness and greater loss of sexual interest, while T+OFS reported more vaginal discharge (each p<.0001). The difference between treatments in bone/joint pain was most pronounced in the short-term in favor of T+OFS, but a difference persisted (each p<.0001). Changes of global QoL indicators (mood, physical wellbeing, and coping effort) from baseline were similar between treatments over the whole treatment period. Conclusion: Overall from a QoL perspective, there is no strong indication to favor either E+OFS or T+OFS. The differential effects of the two treatments on endocrine symptoms burden need to be addressed with patients individually. Clinical trial information: NCT00066783/NCT00066690.

Background: The efficacy and safety of prolonged fluoropyrimidines, either intravenously or orally, prompted their integration with taxanes and anthracyclines in the treatment of advanced breast cancer (ABC). We conducted three subsequent dose-finding studies on first-line chemotherapy in ABC with anthracyclines, either epirubicin (E) or doxorubicin (A), and docetaxel (T), both given on days 1 and 8 every 3 weeks, plus continuous infusion (CI) 5-fluorouracil (F) or capecitabine (X). Patients and methods: Sixty-two patients (37% dominant visceral disease, 48% locally advanced disease, 45% two or more sites involved), received different doses of T (60–80 mg/m²), A (40–50 mg/m²) or E (60–90 mg/m²) and X (1650 and 2000 mg/m²), or CI F at a fixed daily dose of 200 mg/m². Cardiac function was monitored at baseline and then every four cycles by echocardiography. Results: The median number of cycles per patient with all regimens was four (range one to eight). Haematological and gastrointestinal toxicity defined the maximum tolerated doses, at T80/E90 mg/m² with TEF, T70/A50/X2000 mg/m² with TAX and T70/E80/X1650 mg/m² with TEX. Two patients treated with TEF developed transient cardiac toxicity (dilatative cardiomyopathy and coronary subtotal stenosis requiring stenting) after cumulative E doses of 400 mg and 1100 mg/m², respectively. Fifty-nine patients were evaluable for response; the overall response rates (ORR) were comparable between regimens (54% with TEF, 71% with TAX and 86% with TEX), with an 81% ORR in 31 patients with locally advanced disease. Conclusions: The addition of fluoropyrimidines to weekly, intermittent ET is well tolerated and active in ABC.

Background: Toremifene is a chlorinated derivative of tamoxifen, developed to improve its risk–benefit profile. The International Breast Cancer Study Group (IBCSG) conducted two complementary randomized trials for peri- and postmenopausal patients with node-positive breast cancer to compare toremifene versus tamoxifen as the endocrine agent and simultaneously investigate a chemotherapy-oriented question. This is the first report of the endocrine comparison after a median follow-up of 5.5 years. Patients and methods: 1035 patients were available for analysis: 75% had estrogen receptor (ER)-positive primary tumors, the median number of involved axillary lymph nodes was three and 81% received prior adjuvant chemotherapy. Results: Toremifene and tamoxifen yielded similar disease-free (DFS) and overall survival (OS): 5-year DFS rates of 72% and 69%, respectively [risk ratio (RR)=0.95; 95% confidence interval (CI)=0.76–1.18]; 5-year OS rates of 85% and 81%, respectively (RR = 1.03; 95% CI = 0.78–1.36). Similar outcomes were observed in the ER-positive cohort. Toxicities were similar in the two treatment groups with very few women (Conclusions: Toremifene is a valid and safe alternative to tamoxifen in postmenopausal women with endocrine-responsive breast cancer.