Behavioral and health outcomes from the NRG Oncology/NSABP B-36 trial comparing two different adjuvant therapy regimens for early-stage node-negative breast cancer

Abstract

Background: The NSABP B-36 compared four cycles of doxorubicin and cyclophosphamide (AC) with six cycles of 5-fluorouracil, epirubicin, and cyclophosphamide (FEC-100) in node-negative early-stage breast cancer. A sub-study within B-36, focusing on symptoms, quality of life (QOL), menstrual history (MH), and cardiac function (CF) was conducted.

Patients and methods: Patients completed the QOL questionnaire at baseline, during treatment, and every 6 months through 36 months. FACT-B Trial Outcome Index (TOI), symptom severity, and SF-36 Vitality and Physical Functioning (PF) scales scores were compared between the two groups using a mixed model for repeated measures analysis. MH was collected at baseline and subsequently assessed if menstrual bleeding occurred within 12 months prior to randomization. Post-chemotherapy amenorrhea outcome was examined at 18 months and was defined as lack of menses in the preceding year. Logistic regression was used to test for association of amenorrhea and treatment. CF assessment was done at baseline and 12 months. Correlation analysis was used to address associations between changes in baseline and 12-month PF and concurrent CF changes measured by LVEF.

Results: FEC-100 patients had statistically significantly lower TOI scores during chemotherapy (P = 0.02) and at 6 months (P < 0.001); lower Vitality score at 6 months (P < 0.01), and lower PF score during the first year than AC patients. There were no statistically significant QOL score differences between the two groups beyond 12 months. No significant differences in symptom severity between the two groups were observed. Rates of amenorrhea were significantly different between FEC-100 and AC (67.4% vs. 59.1%, P < 0.001). There was no association between changes in LVEF and PF (P = 0.38).

Conclusions: Statistically significant QOL differences between the two groups favored AC; however, the magnitude was small and unlikely to be clinically meaningful. There was a clinical and statistically significant difference in risk for amenorrhea, favoring AC.

Trial registry: NCT00087178; Date of registration: 07/08/2004.

Keywords: Adjuvant chemotherapy; Amenorrhea; Cardiac function; Early-stage breast cancer; Quality of life.

© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Figures

Figure 1,. CONSORT Diagram: NSABP B-36

A. Quality-of-life (QOL) sub-study B. Menstrual History (MH) sub-study C. Cardiac sub-study AC, doxorubicin and cyclophosphamide; FEC-100, 5-fluorouracil, epirubicin and cyclophosphamide.

Figure 2.. FACT-B Trial Outcome Index (TOI) by treatment group and time point.

Adjusted least-square mean scores for all timepoints after baseline are obtained from mixed model for repeated measures analysis of the score. AC, doxorubicin and cyclophosphamide; FEC-100, 5-fluorouracil, epirubicin and cyclophosphamide. Footnote: *statistically significant differences observed: Day 1: FEC-100:60.34; AC:61.76, difference= −1.42, 95%CI=(−2.63,−0.22), P value=0.02; 6 months: FEC-100:66.86; AC:69.21; difference= −2.35, 95%CI=(−3.57,−1.13), P value<0.001.

Figure 3.. SF-36 Vitality scale score by treatment group and time point.

Adjusted least-square mean scores for all timepoints after baseline are obtained from mixed model for repeated measures analysis of the score. AC, doxorubicin and cyclophosphamide; FEC-100, 5-fluorouracil, epirubicin and cyclophosphamide Footnote: *statistically significant differences observed: 6 months: FEC-100:57.06; AC:59.97, difference=−2.91, 95%CI=(− 4.89,−0.93), P value=0.004.

Figure 4.. SF-36 Physical functioning score by treatment group and time point.

Adjusted least-square mean scores for all timepoints after baseline are obtained from mixed model for repeated measures analysis of the score. AC, doxorubicin and cyclophosphamide; FEC-100, 5-fluorouracil, epirubicin and cyclophosphamide. Footnote: *statistically significant differences observed: Day 1: FEC-100:66.97; AC:69.86, difference=−2.90, 95%CI=(−5.15, −0.65), P value=0.01; 6 months: FEC-100:71.40; AC:77.44, difference=−6.04, 95%CI=(−8.32, −3.77), P value<0.001; and 12 months: FEC-100:75.94; AC:79.29, difference=−3.35, 95%CI=(−5.64, −1.06), P value=0.004.