Leukocyte nadir as a predictive factor for efficacy of adjuvant chemotherapy in breast cancer. Results from the prospective trial SBG 2000-1.

Background: Retrospective studies have suggested that chemotherapy-induced leukopenia is associated with improved recurrence-free or overall survival. The SBG 2000-1 trial was designed to verify the favorable prognosis associated with chemotherapy-induced leukopenia in early breast cancer. Patients not experiencing chemotherapy-induced leukopenia were randomized into standard dosed or individually escalated chemotherapy doses based on the grade of leukopenia after a first standard dose.Patients and methods: 1452 women in Sweden and Denmark with operable node-positive or high-risk node-negative breast cancer aged 18-60 years were recruited to participate in this trial. Participants received a first FEC cycle at standard doses (600/60/600 mg/m2). Patients (n = 1052) with nadir leukopenia grade 0-2 after the first cycle were randomized between either 6 standard FEC or 6 tailored FEC courses with doses of epirubicin and cyclophosphamide escalated during courses 2 and 3 and thereafter aimed at achieving grade 3 leukopenia. Patients with nadir leukopenia grade 3-4 after the first course continued treatment with standard FEC. Results of the randomized comparison has been published previously. The present study focuses on chemotherapy-induced leukopenia as a covariable with outcome in randomized and non-randomized patients. The prognostic value of leukopenia after course 3, was studied in a Cox model adjusted for cumulative doses of epirubicin and cyclophosphamide. The association of chemotherapy-induced leukopenia with prognosis was a preplanned secondary endpoint for this trial.Results: The eight-year distant disease-free survival was 73%, 77%, 78% and 83% for patients with leucocyte nadir grade 0, 1, 2 and 3-4, respectively. Higher degree of leukopenia was highly significantly associated to improved distant disease-free survival (HR 0.84, 95% CI 0.74-0.96, p = .008) and overall survival (HR 0.87 (0.76-0.99, p = .032).Conclusion: This prospective study confirms that chemotherapy-induced leukopenia is a covariable with outcome in primary breast cancer, even after adjustment for chemotherapy doses.

Bone loss during neoadjuvant/adjuvant chemotherapy for early stage breast cancer: A retrospective cohort study.

The present study aimed to evaluate the extent of loss in bone mineral density (BMD) during neoadjuvant and adjuvant chemotherapy for early stage breast cancer. A retrospective cohort study was conducted to quantify the loss of BMD one year following the start of chemotherapy and to identify potential risk factors of excessive BMD loss. Based on DXA-scans prior to and one year following chemotherapy, the loss of BMD was evaluated in early stage breast cancer patients treated from January 2012 to December 2014. A total of 492 patients received either eight cycles of neoadjuvant or six cycles of adjuvant chemotherapy. The final analysis included 152 patients with two DXA-scans. The patients had a significant loss of BMD in the hip [-0.0124 g/cm2 (95% confidence interval (CI) -0.018; -0.007) P<0.001] and in the lumbar spine [-0.029 g/cm2 (95% CI: -0.036; -0.023) P<0.001] corresponding to a change of -1, 3 and -2, 9%, respectively. Premenopausal women had a significant loss of BMD in the lumbar spine -0.045 g/cm2 equivalent to -4.3%, which was significantly increased compared with postmenopausal women (P<0.001) in the univariate analysis, whereas only a trend persisted in the multivariate analysis (P=0.60). There was no significant difference in BMD loss (lumbar spine P=0.176) between patients receiving adjuvant and neoadjuvant chemotherapy. In conclusion, neoadjuvant and adjuvant chemotherapy is associated with significant BMD loss in both hip and lumbar spine. Furthermore, the results of the present study indicate that premenopausal women have a pronounced BMD loss in the lumbar spine. Further studies investigating osteoporosis prophylaxis in premenopausal patients are warranted.