Adjuvant dose-dense chemotherapy improves breast cancer (BC) outcomes compared to standard chemotherapy, with no increase in chemotherapy-induced amenorrhea (CIA). However, the impact of menopausal status and the contribution of CIA to outcomes per subtype remain unclear.
PANTHER is a phase 3 trial comparing tailored, according to hematologic nadirs, and dose-dense (tdd) epirubicin/cyclophosphamide (EC) and docetaxel (D) versus standard interval FEC/D. The primary endpoint of the trial is relapse-free survival (BCRFS). This exploratory secondary analysis aimed to evaluate whether there was differential efficacy of tdd therapy according to menopausal status and if differences in CIA, defined as amenorrhea at 2 years following treatment, may contribute to its efficacy.
Baseline menopause status was available for 1913 women; 1036 premenopausal and 877 postmenopausal. Median follow-up was 5.3 years. The administration of tdd EC/D was associated with a non-statistically significant improvement in BCRFS in both premenopausal (HR = 0.83, 95% CI 0.59 – 1.16, p = 0.265) and postmenopausal patients (HR = 0.74, 95% CI 0.51 – 1.06, p = 0.102; pinteraction0.658). On the contrary, a significant interaction was noticed in women with triple negative BC (TNBC, p = 0.043). Tdd EC/D improved BCRFS in postmenopausal women (HR = 0.44, 95% CI 0.19 – 1.03, p = 0.06) but had a trend to opposite effect among premenopausal women (HR = 1.29, 95% CI 0.69 – 2.40, p = 0.426). There was no difference in CIA rates between the two treatment groups (OR = 1.04, 95% CI 0.77 – 1.39).
Tdd EC/D was associated with non-significant improvements in BCRFS, regardless of menopause status, without increasing rates of CIA. Negative effect on TNBC could be a chance finding due to low number of patients but the results warrant caution and necessitate further investigation.
The authors.
Swedish Cancer Society, Swedish Breast Cancer Association (BRO), Radiumhemmet Research funds, Amgen, Roche, Sanofi-Aventis.
G. Steger: Honoraria (self): Amgen. R. Greil: Honoraria (self): Amgen; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self): MSD; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self): BMS; Travel / Accommodation / Expenses: Roche; Travel / Accommodation / Expenses: Amgen; Travel / Accommodation / Expenses: AstraZeneca; Travel / Accommodation / Expenses: Janssen; Research grant / Funding (self): Roche; Research grant / Funding (self): BMS; Research grant / Funding (self): AstraZeneca. S. Loibl: Research grant / Funding (institution): Vigor; Honoraria (institution): AstraZeneca; Honoraria (institution): Amgen; Honoraria (institution): Pfizer; Honoraria (institution): Roche; Honoraria (institution): Puma; Honoraria (institution): Novartis; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Amgen; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche; Advisory / Consultancy: Puma; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Celgene; Travel / Accommodation / Expenses: Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Teva. M. Gnant: Honoraria (self), Travel / Accommodation / Expenses: Amgen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self): Celgene; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Lilly; Honoraria (self): Invectys; Honoraria (self), Travel / Accommodation / Expenses: Pfizer; Honoraria (self): Nano string; Honoraria (self): Novartis; Honoraria (self), Travel / Accommodation / Expenses: Roche; Honoraria (self): Medison; Travel / Accommodation / Expenses: Ipsen; Travel / Accommodation / Expenses: Medison. V. Moebus: Honoraria (self): Amgen; Honoraria (self): Celgene; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Myelotherapeutics; Honoraria (self): AstraZeneca. T. Foukakis: Honoraria (self), Research grant / Funding (institution): Roche; Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self): Novartis; Honoraria (self): UptoDate. J. Bergh: Research grant / Funding (institution): Merck; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Sanofi-Aventis; Honoraria (self): Uptodate. All other authors have declared no conflicts of interest.