Impact of Chemotherapy-Induced Ovarian Dysfunction on Response to Neoadjuvant Chemotherapy in Breast Cancer

The association between chemotherapy-induced ovarian dysfunction (CIOD) and response to neoadjuvant chemotherapy (NAC) is not known. We therefore investigated the impact of CIOD on response to NAC in breast cancer patients according to estrogen receptor (ER) status.

In total, 343 premenopausal breast cancer patients treated with NAC between 2006 and 2010 were analyzed. Clinical responses were determined based on changes in tumor size measured using breast MRI. Patients with complete response or partial response were considered to have clinical response.

After completion of NAC, 264 of 343 patients (76.9 %) developed CIOD. The clinical response rate was significantly higher in patients with CIOD than those without CIOD (65.2 vs. 51.9 %; p = 0.033). Additionally, the mean follicle-stimulating hormone (FSH) level after NAC was significantly higher in patients with clinical response (FSH 68.7 ± 34.5 vs. 59.8 ± 34.3 IU/L; p = 0.021). Multivariate analysis showed an independent association of CIOD to clinical response (OR 0.523, 95 % CI 0.297-0.918; p = 0.024). However, we observed no differences in the pathologic complete response (pCR) rate between patients with and without CIOD (8.7 vs. 6.3 %; p = 0.497). Subgroup analysis according to ER status showed that the association between CIOD and clinical response was significant in ER-positive but not ER-negative breast cancer (p = 0.025 and 0.818, respectively).

CIOD during NAC is significantly associated with clinical response, but not pCR. Moreover, this association is only observed in ER-positive breast cancer, suggesting that the moderate difference in response to NAC is possibly a hormonal effect of chemotherapy-induced ovarian dysfunction.