PURPOSE: The concurrent regimen of docetaxel, doxorubicin, and cyclophosphamide (TAC) has been categorized as a high-risk factor for febrile neutropenia (FN). The incidence of FN was reported to be as high as 17%–26% in studies conducted in Western countries. However, these rates may vary among different ethnic groups. This study aimed to evaluate the incidence of FN and its effect on prognosis following adjuvant TAC chemotherapy in Korean patients with advanced breast cancer. METHODS: We analyzed data from 187 patients who received 6 cycles of adjuvant TAC chemotherapy between July 2005 and December 2014. No patients received long-acting granulocyte-colony stimulating factor (G-CSF) as primary prophylaxis for FN due to guidelines for cost reimbursement in Korea. The incidence rates of FN, dose reduction of TAC, relative dose intensity (RDI), relapse-free survival (RFS), and overall survival (OS) were investigated. RESULTS: A total of 102 (54.5%) patients experienced FN, especially older patients (51 years vs. 49 years, p=0.045). RDI was lower in patients with FN than in those without (96.4% vs. 99.5%, p=0.001, respectively). Death was reported in 2 patients (2.35%) without FN and in 10 patients (9.80%) with FN (hazard ratio [HR]: 6.64; 95% confidence interval [CI]: 1.28 to 34.36; p=0.024). No significant differences in RFS (p=0.235) were found using Kaplan-Meier analysis. CONCLUSION The incidence of FN was significantly higher in Korea than in Western countries, and FN had a negative impact on the patients' prognosis. Primary prophylactic G-CSF should be prioritized in Korean patients with advanced breast cancer who receive adjuvant TAC chemotherapy.

Purpose: The prognostic implications of serum vitamin D status after a 5-year adjuvant endocrine therapy on the risk of late recurrence among hormone receptor (HR)-positive breast cancer patients remain unclear. Hence, we investigated this among Korean HRpositive breast cancer patients. Methods: A total of 455 patients with HR-positive stage I–III invasive breast cancer who underwent curative surgery at St. Vincent's Hospital between February 2004 and April 2012 were included in this retrospective study. Patients were categorized based on their serum 25-hydroxyvitamin D (25(OH)D) levels after the 5-year adjuvant endocrine therapy. Initial recurrence sites were categorized. The primary clinical outcome was late recurrence-free survival (LRFS). Results: Among the 455 patients, 242 and 213 were included in the 25(OH)D-deficient group and 25(OH)D-sufficient group, respectively. Forty-eight patients experienced late recurrence.Across all recurrence sites, the 25(OH)D-deficient group showed significantly worse LRFS rates than the 25(OH)D-sufficient group (hazard ratio [HR], 2.284; 95% confidence interval [CI], 1.155–4.515; p = 0.018). After patient subgrouping based on recurrence site, the 25(OH)D-deficient group also showed significantly worse LRFS rates in terms of regional lymph node (LN) (HR, 17.453; 95% CI, 2.46–128.83; p = 0.005), bone (HR, 2.394; 95% CI, 1.024–5.599; p = 0.044), and visceral (HR, 2.735; 95% CI, 1.182–6.328; p = 0.019) recurrence.However, there was no significant difference between the 2 groups in terms of local recurrence (p = 0.611). Conclusions We found that 25(OH)D deficiency after the 5-year adjuvant endocrine therapy was associated with worse LRFS among HR-positive breast cancer patients, particularly with respect to regional LN, bone, and visceral recurrence.

Purpose: The regimen including concurrent docetaxel, doxorubicin, and cyclophosphamide (TAC) has been categorized as an important risk factor for febrile neutropenia (FN).This comparative study examined the clinical impact of long-acting granulocyte colonystimulating factor (G-CSF) (pegfilgrastim) during adjuvant TAC chemotherapy in Korean patients with advanced breast cancer. Methods: We analyzed data from 239 patients who received 6 cycles of adjuvant TAC chemotherapy. We categorized patients into 2 groups according to the use of primary prophylactic pegfilgrastim and compared the incidence and risk of FN, hospital care costs, and survival in the 2 groups. Results: The incidence of FN decreased from 54.2% to 21.2% in all patients, after the use of pegfilgrastim. The analysis of a total of 1,432 chemotherapy cycles showed that the incidence of FN decreased from 36.1% to 9.1% after the use of pegfilgrastim. Moreover, the decrease in the incidence of FN with the use of pegfilgrastim resulted in a significant decrease in the mean duration of neutropenia (4.15 to 1.29 days), the risk of hospitalization (99.5% to 29.7%) and the mean total hospital care cost (USD 3,038 to USD 2,347). High relative dose intensity (RDI) in patients treated with pegfilgrastim than in those not treated with pegfilgrastim (99.18% vs. 93.85%) was associated with a better overall survival (p = 0.033). Conclusions The use of pegfilgrastim during adjuvant TAC chemotherapy was significantly associated with a decrease in the incidence and risk of FN, hospital care costs, and risk of death compared to the use of adjuvant TAC without primary prophylaxis.

Purpose: Treatment with 4 cycles of docetaxel and cyclophosphamide (TC) in the adjuvant setting is associated with better outcomes than treatment with doxorubicin and cyclophosphamide (AC). However, Western guidelines have indicated that TC confers a high risk (>20%) of febrile neutropenia (FN), while AC confers an intermediate risk (10%–20%) of FN. Threrefore, we evaluated the incidence of FN and the clinical utilization of pegfilgrastim prophylaxis after adjuvant TC chemotherapy. Methods: We categorized 201 patients who received adjuvant TC chemotherapy into 3 groups according to the method of prophylaxis and compared neutropenic events, other adverse events, and hospital care costs in the 3 groups. Results: The incidence of grade 4 neutropenia decreased from 93.0% in patients without prophylaxis to 82.4% in those who received secondary prophylaxis and 16.7% in those who received primary prophylaxis. Although the incidence of FN was not different between patients without prophylaxis and patients who received secondary prophylaxis (15.7% and 14.9%), none of the patients who received primary prophylaxis developed FN. Moreover, a decrease in neutropenic events resulted in a significant decrease in the mean duration of neutropenia (2.50 days to 0.08 days, P < 0.001), the risk of hospitalization (29.8% to 2.2%, P < 0.001), and the mean total hospital care cost for all chemotherapy cycles (790.80 to 486.00 US dollars, P < 0.001). Conclusion The use of pegfilgrastim prophylaxis during adjuvant TC chemotherapy is associated with significant decreases in the incidence of neutropenic events, hospitalization, and hospital care cost compared to those seen in patients without prophylaxis.

Purpose: Neoadjuvant chemotherapy (NAC) involving trastuzumab markedly increases pathologic complete response (pCR) rates in patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer. Despite increasing pCR rates, long-term survival gains are controversial owing to distinctive biologic behavior mediated by the presence of hormonal receptors (HRs) that may interact with HER2 receptors. We, therefore, investigated the differences in relative survival gain provided by neoadjuvant trastuzumab-based chemotherapy on HR positive (HR+) status of patients. Methods: We retrospectively ana Patient clinical characteristics were compared usin lyzed women with stage II or III HER2+ breast cancer who underwent NAC followed by a breast cancer surgery between 2008 and 2013. The survival benefits of adding trastuzumab to NAC were analyzed by classifying patients into HR+ and HR negative (HR−) groups. Results: Of 666 patients included in the study, 374 (52.1%) were HR+ and 319 (47.9%) were HR−. In the HR+ group, trastuzumab treatment led to higher pCR rates and significantly better breast cancer specific survival (BCSS) and overall survival (OS) than no trastuzumab treatment. However, among patients with HR− breast cancer, trastuzumab treatment showed no statistically significant difference between BCSS and OS following multivariate analysis. Conclusion We found that the addition of trastuzumab to NAC improved relative survival benefit in HER2+/HR+ patients than in HER2+/HR− patients, even though the pCR rate increases were lower. Although pCR has been regarded as a surrogate marker for estimating long-term survival benefits after NAC, it alone may not translate into real long-term oncologic outcomes in particular cancer subtypes after trastuzumab-based NAC. Further longer-term evaluation of the objective survival benefit after NAC driven by a dual HER2 block according to HR status is warranted.