For this reason, we retrospectively evaluated the two different dosages of epirubicin in FEC (FEC50 and FEC100) on patients who received neoadjuvant chemotherapy.

Tumor size and axillary assessment for lymph nodes were conducted by ultrasonography, mammography and physical examination. The tumor size was calculated as the product of the two greatest perpendicular diameters assessed ultrasonographically before chemotherapy and surgery. Radiological response was recorded according to the UICC criteria: a) Complete response (CR), disappearance of the primary tumor; b) Partial response (PR), a tumor reduction of .50%; c) stable disease (SD), a tumor reduction <50% or an increase in tumor size of <25%; and d) progressive disease (PD), an increase in tumor size of .25% [7]. Pathologic complete response (pCR) was evaluated in the dissected mammary and axillary specimens and this was defined if no residual invasive tumor was found.

The pretreatment and posttreatment tissue specimens had been fixed in 10% buffered formalin and embedded in paraffin. 5 µm thick sections were cut and stained with hematoxylin and eosin. The primary tumor characteristics studied included tumor size, histologic type according to the World Health Organization recommendations, histologic grade using the Scarff, Bloom and Richardson (SBR) method. Estrogen (ER) and progesteron (PgR) receptor status were assessed by immunohistochemistry. The proportion of ER and PgR positive cells was determined as the percentage of invasive tumor cells. The threshold of 10% positivity was chosen as the cut-off value. All specimens were re-examined by an experienced pathologist who was unaware of the clinical data.

Toxicity was assessed through clinical examination at baseline and before each drug administration. Laboratory tests, including a complete biochemical routine and blood count, were performed at baseline and at the end of each cycle. Blood cell counts were also repeated on days 7 and 10 of each cycle to catch the presumably worst hematologic side effects. A baseline cardiac assessment included an electrocardiogram and evaluation of left ventricular function with echocardiogram. Electrocardiogram was repeated at the end of treatment. Toxicity was evaluated according to World Health Organization (WHO) criteria.

Table 1: Pretreatment characteristics of patients and tumors

Table 2: The response rate and comparison of two different regimens

Table 3: Response rates according to patient and tumor characteristics

Chemotherapy was administered as programmed for both groups. Both regimens were well tolerated. Cardiac toxicity and infection were not seen in both groups. Neutropenic toxicity was observed 20% (95% CI, 4.3-35.6) of FEC50 and 61.5% (95% CI, 42.7-80.7) of FEC100 group. Grade 3-4 neutropenia was found to be 4% (95% CI, 0.0- 11.6) and 23% (95% CI, 6.8-39.1) in FEC50 and FEC100 groups respectively. Neutropenic toxicity rate was highest in FEC100 group. The frequency of other toxicities are similar both groups and are listed in table 4.

Table 4: Chemotherapy-related adverse effect

Table 5: EC and FEC regimens’ response rate in neoadjuvant setting

Previous studies on metastatic patients revealed an increase in response rates as the epirubicin dosage is increased. Three trials were conducted by The French Epirubicin Study Group in metastatic breast cancer. Each trial comparing FEC50 versus FEC75, FEC50 versus FEC100, FEC75 versus FEC100 demonstrated a better response in the high epirubicin dosage group [12-14]. High response rate was observed in ER negative group. In the neoadjuvant setting, it has been reported that ERnegative tumors were more likely associated with higher response rates than ER-positive tumors [15]. This data could be explained by the the statement that tumors most often have an associated poorly differentiated nuclear grade and nuclear grade is correlated with high cell-cycle proliferative activity [16,17]. Thus, high dose epirubicin application to the tumors with these features might increase the response rate but the hypothesis that proliferative activity, negativity of steroid receptors and poor differentiation increases response rate is debatable [18-20].

In this retrospective analysis of our own experience, the response rates observed in FEC50 and FEC100 groups seemed to be similar after 4 cycles of neoadjuvant chemotherapy. Only well-designed, randomized, and prospective clinical trials could contribute to establish the optimum dosage and duration of anthracyclines in neoadjuvant therapy.

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