Page 248 - Haematologica - Vol. 105 n. 6 - June 2020

C. Giaccherini et al.
Outcome
The primary outcome of the present analysis was DR, defined as either loco-regional (limited to the ipsilateral breast or chest wall and/or axillary, infraclavicular, or supraclavicular lymph nodes) or distant metastasis.
Statistical analysis
Categorical data are summarized as frequencies and propor- tions, while for continuous variables, data are summarized as mean and standard deviation or median and 5th-95th percentile range, depending on their distribution. Differences between groups were tested by Pearson’s χ2 test, Student t-test or Mann- Whitney U-test. Survival functions were estimated using the Kaplan-Meier method, assuming as baseline time the beginning of chemotherapy, while survival analyses were performed using Cox’s proportional hazard (PH) model. Statistical analysis was per- formed using SPSS v21.0 (IBM Corp).
Results
Characteristics of study population
Table 1 summarizes clinical and tumor histological char- acteristics of study patients (median age 52; range, 29-79 years). Breast-conserving resection was performed in 61% and mastectomy in 39%. HER-2 expression was positive in 203 and negative in 498 patient sample specimens, respectively. Most frequent molecular subtypes were Luminal B HER2-neg (33.4%) > Luminal A (22.7%) > Luminal B HER2-pos (20.3%) > TN (14.4%) > HER2-pos (8.6%) (4 missing data for ki67 =0.6%). According to his- tological subtype, the largest proportion was classified as invasive ductal carcinoma, diagnosed in 83% of patients. Lymph node involvement was found in 56% of patients. Based on primary tumor characteristics, ER/PR and HER2 status, age, and/or discretion of the treating physician, patients were candidates for systemic adjuvant chemotherapy. An anthracycline-based regimen was indi- cated for 35.1% of patients. The addition of taxane to an anthracycline regimen was considered in case of extensive disease burden or TN disease (50.8% of patients). A tax- ane-based regimen without anthracyclines was adminis- trated to 9.3% of patients. In case of comorbidities or patient preference, intravenous CMF (i.e. cyclophos- phamide, methotrexate and 5-fluorouracil) was given (4.8% of patients). All 203 HER-2 positive breast cancers received (in addition to chemotherapy) trastuzumab every 21 days for one year. Four hundred and seventy-five patients with ER/PR positivity (n=535) received endocrine therapy according to their premenopausal state (data missing in 48 patients).
Disease recurrence
The Kaplan-Meier curve shown in Figure 1 describes the cumulative incidence of DR during four years of follow up. The incidence of DR in the group of patients was 2% (95%CI: 1-3) at one year, 6% (95%CI: 4.3-7.8) at two years, 9.5% (95%CI: 7.2-11.9) at three years, and 11.2% (95%CI:8.5-14) at four years. Specifically, 630 out of 701 patients included into the analysis remained disease-free, while 71 relapsed. Demographics and clinical characteris- tics of patients who developed DR and of those who remained disease-free are shown in Table 1. The group of patients who relapsed comprised 68 females and three males, with a median age of 52 years (range, 34-78 years).
Recurrences consisted of distant metastasis in 69% of cases, and loco-regional relapse in the remaining 31%. According to the molecular subtype, the majority of
Table 1. Characteristics of patients with resected breast cancer.
Gender Male Female
Age
Median (5th-95th)
Stage IA IIA
IIB
IIIA
IIIB
IIIC Unknown
Tumor size ≤ 2 cm 2-5 cm
≥ 5 cm
Unknown
N stage N0
N1
N2
N3 Unknown
Histological type Ductal
Lobular
Mixed
Others
Unknown
Grading G1
G2
G3 Unknown
Molecular subtype Luminal A
Luminal B HER2-neg Luminal B HER2-pos HER2-pos
Triple negative
Unknown Surgery
Breast conserving Mastectomy Unknown
ECOG-PS 0
1
Unknown
All patients 701
11 (1.6) 690 (98.4)
52 (37-73)
173 (24.7) 225 (32.1) 125 (17.8) 85 (12.1) 9 (1.3)
44 (6.3) 40 (5.7)
80 (11.3) 245 (35.0) 342 (48.8) 34 (4.9)
287 (40.9) 268 (38.3) 77 (11.0) 48 (6.8) 21 (3.0)
580 (82.7) 56 (8.0) 4 (0.6) 44 (6.3) 17 (2.4)
14 (2.0) 264 (37.7) 409 (58.3) 14 (2.0)
159 (22.7) 234 (33.4) 142 (20.3) 61 (8.6) 101 (14.4) 4 (0.6)
427 (61.0) 273 (38.9) 1 (0.1)
634 (90.4) 26 (3.7) 41 (5.9)
No DR 630
8 (1.3) 622 (98.7)
52 (36-72)
165 (26.2) 209 (33.2) 104 (16.5) 75 (11.9) 8 (1.3)
38 (6.0) 31 (4.9)
76 (12.1) 227 (36.0) 295 (46.8) 32 (5.1)
268 (42.5) 236 (37.5) 70 (11.1) 40 (6.3) 16 (2.6)
526 (83.5) 49 (7.8) 3 (0.5) 38 (6.0) 14 (2.2)
14 (2.2) 238 (37.8) 365 (57.9) 13 (2.1)
149 (23.7) 201 (31.9) 137 (21.7) 58 (9.2) 82 (13.0) 3 (0.5)
392 (62.2) 238 (37.8) -
569 (90.3) 22 (3.5) 39 (6.2)
DR 71
3 (4.2) 68 (95.8)
52 (37-76)
8 (11.3) 16 (22.5) 21 (29.6) 10 (14.1) 1 (1.4)
6 (8.4) 9 (12.7)
4 (5.6) 18 (25.4) 47 (66.2) 2 (2.8)
19 (26.8) 32 (45.1) 7 (9.8) 8 (11.3) 5 (7.0)
54 (76.1) 7 (9.9) 1 (1.4) 6 (8.4) 3 (4.2)
-
26 (36.6) 44 (62.0) 1 (1.4)
10 (14.1) 33 (46.5) 5 (7.0) 3 (4.2) 19 (26.8) 1 (1.4)
35 (49.3) 35 (49.3) 1 (1.4)
65 (91.6) 4 (5.6) 2 (2.8)
P
0.091
0.893
0.037$
0.011
0.020+
0.193&
0.550£
<0.001
0.047
0.402
Data are presented as number (percentage).P is statistical significance by Pearson’s χ2 test (or by Mann-Whitney test for age) for comparison between patients with disease recurrence (DR) and without relapse (no DR).$χ2 test performed on clustered groups (stage 1/2/3).+χ2 test per- formed on clustered groups (N0 vs.N1,N2,N3).&χ2 test performed on clustered groups (ductal vs. others). £χ2 test performed on clustered groups (G1/G2 vs. G3). HER2: human epidermal growth factor receptor 2; ECOG-PS: Eastern Cooperative Oncology Group Performance Status; N: number; neg: negative; pos: positive.
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