2.1 Baseline patient information
Totally 323 cases of breast cancer with HH were enrolled (table 1). Among them, 238 cases were HR+, with a median age of 46.07±8.08 years, and 85 were HR-, with a median age of 46.73±8.16 years. TNM staging of breast cancer was performed, and most cases were stage II. There were 130 stage II cases (54.62%) in the HR+ group, and 44 (51.76%) in the HR- group (P=0.419). A total of 125 patients (52.52%) had lymph node metastasis in the HR+ group, versus 47 (55.29%) in the HR- group (P=0.660). HH generally presented as single lesions, including 193 (81.09%) and 67 (78.82%) cases in the HR+ and hr- groups, respectively (P=0.650). They were mostly found in the right lobe of the liver (71.85%) versus （27.73%） in the left lobe. There were 171 (71.85%) and 57 (67.06%) cases of HH in the right lobe of the liver in the HR+ and hr- groups, respectively (P=0.650). The selection of the chemotherapy regimen for breast cancer was mainly based on the NCCN guidelines. The most commonly used chemotherapy regimen was epirubicin plus cyclophosphamide with sequential paclitaxel, which was administered in 164 patients (68.91%) of the HR+ group, versus 50 (58.82%) in the hr- group (P=0.531). The initial time of HH diagnosis was before and during chemotherapy in 207 (86.97%) cases of the HR+ group, versus 74 (87.06%) in the HR- group. There were 17 cases (7.14%) of HH in the HR+ group diagnosed after chemotherapy, versus 8 (9.14%) in the HR- group (P=0.584). The enrolled patients were followed up by outpatient review or via the hospital’s medical records until July 1, 2019, at a follow-up frequency of 3 months. The drugs used for endocrine therapy in the HR+ group included tamoxifen, AI (letrozole, anastrozole, and exemestane), fulvestrant and ovarian function inhibitors. Endocrine therapy for breast cancer was based on NCCN guidelines for drug selection. A total of 127 patients (53.36%) were treated with tamoxifen only, 86 (36.13%) were administered AI only, and other treatments were used in 25 patients (10.5%).
2.2 Size change of HH at different time points
Of all the enrolled cases, 221 (65.3%) of HH were found before systematic treatment. During the treatment of breast cancer, a total of 84 patients (26%) had HH during chemotherapy. In addition, less patients developed HH during endocrine drug therapy after a comprehensive treatment of breast cancer, accounting for 28 cases (8.7%). The enrolled breast cancer patients with HH were divided into the experimental (HR+) and control (hr-) groups, and size changes of HH at 14 treatment time points (t1-t14) were analyzed, as shown in table 2. The time of initial diagnosis of HH was considered the first time point (t1), and the time of each detection of HH sequentially corresponded to the respective time point until t14. In some patients, the absence of ultrasound and CT examinations may lead to data loss. The t1 time point was used as the baseline, and cases with no missing data for HH at t1 were included in the analysis. The time points from t1 to t8 comprised the stages of chemotherapy and surgery, with an interval of 21 days. The time points from t9 to t14 encompassed the period of endocrine therapy, with an interval of 6 months.
As shown in Figure 1A and B, HH in the experimental group showed a decreasing trend in size after comprehensive breast cancer treatment, while that of the control group showed no overall decreasing trend. All P values were greater than 0.05, indicating no statistical significance.
2.3 Size changes of HH at different time points
The sizes of HH in the experimental group varied at different treatment time points (Figure 2A and 2B. As shown in Figure 2A, size (longest diameter) changes of HH between the experimental and control groups had no obvious differences (P>0.05). In Figure 2B, a significant difference was obtained at t12 in size change for HH between the experimental and control groups, when the long diameter × short diameter was considered (P=0.049). However, the other time points showed no statistically significant differences between the two groups.
2.4 Relationship between axillary lymph node metastasis and size change of HH
In breast cancer patients with or without axillary lymph node metastasis, once the diagnosis is confirmed, there are certain differences in the selection of therapeutic schedules. In those with axillary lymph node metastasis, chemotherapy regimens and cycle time are more intensive and longer, respectively, compared with those of cases without axillary lymph node metastasis; in addition, the selection of chemotherapy drugs and subsequent endocrine drugs also shows differences. As shown in Figure 3, in both the experimental and control groups, the sizes of HH showed a decreasing trend after the comprehensive treatment of breast cancer at the later time point of t10. However, whether or not axillary lymph node metastasis was present, the longest diameter (Figure 3A, 3B) and (long diameter × short diameter) (Figure 3B, 3D) showed no significant differences between the experimental and control groups.
2.5 relationship between occurrence time and the size change of HH
Most breast cancer patients require chemotherapy because of the invasiveness of breast malignant tumors. according to different occurrence time points of HH in confirmed breast cancer patients administered chemotherapy, the enrolled cases were divided into two groups, with occurrence before or during and after chemotherapy, respectively. Therefore, the patients with HH detected before the initial treatment of breast cancer and those with new HH during chemotherapy were assigned to the “during chemotherapy” group, and cases still with HH and those with new HH after chemotherapy constituted the “after chemotherapy” group. Both groups were compared in Figure 4.
The results showed that HH did not decrease in size significantly during chemotherapy, but also had no increasing trend, tending to be stable. Based on long diameter, the HH were significantly smaller after chemotherapy than during chemotherapy, and the difference between the two groups was significant (P<0.001; Figure 4A and C). In Figure 4B and D, the difference in the size change of HH based on long diameter × short diameter was significantly larger after chemotherapy than during chemotherapy.
2.6 Relationship between endocrine therapy and the size of HH
Endocrine drug treatment is used for subsequent maintenance therapy in HR+ breast cancer patients, with tamoxifen and AI as the first-line drugs . Patient data obtained by follow-up were grouped for statistical analysis. Patients treated with tamoxifen only were assigned to one group; those administered AI only were assigned to another group, and cases treated with combined or sequential use of other endocrine drugs (including tamoxifen + ovarian function inhibitors, tamoxifen sequential AI, fulvestrant, etc.) formed the third group. The experimental results are shown in Figure 5. Compared with the other two groups, patients treated with AI endocrine drugs at t10 showed a statistically significant difference (P<0.05; Figure 5A). The other endocrine drugs at t10 and t11 also showed statistically significant differences (P<0.05), but there were no differences between the whole group and the other two groups (figure 5C). There were no differences among groups based on long diameter × short diameter (Figure 5B and D).
2.7 changes in various groups between t14 and t1
HR positivity, axillary lymph node metastasis, hemangioma occurrence before or after chemotherapy, and the effects of different endocrine drugs on the size of HH at t14 and t1 (Table 3) showed no differences in the “other” group. There was a significant difference in hemangioma size determined as longest diameter between patients treated with AI endocrine drugs and the other two groups, while the tamoxifen group showed no difference compared to the other two groups.