Original Article
Efficiency and prognosis of whole brain irradiation combined with precise radiotherapy on triple-negative breast cancer ABSTRACT Aim: To investigate the treatment efficiency of whole brain irradiation combined with precise radiotherapy on triple-negative (TN) phenotype breast cancer patients with brain metastases and their survival times. Materials and Methods: A total of 112 metastatic breast cancer patients treated with whole brain irradiation and intensity modulated radiotherapy (IMRT) or 3D conformal radiotherapy (3DCRT) were analyzed. Thirty-seven patients were of TN phenotype. Objective response rates were compared. Survival times were estimated by using the Kaplan–Meier method. Log-rank test was used to compare the survival time difference between the TN and non-TN groups. Potential prognostic factors were determined by using a Cox proportional hazard regression model. Results: The efficiency of radiotherapy treatment on TN and non-TN phenotypes was 96.2% and 97%, respectively. TN phenotype was associated with worse survival times than non-TN phenotype after radiotherapy (6.9 months vs. 17 months) (P < 0.01). On multivariate analysis, good prognosis was associated with non-TN status, lower graded prognosis assessment class, and nonexistence of active extracranial metastases. Conclusion: After whole brain irradiation followed by IMRT or 3DCRT treatment, TN phenotype breast cancer patients with intracranial metastasis had high objective response rates but shorter survival time. With respect to survival in breast cancer patients with intracranial metastasis, the TN phenotype represents a significant adverse prognostic factor. KEY WORDS: Breast cancer, brain metastases, precise radiotherapy, triple negative
INTRODUCTION Brain metastases from breast cancer are very common. Whole brain radiotherapy combined with tumor bed boost by means of precise radiotherapy, such as intensity modulated radiotherapy (IMRT) or 3D conformal radiotherapy (3DCRT), has become a common palliative treatment of metastatic breast cancer patient. Triple-negative (TN) breast cancer brain metastasis has overall poor prognosis and short survival time. Effect and prognosis of whole brain radiotherapy combined with precise radiation therapy on these cases has not been reported so far. In this study, we conducted a retrospective analysis of the clinical data of metastatic breast cancer patients who received precise radiotherapy with whole brain irradiation. Treatment efficiency, survival time, and prognosis of precise radiotherapy of brain cancer metastasis are discussed to help the oncologists choose the optimal treatment strategy. MATERIALS AND METHODS A retrospective analysis of 112 patients with brain metastases from breast cancer who were treated
during April 2004-April 2009 was done. These patients met the following criteria: (1) Pathological diagnosis of breast cancer; (2) brain metastases were confirmed by magnetic resonance imaging (MRI) or computed tomography (CT), with brain metastases not more than five; (3) hormone receptor status and human epidermal growth factor receptor 2 (HER2) status was definite; (4) clear date of death; (5) the patients underwent whole brain radiotherapy and precise radiotherapy after diagnosis. Estrogen receptor (ER)-, progesterone receptor (PR)-negative and HER2 non-overexpressed is defined as a triple-negative breast cancer (TNBC), otherwise defined as non-TNBC. ER-, PR-, and HER2-positive diagnostic criteria are as follows. If less than 1% of the nucleus is shown to be positive by the ER or PR immunohistochemical staining, the tumor ER or PR is considered to be negative. If HER2 gene amplification is not displayed under fluorescence hybridization in situ or immunohistochemical staining specimen’s score is less than 3+ (>10% of the cell membrane staining is strongly positive), the tumor is considered to be HER2-negative. There were 37 cases of TNBC and 75 cases of non-TNBC among the patients. The median age at
Journal of Cancer Research and Therapeutics - Supplement 3 - 2013 - Volume 9
Xinhong Wu, Bo Luo1, Shaozhong Wei2, Yan Luo1, Yaojun Feng, Juan Xu, Wei Wei1 Departments of Breast Cancer and 1 Radiotherapy, Hubei Cancer Hospital, 2 Department of Epidemiology, Hubei Cancer Research Institute, Wuhan, China For correspondence: Dr. Bo Luo, Department of Radiotherapy, Hubei Cancer Hospital, 116 Zhuodaoquan South Road, Hongshan District, Wuhan, China 430079. E-mail: luobohb@163. com
Access this article online Website: www.cancerjournal.net DOI: 10.4103/0973-1482.122518 PMID: *** Quick Response Code:
S167
Wu, et al.: Brain precise radiotherapy in triple-negative breast cancer
diagnosis of breast cancer was 45 years and the mean age was 46 years (range 24-73 years). Patients received complementary treatment, including chemotherapy and radiotherapy.
Table 1: Clinical characteristics of TNBC and non-TNBC patients
Clinical target volume (CTV) was expanded to planning target volume (PTV) in 2-3 mm margin after outline gross tumor volume (GTV) and CTV. Also, 6 MV X-ray was used for whole brain radiotherapy. The patients were fixed by mask in supine position. They received whole brain radiation of 2 Gy/day, 5 times/week, total Dt 30-40 Gy in 3DCRT or IMRT local boost. 3DCRT or IMRT dose was 23.5 Gy, with a median dose of 24 Gy, Dt 2-4 Gy/day, 5 times/week. The dose to brain stem, eye, and other organs at risk was controlled within the safe range. One and 3 months after radiotherapy, MR was reviewed. The patients were followed up once in every 3 months. Term effect was evaluated on RECIST 1.1. Intracranial local control time was calculated from the first cranial irradiation day, and the survival time started from the day of brain metastases diagnosis.
n Age, years Median Range Stage I II III IV Control of extracranial lesion No Yes GPA 0-1.0 1.5-2.5 3 3.5-4.0 Chemotherapy Yes None KPS 100 90 80 70 60 Number of intracranial lesions 1 ≥2 Intracranial lesion location Supratentorial Infratentorial Supratentorial and infratentorial Brain stem Treatment modality WBRT+IMRT WBRT+3DCRT
Statistical analysis Survival and local control rates were calculated through the Kaplan–Meier analysis. Cox regression model was used to determine the impact of independent prognostic factors on the survival of metastatic breast cancer by univariate and multivariate analyses. 2 test or Fisher’s exact test was applied to compare categorical variables between groups. RESULTS Clinical features of patients One hundred and twelve cases of breast cancer with brain metastases were studied. There was no difference in age between the TN group and the non-TN group. TNM staging (Fisher’s exact test), Karnofsky performance score (KPS) at diagnosis, and the number and location of brain metastases did not show significant difference as well [Table 1]. From the onset to diagnosis of brain metastasis, the median time was 35 months (range 0-377 months) (26 months in the TN group and 36 months in the non-TN group) (log-rank test, P = 0.442). Local control Patients were followed up until death or the end of the study. The median follow-up time was 19 months (range 3-48) months and three cases were lost to follow-up. After 1 month of administering radiotherapy, the remission rate was reviewed. Results are as follows: In TNBC group: complete response (CR) 10 cases, PR 16 cases, SD 10 cases, PD 1 case, the control rate 96.2% (36/37); non-TN group: CR 19 cases, PR 33 cases, SD 21 cases, PD 2 cases, the control rate 97.0% (73/75), which showed no significant difference (2 = 4.5, P > 0.05). Tumor local control rates of TNBC group and non-TN group at 6, 12, and 24 months were 96.1%, 89.7%, and 79.3%, and 96.6%, 91.1%, and 87.3% respectively, which showed no difference between the two groups (log-rank test, P = 0.755). S168
Clinical characteristics
n 112
TN group 37
Non-TN group 75
45 28-73
44 28-71
49 29-73
9 29 49 18
2 10 19 6
8 21 32 14
32 63
15 21
24 51
17 50 22 6
4 17 12 7
16 37 17 5
31 64
17 20
23 52
6 21 31 27 8
2 4 10 16 5
6 21 26 16 8
24 71
11 26
21 54
58 17 18 2
22 8 6 1
43 13 15 1
14 23
26 49
P 0.167 0.062
0.056 0.770
0.093
0.460 0.335
0.070
P
Efficiency and prognosis of whole brain irradiation combined with precise radiotherapy on triple-negative breast cancer ABSTRACT Aim: To investigate the treatment efficiency of whole brain irradiation combined with precise radiotherapy on triple-negative (TN) phenotype breast cancer patients with brain metastases and their survival times. Materials and Methods: A total of 112 metastatic breast cancer patients treated with whole brain irradiation and intensity modulated radiotherapy (IMRT) or 3D conformal radiotherapy (3DCRT) were analyzed. Thirty-seven patients were of TN phenotype. Objective response rates were compared. Survival times were estimated by using the Kaplan–Meier method. Log-rank test was used to compare the survival time difference between the TN and non-TN groups. Potential prognostic factors were determined by using a Cox proportional hazard regression model. Results: The efficiency of radiotherapy treatment on TN and non-TN phenotypes was 96.2% and 97%, respectively. TN phenotype was associated with worse survival times than non-TN phenotype after radiotherapy (6.9 months vs. 17 months) (P < 0.01). On multivariate analysis, good prognosis was associated with non-TN status, lower graded prognosis assessment class, and nonexistence of active extracranial metastases. Conclusion: After whole brain irradiation followed by IMRT or 3DCRT treatment, TN phenotype breast cancer patients with intracranial metastasis had high objective response rates but shorter survival time. With respect to survival in breast cancer patients with intracranial metastasis, the TN phenotype represents a significant adverse prognostic factor. KEY WORDS: Breast cancer, brain metastases, precise radiotherapy, triple negative
INTRODUCTION Brain metastases from breast cancer are very common. Whole brain radiotherapy combined with tumor bed boost by means of precise radiotherapy, such as intensity modulated radiotherapy (IMRT) or 3D conformal radiotherapy (3DCRT), has become a common palliative treatment of metastatic breast cancer patient. Triple-negative (TN) breast cancer brain metastasis has overall poor prognosis and short survival time. Effect and prognosis of whole brain radiotherapy combined with precise radiation therapy on these cases has not been reported so far. In this study, we conducted a retrospective analysis of the clinical data of metastatic breast cancer patients who received precise radiotherapy with whole brain irradiation. Treatment efficiency, survival time, and prognosis of precise radiotherapy of brain cancer metastasis are discussed to help the oncologists choose the optimal treatment strategy. MATERIALS AND METHODS A retrospective analysis of 112 patients with brain metastases from breast cancer who were treated
during April 2004-April 2009 was done. These patients met the following criteria: (1) Pathological diagnosis of breast cancer; (2) brain metastases were confirmed by magnetic resonance imaging (MRI) or computed tomography (CT), with brain metastases not more than five; (3) hormone receptor status and human epidermal growth factor receptor 2 (HER2) status was definite; (4) clear date of death; (5) the patients underwent whole brain radiotherapy and precise radiotherapy after diagnosis. Estrogen receptor (ER)-, progesterone receptor (PR)-negative and HER2 non-overexpressed is defined as a triple-negative breast cancer (TNBC), otherwise defined as non-TNBC. ER-, PR-, and HER2-positive diagnostic criteria are as follows. If less than 1% of the nucleus is shown to be positive by the ER or PR immunohistochemical staining, the tumor ER or PR is considered to be negative. If HER2 gene amplification is not displayed under fluorescence hybridization in situ or immunohistochemical staining specimen’s score is less than 3+ (>10% of the cell membrane staining is strongly positive), the tumor is considered to be HER2-negative. There were 37 cases of TNBC and 75 cases of non-TNBC among the patients. The median age at
Journal of Cancer Research and Therapeutics - Supplement 3 - 2013 - Volume 9
Xinhong Wu, Bo Luo1, Shaozhong Wei2, Yan Luo1, Yaojun Feng, Juan Xu, Wei Wei1 Departments of Breast Cancer and 1 Radiotherapy, Hubei Cancer Hospital, 2 Department of Epidemiology, Hubei Cancer Research Institute, Wuhan, China For correspondence: Dr. Bo Luo, Department of Radiotherapy, Hubei Cancer Hospital, 116 Zhuodaoquan South Road, Hongshan District, Wuhan, China 430079. E-mail: luobohb@163. com
Access this article online Website: www.cancerjournal.net DOI: 10.4103/0973-1482.122518 PMID: *** Quick Response Code:
S167
Wu, et al.: Brain precise radiotherapy in triple-negative breast cancer
diagnosis of breast cancer was 45 years and the mean age was 46 years (range 24-73 years). Patients received complementary treatment, including chemotherapy and radiotherapy.
Table 1: Clinical characteristics of TNBC and non-TNBC patients
Clinical target volume (CTV) was expanded to planning target volume (PTV) in 2-3 mm margin after outline gross tumor volume (GTV) and CTV. Also, 6 MV X-ray was used for whole brain radiotherapy. The patients were fixed by mask in supine position. They received whole brain radiation of 2 Gy/day, 5 times/week, total Dt 30-40 Gy in 3DCRT or IMRT local boost. 3DCRT or IMRT dose was 23.5 Gy, with a median dose of 24 Gy, Dt 2-4 Gy/day, 5 times/week. The dose to brain stem, eye, and other organs at risk was controlled within the safe range. One and 3 months after radiotherapy, MR was reviewed. The patients were followed up once in every 3 months. Term effect was evaluated on RECIST 1.1. Intracranial local control time was calculated from the first cranial irradiation day, and the survival time started from the day of brain metastases diagnosis.
n Age, years Median Range Stage I II III IV Control of extracranial lesion No Yes GPA 0-1.0 1.5-2.5 3 3.5-4.0 Chemotherapy Yes None KPS 100 90 80 70 60 Number of intracranial lesions 1 ≥2 Intracranial lesion location Supratentorial Infratentorial Supratentorial and infratentorial Brain stem Treatment modality WBRT+IMRT WBRT+3DCRT
Statistical analysis Survival and local control rates were calculated through the Kaplan–Meier analysis. Cox regression model was used to determine the impact of independent prognostic factors on the survival of metastatic breast cancer by univariate and multivariate analyses. 2 test or Fisher’s exact test was applied to compare categorical variables between groups. RESULTS Clinical features of patients One hundred and twelve cases of breast cancer with brain metastases were studied. There was no difference in age between the TN group and the non-TN group. TNM staging (Fisher’s exact test), Karnofsky performance score (KPS) at diagnosis, and the number and location of brain metastases did not show significant difference as well [Table 1]. From the onset to diagnosis of brain metastasis, the median time was 35 months (range 0-377 months) (26 months in the TN group and 36 months in the non-TN group) (log-rank test, P = 0.442). Local control Patients were followed up until death or the end of the study. The median follow-up time was 19 months (range 3-48) months and three cases were lost to follow-up. After 1 month of administering radiotherapy, the remission rate was reviewed. Results are as follows: In TNBC group: complete response (CR) 10 cases, PR 16 cases, SD 10 cases, PD 1 case, the control rate 96.2% (36/37); non-TN group: CR 19 cases, PR 33 cases, SD 21 cases, PD 2 cases, the control rate 97.0% (73/75), which showed no significant difference (2 = 4.5, P > 0.05). Tumor local control rates of TNBC group and non-TN group at 6, 12, and 24 months were 96.1%, 89.7%, and 79.3%, and 96.6%, 91.1%, and 87.3% respectively, which showed no difference between the two groups (log-rank test, P = 0.755). S168
Clinical characteristics
n 112
TN group 37
Non-TN group 75
45 28-73
44 28-71
49 29-73
9 29 49 18
2 10 19 6
8 21 32 14
32 63
15 21
24 51
17 50 22 6
4 17 12 7
16 37 17 5
31 64
17 20
23 52
6 21 31 27 8
2 4 10 16 5
6 21 26 16 8
24 71
11 26
21 54
58 17 18 2
22 8 6 1
43 13 15 1
14 23
26 49
P 0.167 0.062
0.056 0.770
0.093
0.460 0.335
0.070
P
