Japanese Journal of Clinical Oncology, 2015, 45(8) 713–718 doi: 10.1093/jjco/hyv067 Advance Access Publication Date: 15 May 2015 Original Article
Original Article
Prolonged survival after diagnosis of brain metastasis from breast cancer: contributing factors and treatment implications Downloaded from http://jjco.oxfordjournals.org/ at Florida International University on November 17, 2015
Yayoi Honda*, Tomoyuki Aruga, Toshinari Yamashita, Hiromi Miyamoto, Kazumi Horiguchi, Dai Kitagawa, Nami Idera, Risa Goto, and Katsumasa Kuroi Division of Breast Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan *For reprints and all correspondence: Yayoi Honda, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8677, Japan. E-mail: [email protected] Received 31 January 2015; Accepted 7 April 2015
Abstract Objective: The prognosis of breast cancer-derived brain metastasis is poor, but new drugs and recent therapeutic strategies have helped extend survival in patients. Prediction of therapeutic responses and outcomes is not yet possible, however. In a retrospective study, we examined prognostic factors in patients with breast cancer-derived brain metastasis, and we tested the prognostic utility of a breast cancer-specific Graded Prognostic Assessment in these patients. Methods: Sixty-three patients diagnosed with brain metastasis from breast cancer treated surgically and adjuvantly were included. We examined clinical variables per primary tumor subtype: ER+/HER2 − (luminal), HER2+ (human epidermal growth factor receptor type 2-enriched) or ER−/PR−/HER2− (triple negative). We also categorized patients’ breast cancer-specific Graded Prognostic Assessment scores and analyzed post-brain metastasis survival time in relation to these categories. Results: The breast cancers comprised the following subtypes: luminal, n = 18; human epidermal growth factor receptor type 2-enriched, n = 27 and triple-negative, n = 18; median survival per subtype was 11, 37 and 3 months, respectively. Survival of human epidermal growth factor receptor type 2-enriched patients was longer, though not significantly (P = 0.188), than that of luminal patients. Survival of triple-negative patients was significantly short (vs. human epidermal growth factor receptor type 2-enriched patients, P < 0.001). Karnofsky performance status, HER2 status and the disease-free interval (from initial treatment to first recurrence) were shown to be significant prognostic factors (Karnofsky performance status < 70: relative risk 2.08, P = 0.028; HER2+: relative risk 2.911, P = 0.004; disease-free interval < 24 months: relative risk 1.933, P = 0.011). Breast cancer-specific Graded Prognostic Assessment scores reflected disease-free intervals and survival times. Conclusions: Our data indicate that breast cancer-specific Graded Prognostic Assessment-based prediction will be helpful in determining appropriate therapeutic strategies for patients with brain metastasis from breast cancer. Key words: breast cancer, brain metastasis, retrospective study, subtype, prognostic factor, breast cancer-specific GPA
© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected]
713
714
Survival after diagnosis of brain metastasis
Introduction
Patients and methods Patients Between 2000 and 2012, 2673 patients were treated surgically for breast cancer at the Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital. BM from breast cancer was diagnosed in 63 of these patients (not including patients with Stage IV breast cancer). In all 63 cases, the primary tumor was identified pathologically as an invasive ductal carcinoma or invasive lobular carcinoma, and patients had undergone radical surgery and had received appropriate adjuvant therapy. Estrogen receptor (ER) expression was determined by immunohistochemistry (IHC), and ER positivity was defined as 1% or more ER-positive cells. Human epidermal growth factor receptor type 2 (HER2) expression was evaluated by means of IHC or fluorescent in situ hybridization (FISH), and tumors with a respective score of 3+ or a >2.0-fold increase in HER2 gene expression were considered positive for HER2. The primary tumor was classified by subtype as ER+/HER2− (luminal), ER+ or ER−/HER2+ (HER2-enriched [HER2-E]) or ER−/PR−/HER2− (TN or basal-like) breast cancer. BM was diagnosed by magnetic resonance imaging (MRI) or computed tomography (CT). The study was approved by the research ethics committee of Komagome Hospital.
Data obtained The following data were obtained from the patients’ online medical records: age at the time of initial treatment for breast cancer, TN status, ER and HER2 statuses of the primary tumor, follow-up time, the disease-free interval (DFI) from the time of initial treatment of breast cancer to the first recurrence (≥2 years vs.
Original Article
Prolonged survival after diagnosis of brain metastasis from breast cancer: contributing factors and treatment implications Downloaded from http://jjco.oxfordjournals.org/ at Florida International University on November 17, 2015
Yayoi Honda*, Tomoyuki Aruga, Toshinari Yamashita, Hiromi Miyamoto, Kazumi Horiguchi, Dai Kitagawa, Nami Idera, Risa Goto, and Katsumasa Kuroi Division of Breast Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan *For reprints and all correspondence: Yayoi Honda, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8677, Japan. E-mail: [email protected] Received 31 January 2015; Accepted 7 April 2015
Abstract Objective: The prognosis of breast cancer-derived brain metastasis is poor, but new drugs and recent therapeutic strategies have helped extend survival in patients. Prediction of therapeutic responses and outcomes is not yet possible, however. In a retrospective study, we examined prognostic factors in patients with breast cancer-derived brain metastasis, and we tested the prognostic utility of a breast cancer-specific Graded Prognostic Assessment in these patients. Methods: Sixty-three patients diagnosed with brain metastasis from breast cancer treated surgically and adjuvantly were included. We examined clinical variables per primary tumor subtype: ER+/HER2 − (luminal), HER2+ (human epidermal growth factor receptor type 2-enriched) or ER−/PR−/HER2− (triple negative). We also categorized patients’ breast cancer-specific Graded Prognostic Assessment scores and analyzed post-brain metastasis survival time in relation to these categories. Results: The breast cancers comprised the following subtypes: luminal, n = 18; human epidermal growth factor receptor type 2-enriched, n = 27 and triple-negative, n = 18; median survival per subtype was 11, 37 and 3 months, respectively. Survival of human epidermal growth factor receptor type 2-enriched patients was longer, though not significantly (P = 0.188), than that of luminal patients. Survival of triple-negative patients was significantly short (vs. human epidermal growth factor receptor type 2-enriched patients, P < 0.001). Karnofsky performance status, HER2 status and the disease-free interval (from initial treatment to first recurrence) were shown to be significant prognostic factors (Karnofsky performance status < 70: relative risk 2.08, P = 0.028; HER2+: relative risk 2.911, P = 0.004; disease-free interval < 24 months: relative risk 1.933, P = 0.011). Breast cancer-specific Graded Prognostic Assessment scores reflected disease-free intervals and survival times. Conclusions: Our data indicate that breast cancer-specific Graded Prognostic Assessment-based prediction will be helpful in determining appropriate therapeutic strategies for patients with brain metastasis from breast cancer. Key words: breast cancer, brain metastasis, retrospective study, subtype, prognostic factor, breast cancer-specific GPA
© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected]
713
714
Survival after diagnosis of brain metastasis
Introduction
Patients and methods Patients Between 2000 and 2012, 2673 patients were treated surgically for breast cancer at the Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital. BM from breast cancer was diagnosed in 63 of these patients (not including patients with Stage IV breast cancer). In all 63 cases, the primary tumor was identified pathologically as an invasive ductal carcinoma or invasive lobular carcinoma, and patients had undergone radical surgery and had received appropriate adjuvant therapy. Estrogen receptor (ER) expression was determined by immunohistochemistry (IHC), and ER positivity was defined as 1% or more ER-positive cells. Human epidermal growth factor receptor type 2 (HER2) expression was evaluated by means of IHC or fluorescent in situ hybridization (FISH), and tumors with a respective score of 3+ or a >2.0-fold increase in HER2 gene expression were considered positive for HER2. The primary tumor was classified by subtype as ER+/HER2− (luminal), ER+ or ER−/HER2+ (HER2-enriched [HER2-E]) or ER−/PR−/HER2− (TN or basal-like) breast cancer. BM was diagnosed by magnetic resonance imaging (MRI) or computed tomography (CT). The study was approved by the research ethics committee of Komagome Hospital.
Data obtained The following data were obtained from the patients’ online medical records: age at the time of initial treatment for breast cancer, TN status, ER and HER2 statuses of the primary tumor, follow-up time, the disease-free interval (DFI) from the time of initial treatment of breast cancer to the first recurrence (≥2 years vs.
