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Findings from ipsilateral breast tumor recurrence after breast-conserving surgery of 4065 cases at our hospital
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Poster Abstracts II / The Breast 32S1 (2017) S78–S132
many human solid tumors including breast cancer and is known to promote cancer progression. The aims of this study were to analyze whether the expression of CD73 is associated with a particular molecular subtype of breast cancer and to evaluate prognostic significance of CD73 expression. Methods: Specimens from 114 patients with primary breast cancer were enrolled, and representative paraffin tumor blocks were selected for constructing tissue microarrarys (TMA). Immunohistochemical staining for CD73 was performed using TMA. We compared the expression of CD73 across the molecular subtypes of breast cancer and correlated it with clinicopathological characteristics. Results: The average age was 50.85 ± 10.91 with a range of 26–78. 112 cases accounted for invasive ductal carcinoma, and 2 cases were invasive medullary carcinoma and metaplastic carcinoma. Positive expression rate of CD73 was 30.6%. Our analysis revealed positive expression of CD73 was significantly associated with molecular subtypes of breast cancer ( p = 0.035), specifically CD73 expression was significantly lower in the HER2 subtype. When all cases were stratified by molecular subtypes, CD73 expression was significantly associated with tumor size and histologic grade ( p = 0.025 and 0.043, respectively) in luminal type breast cancer. Survival analysis across the molecular subtypes showed no significant association between CD73 expression and survival. We also found that CD73 expression was correlated with tumor size and positive expression of progesterone receptor ( p = 0.030 and 0.008, respectively) for all cases. Correlation between CD73 and other immunohistochemical markers showed that CD73 expression was associated with leptin and leptin receptor expression ( p = 0.001 and 0.016, respectively). The diseasefree survival (DFS) and overall survival (OS) rate at 5 years were 86.4% and 95.1%, respectively. There was no difference in DFS and OS based on CD73 expression. Conclusion: Our study showed that CD73 expression was associated with molecular subtypes of breast cancer. Further studies are needed to clarify the role of CD73 in breast cancer. Disclosure of Interest: No significant relationships. P221 Notch-4 is a novel therapeutic target and prognostic marker for triple negative breast cancer M. Kai*, H. Mori, M. Yamada, M. Kubo, M. Nakamura. Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan Background: Triple negative breast cancer (TNBC) accounts for approximately 15% of all breast cancers and is defined by absence of the estrogen receptor (ER) and progesterone receptor (PR), and no amplification of the human epidermal growth factor receptor 2 (HER2). TNBC is an aggressive breast cancer subtype that does not respond to targeted therapies, and patients with TNBC have a poorer prognosis than patients with hormone receptor-positive or HER2positive cancers. Our previous reports showed Notch-4 was activated in TNBC. Based on these findings, we determine the usefulness of Notch-4 as a therapeutic target and prognostic marker. Materials and methods: The TNBC cell lines (HCC1937, MDA-MB231) and non-TNBC cell lines (MCF7, BT474 and SK-BR-3) were used for the in vitro analysis. For the analysis of clinicopathological features and the biomarkers including Notch-4, 69 tissue samples which were surgically resected in Kyusyu University Hospital from 2004 to 2010 were used. Results: The mRNA expressions of Notch-4 in TNBC cell lines were higher than in non-TNBC cell lines. The invaded cells showed high protein expressions of Notch-4 and MMP9, and low expression of Ecadherin. The Notch inhibitor, γ-secretase, inhibited the invasive capacity of TNBC. In the clinical samples, the nuclear location rates of Notch-4 were highest in the TNBC compared to the other subtypes. In the prognostic analysis, the Notch-4 high group revealed significantly poorer overall survival compared to the Notch-4 low group ( p < 0.05).
Discussion: In our previous studies, Notch-4 was highly activated in TNBC [Nagamatsu et. al. Ancticancer Res. 34: 69–80 (2014)]. In our current study, Notch-4 may have a role for the invasion of TNBC and be a potential therapeutic target. Furthermore, Notch-4 could be a prognostic marker for the TNBC. Conclusion: Notch-4 could offer a new targeted therapeutic strategy and warrants prognostic marker for TNBC. Disclosure of Interest: No significant relationships. P222 Findings from ipsilateral breast tumor recurrence after breastconserving surgery of 4065 cases at our hospital Y. Kajiwara*, S. Ohtani, T. Kin, M. Fujihara, Y. Yoshimura, M. Ito. Department of Breast Surgery, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan Background: Breast-conserving surgery is the standard treatment for early-stage breast cancer, with similar long-term overall survival to mastectomy. However, it is common for patients with ipsilateral breast tumor recurrence (IBTR) after initial surgery to develop systemic recurrence. Data on the recommendation of systemic treatment for IBTR are limited. Therefore, we recommend systemic treatment according to the IBTR subtype on immunohistochemical staining for patients with completely resected IBTR. Aims: Herein, we evaluated the IBTR pattern after breast-conserving surgery in each subtype of primary breast cancer and the difference in distant disease-free survival (DDFS) among IBTR subtypes. Methods: We retrospectively reviewed the medical records of 4065 breast cancer patients who underwent breast-conserving surgery between 1992 and 2014 at our hospital. Overall, 130 patients developed IBTR for the first time, without evidence of synchronous metastatic disease, and underwent salvage surgery. We retrospectively analyzed the time interval from initial surgery to IBTR (TTI) and DDFS in every subtype. Results: The IBTR rate was 3.20%, and the median TTI was 47 months. There was a significant difference in TTI according to hormone receptor and HER2 status. The patients with hormone receptor status negative ( positive: 54 months vs negative: 35 months p = 0.02) and HER2 status positive ( positive: 27 months vs negative: 40 months p = 0.002) developed IBTR early. TTI was within 5 years in 94% patients with primary breast cancer HER2 status positive. Systemic treatment after salvage surgery was recommended according to IBTR subtypes. In 15 DCIS patients, there was no recurrent without any adjuvant therapy. The 3- and 5-year DDFS rates for patients with hormone receptor status of IBTR positive (Luminal type) were 88% and 79%, respectively. Overall, 7/14 patients with hormone receptor and HER2 status of IBTR negative (triple negative type), despite adjuvant chemotherapy for IBTR, experienced distant recurrence. The 3- and 5-year DDFS rates were 58%. Additionally, 2/27 patients with HER2 status positive experienced distant recurrence. The 3- and 5-year DDFS rates were 92%. Therefore, in patients with IBTR, IBTR subtypes were also a predictive factor of distant recurrence. Conclusions: Our study suggests that the breast cancer subtype of IBTR predicts DDFS of patients with IBTR. Disclosure of Interest: No significant relationships. P223 Study of axillary lymph node staging based on a combined used of histology and one-step nucleic acid amplification method for breast cancer patients without axillary lymph node dissection T. Kinoshita*, T. Kurihara, K. Ogisawa, K. Jimbo, S. Shiino, S. Asaga, S. Takayama. National Cancer Center Hospital, Tokyo, Japan Aims: We developed the National Cancer Center–sentinel lymph node (SLN) metastatic score (NCS score) based on detailed evaluation of SLNs in breast cancer patients by a combined use of histology and one-step nucleic acid amplification (OSNA), to determine breast cancer patients in whom axillary lymph node dissection (ALND) can
Poster Abstracts II / The Breast 32S1 (2017) S78–S132
many human solid tumors including breast cancer and is known to promote cancer progression. The aims of this study were to analyze whether the expression of CD73 is associated with a particular molecular subtype of breast cancer and to evaluate prognostic significance of CD73 expression. Methods: Specimens from 114 patients with primary breast cancer were enrolled, and representative paraffin tumor blocks were selected for constructing tissue microarrarys (TMA). Immunohistochemical staining for CD73 was performed using TMA. We compared the expression of CD73 across the molecular subtypes of breast cancer and correlated it with clinicopathological characteristics. Results: The average age was 50.85 ± 10.91 with a range of 26–78. 112 cases accounted for invasive ductal carcinoma, and 2 cases were invasive medullary carcinoma and metaplastic carcinoma. Positive expression rate of CD73 was 30.6%. Our analysis revealed positive expression of CD73 was significantly associated with molecular subtypes of breast cancer ( p = 0.035), specifically CD73 expression was significantly lower in the HER2 subtype. When all cases were stratified by molecular subtypes, CD73 expression was significantly associated with tumor size and histologic grade ( p = 0.025 and 0.043, respectively) in luminal type breast cancer. Survival analysis across the molecular subtypes showed no significant association between CD73 expression and survival. We also found that CD73 expression was correlated with tumor size and positive expression of progesterone receptor ( p = 0.030 and 0.008, respectively) for all cases. Correlation between CD73 and other immunohistochemical markers showed that CD73 expression was associated with leptin and leptin receptor expression ( p = 0.001 and 0.016, respectively). The diseasefree survival (DFS) and overall survival (OS) rate at 5 years were 86.4% and 95.1%, respectively. There was no difference in DFS and OS based on CD73 expression. Conclusion: Our study showed that CD73 expression was associated with molecular subtypes of breast cancer. Further studies are needed to clarify the role of CD73 in breast cancer. Disclosure of Interest: No significant relationships. P221 Notch-4 is a novel therapeutic target and prognostic marker for triple negative breast cancer M. Kai*, H. Mori, M. Yamada, M. Kubo, M. Nakamura. Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan Background: Triple negative breast cancer (TNBC) accounts for approximately 15% of all breast cancers and is defined by absence of the estrogen receptor (ER) and progesterone receptor (PR), and no amplification of the human epidermal growth factor receptor 2 (HER2). TNBC is an aggressive breast cancer subtype that does not respond to targeted therapies, and patients with TNBC have a poorer prognosis than patients with hormone receptor-positive or HER2positive cancers. Our previous reports showed Notch-4 was activated in TNBC. Based on these findings, we determine the usefulness of Notch-4 as a therapeutic target and prognostic marker. Materials and methods: The TNBC cell lines (HCC1937, MDA-MB231) and non-TNBC cell lines (MCF7, BT474 and SK-BR-3) were used for the in vitro analysis. For the analysis of clinicopathological features and the biomarkers including Notch-4, 69 tissue samples which were surgically resected in Kyusyu University Hospital from 2004 to 2010 were used. Results: The mRNA expressions of Notch-4 in TNBC cell lines were higher than in non-TNBC cell lines. The invaded cells showed high protein expressions of Notch-4 and MMP9, and low expression of Ecadherin. The Notch inhibitor, γ-secretase, inhibited the invasive capacity of TNBC. In the clinical samples, the nuclear location rates of Notch-4 were highest in the TNBC compared to the other subtypes. In the prognostic analysis, the Notch-4 high group revealed significantly poorer overall survival compared to the Notch-4 low group ( p < 0.05).
Discussion: In our previous studies, Notch-4 was highly activated in TNBC [Nagamatsu et. al. Ancticancer Res. 34: 69–80 (2014)]. In our current study, Notch-4 may have a role for the invasion of TNBC and be a potential therapeutic target. Furthermore, Notch-4 could be a prognostic marker for the TNBC. Conclusion: Notch-4 could offer a new targeted therapeutic strategy and warrants prognostic marker for TNBC. Disclosure of Interest: No significant relationships. P222 Findings from ipsilateral breast tumor recurrence after breastconserving surgery of 4065 cases at our hospital Y. Kajiwara*, S. Ohtani, T. Kin, M. Fujihara, Y. Yoshimura, M. Ito. Department of Breast Surgery, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan Background: Breast-conserving surgery is the standard treatment for early-stage breast cancer, with similar long-term overall survival to mastectomy. However, it is common for patients with ipsilateral breast tumor recurrence (IBTR) after initial surgery to develop systemic recurrence. Data on the recommendation of systemic treatment for IBTR are limited. Therefore, we recommend systemic treatment according to the IBTR subtype on immunohistochemical staining for patients with completely resected IBTR. Aims: Herein, we evaluated the IBTR pattern after breast-conserving surgery in each subtype of primary breast cancer and the difference in distant disease-free survival (DDFS) among IBTR subtypes. Methods: We retrospectively reviewed the medical records of 4065 breast cancer patients who underwent breast-conserving surgery between 1992 and 2014 at our hospital. Overall, 130 patients developed IBTR for the first time, without evidence of synchronous metastatic disease, and underwent salvage surgery. We retrospectively analyzed the time interval from initial surgery to IBTR (TTI) and DDFS in every subtype. Results: The IBTR rate was 3.20%, and the median TTI was 47 months. There was a significant difference in TTI according to hormone receptor and HER2 status. The patients with hormone receptor status negative ( positive: 54 months vs negative: 35 months p = 0.02) and HER2 status positive ( positive: 27 months vs negative: 40 months p = 0.002) developed IBTR early. TTI was within 5 years in 94% patients with primary breast cancer HER2 status positive. Systemic treatment after salvage surgery was recommended according to IBTR subtypes. In 15 DCIS patients, there was no recurrent without any adjuvant therapy. The 3- and 5-year DDFS rates for patients with hormone receptor status of IBTR positive (Luminal type) were 88% and 79%, respectively. Overall, 7/14 patients with hormone receptor and HER2 status of IBTR negative (triple negative type), despite adjuvant chemotherapy for IBTR, experienced distant recurrence. The 3- and 5-year DDFS rates were 58%. Additionally, 2/27 patients with HER2 status positive experienced distant recurrence. The 3- and 5-year DDFS rates were 92%. Therefore, in patients with IBTR, IBTR subtypes were also a predictive factor of distant recurrence. Conclusions: Our study suggests that the breast cancer subtype of IBTR predicts DDFS of patients with IBTR. Disclosure of Interest: No significant relationships. P223 Study of axillary lymph node staging based on a combined used of histology and one-step nucleic acid amplification method for breast cancer patients without axillary lymph node dissection T. Kinoshita*, T. Kurihara, K. Ogisawa, K. Jimbo, S. Shiino, S. Asaga, S. Takayama. National Cancer Center Hospital, Tokyo, Japan Aims: We developed the National Cancer Center–sentinel lymph node (SLN) metastatic score (NCS score) based on detailed evaluation of SLNs in breast cancer patients by a combined use of histology and one-step nucleic acid amplification (OSNA), to determine breast cancer patients in whom axillary lymph node dissection (ALND) can