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Background: The peak age at diagnosis of breast cancer differs between patients in Asian countries (40 - 50 years), and those in Western countries (60 - 70 years). With the increasing use of screening mammography, the incidence of ductal carcinoma in situ (DCIS) has increased significantly in younger Asian women. Nevertheless, our knowledge of the clinicopathological features and prognosis in young patients with DCIS is relatively limited. We aimed to compare the clinicopathological features of younger patients with that of older patients with DCIS and to evaluate their prognostic factors.Methods: A total of 1445 women were diagnosed with DCIS between the years 2005 and 2015. Patients with the past history of breast cancer and managed without surgery were excluded. The young age group included patients Citation Format: Seki A, Matsuda N, Kajiura Y, Kobayashi D, Hayashi N, Tsunoda H, Suzuki K, Yoshida A, Takei J, Yamauchi H. Clinicopathological characteristics and prognosis of young patients with ductal carcinoma in situ [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-18-05.

Background: Lymphocyte predominant breast cancer subgroup, defined as ≥ 50% stromal tumor-infiltrating lymphocytes (sTILs), is associated with high pathological complete response (pCR) rate after neoadjuvant therapy (NAT) and favorable outcome. In a cohort of triple negative (TNBC) and HER2+ breast cancer (BC) patients treated with NAT, we aimed to assess the predictive and prognostic value of pre- and post-NAT sTILs and the information provided by the change in sTILs during NAT. Materials and methods: Two-hundred and nine consecutive patients (n=80 TNBC; and n=129 HER2+) who received NAT between 2001 and 2009 in our institution were evaluated. Pre-NAT sTILs were assessed on biopsy sample (baseline) and post-NAT sTILs on surgical specimens just for non-pCR patients. sTILs level was categorized as low 0-9%, intermediate 10-49%, and high ≥50%. The change in sTILs during NAT was calculated as the absolute difference between pre- and post-NAT sTILs. We evaluated the association of pre-NAT sTILs and pCR, and the association between pre- and post-NAT sTILs, and their change with relapse-free survival (RFS). Results: Overall pCR rate was 37.8% (31.3% for TNBC, 41.2% for ER+/HER2+BC, 42.3% for ER-/HER2+BC). In each subtype, pre-NAT low sTILs group was significantly associated with lower pCR rate. During the median follow-up period of 98 months, 44 recurrences (21.1%) were observed. For TNBC, low pre-NAT sTILs group was associated with higher recurrence risk compared with int/high sTILs (HR=4.675 [2.013-10.859], p Conclusion: In TN and HER2+ BCs, tumors with low pre-NAT sTILs have a low likelihood to achieve a pCR (predictive marker). In TNBC, low pre-NAT sTILs were associated with higher recurrence risk. In non-pCR TNBC patients, both low pre- and post-NAT sTILs were associated with shorter RFS. These results suggest that sTILs information should be taken into account when additional post-surgery treatments are considered in non-pCR patients. Citation Format: Ochi T, Giampaolo B, Murai M, Nozaki F, Kobayashi D, Iwamoto T, Niikura N, Suzuki K, Yamauchi H, Hayashi N. Predictive and prognostic value of stromal tumor-infiltrating lymphocytes before and after neoadjuvant therapy in triple negative and HER2-positive breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-08-31.

Background Nipple-sparing mastectomy (NSM) is an alternative procedure to skin-sparing mastectomy (SSM) for selected patients who undergo immediate reconstruction. However, the evidence of long-term oncologic safety of NSM has not been established. In this study, we aimed to compare the prognosis of breast cancer patients who underwent NSM to those who underwent SSM with immediate reconstruction. Methods The clinicopathological factors including recurrence site, pathologic stage, nipple-tumor distance, histological type, lymphovascular invasion, margin status, ER, PgR and HER2 status of stage 0–III primary breast cancer patients who underwent NSM or SSM with immediate primary reconstruction with tissue expander from our breast center database was retrospectively assessed. Patients with a nipple tumor distance of Results The median follow-up period was 71 months (range: 10 - 131 months) for the NSM group and 79 months (range: 9 - 140 months) for the SSM group. There were no significant difference of clinicopathological factors between the NSM group and the SSM group, except of the larger diameter of tumor in the SSM group. NSM was performed for 60 patients (32%) with stage 0, 71 patients (37%) with stage I, and 59 patients (31%) with stage II/III. SSM was performed for 185 patients (26%) with stage 0, 268 patients (37%) with stage I, and 276 patients (37%) with stage II/III. Local recurrence was found in 11 (5.8%) patients in the NSM group and in 44 (6.0%) patients in the SSM group. In the NSM group, only one (0.5%) patient had local recurrence in the nipple areola complex. In terms of DFS and overall survival (OS) rate, there was no difference between the NSM group and the SSM group (DFS; 89.5% vs 89.2%, HR, 1.044; p = 0.8992; 95% CI, 0.5116–1.9519, and OS; 98.4% vs 96.4%, HR, 0.963; p = 0.9116; 95% CI, 0.473–1.793). According to breast cancer subtype, in the NSM group, all of the 11 patients (100%) who developed local recurrence in the NSM group was hormone receptor (HR)-positive/HER2-negative breast cancer. 29 of the 44 patients (65.9%) who developed local recurrence in the SSM group was HR-positive/HER2-negative, 6 patients (13.6%) was HR-negative/HER2-positive, and 7 patients (15.9%) was triple-negative breast cancer. Among patients who had received neoadjuvant chemotherapy, the NSM group (3 of 14 patients, 21.4%) had a trend for higher local recurrence rate than the SSM group 7 of 116 patients (6.0%) (p = 0.0813). However, no local recurrence in the nipple areola complex was observed for the NSM group. In addition, there was no difference of OS between the NSM group (92.9%) and the SSM group (90.5%) (HR, 0.903; p = 0.9943; 95% CI, 0.049-4.739). Conclusions Our results suggested that NSM with immediate reconstruction might be safe as well as SSM for breast cancer with the nipple–tumor distance of >1 cm with respect to their prognosis and local control regardless of breast cancer subtype or invasiveness. Further studies with a large sample size to assess the risk of local recurrence for NSM after neoadjuvant chemotherapy. Citation Format: Yamashita Y, Hayashi N, Nagura N, Kajiura Y, Yoshida A, Takei J, Suzuki K, Tsunoda H, Yamauchi H. Long-term oncologic safety of nipple-sparing mastectomy with immediate reconstruction [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-14-17.

Background: It is not known which population of estrogen receptor (ER)-positive breast cancer patients should continue endocrine treatment beyond 5 years to overcome late recurrences. The aim of this study was to examine a combination of nuclear grade (NG) and expression level of ER and progesterone receptor (PR) to predict late recurrences. Methods: We assessed retrospectively 1677 consecutive ER-positive/HER2-negative patients who underwent surgical resection between 2004 and 2009. Patients with T2 or larger tumor and/or node-positive received pre- or postoperative chemotherapy following the international consensus panel from the St Gallen Conference, 2003. All patients had received adjuvant endocrine treatment. NG, ER and PR statuses were determined by immunohistochemistory on surgical specimen. We classified the patients into 3 groups as follows; ER-high (+++ or Allred score 7, 8)/PR-high (++ to +++ or 5-8) (n=212), ER-high / PR-low (- to + or 3-6) (n=208), and ER-low (+ to ++ or 3-6) / PR-any (n=255). We compared distant disease-free survival (DDFS) in each cohort based on the NG (1:low, and 2 or 3: high). Results: A median follow-up period was 77.0 months. Four hundred sixty seven patients (27.8%) received neoadjuvant chemotherapy, 208 patients (12.4%) received adjuvant chemotherapy, and 1002 patients (59.8%) did not received chemotherapy. Of the 467 patients with neoadjuvant chemotherapy, 65 patients (13.9%) had developed distant metastasis during study period (before 5 years in 51 (11.0%); and after 5 years in 14 (3.0%)). NG-low had significantly higher risk of late recurrence after 5 years than that of NG-high (p=0.005). According to hormonal receptor expression levels, in patients with NG-low, ER-low/PR-any had significantly higher overall DDFS rate than ER-high/PR-low (p=0.016). A similar trend was found before 5 years (p=0.077). However, ER-high/PR-high turned to have significantly high risk of recurrence after 5 years compared to ER-low/PR-any (p=0.024). Of the 208 patients with adjuvant chemotherapy, 16 patients (7.6%) had developed distant metastasis during study period (before 5 years in 5 (2.4%), and after 5 years in 11 (5.2%)). there was no association between a risk of recurrence and hormone receptor statuses at any study period. In the patients did not received chemotherapy, ER-high/PR-high had a trend of higher DDFS rate than others before 5 years (p=0.067). Of the 1002 patients without chemotherapy, only 36 patients (3.6%) had developed distant metastasis during study period (before 5 years in 27 (2.7%), and after 5 years in 9 (0.9%)). There was no difference of late recurrence after 5 years among the patients regardless of ER and PR expression level and NG with only low recurrence rate (0.9%). Conclusions: Our results demonstrated that, in ER-positive/HER2-negative patients who underwent neoadjuvant chemotherapy, NG-low/ER-high/PR-high should receive extend hormonal treatment over 5 years because of the high risk of late recurrence but NG-high/ER-high might not need. Furthermore, patients with T1 and node-negative may not need extend hormonal treatment because of the extremely low risk of late recurrence regardless of NG and hormone receptor statuses. Citation Format: Iwase M, Hayashi N, Yoshida A, Kajiura Y, Takahashi Y, Takei J, Suzuki K, Nakamura S, Yamauchi H. Hormone receptor expression level and nuclear grade associated with late recurrence in estrogen receptor-positive breast cancer patients. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-12-12.

Background Predictors of synchronous invasive breast cancer in patients diagnosed with only ductal carcinoma in situ (DCIS) in pre-operative needle biopsies have not been well-defined. Establishing such predictors of invasion has potential to significantly alter management by identifying those patients for whom surgery may be avoidable en lieu of conservative management. This study aims to identify clinicopathologic factors from pre-operative needle biopsies that are predictive of invasive cancer on subsequent surgical excision. Methods The study population consisted of 69 breasts from 67 patients initially diagnosed with only DCIS on needle biopsy (core needle or mammotome) at St. Luke's International Hospital, Japan from 2006 until 2008. Parameters analyzed included presenting clinical features, DCIS nuclear grade and morphologic pattern, and immunohistochemical expression of estrogen receptor (ER), progesterone receptor (PR), epidermal growth factor receptor-2 (HER2), Ki-67 antigen, p16, p53 and cyclooxygenase-2 (COX2) in biopsy specimens. These immunohistochemical markers were previously identified to foretell invasive carcinoma subsequent to DCIS (Kerlikowske, JNCI 2010). Associations between clinical, pathological, and immunohistochemical findings in initial biopsy specimens and the presence of invasive cancer on subsequent excision were analyzed for significance using univariate and multivariate analysis. Results Of 69 breasts with only DCIS on initial needle biopsy, subsequent surgical excision revealed pure DCIS in 46 (66.7%), microinvasive carcinoma in 4 (5.8%), and invasive carcinoma in 19 (27.5%) cases. Sentinel node biopsy was performed in 57 (82.6%) of 69 cases, and 53 (93.0%) of these showed no evidence of lymph node metastases. All 4 cases with lymph node metastases revealed invasive carcinoma in surgical excisions. By univariate analysis, pre-operative factors significantly associated with invasion on surgical excision included detection of a lump by palpation (p Conclusion If confirmed in a larger sample, predictive clinical and biomarker parameters can help identify those patients diagnosed with only DCIS in needle biopsy who are at high risk of harboring unsampled invasive cancer on final pathology. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-16-04.

Background: While pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) improves patients’ survival with HER2-positive and triple-negative (TN) breast cancers, it has been reported not to be the same for patients with hormone receptor (HR)-positive breast cancer. However, it is not well known whether chemosensitivity presented by change in tumor stage or nodal status after NAC contributes to improve the prognosis with HR-positive breast cancer. The aim of this study was to evaluate the impact of change in tumor stage or nodal status after NAC on prognosis in patients with primary breast cancer. Patients and Methods: We assessed retrospectively 599 consecutive patients with primary breast cancer (a median age of 49 years, ranging 26-79 years) who underwent surgical resection after NAC between 2001 and 2008. HR (ER and PR) statuses were determined by immunohistochemistory (IHC). HER2 status was determined by IHC and/or fluorescent in situ hybridization assays. ER-positive and PR-positive patients were 426 (71.1%) and 353 patients (58.9%), respectively. HER2 status was positive in 130 patients (21.7%). HR-positive subtype was defined as ER and/or PR-positive and HER2 negative. We compared the patients with respect to disease-free survival (DFS) and overall survival (OS) based on change in tumor stage and nodal status after NAC. pCR was defined as no residual invasive tumor and ypN0. Results: After NAC, 84 (14.0%) patients had pCR. Two hundred ninety one (48.6%) decreased tumor stage and 308 (51.4%) did not decrease tumor stage. Regarding nodal status, 190 (31.7%) had cN0 and 409 (68.3%) had cN+ before NAC, and 286 had ypN0 (47.7%) and 313 had ypN+ (52.2%). For patients with TN breast cancer, patients with pCR had excellent prognosis compared to those with residual tumor in either the breast or lymph node (non-pCR) (DFS, p Conclusions: Our results revealed that HR-positive breast cancer patients with conversion to lymph nodes metastasis after NAC have a good prognosis even if they have residual tumor in the breast, while TN breast cancer patients require pCR to have a good prognosis. It indicated that conversion to node-negative after neoadjuvant chemotherapy might be a surrogate prognostic marker in patients with HR-positive breast cancer. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-14-10.

Purpose:While the sensitivity to neoadjuvant chemotherapy (NAC) depends on breast cancer subtype, it has been reported that over 30% of patients with node-positive breast cancer achieved an axillary pathologic complete response (pCR) after NAC. However, axillary lymph node dissection (ALND) still remains as a standard treatment because of the difficulty of assessment of lymph node (LN) status after NAC. ALND will be omitted if axillary LN status is accurately assessed. Our purpose of this study was to predict the loss of axillary LN metastasis after NAC in primary breast cancer patients. Patients and Methods: Among 997 consecutive patients who underwent surgery after NAC from January 2006, to December 2016, 279 patients with cytologically proven node-positive were included in this analysis. All patients were assessed using CT or PET-CT, and ultrasonography (US) before NAC. LN status after NAC was assessed by US. Patients with cT4 tumor, and supra/subclavicular and parasternal LN metastasis were excluded. Clinical LN status after NAC (ycN) was compared to pathological LN status (ypN) on surgical specimen. The association between LN status and clinicopathological factors including nuclear grade (NG), tumor size, the use of trastuzumab, and breast cancer subtypes, was assessed. Result: Of the 279 patients with LN-positive before NAC, 166 patients (59.5%) had ER+/HER2- tumor, 51 patients (18.3%) had ER+/HER2+ tumor, 33 patients (11.8%) had ER-/HER2- tumor, and 29 patients (10.4%) had ER-/HER2+ tumor. 179 patients (64.2%) had ycN0 and 102 patients (36.6%)had ypN0. There was significant difference of rate of the loss of LN metastasis after NAC; 37 of 166 patients (22.3%) with ER+/HER2- tumor, 24 of 51 patients (47.1%) with ER+HER2+ tumor, 19 of 33 patients (57.6%) with ER-HER2- tumor, and 22 of 29 patients (75.9%) with ER-HER2+ tumor, (p Conclusion: Our results showed patients with ER-/HER2+ tumor and cytologically proven LN metastasis who received NAC with trastuzumab might have the loss of LN metastasis if assessed as ycN0 by US after NAC, whereas, the patients in ER+ tumor have a high risk to have residual LN metastases after NAC even if assessed as ycN0. Further studies are warranted the prognostic impact of the omission of ALND for these populations. Citation Format: Namura M, Hayashi N, Tsunoda H, Yoshida A, Takei J, Suzuki K, Nakamura S, Yamauchi H. The loss of lymph node metastasis after neoadjuvant chemotherapy in patients with cytologically proven node-positive primary breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-01-03.

Purpose: Accurate assessment of metastasis in sentinel lymph nodes (SLN) of breast cancer is important but involves a heavy workload for the pathologist. We conducted a multicenter clinical trial in Japan to evaluate a new automated assay system for cytokeratin 19 mRNA, the one-step nucleic acid amplification (OSNA) assay (Sysmex), to detect lymph node metastasis of breast cancer. Experimental Design: Surgically obtained axillary lymph nodes were sectioned into four pieces, two of which were examined with the OSNA assay. The other two adjacent pieces were examined with H&E and immunohistochemical staining for cytokeratin 19. Serial sections at 0.2-mm intervals were used in trial 1 to determine the specificity of the OSNA assay, and three pairs of sections cut from the sliced surfaces of the pieces were used in trial 2 to compare the accuracy of the OSNA assay with that of a routine pathologic examination for SLNs in Japan. Results: In trial 1, the sensitivity and specificity were 95.0% [95% confidence interval (95% CI), 75.1-99.9%] and 97.1% (95% CI, 91.8-99.4%), respectively, for 124 axillary lymph nodes obtained from 34 patients. In trial 2, the agreement between findings of the assay and of the pathologic examination was 92.9% (95% CI, 90.1-95.1%) for 450 axillary lymph nodes obtained from 164 patients. Conclusion: The OSNA assay can detect lymph node metastasis as accurately as can conventional pathology and thus can be an effective addition to or alternative for rapid intraoperative examination of SLNs.

Purpose: Detection of sentinel lymph node (SLN) metastasis in breast cancer patients has conventionally been determined by intraoperative histopathologic examination of frozen sections followed by definitive postoperative examination of permanent sections. The purpose of this study is to develop a more efficient method for intraoperative detection of lymph node metastasis. Experimental Design: Cutoff values to distinguish macrometastasis, micrometastasis, and nonmetastasis were determined by measuring cytokeratin 19 (CK19) mRNA in histopathologically positive and negative lymph nodes using one-step nucleic acid amplification (OSNA). In an intraoperative clinical study involving six facilities, 325 lymph nodes (101 patients), including 81 SLNs, were divided into four blocks. Alternate blocks were used for the OSNA assay with CK19 mRNA, and the remaining blocks were used for H&E and CK19 immunohistochemistry–based three-level histopathologic examination. The results from the two methods were then compared. Results: We established CK19 mRNA cutoff values of 2.5 × 102 and 5 × 103 copies/μL. In the clinical study, an overall concordance rate between the OSNA assay and the three-level histopathology was 98.2%. Similar results were obtained with 81 SLNs. The OSNA assay discriminated macrometastasis from micrometastasis. No false positive was observed in the OSNA assay of 144 histopathologically negative lymph nodes from pN0 patients, indicating an extremely low false positive for the OSNA assay. Conclusion: The OSNA assay of half of a lymph node provided results similar to those of three-level histopathology. Clinical results indicate that the OSNA assay provides a useful intraoperative detection method of lymph node metastasis in breast cancer patients.

Background: The incidence of change in HER2 status in primary breast cancer after neoadjuvant chemotherapy (NAC) and whether the prognosis is affected by the change in HER2 status is not well known. Patients and Methods: Five hundred and eighty-eight patients who were treated with anthracycline- and/or taxane-based NAC and had non-pathologic complete response between 2001 and 2008 in our hospital were enrolled. Human epidermal growth factor receptor-2 (HER2) status was assessed in specimen by needle biopsy before NAC and on the residual tumor of surgical specimen. We determine the impact of change in HER2 status on recurrence-free survival (RFS). Twenty-eight patients had received trastuzumab with NAC, and 57 patients had received trastuzumab as adjuvant therapy. HER2-positive was defined as 3+ by immunohistochemistry and/or amplification by fluorescent in situ hybridization. Association between change in HER2 status after NAC and clinicopathologic factors, including age, clinical T stage, estrogen receptor (ER), progesterone receptor (PR), Nuclear grade (NG), lymphovascular invasion (LVI) and Trastuzumab usage (NAC and Adjuvant setting) were determined. Result: A median follow-up period was 57 months (range, 3 to 131 months). Four hundred eighty-nine of the 588 patients (83.1%) had HER2-negative tumors and 99 patients (16.8%) had HER2-positive tumor before NAC. In 11 of the 489 patients (2.2%) HER2-negative changed to HER2-positive.In 33 of the 99 patients (30%) HER2-positive changed to HER2-negative. In clinicopathologic factors, ER and PR positive before NAC were associated with incidence of change in HER2 status after NAC. Receiving trastuzumab was not correlated with incidence of change in HER2 status. In terms of RFS, there was no difference between patients with and without change in HER2 status in both of the 489 patients with HER2-negative tumors and 99 patients with HER2-positive tumors before NAC (p=0.26, p=0.23, respectively). Conclusion: We herein reported the incidence of change in HER2 status after NAC with the largest sample size. However, change in HER2 status did not seems to affect prognosis. Further prospective study is needed to confirm the prognostic impact of change in HER2 status. Citation Format: Atsushi Yoshida, Naoki Hayashi, Hiroshi Yagata, Koyu Suzuki, Seigo Nakamura, Hideko Yamauchi. Change of HER2 status following neoadjuvant systemic therapy in primary breast cancer patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-01-03.

Background: Intra-operative sentinel node biopsy (SNB) is performed for clinically node negative invasive carcinoma (IC). Despite a negative result for metastasis from rapid frozen section (FS) diagnosis of intra-operative SNB, some cases may be diagnosed positive when permanent sections (PS) are analyzed (i.e., false negative). In order to reduce the false-negative rate, it is necessary to determine why macrometastases measuring greater than 2 mm cannot be accurately diagnosed using frozen specimens. The aim of this study was to compare the pathological characteristics of false-negative and positive cases of macrometastasis using FSs. We also reviewed whether there were differences in postoperative prognoses between positive and false-negative cases. Methods: We retrospectively reviewed 1632 intra-operative SNBs collected from 2008 to 2011 at St. Luke’s International Hospital, Tokyo, JAPAN. Of these, 980 patients had undergone surgery for the treatment of IC without neoadjuvant chemotherapy. Lymph nodes were sectioned every 2 mm and examined. For FSs, we performed hematoxylin and eosin (HE) staining, and for PSs, we used HE and cytokeratin (AE1/AE3) staining. Image J (NIH Image, Bethesda, MD, USA) was used for assessment of the metastatic area of lymph nodes. Micro- and macrometastases were defined as metastatic lesions measuring between 0.2 and 2 mm or measuring 2 mm or more, according to TMN classification. Results: Using FSs, we identified 104 patients (10.6%) who were positive for macrometastasis, 16 patients (1.6%) who were positive for micrometastasis, and 860 patients (87.8%) who were negative for metastasis. Of the negative cases, the result was changed to micrometastasis in 37 cases (4.3%) and to macrometastasis (false-negative cases) in 14 cases (1.6%). Ten of the 14 patients did not have additional axillary lymph nodes dissection. The mean age of the patients was 55.1 ± 3.1 years for false-negative cases and 52.3 ± 1.2 years for positive cases. In terms of histological features, there were statistically significant differences between false-negative and positive cases for invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC), and IDC plus ILC (p < 0.05). There were no statistically significant differences between false-negative and positive cases in terms of the total number of slices for lymph nodes (8.4 ± 1.6 vs. 9.7 ± 0.6, respectively; p = 0.41) but tendency in the number of slices for metastases (2.4 ± 1.2 vs. 4.8 ± 0.5, respectively; p = 0.07). The maximum area ratio of metastasis was significantly lower in false-negative cases than in positive cases (3.0% ± 0.1% vs. 20.0% ± 0.2%, respectively; p < 0.05). There was no significant difference in disease-free survival between false-negative and positive cases (p = 0.43). Conclusions: Although it is necessary to reduce false-negative cases, no difference in prognosis was detected in our study. False-negative cases had lower metastasis area ratios than positive cases diagnosed using rapid diagnosis of intra-operative SNBs, and ILC is known to be high in histological features. Therefore, using AE1/AE3 stain together with rapid diagnosis of intra-operative SNBs may lower the false-negative rate when a diagnosis includes ILC in pre-operation analysis. Citation Format: Eriko Abe, Naoki Hayashi, Toshinao Onoda, Yang Yang, Mieko Uno, Hideko Yamauchi, Sachiko Ohde, Koyu Suzuki. Comparison between positive and false-negative sentinel lymph nodes in breast cancer patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-01-32.

Background: Surgical treatment could be omitted if we could predict pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in primary breast cancer patients by radiological findings accurately. The aim of this study is to assess the accuracy of MRI and ultrasonography (US) in predicting pathologic complete response in breast cancer patients treated with NAC. Methods: Five hundred sixty nine primary breast cancer patients who underwent breast conserving surgery after NAC between 2004 and 2008 were reviewed. Sensitivity and specificity of clinical complete response (cCR) by MRI alone and in combination with US were retrospectively assessed. pCR in primary tumor was defined as no residual invasive carcinoma. Spotted, linear or trabecular lesions without vascularity detected by US and/or enhanced on late phase of MRI findings were suspected to be residual in situ carcinoma. Results: The median age of the 569 patients analyzed was 50 years (range, 26-76 years). Of the patients, 86 (15.1%) had pCR. Of 79 patients who were diagnosed cCR by MRI alone, 72 patients (91.1%) were accurately predicted. Of 490 patients who were diagnosed to have residual invasive carcinoma, 14 patients (2.9%) had pCR. Of 75 patients who were diagnosed cCR by MRI in combination with US, 68 patients (90.7%) was accurately predicted. Of the 494 patients who were diagnosed to have residual invasive carcinoma, 18 patients (3.6%) had pCR. The combination of MRI and US had a sensitivity of 79.1%, specificity of 98.6%. prediction of pCR by MRI alone and in combination with US MRI aloneMRI + US cCRnon-cCRcCRnon-cCR (n = 79)(n = 490)(n = 75)(n = 494)pCR72146818(n = 86)(91.1%)(2.9%)(90.6%)(3.6%)non-pCR74767476(n = 483)(8.9%)(97.1%)(9.4%)(96.4%) For 85 patients who were diagnosed cCR by MRI and/or US, positive predictive value was 89.4% in ER-positive breast cancer, 100% in ER-negative/HER2-positive breast cancer, and 81.5% in triple negative breast cancer. In terms of prediction of residual in situ carcinoma, of the 86 patients with pCR, 43 (50%) had residual in situ carcinoma. The median size of residual tumor was 2.0 cm (range, 0.01-8.0 cm). Twenty five of 37 patients (67.6%) who are diagnosed cCR without any residual in situ carcinoma by both MRI and US were accurately predicted. Twelve of the 37 patients (31.6%) had residual carcinoma (in situ carcinoma, n = 10, and invasive carcinoma, n = 2) on surgical specimen. Twenty one of 38 patients (55.3%) who are diagnosed cCR with residual in situ carcinoma by both MRI and US had pCR with residual in situ carcinoma accurately. Twelve of the 38 patients (31.6%) had pCR without any in situ carcinoma and 5 (13.2%) had residual invasive carcinoma on surgical specimen. Conclusions: Our results indicated that MRI in combination with US was highly useful to predict pCR in breast cancer patients treated with NAC, although it was hard to predict a presence of residual in situ carcinoma. Pathological intervention using a vacuum-assisted breast biopsy in addition to these radiological modalities is expected for higher accuracy of predicting pCR. We are going to conduct a prospective multi-institutional study to assess predictive value of the method. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-02-11.

Abstract #5020 Background: HER-2 Overexpression in breast cancer is associated with poor prognosis. The circulating tumor cells (CTCs) in peripheral blood can be identified in patients with breast cancer. They are recognized as a predictor of the effect of systemic therapy, and also as a prognostic marker recently. Cristofanilli et al reported that progression-free Survival (PFS) and overall survival(OS) in metastatic breast cancer patients with 5CTCs before initiation of a new line of therapy and at the 1st follow-up visit. However, the detection rate and value of HER-2 Overexpression on CTCs has been not determined well.Materials and Methods:CTCs were obtained prospectively for 22 patients with metastatic breast cancer to start a new line of treatment at single institution. Blood specimens were collected at monthly intervals for a period of up to 12 weeks. CT scans were also performed before start of the treatment and 12 weeks after. HER-2 expression on primary lesions and CTCs were determined by both immunohistochemical methods and fluorescence in situ hybridization (FISH) analysis. Mean age was 54.4 years (range, 32-75 years). 8 patients received first line therapy, one patient received second line therapy, and 13 patients received over third line therapy. Of the 22 primary cancer, 7(31.8%) were HER-2 positive(score,+3 or +2/FISH positive) and 15 (68.2%) were HER-2 negative. CTCs were determined using Cell Search™ System.Results:14(63.6%) patients had clinical benefit (partial response and stable disease) during the course. CTCs were detected in 16 patients (72.7%). OS for patients with Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5020.

Abstract #1164 Background: Since ductal carcinoma in situ (DCIS) often spreads diffusely along a lactiferous duct as multicentric lesions, it is generally treated by mastectomy. The response rate to letrozole is approximately 60%, which is relatively high among the preoperative endocrine therapies for invasive cancer, and it enables at least 50% of patients with little chance of saving the breast to actually receive breast-conserving surgery. This study was conducted to determine the value of preoperative endocrine therapy with letrozole for postmenopausal patients with hormone receptor (HR)-positive DCIS. Methods: Postmenopausal women who had been diagnosed with HR-positive DCIS by needle biopsy (Allred score ≥3) were treated with letrozole for 12 weeks. The primary endpoint was the response of target lesions evaluated by MRI based on the RECIST criteria. Patients who had no safety problems, except PD, continued letrozole therapy for up to 24 weeks, and the tumor response after 24 weeks and the rate of breast-conserving surgery were assessed. In addition to RECIST-based evaluation, changes of tumor volume on MRI were examined. Changes of Ki67, bcl-2, ER, and PgR with letrozole therapy were also assessed. Results: Twelve postmenopausal women with DCIS were enrolled, but one patient was excluded because her Allred score was 2. Using by RECIST criteria , the tumor response after 12 weeks was CR in 1 patient and SD in 10 patients. All 6 patients who could be evaluated after 24 weeks showed SD. But the evaluation by tumor volumetoric method, tumor was significantly reduced to an average of 42.2% after 12 weeks compared to before treatment.(p=0.0057) Two patients continued letrozole therapy for longer than 24 weeks. After 24 weeks of therapy, 3 patients underwent breast-conserving surgery and no mastectomies were performed. Pathological findings showed that the spread of tumor was likely to that of preoperative MRMammogrraphy. PgR was significantly reduced by letrozole therapy. There were no safety problems was not observed. Discussion: The efficacy of preoperative treatment with letrozole for 12 weeks was verified in postmenopausal patients with HR-positive DCIS. Two patients received breast-conserving surgery after letrozole therapy that had been considered impossible before treatment. Evaluation of treatment to DCIS using by RECIST criteria is unsutable,but the evaluation by MRMammography is considered to be a suitable method for determining the efficacy of therapy for DCIS. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1164.

Abstract #6069 Background: Triple negative breast cancer (TNBC) is defined by the lack of estrogen receptor(ER), progesterone receptor (PR), and human epidermal growth factor receptor2 (HER-2) expression. TNBC has poor outcome due to no specific therapeutic agents. But TNBC includes two major phenotypes, basal-like and non basal-like phenotypes. Basal-like phenotype has poor prognosis and is associated with positive expression of basal markers. We compared response to neoadjuvant chemotherapy between patients with TNBC and non-TNBC, in addition, basal-like and non basal-like phenotype. Material and Methods: We retrospectively reviewed a total of 1948 operated patients with a diagnosis of primary breast cancer from November 2002 to December 2006 at St. Luke's International Hospital. 369 (18.9%) patients received neoadjuvant chemotherapy. Clinical and pathological response rates, survival measurements and relapse rates were compared between patients with TNBC and non-TNBC. Clinical response was determined by MRI or CT which was performed before and after neoadjuvant chemotherapy. Histopathological parameter(ER, PGR, HER-2, nuclear grade, mitosis) were confirmed from the specimens of needle biopsy performed before treatment. The specimens were also stained with basal markers (cytokeratin 5/6 and EGFR) to identify basal-like phenotype in TNBC. Basal-like phenotype was defined by the expression of CK5/6 and/or EGFR in >10% of tumor cells. Results: Fifty-four of 369 patients (14.6%) had TNBC. Progressive disease (PD) rate was significantly higher in patients with TNBC than those patients with non-TNBC (20.7% v 2.3%).And pathologic complete response rate (pCR) was also higher in patients with TNBC than those patients with non-TNBC (17% v 9.6%).14of 48 patients (29.1%) was diagnosed as Basal-like phenotype in TNBC. Clinical response rate for basal-like phenotype was worse than non basal-like phenotype (42.9% v 67.6%). Furthermore, both disease free survival and overall survival for basal-like subtype were significantly worse than non basal-like phenotype (p Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6069.