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Introduction Scalp cooling during chemotherapy infusion to mitigate hair loss for breast cancer patients is becoming popular in European and North American countries. But there is little prospective data regarding hair recovery after chemotherapy with scalp cooling. We reported on the results of hair loss prevention with scalp cooling during (neo)adjuvant chemotherapy with anthracyclines and/or taxanes for 122 Japanese breast cancer patients at the 2018 San Antonio Breast Cancer Symposium. Now we report on the prospective data of hair recovery of our 122 patients. Patients and Methods One hundred and twenty two Japanese breast cancer female patients who completed planned (neo)adjuvant chemotherapy used Paxman Scalp Cooling System for alopecia prevention and were evaluable for hair loss prevention in our prospective study. The scalp cooling was done 30 minutes prior to and during and 90 minutes after each chemotherapy infusion. We evaluated their hair recovery 1, 4, 7, 10, and 13 months after completion of the chemotherapy. We took photographs of the heads of the patients from 5 directions, namely front, back, both sides, and top and asked the patients about the use of a wig or hat to conceal the hair loss using a questionnaire at the times mentioned above. Primary outcomes were grades of alopecia judged by two investigators (defined as Grade 0: 0% of hair loss, G1: 1~25 %, G2: 26~50%, G3: > 50%)(objective grade) and patients' answers to the questionnaire (defined as Grade 0: not at all, G1: sometimes, G2: almost always)(subjective grade). Among 122 patients 79 completed scalp cooling during the whole planned chemotherapy cycles, but 43 discontinued it mostly after the first cycle due to several reasons. We compared the objective and subjective grades of hair loss between the patients who had completed the scalp cooling (79 patients: Group A) and those who had discontinued it (43 patients: Group B). Results Objective grades 1 month after completion of the chemotherapy were Grade 0 in 6 patients (4.9 %), G1 in 13, G2 in 29, and G3 in 74, and subjective grades at 1 month were Grade 0 in 3 patients (2.5 %), G1 in 13, G2 in 105, and unknown in 1. The changes over time in objective grades were as follows; 4 months: G0 55 (47.0 %), G1 52, G2 9, G3 1, unknown 5, 7 months: G0 99 (85.3 %), G1 15, G2 1, G3 1, unknown 6, 10 months: G0 105 (89.7 %), G1 10, G2 1, G3 1, unknown 5, 13 months: G0 104 (92.0 %), G1 7, G2 1, G3 1, unknown 9. On the other hand, the changes in subjective grades were as follows; 4 months: G0 12 (10.3 %), G1 29, G2 76, unknown 5, 7 months: G0 53 (45.7 %), G1 22, G2 41, unknown 6, 10 months: G0 80 (68.4 %), G1 15, G2 22, unknown 5, 13 months: G0 93 (82.3%), G1 7, G2 13, unknown 9. When we compared Group A with Group B, the rates of objective G0 were statistically significantly higher in Group A than Group B, at 4, 10, and 13 months (4 months: 55.7% vs. 28.9%, P = 0.010, 10 months: 96.1% vs. 78.0%, P = 0.006, 13 months: 97.3% vs. 81.6%, P = 0.011) and the rate of subjective G0 was also statistically significantly higher in Group A than Group B at 7 months (53.2 % vs. 30.8 %, P = 0.022). When we restricted the data to those with objective Grade 3 at 1 month, Group A showed tendency of faster hair recovery in the objective grades than Group B. Conclusion It is concluded that scalp cooling during chemotherapy infusion for Japanese breast cancer patients made their hair recovery faster. Citation Format: Shozo Ohsumi, Sachiko Kiyoto, Yuichiro Miyoshi, Mina Takahashi, Seiki Takashima, Kenjiro Aogi, Sachie Shimizu, Miyuki Doi. Prospective study of hair recovery after (neo)adjuvant chemotherapy with scalp cooling in Japanese breast cancer patients [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-14-21.

Background: Two randomized controlled trials comparing the efficacy of oral tegafur-uracil (UFT) (2 years) with that of classical cyclophosphamide, methotrexate, and fluorouracil (CMF) (6 courses) were conducted in patients with resected early breast cancer (N-SAS-BC01 trial [Watanabe et al, J Clin Oncol 2009] and CUBC trial [Park et al, Br J Cancer 2009]). Pooled analysis of these two randomized controlled trials using individual patient data has been published (Ohashi et al, Breast Cancer Res Treat 2010) and long-term follow-up data has also been reported (Yonemori et al, SABCS 2018). However, because the pathological factors evaluated in those studies are insufficient and based on old criteria, a re-evaluation using the current standard pathological factors is requited to use the data in the clinical practice. Methods: Paraffin-embedded sections of surgically excised tumor tissue were available for patients with resected stage I-IIIA breast cancer. The expression of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2) and the Ki67 labeling index were assessed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH), and the grades of TILs were evaluated by hematoxylin and eosin (H&E) staining by pathology central review. The relationship of these pathological factors to relapse free survival (RFS) and overall survival (OS) was evaluated using long-term follow-up data. Hazard ratios were determined using the Cox model adjusted for clinical characteristics, namely tumor size and nodal status. Survival curves were estimated by the Kaplan-Meier method. This study is registered with the University Hospital Medical Information Network (UMIN), Japan (UMIN000022571). Results: Paraffin-embedded sections were available from 689 of the total of 1,057 (65.2%) patients (CMF, n=342; UFT n=347). The median follow-up time was 11.1 years (12.1 years in the N-SAS-BC 01 trial and 8.3 years in the CUBC trial). Baseline characteristics were similar in each group. The 10-year RFS and OS was 79.9%, 87.7% in the CMF arm, and 77.1%, 88.8% in the UFT arm, respectively. The hazard ratio (UFT vs. CMF) was 0.962 (95% CI 0.712-1.300) for RFS and 0.929 (95% CI 0.639-1.350) for OS. Table 1 shows the 10-year RFS and OS in each IHC-defined breast cancer subtype. 10-year OS in UFT arm and in CMF arm were similar in Hormone receptor (HR) + groups. Although this is not expected, there is a positive signal of benefit of UFT in HR-HER2+ group (RFS; hazard ratio 0.296 (95% CI 0.100-0.878)). High TILs were associated with better prognosis in all patient group (vs. low TILs: hazard ratio 0.347 (95% CI 0.140-0.855)), however in HR+ HER2- group, there was no association between TIL status and prognosis (High vs. low: hazard ratio 0.787 (95% CI 0.240-2.581)). TILs status could not predict the benefit of UFT in the subset analysis of all patient group and of each subtype group. Conclusion: This long-term follow-up study using randomized controlled trials shows that RFS and OS are similar in luminal type patients treated with UFT and CMF. Funding: Taiho Pharmaceutical CO., LTD. Table 1. 10-year RFS and OS in each IHC-defined breast cancer subtypeUFT (%)CMF (%)hazard ratio (UFT vs. CMF)10-year RFSHormone receptor (HR)+ HER2-76.7 (n=210)81.2 (n=210)1.034 (95%CI: 0.705-1.517)HR+ HER2+71.4 (n=26)73.7 (n=42)1.237 (0.499-3.069)HR- HER2+81.2 (n=29)68.4 (n=29)0.296 (0.100-0.878)HR- HER2-78.2 (n=73)84.7 (n=59)1.263 (0.596-2.675)10-year OSHR+ HER2-91.0 (n=210)89.5 (n=210)0.907 (0.551-1.491)HR+ HER2+83.9 (n=26)82.6 (n=42)0.993 (0.345-2.856)HR- HER2+90.9 (n=29)78.9 (n=29)0.335 (0.081-1.394)HR- HER2-84.6 (n=73)89.4 (n=59)1.455 (0.628-3.367) Citation Format: Shigehira Saji, Shinji Ohno, Norikazu Masuda, Hitoshi Tsuda, Futoshi Akiyama, Masafumi Kurosumi, Akihiko Shimomura, Nobuaki Sato, Shintaro Takao, Shozo Ohsumi, Yutaka Tokuda, Hideo Inaji, Toru Watanabe, Yasuo Ohashi. Pooled analysis of long-term outcome of patients enrolled in two trials comparing the efficacy of oral tegafur-uracil with CMF (N-SAS-BC01 and CUBC trials) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-14-17.

Background: It is critical that a large proportion of eligible patients should participate in clinical trials. However, recruitment into clinical trials requires informed consent and involves some difficult and complex problems. Therefore, it is important to know what factors affect the participation of eligible patients in clinical trials. Patients and Methods: Patients with metastatic breast cancer (MBC) who were eligible to participate in the SELECT BC or SELECT BC-CONFIRM trials were recruited to a prospective study accompanying them named SELECT BCFEEL. The SELECT BC and SELECT BC-CONFIRM trials were randomised controlled trials (RCTs) that compared taxanes or anthracyclines, respectively, with the oral regimen of S-1 in the first line setting for Japanese patients with MBC. The SELECT BC FEEL was conducted to identify factors affecting the rates at which informed consent was obtained, using a self-administered questionnaire we developed. The questionnaire included the following items: Physician recommendation, family or friend recommendation, satisfaction with the explanation about the trial, both from the doctor or clinical research coordinator and from printed matter, regimens used, understanding of the concept of the trial, benefit to future patients, relationship with the doctor, attitude toward random assignment, concerns about privacy, burden on the patient, and potential adverse effects. We also asked the patients their age, whether they received prior chemotherapy, and about the time needed to decide whether or not to participate, communication with their doctor or other patients, potential adverse effects they were concerned about, and other people's opinions that affected their decision. The patients were asked to answer most of the questions in 5-point Likert scales. To investigate the associations between patients’ decision regarding whether or not to participate in the RCTs and their responses to each question, the Chi-square test, the Mann-Whitney U test, and the t-test were used. P values of < 0.05 were considered statistically significant. Results: Two hundred and thirty-two patients participated in the present study. Data were missing for 3 patients, and they were excluded from the analyses. One hundred and eighty five participated in the RCT, but 44 did not. The patients who chose to participate in these RCTs were more likely to answer that they decided to participate because "My doctor wanted me to participate in this trial" (69.2% vs. 25.6%; P Conclusions: To enhance the consent rate in randomised trials of Japanese breast cancer patients, the concepts of the trials must be considered important and acceptable by the doctors and families of the patients. Citation Format: Yasuo Hozumi, Shozo Ohsumi, Hirofumi Mukai, Masato Takahashi, Hiromitsu Akabane, Youngjin Park, Eriko Tokunaga, Tsutomu Takashima, Takanori Watanabe, Yoshiaki Sagara, Tetsuji Kaneko, Yasuo Ohashi. Factors affecting enrolment in randomised controlled trials of Japanese patients with metastatic breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-21-01.

Introduction Recently scalp cooling during chemotherapy infusion has been reported to be quite effective to mitigate chemotherapy-induced alopecia. But data in Asian patients are quite limited. Patients and methods Japanese breast cancer female patients who planned to receive (neo)adjuvant chemotherapy were offered to participate in this prospective study of scalp cooling with Paxman Scalp Cooling System for alopecia prevention. The scalp cooling was done 30 minutes prior to and during and 90 minutes after each chemotherapy infusion. Photographs of the head of the participants were taken from 5 directions, namely front, back, both sides, and top, on the day of chemotherapy infusion and 1 month after the last infusion. Two investigators consisting of a physician and a nurse judged the grade of alopecia by looking at the photographs according to the WHO classification. The primary outcomes were the rates of patients with Grade 3 alopecia (defined as hair loss of > 50%) and the rates of patients who used a wig or hat to conceal the hair loss one month after the last infusion of chemotherapy. This paper reports on the former outcome mainly. They were asked to answer a brief questionnaire regarding headache, fatigue, chill etc. shortly after each cooling. They could use the cooling cap for free on the first cycle of chemotherapy. But they were required to purchase it (about 1,130 US$) for the scalp cooling of the following cycles. Results One hundred forty three patients participated in the study and actually used the cooling cap at least once. The mean and median age of them are 50.6 and 50, respectively (28 - 76). One hundred twenty nine patients completed the planned chemotherapy of 4 to 8 cycles (89 Pts 4 cycles, 1 Pt 6 cycles, 39 Pts 8 cycles). Among them (7 patients were not evaluable), 74 patients (60.7 %) had Grade 3 alopecia 1 month after chemotherapy. In 80 patients who used the scalp cooling system throughout the planned chemotherapy (1 patient was not evaluable), 36 patients (45.6 %) experienced Grade 3 alopecia. On the other hand, among 49 patients who discontinued the cooling mostly after the 1st cycle (6 were not evaluable), 38 (88.3 %) had Grade 3 alopecia. When we restrict them to 33 (5 were not evaluable) who decided to discontinue the cooling by day10 of the first cycle of chemotherapy to exclude the patients who discontinued it because of less effect on alopecia prevention than they expected, 25 (89.3 %) experienced Grade 3 alopecia. Comparing the results of those who completed the cooling and patients who decided to discontinue it by day10 of the first cycle, the rates of Grade 3 alopecia (45.6 % vs. 89.3 %) were statistically significantly different in favor of the former (P = 0.0001). Most patients complained of some headache, chill, and pain of the jaw. Conclusion Scalp cooling with Paxman Scalp Cooling System during chemotherapy infusion in Asian women seems as effective for hair loss mitigation as in Caucasian women. Citation Format: Ohsumi S, Kiyoto S, Takahashi M, Hara F, Takashima S, Aogi K, Matsuda M, Yamamura N, Matsuda A, Yamauchi T, Doi M. Prospective study of scalp cooling for hair loss prevention in Japanese breast cancer women receiving (neo)adjuvant chemotherapy [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 P4-16-13.

Background: Two randomized controlled trials comparing the efficacy of oral tegafur-uracil (UFT) (2 years) with that of classical cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) (6 courses) were conducted in patients with resected early breast cancer. UFT is an oral fluoropyrimidine that combines tegafur, a prodrug of 5-fluorouracil, with uracil in a 1:4 molar ratio. One study was the N-SAS-BC01 trial (Watanabe et al, J Clin Oncol 2009), which was conducted in patients with high-risk node-negative breast cancer (n=733). The other was the CUBC trial (Park et al, Br J Cancer 2009), which was performed in patients with node-positive breast cancer (n=377). We reported the pooled analysis of these two randomized control trials using individual patient data (Ohashi et al, Breast Cancer Res Treat 2010). This pooled analysis showed that UFT was non-inferior to CMF in terms of inhibiting recurrence of estrogen receptor (ER)-positive early breast cancer. In addition, an exploratory subgroup analysis showed that UFT may be more effective in ER-positive patients who were 50 years or older. The present study was conducted to investigate the long-term efficacy of UFT or CMF in patients with early breast cancer. Methods: Long-term follow-up data for disease recurrence and survival were collected. Hazard ratios (HR) were determined using the Cox model stratified by study and adjusted for clinical characteristics, namely age, tumor size, nodal status, histological type, ER, and progesterone receptor (PgR). Survival curves were estimated by the Kaplan-Meier method. Hochberg multiplicity adjustment was applied in the previous pooled analysis, and non-inferiority of UFT versus CMF was shown in terms of relapse-free survival (RFS) in the ER-positive patient group. We investigated the non-inferiority of UFT in the same patient group with updated data. Restricted mean survival time (RMST) was calculated to consider the relative efficacy of UFT. This study is registered with JapicCTI-163321. Results: In total, 1,057 patients were analyzed (CMF, n=528; UFT n=529). The median follow-up time was 11.1 years (12.1 years in the N-SAS-BC 01 trial and 8.3 years in the CUBC trial). Table 1 shows the 10-year RFS and overall survival (OS) in all patients and ER-positive patients. The difference in RMST between arms at 20 years in terms of RFS was -2.7 months in all patients and 3.4 months in ER-positive patients. Table 2 shows the HR for RFS according to ER status and age. UFT (%)CMF (%)UFT to CMF; HR (95% CI)10-year RFSall patients74.477.11.02 (0.81–1.30)ER-positive patients75.075.10.91 (0.66–1.27)10-year OSall patients86.886.90.98 (0.72–1.34)ER-positive patients89.987.90.86 (0.54–1.37) Age Conclusion: This study shows that UFT was shown to be non-inferior to CMF in terms of RFS in ER-positive early breast cancer. This result is similar to that of the previous pooled analysis. Sponsor: Taiho Pharmaceutical Co., LTD Citation Format: Yonemori K, Ohsumi S, Takao S, Tokuda Y, Ito Y, Nakagami K, Takahashi M, Yoshidome K, Nakayama T, Yamaguchi Y, Ohashi Y, Inaji H, Watanabe T. Long-term follow-up of two randomized controlled trials (N-SAS-BC01 trial and CUBC trial) comparing oral tegafur-uracil (UFT) versus classical cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) as adjuvant therapy in early 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 P1-13-09.

Background: Breast conserving surgery with radiotherapy is one of the standard treatment methods for early breast cancer. However, it is regarded as an option to treat elderly patients with small hormone receptor positive breast cancer with breast conserving surgery and hormone therapy without radiotherapy. Two sequential prospective studies were conducted to examine the efficacy of breast conserving surgery without radiotherapy from 2002. Patients and Methods: Primary breast cancer patients were divided into the WORTH 1 (n=123) group (Oct. 2002 and Mar. 2005) and the WORTH 2 (n=198) group (Dec. 2006 and Nov. 2011) and the data was retrospectively combined and analyzed. The eligibility criteria of the two sequential studies were a tumor ≥3cm determined by palpation, pathologically node negative by axillary dissection or sentinel node biopsy and M0, no preoperative treatment, postmenopausal patients ≥50 years of age at surgery, no tumor cells within 5 mm from the margins, no lymphatic invasion around the primary tumor, and estrogen receptor positive. The surgical specimens were sliced at 5 mm intervals and all the slices were examined microscopically. Postoperative radiotherapy was not conducted and adjuvant chemotherapy was optional. The patients were treated with tamoxifen or anastrozole in WORTH 1 and anastrozole in WORTH 2 for 5 years. Ipsilateral breast tumor recurrence (IBTR)-free survival and distant relapse-free survival (DRFS) were recorded as the interval from initial surgery until IRTR or distant relapse. The factors related to IBTR were evaluated using the proportional hazard model. Patients who did not develop IBTR or distant relapse were statistically censored at the time of the last follow-up or death. Survival rates were calculated using the Kaplan-Mayer method. Statistical analyses were conducted using the log rank test. Values < 0.05 were considered statistically significant. Results: The median age at surgery was 65 (range 50-84). The median tumor size was 1.5 cm (range 0-4.0 cm). The median follow-up period for IBTR was 95 months (range 4-192 months). Only 3 patients were treated with adjuvant chemotherapy. The 5- and 10-year overall survival rates were 98.7% and 95.1%, respectively and the 5- and 10-year distant DRFS rates were 99.3% and 96.3%, respectively. The 5- and 10-year IBTR free rates were 97.0% and 89.7%, respectively. Older patients had significantly less IBTR rates (5-year IBTR free rates: 95.8% for ≤64 vs. 98.1% for ≥65, p=0.019). There was no difference in IBTR rates between the large and small tumors (5-year IBTR free rates: 96.9% ≤1.4 cm vs. 96.8% for ≥1.5 cm, p=0.094). PR positivity had a significantly lower IBTR free rates (5-year IBTR free rates: 98.3% for PR positive vs. 91.5% for PR negative, p=0.009). The age at surgery (≤64, p=0.017, Hazard ratio 3.07, 95% CI 1.22-7.70) and the PR status (PR negative, p=0.024, Hazard ratio 2.54, 95% Cl 1.13-5.69) independently affected the IBTR rates. Both the 5- and 10-year IBTR free rates of the patients who were ≥65 at surgery and had PR positive tumors (n=136) were 98.4%. Conclusions: The findings suggest that the “5-mm thick slice and 5-mm free margin” method may be effective in selecting patients who can be treated with breast conserving surgery and hormone therapy without radiotherapy. Citation Format: Norikazu Masuda, Shozo Ohsumi, Reiki Nishimura, Sadako Akashi-Tanaka, Kimito Suemasu, Hideko Yamauchi, Eriko Tokunaga, Tadashi Ikeda, Tsunehiro Nishi, Hiroto Hayashi, Yuichi Iino, Yuichi Takatsuka, Hideo Inaji. Combined analysis of the WORTH 1 and WORTH 2 studies of ipsilateral breast tumor recurrence after breast conservative surgery without radiotherapyusing the “5-mm thick slice and 5-mm free margin method” [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS1-01.

Background: Obesity is reported to be associated with worse prognosis in early breast cancer. However, there is little data regarding the impact of low BMI on survival in patients with breast cancer. As obesity is rare and low BMI is relatively common in Japanese population compared to Caucasians, Japanese cohort is suitable to assess the impact of low BMI on survival in patients with early breast cancer. Recently an exploratory analysis of a small Japanese randomized phase II trial (JFMC 34-0601) suggested that low BMI was associated with a decreased overall response rate to neoadjuvant endocrine therapy with exemestane. We further explored the impact of low BMI on survival in patients with early breast cancer using a dataset of randomized phase III trials in Japan. Methods: Patients included in prospective randomized phase III trial N-SAS BC02 and BC03 were retrospectively analyzed. N-SAS BC02 investigated four arms of adjuvant chemotherapy consisted of taxane alone or in combination with anthracycline-containing regimen (median follow up of 6.1 years). NSAS BC03 compared anastorozole with tamoxifen as adjuvant endocrine therapy (median follow up of 6.4 years). The correlation of BMI and overall survival was exploratory analyzed. This study was supported by the Public Health Research Center Foundation CSPOR. Results: A total of 1726 patients were included in our study. Median age was 56 (24 – 82) years, 71.2% of tumors were ER positive, and 9.7% were HER2 overexpressed. Lymph node metastases were observed in 76% of patients. Mean value of BMI was 23.3 and only 4.6% of patients had BMI over 30. 33.1% of patients had BMI under 22 and 4.8% had BMI under 18.5. In the univariate Cox proportional hazard model, lower BMI was significantly associated with worse prognosis (BMI27, HR 0.55, 95% CI 0.32 – 0.93, p = 0.025). The same trend was observed in multivariate analysis (HR 0.61, p = 0.064). Conclusion: We confirmed that obese patients were relatively rare in Japanese patients with early breast cancer. In this non-obese population, lower BMI was correlated with worse prognosis. However these results should be cautiously interpreted. Our findings suggest that there may be an optimal BMI in patients with early breast cancer and it should be confirmed by another cohort. Citation Format: Yoichi Naito, Yasuo Ohashi, Isao Yokota, Toru Watanabe, Hiroji Iwata, Shozo Ohsumi, Shinji Ohno, Yasuo Hozumi, Seiichiro Yamamoto, Masato Takahashi, Tomohiko Aihara, Hirofumi Mukai. Low body mass index (BMI) is associated with poor survival in Japanese patients with early breast cancer; an exploratory analysis of prospective randomized phase III trials N-SAS BC02 and 03 [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 P6-08-21.

Background: Sensory loss or paresthesia due to division of the intercostobrachial nerve (ICBN) is a complication of axillary lymph node dissection (ALND). Preservation of the ICBN may be of value, but few prospective studies have shown an impact of preservation on sensory changes or health related quality of life (HRQOL) after breast cancer surgery. Methods: Prospective study was performed to evaluate the association of ICBN preservation with sensory change and HRQOL at 1 (baseline), 6, 12 and 24 months after breast cancer surgery in 140 patients. The sensory examination included dysesthesia, paresthesia, abnormal touch and pain sensation in the upper arm. Results: Division of the ICBN did not influence the frequency or severity of subjective dysesthesia and paresthesia. There was no marked difference in touch or pain sensation at baseline between patients with a preserved (group P) and divided (group D) ICBN. In group P, the percentage of patients aware of a sensory deficit or loss decreased with time, and that of patients aware of a hypersensitive sensation increased. These changes did not occur in group D, leading to a significant difference between the groups at 24 months. The main difference between the groups was the area with reduced touch or pain sensation. This area decreased with time in group P, but not in group D. ICBN preservation or division did not influence HRQOL. Conclusion: ICBN preservation in ALND has a benefit of a reduced area with long-term axillary hypoesthesia, but has no influence on improvement of pain and HRQOL. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-14-07.

Background: Aromatase inhibitors (AIs) are standard treatment in the adjuvant setting such as initial, switch and extended treatment in postmenopausal hormone-sensitive breast cancer patients overseas. Non-steroidal AIs have usually been used as adjuvant treatment in Japanese practice. We already reported the efficacy and short term adverse events by switching therapy from tamoxifen (TAM) to anastrozole (ANA) in Japan (Breast Cancer Res Treat. 2010;121:379–87). However, the usage of adjuvant hormone therapy currently shows a trend to continue for a long time. Furthermore, long-term follow-up data is very important for the safe use of AIs. Off course, there are many data on safety profiles in Western countries. However, there are limited data in the Asian population. Methods: We investigated the planned analyses by using the data of a randomized adjuvant study of tamoxifen alone versus sequential tamoxifen and anastrozole in hormone-responsive postmenopausal breast cancer patients (N-SAS BC 03 trial. UMIN CTRID: C000000056). We examined the chronological changes from baseline to 36 months after randomization between the TAM arm (351 cases) and the ANA arm (345 cases) according to the case report forms (CRFs). We prospectively collected the data and compared data on hot flushes, nausea & vomiting, anorexia, fatigue, mood distress, headaches, arthralgia, leukocytopenia, liver transaminase changes, thromboembolism, vaginal bleeding, vaginal discharge, cardio-vascular events, second primary cancer and contra-lateral breast cancer between the two arms every 3 months from baseline to 12 months, and every 6 months up to 36 months after randomization. The data were expressed as the difference in the incidence over the time course and were analyzed using chi-square tests and logistic regressions with the baseline value as a covariate via generalized estimating equation using robust standard errors. Results: The incidence of arthralgia are significantly better in the TAM arm than the ANA arm (p = 0.00002). However, there are no differences concerning all events excluding arthralgia between the two arms. Ten and twelve cases of second primary cancer occurred in the TAM and ANA arms, respectively (p = 0.6). Six and three cases of contralateral breast cancer occurred in the TAM and ANA arms, respectively (p = 0.3). According to analyses of the chronological changes, significant changes were observed in hot flushes (p = 0.001) and vaginal discharge (P < 0.001) in favor of ANA, and it developed gradually after randomization and continued until 36 months after randomization. Adverse events of arthralgia increased chronologically up to 12 months after randomization in the ANA arm, but the difference between the two arms gradually decreased up to 36 months after randomization. Interestingly, concerning the liver transaminase change, the TAM arm is better until 9 months after randomization and the ANA arm is better from 12 months. There are no other differences between the two arms. Conclusion: Safety profiles of ANA were confirmed by long-term follow-up data of a clinical trial in Japanese women. Adjuvant switch ANA therapy is also one of the standard hormone treatments for hormone-sensitive postmenopausal Japanese women. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-13-07.

Background: Preoperative chemotherapy (PCT) is widely used to increase the possibility of breast-conserving treatment (BCT). However, the appropriate indication for BCT after PCT is controversial, because the rates of ipsilateral breast tumor recurrence (IBTR) may be higher than those reported for BCT when surgery is used first. We performed a multicenter retrospective study to evaluate factors that were associated with IBTR in patients with BCT after PCT, and validated M. D. Anderson Prognostic Index (MDAPI) (Cancer 2005;103:689–95) using our data set. Patients and Methods: From eight Japanese hospitals, data were extracted on a total of 381 patients with invasive breast cancer (BC) who were treated with ≥3 cycles of PCT followed by breast-conserving surgery and irradiation. The rates of IBTR were evaluated by MDAPI including clinical N2 or N3 disease, pathologic residual tumor >2 cm, multifocal pattern of residual disease, and lymphovascular space invasion in the specimen. Kaplan-Meier method was used to estimate cumulative recurrence rates. Log-rank test and Cox's proportional hazard model were used for statistical analyses. Results: Median age at diagnosis of the primary tumor was 48 years; median size of the primary tumor at diagnosis was 4.0 cm. One hundred and forty-six patients received postoperative chemotherapy and 211 received postoperative endocrine therapy. At a median follow-up period of 50 months, 18 of 381 patients developed IBTR, which resulted in 5-year IBTR-free rate of 94.1%. Univariate analyses revealed that estrogen receptor (ER) status both before and after PCT (positive vs. negative), pathological nodal status after PCT (≥4 vs. 0–3 positive nodes), and pathologically residual invasive tumor (≥1.8 vs. ≤1.7 cm) were significantly associated with IBTR (all P < 0.05). Pathological margin status did not affect IBTR rate (P=0.88). Multivariate analysis revealed that significant independent predictors of IBTR included ER status after PCT (Hazard Ratio [HR], 0.10; P Conclusion: Our prognostic index (MDAPI plus ER status) would be useful for clinical decision making according to surgical procedures after PCT. BCT is an appropriate treatment option for patients with the low prognostic index (0 to 2). The high risk population with the high prognostic index (3 to 5) may benefit from mastectomy. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-12-03.

OBJECTIVE: Although resection of isolated pulmonary metastases is a common treatment in other primaries such as colon cancer, the role of lung metastasectomy of breast cancer is still unclear. The objective of the present study was to investigate the clinical outcome of our operated patients with isolated pulmonary breast cancer metastases and discuss the clinical implication of resection with curative intent for them. METHODS: We retrospectively analyzed 86 female patients with histologically proven isolated pulmonary metastases from breast cancer who were treated with surgery of curative intent between January 1980 and September 2010 at 7 Japanese hospitals. The mean age of them was 50 years, the median disease free interval (DFI) from the definitive surgery for the primary breast cancer was 4.6 years (range: 0.5−20.4 years) and the median follow-up after lung metastasectomy was 4.1 years (range: 0.3−30.9 years). RESULTS: Lung metastasectomy was performed by thoracotomy in 22 patients and by video-assisted thoracoscopic surgical resection in 64 patients. The number of metastatic foci resected was one for 79 patients, two for 6, and unknown for 1. Lymph node resection was performed for 12 patients, was not done for 69, and unknown for 5. Five-year survival rates after lung metastasectomy were 68% in the patients. The main prognostic factor was the DFI. Five-year survival rates for patients with DFI of longer than 2 years (n = 72) and those with DFI of shorter than 2 years (n=14) were 74.5% and 33.8%, respectively (p = 0.0006). Five-year survival rates after lung metastasectomy were 68% in patients without macroscopic residual pulmonary tumor after lung metastasectomy (n = 69) and 34% in those with macroscopic residual tumor (n = 12) (p = 0.023). Five-year disease free survival after lung metastasectomy for patients without macroscopic residual tumor was 51 %. Five-year survival rates were 78% in patient with endocrine hormonal therapy following lung metastasectomy (n = 51) and 53% in those without endocrine hormonal therapy (n = 35) (p = 0.045). No prognostic influence could be demonstrated for age, number of initial axillary node metastases, primary tumor size. CONCLUSION: The prognosis of the breast cancer patients with isolated pulmonary metastases who underwent metastasectomy with curative intent was good. It was affected by the biological aspects of the primary tumor, “curativity” of the resection, and systemic treatments after lung resection. It may be expected that some of those patients will be cured by surgery with curative intent. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-15-04.

Background Axillary surgery for breast cancer causes several postoperative complications including edema of the ipsilateral arm and sensory disturbance of the ipsilateral upper arm. Although sentinel node biopsy has been considered as a standard procedure for node-negative patients, some complications bother patients even after it. Although data regarding the quality of life of patients and/or subjective and objective assessment of arm morbidity after axillary surgery have been reported, to our knowledge, quite a few data have been reported on actual examination of sensory disturbance of the ipsilateral upper arm after sentinel node biopsy alone. We report comparative data regarding the objective and subjective degrees of postoperative sensory disturbance of the ipsilateral upper arm examined prospectively between sentinel node biopsy alone and axillary dissection. Patients and Methods A total of 118 patients, who received breast cancer surgery with sentinel node biopsy alone (51 patients)(SN group) or axillary dissection (67 patients)(AD group) at NHO Shikoku Cancer Center, were prospectively evaluated sensory disturbance regarding the following: (a) dysesthesia, (b) paresthesia, (c) degree of disturbed tactile sensation, (d) degree of disturbed pain sensation, (e) ratio of disturbed area of tactile sensation (defined as (A) length of disturbed area/(B) total length of upper arm), and (f) ratio of disturbed area of pain sensation (defined as A/B). Patients were either asked about the above or examined for them at one month, 6 months and 1 year, respectively, after surgery. At surgery it was recorded whether or not the intercostobrachial nerve(s) were totally preserved in patients who underwent axillary dissection. Unpaired t-test, Mann-Whitney U-test and Wilcoxon signed rank test were used to test statistical significance. Results: The mean ages at surgery were 54.7 and 53.7 years in the SN and AD groups, respectively (P = 0.66). The mean number of biopsied lymph nodes in the SN group was 2.4 (range: 1–5). In 22 patients of the AD group the intercostobrachial nerves were totally preserved. There was no difference in dysesthesia, paresthesia, and the level of disturbed pain sensation between the two groups throughout one year after surgery. However, the patients in the SN group showed milder disturbed tactile sensation at one and 6 months than those in the AD group (P = 0.04 and 0.03, respectively). Both the ratios of disturbed area of tactile and pain sensation were statistically significantly lower in the SN group than in the AD group throughout one year (P = 0.03 ∼ 0.12 for any comparison). On the other hand, the mean ratios in the AD group became lower from 0.23 to 0.17 for tactile sensation and from 0.20 to 0.13 in pain sensation (P = 0.02, and 0.05 for tactile and pain sensations, respectively). Conclusion: Sensory disturbance of the ipsilateral upper arm after sentinel node biopsy alone was much milder than after axillary dissection throughout the study period. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-14.

Background The steroidal irreversible aromatase inhibitor (AI) exemestane (E), the non-steroidal reversible AI anastrozole (A) and tamoxifen (T) are approved for the first-line treatment of the postmenopausal women with hormone receptor (HR) positive advanced breast cancer (ABC) in Japan. Although there are some studies which compare the efficacy and safety of AIs and T in the first-line disease setting, the number of studies that compare efficacy and safety of AIs is limited. We conducted this multicenter, randomized, double-blinded non-inferiority study, to evaluate the time to progression (TTP) in HR positive ABC randomized to therapy with E or A. Methods Patients (pts) who were ≥20 years [yrs], postmenopausal, ECOG PS ≤1 and had HR positive ABC that recurred after the adjuvant therapy or metastatic disease settings were eligible and randomized (1:1) to 25 mg/day of E or to 1 mg/day of A. Data were evaluated for non-inferiority of E compared to A defined as the upper limit of a two-sided 95% confidence interval (CI) of the hazard ratio (HR) of TTP being less than or equal to 1.25. The primary endpoint was TTP assessed by the independent radiological images review committee (RIRC). Secondary endpoints included TTP by investigator, time to treatment failure, overall survival (OS), objective response rate (ORR), clinical benefit rate, and safety. Results A total of 298 pts from 58 sites were randomized to E (n=149; mean age: 63.4 yrs) or A (n=149; mean age: 64.0 yrs). The mean BMI for the E and A arms were 23.0 kg/m2 and 23.6 kg/m2, respectively. Six pts (2 pts in E arm, 4 pts in A arm) were excluded from the full analysis set due to lack of evaluation for anti-tumor response after study medication started. Median TTP (as per RIRC) was 13.8 months (M) vs. 11.1 M for E vs. A, respectively (HR 1.007; 95% CI: 0.771−1.317). Median TTP (Investigator) was 13.8 M vs. 13.7 M for E vs. A, respectively (HR 1.059; 95% CI: 0.816−1.374). The median OS for A treated pts was 60.1 M, OS for E was not reached (as of data cut-off: December 8, 2010). ORR for E was 43.9% (95% CI: 35.3−52.8) and 39.1% (95% CI: 30.6−18.1) for A. Other analyses, including sub-population analyses are ongoing. The incidence of treatment related adverse events (AEs) in E arm was 71.1% (n=106) and in A arm 59.7% (n=89); the AEs were mostly grade 1 and 2 in 61.7% (n=92) and 53.7% (n=80) of pts respectively. They were expected and manageable. Treatment related SAEs were similar in both groups: 6 (4.0%) in E arm and 5 (3.4%) in A arm. The most common AEs for E were hot flushes (22.1%), arthralgias (16.8%), musculoskeletal stiffness (11.4%) and γ-GTP increased (10.1%); in A arm, hot flushes (14.8%) and arthralgia (16.8%) were observed in >10% pts. Conclusions Although median TTP (RIRC) of E is slightly improved compared with that of A, the result of TTP did not meet the non-inferiority criteria. There were no significant differences found between E and A in ORR. Although AEs in E were numerically higher, the observed AE profiles were similar to those previously reported for E and A. This study shows that E is comparable to A in efficacy and safety. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-16-01.

Background: Although preoperative chemotherapy (PCT) was originally used to make locally advanced breast cancers (BC) operable, it is now frequently utilized to make relatively large primary tumors small enough for breast conserving treatment (BCT). A large number of studies have been performed to identify risk factors of ipsilateral breast tumor recurrence (IBTR) after breast conserving treatment for originally small tumors. However, those studies for patients (Pts) who received BCT after PCT for relatively large tumors are limited. We have done a multicenter retrospective study to identify factors which were associated with IBTR in Pts treated with BCT after PCT. Patients and methods: From 7 Japanese hospitals, data, which regard characteristics of tumors and Pts, and treatment, of Pts who fulfilled the following criteria; 1. Female BC Pts who started PCT before January 2007 2. Her tumor was invasive, clinically solitary, and 2 cm or largerby palpation at diagnosis 3. She received 3 or more cycles of PCT 4. She received breast conserving surgery as a definitive surgery after PCT including axillary dissection or sentinel node biopsy 5. She received radiotherapy at least to the conserved breast. Pts with inflammatory BC and BC Pts who received preoperative treatment(s) other than chemotherapy were excluded. Kaplan-Meier method was used to estimate cumulative recurrence rates. Log rank test and Cox's proportional hazard model were used for statistical analyses. Receiver Operating Characteristic (ROC) Curves and C statistics were used for evaluating the prediction ability of Cox's proportional hazard model about IBTR. Results: A total of 324 Pts were registered. The median age at diagnosis of them was 48 years old. The median size of the primary tumors by palpation at diagnosis was 4 cm. For PCT anthracycline-based regimens were used for 83 Pts, taxane-based regimens were for 29, and anthracycline-taxane regimens were for 212. One hundred forty two Pts (43.8%) received postoperative chemotherapy, 180 (55.6%) had postoperative endocrine therapy, and only 7 had postoperative trastuzumab therapy. The median follow-up period was 45 months. Nineteen Pts (5.9%) developed IBTR. The cumulative 4-year IBTR rate was 5.5%. Univariate analyses revealed that estrogen receptor (ER) status both before and after PCT, pathological nodal status after PCT, and pathologically residual invasive tumor (solitary vs. multifocal, 1.7 cm or smaller vs. 1.8 cm or larger) were statistically significantly associated with IBTR (P < 0.05 for all of them). Pathological margin status did not affect IBTR rate (P=0.73). ER status prior to PCT (positive vs. negative)(Hazard Ratio [HR], 6.76; P=0.012), size of the residual invasive tumor (1.7 cm or smaller vs. 1.8 cm or larger)(HR, 4.74; P=0.020), and pathological nodal status after PCT (0-3 positive nodes vs. 4 or more)(HR, 3.03; P=0.041) were associated with IBTR on multivariate analysis. C statistic was 78.3%. Conclusion: Mastectomy may be a better choice for the Pts who have tumors with negative ER, pathologically large (1.8 cm or larger) residual invasive lesions after PCT, or 4 or more pathologically positive nodes after PCT in terms of local control. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-10-05.

Background: The treatment for metastatic breast cancer (MBC) is usually systemic therapy decided by the hormone and HER2 status of primary breast cancer lesion. There are some reports about the discrepancy in hormone and HER2 status between primary and metastatic lesion in these days. We have reported previously that the expression of ALDH-1 which considered the pathological markers of breast cancer stem cell in axillary lymph node matastases is a significant predictor of poor outcome in primary breast cancer patients (Figure 1). We evaluated the role of surgery in the diagnosis and treatment of a solitary pulmonary nodule (SPN) in breast cancer patients and demonstrated the significance of analyzing the immunopathological features in metastatic breast cancer lesion. Methods: Between 1990 and 2006, 17 patients (PM) with SPN which were diagnosed breast cancer metastases underwent complete pulmonary resection and 36 MBC patients (AP) underwent autopsy after breast cancer related death in our hospitals. We retrospectively analyzed clinicopathological features and the expression of ER, HER2, Ki-67 and ALDH-1 in both primary and metastatic breast cancer lesions. Results: The median age of PM patients was 53 (range 30-80). All PM patients had not other metastases and had undergone curative breast cancer operation. The pulmonary operation were partial pulmonary resection in 15(88%) and lobectomy in 2 (12%) patients. The median disease free survival (DFS) was 63 months (range 9-175). Median overall survival (OS) was 181 months and the median OS after pulmonary operation was 48 months. The median DFS and OS of AP patients were 21 and 43 months. All AP patients had multiple visceral metastases. We compared the immunohistlogical status between primary and metastatic lesion and evaluated the colletation with these status in metastatic lesion and prognosis in all patients. Conclusion: Pulmonary resection was effective to diagnose and the OS after resection was relatively long in PM patients. We report the value of the expression of ER, HER2, Ki67 and ALDH-1 in distant metastatic lesions. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-14-20.

PURPOSE: The clinical efficacy of tamoxifen is suspected to be influenced by the activity of drug-metabolizing enzymes and transporters involved in the formation, metabolism and elimination of its active forms. We investigated relations of polymorphisms in transporter genes as well as CYP2D6 to clinical outcome of patients with tamoxifen treatment. PATIENTS AND METHODS: We enrolled 282 hormone receptor-positive, invasive breast cancer patients receiving tamoxifen monotherapy. We investigated the effects of allelic variants of CYP2D6 and tag-SNPs of DT-1, DT-2 and DT-3 on recurrence-free survivals using Kaplan-Meier and Cox regression analyses. Plasma concentrations of tamoxifen metabolites were measured in 98 patients taking 20 mg/day of tamoxifen. RESULTS: CYP2D6 variants were significantly associated with shorter recurrence-free survival (P = 3.6×10−5; hazard ratio (HR) 9.52 [95% CI 2.79-32.45] in patients with 2 variant alleles vs without variant allele). Among 51 tag-SNPs in transporter genes, a significant association was found at SNPY in DT-1(P = 1.7×10−4; HR 10.64 [95% CI 1.44-78.88] in patients with AA vs GG genotypes). The number of risk alleles of CYP2D6 and DT-1 showed cumulative effects on recurrence-free survivals (P = 5.5×10−8). The patients carrying 4 risk alleles had 45.25-times higher risk compared to those with ≤1 risk allele. CYP2D6 variants were associated with lower plasma levels of endoxifen and 4-hydroxytamoxifen (P = 4.3×10−6 and 5.2×10−4), whereas no significant difference was found among DT-1 genotype groups. CONCLUSION: Our results indicated that polymorphisms in CYP2D6 and DT-1 are important predictors for the prognosis of breast cancer patients treated with tamoxifen. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3604.

Background:In order to obtain negative margins after breast conserving surgery (BCS), even repeated surgery is widely accepted. Before surgery, it is important to conduct a precise assessment of the extent of the breast cancer so that each patient can receive individualized surgery. To evaluate the utility of breast computed tomography (CT) as a tool to manage BCS, a multi-institutional prospective study was conducted in Japan.Patients and Methods:Patients were eligible to participate in this study if they had histologically proven breast cancer and were determined to be BCS candidates based on palpation, mammography (MMG) and ultrasonography (US). Written informed consent was obtained from each patient. First, the surgeon marked the line of planned excision on the skin using information from the MMG and US. Next, an expired angiographic catheter was placed on the mark to show the original surgical margin on the CT image. Breast CT was scanned 60 seconds after the bolus injection of the contrast material in the supine surgical position. The surgeon determined the extent of surgery based on the breast CT results. Surgical specimens were serially sectioned in 5-mm slices.Results:Three hundred and two patients were enrolled in this study. The CT scanners used in this study varied from a single helical CT to a 64-row multidetector CT. The results of the breast CT changed the extent of resection in 14.7% of patients. Among the 5 patients who were recommended to undergo a mastectomy, 4 patients had multicentric tumors pathologically and 1 patient had a widely spread intraductal component. The other patients were recommended to have a quadrantectomy based on the extent of breast cancer that was visualized by CT. Three patients (1%) who required conversion from a lumpectomy to quadrantectomy resulted in overexcision. In short, breast CT correctly changed the extent of surgery in 13.7% of the examined patients.Conclusion:This prospective study suggested that breast CT is useful for hospitals equipped with any type of CT and can be used to provide patients with individualized surgery. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5021.

Background: Taxanes are frequently used in treatment of breast cancer (BC) patients. However, some patients treated with taxanes, especially docetaxel (DTX), experience severe edema during and following the treatment. We prospectively assessed body weight and health-related quality of life (HRQOL) related to edema in a randomized controlled trial (RCT) comparing four taxane-containing regimens in an adjuvant setting.Patients and Method: We conducted NSAS BC02 trial in which postoperative patients with node positive BC were randomly assigned to receive one of the following four adjuvant chemotherapeutic regimens; (1) ACP regimen: 4 cycles of doxorubicin 60mg/m2 plus cyclophosphamide 600mg/m2 q3weeks (AC) followed by 4 cycles of paclitaxel (PTX) 175 mg/m2 q3weeks, (2) ACD regimen: 4 cycles of AC followed by 4 cycles of DTX 75mg/m2 q3weeks, (3) PTX regimen: 8 cycles of PTX, (4) DTX regimen: 8 cycles of DTX. During the study we recorded body weight at baseline (at study entry), on day 1 of each cycle and at 8 months, and every 6 months thereafter. And we asked the patients to answer FACT-B, and -Taxane at baseline, on day 1 of cycle 3, 5, and 7, and at 8 and 12 months. We compared the change of weight and the scores of 4 items regarding edema in FACT-B (B8) (change in weight) and FACT-Taxane (Tax1 [anasarca], Tax2 [edema of hands], and Tax3 [edema of legs]) among the four regimens. Data were analyzed on an intent-to-treat basis. The statistical significance of the differences among the regimens was examined with analysis of covariance and t-test.Results: Of 1060 patients who entered N-SAS BC 02 trial, first 300 patients participated in this HRQOL study (ACP 74 patients, ACD 75, PTX 76, and DTX 75). The weight increased markedly and recovered by 8 months in the patients of DTX regimen, increased slightly in those of ACD regimen, and was almost stable in those of ACP and PTX regimens. The difference in the change of weight from the baseline to the 8th cycle between the patients of DTX plus ACD regimens and those of ACP plus PTX regimens was statistically significant (P< .0001). The compliance of FACT-B, and -Taxane was high throughout the study period (> 85 % at each point). The scores of B8, Tax1, Tax2, or Tax3 were relatively stable in ACP, ACD, and PTX regimens over the study period, but those of DTX regimen became lower (indicating worse HRQOL) up to 8 months, then recovered to the baseline except the scores of Tax2 which were still lower than those of other 3 regimens at 12 months. When the scores of the patients of DTX regimen were compared with those of other 3 regimens combined, the differences were statistically significant in all items of B8 (P= .0450), Tax1 (P= .0016), Tax2 (P< .0001), and Tax3 (P< .0001).Discussion: The patients who received 8 cycles of DTX were agonized by chemotherapy (CT)-related edema. However, the agony seemed to disappear by 6 months after the completion of CT except for that of edema of hands. The reason why only the scores of Tax2 did not recover at 12 months in the patients of DTX regimen is suspected to be the ipsilateral hand and arm edema affected by axillary dissection which might have lasted for a long time. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2090.

Background: National Surgical Adjuvant Study of Breast Cancer (N-SAS BC) 04, a sub-study of Tamoxifen (TAM) and Exemestane (EXE) Adjuvant Multinational (TEAM) trial, analyzed lipid metabolism (LM), bone mineral density (BMD), health-related quality of life (HRQOL), psychological distress, and blood coagulation between patients (pts) randomly assigned to take TAM, EXE or anastrozole (ANA). We report here a final analysis for HRQOL and psychological distress in N-SAS BC 04.Patients and Methods: Eligible pts were postmenopausal women with surgically treated stage I to IIIA hormone responsive breast cancer (BC), and with at least one of following criteria; pathologically ≥3 cm, pathologically positive nodes, nuclear grade 3, invasive lobular carcinoma or metaplastic carcinoma. They were randomly assigned to take EXE or TAM (TEAM International groups) when they were receiving treatment of hyperlipidemia or osteoporosis, when they had a high level of total cholesterol (≥260 mg/dl) or triglyceride (≥300 mg/dl) and a low BMD ( 84%) in each group. Scores of FACT-G, -B and -ES increased at 3 and 12 months from baseline in pts on TAM; however, these did not in pts on EXE or ANA. In result the scores of FACT-B were statistically significantly better in the TAM group than the EXE or ANA groups (P Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5041.

Abstract #1136 Backgroud: Three years ago, we reported the interim results regarding heath-related quality of life (HRQOL) outcomes of the patients who switched their adjuvant endocrine therapy from several years of tamoxifen (TAM) to anastrozole (ANA) and those who had TAM for a total of 5 years in the randomized trial, National Surgical Adjuvant Study of Breast Cancer (NSAS BC) 03. We present the final results of HRQOL and psychological distress in the NSAS BC 03. Patients and Methods: Recurrence-free postmenopausal breast cancer patients who had received definitive surgery for hormone receptor positive breast cancer, and had been taking TAM for 1 to 4 years after the surgery were enrolled in the randomized trial: N-SAS BC 03. They were randomly assigned to continue TAM for the remaining periods of a total of 5 years or to switch from TAM to ANA and take the latter for the remaining periods. Primary endpoints of the N-SAS BC 03 trial were disease-free survival and adverse events. HRQOL and psychological distress were evaluated as secondary endpoints. They were asked to answer patient-administered instruments to assess HRQOL (FACT-B [breast cancer scale] and FACT-ES [endocrine symptom scale]) and psychological distress (CES-D: Center for Epidemiologic Studies Depression scale) at the randomization (baseline), 3 months, 1 and 2 years after the randomization. HRQOL and psychological distress scores during this period were compared using t-test and the general linear model with correlated errors. Results: There was no difference in demographic and medical characteristics between the two treatment groups. The response rates of the questionnaires were 98.6%, 97.2%, 90.9% and 78.5% at baseline, 3 months, 1 and 2 years after the randomization, respectively. At baseline 694 patients (346 in the TAM group and 348 in the ANA group) answered them. The total scores of FACT-G, and FACT-ES and the scores of FACT-G physical well-being (PWB) subscale were statistically significantly better in the TAM group than in the ANA group (P = 0.042, 0.038, and 0.005, respectively) after the randomization, while those of FACT-B in the former were marginally better than those in the latter (P= 0.066). However, there were no statistically significant differences between the two treatment groups for the scores of CES-D, and subscales other than PWB of FACT-G, FACT-B, and FACT-ES. Conclusions: Further TAM treatment after adjuvant TAM for 1 to 4 years may provide postmenopausal breast cancer patients with slightly better HRQOL comparing with switching to ANA. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1136.