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Background The Safari study (UMIN000015168) was a retrospective, multicenter study in which 1072 consecutive cases of estrogen receptor-positive advanced breast cancer treated using 500 mg fulvestrant were registered. We previously reported the relationship between the patient factors and overall survival after the diagnosis using the same cases and the same factors for the analysis of time to treatment failure in patients with estrogen receptor-positive advanced breast cancer. The current study is an ad hoc analysis that focused on the relationship between the patient factors and overall survival after recurrence by adding factors generally associated with overall survival after recurrence. Methods The overall survival after recurrence in patients with estrogen receptor-positive human epidermal growth factor receptor 2 negative recurrent breast cancer was analyzed via univariate and multivariate analyses with a Cox proportional hazards model. Results A total of 598 cases were used for the analysis of overall survival after recurrence. Multivariate analysis revealed that favorable overall survival (median, 6.4 years) was significantly correlated with long time from recurrence to fulvestrant use (≥3 years), low nuclear or histological grade (G3 vs. G1), long time to treatment failure of initial palliative endocrine therapy (≥12 months) and long time to initial palliative chemotherapy (≥2 years). Conclusion The results of this study indicate that sequential endocrine monotherapy may be a useful treatment option for patients with estrogen receptor-positive/human epidermal growth factor receptor 2 negative recurrent breast cancer who have been successfully treated with initial long-term palliative endocrine therapy.

Background: Only old evidence exist to back up the use of medroxyprogesterone acetate (MPA) in endocrine therapy. Therefore, this study aimed to explore the factors that influence the time to treatment failure (TTF) of MPA in real world settings as late-line treatment following aromatase inhibitors and fulvestrant. Methods: This was a cohort study that used the database of the Safari study, on estrogen receptor-positive (ER+) post-menopausal advanced breast cancer previously treated with fulvestrant (UMIN000015168). We created Kaplan-Meier curves for TTF treated with MPA. Further, univariate and multivariate analyses were performed using a Cox hazard model of the clinicopathological factors involved in the TTF of MPA. Results: Fist, we made Kaplan-Meier curves by treatment line for MPA in TTF analysis population 1 (n = 244), excluding HER2+ and HER2 with unknown status. The median TTF for MPA was 8.2 months (95% CI 5.1–14.9) for first- and second-line treatments, 3.0 months (95% CI 2.5–3.9) for third-line treatment, and 4.1 months (95% CI 3.5–5.0) for fourth or later treatment lines. The first- and second-line treatments had significantly longer TTF than the third-line treatment (P < 0.001) and fourth-line or later treatments (P < 0.001). No difference in TTF was observed between the third and fourth or later treatment lines. Similar results were obtained in the analysis population 2 (n = 203) for TTF, excluding cases in which MPA was considered to have been used in palliative care. The median TTF for MPA was 7.9 months (95% CI, 5.1-16.0) for first- and second-line treatments, 3.0 months (95% CI 2.8–4.6) for third-line treatment, and 4.3 months (95% CI 3.7–5.6) for fourth or later treatment lines. The first- and second-line treatments had significantly longer TTF than the third-line treatment (P < 0.001) and the fourth-line or later treatments (P < 0.001). No difference in TTF was observed between the third and fourth or later treatment lines. Second, Table 1 shows the clinicopathological factors involved in the TTF of MPA. In univariate analysis, long DFI (≥ 6 years), small nuclear or histological grade, and the presence of visceral metastases correlated with significantly long TTF (P < 0.05). Whereas PgR, adjuvant chemotherapy, and adjuvant endocrine therapy did not affect the TTF of patients treated with MPA. However, in the multivariate regression analysis, only longer DFI (≥ 6 years) was correlated with a significantly longer TTF. Third, we compared the clinicopathologic factors in the groups that received MPA as the fourth or later treatment lines and achieved a TTF of more than 1 year with those that did not. There were no characteristic clinicopathological factors distinct between the two groups. Conclusion: In actual clinical practice, patients treated with MPA alone as the fourth or subsequent treatment lines showed a TTF of 4 months, suggesting that there is merit in using MPA even in late treatment lines, especially in patients with long DFI and those who are difficult to treat with other antineoplastic agents. Table 1. Univariate and Multivariate analyses to investigate association between clinicopathological factors and TTF of MPA (n=170) Citation Format: Kaho Utsunomiya, Hidetoshi Kawaguchi, Yutaka Yamamoto, Shigehira Saji, Norikazu Masuda, Takahiro Nakayama, Kenjiro Aogi, Keisei Anan, Shoichiro Ohtani, Nobuaki Sato, Toshimi Takano, Eriko Tokunaga, Seigo Nakamura, Yoshie Hasegawa, Masaya Hattori, Tomomi Fujisawa, Satoshi Morita, Miki Yamaguchi, Toshinari Yamashita, Daisuke Yotsumoto, Masakazu Toi, Shinji Ohno. Retrospective study using database for the effectiveness of medroxyprogesterone acetate in patients with ER-positive/HER2-negative postmenopausal advanced breast cancer: An additional analysis of the JBCRG-C06 Safari study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-03-15.

BackgroundOnly old evidence exists to back up the use of medroxyprogesterone acetate. Therefore, this study aimed to explore the factors that influence the time to treatment failure of medroxyprogesterone acetate in real-world settings as late-line treatment.MethodsThis was a cohort study that used the database of the Safari study on oestrogen receptor-positive post-menopausal advanced breast cancer (UMIN000015168). We created Kaplan–Meier curves for time to treatment failure with medroxyprogesterone acetate. Further, univariate and multivariate analyses were performed using a Cox hazard model of the clinicopathological factors involved in the time to treatment failure of medroxyprogesterone acetate.ResultsFrom the 1031 patients in the Safari study, 279 patients were selected as the population for the analysis of effectiveness of medroxyprogesterone acetate monotherapy. In the analysis of medroxyprogesterone acetate by treatment line, the median time to treatment failure was 3.0 months for third-line treatment and 4.1 months for fourth and subsequent treatment lines. In cases where medroxyprogesterone acetate was used as a third-line or later endocrine treatment, multivariate analysis showed that the length of the disease-free interval was correlated with the length of time to treatment failure of medroxyprogesterone acetate (P = 0.004). With medroxyprogesterone acetate monotherapy as the fourth-line or later treatment, 20% of the patients achieved a time to treatment failure of 12 months or longer.ConclusionIn actual clinical practice, patients treated with medroxyprogesterone acetate alone as the fourth or subsequent treatment lines showed a time to treatment failure of 4 months, suggesting that there is merit in using medroxyprogesterone acetate even in late treatment lines, especially in patients with long disease-free interval and those who are difficult to treat using other antineoplastic agents.

Background/aim Irinotecan is rarely used on the metastatic breast cancer (MBC) setting. S-1 is an oral mixture of tegafur, gimeracil and oteracil. We conducted this pilot study to assess efficacy and safty of chemotherapy with combined irinotecan and S-1 (IRIS). Patients and methods Irinotecan was given intravenously at 80 mg/m2 on days 1 and 8 and S-1 was given orally at 80-120 mg/day depending on body surface area for 2 weeks, repeating the cycle every 3 weeks. Results Twenty-two patients were enrolled in the study. Median age was 50.5 years (range=26-72). Nineteen patients were evaluable for response. Median overall survival and progression-free survival were 672 days (95% CI=420-967) and 166 days (95% CI=76-814), respectively. Conclusion The IRIS regimen has an acceptable safety profile and modest efficacy against MBC in patients previously heavily treated with chemotherapy. This regimen has potential to treat MBC.

Background: There are now many treatment options for estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative (HER2−) advanced breast cancer (ABC). However, there are few reports indicating the optimal treatment sequence for this disease. Information to predict response to treatment is vital for personalized therapy and determining the most beneficial approach for individual patients. In this study, we attempted to determine predictive factors of response to hormonal therapy and survival outcomes using the large-scale databases constructed in the Safari study (UMIN000015168), a retrospective, multicenter cohort study involving 1,072 Japanese patients receiving fulvestrant 500mg for ER+ ABC. We examined the association between clinicopathological factors and time to failure (TTF) of fulvestrant in Japanese ABC patients. Methods: Among 1072 patients, 247 patients were selected for this study. Inclusion criteria was as follows: 1) patients treated with either SERM or AI in the adjuvant setting (AS) with known starting and finishing date of the treatment (patients relapsed on adjuvant treatment were excluded), 2) patients treated with SERM, AI and SERD in the metastatic setting (MS) as the first and the second line treatment. Influence of the adjuvant hormonal therapy on the TTF of the first line and the second line treatment and overall survival (OS) was assessed. Cox proportional hazards model was used for this analysis. Results: Patients treated with SERM in AS had significantly longer TTF of 1st line and 1st+2nd line of hormonal therapy in MS (1st line: HR 1.519, 95% CI 1.04-2.218, p=0.0307, 1st+2nd line: HR 2.372, 95% CI 1.584-3.551, p Conclusions: Interestingly, once AI-treated patients in AS have relapsed, their hormone sensitivity is lower and survival outcomes are worse compared with SERM-treated patients in AS in this cohort. Our results have consistency with the results of ABCSG-12 trial showing a pronounced higher risk of death for anastrozole-treated patients (Annals of Oncology 26: 313–320, 2015). Since it is a cohort of selected patients who were successfully treated with fulvestrant, prospective analysis would be therefore warranted. Citation Format: Takahiro Nakayama, Hidetoshi Kawaguchi, Norikazu Masuda, Kenjiro Aogi, Keisei Anan, Yoshinori Ito, Shoichiro Ohtani, Nobuaki Sato, Shigehira Saji, Toshimi Takano, Eriko Tokunaga, Seigo Nakamura, Yoshie Hasegawa, Masaya Hattori, Tomomi Fujisawa, Satoshi Morita, Miki Yamaguchi, Hiroko Yamashita, Toshinari Yamashita, Yutaka Yamamoto, Daisuke Yotsumoto, Masakazu Toi, Shinji Ohno. Influence of the adjuvant hormonal therapy on hormone sensitivity and survival outcomes in ER+ and HER2−advanced breast cancer: A subgroup analysis of the JBCRG-C06 Safari study [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 P5-11-11.

Background: After the CONFIRM trial, fulvestrant 500 mg (F500) became a standard treatment for patients with estrogen receptor positive (ER+) advanced/metastatic breast cancer (AMBC). The JBCRG-C06 Safari study (UMIN 000015168) showed that earlier F500 use, a longer time from diagnosis to F500 use, and no prior chemotherapy were associated with significantly longer time to treatment failure (TTF) among Japanese patients with ER+ and HER2-negative AMBC (Kawaguchi H, et al. Breast Cancer Res Treat, 2017; Kawaguchi H, et al. Curr Med Res Opin, 2018). We had carried out subgroup analyses on real world data from the Safari study focusing on ER+ and HER2+ AMBC with the objective to examine further on potential interactions between TTF and the following: F500 single treatment or F500 with anti-HER2 therapy; presence or absence of visceral metastasis; progesterone receptor (PgR) status; and prior chemotherapy for AMBC. Material & methods: The Safari study was a retrospective, multicenter cohort study, conducted in 1072 patients at 16 sites in Japan for ER+ AMBC. Patients starting treatment with F500 between Nov 2011 and Dec 2014 were registered. After the data cleaning through the central review, 94 patients (9.6%) has been included in this sub-analysis among the 978 patients in which HER2 status was confirmed by the documentation. The relationship between baseline clinical/pathological factors, treatment line, and TTF (time from start to cessation of F500 treatment for any reason, including toxicity and death) were analyzed using Kaplan-Meier methods. Univariate analysis of TTF data was performed by Cox hazards model using: age, histological type, histological/nuclear grade, visceral-metastases, stage, PgR, period from AMBC diagnosis to F500 use, treatment line of F500, prior chemotherapy. Results: Median age at diagnosis of AMBC was 57.5yrs (33-85); 59(33-85) and 56.5(39-75) for F500 with/ without anti-HER2 therapy. Median age of fulvestrant start was 61yrs (35-96). 21.3% had de novo metastatic disease; 78.7% recurrent disease; 37.2% visceral metastases. All patients’ ER status was positive, and PgR status was positive in 65.9%, negative 25.5% respectively. HER2 IHC 3+ patients accounted for 44.7%, IHC 2+/1+ for 38.3%. In the case of IHC 2+/1+, HER2-positivity was confirmed by FISH. F500 alone was administered in 52 patients, while F500 with anti-HER2 therapy in 42 patients. At median follow up of 3.9 years, median TTF was 4.4m (95% CI: 3.3-5.7); 3.7m (95% CI: 2.9-5.9), 5.1m(95% CI: 3.6-6.4) for the F500 alone group, F500 with anti-HER2 therapy group respectively (p = 0.5973). F500 with/ without anti-HER2 therapy was administered in 1stor 2nd-line in 20 (21.3%), and ≥3rd-line in 74(78.7%) patients. Median TTF was 6.6m (95% CI: 4.6-8.5) and 3.7m (95% CI: 2.8-5.2) in the 1stor 2nd-line and ≥3rd-line respectively (p value:0.0145). Although no statistically significant difference was found, TTF tended to be shorter in the group receiving chemotherapy prior to F500 (median TTF: 3.7m vs 5.5m). No other clinical parameters including age, PgR status, metastatic sites were associated with the effectiveness. The median OS was 7.8-years (95% CI: 5.9-9.5), which had not been influenced by with/ without anti-HER2 therapy. The toxicity profile we observed was similar to that in the registration trial. Conclusions: Our findings suggest that F500 with/without anti-HER2 therapy appears to be effective also in the ER+ and HER2-positive ABMC setting which is consistent with the limited results previously published. Earlier line use of F500 use may be useful in HER2-positive patients as well as HER2-negative patients. Citation Format: Misato Hagi, Hidetoshi Kawaguchi, Norikazu Masuda, Shigehira Saji, Yutaka Yamamoto, Takahiro Nakayama, Kenjiro Aogi, Keisei Anan, Yoshinori Ito, Shoichiro Ohtani, Nobuaki Sato, Toshimi Takano, Eriko Tokunaga, Seigo Nakamura, Yoshie Hasegawa, Masaya Hattori, Tomomi Fujisawa, Miki Yamaguchi, Hiroko Yamashita, Toshinari Yamashita, Daisuke Yotsumoto, Satoshi Morita, Masakazu Toi, Shinji Ohno. Outcomes of fulvestrant therapy among Japanese women with ER-positive HER2-positive advanced or metastatic breast cancer: A subgroup analysis of the JBCRG-C06 safari study [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 P5-11-13.

Background: To evaluate the survival risk is an important factor to decide or treatment options for recurrent breast cancer patients with estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2 negative (HER2−), though there are not enough supporting reports from large-scale databases. The Safari study (UMIN000015168) is a newly conducted retrospective, multicenter cohort study including 1072 ER+ advanced breast cancer Japanese patients treated with fulvestrant 500 mg mostly as a second or later line hormonal therapy. The follow-up data of Safari study is evaluated to focus on any relationship between clinicopathological factors and post-recurrence survival (PRS) in ER+ HER2− recurrent breast cancer patients. Methods: PRS was defined as the duration from the date of initial treatment for recurrent breast cancer to death. The Cox hazards model was used to evaluate the relationship between the clinical factors and PRS. We also performed multivariate analysis on PRS using factors that showed a statistical difference (p < 0.15) in univariate analysis. Hazard ratios (HRs) with 95% confidence intervals (CIs) and p-values are described. All tests were two-sided and p Citation Format: Kenjiro Aogi, Hidetoshi Kawaguchi, Norikazu Masuda, Takahiro Nakayama, Keisei Anan, Yoshinori Ito, Shoichiro Ohtani, Nobuaki Sato, Shigehira Saji, Toshimi Takano, Eriko Tokunaga, Seigo Nakamura, Yoshie Hasegawa, Masaya Hattori, Tomomi Fujisawa, Satoshi Morita, Miki Yamaguchi, Hiroko Yamashita, Toshinari Yamashita, Yutaka Yamamoto, Daisuke Yotsumoto, Masakazu Toi, Shinji Ohno. Factors associated with prolonged post-recurrence survival in patients with postmenopausal estrogen receptor-positive breast cancer taking fulvestrant: A follow-up data of the JBCRG-C06 Safari study factors associated with prolonged post-recurrence survival in patients with postmenopausal estrogen receptor-positive breast cancer taking fulvestrant: A follow-up data of the JBCRG-C06 Safari study [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 P3-08-55.

Background Assessing survival risk is important for discussing treatment options with estrogen receptor-positive (ER+) advanced breast cancer (ABC) patients. However, there are few reports from large-scale databases on the survival risk factors in ER+ ABC. The Safari study (UMIN000015168) was a retrospective, multicenter cohort study involving 1072 Japanese patients receiving fulvestrant 500 mg mostly as a second- or later-line endocrine therapy for ER+ ABC. The follow-up data after the Safari study were examined, focusing on any relationship between clinicopathological factors and overall survival (OS) in ER+ ABC patients. Methods OS in patients with ER+ ABC was analyzed by univariate and multivariate analyses with a Cox proportional hazards model in this study. Results A total of 1031 cases were evaluable for OS analysis. Multivariate analysis showed that younger age ( Conclusions In ER+ ABC patients whose treatment history included fulvestrant, younger age, longer time from ABC diagnosis to fulvestrant use, no prior palliative chemotherapy use, PgR−, and lower histological or nuclear grade correlated positively with prolonged OS.

Adding taxane to an anthracycline-based regimen improves survival in node-positive breast cancer patients, as shown by clinical trials and meta-analyses. However, no studies have analyzed the number of metastatic lymph nodes in patients with estrogen receptor (ER)-positive cancer. This study investigated whether adding a taxane to an anthracycline-based regimen improved prognosis in node-positive, ER-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients in a real-world setting. Using Japanese Breast Cancer Society registry data, we compared disease-free survival (DFS) of patients with ER-positive, HER2-negative breast cancer, excluding those receiving neoadjuvant chemotherapy, between those who received an anthracycline-based regimen followed by a taxane-based regimen (A + T) and those who received only an anthracycline-based regimen (A w/o T), stratified by lymph node status. A Cox proportional hazards model was used to evaluate DFS in both groups. There were 4566 eligible patients with ER-positive, HER2-negative breast cancer. During the median follow-up period of 60 months, there were 481 recurrences and 149 deaths. There was no significant difference in DFS between the A + T and A w/o T groups among patients with 1–3 positive nodes, while there was a significant difference among patients with ≥ 4 positive nodes. In patients with ER-positive, HER2-negative breast cancer, adding taxane to an anthracycline regimen did not improve DFS in patients with metastasis in 1–3 lymph nodes. We considered that the group without the addition of taxane might be present in patients with ER-positive, HER2-negative lymph node metastases.

Background The Safari study (UMIN 000015168) was a retrospective, multicenter study in which 1072 consecutive cases of estrogen receptor-positive (ER+) advanced breast cancer (ABC) treated using 500 mg fulvestrant were registered. We previously reported the relationship between the patient factors and overall survival (OS) after the diagnosis using the same cases and the same factors for the analysis of time to treatment failure (TTF) in patients with ER + ABC. The current study is an ad-hoc analysis that focused on the relationship between the patient factors and OS after recurrence by adding factors generally associated with OS after recurrence. Methods The OS after recurrence in patients with ER + human epidermal growth factor receptor 2 negative (HER2−) recurrent breast cancer was analyzed via univariate and multivariate analyses with a Cox proportional hazards model. Results A total of 598 cases were used for the analysis of OS after recurrence. Multivariate analysis revealed that favorable OS (median, 6.4 years) was significantly correlated with long time from recurrence to fulvestrant use (≥ 3 years), low nuclear or histological grade (G3 vs. G1), long TTF of initial palliative endocrine therapy (≥ 12 months), and long time to initial palliative chemotherapy (≥ 2 years). Conclusion In patients with ER + HER2 − recurrent breast cancer who received endocrine therapy as the primary palliative treatment, the low proliferation activity of the tumor at the first diagnosis, sensitivity to initial endocrine therapy after the recurrence, and long time to the initiation of chemotherapy might be correlated with the favorable OS after recurrence. Trial registration: University Hospital Medical Information Network: UMIN 000015168, 2014/09/16

Breast cancer survival outcomes vary across different ethnic groups. We clarified the differences in clinicopathological and survival characteristics of breast cancer among Japanese, US residents with Japanese origin (USJ), and US residents with other origins (USO). Using Surveillance, Epidemiology, and End Results (SEER) 18 dataset and Japanese Breast Cancer Society (JBCS) registry, we included patients first diagnosed with breast cancer between 2004 and 2015. We categorized the patients into three groups based on the database and the recorded ethnicity: Japanese (all those from the JBCS registry), USJ (those from SEER with ethnicity: Japanese), and USO (those from SEER with ethnicity other than Japanese). Excluding patients diagnosed after 2012, stage 0, and 4 patients, we examined the overall survival (OS) and breast cancer-specific survival (BCSS) using the Kaplan–Meier method and Cox proportional hazards models, adjusting for age, sex, cancer stage, and hormone receptor (HR) status. We identified 7362 USJ, 701,751 USO, and 503,013 Japanese breast cancer patients. The proportion of HR-positive breast cancer was the highest among USJ (71%). OS was significantly longer among Japanese and USJ than USO (Hazard ratio 0.46; 95% Confidence Interval [CI] 0.45–0.47 for Japanese and 0.66 [95% CI 0.59–0.74] for USJ) after adjusting for baseline covariates. BCSS was also significantly higher in the two groups (HR 0.53 [95% CI 0.51–0.55] for Japanese and 0.53 [95% CI 0.52–0.74] for USJ). In stage I–III breast cancer, Japanese and US residents with Japanese origin experienced significantly longer survival than US residents with non-Japanese origins.

Background Primary sarcomas of the breast are rare and account for less than 1% of all primary breast malignancies. We experienced a case of extraskeletal osteosarcoma of the breast that had a unique clinical course and remarkable findings of mammography and magnetic resonance imaging (MRI). A review of the case reports published in the past few decades showed no reports of a case in which a calcified lesion was followed up three different times on mammography, making this a valuable case report. Case presentation A 52-year-old woman noticed a right breast mass and underwent a breast examination. Mammography showed a 1.5-cm coarse calcified lesion in the upper outer portion of the right breast. Because fine-needle aspiration (FNA) revealed no suspicion of malignancy, she was followed up. Sixteen months later, the tumor grew progressively to 4.5 cm in size with new calcifications that were fine and irregular in shape and density surrounding an enlarged, coarse calcified lesion. Contrast-enhanced magnetic resonance imaging (MRI) showed a high signal intensity in the periphery of the tumor. Extirpation of the tumor was indicated. The pathological findings were extraskeletal osteosarcoma. She underwent additional resection and latissimus dorsi flap reconstruction at the Department of Orthopedic Surgery. Conclusion The present case suggests that mammography findings of a tumor with coarse calcifications that are not typical of benign lesions may be extraskeletal osteosarcoma. A diagnosis must be made as early as possible in order to improve the prognosis of this disease.

The JBCRG-C06 Safari study showed that earlier fulvestrant 500 mg (F500) use, a longer time from diagnosis to F500 use, and no prior palliative chemotherapy were associated with significantly longer time to treatment failure (TTF) among Japanese patients with estrogen receptor-positive (ER+) advanced breast cancer (ABC). The objective of this sub-group analysis was to further examine data from the Safari study, focusing on ER + and human epidermal growth factor receptor-negative (HER2-) cases.The Safari study (UMIN000015168) was a retrospective, multi-center cohort study, conducted in 1,072 patients in Japan taking F500 for ER + ABC. The sub-analysis included only patients administered F500 as second-line or later therapy (n = 960). Of these, 828 patients were HER2-. Results Multivariate analysis showed that advanced age (≥65 years; p = .035), longer time (≥3 years) from ABC diagnosis to F500 use (p .001), no prior chemotherapy (p .001), and F500 treatment line (p .001) were correlated with prolonged TTF (median = 5.39 months).In ER+/HER2- patients receiving F500 as a second-line or later therapy, treatment line, advanced age, no prior palliative chemotherapy use, and a longer period from ABC diagnosis to F500 use were associated with longer TTF.

This retrospective study evaluated the effect of clinical background and treatment line on time to treatment failure (TTF) in advanced/metastatic breast cancer (AMBC) patients receiving F500 in Japan (UMIN 000015168). Patients who commenced F500 treatment were registered at 16 sites in Japan. Correlations between baseline clinicopathological factors, treatment line, and TTF were investigated by Kaplan–Meier analysis. TTF data were analyzed using univariate analysis and multivariate analysis with a Cox proportional hazards model. Data for 1072 patients were available; 1031 patients (96.2%) were evaluable for efficacy. F500 was administered as first-line treatment in 2.0%, second-line in 22.7%, third-line in 26.7%, and ≥fourth-line in 48.6% patients. Median TTF was 5.4 months. Multivariate analysis found that earlier F500 use (first and second vs. third vs. ≥fourth line; hazard ratio (HR) = 0.80, 95% confidence interval (CI) 0.74–0.86; P

The role of postmastectomy radiotherapy (PMRT) in breast cancer patients receiving neoadjuvant chemotherapy (NAC) is controversial. We aimed to evaluate the effectiveness of radiotherapy in patients treated with NAC and mastectomy in the Japanese Breast Cancer Registry. We enrolled patients who received NAC and mastectomy for cT1–4 cN0–2 M0 breast cancer. We evaluated the association between radiotherapy and outcomes, locoregional recurrence (LRR), distant disease-free survival (DDFS), and overall survival (OS) based on ypN status by multivariable analysis. Of the 145,530 patients, we identified 3226 who met the inclusion criteria. Among ypN1 patients, no differences were found in LRR, DDFS, or OS between groups with and without radiotherapy (p = 0.72, p = 0.29, and p = 0.36, respectively). Radiotherapy was associated with improved LRR-free survival (p

The criteria for biological postmenopause have not been clearly defined, although determining the menopausal status is crucial for selecting agents for adjuvant endocrine therapy for patients with breast cancer. The long-term effects of adjuvant toremifene(TOR)and anastrozole(ANA)on serum follicle-stimulating hormone(FSH)and estradiol(E2)levels in Japanese women were examined using data from a prospective randomized study that mainly studied serum lipids and bone metabolism for 2 years. The study medications were administered orally daily at 40 mg and 1 mg for TOR and ANA, respectively. Sixty-nine patients were randomly assigned to the TOR group(n=36)or ANA group(n=33). FSH and E2 levels were measured using chemiluminescent immunoassay. The mean ages of the patients in the TOR and ANA groups were 62.5 and 60.0 years, respectively. None of the patients experienced menstruation during the course of the study. The baseline serum FSH level in the TOR group(69.6mIU/mL)decreased to 59.2%, 54.6%, and 50.0% at 6, 12, and 24 months, respectively, after therapy commencement. The FSH levels ranged from 8.6 to 68.1mIU/mL and were20mIU/mL in 2 patients(9.5%; 8.6 and 14.4mIU/mL). The serum FSH levels in the ANA group did not change markedly over 24months. The baseline serum E2 level in the ANA group(11.6 pg/mL)decreased to 72.4%, 70.7%, and 61.2%at 6, 12, and 24months, respectively, after therapy commencement. The serum E2 level in the TOR group did not change markedly over 24 months. When switching to other endocrine agents as adjuvant therapy for patients with breast cancer treated with TOR, the serum FSH level decreased to half of the preinitiation level, and one-tenth of the FSH levels was20mIU/mL, while the postmenopausal serum E2 level was maintained.

e13005 Background: In Japan, eribulin has been approved for inoperative or recurrent breast cancer, following treatment with an anthracyclines and a taxanes. We reported the efficacy and safety of eribulin as a first-line to third-line treatment in patients with advanced/metastatic breast cancer (MBC) previously treated with anthracylinsanthracyclines and taxanes (Breast 2017). Briefly, the main inclusion criteria were as follows: no history of eribulin administration; an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 2,; human epidermal growth factor receptor 2 (HER2)-negative,; 20–75 years; ≥4 weeks from the last dose of chemotherapy, or ≥2 weeks from the last dosing of endocrine or radiation therapy; measurable lesion based on Response Evaluation Criteria in Solid Tumors (RECIST) ver. 1.1; sufficient organ function; life expectancy of ≥3 months; and no significant abnormalities on electrocardiogram. Patients in this clinical trial were enrolled between December 1, 2011, and November 30, 2013. Eribulin was administered intravenously at a dose of 1.4 mg/m2 during a 2-5 min infusion on days 1 and 8 every 3 weeks. In contrast, baseline neutrophil-to-lymphocyte ratio (NLR) and absolute lymphocyte count (ALC) were reported to predict progression-free survival (PFS) or overall survival (OS). However, these reports were mainly retrospective analysis. Therefore, retrospective evaluation of NLR/ALC in a prospective clinical trial is important to understand the association between NLR/ALC and OS/PFS. Methods: Of 47 prospectively enrolled patients in a previous trial, 45 patients were retrospectively evaluated for baseline NLR/ACL and at the time of 3 cycles of eribulin. The association between NLR/ALC and OS/PFS was also were analyzed for association with OS/PFS. The Kaplan-Meier method was used to estimate the OS/PFS distribution. The cut-off values for baseline NLR and ALC were set at 3 and 1500 /ul, respectively. Results: The median OS of patients with a baseline NLR < 3 was significantly longer than that of patients with a baseline NLR ≥ ≧3 (769 days vs. 409 days; log-rank test p = 0.0333). The median OS of patients with a baseline ALC ≥ ≧1500 was also significantly longer than that of patients with a baseline ALC < 1500 (964 days vs.vs 427 days; log-rank test p = 0.0425). Association between baseline NLR/ALC and PFS were not seen, and also association between at the time of 3 cycles of NLR/ALC and OS/PFS were not seen neither. Conclusions: Baseline NLR and ALC in the patients with HER2- negative breast cancer who plan to treat eribulin may predict overall survival. Clinical trial information: UMIN000007121.

The rate of breast cancer screening for women of all ages in Japan is increasing. However, little is known about the biological differences between screen- and self-detected tumors. We used data from the Japanese Breast Cancer Registry (JBCR), a nationwide registry of newly diagnosed breast cancer cases in Japan, to investigate patients diagnosed between January 1, 2004 and December 31, 2011. We compared the clinicopathological features of tumors and assessed yearly trends regarding the proportion of screen-detected cases during the study period. We found that 31.8 % (65,358/205,544) of cancers were detected by screening. Asymptomatic tumors detected by screening (asymptomatic) were more likely to have favorable prognostic features than those that were self-detected (ductal carcinoma in situ [DCIS]: 19.8 versus 4.1 %, node-negative: 77.0 versus 61.6 %, and estrogen receptor-positive [ER+]: 82.0 versus 72.9 %, respectively). All these findings were statistically significant (p

Background We investigate rates of pathologic complete response (pCR) and tumor expression of ER, PgR, HER2 discordance after neoadjuvant chemotherapy using Japanese breast cancer registry data. Patients and methods Records of more than 300 000 breast cancer cases treated at 800 hospitals from 2004 to 2013 were retrieved from the breast cancer registry. After data cleanup, we included 21 755 patients who received neoadjuvant chemotherapy and had no distant metastases. pCR was defined as no invasive tumor in the breast detected during surgery after neoadjuvant chemotherapy. HER2 overexpression was determined immunohistochemically and/or using fluorescence in situ hybridization. Results pCR was achieved in 5.7% of luminal tumors (n = 8730), 24.6% of HER2-positive tumors (n = 4403), and 18.9% of triple-negative tumors (n = 3660). Among HER2-positive tumors, pCR was achieved in 31.6% of ER-negative tumors (n = 2252), 17.0% of ER-positive ones (n = 2132), 31.4% of patients who received trastuzumab as neoadjuvant chemotherapy (n = 2437), and 16.2% of patients who did not receive trastuzumab (n = 1966). Of the 2811 patients who were HER2-positive before treatment, 601 (21.4%) had HER2-negative tumors after neoadjuvant chemotherapy, whereas 340 (3.4%) of the 9947 patients with HER2-negative tumors before treatment had HER2-positive tumors afterward. Of the 10 973 patients with ER-positive tumors before treatment, 499 (4.6%) had ER-negative tumors after neoadjuvant chemotherapy, whereas 519 (9.3%) of the 5607 patients who were ER-negative before treatment had ER-positive tumors afterward. Conclusion We confirmed that loss of HER2-positive status can occur after neoadjuvant treatment in patients with primary HER2-positive breast cancer. We also confirmed that in practice, differences in pCR rates between breast cancer subtypes are the same as in clinical trials. Our data strongly support the need for retest ER, PgR, HER2 of surgical sample after neoadjuvant therapy in order to accurately determine appropriate use of targeted therapy.

Few studies have reported the association between body mass index (BMI) and outcome among Asian breast cancer patients. We analyzed data for 20,090 female invasive breast cancer patients who had been followed‐up for a median period of 6.7 years entered in the National Clinical Database–Breast Cancer Registry between 2004 and 2006. We used mainly the WHO criteria for BMI (kg/m2) categories

Metaplastic carcinoma is a rare type of breast carcinoma, which tends to be chemo-resistant. We report a case of metaplastic squamous cell carcinoma of the breast diagnosed after neoadjuvant chemotherapy(NAC). A 56-year-old woman was diagnosed as having right-sided breast cancer(invasive ductal carcinoma[IDC], triple negative), cT1cN1M0, stage II A. NAC with 5-fluorouracil, epirubicin, and cyclophosphamide(FEC)followed by docetaxel(DTX)was administered. Tumor progression occurred during both the FEC and DTX regimens. We discontinued NAC and performed breast conserving surgery with axillary lymph node dissection. Histological findings of the resected specimen showed mixed IDC and widely spread squamous metaplasia. Weekly paclitaxel and radiotherapy were administered and the patient is alive with no recurrence 3 years after surgery.

The aim of this study was to investigate preoperative factors associated with ductal carcinoma in situ (DCIS) upstaged to invasive ductal carcinoma (IDC) and sentinel lymph node (SLN) status in patients who underwent mastectomy for a preoperative diagnosis of DCIS. The medical records of 220 patients who underwent mastectomy for a preoperative diagnosis of DCIS were retrospectively reviewed. Fifty-one (22.6%) of 226 lesions were upgraded to IDC after mastectomy. Preoperative factors associated with upstaging to IDC included patient-reported signs and symptoms, a clinically palpable mass, ultrasound findings classified as category 4 or 5, the ultrasound appearance of a mass or widely distributed non-mass abnormality (NMA), and a high Ki67 index. The prevalence of SLN macrometastasis was 0.9%. IDC was diagnosed for 10.9% of lesions of a preoperative ultrasound category of 0–3, 13.0% of those with no mass or NMA detected by ultrasonography, and 14.1% of lesions preoperatively diagnosed by methods other than core needle biopsy (CNB). Of those lesions, none was associated with SLN metastasis. Routinely performing SLN biopsy for patients undergoing mastectomy for a preoperative diagnosis of DCIS is overtreatment, because the prevalence of SLN metastasis was low. SLN biopsy can be omitted for most patients. In particular, we suggest omitting SLN biopsy for patients who have lesions of ultrasound category 0–3, who have neither a mass nor NMA detected by ultrasound, or whose initial diagnosis was made based on a specimen obtained by methods other than CNB.

A population-based cancer registry has been used for the planning and evaluation of cancer control activities based on administration and the care of individual cancer patients by those in the medical profession. The Japanese Breast Cancer Society (JBCS) registry was started in 1975. In 2004, the registry system was moved to a new system using web registration with the cooperation of the Non-Profit Organization Japan Clinical Research Support Unit and Public Health Research Foundation (Tokyo, Japan). Comprehensive individual patient data were recorded according to the Unio Internationalis Contra Cancrum (UICC) TNM classification [1] and the World Health Organization histological classification [2]. The details are described elsewhere [3]. Annual reports on this registry have since been published in Japanese and publicized through the JBCS web site to active members of the JBCS [4]. We herein report the results of a 5-year prognostic analysis of cases registered in 2005 (Figs. 1, 2, 3, 4, 5, 6, 7, 8 and 9; Supplementary Tables 1–9). The number of facilities involved in the 2005 registration was 354 and the total number of cases was 20,786. The estimated incidence of breast cancer was reported to be 50,695 cases in 2005 by the National Cancer Center [5]. Therefore, approximately Electronic supplementary material The online version of this article (doi:10.1007/s12282-015-0645-4) contains supplementary material, which is available to authorized users.

Breast carcinoma arising in a benign fibroepithelial tumor is rare, and is usually discovered incidentally during examination of the breast mass. We evaluated the clinicopathological features, treatment, and prognosis of seven women with breast carcinomas within benign fibroepithelial tumors, diagnosed and treated at a single institution between 2011 and 2015. Seven women, aged 21–64 years, visited our hospital complaining of a breast mass detected by self-checking or screening examination. All patients had well-demarcated movable breast masses. Ultrasonography showed circumscribed masses suggesting benign tumors in all cases, and mammography revealed well-defined, high-density masses, with or without calcification. The masses progressed in two patients. A preoperative histological diagnosis of carcinoma was made following needle biopsy in four patients. Tumorectomy, breast-conserving surgery, and mastectomy were performed in three, two, and two patients, respectively. One patient underwent lymph node dissection and another underwent sentinel node biopsy. Histologically, the masses were diagnosed as invasive ductal carcinoma, ductal carcinoma in situ or lobular carcinoma in situ, arising in a benign phyllodes tumor, fibroadenoma, or fibroadenomatoid mastopathy. Lymph node metastasis was detected in two patients. There was no recurrence in any of the patients. Although a carcinoma within a preexisting benign fibroepithelial tumor is extremely rare, it is important to be aware of the possibility of invasive and metastatic disease.

A prospective randomized phase II trial was conducted to evaluate the time course effects of toremifene (TOR) and letrozole (LET), as adjuvant hormone therapy, on serum lipid profiles and bone metabolism in estrogen receptor (ER)-positive, postmenopausal breast cancer patients.Fifty-four postmenopausal breast cancer patients [ER positive, HER2 negative, T1–2, node metastases (n = 0–3), M0] who had undergone curative resection were enrolled. They were randomized to receive either TOR 40 mg/day or LET 2.5 mg/day as adjuvant hormone therapy. Serum lipids and bone markers were measured prior to, and again at 6, 12, and 24 months after initiation of treatment. Changes in serum lipids and bone markers were compared. Serum levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were decreased compared with the baseline values at 6 months in 6.5 and 14.0% of patients, respectively, receiving TOR. Lipid levels did not change in patients administered LET. Significant differences were observed in TC and LDL-C between the two groups at 12 and 24 months. In the TOR group, serum bone-specific alkaline phosphatase (BAP) was decreased by 25.0% at 12 months, and serum cross-linked N-telopeptide of type-I collagen (NTx) was decreased by 13.6% at 6 months, and these reductions were maintained for at least 24 months. In contrast, in the LET group, serum BAP did not change and NTx was increased by 16.0% at 6 months and by 18.6% at 24 months, as compared with the baseline.TOR and LET exert different effects on serum lipid profiles and bone metabolism markers. The effects of TOR, as adjuvant hormone therapy, on both lipids and bone metabolism in postmenopausal breast cancer patients are superior to those of LET.

Objective: The JBCRG-C06 Safari study showed that earlier fulvestrant 500 mg (F500) use, a longer time from diagnosis to F500 use, and no prior palliative chemotherapy were associated with significantly longer time to treatment failure (TTF) among Japanese patients with estrogen receptor-positive (ER+) advanced breast cancer (ABC). The objective of this subgroup analysis was to further examine data from the Safari study, focusing on ER+ and human epidermal growth factor receptor-negative (HER2−) cases. Methods: The Safari study (UMIN000015168) was a retrospective, multicenter cohort study, conducted in 1072 patients in Japan taking F500 for ER+ ABC. The subanalysis included only patients administered F500 as second-line or later therapy (n = 960). Of these, 828 patients were HER2−. Results: Multivariate analysis showed that advanced age (≥65 years; p = 0.035), longer time (≥3 years) from AMBC ABC diagnosis to F500 use (p < 0.001), no prior chemotherapy (p < 0.001), and F500 treatment line (p < 0.001) were correlated with prolonged TTF (median 5.39 months). Conclusions: In ER+/HER2− patients receiving F500 as a second-line or later therapy, treatment line, advanced age, no prior palliative chemotherapy use, and a longer period from ABC diagnosis to F500 use were associated with longer TTF.

Introduction Endoscopic surgery is reportedly associated with smaller scars and greater patient satisfaction. Herein we evaluate the early results of endoscopy-assisted breast-conserving surgery(E-BCS). Methods Between May 2009 and October 2010, 61 women with breast cancer underwent E-BCS. We performed E-BCS on patients with tumors measuring less than 2 cm, without skin or pectoralis muscles invasion. Any patients with microcalcified lesions or axillary lymph node metastasis were excluded. We used an endoscopic vein retractor to dissect the dorsal layer of the mammary gland from a small axillar incision. We dissected the subcutaneous layer and cut the mammary gland vertically from a periareolar incision. We evaluated the clinicopathological characteristics, the surgical outcomes, and early cosmetic results. Results The mean age of the patients was 58.5 years, and the mean tumor size was 1.4 cm. Sentinel node biopsy was positive in seven patients, all of whom underwent axillary node dissection. An additional intraoperative resection of the breast was performed in 12 patients. The mean length of the operation was 167 min, and the mean blood loss was 27 mL. Eight patients received a boost to the tumor bed. The cosmetic results were satisfactory, and the wound scar was inconspicuous in most patients. Conclusion Herein we demonstrate that E-BCS is a feasible and safe procedure for patients with early breast cancer. It allows for a better cosmetic scar location and offers patients favorable aesthetic results in the short-term follow-up results.

Trastuzumab (T) has contributed to improving the prognosis of human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Although some patients have been unresponsive or resistant to T. Loss of phosphatase and tensin homolog (PTEN) deleted on chromosome 10, PIK3CA mutation and p95HER2 expression have been reported to potentially be responsible for the poor response to T. This is a small-scale pilot study to be followed by a large-scale investigation examining the association between the biomarkers and clinical response. Based on the response to T, patients were divided into 3 groups in terms of progression-free survival (PFS): PFS >8 months (group A, n=15), 3–8 months (group B, n=7) and PFS

We herein report a rare case of primary angiosarcoma of the breast. A 31-year-old pregnant woman noted a progressing mass in her left breast, and it was suspected to be a phyllodes tumor on the basis of images acquired after the delivery. The histological diagnosis by excisional biopsy was well-differentiated angiosarcoma, so she was referred to our hospital for further treatment. CT and MRI suggested that there was a residual lesion in the remnant breast and multiple bone metastases. She underwent a simple mastectomy, and chemotherapy was performed postoperatively. Four months after surgery, liver, ovary, and mandibular gingival metastases became apparent, although these metastatic lesions had not been distinguished at first. They rapidly progressed, and the regimen of chemotherapy was changed from weekly paclitaxel, MAID (mesna/ifosfamide/doxorubicin/dacarbazine) combination therapy, to docetaxel. Radiation therapy to the gingival tumor was relatively effective. However, the liver and ovary metastases continued to progress under chemotherapy and caused a fatal hemorrhage. Early diagnosis is very important in this highly aggressive disease, and a novel strategy for treatment is needed to prolong the survival and maintain the quality of life of such patients.

The potential long-term adverse effects on quality of life have to be considered when selecting agents for adjuvant hormonal treatment for postmenopausal patients with estrogen receptor-positive breast cancer. We performed a 2-year multicenter randomized study to assess the differences in the time course effects between toremifene (TOR) and anastrozole (ANA) on serum lipid profiles and bone metabolism. This study assessed the serum levels of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A-1 (Apo A1), and apolipoprotein B (Apo B) as lipid profiles and bone-specific alkaline phosphatase (BAP) and the N-telopeptide of type-I collagen (NTX) as bone turnover markers in patients who received daily doses of 40 mg and 1 mg for TOR and ANA, respectively. A decreased serum level of TC, LDL-C, and Apo B was, respectively, observed at 6 months in 6.2, 12.9, and 13.8% of the patients who received TOR compared with the baseline. These decreases were maintained for at least 24 months. These lipid levels were not changed in those who received ANA. In the TOR patients, there was an increase in the serum level of HDL-C and Apo A1 at 6 months in 17.1 and 16.3%, respectively, which was maintained for at least 24 months, whereas these levels were almost stable in the patients who received ANA. Serum BAP decreased by 12.1% at 12 months and further decreased at 24 months and the serum NTX decreased by 22.0% at 6 months, which was maintained for at least 24 months in the patients who received TOR. In contrast, the serum BAP was increased by 26.0% at 6 months and by 29.2% at 12 months and the serum NTX increased by 21.3% at 24 months compared with baseline in those received ANA. However, the serum BAP increase was not significant at 24 months. TOR provides better effects than ANA in terms of lipid profiles and bone metabolism in postmenopausal females with early breast cancer.

This study compared the efficacy and safety of a 3-monthly 10.8-mg depot goserelin (Zoladex(TM)) injection with the current 3.6 mg monthly dose in pre-menopausal Japanese women with estrogen receptor-positive (ER+) early breast cancer. This was a multicenter, open-label, randomized study. Primary endpoint was a non-inferiority analysis (10.8/3.6 mg) of the area under the concentration-time curve (AUC) of estradiol (E(2)) over the first 24 weeks. Secondary endpoints included E(2) and follicle-stimulating hormone (FSH) concentrations, menstruation, and safety and tolerability. In total, 170 patients were randomized to receive goserelin 10.8 mg every 3 months (n = 86) or 3.6 mg every month (n = 84). Mean AUCs for E(2) were similar between treatment groups (18.32 and 18.95 pg/ml·week for goserelin 10.8 and 3.6 mg, respectively). AUC ratio was 0.974 (95% confidence interval, 0.80, 1.19), indicating non-inferiority for goserelin 10.8 mg. Serum E(2) and FSH remained suppressed throughout the study and no patient experienced menses after week 16. No clinically important differences in safety and tolerability were observed between the two groups. In terms of E(2) suppression, 3-monthly goserelin 10.8 mg was non-inferior to monthly goserelin 3.6 mg in pre-menopausal women with ER+ breast cancer.

Patients with metastatic breast cancer (MBC) are often treated with multiple regimens, and viable options may soon be exhausted. Irinotecan (CPT-11), a topoisomerase 1 inhibitor, is rarely used in this setting, however. Approved for advanced breast cancer in Japan, S-1 is a pyrimidine derivative comprising the combination of tegafur, gimeracil and oteracil. Irinotecan is combined with S-1 (IRIS) to obtain an additive effect, even in the presence of high thymidylate synthase in breast cancer cells. This combination has also been successfully used for gastro-intestinal malignancies in Japan. Method: This study was divided into two steps: step 1, in which the safety profile of the regimen was determined; and step 2, in which tumor response was evaluated if the safety profile was considered acceptable. Irinotecan was given intravenously at a dose of 80 mg/m2 on days 1 and 8 and S-1 orally at 80-120 mg/day depending on body surface area for 2 weeks. The cycle was repeated every 3 weeks. Results: A total of 21 patients were registered in the study. Median age was 50 years (range, 26 -69 years). Performance status was 0 and 1 in 20 and 1 patients, respectively. Six patients were enrolled in step 1. Grade (G) 3 fatigue and vomiting were observed in 1 patients, G 3-4 neutropenia in 4 and G 3 anemia in 1. The toxicity profile in step 1 was determined acceptable to move on to step 2. Step 2 included 15 patients treated with IRIS. Grade 3-4 neutropenia occurred in 7 out of these 15 patients, fatigue in 1, diarrhea in 3 and anorexia in 1. All patients had previously received anthracyclines and taxanes. Eighteen patients, including 3 patients in step 1, were evaluable for response. A partial response was obtained in 5 patients (27.8%), including in 1 patient who had a history of 4 previous treatments. Progression-free survival in these patients was 137+, 147, 168+, 304+ and 364+ days; no progressive disease was observed in 4 of them. In addition, stable disease was obtained in 5 patients (27.8%) in whom 2 patients experienced SD for longer than 6 months. Conclusion: These results indicate that the IRIS regimen has an acceptable safety profile and modest activity against breast cancer in patients who have been heavily treated with chemotherapy for MBC. We believe the patients responded to the IRIS regimen because irinotecan has a different mechanism of action as compared to other drugs commonly used for breast cancer and complete cross-resistance may not exist between S-1 and capecitabine. This regimen is commonly used for gastric or colorectal cancer in Japan and is considered to be highly tolerable. Therefore, we conclude that this regimen has potential as an option to treat advanced and metastatic breast cancer, although attention must be paid to diarrhea, the dose-limiting toxicity of irinotecan and S-1. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P6-11-09.

Capecitabine (Xeloda, X) and cyclophosphamide (C) can be given orally and they have synergistic effects with nonoverlapping toxicities in preclinical studies. A phase I study of the XC combination therapy was conducted in patients with metastatic breast cancer (MBC) and determined the recommended dose and schedule of 1657 mg/m/day capecitabine and 65 mg/m/day cyclophosphamide given orally for 2 weeks at a 3-week interval. A phase II study of the oral XC regimen was then conducted. This study enrolled patients with HER2-negative MBC who were earlier treated with anthracyclines. XC was given at the recommended doses on a 3-week schedule for at least six courses unless disease progression or unacceptable toxicities occurred. The primary endpoint was the response rate. Progression-free survival, overall survival, and adverse events were investigated as secondary endpoints. Forty-eight patients with the median age of 58 (range 32-72 years) years were registered. Three patients withdrew by choice before starting the treatment. A complete response was obtained in two of the 45 evaluable patients, and partial response in 14, resulting in an overall response rate of 35.6%. The median progression-free survival and overall survival were 199 (115-231) days and 677 (437 approximately ) days, respectively. Grade 3 neutropenia and leukopenia developed in 11%, and that of anemia and thrombocytopenia in 2% patients. Nonhematological toxicities were mild. Hand--foot syndrome was observed in 14 patients but no one had grade 3-4 toxicity. Oral XC combination is effective with acceptable toxicities in patients with MBC.

肉眼的腹膜播種のない腹腔内洗浄細胞診陽性（P0cy1）ss以深胃癌の予後因子について検討した．腹腔内細胞診陽性率はP0 5.4％，P1 67％，ss 10％ se 40％ si 29％であった．ss以深胃癌987例のうちP0cy1胃癌は86例で，P0cy0，P0cy1，P1のMST（生存期間中央値），1年，2年，3年，4年，5年生存率は1678日，83％，70％，58％，51％，48％，446日，56％，30％，21％，14％，9.6％，244日，36％，18％，11％，3％，2％であった．P0cy1の予後はP0cy0とP1との中間に位置している．P0cy1胃癌の予後因子は単変量解析では肉眼分類，肝転移，リンパ節転移度，転移リンパ節個数，リンパ節郭清度，PM，DM，間質，INF，リンパ管侵襲，細胞診の細胞数，細胞診の細胞の大きさ，術後化学療法，化学療法の14因子であったが，多変量解析ではDM，リンパ節郭清度，術後化学療法の3因子であった．P0cy1ss以深胃癌の予後は不良だが，切除断端を陰性にし，D2以上のリンパ節郭清を行い，術後化学療法を行うことができれば予後が良好なことが期待される．

The therapeutic advances in breast cancer have improved the survival of patients with early disease; however, survival improvement of patients with recurrent disease remains ambiguous. In this retrospective study, we examined whether disparities in survival improvement exist in patients with recurrent breast cancer with distant metastasis.The survival time of 126 patients who experienced recurrence at distant sites from 1990 through 1996 was compared to that of 195 patients who did from 1997 through 2003.A significant survival improvement was observed in the patients who experienced recurrence in the period of 1997-2003 in comparison to the other period in the subsets with estrogen receptor (ER)-positive disease, those who received adjuvant hormonal therapy, and those with a disease-free interval (DFI) of 24 months or more. However, no significant survival improvement was observed in each counterpart. The median survival time (MST) from the first relapse of patients with ER-positive disease in the recurrence period of 1997-2003 was 18.8 months longer than that in the recurrence period of 1990-1996 (46.6 months vs. 27.8 months). The MST of patients with a DFI of 24 months or more in 1997-2003 was 20.3 months longer than that in the other time period (47.2 months vs. 26.9 months).The survival of recurrent breast cancer has improved with disparities. The ER status and the DFI are associated with a survival improvement of women with recurrent breast cancer with distant metastases.

This study examined the pathological complete response (pCR )rate and safety of induction chemotherapy with 12 cycles of weekly paclitaxel (80 mg/m²) followed by 4 cycles of 5-fluorouracil (500 mg/m²), epirubicin (100 mg/m²), and cyclo- phosphamide (500 mg/m²). The study medication was administered to female patients (n=31)with a mean age of 51 years, diagnosed with stage II A (n=18), II B (n=11) and III A (n=2) disease and with an estrogen receptor positive rate of 65% (20/31). No patient was HER2-IHC [human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC)](3+) or HER2-FISH (fluorescence in situ hybridization) positive. Twenty-eight patients completed the treatment regimen. Treatment was halted in 2/31 patients due to progression of disease in one patient and a Grade 3 non-hematological adverse effect of skin eruption and itching in the other patient. A third patient died of causes unrelated to the study medication. Central review ascertained a pCR in 6 patients. In patients with triple-negative disease we observed a pCR rate of 67% (6/9). In patients with the Luminal (A+B) subtype, 0% (0/19) had a pCR. Grade 3/4 toxicity included leucopenia (58%), neutropenia (58%), febrile neutropenia (26%), fatigue (10%), and ALT elevation (7%). In terms of pCR, patients presenting with triple-negative disease and manageable safety profiles appear to respond well to this treatment regimen, while only a modest response was observed in patients with Luminal subtype disease.

症例は60歳,女性.右腎細胞癌(clear cell type)の根治術術後4年で,左内下部に腫瘤を自覚し,徐々に増大のため当科紹介. 2.6cmの腫瘤に対し, core needle biopsy (CNB)施行し,腎細胞癌からの転移が強く疑われた.他部位に転移はみられず,乳房円状部分切除とセンチネルリンパ節生検(SNB)を施行した.病理診断は腎細胞癌からの転移でリンパ節転移はみられなかった.術後無治療で経過観察中である.腎細胞癌からの乳腺転移は非常に稀のため,文献的考察を加える.

Background and Objectives Although studies have focused on modulating the bioavailability of 5-FU through inhibition of dihydropyrimidine dehydrogenase (DPD) to improve efficacy of the drug, activity of this enzyme in breast cancer has not been thoroughly examined. We measured DPD activity in primary and metastatic lesions and benign breast tumors to evaluate the clinical significance of this enzyme in the treatment of breast cancer. Methods DPD activity was measured by catalytic assay and compared in 100 primary tumors (95 invasive carcinomas, 5 intraductal carcinomas), 26 uninvolved adjacent breast tissue specimens, 6 metastatic sites, and 7 intraductal papillomas. Results The enzyme level in the carcinomas was 4-fold that of adjacent uninvolved breast tissues (101 vs 23 pmol/min/mg protein, P

The purpose of this study was to determine the most appropriate tests and procedures to detect disease progression effectively during the postoperative follow-up of patients with early breast cancer. We reevaluated our current surveillance protocol which involves the intensive follow-up of 643 patients with stage I disease. With the exception of one case of bone metastasis, all cases of recurrence (97%) were suspected from abnormal results detected during surveillance involving physical examination, serial determination of tumor markers, and chest roentgenography. Among 15 patients with asymptomatic distant metastasis, disease recurrence was suspected in 12 (80%) because of increased levels of serum tumor markers. No disease recurrence was detected by routine complete blood counts or automated chemistry studies alone. Our experience indicates that an effective follow-up regimen for patients with early breast cancer may include careful history-taking, physical examination, and the determination of serum tumor markers every 3-6 months for the first 3 years, then less frequently thereafter, and chest roentgenography every 6 months for 5 years, in addition to annual mammography. Serial determination of the tumor markers tumor polypeptide antigen, NCC-ST-439, and either carcinoembryonic antigen or carbohydrate antigen 15-3, seems to be of value for the selection of patients who should undergo radiologic exploration. The health benefits and cost-effectiveness of a follow-up focused on the measurement of serum tumor markers need to be evaluated in large prospective randomized trials.

乳腺扁平上皮癌は稀な腫瘍であり,その術前診断法についての報告は少ない.今回われわれは当院で経験した乳腺扁平上皮癌9例を報告し,術前診断法について検討した.平均年齢は63.6歳,平均腫瘤径は3.9cmと,通常型乳癌に比べ年齢が高く,腫瘤径の大きい進行癌が多かった.癌としての術前診断率は,触診8/8:100%,マンモグラフィー(MMG)6/8:75%, 乳腺超音波(US)7/8:88%,穿刺吸引細胞診(FNA)6/6:100%であった. MMGで特徴的な所見はなかったが, USでは8例中4例に腫瘍内にcystic partを認め,うち2例は急速に増大する腫瘍であった.FNAは6例中3例が扁平上皮癌と診断され,細胞の多形性,細胞質の重層性,多染性,核の不整,中心性,粗大凝塊状のクロマチンなどで腺癌との鑑別が可能であった.USで乳腺にcystic partを伴う腫瘤を認める場合は,扁平上皮癌の可能性があるため, FNAによる診断が有用となる.

We reviewed the clinical and pathologic features of pure tubular carcinoma of the breast with particular emphasis on the reported risk factors associated with local recurrences and survival following breast-conserving therapy. Of 1653 cases of invasive breast cancer, 12 (0.7%) were identified as pure tubular carcinoma. Clinical/pathologic features of pure tubular carcinoma were compared with those of T1 invasive carcinoma of all other histologic types (T1 IC). Of the 12 patients with pure tubular carcinoma (median tumor diameter 1.4 cm; range 0.5-3.0 cm), a multicentric association was identified in one patient while a multifocal association was seen in two. One patient had nodal metastatic disease out of the ten who underwent axillary dissection. No lymphatic vessel invasion was identified in any tumors (P < 0.1 vs T1 IC). In addition, extensive intraductal spread was not present in any tumors (P < 0.05 vs T1 IC). This study shows that patients with pure tubular carcinoma are appropriate candidates for breast-conserving therapy based on the clinical/ pathologic features. When a multifocal association is suspected preoperatively, either a wide local excision or a quadrantectomy which includes other lesions is thus recommended.

BACKGROUND: A tumor 30 mm or less in diameter is a standard candidate for breast conserving surgery (BCS) in Japan. Axillary lymph node metastases (ALNM) is the most important prognostic factor for survival in patients with breast cancer, but the role of axillary node dissection has been controversial. Histopathological predictive factors of axillary lymph node involvement have not been established. The purpose of this study was to determine the association between the incidence of ALNM and histopathological factors by univariate and multivariate analysis METHODS: Sixty-five patients with noninvasive ductal carcinoma, and 993 patients with tumors 30 mm or less in diameter who underwent axillary dissection between 1988 and 1997 at our institute were reviewed. The association between ALNM and 13 histopathological factors (size, age, histological subtype, histological invasiveness, lymphatic invasion, vascular invasion, macroscopic classification, histological daughter mass, ductal spread, ER, PgR, p-53, and c-erbB-2) were analyzed by univariate and, when significant, by multivariate analysis. RESULTS: Only one patient with noninvasive ductal carcinoma had ALNM, and 33.1% of 993 patients with a tumor 30 mm or less in size had ALNM. Multivariate analysis identified six factors as independent predictors for ALNM: lymphatic invasion, size, histological invasiveness, macroscopic classification, age and histological daughter mass. CONCLUSION: Axillary lymph node dissection can be omitted in patients with noninvasive ductal carcinoma. Histopathological features of tumors 30 mm or less in diameter can be used to estimate the risk of ALNM, and routine axillary node dissection might be spared in selected patients at minimal risk of ALNM, if the treatment decision is not influenced by lymph node status, such as in elderly patients.

Aims Although axillary lymph nodes status, tumour size, hormonal-receptor status and histological grade at diagnosis are frequently used to orient the treatment of breast cancer patients, some tumours recur in patients with early stage disease. Pre-operative assessment of individual tumour characteristics, based on oncogenes and growth factors related to tumour growth, invasion or metastasis, may guide the treatment for patients with breast carcinomas. Methods We examine here the prognostic significance of cyclin D1, urokinase type plasminogen activator, vascular endothelial growth factor (VEGF), platelet-derived growth factor, and c-erbB2 expression in pre-operatively obtained fine-needle aspirates from breast carcinomas less than or equal to 3cm in size. Correlation between mRNA expression of these factors and clinicopathological characteristics was analysed. Results The level of c-erbB2 mRNA expression was significantly higher in tumours with lymph node metastases than in those without lymph node metastases. VEGF mRNA expression positively correlated with the degree of angiogenesis as quantitated by immunohistological staining with a CD31 monoclonal antibody. Conclusions Analysis of c-erbB2 and VEGF mRNA expression in fine-needle aspirates may be useful in assessing the malignant potential of individual breast carcinomas, leading to a pre-operative discrimination of a high-risk group.