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Non-invasive breast carcinoma is considered to be localized disease and is distinguished from invasive ductal and lobular carcinomas. The local recurrence of non-invasive carcinoma after surgery may lead to development of invasive carcinoma and promote distant metastasis, which worsens the prognosis for breast cancer mortality. The distant metastasis of non-invasive carcinoma may involve the ductal microvasculature without invasion. The outcomes of non-invasive breast carcinoma were examined in this retrospective cohort study.Of 872 primary breast cancers diagnosed at a single center between May 2008 and March 2022, 93 (10.6%) were found to be non-invasive carcinomas and were examined in this study. The breast cancer recurrence and survival rates of patients with non-invasive carcinoma were analyzed retrospectively. The median follow-up period was 1891 (range, 5-4804) days. All patients underwent surgical treatment [mastectomy with sentinel lymph node biopsy (SLNB) and partial mastectomy with or without SLNB, tumorectomy, and microdochectomy]. Postoperatively, radiation therapy was administered to 73 (78.4%) of the patients and endocrine therapy was administered to 64 (81.0%) of 79 patients with hormone-receptor positivity. Of 26 patients who underwent partial mastectomy with SLNB, 24 (92.3%) showed isolated tumor cells in the SLNs on one-step nucleic acid amplification. Local recurrence was observed in three (0.3%) patients; no distant metastasis was observed. One patient died of a noncancerous disease. The overall survival rate was 98.0% and the breast cancer-specific survival rate was 100.0%.Non-invasive breast carcinoma, like invasive breast carcinoma, causes local recurrence, but has a good prognosis without distant metastasis. The clinical significance of isolated tumor cells in the SLNs as a systemic component of non-invasive breast carcinoma remains to be elucidated.

[Background] Nanoparticle albumin-bound paclitaxel (Nab-PTX) is a novel taxane formulation that was developed to avoid Cremophor/ethanol associated toxicities such as peripheral neuropathy and hypersensitive reactions. Since Taxol plays an important role in breast cancer therapy, Nab-PTX is considered safe and effective for metastatic breast cancer (MBC). According to these reports, a regimen including Nab-PTX in a neoadjuvant setting may induce preferable results. Several recent reports using a combination of Nab-PTX and anthracycline in neoadjuvant chemotherapy (NAC) have been published. In Japan, at least 34 small phase II studies using a Nab-PTX regimen have been registered with the University hospital Medical Information Network-Clinical Trial Registry (UMIN-CTR). We believe that integration of these data is important to evaluate the power of Nab-PTX, so we conducted a meta-analysis based on individual patient data (IPD). [Materials and Methods] This study is a collaborative meta-analysis of single arm trials using IPD to summarize the published and unpublished evidence of Nab-PTX-containing regimen efficacy. The main objective was to assess the rate of pathological complete response (pCR). Definitions of pCR were (1) ypT0 ypN0, (2) ypT0/is ypN0, and (3) ypT0/is ypNX. The secondary objectives were adverse events (AEs) (≥G3) and dose of administered Nab-PTX (mg/m2). First, we found 34 phase II studies registered from Feb 2011 to Jun 2016 using an electron search of UMIN-CTR. Second, we contacted each principal investigator (PI) to ask if they would participate in this study by providing individual data. Inclusion criteria were as follows: (1) Clinical trial(s) started after July 2010, (2) Principal investigator(s) in each trial agreed with study participation, (3) Nab-PTX-containing regimen was used for neoadjuvant chemotherapy in naive operable breast cancer patients, (4) Registered in UMIN with ethical review, (5) Clinical trials with more than 10 patients, (6) Completed clinical trials only were included (unpublished data are available), and (7) Each researcher was authorized by the research ethics committee to submit the data. pCR rates in all cases/each subtype were calculated with a 95% confidence interval (CI). The proportion of AEs and total Nab-PTX dose were also calculated. [Results] Among 34 studies, 16 studies (4 published, 12 unpublished) included 758 patients. Among these 16 studies, 5 (2 metastatic, 3 no treatment) were excluded for all analyses (n=753). After excluding 8 (3 declined surgery, 1 hospital transfer, 4 unknown), a total of 745 (including 2 PD, 1 death) were analyzed for the primary analysis. All HER2-positive cases were treated by combining Nab-PTX and trastuzumab. Crude overall percentages of pCR (ypT0ypN0, ypT0/isypN0, and ypT0/isypNX) were 18.1%, 26.0%, and 28.6%, respectively. In detail, 6.7%, 10.2%, and 13.4% for Luminal type (n=343), 26.3%, 31.5%, and 32.3% for triple negative (TNBC, n=232), 40.5%, 63.5%, and 68.9% for HER2-rich (n=74), 21.9%, 40.6%, and 42.7% for Luminal/HER2 type (n=96), respectively. AEs (≥G3) were observed as follows: 41.5% neutropenia, 32.3% leukopenia, 10.6% febrile neutropenia, 10.6% peripheral sensory neuropathy, 2.5% peripheral motor neuropathy, 6.4% myalgia, 5.5% arthralgia, 6.1% hepatobiliary disorders, 4.5% vomiting, 0.7%, cardiac disorders, and 0.9% infusion reaction. Only one patient died during FEC followed by Nab-PTX. [Conclusion] NAC regimen containing Nab-PTX was safe, and the efficacy was equal to or greater than regimens containing other taxanes. The combination Nab-PTX and trastuzumab is particularly useful and powerful against the HER2-positive subtype. However, the Nab-PTX-containing regimen is not as powerful against TNBC in a neoadjuvant setting. Citation Format: Manabu Futamura, Mari Oba, Norikazu Masuda, Hiroko Bando, Yutaka Yamamoto, Takanori Kin, Toshiaki Saeki, Takeshi Nagashima, Takashi Kuwayama, Uhi Toh, Akira Hirano, Masafumi Inokuchi, Kazuhiko Yamagami, Yutaka Mizuno, Yasuyuki Kojima, Takahiro Nakayama, Hiroyuki Yasojima, Morihito Okada, Shinji Ohno. Meta-analysis of nanoparticle albumin-bound paclitaxel (Nab-PTX) used as a neoadjuvant chemotherapy for operable breast cancer based on individual patient data (JBCRG-S01) [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 P2-16-13.

Background and Aims: Eribulin is a cytotoxic anti-cancer agent targeting microtubule dynamics, which improves the prognosis of patients with metastatic breast cancer. Preclinical studies have shown that eribulin enhances anti-tumor immunity by inhibiting regulatory T cells and M2 macrophages. Along with advances of immunotherapy for breast cancer, there has been growing interest in such immunologic effects of eribulin. Here we investigated the association between the immunological status of peripheral blood and survival outcomes in patients receiving eribulin for metastatic breast cancer. Methods: Medical records of 125 patients who received eribulin for metastatic breast cancer at Hiroshima City Hiroshima Citizens Hospital between July 2011 and April 2019 were retrospectively reviewed. We collected the data on patients’ baseline characteristics, laboratory tests and clinical courses. Absolute lymphocyte count (ALC) and neutrophil-lymphocyte ratio (NLR) in peripheral blood at the start of treatment with eribulin were calculated, and their association with progression-free survival (PFS) and overall survival (OS) were analyzed with log-rank test. The cutoff values for ALC and NLR were determined based on their distribution in this cohort. Subgroup analyses by breast cancer subtypes were also conducted. Results: The mean age was 57 years (range, 28-88). Eighty (64%) and 14 (11.2%) patients were positive for hormone receptors and HER2 overexpression. One hundred and ten patients (88%) had received one or more lines of chemotherapy for metastatic disease. We divided the entire cohort into three groups, using the cutoff values of 1500 /µL for ALC and 5 for NLR. Accordingly, 30 patients (24%) had favorable immune status (i.e., ALC ≥1500 /µL), whereas immune systems were considered to be suppressed (i.e., NLR ≥5) in 19 patients (15.2%); the rest 76 patients (60.8%) had neutral immune status (i.e., ALC Citation Format: Ayako Ueno, Shoichiro Ohtani, Kensuke Kawasaki, Mitsuya Ito, Takanori Kin, Reina Maeda. Survival benefit of eribulin for metastatic breast cancer depends on absolute lymphocyte count and neutrophil-lymphocyte ratio in peripheral blood [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 P1-10-30.

Background: The aim of this phase II study was to evaluate combined nab-paclitaxel (nab-PTX) with sequential anthracycline-based therapy as a neoadjuvant chemotherapy. Methods: We enrolled 41 patients with advanced breast cancer (stage IIA - IIIC). All patients were to receive three-weekly nab-PTX (260 mg/m 2 ) for four cycles followed by three-weekly 5-fluorouracil, epirubicin and cyclophosphamide (FEC) for four cycles. Trastuzumab administration was permitted in human epidermal growth factor receptor 2 (HER2)-positive patients. Results: The overall pathological complete response (pCR) rate was 24% (10 of 41). In patients with luminal A, luminal B (HER2-), luminal B (HER2+), triple-negative and HER2, the pCR rates were 0% (0/2), 7% (1/14), 42% (3/7), 25% (4/16) and 100% (2/2), respectively. The most significant toxicities of nab-PTX were grade 2/3 peripheral sensory neuropathy (24%) and grade 3/4 neutropenia (26%). Febrile neutropenia was not observed in any patient. The most significant toxicities of FEC were grade 3/4 neutropenia (24%) and grade 3 febrile neutropenia (9%). One patient died of sepsis secondary to pneumonia during FEC treatment. Conclusions: Neoadjuvant chemotherapy using nab-PTX with trastuzumab every 3 weeks followed by FEC was suitably tolerated and associated with a high pCR rate of 55% for patients with HER2-positive breast cancer. World J Oncol. 2020;11(5):197-203 doi: https://doi.org/10.14740/wjon1333

Recurrence after primary treatment is an important obstacle to the curing of primary breast cancer. Less-immunosuppressive anesthetic techniques, such as local anesthesia with lidocaine, intravenous anesthesia (IVA) with propofol, and/or sedation with midazolam under spontaneous breathing may reduce breast cancer recurrence compared with standard general anesthesia techniques such as IVA and inhalation anesthesia with opioids under mechanical ventilation.The aim of this study was to analyze the factors involved in breast cancer recurrence in patients who underwent breast-conserving surgery (BCS) under non-mechanically ventilated anesthesia.The study included 491 consecutive patients with stages 0-III breast cancer who underwent BCS/axillary lymph-node management with local anesthesia and IVA and/or sedation under non-mechanical ventilation between May 2008 and September 2021. Survival and recurrence were assessed by retrospective cohort analysis.The median follow-up period was 2565 days (range, 28-4834 days). The overall and breast cancer-specific survival rates were 92.9% and 95.6%, respectively. Twenty-one deaths, of which 11 were breast cancer-related, occurred. Disease recurred in 29 (5.9%) patients, of whom 15 patients received neoadjuvant chemotherapy (NAC) and 14 patients received adjuvant therapy (chemotherapy in 12 cases). The surgical procedure performed, but not other clinicopathological factors [recurrence site, P stage, tumor subtype, and disease-free interval (DFI)], differed between the NAC and adjuvant therapy groups. The DFI tended to be shorter in the NAC group than in the adjuvant therapy group. The pathological therapeutic effect grade after NAC was 1 in 12 patients and ≥2 in 3 patients.More than 50% (15/29) of patients with recurrence who underwent BCS were given NAC, but most patients did not respond to it. Similarly, adjuvant chemotherapy may not have contributed to the eradication of residual tumor cells after BCS. To reduce breast cancer recurrence in patients undergoing BCS, treatment strategies, especially for patients who do not respond to NAC or adjuvant chemotherapy, need to be developed. Non-mechanical ventilation anesthesia may also affect the incidence of breast cancer recurrence.

The relationship between the anesthetic technique and cancer recurrence has not yet been clarified in cancer surgery. Surgical stress and inhalation anesthesia suppress cell-mediated immunity (CMI), whereas intravenous (IV) anesthesia with propofol and regional anesthesia (RA) are known to be protective for CMI. Surgical stress, general anesthesia (GA) with inhalation anesthesia and opioids contribute to perioperative immunosuppression and may increase cancer recurrence and decrease survival. Surgical stress and GA activate the hypothalamic-pituitary-adrenal axis and release neuroendocrine mediators such as cortisol, catecholamines, and prostaglandin E2, which may reduce host defense immunity and promote distant metastasis. On the other hand, IV anesthesia with propofol and RA with paravertebral block or epidural anesthesia can weaken surgical stress and GA-induced immunosuppression and protect the host defense immunity. IV anesthesia with propofol and RA or in combination with GA may reduce cancer recurrence and improve patient survival compared to GA alone. We review the current status of the relationship between anesthesia and breast cancer recurrence using retrospective and prospective studies conducted with animal models and clinical samples, and discuss the future prospects for reducing breast cancer recurrence and improving survival rates in breast cancer surgery.

Simple Summary How a cure for primary breast cancer after (neo)adjuvant therapy can be achieved at the molecular level remains unclear. Immune activation by anticancer drugs may contribute to the eradication of residual tumor cells by postoperative (neo)adjuvant chemotherapy. In addition, chemotherapy-induced immunogenic cell death (ICD) may result in long-term immune activation by memory effector T cells, leading to the curing of primary breast cancer. In this review, we discuss the molecular mechanisms by which anticancer drugs induce ICD and immunogenic modifications for antitumor immunity and targeted therapy against damage-associated molecular patterns. Our aim was to gain a better understanding of how to eradicate residual tumor cells treated with anticancer drugs and cure primary breast cancer by enhancing antitumor immunity with immune checkpoint inhibitors and vaccines. Abstract How primary breast cancer can be cured after (neo)adjuvant therapy remains unclear at the molecular level. Immune activation by anticancer agents may contribute to residual tumor cell eradication with postsurgical (neo)adjuvant chemotherapy. Chemotherapy-induced immunogenic cell death (ICD) may result in long-term immune activation with memory effector T cells, leading to a primary breast cancer cure. Anthracycline and taxane treatments cause ICD and immunogenic modulations, resulting in the activation of antitumor immunity through damage-associated molecular patterns (DAMPs), such as adenosine triphosphate, calreticulin, high mobility group box 1, heat shock proteins 70/90, and annexin A1. This response may eradicate residual tumor cells after surgical treatment. Although DAMP release is also implicated in tumor progression, metastasis, and drug resistance, thereby representing a double-edged sword, robust immune activation by anticancer agents and the subsequent acquisition of long-term antitumor immune memory can be essential components of the primary breast cancer cure. This review discusses the molecular mechanisms by which anticancer drugs induce ICD and immunogenic modifications for antitumor immunity and targeted anti-DAMP therapy. Our aim was to improve the understanding of how to eradicate residual tumor cells treated with anticancer drugs and cure primary breast cancer by enhancing antitumor immunity with immune checkpoint inhibitors and vaccines.

Background The number of patients desiring implant-based breast reconstruction has been increasing. While local recurrence is observed in patients with breast reconstruction, only a few reports have focused on the risk factors for local recurrence and the prognosis after developing local recurrence. Methods We analyzed 387 patients who underwent implant-based breast reconstruction during the period from 2004 to 2017 in Hiroshima City Hospital. We retrospectively examined the risk factors for local recurrence and the outcomes of patients developing such recurrence after implant-based breast reconstruction. Results The median follow-up time was 59 months. The local recurrence rate was 3.1% (n = 12). The most common reason for detecting local recurrence was a palpable mass. Four patients with local recurrence had recurrence involving the skin just above the primary lesion and needle biopsy tract. All patients with local recurrence received surgery and systemic therapy and most patients received radiation therapy, all have remained free of new recurrence to date. Multivariate analysis showed lymphatic vessel invasion (HR, 6.63; 95% CI, 1.40–31.36; p = 0.017) and positive or p = 0.047) to be associated with significantly increased risk of local recurrence. Conclusions The risk factors for local recurrence following implant-based breast reconstruction were lymphatic vessel invasion and positive or

Simple Summary The development of adjuvant and neoadjuvant therapies, and breast cancer surgery for primary breast cancer has led to the dramatic improvements in the survival rates of breast cancer patients over the past 50 years. However, recurrence with distant metastasis during the 10 years after surgical treatment is still seen, although not often. Current clinical perspectives are summarized to address unsolved issues in (neo)adjuvant therapy for primary breast cancer. It is necessary to elucidate the gain of antitumor immunity via anticancer agents, the enhancement of drug sensitivity by overcoming drug resistance, and the targeting of therapy based on genomic profiles, which will lead to the complete curing of primary breast cancer. Abstract The treatment of primary breast cancer has evolved over the past 50 years based on the concept that breast cancer is a systemic disease, with the escalation of adjuvant and neoadjuvant therapies and de-escalation of breast cancer surgery. Despite the development of these therapies, recurrence with distant metastasis during the 10 years after surgical treatment is observed, albeit infrequently. Recent advances in genomic analysis based on circulating tumor cells and circulating tumor DNA have enabled the development of targeted therapies based on genetic mutations in residual tumor cells. A paradigm shift involving the application of neoadjuvant chemotherapy (NAC) has enabled the prediction of treatment response and long-term prognoses; additional adjuvant chemotherapy targeting remaining tumor cells after NAC improves survival. The activation of antitumor immunity by anticancer agents may be involved in the eradication of residual tumor cells. Elucidation of the manner in which antitumor immunity is induced by anticancer agents and unknown factors, and the overcoming of drug resistance via the targeted eradication of residual tumor cells based on genomic profiles, will inevitably lead to the achievement of 0% distant recurrence and a complete cure for primary breast cancer.

Highlights • The immune factors that determine the pathological and therapeutic effects of preoperative chemotherapy in patients with breast cancer are associated with local and systemic immune responses in the presence of tumor-infiltrating lymphocytes, in collaboration with downregulation of immunosuppressive factors mediated by vascular endothelial growth factor (VEGF) and cytotoxic T lymphocyte antigen 4 (CTLA-4) in regulatory T cells (Tregs) in the tumor microenvironment. • Multivariate analysis showed that grade 2 and better therapeutic effects tended to be associated with higher natural killer cell levels after preoperative chemotherapy (odds ratio = 1.02; 95% confidence interval, 0.99–1.05; p = 0.07). • Therapy targeting VEGF and CTLA-4 in Tregs to overcome tumor-derived immunosuppression may enhance the pathological and therapeutic responses to preoperative chemotherapy in patients with breast cancer., Immune activation plays an important role in achieving the pathological and therapeutic effects of preoperative chemotherapy in patients with breast cancer. We evaluated how the immune response contributes to various therapeutic effects. This study was conducted on 43 patients with stages II–IV breast cancer who received preoperative chemotherapy followed by surgery. Peripheral natural killer (pNK) cell activity and the neutrophil-lymphocyte ratio, lymphocyte-monocyte ratio, and platelet-lymphocyte ratio (PLR) were assessed before and after chemotherapy. Tumor-infiltrating lymphocytes (TILs) and levels of 14 tumor microenvironmental factors, analyzed by next-generation sequencing, were assessed in formalin-fixed, paraffin-embedded sections of preoperative biopsy samples and surgical specimens. Univariate analysis showed that grade 2 (G2) and better therapeutic effects were significantly associated with human epidermal growth factor receptor 2 (HER-2)-positive cancer, lower PLRs, and higher NK cell and interleukin-6 levels after chemotherapy. The disappearance of axillary lymph-node metastasis was significantly associated with HER-2-positive cancer; increased pNK cell activity and lower PLRs and vascular endothelial growth factor (VEGF) levels after chemotherapy; and increased cytotoxic T lymphocyte antigen 4 (CTLA-4) levels in regulatory T cells (Tregs) and ≥5% TILs before chemotherapy. Multivariate analysis showed that G2 and better therapeutic effects tended to be associated with higher NK cell levels after chemotherapy (odds ratio = 1.02; 95% confidence interval, 0.99–1.05; P = 0.07). The activation of local and systemic immune responses by downregulation of immunosuppressive factors, such as VEGF and CTLA-4 in Tregs, had variable pathological and therapeutic effects after preoperative chemotherapy in patients with breast cancer.

Background Nanoparticle albumin-bound paclitaxel (nab-PTX), a novel taxane formulation, was developed to avoid cremophor/ethanol-associated toxicities including peripheral neuropathy and hypersensitivity. At least 35 phase II studies using combined nab-PTX and anthracycline in neoadjuvant settings are registered in Japan. We analyzed the efficacy and safety of nab-PTX based on patient characteristics in these studies. Methods We conducted a meta-analysis using individual patient data (IPD) to investigate the average efficacy of nab-PTX-containing regimens as neoadjuvant chemotherapy for operable breast cancer. IPD were provided by principal investigators who agreed to participate. The primary endpoint was pathological complete response (pCR) rate of each breast cancer subtype. Results We analyzed the data of 16 studies involving 753 patients. The overall crude frequencies of pCR (ypT0 ypN0, ypT0/is ypN0, and ypT0/is ypNX) were 18.1, 26.0, and 28.6%, respectively. Specifically, the frequencies were 6.7, 10.2, and 13.4% for luminal (n = 343); 40.5, 63.5, and 68.9% for human epidermal growth factor receptor 2 (HER2)-rich, (n = 74); 21.9, 40.6, and 42.7% for luminal/HER2 (n = 96); and 26.3, 31.5, and 32.3% for triple-negative breast cancers (TNBC) (n = 232). The multivariate analyses indicated that HER2 positivity, TNBC, high Ki-67, high nuclear grade, and weekly nab-PTX administration were significantly associated with the pCR. The proportion of hematological toxicities (neutropenia (39.7%) and leukopenia (22.5%)), peripheral sensory neuropathy (9.7%), myalgia (5.7%), and arthralgia (4.7%) was higher than grade 3 adverse events, but most patients recovered. Conclusions Nab-PTX is a safe and acceptable chemotherapeutic agent in neoadjuvant settings, particularly for aggressive cancers. UMIN-CTR#: UMIN000028774

Background The use of general anesthesia (GA) with inhalational anesthetics for breast cancer surgery may be associated with breast cancer recurrence and increased mortality due to the immunosuppressive effects of these drugs. Less-immunosuppressive anesthetic techniques may reduce breast cancer recurrence. We evaluated the feasibility, safety, and efficacy of outpatient breast-conserving surgery (BCS) for breast cancer in a breast clinic in terms of the anesthetic technique used, complications occurring, recurrence, and survival. Methods: The sample comprised 456 consecutive patients with stage 0–III breast cancer who underwent BCS/axillary lymph node (ALN) management using local and intravenous anesthesia and/or sedation between May 2008 and January 2020. Most patients received adjuvant chemotherapy and/or endocrine therapy and radiotherapy after surgery. Patient outcomes were evaluated retrospectively. Results: All patients recovered and were discharged after resting for 3–4 h postoperatively. No procedure-related severe complication or death occurred. Sixty-four complications (14.0%) were observed: 14 wound infections, 17 hematomas, and 33 axillary lymphoceles. The median follow-up period was 2259 days (range, 9–4190 days), during which disease recurrence was observed in 25 (5.4%) patients. The overall survival and breast cancer–specific survival rates were 92.3% and 94.7%, respectively. Conclusions: Outpatient surgery for breast cancer involving BCS and ALN management under local and intravenous anesthesia and/or sedation can be performed safely, without serious complication or death. Less-immunosuppressive anesthetic techniques with spontaneous breathing may reduce the recurrence of breast cancer and improve survival relative to GA., Highlights • Outpatient surgery for breast cancer involving breast-conserving surgery (BCS) and axillary lymph node (ALN) management under local and intravenous anesthesia and/or sedation can be performed safely. • Less-immunosuppressive anesthetic techniques with spontaneous breathing may reduce the recurrence of breast cancer and improve survival compared with general anesthesia.

Introduction: Previous studies have suggested that the efficacy of eribulin is influenced by the activity of antitumor immunity of patients. Absolute lymphocyte count (ALC) and the neutrophil/lymphocyte ratio (NLR) are easily available parameters associated with the immunological status of patients. Objective: Here we tried to classify patients’ immunological status by using the scatter plot of ALC and NLR, and investigated its utility for predicting survival among patients with metastatic breast cancer receiving eribulin. Methods: The medical records of 125 patients who received eribulin for metastatic breast cancer at our hospital between July 2011 and April 2019 were retrospectively reviewed. Uni- and multivariate analyses were performed to determine the association between baseline ALC/NLR and progression-free survival (PFS)/overall survival (OS). The cutoff values for ALC and NLR were determined using scatter plot analysis. Results: The entire cohort was classified into immunologically favorable (ALC ≥1,500/µL, 30 patients), intermediate (ALC p = 0.013). Conclusions: Among patients with metastatic breast cancer receiving eribulin, survival outcomes were well stratified according to baseline peripheral blood ALC and NLR. Accordingly, high ALC and NLR can be used as predictive markers for longer disease control and worse survival, respectively.

Background: Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) is not necessarily linked to long-term survival. Response to chemotherapy and outcomes after NAC differ among breast cancer subtypes, so we analyzed prognostic factors by subtype. Methods: We retrospectively analyzed 451 patients treated with anthracycline and taxane-based NAC between 2007 and 2015. Trastuzumab was added for human epidermal growth factor receptor (HER)-2-positive breast cancer. pCR was defined as no residual invasive breast carcinoma; noninvasive residuals and infiltrated lymph nodes were allowed. In our institute, mastectomy was performed in patients in whom the breast could not be preserved, such as patients with large residual tumors and diffusely spread tumors throughout the breast after NAC. Kaplan–Meier and univariate and multivariate cox regression analyses were used to evaluate disease-free interval (DFI) and DFI prognostic values, respectively. Results: Median follow-up was 43 months; median age was 56 (range, 23–88) years. The 3-year DFI and OS were 82.1% and 94.4%, respectively. In total, 85 patients had recurrence (18.8%) and 31 patients died (6.9%). Response rate (RR) was 93.4% (421/457).pCR rate was 26.2% (118/451) in all cases: 0% (0/82), luminal A; 10.9% (14/128), luminal B HER2(−); 43.1% (31/71), luminal B HER2(+); 59.4% (38/64), HER2; and 34% (36/106), triple negative (TN). For all subtypes, patients who achieved pCR had a non-significantly higher DFI. Multivariate cox regression showed these associations with DFI: surgery type and Ki-67 > 30% for all cases and luminal B HER2(-); ypN (lymph node status after NAC), luminal B HER2(+);ypN and menopausal status, HER2; and age, surgery type, and clinical lymph node status (cN), TN. Kaplan–Meier analysis showed that surgery type was strongly associated with DFI after NAC. Mastectomy patients had significantly poorer prognoses than partial mastectomy patients for all subtypes except HER2. For all cases, the median DFI in mastectomy patients was 73 months, but DFI was not reached in partial mastectomy patients (p < 0.0001). Compared with partial mastectomy patients, mastectomy patients had more advanced disease in terms of tumor size, lymph node status, and stage and showed lesser clinical and pathological responses to NAC and effects on ypN. Furthermore, first recurrences in mastectomy patients were often distant metastases, leading to poor prognosis. Moreover, we analyzed the prognostic factors in 118 patients who achieved pCR. Univariate Cox regression analysis showed the association of the following with DFI: age (≤40, >40), cN, stage, surgery type, and ypN for all cases; decreasing Ki-67 values after NAC, luminal B HER2(−); clinical tumor size (cT), cN, surgery type, and luminal B HER2(+); ypN and HER2; age (≤40, >40), cN, stage, surgery type, and TN. In multivariate cox regression analysis, age (≤40, >40), surgery type, and ypN were independent predicting factors for all cases. Conclusions: Prognostic factors after NAC differ among subtypes. Surgery type was strongly associated with outcomes after NAC, so it could be an independent prognostic factor. Citation Format: Fujihara M, Kin T, Yoshimura Y, Kajiwara Y, Ito M, Ohtani S. Prognostic factors after neoadjuvant chemotherapy in breast cancer: Surgery type as a new prognostic factor [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-16-24.

【Background】 Contrast Enhanced Subtraction Mammography (CESM) has gained worldwide popularity. It is said that CESM can not only identify tumors but also delineate high-density lesions of the mammary gland that are difficult to be identified by normal mammography (MMG), as well as intraductal progress, and tumor hemodynamics. 一In general, imaging is commenced two minutes after injection of the contrast medium, and is conducted in two directions, i.e., left to right craniocaudal view and mediolateral oblique view in the similar manner to the normal MMG. 【Subjects and purpose】 The study was performed upon the approval of the institutional review board, and included 70 patients who had undergone CESM during the nine-month period from August 2015 to April 2016 using the method that MMG was performed within 2-8 minutes after injection of the contrast medium during contrast enhanced computed tomography. The scan was performed as postoperative follow-up in 29 patients, and as preoperative testing in 41 patients. This method allowed us to obtain additional data with contrast imaging without placing financial burden on the patient, and we investigated whether this method was effective as CESM in the present study. 【Results】 Of the 41 patients who had undergone the scan as a preoperative test (bilateral scans in 3 patients, and 44 breasts), it was in 43 breasts (97.7 %) that lesions could be identified by MMG, and in 42 breasts (95.5 %) that lesions could be identified by CESM. Of the 44 breasts, three breasts showed high-density mammary glands, in two of which the mass was lateral to the margin of the mammary gland, and therefore could be identified by normal MMG; however, in one breast the mass was medial to the margin of the mammary gland and difficult to be identified by MMG, and could only be identified by CESM. The lesions in the two breasts that were difficult to be identified by CESM exhibited the histological type of DCIS, and the lesions were able to be identified as calcification with normal MMG. The tumor diameter was compared using invasion size determined by CESM, contrast-enhanced MRI, and postoperative pathological specimen, respectively. The correlation coefficient for CESM and contrast-enhanced MRI was 0.9668, and the correlation coefficient for CESM and postoperative pathological specimen was 0.984887, with a strong correlation observed (Pearson's correlation coefficient test). 【Conclusion】 To the best of our knowledge, no reports of CESM in which MMG is performed immediately after contrast-enhanced CT have been published to date, and thus this is the world's first attempt of such method performed at our hospital. CESM ensures diagnosability without being invasive or placing financial burden on the patient. It was suggested that CESM can be clinically useful particularly for those who cannot undergo contrast-enhanced MRI due to hardware problems, financial difficulties, or metal embedded within the body. Citation Format: Ohtani S, Yoshimura Y, Kin T, Fujihara M, Kajiwara Y, Ito M, Okada N, Urashima M. Potential clinical application of mammography conducted immediately after contrast enhanced CT as contrast enhanced subtraction mammography [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-01-04.

Metronomic chemotherapy is based on administration of anticancer agents at low-doses at close regular intervals with no prolonged breaks, and aims to inhibit vascular endothelial cells as well as tumor cells. Recently, it was suggested that metronomic chemotherapy exerts anti-angiogenic effects by inducing thrombospondin-1 (TSP-1) and early growth response-1 (EGR-1), and antitumor effects by suppressing cancer stem cells. S-1 is a novel orally administered anticancer drug that is a combination of tegafur, 5-chloro-2, 4-dihydroxypyridine and oteracil potassium for maintaining efficacious concentrations of 5-FU and reducing the serious gastrointestinal toxicity associated with 5-FU. In the present study, we tried to determine the suitable administration method of S-1 against oral squamous cell carcinoma as a metronomic chemotherapy. We performed in vivo experiments in which tumor-bearing nude mice were used to examine the antitumor activity of S-1 (6.9 mg/kg). HSC2 tumors were treated with three different regimens, given as 4-week treatment and 2-week rest (4W-2W, 1 cycle); 2-week treatment and 1-week rest (2W-1W, 2 cycles); or alternate days treatment (1D-1D, 6 weeks). A fourth group served as control. Antitumor effects and body weight changes were compared in each group. Expression of TSP-1, EGR-1, CD31 and CD44 in HSC2 tumors was examined by immunohistochemistry. The treated groups showed higher tumor growth inhibition compared to the control group, and the relative tumor growth inhibition was not different between the treated groups. Briefly, each relative tumor growth inhibition was 32.4% (4W-2W), 39.6% (2W-1W) and 37.0% (1D-1D). During treatment periods, body weights were lower in the mice with 4W-2W or 2W-1W than 1D-1D or control. Moreover, reduction of microvessel density and CD44 expression, and induction of TSP-1 and EGR-1 expression was markedly seen in 1D-1D-treated tumors compared to 4W-2W-, 2W-1W-treated tumors or untreated control tumors by immunohistochemistry. These findings suggest that the 1D-1D regimen is more useful than the 4W-2W or 2W-1W regimen as a metronomic chemotherapy.