Real-world progression-free survival and overall survival of palbociclib plus endocrine therapy (ET) in Japanese patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer in the first-line or second-line setting: an observational study.

BACKGROUND: A recent large real-world study conducted in the United States reported the effectiveness of palbociclib plus aromatase inhibitor in HR+/HER2- advanced breast cancer (ABC). However, local clinical practice and available medical treatment can vary between Japan and Western countries. Thus, it is important to investigate Japanese real-world data. This observational, multicenter study (NCT05399329) reports the interim analysis of effectiveness of palbociclib plus ET as first-line or second-line treatment for HR+/HER2- ABC by estimating real-world progression-free survival (rwPFS) and overall survival (OS) in Japanese routine clinical practice. METHODS: Real-world clinical outcomes and treatment patterns of palbociclib plus ET were captured using a medical record review of patients diagnosed with HR+/HER2- ABC who had received palbociclib plus ET in the first-line or second-line treatment across 20 sites in Japan. The primary endpoint was rwPFS; secondary endpoints were OS, real-world overall response rate, real-world clinical benefit rate, and chemotherapy-free survival. RESULTS: Of the 677 eligible patients, 420 and 257 patients, respectively, had received palbociclib with ET as first-line and second-line treatments. Median rwPFS (95% confidence interval) was 24.5 months (19.9-29.4) for first-line and 14.5 months (10.2-19.0) for second-line treatment groups. Median OS was not reached in the first-line group and was 46.7 months (38.8-not estimated) for the second-line group. The 36-month OS rates for de novo metastasis, treatment-free interval (TFI) ≥ 12 months, and TFI < 12 months were 80.2% (69.1-87.7), 82.0% (70.7-89.3), and 66.0% (57.9-72.9), respectively. CONCLUSION: The addition of palbociclib to ET was effective for treating HR+/HER2- ABC in Japanese routine clinical practice.

Metformin Alters Tumor Immune Microenvironment, Improving the Outcomes of Breast Cancer Patients With Type 2 Diabetes Mellitus.

This study investigated the clinical effect of metformin on breast cancer patients with preexisting type 2 diabetes mellitus (T2DM). We analyzed 177 patients with T2DM who underwent breast cancer surgery and assessed tumor-associated macrophages (TAMs) and tumor-infiltrating lymphocytes (TILs) in patients who underwent tumor resection with or without metformin treatment using multiplex immunohistochemistry (IHC). Patients who received metformin either pre- or postoperatively exhibited reduced distant organ recurrence and improved postoperative recurrence-free survival compared to those of patients who did not. Additionally, in a subgroup of 40 patients receiving preoperative systemic therapy, metformin treatment was associated with increased rates of pathological complete response. IHC analysis revealed significantly lower levels of cluster of differentiation (CD) 68(+) CD163(+) M2-type TAMs (p < 0.01) but higher CD3(+) and CD8(+) TIL densities in the metformin-treated group compared with the same parameters in those without metformin treatment, with a significant difference in the CD8(+)/CD3(+) TIL ratio (p < 0.01). Despite the constraints posed by our small sample size, our findings suggest a potential role for metformin in modulating the immunological microenvironment, which may contribute to improved outcomes in diabetes patients with breast cancer.

The Japanese Breast Cancer Society Clinical Practice Guidelines for systemic treatment of breast cancer, 2022 edition.

The Japanese Breast Cancer Society (JBCS) Clinical Practice Guidelines for systemic treatment of breast cancer were updated to the 2022 edition through a process started in 2018. The updated guidelines consist of 12 background questions (BQs), 33 clinical questions (CQs), and 20 future research questions (FRQs). Multiple outcomes including efficacy and safety were selected in each CQ, and then quantitative and qualitative systematic reviews were conducted to determine the strength of evidence and strength of recommendation, which was finally determined through a voting process among designated committee members. Here, we describe eight selected CQs as important updates from the previous guidelines, including novel practice-changing updates, and recommendations based on evidence that has emerged specifically from Japanese clinical trials.

Efficacy and safety of surgical energy devices for axillary node dissection: a systematic review and network meta-analysis.

Various surgical energy devices are used for axillary lymph-node dissection. However, those that reduce seroma during axillary lymph-node dissection are unknown. We aimed to determine the best surgical energy device for reducing seroma by performing a network meta-analysis to synthesize the current evidence on the effectiveness of surgical energy devices for axillary node dissection for breast cancer patients. We searched MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, and World Health Organization International Clinical Trials Platform Search Portal. Two reviewers independently selected randomized controlled trials (RCTs) comparing electrosurgical bipolar vessel sealing (EBVS), ultrasonic coagulation shears (UCS), and conventional techniques for axillary node dissection. Primary outcomes were seroma, drained fluid volume (mL), and drainage duration (days). We analyzed random-effects and Bayesian network meta-analyses. We evaluated the confidence of each outcome using the CINeMA tool. We registered with PROSPERO (CRD42022335434). We included 34 RCTs with 2916 participants. Compared to the conventional techniques, UCS likely reduces seroma (risk ratio [RR], 0.61; 95% credible interval [CrI], 0.49-0.73), the drained fluid volume (mean difference [MD], - 313 mL; 95% CrI - 496 to - 130), and drainage duration (MD - 1.79 days; 95% CrI - 2.91 to - 0.66). EBVS might have little effect on seroma, the drained fluid volume, and drainage duration compared to conventional techniques. UCS likely reduce seroma (RR 0.44; 95% CrI 0.28-0.69) compared to EBVS. Confidence levels were low to moderate. In conclusion, UCS are likely the best surgical energy device for seroma reduction during axillary node dissection for breast cancer patients.

[Long-Term Survival of a Patient with Triple-Negative Breast Cancer with Hormone Receptor Status Conversion between Primary and Metastatic Tumors].

Patients with triple-negative breast cancer have poor survival after recurrence. However, previous studies have shown that receptor conversion can occur between primary breast tumor and metastatic sites. Herein, we describe the case of a 54- year-old woman with advanced breast cancer, which showed receptor conversion from primary tumor(triple-negative)to distant metastases(Luminal type). The patient had undergone left radical mastectomy and left axillary lymph node dissection at another hospital(pT3N0M0, Stage ⅡB, ER-negative, PgR-negative, and HER2-negative). She was referred to our hospital for adjuvant chemotherapy with 3 courses of 5-fluorouracil, epirubicin, and cyclophosphamide and 3 courses of docetaxel. Around 26 months after the surgery, the follow-up CT scan showed multiple lung nodules. Another 9 months later, her left axillary and mediastinal lymph nodes were enlarged. She received several courses of anticancer chemotherapy. After paclitaxel and bevacizumab were administered as seventh-line chemotherapy, a vacuum-assisted biopsy of the left axillary lymph node was performed to confirm the presence of metastasis. Furthermore, immunohistochemistry results showed that the metastatic tumor was ER-positive, PgR-positive, and HER2-negative. Fulvestrant and palbociclib were then initiated as first-line endocrine therapy. She has been stable for more than 18 months since. It is essential to perform biopsies of metastatic sites for optimal management of patients with metastatic breast cancer.

Making the upper edge of a silicone breast implant invisible by fat onlay-grafting harvested from the affected inframammary fold.

BACKGROUND: In silicone breast implant (SBI)-based breast reconstructions, aesthetic outcomes are often low due to the visible upper edge of the SBI. To ameliorate this, grafting fat harvested from the SBI operative field has not been reported to date. Therefore, we aimed to develop a novel technique for fat onlay-grafting, harvested from the inframammary fold (IMF) of the reconstructed breast, and investigate its usefulness. METHODS: A total of 90 patients who underwent SBI-based breast reconstruction after a simple mastectomy were included in this study. The harvested fat was recorded by weight and grafted evenly to the medial and median upper edge of the SBI on the pectoralis major muscle. We applied this technique to 30 patients (fat onlay-grafting group) and compared them with the 60 patients (no-grafting group) who did not undergo our technique using the postoperative 1-year aesthetic outcome scores of the medial and median upper edge of the SBI. Furthermore, we investigated the correlation between the weight of harvested fat and body mass index. RESULTS: No postoperative wound complications occurred, and infection, hardened fat, and fat lysis were not found in the fat onlay-grafting group. The medial and total aesthetic outcome scores in the fat onlay-grafting group were significantly higher than those in the no-grafting group (P<0.05). The average weight of harvested fat was 11.9 [5-32] g. The correlation between the weight of the harvested fat and body mass index was significantly positive (R2=0.7119, P<0.05). CONCLUSIONS: Our technique made the upper edge of the SBI invisible. Further, it was simple and less invasive with safe augmentation. Therefore, we believe that this technique can contribute to better aesthetic outcomes in SBI-based breast reconstruction.

Influence of Flap Thickness on Nipple Projection After Nipple Reconstruction Using a Modified Star Flap.

BACKGROUND: In nipple reconstruction, the width, length, and thickness of modified star flaps are concerns for long-term reconstructed nipple projection. However, the flap's projection has not been analyzed, based on its thickness. The aim of the present study was to investigate how flap thickness in a modified star flap influences the resulting reconstructed nipple and achieves an appropriate flap width in design. METHODS: Sixty-three patients who underwent nipple reconstruction using a modified star flap following implant-based breast reconstruction between August 2014 and July 2016 were included in this case-controlled study. The length of laterally diverging flaps was 1.5 times their width. The thickness of each flap was measured using ultrasonography, and the average thickness was defined as the flap thickness. We investigated the correlation between the resulting reconstructed nipple and flap thickness, and the difference of the change in the reconstructed nipple projection after using a thin or thick flap. RESULTS: The average flap thickness was 3.8 ± 1.7 (range 2.5-6.0) mm. There was a significant, linear correlation between the flap thickness and resulting reconstructed nipple projection (ß = 0.853, p < 0.01). Furthermore, the difference between the thin and thick flaps in the resulting reconstructed nipple projection was significant (p < 0.01). CONCLUSION: Measuring the flap thickness preoperatively may allow surgeons to achieve an appropriate flap width; otherwise, alternative methods for higher projection might be used. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Individual difference in pectoralis major muscle thickness and its effect on single-stage breast reconstruction using a tissue expander.

BACKGROUND: In breast reconstruction using a tissue expander (TE), sufficient coverage of the TE with the pectoralis major (PM) muscle, particularly with a musculofascial flap, is highly important for avoiding postoperative complications. In patients in whom the PM is thin, intraoperative trauma often occurs, leading to troublesome repair. The present study aimed to investigate the usefulness of preoperative measurement of PM thickness in planning of breast reconstruction using a TE. METHODS: In this case-control study, we identified 68 patients (70 breasts) with mammary carcinoma treated with simple mastectomy and TE insertion from April 2014 to December 2016. We measured average PM thickness at two specific points, sternocostal PM distance on the long axis and sternocostal PM area preoperatively using magnetic resonance imaging. Then, we analyzed the difference in PM thickness among individuals and its relationship to intraoperative trauma to the PM or surgical difficulty creating a muscular pocket (delicate PM). RESULTS: Average PM thickness was significantly larger in younger patients (p = 0.046) and those with larger breasts (p < 0.01). In addition, average PM thickness on the affected side was significantly smaller in patients with delicate PM (12 breasts) (p < 0.01). PM thickness had a significant influence on delicate or firm PM (odds ratio 27.40; 95% confidence interval 2.01-372.00; p = 0.013). CONCLUSION: These findings demonstrate the usefulness of preoperative measurement of PM thickness in planning of breast reconstruction using a TE. Dissection should be performed more carefully in patients with average PM thickness less than 2.9 mm.

Peritoneal cancer arising after total abdominal hysterectomy and bilateral salpingo-oophorectomy for cervical cancer in a patient with right breast cancer and germline mutation of BRCA1 gene: a case report and literature review.

Primary peritoneal carcinoma is usually advanced at diagnosis and curability is low unless the patient has a small tumor burden. Peritoneal carcinoma can occur in association with hereditary breast and ovarian cancer syndrome, which is thought to account for 5-6% of all breast cancer. Mutations of two breast cancer susceptibility genes, BRCA1 and BRCA2, are responsible for hereditary breast and ovarian cancer. Women with BRCA1/2 mutations often undergo risk-reducing salpingo-oophorectomy (RRSO) to prevent both ovarian and breast cancer. However, peritoneal carcinoma has been reported to develop after RRSO in patients with BRCA1/2 mutations. We experienced a patient with peritoneal carcinoma and inguinal lymph node metastasis after surgical resection of breast cancer and subsequent RRSO. This report describes the first case of peritoneal carcinoma arising after RRSO in a Japanese patient with BRCA1 mutation, including a review of the literature on peritoneal carcinoma associated with BRCA1/2 mutation.

A Simple and Practical Method for Setting Up a Criterion of Projection of Silicone Breast Implant After Simple Mastectomy.

Objective: In breast reconstruction, decision of projection of silicone breast implant in tissue expander replacement is difficult because of the need to consider several parameters that cannot be expressed in accurate numerical form. The present study aimed at a quantitative analysis based on decreased projection of the reconstructed side compared with silicone breast implant projection and to develop a new method for simple and practical decision of silicone breast implant projection. Methods: Thirty-five patients who had mammary carcinoma and were treated with simple mastectomy, tissue expander insertion, and replacement with anatomical silicone breast implant from April 2013 to March 2016 were retrospectively identified. We recorded the projection of used silicone breast implant (Pi). The projections of reconstructed breast 6 months after silicone breast implant insertion (Pr) and that of the unaffected breast during silicone breast implant selection (Pu) were measured. The difference between Pi and Pr was defined as the revised numerical value (Rev). We investigated whether Rev significantly differed according to age, body mass index, or Pu and analyzed correlations between Rev and age, Pu, and body mass index. Results: Mean Rev in all patients was 1.2 ± 0.3 cm. Rev was significantly higher in patients with higher body mass index than in those with lower body mass index (P < .01) and in patients with higher Pu than in those with lower Pu (P < .01). Significant positive correlations of Rev with body mass index and Pu were found (ß = .63, P < .01 and ß = .67, P < .01, respectively). Conclusions: Rev was a simple, practical, and cost-effective concept. We believe that it is a useful indicator for deciding silicone breast implant projection.

A New Criterion for the Application of 2-Stage Implant-Only Breast Reconstruction Using a Classification Based on the Rostrocaudal Distance Along the Chest Wall Between the Lowest Point of the Breast and Inframammary Fold.

Objective: It is generally difficult to achieve symmetry in implant-only breast reconstruction with ptosis, and it remains unclear what quantitative criterion may be applied in cases of breast ptosis regarding the application of this modality. Our study aimed to suggest a criterion for obtaining good aesthetic outcomes and a symmetrical inframammary fold that is well-fitting for the brassiere in implant-only breast reconstruction after simple mastectomy. Methods: We classified into 3 groups 50 consecutive patients who underwent implant-only breast reconstruction that created an inframammary fold using a modified internal method after simple mastectomy. The classification was based on the rostrocaudal distance along the chest wall between the lowest point of the breast the and the inframammary fold on the contralateral side (Dc, in millimeters). Thereafter, we compared this distance on the reconstructed side (Dr, in millimeters), Dc-Dr, and projection of the implant (Pi, in centimeters) between the groups and investigated the correlation between Dr and lower (Pi < 5.0 cm) and higher Pi (Pi ≥ 5.0 cm). Results: Dr was similar to Dc in groups 1 and 2 (0 ≤ Dc < 10 mm, 40/50 [80%]); however, Dr was significantly lesser than Dc in group 3 (Dc ≥ 10 mm, 10/50 [20%]). In addition, we found significant positive correlations between Dr and lower Pi and between Dr and higher Pi. Conclusions: A Dc below 10 mm may be a good indication for implant-only breast reconstruction. Furthermore, the modality may be applied where Dc is 7 mm or less in cases with lower Pi and where Dc is 13 mm or less in cases with higher Pi.

Decreased contralateral breast volume after mastectomy, adjuvant chemotherapy, and anti-estrogen therapy, in particular in breasts with high density.

Adjuvant chemotherapy and anti-estrogenic therapy can result in decreased volume of the contralateral breast, following mastectomy for the treatment of breast cancer. However, no data on the effect of adjuvant therapy on contralateral breast volume have previously been reported. We aimed to evaluate the extent to which adjuvant therapy and differences in breast density contribute to decreased breast volume. We conducted a prospective cohort study, selecting 40 nonconsecutive patients who underwent immediate breast reconstruction with mastectomy and expander insertion followed by expander replacement. We measured the contralateral breast volume before each procedure. The extent of the change was analyzed with respect to adjuvant therapy and breast density measured by preoperative mammography. The greatest decrease in breast volume was 135.1 cm3. The decrease in breast volume was significantly larger in the adjuvant therapy (+) group, particularly in patients with high breast density, than in the adjuvant therapy (-) group. Significant differences between the chemotherapy (+), tamoxifen (+) group and the chemotherapy (-), tamoxifen (+) group were not found. Breast density scores had a range of 2.0-3.3 (mean: 2.8). In breast reconstruction, particularly when performed in one stage, preoperative mammography findings are valuable to plastic surgeons, and possible decreases in the contralateral breast volume due to adjuvant therapy, particularly in patients with high breast density, should be considered carefully.

4-1BB-Enhanced Expansion of CD8+ TIL from Triple-Negative Breast Cancer Unveils Mutation-Specific CD8+ T Cells.

Triple-negative breast cancer (TNBC) highly infiltrated with CD8+ tumor-infiltrating lymphocytes (TIL) has been associated with improved prognosis. This observation led us to hypothesize that CD8+ TIL could be utilized in autologous adoptive cell therapy for TNBC, although this concept has proven to be challenging, given the difficulty in expanding CD8+ TILs in solid cancers other than in melanoma. To overcome this obstacle, we used an agonistic antibody (urelumab) to a TNFR family member, 4-1BB/CD137, which is expressed by recently activated CD8+ T cells. This approach was first utilized in melanoma and, in this study, led to advantageous growth of TILs for the majority of TNBC tumors tested. The agonistic antibody was only added in the initial setting of the culture and yet favored the propagation of CD8+ TILs from TNBC tumors. These expanded CD8+ TILs were capable of cytotoxic functions and were successfully utilized to demonstrate the presence of immunogenic mutations in autologous TNBC tumor tissue without recognition of the wild-type counterpart. Our findings open the way for a successful adoptive immunotherapy for TNBC. Cancer Immunol Res; 5(6); 439-45. ©2017 AACR.

Breast reconstruction of an unusual configuration using two paranemic implants.

Implant-based breast reconstruction can be performed using a choice of various types of breast implants. However, cases where the breast shapes are unsuitable for implant-based reconstruction method are occasionally encountered. We present two patients with wide trunks who underwent breast reconstruction using an unusual configuration that involved a latissimus dorsi myocutaneous flap combined with two paranemic implants.

Multicystic dedifferentiated retroperitoneal liposarcoma: tumour cyst fluid analysis and implications for management.

Liposarcomas are soft tissue sarcomas of adipocyte origin. We describe a case of a dedifferentiated retroperitoneal liposarcoma with an unusual presentation on recurrence as a large, multicystic tumour. The patient was a 72-year-old woman who had undergone multiple treatments including two prior resections. For her most recent locoregional disease recurrence, the patient was offered surgical debulking for symptom palliation. At this operation, performed after two cycles of chemotherapy, the tumour cyst fluid was analysed and found to have a predominance of immune cells with no identifiable malignant cells. This case and the results of our tumour cyst fluid analysis raise several interesting considerations for the management of this unique situation in a rare disease.

Peptide-based vaccination and induction of CD8+ T-cell responses against tumor antigens in breast cancer.

Tumor-associated antigens (TAAs) have been identified in many malignant tumors. Within these TAAs are peptide sequences that bind major histocompatibility complex (MHC) class I and class II molecules recognized by T cells triggering antigen-specific CD8+ cytotoxic T-cell and CD4+ T-helper cell responses. Efforts to develop vaccines for breast cancer have been underway for more than 20 years, including peptide and whole inactivated tumor cell vaccines as well as antigen-loaded dendritic cell vaccines. The majority of vaccine trials have used peptides, including single-peptide and multiple-peptide formulations using either MHC class I and class II epitopes in oil-based emulsions alone or in combination with an adjuvant, such as granulocyte-macrophage colony-stimulating factor, and Toll-like receptor agonists. Preclinical research in vitro and in animal models has been aimed at improving vaccine efficacy by identifying more immunogenic peptides and combinations of peptides and adjuvants and cytokine adjuvants that induce stronger immune responses and prolong T-cell memory. Clinical studies investigating the therapeutic potential of active immunization using peptide vaccines has found no serious side effects. In this review, we examine TAA peptide-based vaccination regimens showing promise in breast cancer patients that are also being investigated in clinical trials of safety and efficacy. We also discuss the current limitations in the peptide vaccination field and areas for future development.

Peptides derived from human insulin-like growth factor-II mRNA binding protein 3 can induce human leukocyte antigen-A2-restricted cytotoxic T lymphocytes reactive to cancer cells.

Insulin-like growth factor-II mRNA binding protein 3 (IMP-3) is an oncofetal protein expressed in various malignancies including lung cancer. This study aimed to identify immunogenic peptides derived from IMP-3 that can induce tumor-reactive and human leukocyte antigen (HLA)-A2 (A*02:01)-restricted cytotoxic T lymphocytes (CTL) for lung cancer immunotherapy. Forty human IMP-3-derived peptides predicted to bind to HLA-A2 were analyzed to determine their capacity to induce HLA-A2-restricted T cells in HLA-A2.1 (HHD) transgenic mice (Tgm). We found that three IMP-3 peptides primed HLA-A2-restricted CTL in the HLA-A2.1 Tgm. Among them, human CTL lines reactive to IMP-3 (515) NLSSAEVVV(523) were reproducibly established from HLA-A2-positive healthy donors and lung cancer patients. On the other hand, IMP-3 (199) RLLVPTQFV(207) reproducibly induced IMP-3-specific and HLA-A2-restricted CTL from healthy donors, but did not sensitize CTL in the HLA-A2.1 Tgm. Importantly, these two IMP-3 peptide-specific CTL generated from healthy donors and cancer patients effectively killed the cancer cells naturally expressing both IMP-3 and HLA-A2. Cytotoxicity was significantly inhibited by anti-HLA class I and anti-HLA-A2 monoclonal antibodies, but not by the anti-HLA-class II monoclonal antibody. In addition, natural processing of these two epitopes derived from the IMP-3 protein was confirmed by specific killing of HLA-A2-positive IMP-3-transfectants but not the parental IMP-negative cell line by peptide-induced CTL. This suggests that these two IMP-3-derived peptides represent highly immunogenic CTL epitopes that may be attractive targets for lung cancer immunotherapy.

Identification of SPARC as a candidate target antigen for immunotherapy of various cancers.

To establish efficient anticancer immunotherary, it is important to identify tumor-associated antigens (TAAs) directing the immune system to attack cancer. A genome-wide cDNA microarray analysis identified that secreted protein acidic and rich in cysteine (SPARC) gene is overexpressed in the gastric, pancreatic and colorectal cancer tissues but not in their noncancerous counterparts. This study attempted to identify HLA-A24 (A*2402)-restricted and SPARC-derived CTL epitopes. We previously identified H-2K(d)-restricted and SPARC-derived CTL epitope peptides in BALB/c mice, of which H-2K(d)-binding peptide motif is comparable with that of HLA-A24 binding peptides. By using these peptides, we tried to induce HLA-A24 (A*2402)-restricted and SPARC-reactive human CTLs and demonstrated an antitumor immune response. The SPARC-A24-1(143-151) (DYIGPCKYI) and SPARC-A24-4(225-234) (MYIFPVHWQF) peptides-reactive CTLs were successfully induced from peripheral blood mononuclear cells by in vitro stimulation with these two peptides in HLA-A24 (A*2402) positive healthy donors and cancer patients, and these CTLs exhibited cytotoxicity specific to cancer cells expressing both SPARC and HLA-A24 (A*2402). Furthermore, the adoptive transfer of the SPARC-specific CTLs could inhibit the tumor growth in nonobese diabetic/severe combined immunodeficient mice bearing human cancer cells expressing both HLA-A24 (A*2402) and SPARC. These findings suggest that SPARC is a potentially useful target candidate for cancer immunotherapy.

The forkhead box M1 transcription factor as a candidate of target for anti-cancer immunotherapy.

The present study attempted to identify a target antigen for immunotherapy for cholangiocarcinoma. Forkhead box M1 (FOXM1) was selected as a candidate antigen based on the data of previous cDNA microarray analysis of clinical samples of cholangiocarcinoma. The level of FOXM1 mRNA was more than 4 times higher in cancer cells in comparison to adjacent normal epithelial cells, in all of 24 samples of cholangiocarcinoma tissues. An immunohistochemical analysis also detected FOXM1 protein in the cancer cells but not in the normal cells. Twenty-three human FOXM1-derived peptides predicted to bind to HLA-A2 were analyzed to determine their ability to induce HLA-A2-restricted T cells in HLA-A2 transgenic mice. FOXM1(362-370) (YLVPIQFPV), FOXM1(373-382) (SLVLQPSVKV), and FOXM1(640-649) (GLMDLSTTPL) peptides primed HLA-A2-restricted cytotoxic T lymphocytes (CTLs) in the HLA-A2 transgenic mice. Human CTL lines reactive to these 3 peptides could also be established from HLA-A2-positive healthy donors and cancer patients. Natural processing of the 3 epitopes from FOXM1 protein was confirmed by specific killing of HLA-A2-positive FOXM1-transfectants by peptide-induced CTLs. FOXM1 is expressed in various types of cancers and it is also functionally involved in oncogenic transformation and the survival of cancer cells. Therefore, FOXM1 may be a suitable target for immunotherapy against various cancers including cholangiocarcinoma.