Lung Oligometastasis of Breast Cancer: Prospective Cohort Study of Treatment Strategies (SBP-06).

While local treatment of metastases is considered to be unrelated to prognosis, previous studies have suggested that local treatment of isolated lung metastases may have positive prognostic impact. We designed this prospective cohort study to investigate the clinical situation and its outcomes. We enrolled patients with fewer than 3 lung nodules suspected of being oligometastases after curative breast cancer surgery. Treatments, including local and systemic therapy, were selected by the physician and patient in consultation. The primary outcome was overall survival (OS); secondary outcomes were the efficacy and the safety of the surgery for lung oligometastases. Between May 2015 and May 2019, 14 patients were enrolled. Resection of lung nodules (metastasectomy) was performed in 11 (78.6%) of 14 patients, and one of these cases was diagnosed as primary lung cancer. Metastasectomies were all performed employing video-assisted thoracic surgery (VATS) without perioperative complications. Systemic therapies were administered to all patients except one. The respective 3-year and 5-year OS rates of patients with lung oligometastases were 91.6% and 81.5%, respectively. Progression occurred in 6 patients: 3 of the 10 with metastasectomy and all 3 without this surgical procedure. Lung metastasectomy was worthwhile as a diagnostic evaluation and may provide long-term benefit in some patients.

Effect of isoflavones on breast cancer cell development and their impact on breast cancer treatments.

PURPOSE: Epidemiological studies have suggested that intake of soy isoflavones is associated with a reduced risk of development of breast cancer and an improved prognosis in patients with breast cancer. In addition, basic research has demonstrated the antitumor effects of these compounds on breast cancer cell lines. However, the detailed effects of the intake of equol, which is one of the metabolites of the soy isoflavones, are yet to be clarified on the risk of development and recurrence of breast cancer and its interactions with drugs used for treating breast cancer. This study aimed to determine the antitumor effects of equol and investigate the impact of adding equol to therapeutic agents for breast cancer using breast cancer cell lines. METHODS: We examined the antitumor effect of equol on breast cancer cell lines using MTS assay. We also studied the combined effect of equol and the existing hormonal or chemotherapeutic agents using combination index. We evaluated the expressions of the related proteins by Western blot analysis and correlated the findings with the antitumor effect. RESULTS: Equol showed bi-phasic protumor and antitumor effects; at a low concentration, it promoted the tumor growth in hormone receptor-positive cell lines, whereas antitumor effects were generally observed when an excessive amount of dose unexpected in the blood and the tissue was administered. When used with tamoxifen, equol might have some antagonistic effect, although it depends on equol concentration and the type of cancer cells. CONCLUSIONS: We confirmed that equol has dual action, specifically a tumor growth-promoting effect and an antitumor effect. Although the results suggested that equol might exert an antagonistic effect against tamoxifen depending on the concentration, equol did not exert an antagonistic effect on other therapeutic agents.

Evaluation of Prognosis of Juvenile Differentiated Thyroid Carcinoma.

Differentiated thyroid carcinoma (DTC) in juvenile patients is often an extensive and aggressive disease with a high frequency of recurrence. However, the prognosis is excellent, with a low mortality rate even when advanced disease is present, although prognostic factors and treatment strategy remain uncertain. Between April 2004 and March 2017, 33 juvenile patients (< 30 years old) were diagnosed with DTC and treated at our institution. We retrospectively investigated prognosis and factors including sex, reason for discovery, treatment, pathological factors and treatment progress to clarify the risk factors. All patients underwent curative surgical treatment. Pathologically, lymph node metastasis was identified in 25 patients (75%). Thirteen patients (39%) had bilateral cervical metastasis. In addition, 9 (27%) had more than 10 metastatic lymph nodes. The 2 patients with more than 20 metastatic lymph nodes were treated with radioactive iodine (RAI). Five patients (15%) had local recurrences and received surgery. There have been no further recurrences or deaths. However, no factors were determined to significantly predict the recurrence of juvenile DTC. Local recurrent disease was treated with surgery and/or RAI until remission, and survival was excellent in juvenile DTC.

Current Multidisciplinary Approach to Fertility Preservation for Breast Cancer Patients.

Adverse effects on fertility are a significant problem for premenopausal breast cancer patients. Since April 2009, we have been referring young patients for fertility counseling provided by a multidisciplinary team. Here we evaluated the efficacy and safety of our current fertility preservation approach. We retrospectively analyzed the cases of 277 patients < 45 years old at diagnosis, which was made between 2009 and 2016. Seventy-two (26%) patients received fertility counseling. Seventeen (6%) of the 277 patients decided to preserve their fertility before starting adjuvant systemic therapy. Six (35%) patients underwent oocyte cryopreservation, and 11 (65%) married patients opted for embryo cryopreservation. There were no pregnancies among the patients undergoing oocyte cryopreservation, whereas 3 (27%) of the patients who opted for embryo cryopreservation became pregnant. Two (12%) patients stopped endocrine therapy after 2 years in an effort to become pregnant, but their breast cancers recurred. Though the problem of fertility loss for breast cancer patients is important and we should assess the infertility risk for all patients, we should also consider the prognosis. In June 2016, we launched a prospective multicenter cohort study to evaluate the efficacy and safety of fertility preservation in greater detail.

Ten Cases of Colovesical Fistula due to Sigmoid Diverticulitis.

Colovesical fistula (CVF) resulting from colon diverticulosis is a comparatively rare disease, and neither the diagnosis nor treatment has been established. Our experience with CVF due to sigmoid diverticulitis over a 9-year period was reviewed to clarify the clinical presentation and diagnostic confirmation. Ten patients with CVF were identified in this period, and chief complaints, laboratory findings, presenting symptoms, diagnostic investigations, and subsequent treatments were reviewed. Preoperative urinalysis showing bacteriuria (100%) was the most common presentation, followed by fecaluria (40%), abdominal pain (40%), pneumaturia (30%), hematuria (30%), pain on urination (30%), pollakiuria (10%), and dysuria (10%). The abilities of various preoperative investigations to identify CVF were: computed tomography (CT), 88.9%; magnetic resonance imaging, 40%; cystoscopy, 30%, and gastrografin irrigoscopy, 22.2%. Colonoscopy (0%) was not diagnostic. Bowel resection was performed in nine of ten patients. When inflammation was intense, covering ileostomy was performed, and an omental plasty was placed between the bowel anastomosis and bladder. When CVF is suspected, we recommend CT followed by colonoscopy and cystoscopy as a first-line investigation to rule out malignancy as a cause. Other modalities should only be used if the diagnosis is in doubt or additional information is needed to plan operative management. Primary colic anastomosis appears to be safely performed by applying omental plasty and covering ileostomy.

Long-Term Physical Activity and Body Composition After Exercise and Educational Programs for Breast Cancer: A Randomized Controlled Trial From the Setouchi Breast Project-10.

BACKGROUND: It is unclear what interventions can sustain long-term higher physical activity (PA) to improve breast cancer outcomes. Thus, this study aimed to evaluate the long-term effects of interventions on PA after breast cancer treatment. METHODS: This was a prospective randomized controlled trial for patients with stage 0 to III breast cancer evaluating the efficacy of exercise and educational programs on long-term PA compared with usual care. The primary endpoint was proportion of patients with recreational PA (RPA) ≥5 metabolic equivalents (METs)/week at 1 year after registration. RESULTS: From March 16, 2016, to March 15, 2020, breast cancer patients were registered in the control (n = 120), education (n = 121), or exercise (n = 115) group. There were no significant differences in proportion of RPA ≥5 METs/week at 1 year between the exercise and control groups (54% and 53%, P = .492) and between the education and control groups (62% and 53%, P = .126). Significant difference in reductions from baseline at 1 year were noted on body weight (P = .0083), BMI (P = .0034), and body fat percentage (P = .0027) between education and control groups. Similarly, the exercise group showed significant difference in reduction in body fat percentage (P = .0038) compared to control group. CONCLUSION: Although there were no significant effects on RPA 1 year after exercise and educational programs for breast cancer survivors, both interventions reduced body composition. Future studies on PA should investigate appropriate interventions to improve overall survival.

The effect of exercise and educational programs for breast cancer patients on the development of breast cancer-related lymphoedema: secondary endpoint from a randomized controlled trial in the Setouchi Breast Project-10.

BACKGROUND: Although the association between higher physical activity and preventive effect on breast-cancer-related lymphoedema (BCRL) has been reported, it is unclear what intervention is optimal. We aimed to investigate the effect of exercise and educational programs on BCRL development. METHODS: This study was a secondary endpoint analysis from a prospective randomized controlled trial. We enrolled patients with stage 0-III breast cancer from March 2016 to March 2020 and randomly assigned them to the control (n = 111), education (n = 115), or exercise (n = 104) group. As secondary endpoint, we assessed the incidence of and preventive effect on BCRL at 12 months post-intervention. RESULTS: There were no significant differences in the incidence of BCRL at 12 months post-intervention between the exercise and control groups (9.8% and 10.8%, P = 0.83) and the education and control groups (11.6% and 10.8%, P = 1.00). There were no significant differences in time to BCRL onset from the day of surgery between the exercise and control groups (event rate at 12 months: 20.7% and 17.2%, log-rank, P = 0.54) and the education and control groups (18.8% and 17.2%, log-rank, P = 0.57). The multivariable analyses indicated that axillary dissection and obesity significantly increased the risk of BCRL [hazard ratio (HR): 2.36, 95% confidence interval (CI) 1.52-3.67 and HR: 1.68, 95% CI 1.07-2.63, respectively]. CONCLUSIONS: The intervention did not decrease the risk of BCRL, and axillary dissection and obesity were the risk factors of BCRL. TRIAL REGISTRATION NUMBER: UMIN000020595 at UMIN Clinical Trial Registry.

Relationships of physical and breast cancer phenotypes with three single-nucleotide polymorphisms (rs2046210, rs3757318, and rs3803662) associated with breast cancer risk in Japanese women.

BACKGROUND: Recent genome-wide association studies have shown that many single-nucleotide polymorphisms (SNPs) are associated with breast cancer risk. However, it is often unclear how these SNPs are related to breast cancer. Analysis of associations between SNPs and phenotypes may be important for determining mechanisms of action, including carcinogenesis. METHODS: In previous case-control studies, we found three SNPs (rs2046210, rs3757318, and rs3573318) associated with breast cancer risk in Japanese women. Among these SNPs, two (rs2046210 and rs3757318) are located at 6q25.1, in proximity to the estrogen receptor 1 gene (ESR1). Using data from these studies, we examined associations between factors related to breast cancer risk, such as height, weight, and breast density, and the three SNPs in cases and controls. We also investigated whether the SNPs correlated with breast cancer features, such as estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor type-2 (HER2) status, and clinical stage. RESULTS: There was a significant difference in mean height between risk and non-risk allele carriers for rs2046210 (156.0 ± 5.8 vs. 154.3 ± 5.5 cm, p = 0.002), and rs3757318 (155.8 ± 5.7 vs. 154.7 ± 5.6 cm, p = 0.035) in cases, but no significant associations between height and these SNPs in controls. There was also a significant difference in breast density between risk and non-risk allele carriers for rs2046210 (p = 0.040) and rs3757318 (p = 0.044) in cases. rs2046210 and rs3757318 risk allele carriers tended to have higher breast density in all subjects and in controls. In cases, rs3757318 risk allele carriers were also significantly more likely to be ER-negative compared to non-risk allele carriers (ER-positive rate: 77% vs. 84%, p = 0.036). CONCLUSIONS: SNPs rs2046210 and rs3757318, which are associated with breast cancer risk in Japanese women, were significantly associated with height and high breast density, and this association was particularly strong in those with breast cancer. These findings suggest that SNPs in the ESR1 gene region affect phenotypes such as height and breast density.

Influences of preoperative metformin on immunological factors in early breast cancer.

PURPOSE: Metformin has been suggested to possibly reduce cancer risk. However, the mechanism underlying the positive effects of metformin on cancer treatment remains unclear. We conducted a prospective study to evaluate the effects of preoperative metformin in patients with early breast cancer. METHOD: We evaluated the effects on immunological factors (TILs, CD4 + , CD8 + , PD-L1, IFNγ and IL-2) by comparing core needle biopsies (CNB) obtained before metformin treatment with surgical specimens. Seventeen patients were enrolled in this prospective study from January to December 2016. We also analyzed 59 patients undergoing surgery during the same period to reveal the correlation of immune factors between CNB and surgical specimen. RESULT: There was a moderate correlation between CNB and surgical specimens on TILs and CD8 + lymphocyte. (TILs Rs = 0.63, CD4 + Rs = 0.224, CD8 + Rs = 0.42) In the metformin group, TILs increases were confirmed in five (29%) patients, while a decrease was confirmed in two (12%). The expressions of CD4 + and CD8 + by TILs were increased in 41% and 18% of surgical specimens, respectively. However, TILs number (p = 0.0554), CD4+ (p = 0.0613) and CD8 + (p = 0.0646) expressions did not significantly increased. Furthermore, IFNγ expression appeared to be increased in response to metformin (p = 0.08). CONCLUSION: Preoperative metformin tends to increase TILs, as well as the numbers of CD4 and CD8 positive lymphocytes, and IFNγ levels. Metformin might improve immune function and have a possibility of chemo-sensitivity and thereby increase the effectiveness of immunotherapy, based on the results of this preliminary study.

Recurring radiation-induced angiosarcoma of the breast that was treated with paclitaxel chemotherapy: a case report.

BACKGROUND: Angiosarcoma of the breast is very rare and can be divided into primary and secondary angiosarcoma. Radiation-induced angiosarcoma (RIAS) is classified as secondary angiosarcoma. Diagnosis of RIAS is difficult due to its rarity, and the interpretation of pathological imaging is complicated. In the National Comprehensive Care Network (NCCN) guidelines, the first choice of treatment is surgery with negative margins. Adjuvant radiotherapy (RT) for close soft tissue margins should be considered. Preoperative or adjuvant chemotherapy of nonmetastatic disease is not recommended for angiosarcoma. We report a case of RIAS, which was impossible to diagnose with core needle biopsy (CNB) but was diagnosed by excisional biopsy. The patient was then administered adjuvant chemotherapy using conjugated paclitaxel (PTX). CASE PRESENTATION: A 62-year-old woman noticed a tumor in her right breast. She had a history of right breast cancer and had undergone breast-conserving surgery, RT, and tamoxifen therapy 8 years previously. CNB, which was performed twice, was inconclusive. The tumor was surgically excised and pathological analysis yielded a diagnosis of angiosarcoma. She then underwent a right mastectomy. One month after she underwent right mastectomy, a nodule reappeared on the skin of her right breast, and excisional biopsy revealed recurrence of angiosarcoma. A few weeks later another nodule reappeared near the post-operative scar and excisional biopsy revealed recurrence of angiosarcoma. We assumed that surgical therapy was insufficient because the patient experienced relapse of angiosarcoma after complete mastectomy. After the second recurrence, we treated her with systemic chemotherapy using PTX. There was no evidence of recurrence 8 months after chemotherapy. CONCLUSION: Although angiosarcoma is difficult to diagnose, many patients have a poor prognosis. Therefore, prompt treatment intervention is desired. Moreover, there is little evidence regarding adjuvant therapy of angiosarcoma since it is a rare disease. We consider that adjuvant therapy helped to effectively prevent recurrence in the patient after complete excision.

Evaluation of Therapeutic Target Gene Expression Based on Residual Cancer Burden Classification After Neoadjuvant Chemotherapy for HER2-Negative Breast Cancer.

INTRODUCTION: Patients with residual disease usually have a poor prognosis after neoadjuvant chemotherapy for breast cancer. The aim of this study was to explore therapeutic targets and potential additional adjuvant treatments for patients with residual disease after standard neoadjuvant chemotherapy. PATIENTS AND METHODS: We retrieved publicly available complementary DNA microarray data from 399 human epidermal growth factor receptor 2 (HER2)-negative primary breast cancer samples from patients who underwent standard neoadjuvant chemotherapy. We analyzed the messenger RNA (mRNA) expression levels of key breast cancer markers and therapeutic target genes according to residual cancer burden (RCB) classification: RCB-0/I, RCB-II, and RCB-III. RESULTS: Among hormone receptor-positive samples, there were more luminal A tumors by PAM50 (Prediction Analysis of Microarray 50 [Prosigna], aka Prosigna Breast Cancer Prognostic Gene Signature Assay) in RCB-III than in RCB-0/I and RCB-II (P < .01). The mRNA expressions of ESR1 and PGR were significantly higher, and that of MKI67 was lower in RCB-II and RCB-III than in RCB-0/I. The mRNA expression of cyclin D1 was up-regulated in RCB-III and that of CDKN2A was down-regulated in RCB-III (P = .027 and < .01). Among triple-negative (TN) samples, RCB-III had higher clinical stage and more lymph node-positive samples than RCB-0/1 and RCB-II (P < .01). In both subtypes, VEGF-C expression was significantly higher in RCB-III than in RCB-0/I and RCB-II. CONCLUSION: In hormone receptor-positive breast cancer, biological features such as luminal A were associated with RCB; this trend was not observed in TN breast cancer. Further, some targeted therapies should be tested as new strategies after standard neoadjuvant chemotherapy in future clinical trials.