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.

Baseline gut microbiota as a predictive marker for the efficacy of neoadjuvant chemotherapy in patients with early breast cancer: a multicenter prospective cohort study in the Setouchi Breast Project-14.

PURPOSE: Various studies have demonstrated the causal relationship between gut microbiota and efficacy of chemotherapy; however, the impact of gut microbiota on breast cancer has not been fully elucidated. This study aimed to evaluate the associations between the gut microbiota before neoadjuvant chemotherapy and its consequent efficacy in breast cancer. METHODS: This prospective observational study included patients who received neoadjuvant chemotherapy for primary early breast cancer at eight institutions between October 1, 2019, and March 31, 2022. We performed 16S rRNA analysis of fecal samples and α and ß diversity analyses of the gut microbiota. The primary endpoint was the association between the gut microbiota and pathological complete response (pCR) to neoadjuvant chemotherapy. RESULTS: Among the 183 patients, the pCR rate after neoadjuvant chemotherapy was 36.1% in all patients and 12.9% (9/70), 69.5% (41/59), and 29.6% (16/54) in those with the luminal, human epidermal growth factor receptor 2, and triple-negative types, respectively. The α diversity of the gut microbiota did not significantly differ between patients with pCR and those without pCR. Among the gut microbiota, two species (Victivallales, P = 0.001 and Anaerolineales, P = 0.001) were associated with pCR, and one (Gemellales, P = 0.002) was associated with non-pCR. CONCLUSION: Three species in the gut microbiota had potential associations with neoadjuvant chemotherapy efficacy, but the diversity of the gut microbiota was not associated with response to chemotherapy. Further research is needed to validate our findings.

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.

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.

Optimizing the timing of 3.6 mg Pegfilgrastim Administration for Dose-Dense Chemotherapy in Japanese Patients with Breast Cancer.

Perioperative dose-dense chemotherapy (DDCT) with pegfilgrastim (Peg) prophylaxis is a standard treatment for high-risk breast cancer. We explored the optimal timing of administration of 3.6 mg Peg, the dose approved in Japan. In the phase II feasibility study of DDCT (adriamycin+cyclophosphamide or epirubicin+cyclophosphamide followed by paclitaxel) for breast cancer, we investigated the feasibility, safety, neutrophil transition, and optimal timing of Peg treatment by administering Peg at days 2, 3, and 4 post-chemotherapy (P2, P3, and P4 groups, respectively). Among the 52 women enrolled, 13 were aged > 60 years. The anthracycline sequence was administered to P2 (n=33), P3 (n=5), and P4 (n=14) patients, and the taxane sequence to P2 (n=38) and P3 (n=6) patients. Both sequences showed no interaction between Peg administration timing and treatment discontinuation, treatment delay, or dose reduction. However, the relative dose intensity (RDI) was significantly different among the groups. The neutrophil count transition differed significantly among the groups receiving the anthracycline sequence. However, the neutrophil count remained in the appropriate range for both sequences in the P2 group. The timing of Peg administration did not substantially affect the feasibility or safety of DDCT. Postoperative day 2 might be the optimal timing for DDCT.

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.

Influence of breast density on breast cancer risk: a case control study in Japanese women.

BACKGROUND: Mammography is the standard examination for breast cancer screening of woman aged ≥ 40 years. High breast density on mammography indicates that mammary gland parenchyma occupy a high percentage of the breast. The objective of this study was to investigate factors associated with breast density and the risk of high breast density for breast cancer. METHODS: A multicenter case-control study was performed in 530 patients and 1043 controls. Breast density was classified as C1-C4 using the Breast Imaging Reporting and Data System (BI-RADS). Clinical factors were obtained from questionnaires or medical records, and the influence of each factor (breast density, menopausal status, body mass index (BMI), parity, presence or absence of breastfeeding history, age at menarche, age at first birth, and familial history of breast cancer) on breast cancer risk in all patients was calculated as an age-adjusted odds ratio (OR). Multivariate logistic regression analyses were then performed in all patients and in pre- and postmenopausal and BMI-stratified groups using factors with a significant age-adjusted OR as adjustment factors. RESULTS: Age-adjusted ORs for breast cancer were significant for breast density, BMI, parity, and breast feeding, but not for age at menarche, age at first birth, or family history of breast cancer. In multivariate analysis, there was a significant correlation between breast density and breast cancer in postmenopausal women (OR for C1 vs. C2 1.90 [95% CI 1.34-2.70]; C1 vs. C4 2.85 [95% CI 1.10-7.16]). This correlation was also significant in patients in the third BMI quartile (22.3-24.5 kg/m2) (OR for C1 vs. C4 8.76 [95% CI 2.38-42.47]); and fourth BMI quartile (>24.5 kg/m2) (OR for C1 vs. C2 1.92 [95% CI 1.17-3.15]; C1 vs. C4 11.89 [95% CI 1.56-245.17]). CONCLUSION: Breast density on mammography is a risk factor for breast cancer after adjustment for other risk factors. This risk is particularly high in postmenopausal women and those with a high BMI.

The efficacy and feasibility of dose-dense sequential chemotherapy for Japanese patients with breast cancer.

BACKGROUND: Perioperative dose-dense chemotherapy (DDCT) with granulocyte-colony stimulating factor (G-CSF) prophylaxis is a standard treatment for patients with high-risk breast cancer. The approval of this approach in Japan led to the widespread adoption of DDCT, despite limited efficacy and safety data among Japanese patients. We evaluated the efficacy and safety of neoadjuvant DDCT for Japanese patients with breast cancer. METHODS: This prospective, multicenter, phase II study evaluated 52 women with operable human epidermal growth factor receptor 2-negative breast cancer and axillary lymph node metastasis. Neoadjuvant DDCT (adriamycin plus cyclophosphamide or epirubicin plus cyclophosphamide followed by paclitaxel) was administrated every 2 weeks with G-CSF support. The study endpoints were the rates of pathological complete response (pCR), febrile neutropenia, treatment completion, toxicities, and the relative dose intensity (RDI). RESULTS: The pCR rate was 21.9% (9/41) and the triple-negative (TN) subtype was significantly associated with a high pCR rate (triple-negative: 53.3% vs. luminal A: 7.7% and luminal B: 0%; p = 0.003). The treatment completion rate was 80.8% (42/52) and the average RDI was 98.9%. Most adverse events were manageable and tolerable. Six patients (11.5%) developed febrile neutropenia. Grade 3-4 adverse events were slightly more common among older patients (57%) with a low protocol completion rate (≥ 65 years: 42.9% vs. <65 years: 86.7%, p = 0.0062). CONCLUSION: The pCR rate for DDCT was similar to that of standard chemotherapy, although it was remarkably effective for the TN subtype. DDCT may be feasible for Japanese patients with breast cancer although caution is needed for older patients.

N-acetyltransferase 2 polymorphism and breast cancer risk with smoking: a case control study in Japanese women.

BACKGROUND: Recent studies have suggested that the association between smoking and breast cancer risk might be modified by polymorphisms in the N-acetyltransferase 2 gene (NAT2). Most of these studies were conducted in Western countries, with few reports from East Asia. METHODS: We conducted a case-control study of 511 breast cancer cases and 527 unmatched healthy controls from December 2010 to November 2011 in Japan. Unconditional logistic regression was used to analyze the association of smoking with breast cancer risk stratified by NAT2 phenotype. RESULTS: In this population, 11 % of the cases and 10 % of the controls were classified as a slow acetylator phenotype. Compared to never smokers, current smokers had an increased breast cancer risk in multivariate analysis [odds ratio (OR) = 2.27, 95 % confidence interval (95 %CI) = 1.38-3.82]. Subgroup analyses of menopausal status indicated the same tendency. Subgroup analyses of NAT2 phenotype, the ORs in both of rapid and slow acetylator phenotype subgroups were comparable, and no interactions were observed between smoking status and NAT2 phenotype (p = 0.97). A dose-dependent effect of smoking on breast cancer risk was seen for the rapid acetylator phenotype, but not for the slow acetylator phenotype. CONCLUSION: Given the high frequency of the rapid acetylator phenotype, these results show that smoking is a risk factor for breast cancer among most Japanese women. It may be of little significance to identify the NAT2 phenotype in the Japanese population.

A phase 1, dose-finding and pharmacokinetic study of gemcitabine with nab-paclitaxel in patients with metastatic breast cancer.

PURPOSE: Gemcitabine (Gem) with paclitaxel (Pac) is used for patients with metastatic breast cancer who require cytoreduction with manageable toxicities. Nanoparticle albumin-bound (nab)-Pac exhibits better efficacy and reduces the risk of hypersensitivity reactions associated with solvent-based Pac. Therefore, Gem plus nab-Pac (GA) therapy may be effective for metastatic breast cancer. The purpose of this study was to determine the maximum tolerated dose for GA therapy. METHODS: The subjects were patients with metastatic breast cancer with performance status 0 or 1 and normal hepatic, renal and marrow function. Leukopenia, neutropenia or thrombocytopenia of grade 4, neutropenic fever, or non-hematological toxicity of grade 3 or higher during the 1st cycle, and chemotherapy-induced peripheral neurotoxicity of grade 2 or higher at the end of the 1st cycle were defined as dose-limiting toxicities (DLTs). Gem (1250 mg/m(2)) was administered on days 1 and 8. nab-Pac was administered at a starting dose of 180 mg/m(2) (cohort 1) and escalated to 220 mg/m(2) (cohort 2) and 260 mg/m(2) (cohort 3) on day 1 of the 21-day cycle, using a 3 + 3 design. RESULTS: Nine patients (n = 3, 3, and 3 in cohorts 1, 2, and 3, respectively) were included in the study (median age 56 years; range 43-75 years). DLTs did not occur in any cohorts. CONCLUSIONS: The initial recommend dose in GA therapy is 1250 mg/m(2) Gem and 260 mg/m(2) nab-Pac. It is well known that nab-Pac has cumulative toxicities, and thus the efficacy and safety of GA therapy require validation in a phase 2 study.

Effects of lifestyle and single nucleotide polymorphisms on breast cancer risk: a case-control study in Japanese women.

BACKGROUND: Lifestyle factors, including food and nutrition, physical activity, body composition and reproductive factors, and single nucleotide polymorphisms (SNPs) are associated with breast cancer risk, but few studies of these factors have been performed in the Japanese population. Thus, the goals of this study were to validate the association between reported SNPs and breast cancer risk in the Japanese population and to evaluate the effects of SNP genotypes and lifestyle factors on breast cancer risk. METHODS: A case-control study in 472 patients and 464 controls was conducted from December 2010 to November 2011. Lifestyle was examined using a self-administered questionnaire. We analyzed 16 breast cancer-associated SNPs based on previous GWAS or candidate-gene association studies. Age or multivariate-adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were estimated from logistic regression analyses. RESULTS: High BMI and current or former smoking were significantly associated with an increased breast cancer risk, while intake of meat, mushrooms, yellow and green vegetables, coffee, and green tea, current leisure-time exercise, and education were significantly associated with a decreased risk. Three SNPs were significantly associated with a breast cancer risk in multivariate analysis: rs2046210 (per allele OR=1.37 [95% CI: 1.11-1.70]), rs3757318 (OR=1.33[1.05-1.69]), and rs3803662 (OR=1.28 [1.07-1.55]). In 2046210 risk allele carriers, leisure-time exercise was associated with a significantly decreased risk for breast cancer, whereas current smoking and high BMI were associated with a significantly decreased risk in non-risk allele carriers. CONCLUSION: In Japanese women, rs2046210 and 3757318 located near the ESR1 gene are associated with a risk of breast cancer, as in other Asian women. However, our findings suggest that exercise can decrease this risk in allele carriers.

ORAC and DPPH assay comparison to assess antioxidant capacity of tea infusions: relationship between total polyphenol and individual catechin content.

Commercially available tea infusions are the major source of catechins for preparing bottled tea beverages and tea supplements available in the market today. In the present study, we analyzed five tea infusions to measure the total antioxidant capacity (TAC) by oxygen radical absorbance capacity (ORAC) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging capacity (DRSC) assays, total polyphenol content by the colorimetric method and individual catechin content by high-performance liquid chromatography. Four major tea catechins were also analyzed for their TAC to reveal differential antioxidant behavior of the tea infusions, resulting in the ORAC and DRSC methods. The correlation coefficients between DRSC and the total polyphenol or total catechin content of the tea infusions were 1.0 and 0.99. However, the values fall to 0.73 and 0.69, respectively, while the ORAC activity was correlated with total polyphenol and total catechin content. Determining the TAC of individual tea catechins showed that ORAC of epicatechin was seven-fold higher than that of epigallocatechin gallate; on the contrary, epigallocatechin gallate showed significantly (P < 0.05) stronger DRSC activity than epicatechin. By evaluating the structure-activity relationship, this study further revealed that OH substitution at the 3' position in pyrogallol moieties contributes to the lower ORAC value of epigallocatechin and epigallocatechin gallate comparing with their non-3'-OH counterparts, such as epicatechin and epicatechin gallate, respectively. Also, numbers of OH substitutions were poorly correlated with the observed ORAC value unlike the DRSC. Overall, results of this study enabled us to hypothesize that substances having a lower TAC value in the ORAC assay compared with that in DPPH assays may pertain to a pro-oxidant effect by generating reactive oxygen species in an aqueous buffer, at a physiological pH. We also propose that substances exhibiting lower TAC value in the ORAC assay compared with that in the DPPH assay are powerful pro-oxidants compared with the substances showing a higher TAC value in the ORAC assay than that in the DPPH assay.

Bilateral angiosarcoma of the breast detected by magnetic resonance imaging during pregnancy.

Angiosarcoma of the breast is an aggressive malignancy of endothelial origin with a tendency for local regional recurrence. The involvement of angiosarcomas in the bilateral breasts has rarely been documented. Of note, due to its rarity and typically unclear clinical findings upon examination, the diagnosis of a contralateral lesion can be difficult, particularly in women during pregnancy. Here we present a rare case of bilateral angiosarcoma of the breast during pregnancy. A 32-year-old woman was referred to our unit with complaints of progressive swelling of the left breast, with tenderness. Magnetic resonance imaging showed a small, circumscribed high-intensity area in the contralateral breast, with pattern similar to that of the lesion found in the left breast. The contralateral lesion revealed only equivocal findings with the other diagnostic modalities. Diagnosed as angiosarcoma preoperatively, excision of the bilateral tumors was performed. Histological findings of the removed bilateral tumors were compatible with high-grade angiosarcoma of the breast.

Solitary cranial metastasis of thyroid carcinoma 13 years after primary surgery: report of a case.

Thyroid cancers rarely metastasize to the brain: the incidence of brain metastasis of differential thyroid carcinomas has been reported at only 0.69%-1.3%. We report a case of a solitary brain metastasis from thyroid follicular carcinoma found 13 years after primary surgery. A 73-year-old woman was admitted to our hospital for investigation of headaches, double vision, and facial nerve palsy, 13 years after a subtotal thyroidectomy for thyroid follicular carcinoma. Magnetic resonance imaging (MRI) showed a solitary mass in the midbrain associated with a focal osteolytic lesion of the temporal bone. Further radiological examinations revealed no other mass lesion. After making a provisional preoperative diagnosis of a primary brain tumor, we performed subtotal removal of the tumor. Histopathological examination confirmed metastasis of thyroid follicular carcinoma. Thus, the patient underwent completion thyroidectomy followed by internal radiotherapy. She has remained well in the 4 years since her operation, without any signs of further recurrence.

Clinicopathological relevance of UbcH10 in breast cancer.

Abrogated mitotic progression is a common hallmark of cancer. UbcH10, one of the components of the ubiquitin/proteasome pathway, plays a pivotal role in the regulation of mitotic progression. Abnormal UbcH10 activity is reported in certain types of human cancers; its overexpression is occasionally encountered in cancerous tissue compared with adjacent normal tissue. Current studies have suggested the critical role of UbcH10 in the spindle assembly checkpoint and the subsequent accurate separation of sister chromatids, which is orchestrated by a series of molecular interactions governed by the complex and diverse cell cycle machinery. To validate the potential role of UbcH10 in cell proliferation in cancer, we have analyzed the clinicopathological relevance of UbcH10 in progression of breast cancer using a combinatorial approach of human tumor arrays and biochemical analyses. Our results show that the percentage of tested samples which stained positive for UbcH10 in breast cancer tissues is significantly higher compared to the adjacent nonmalignant tissue. Furthermore, results from the clinicopathological analysis have revealed that elevated expression of UbcH10 is associated with higher histological grade tumors. In addition, depletion of UbcH10 by RNA interference in breast cancer cells resulted in decreased cellular proliferation, while overexpression of UbcH10 significantly enhanced cellular growth in breast cancer. Our results suggest a pathological correlation between UbcH10 and cell proliferation in breast cancer. Thus, aberrant UbcH10 activity may induce the dysfunction of proper cell cycle progression and result in the aggressive behavior of tumor cells in patients with breast cancer.

[Chemotherapy after second-line chemotherapy for patients with advanced or metastatic breast cancer].

PURPOSE: We evaluated chemotherapy after second-line chemotherapy for patients with advanced or metastatic breast cancer. PATIENTS & METHODS: Retrospectively, we evaluated 27 patients who received chemotherapy after second line chemotherapy. RESULTS: Eighteen patients received anthracycline(A)and/or taxane(T)containing chemotherapy regimens, 16 patients received chemotherapy regimens containing anticancer drugs except A and T, and 13 patients received oral fluoropyrimidines. Of all 48 chemotherapy regimens, 15(31.4%)regimens demonstrated response to chemotherapy. The clinical response rate was statistically equal among each chemotherapy regimen, and whenever patients received chemotherapy in any line. In univariate analysis, hormone receptor status, ECOG performance status(PS), and response to the first- or second-line chemotherapy were significantly associated with clinical response to chemotherapy after second-line chemotherapy. In multivariate analysis, only hormone receptor was significant. For overall survival according to response to first- or second-line chemotherapy, the difference was not significant. Meanwhile, overall survival according to response to chemotherapy after second-line chemotherapy was significant. CONCLUSIONS: Chemotherapy after second-line chemotherapy demonstrated a response similar to any regimen or any line. Patients having negative hormone receptor should receive chemotherapy after second-line chemotherapy.

Effect of combined therapy with the antiestrogen agent toremifene and local hyperthermia on breast cancer cells implanted in nude mice.

PURPOSE: We evaluated the effects of combined treatment with the antiestrogen agent toremifene (TOR) and local hyperthermia (LHT) on the MCF-7 breast cancer cell line. METHODS: BALB/c mice implanted with MCF-7 cells were divided into six treatment groups: a control group, a TOR30 group (given 30 mg/kg/day), a TOR120 group (given 120 mg/kg/day), an LHT group (43.5 degrees C), a TOR30 + LHT group, and a TOR120 + LHT group. The effects of the treatments on tumor cells, estrogen receptor (ER) expression, and cell cycle kinetics were measured after 21 days. We calculated the apoptotic index and vascular density inside the tumors and evaluated the efficacy of the transmigration of TOR into the tumors. RESULTS: The antitumor effects were significantly greater in both combined therapy groups than in any of the single therapy groups. Estrogen receptor expression was weaker in the combined therapy groups than in the single therapy groups, and there were more G0/G1-phase cells and fewer S-phase cells in both combined therapy groups than in the single therapy groups. The apoptotic index was increased and the tumor vascular density was decreased in the combined therapy groups. CONCLUSIONS: We attributed the effects of this combined therapy to the induction of apoptosis, the decrease in vascular density, and the increase and decrease in G0/G1-phase and S-phase cells, respectively, in the tumors.

Evaluation of breast lymphatic pathways with indocyanine green fluorescence imaging in patients with breast cancer.

BACKGROUND: In patients with early breast cancer, sentinel lymph node biopsy (SLNB) has been emerging as a new standard of care. The use of SLNB with a blue dye is convenient and safe, but it requires a high level of technical skill. Recently, an instrument that can provide fluorescence imaging of lymphatic flow has been introduced. In the present study, we analyzed breast lymphatic pathways and discussed its potential as a modality to complement the use of SLNB with a blue dye. METHODS: Thirty-seven consecutive patients with breast cancer were examined. To obtain fluorescence imaging, an invisible near-infrared fluorescence imaging system was used. After indocyanine green was subdermally injected in the subareolar site and at two sites around the tumor, the subcutaneous lymphatic drainage pathway (LDP) was observed. RESULTS: In 27 (72.9%) of the patients, the number of LDP from the periareolar area was one or two. In 21(63.6%) of 33 patients with subdermal injection around the tumor, no LDP was observed from the peritumoral area. Lymphatic connection between the peritumoral area and the periareolar area was observed very frequently (91.7%). In 26 (70.3%) of the patients, multiple routes joined together and only one route was ultimately directed to the axilla. Significant correlation was seen between body mass index (BMI) and the transit time to the axilla after injection (p = 0.0038). Additionally, a significant correlation was seen between the number of LPD from the periareolar area and the distance between detected SLNs and the fluorescence line-disappearing point (p = 0.034). CONCLUSIONS: This instrument can provide some important information, and can be an available and reliable navigator for SLNB with a blue dye.

Clinical significance of preoperative lymphoscintigraphy for sentinel lymph node biopsy in breast cancer.

BACKGROUND: Lymphoscintigraphy (LSG) has been widely used as an additional modality to sentinel lymph node biopsy (SLNB) using isotope. However, the significance of the number of LSG-visualized axillary nodes has not been fully understood. We analyzed this and discussed its potential as a modality to complement SLNB. METHODS: Ninety-one breasts and axillary lymph nodal status were evaluated retrospectively. All patients were examined by LSG using isotope and subsequently by SLNB. RESULTS: Nine patients (9.9%) had no LSG-visualized axillary node, while 61 patients (67.0%) had only 1 node, and 21 patients (23.1%) had multiple nodes. Overall, sentinel lymph node (SLN) identification rate was 96.7%, and the mean number of removed SLNs was 1.5 nodes per patient. In patients with nonvisualized nodes, 66.7% of SLNs were successfully identified, while 100% of SLNs were identified in those with LSG-visualized nodes. Compared with patients with less than one visualized node, significantly more SLNs were removed in patients with multiple visualized nodes. The number of LSG-visualized nodes correlated with that of metastatic nodes. CONCLUSIONS: Preoperative LSG is effective in evaluating SLN status, and the LSG status could be associated with the number of dissected SLN. Moreover, the results of LSG potentially reflect the histological nodal status.

Multidetector-row computed tomography for the preoperative evaluation of axillary nodal status in patients with breast cancer.

PURPOSE: We evaluated the effectiveness of multidetector-row computed tomography (MD-CT) for detecting axillary lymph nodal status (ALNS) in patients with breast cancer. METHODS: We reviewed 42 patients with breast cancer. A metastatic lymph node on MD-CT was defined as oval or round, with more than 5 mm on the short axis. We evaluated ALNS preoperatively by both palpation and MD-CT findings and performed sentinel lymph node biopsy (SLNB) and complete axillary lymph node dissection (ALND). RESULTS: For establishing the ALNS, MD-CT showed a sensitivity of 76.9%, a specificity of 96.6%, and an accuracy of 90.5%. On the basis of the MD-CT findings, misdiagnosis was made in 4 of the 42 patients, only one of which was false positive. On the other hand, one patient with a histologically negative sentinel lymph node (SLN) result had metastasis only in a non-SLN. Preoperative MD-CT showed a positive node in this patient. CONCLUSIONS: Multidetector-row computed tomography assists in identifying women who require ALND without SLNB, with sufficient positive predictive value. False-negative detection by SLNB could be avoided with careful interpretation of the axillary lymph nodes shown by MD-CT.