Breast cancer local recurrence after mastectomy with immediate latissimus dorsi myocutaneous flap reconstruction: A case report.

Even though most local recurrences after autologous breast reconstruction occur in superficial tissue, they also occur in deep tissue in the reconstructed breast. A 49-year-old woman presented with a bloody discharge from the right nipple. Ultrasonography revealed a hypoechoic area in her right breast, which was diagnosed as ductal carcinoma in situ on histopathology. We performed nipple-sparing mastectomy and immediate reconstruction of the breast with a latissimus dorsi myocutaneous flap. At 6 years postoperatively, the patient presented with a palpable mass. Ultrasonography revealed a solid mass lesion subcutaneously in the right breast. Computed tomography revealed multiple enhanced solid mass lesions in the subcutaneous and deep tissues of the reconstructed breast. The mass in the deep tissue of the reconstructed breast was diagnosed as an invasive micropapillary carcinoma by biopsy. For local recurrence, we performed wide excision of the reconstructed breast. The masses in the subcutaneous and deep tissues of the reconstructed breast were diagnosed as invasive micropapillary carcinoma. Superficial recurrence was first detected by physical examination, and deep recurrence was later detected with further imaging. We present a case of local recurrences that occurred in the deep tissue, in addition to superficial tissue of the reconstructed breast.

Postoperative Adjuvant Anastrozole for 10 or 5 Years in Patients With Hormone Receptor-Positive Breast Cancer: AERAS, a Randomized Multicenter Open-Label Phase III Trial.

PURPOSE: Treatment with an aromatase inhibitor for 5 years is the standard treatment for postmenopausal hormone receptor-positive breast cancer. We investigated the effects of extending this treatment to 10 years on disease-free survival (DFS). PATIENTS AND METHODS: This prospective, randomized, multicenter open-label phase III study assessed the effect of extending anastrozole treatment for an additional 5 years in postmenopausal patients who were disease-free after treatment with either 5 years of anastrozole alone or 2-3 years of tamoxifen followed by 2-3 years of anastrozole. Patients were allocated randomly (1:1) to continue anastrozole for an additional 5 years or stop anastrozole. The primary end point was DFS, including breast cancer recurrence, second primary cancers, and death from any cause. This study is registered with University Hospital Medical Information Network, Japan (UMIN) clinical trials registry (UMIN000000818). RESULTS: We enrolled 1,697 patients from 117 facilities between November 2007 and November 2012. Follow-up information was available for 1,593 patients (n = 787 in the continue group, n = 806 in the stop group), who were defined as the full analysis set, including 144 patients previously treated with tamoxifen and 259 patients who underwent breast-conserving surgery without irradiation. The 5-year DFS rates were 91% (95% CI, 89 to 93) in the continue group and 86% (95% CI, 83 to 88) in the stop group (hazard ratio, 0.61; 95% CI, 0.46 to 0.82; P < .0010). Notably, extended anastrozole treatment reduced the incidence of local recurrence (continue group, n = 10; stop group, n = 27) and second primary cancers (continue group, n = 27; stop group, n = 52). There was no significant difference in overall or distant DFS. Menopausal or bone-related all-grade adverse events were more frequent among patients in the continue group than those in the stop group, but the incidence of grade ≥3 adverse events was <1% in both groups. CONCLUSION: Continuing adjuvant anastrozole for an additional 5 years after 5 years of initial treatment with anastrozole or tamoxifen followed by anastrozole was well tolerated and improved DFS. Although no difference in overall survival was observed as in other trials, extended anastrozole therapy could be one treatment choice in postmenopausal patients with hormone receptor-positive breast cancer.

Organ-Specific Positron Emission Tomography Scanners for Breast Imaging: Comparison between the Performances of Prior and Novel Models.

The performances of photomultiplier tube (PMT)-based dedicated breast positron emission tomography (PET) and silicon photomultiplier tube (SiPM)-based time-of-flight (TOF) PET, which is applicable not only to breast imaging but also to head imaging, were compared using a phantom study. A cylindrical phantom containing four spheres (3-10 mm in diameter) filled with 18F-FDG at two signal-to-background ratios (SBRs), 4:1 and 8:1, was scanned. The phantom images, which were reconstructed using three-dimensional list-mode dynamic row-action maximum likelihood algorithm with various ß-values and post-smoothing filters, were visually and quantitatively compared. Visual evaluation showed that the 3 mm sphere was more clearly visualized with higher ß and smaller post-filters, while the background was noisier; SiPM-based TOF-PET was superior to PMT-based dbPET in sharpness, smoothness, and detectability, although the background was noisier at the SBR of 8:1. Quantitative evaluation revealed that the detection index (DI) and recovery coefficient (CRC) of SiPM-based TOF-PET images were higher than those of PMT-based PET images, despite a higher background coefficient of variation (CVBG). The two organ-specific PET systems showed that a 3 mm lesion in the breast could be visualized at the center of the detector, and there was less noise in the SiPM-based TOF-PET image.

Evidence-Based Practice Guideline for the Management of Lymphedema Proposed by the Japanese Lymphedema Society.

Background: Secondary lymphedema mostly occurs as an aftereffect of cancer treatment, and it is estimated that 100,000-150,000 patients are affected in Japan. An estimated 3500 patients, develop lymphedema of the lower and upper extremities each year secondary to uterine and breast cancer treatment. Medical reimbursement was first instituted in April 2008 by the Ministry of Health, Labour and Welfare in Japan. Since 2008, we have developed guidelines regarding treatment options for patients with lymphedema based on scientific evidence. This is the third edition of the guidelines established by the Japanese Lymphedema Society (JLES), published in 2018. The JLES Practice Guideline-Making Committee (PGMC) developed 21 clinical questions (CQs). Methods and Results: A review of these 15 CQs was performed in accordance with the methodology for establishing clinical guidelines. The 15 recommendations for each of these CQs were developed and discussed until consensus by the PGMC was reached. Moreover, outside members who had no involvement in these guidelines evaluated the contents using the Appraisal of Guidelines for Research and Evaluation (AGREE) II reporting checklist. Conclusion: These guidelines have been produced for the adequate management of lymphedema by doctors and other medical staff on the lymphedema management team of medical institutes, including nurses, physical technicians, and occupational therapists.

Relationship between endocrine resistance and the periods of adjuvant endocrine treatment for hormone receptor-positive, HER2-negative breast cancer.

BACKGROUND: Current guidelines define primary and secondary endocrine resistance according to the periods of adjuvant endocrine therapy (adj-ET); however, the relationship between adj-ET period and endocrine resistance remains unclear. OBJECTIVE: We examined progression-free survival (PFS) after primary ET for recurrent hormone receptor-positive/HER2-negative breast cancer, and evaluated the relationship between endocrine resistance and the periods of adj-ET. METHODS: We assessed PFS among 183 patients who received ET as primary treatment for the first recurrence, according to the period of adj-ET (adj-ET < 1 year, 1-2 years, ≥2 years, and completion). RESULTS: Patients who relapsed during the first year of adj-ET had the significantly shortest PFS. PFS did not significantly differ between patients who relapsed at 1-2 years of adj-ET and patients who relapsed while on adj-ET but after the first 2 years. CONCLUSIONS: Relapse at 1-2 years after adj-ET initiation might be better classified as secondary endocrine resistance rather than primary endocrine resistance.

Capecitabine in Combination with Endocrine Therapy as Maintenance Therapy after Bevacizumab Plus Paclitaxel Induction Therapy for Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: KBCSG-TR1214.

Optimal treatment strategies for hormone receptor (HR)-positive, HER2-negative advanced and/or metastatic breast cancer (AMBC) remain uncertain. We investigated the clinical usefulness of adding capecitabine to maintenance endocrine therapy after induction chemotherapy and the efficacy of reinduction chemotherapy. Patients who had received bevacizumab-paclitaxel induction therapy and did not have progressive disease (PD) were randomized to maintenance therapy with endocrine therapy alone (group E) or endocrine plus capecitabine (1657 mg/m2/day on days 1-21, q4w) (group EC). In case of PD after maintenance therapy, patients received bevacizumab-paclitaxel reinduction therapy. Ninety patients were randomized. The median progression-free survival (PFS) under maintenance therapy (primary endpoint) was significantly longer in group EC (11.1 {95% CI, 8.0-11.8} months) than in group E (4.3 {3.6-6.0} months) (hazard ratio, 0.53; p < 0.01). At 24 months from the induction therapy start, the overall survival (OS) was significantly longer in group EC than in group E (hazard ratio, 0.41; p = 0.046). No difference was found in the time to failure of strategy (13.9 and 16.6 months in groups E and EC, respectively). Increased capecitabine-associated toxicities in group EC were tolerable. Addition of capecitabine to maintenance endocrine therapy may be a beneficial option after induction chemotherapy for HR-positive, HER2-negative AMBC patients.

New insights into patterns of first metastatic sites influencing survival of patients with hormone receptor-positive, HER2-negative breast cancer: a multicenter study of 271 patients.

BACKGROUND: The initial therapeutic strategy for hormone receptor-positive (HR+), HER2-negative (HER2-) breast cancer is based on the first metastatic site; however, little evidence is available regarding the influence of metastatic distribution patterns of first metastatic sites on prognosis. In this study, we aimed to identify the metastatic distribution patterns of first metastatic sites that significantly correlate with survival after recurrence. METHODS: We performed a retrospective review of records from 271 patients with recurrent metastatic HR+/HER2- breast cancer diagnosed between January 2000 and December 2015. We assessed survival after recurrence according to the metastatic distribution patterns of the first metastatic sites and identified significant prognostic factors among patients with single and multiple metastases. RESULTS: Prognosis was significantly better in patients with a single metastasis than in those with multiple metastases (median overall survival after recurrence: 5.86 years vs. 2.50 years, respectively, p < 0.001). No metastatic organ site with single metastasis was significantly associated with prognostic outcome, although single metastasis with diffuse lesions was an independent risk factor for worse prognosis (HR: 3.641; 95% CI: 1.856-7.141) and more easily progressing to multiple metastases (p = 0.002). Multiple metastases, including liver metastasis (HR: 3.145; 95% CI: 1.802-5.495) or brain metastasis (HR: 3.289; 95% CI: 1.355-7.937), were regarded as significant independent poor prognostic factors; however, multiple metastases not involving liver or brain metastasis were not significantly related to prognosis after recurrence. CONCLUSIONS: Single metastases with diffuse lesions could more easily disseminate systemically and progress to multiple metastases, leading to a poor prognosis similar to multiple metastases. Our findings indicate that the reconsideration of the determinant factors of therapeutic strategies for first recurrence in HR+/HER2- breast cancer may be needed.

The efficacy and safety of pertuzumab plus trastuzumab and docetaxel as a first-line therapy in Japanese patients with inoperable or recurrent HER2-positive breast cancer: the COMACHI study.

PURPOSE: In the CLEOPATRA study of patients with human epidermal growth factor receptor 2 (HER2)-positive recurrent or metastatic breast cancer, the Japanese patient subgroup did not demonstrate the improved progression-free survival (PFS) of pertuzumab plus trastuzumab and docetaxel vs. placebo that was seen in the overall population. Therefore, COMACHI was conducted to confirm the efficacy and safety of this treatment regimen in this patient subgroup. METHODS: This was a phase IV study of pertuzumab plus trastuzumab and docetaxel in Japanese patients with histologically/cytologically confirmed inoperable or recurrent HER2-positive breast cancer. All patients received pertuzumab, trastuzumab, and docetaxel intravenously every 3 weeks until disease progression/unacceptable toxicity. The primary endpoint was investigator-assessed PFS. Secondary endpoints were overall survival (OS), investigator-assessed objective response rate, and duration of response (DoR). Safety was also assessed. RESULTS: At final analysis, median investigator-assessed PFS was 22.8 months (95% CI 16.9-37.5). From first dose, OS rate at 1 year was 97.7%; and at 2 and 3 years were 88.5% and 79.1%, respectively. Of the 118 patients with measurable disease at baseline, response rate was 83.9% (95% CI 77.3-90.5) and median investigator-assessed DoR was 26.3 months (95% CI 17.1-not evaluable). Treatment was well tolerated, with no new safety signals detected. CONCLUSIONS: Our results suggest similar efficacy and safety for pertuzumab plus trastuzumab and docetaxel in Japanese patients compared with the overall population of CLEOPATRA, providing further support for this combination therapy as standard of care for Japanese patients with inoperable or recurrent HER2-positive breast cancer.

Surgical therapy for pulmonary metastasis of breast cancer.

Metastatic breast cancer (MBC) is a disease with heterogeneous manifestations that arise from a variety of modes of spread from the primary disease. The lung is a common site of metastasis from breast cancer. A solitary lung nodule appearing on radiological examination following breast cancer treatment is likely to be diagnosed as pulmonary metastasis from breast cancer. However, the reported final pathological diagnoses include primary lung cancer and MBC in approximately 48-67% and 23-43% of cases, respectively. Moreover, some pulmonary metastases of breast cancer have radiological and histological characteristics similar to those of primary lung cancer. Thus, the differential diagnosis of a solitary lung nodule after treatment of breast cancer is challenging. Oligometastatic disease (OMD) is characterized by solitary or limited numbers of detectable metastatic lesions. OMD in the lung from colorectal cancer can be considered for locoregional treatments either alone or in combination with systemic therapy. In MBC patients, the indication for locoregional treatments for pulmonary metastasis is controversial, whereas surgical intervention can be performed to obtain tissue for histological and molecular confirmation and occasionally for curative intent in selected MBC patients. While several retrospective studies have examined the clinical impact of pulmonary metastasectomy (PM) in MBC patients, no prospective randomized trials have been conducted. Our systematic review of PM in MBC patients found that PM might offer a survival advantage in selected MBC patients with a long disease-free interval (DFI), small number of pulmonary metastases, complete resection, and/or hormone receptor positivity. Metastases are usually detected by radiological examinations such as computed tomography (CT) and positron emission tomography-CT. The detectability of these radiological examinations mainly depends on tumor size (size-dependent manner). By contrast, the amount of circulating tumor DNA (ctDNA) released by apoptotic or necrotic tumor cells depends on the tumor burden in the whole body, regardless of radiological detectability (dose-dependent manner). Since ctDNA assays reportedly reveal residual disease several weeks earlier than radiologic imaging does, monitoring for radiological tumor size and ctDNA concentration during the clinical course may help to inform the indication for local treatment in patients with MBC and may improve their clinical outcomes. This article reviewed the current status of PM in MBC patients with pulmonary metastasis and discussed future perspectives.

Multicentre, phase II study of eribulin in combination with S-1 in patients with advanced breast cancer.

BACKGROUND: We previously reported the synergistic effect of S-1 and eribulin in preclinical models. In addition, our phase I study revealed the recommended dose for the phase II study of the combination therapy in advanced breast cancer (ABC) patients pre-treated with anthracycline and taxane. Our current study reports on the efficacy and safety of the combined use of eribulin and S-1 in patients with ABC and poor prognosis. METHODS: Patients with breast cancer who received prior anthracycline- and/or taxane-based therapy were assigned to receive a combination therapy of eribulin (1.4 mg/m2 on days 1 and 8, every 21 days) and S-1 (65 mg/m2, on days 1 to 14, every 21 days) for advanced/metastatic disease. All patients had at least one clinicopathological factor such as being oestrogen receptor negative, Human Epidermal Growth Factor Receptor 2 (HER2) receptor negative, presence of visceral involvement, presence of three or more metastatic sites, or having a disease-free interval shorter than 2 years. The primary endpoint was the independent-reviewer assessed objective response rate (ORR). Secondary endpoints were clinical benefit rate, disease control rate, progression-free survival (PFS), and overall survival (OS). RESULTS: This study enrolled 33 patients. Confirmed ORR was 33.3% (95% CI: 17.3 to 52.8). Median PFS was 7.5 months (95% CI: 4.0 to 14.3). Median OS time was not reached during the current experimental periods. The most common grade 3/4 adverse event was neutropenia (68.8%). CONCLUSIONS: The combination of eribulin and S-1 is safe and effective for treatment in patients with ABC and poor prognosis. TRIAL REGISTRATION: Current Controlled Trials UMIN000015049 , date of registration: September 5th 2014.

Carcinosarcoma of the breast: A case of breast conservation surgery and breast reconstruction.

Breast carcinosarcoma is an extremely rare, clinically aggressive tumor, and no standard treatment has been established. We report about a 34-year-old woman presenting with a 2.5-cm-sized carcinosarcoma in her right breast. She presented to our hospital for examination of this mass. Ultrasonography showed a hypoechoic mass with partially irregular margins. Fine-needle aspiration cytology indicated malignancy. No enlarged lymph nodes or distant metastases were detected. We diagnosed right breast cancer and performed partial mastectomy, sentinel lymph node biopsy, and latissimus dorsi muscle flap transfer. Histological findings revealed that the tumor consisted of a mixture of an epithelial component and a mesenchymal component. The final diagnosis was carcinosarcoma. After undergoing adjuvant chemotherapy and radiotherapy, the patient has had no recurrence, and her cosmesis is maintained. Clinical data of carcinosarcoma are insufficient. Breast conservation and reconstruction for carcinosarcoma may be suitable as local treatments; however, the most appropriate treatment method has not been established.

PI3K/Akt/mTOR signalling pathway activation in patients with ER-positive, metachronous, contralateral breast cancer treated with hormone therapy.

Oestrogen receptor (ER)-positive, metachronous, contralateral breast cancer (MCBC) sometimes develops during or soon after completion of hormone therapy (HT), but it is uncertain whether it is HT-resistant. We examined the association between ER-positive second cancer and activation of the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) and mitogen-activated protein kinase (MAPK) pathways, which are associated with HT resistance. We examined the treatment-free interval (time after completion of HT for initial cancer) in 41 patients with ER-positive MCBC with a history of adjuvant HT for initial cancer (HT group), and initial-to-second period duration (time after operation of initial cancer to onset of second cancer) in 17 patients with ER-positive MCBC in whom adjuvant HT was not applied to the initial tumour (control group or no HT group). Phosphorylated S6 (pS6) and phosphorylated MAPK (pMAPK) were used as indicators of PI3K/Akt/mTOR and MAPK pathway activity, respectively. Tumours were classified as showing negative, positive or strongly positive staining, and the correlation between staining and treatment-free interval or initial-to-second period duration was evaluated using the Spearman's rank correlation coefficient (ρ). Treatment-free interval and pS6 staining showed a negative correlation (ρ=-0.5355; P=0.0003) in the HT group. There was no correlation between initial-to-second period duration and pS6 staining in the no HT group (ρ=-0.0814; P=0.756). There was no correlation between pMAPK signalling and the treatment-free interval in the HT group (ρ=-0.1560; P=0.330) or the initial-to-second period duration in the no HT group (ρ=-0.0116; P=0.965). Development of a second ER-positive cancer during or soon after completion of HT for the initial cancer may be associated with activation of the PI3K/Akt/mTOR pathway. Care should be taken during follow-up and when selecting adjuvant therapy for second cancer.

Response to First-line Recurrence Treatment Influences Survival in Hormone Receptor-positive, HER2-negative Breast Cancer: A Multicenter Study.

BACKGROUND/AIM: Little evidence is currently available on significant determinants of post-recurrence survival for patients with hormone receptor-positive (HR+), HER2-negative (HER2-) breast cancer. The objective of this study was to evaluate factors influencing post-recurrence survival in HR+/HER2-breast cancer. PATIENTS AND METHODS: A cohort of 236 patients with recurrent HR+/HER2- breast cancer was retrospectively analyzed to identify significant factors correlating with prognosis after recurrence. RESULTS: Multivariate analysis revealed independent prognostic factors of poor survival as follows: short intervals between recurrence and the end of adjuvant endocrine therapy (ET; p=0.046); short disease-free intervals (p=0.019); liver metastasis (p=0.007) or multiple metastases (p<0.001) at recurrence; and a poor response to first-line treatment (p<0.001). A poor first-line treatment response was significantly associated with a shorter response to a subsequent treatment line (p=0.007). Logistic regression analysis indicated that liver metastasis significantly increased the risk of a poor first-line-ET response (p=0.009). CONCLUSION: The first-line treatment response was the key to post-recurrence survival in patients with HR+/HER2- breast cancer. Particularly poor responses led to subsequent unfavorable prognostic outcomes.

HER2 genomic amplification in circulating tumor DNA and estrogen receptor positivity predict primary resistance to trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer.

BACKGROUND: Trastuzumab emtansine (T-DM1) is approved for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer (ABC), and has high efficacy. However, some patients exhibit primary resistance to T-DM1, and thus methods that can predict resistance in clinical practice are needed. Genomic analysis of circulating tumor DNA (ctDNA) in plasma is a non-invasive and reproducible method. This study aimed to predict primary resistance to T-DM1 by combining genomic analysis of ctDNA and other clinicopathological features of patients with HER2-positive ABC. METHODS: The study population comprised 34 patients with HER2-positive ABC who had been treated with T-DM1. Correlations between clinicopathological characteristics of patients and primary resistance to T-DM1 were examined, and HER2 gene copy number and PIK3CA gene mutations were analyzed using plasma ctDNA samples obtained from 16 patients before T-DM1 administration. RESULTS: Among the 34 patients, nine (26.5%) had progressive disease at the first efficacy analysis; these patients were considered to have primary resistance to T-DM1. No significant difference was found in the rate of primary resistance to T-DM1 between groups. Among 16 patients whose ctDNA was analyzed, four showed primary resistance to T-DM1. These four patients showed negative HER2 gene amplification in ctDNA and were ER-positive and/or PR-positive by immunohistochemistry. CONCLUSIONS: HER2 gene amplification in ctDNA and ER and PR status may predict primary resistance to T-DM1. A liquid biopsy before the initiation of T-DM1 treatment could be a non-invasive way to predict whether a patient would exhibit primary resistance to T-DM1.

The Difference in Prognostic Outcomes Between De Novo Stage IV and Recurrent Metastatic Patients with Hormone Receptor-positive, HER2-negative Breast Cancer.

BACKGROUND/AIM: Patients with de novo stage IV and recurrent metastatic breast cancer are often treated with the same strategies, although the difference in prognostic outcomes remains unclear. The objective of this retrospective chart review study was to compare the prognostic outcomes between two types of patients with hormone receptor-positive (HR+), HER2-negative (HER2-) breast cancer. PATIENTS AND METHODS: We estimated overall survival of the two groups and evaluated the progressive course of the disease using disease-free interval (DFI) and interval from the end of adjuvant treatment to the first recurrence (AFI). RESULTS: We studied 172 patients with HR+/HER2- breast cancer, of which 65 were de novo and 107 were recurrent. Median OS between de novo and recurrent BC was 4.85 and 3.45 years, respectively (p=0.046). Recurrent patients with a DFI<2 years were found to have a significantly poorer prognosis than recurrent patients with a DFI≥2 years (p=0.016) and de novo patients (p=0.002). Similarly, recurrent patients with an AFI<1 year had a significantly poorer prognosis compared to de novo patients (p=0.026). CONCLUSION: De novo patients had better prognoses than recurrent patients with DFI<2 years or AFI<1 year, likely due to their therapy-naïve status or lower resistance to systemic treatment.

Case report: schwannoma arising from the unilateral adrenal area with bilateral hyperaldosteronism.

BACKGROUND: We report a rare case of a juxta-adrenal schwannoma that could not be discriminated from an adrenal tumor before surgical resection and was complicated by bilateral hyperaldosteronism. To the best of our knowledge, this is first case in which both a juxta-adrenal schwannoma and hyperaldosteronism co-existed. CASE PRESENTATION: A 69-year-old male treated for hypertension was found to have a left supra-renal mass (5.8 × 5.2 cm) by abdominal computed tomography. His laboratory data showed that his plasma aldosterone concentration (PAC) was within the normal range, but his plasma renin activity (PRA) was reduced, resulting in an increased aldosterone/renin ratio (ARR). Load tests of captopril or furosemide in the standing position demonstrated autonomous aldosterone secretion and renin suppression. Adrenal venous sampling (AVS) with ACTH stimulation indicated bilateral hypersecretion of aldosterone. A left supra-renal tumor was resected because of the possibility of malignancy and was found to be a benign schwannoma arising from the juxta-adrenal region together with an adrenal gland. The dissected left adrenal gland was morphologically hyperplastic in the zona glomerulosa, but was immunohistochemically negative for CYP11B2 (aldosterone synthase). Multiple CYP11B2-positive adrenocortical micronodules were detected in the adrenal gland, indicating micronodular hyperplasia. Although bilateral aldosteronism was indicated by AVS before the operation, the PRA, PAC and ARR values were within their respective reference ranges after resection of the unilateral tumor, suggesting that the slight increase in hormone secretion from the remaining right-sided lesion could not be detected after resection. CONCLUSION: A clinical and morphologic diagnosis of juxta-adrenal schwannoma is difficult, particularly in a case of hyperaldosteronism, as shown in this case. These data suggest the complexity and difficulty diagnosing adrenal incidentaloma.

Increased risk of SSEs in bone-only metastatic breast cancer patients treated with zoledronic acid.

BACKGROUND: Bone represents one of the most common sites to which breast cancer cells metastasize. Patients experience skeletal related adverse events (pathological fractures, spinal cord compressions, and irradiation for deteriorated pain on bone) even during treatment with zoledronic acid (ZA). Therefore, we conducted a retrospective cohort study to investigate the predictive factors for symptomatic skeletal events (SSEs) in bone-metastasized breast cancer (b-MBC) patients. METHODS: We retrospectively collected data on b-MBC patients treated with ZA. Patient characteristics, including age, subtype, the presence of non-bone lesions, the presence of multiple bone metastases at the commencement of ZA therapy, duration of ZA therapy, the time interval between breast cancer diagnosis and the initiation of ZA therapy, and type of systemic therapy, presence of previous SSE were analyzed using multivariable logistic regression analysis. RESULTS: The medical records of 183 patients were reviewed and 176 eligible patients were analyzed. The median age was 59 (range, 30-87) years. Eighty-seven patients were aged ≥60 years and 89 patients were aged < 60 years. The proportions of patients with estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2-positive disease were 81.8%, 63.1%, and 17.6%, respectively. Fifty-three patients had bone-only MBC at the commencement of ZA therapy. SSEs were observed in 42 patients. In the multivariable logistic regression analysis, bone-only MBC but not a breast cancer subtype was an independent risk factor for an SSE during ZA therapy (odds ratio: 3.878, 95% confidence interval: 1.647-9.481; p = 0.002). CONCLUSIONS: Bone-only MBC patients are more likely to experience an SSE even after treatment with ZA.

Lentinula edodes mycelia extract plus adjuvant chemotherapy for breast cancer patients: Results of a randomized study on host quality of life and immune function improvement.

Anthracycline-based chemotherapies for breast cancer are known to adversely affect patients' quality of life (QOL) and immune function. For that reason, adjuvants that improve those impairments are required. A randomized double-blind study was conducted to evaluate the effectiveness of Lentinula edodes mycelia extract (LEM), which is an oral biological response modifier (BRM) medicine for cancer patients as such an adjuvant. A total of 47 breast cancer patients who were scheduled to receive postoperative adjuvant anthracycline-based chemotherapy, i.e., 5-fluorouracil (5-FU) + cyclophosphamide + epirubicin (FEC regimen), 5-FU + cyclophosphamide + doxorubicin/pirarubicin (FAC regimen), cyclophosphamide + doxorubicin/pirarubicin (AC regimen) and cyclophosphamide + epirubicin (EC regimen), were entered in the study. The patients were randomly divided into either an LEM or a placebo tablet group; the tablets were orally ingested daily over 2 courses of each therapy. In the placebo group, the total scores for QOL were lower on day 8 of the second course of chemotherapy compared with the baseline scores, whereas in the LEM group the scores had not decreased. In the placebo group, the QOL functional well-being score was lower on day 8 after both the first and second courses of chemotherapy compared with the baseline score, but it had not decreased in the LEM group. Evaluation of immunological parameters indicated that an increase in the proportion of regulatory T cells to peripheral blood CD4+ cells tended to be inhibited in the LEM group compared with the placebo group. Oral LEM that was coadministered with anthracycline-based chemotherapies was useful for maintaining patients' QOL and immune function. Thus, LEM appears to be a useful oral adjuvant for patients receiving anthracycline-based chemotherapy.