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.

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.

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.

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.

One-step nucleic acid amplification assay for intraoperative prediction of advanced axillary lymph node metastases in breast cancer patients with sentinel lymph node metastasis.

The one-step nucleic acid amplification (OSNA) assay is used to semiquantitatively measure the cytokeratin (CK)19 mRNA copy numbers of each sentinel lymph node (SLN) in breast cancer patients. The aim of the present study was to evaluate whether the diagnosis of ≥4 LN metastases is possible using the OSNA assay intraoperatively. Between May, 2010 and December, 2014, a total of 134 patients who underwent axillary lymph node dissection (ALND) of positive SLNs were analyzed. The total tumor load (TTL) was defined as the total CK19 mRNA copies of all positive SLNs. The correlation between TTL and ≥4 LN metastases was evaluated. Of the 134 patients, 31 (23.1%) had ≥4 LN metastases. TTL ≥5.4×104 copies/µl evaluated by receiver operator characteristic curve analysis was examined along with other clinicopathological variables. In the multivariate analysis, only TTL ≥5.4×104 copies/µl was correlated with ≥4 LN metastases (odds ratio = 2.95, 95% confidence interval: 1.17-7.97, P=0.022). Therefore, TTL assessed by the OSNA assay has the potential to be a predictor of ≥4 LN metastases and it may be useful for the selection of patients with positive SLNs in whom ALND may be safely omitted.

Effects of the omega-6:omega-3 fatty acid ratio of fat emulsions on the fatty acid composition in cell membranes and the anti-inflammatory action.

BACKGROUND: This study investigated the effects of parenterally administered fish oil (FO) on the fatty acid composition in rats to determine the optimal omega-6:omega-3 polyunsaturated fatty acid (PUFA) ratio of fat emulsions to achieve an anti-inflammatory effect. METHODS: Male Sprague-Dawley rats were infused a parenteral nutrition (PN) solution containing fat emulsions with different omega-6:omega-3 PUFA ratios. The fatty acid content of phospholipids in the membranes of splenocytes was analyzed by gas chromatography (experiment 1). In addition, the amounts of leukotriene (LT) B(4) and LTB(5) released from peritoneal polymorphonuclear leukocytes (PMNs) were measured by high-performance liquid chromatography (experiment 2). RESULTS: In experiment 1, after infusion of the fat emulsion containing FO, the omega-3 PUFA content in cell membranes rose to 70% of the peak value on day 1 and nearly reached a plateau on day 3. The highest ratio of eicosapentaenoic acid (EPA) to arachidonic acid (AA) was achieved by administering a PN solution with the smallest omega-6:omega-3 PUFA ratio. In experiment 2, a larger amount of LTB(5) was released from Ca-ionophore-stimulated PMNs taken from rats given a larger quantity of FO. The ratio of LTB(5):LTB(4) released from PMNs correlated positively with the EPA:AA ratio in the membranous phospholipid and in serum. CONCLUSIONS: The omega-3 PUFAs were readily incorporated into the cell membrane within 3 days of infusion with the fat emulsion. The EPA:AA ratio in membranous phospholipid in PMNs was positively correlated with the LTB(5):LTB(4) production ratio and was a good indicator of anti-inflammatory effects.

Plasma tissue factor pathway inhibitor levels in patients with acute pancreatitis.

BACKGROUND: In acute pancreatitis (AP), disorders of the coagulation-fibrinolysis system are closely related to the severity of the AP and to organ dysfunctions. We previously reported that plasma tissue factor (TF) levels were elevated in patients with AP, particularly in cases of alcoholic AP with pancreatic necrosis. Tissue factor pathway inhibitor (TFPI) is a key regulator of the extrinsic coagulation pathway, but plasma TFPI levels in AP have not yet been determined. METHODS: Plasma TFPI concentrations were measured by enzyme-linked immunosorbent assay in 44 patients with AP on admission. The relationships between AP severity, pancreatic necrosis, organ dysfunction, infection, and prognosis were analyzed. RESULTS: Plasma TFPI levels were increased in AP patients compared with healthy volunteers. Plasma TFPI levels in severe AP were greater than those in mild AP. Plasma TFPI levels significantly correlated with Ranson score, APACHE II score, and Japanese severity score. Plasma TFPI levels in patients with pancreatic necrosis were greater than those in patients without pancreatic necrosis. Plasma TFPI levels in patients with organ dysfunction were greater than those in patients without organ dysfunction. In patients with pancreatic necrosis, the TF/TFPI ratios in non-survivors were lower than those in survivors. Moreover, the mortality rates in patients with TF/TFPI ratios > or = 2.0 were lower than those in patients with TF/TFPI ratios < 2.0. CONCLUSIONS: Plasma TFPI levels were significantly increased in patients with AP, and the elevation was markedly related to the severity, pancreatic necrosis and organ dysfunctions. The imbalance of TF and TFPI may influence the disease state and thereby the prognosis in AP.