Patterns of Recurrence after Breast-Conserving Treatment for Early Stage Breast Cancer by Molecular Subtype

Purpose

To study clinical features and patterns of recurrence after breast-conserving treatment (BCT) for three molecular subtypes of early stage breast cancer.

Methods

The sample studied included 596 patients with T1-2N0-1 breast cancer who received BCT. Three groups were defined by receptor status. Luminal: estrogen receptor (ER) or progesterone receptor (PR) positive; triple negative (TN): ER, PR, and epidermal growth factor receptor-2 (HER2) receptor negative; and HER2 overexpressing: ER and PR negative but HER2 receptor positive.

Results

The number of patients in each group was 408 (68.5%), 105 (17.6%), and 83 (13.9%), respectively. The median follow-up period was 79 months. The TN and HER2 subtypes occurred in younger patients (p=0.0007) and had higher nuclear grade and poorer histologic grade (p<0.0001 and 0.0071, respectively). During the follow-up period, locoregional recurrence was detected as the first site of recurrence in 26 (6.4%), 11 (10.5%), and 9 (10.8%) patients in the luminal, TN, and HER2 subtypes, respectively (p=0.1924). Thirty-one (7.6%), 7 (6.7%), and 7 (8.4%) patients in each group had distant metastases as the first sign of recurrence (p=0.8996). Median time to locoregional and distant recurrence was shorter in the HER2 subtype (p=0.0889 and 0.0780, respectively), and the HER2 subtype was significantly associated with poor overall survival (p=0.0009).

Conclusion

After BCT in Korean women with early stage breast cancer, the patterns of recurrence were not different among the molecular subtypes, although the TN and HER2 subtypes were associated with younger age, higher nuclear grade, and poorer histologic grade.     

Efficacy of Fulvestrant in Heavily Pretreated Postmenopausal Women with Advanced Breast Cancer: A Preliminary Report

Purpose

Fulvestrant, a potent estrogen receptor (ER) antagonist with a novel mechanism of action, has shown efficacy in pretreated patients with advanced breast cancer. We assessed the efficacy and tolerability of fulvestrant in Korean postmenopausal women.

Methods

Of the 25 candidates identified at Asan Medical Center, Seoul, Korea, six were deemed ineligible due to inadequate baseline and follow-up imaging. The 19 patients included in this retrospective analysis received the approved dose of fulvestrant (250 mg intramuscular injection, once per month) as second- (n=8), third- (n=7), or fourth-line (n=4) endocrine therapy.

Results

At a median follow-up of 7.4 months (range, 1.2-34.8 months), the 19 patients received a median of four cycles (range, 1-34 cycles) of fulvestrant. Median time to progression was 5.5 months (95% confidence interval [CI], 0.4-10.7 months), and median overall survival was 17.9 months (95% CI, 2.7-33.1 months). Among 17 evaluable patients, one (5.3%) achieved a partial response, 10 (52.6%) showed stable disease, and six (31.6%) showed progressive disease. The clinical benefit rate was 26.3%. Four patients (21.1%) reported adverse events, but all were grade 1 or 2.

Conclusion

Fulvestrant was effective and well tolerated in patients with advanced breast cancer who had been previously treated with several lines of endocrine and chemotherapeutic agents.     

Giant mesenteric cystic lymphangioma originating from the lesser omentum in the abdominal cavity

A 48 year old woman was diagnosed with a huge cystic mass in her abdominal cavity. She complained of significant abdominal discomfort due to the mass. The abdominal computed tomography revealed a giant multi-lobulated mass, measuring 26×12 cm in size, adjacent to the lesser curvature of the stomach. In the operation field, the mass was found to originate from the lesser omentum, including the right and left gastric vessels and the vagus nerves, and to invade the lesser curvature of the stomach. For curative resection, distal subtotal gastrectomy with mass excision followed by gastroduodenostomy were performed. This mass was pathologically diagnosed to be a mesenteric cystic lymphangioma; in fact, the largest ever reported. The patient had no complications during the postoperative period and was discharged from the hospital on the seventh day after surgery.     

Extracts from Citrus unshiu promote immune-mediated inhibition of tumor growth in a murine renal cell carcinoma model

Aim of this study

Citrus unshiu (Satsuma mandarin, SM) is a citrus fruit the peel of which has been used as a traditional Chinese medicine to treat common cold, relieve exhaustion, and cancer. In this study, we examined how effectively the content and peel extracts of SM can suppress cancer growth. The mechanism underlying cancer-suppressing properties of SM was investigated in tumor-bearing mice with renal carcinoma cell, Renca.

Materials and methods

Effectiveness of SM in tumor suppression was evaluated by measuring size of tumor mass in tumor-bearing mice treated with various doses of SM content and peel extracts. Proliferation of tumor cells and splenocytes was determined by MTT assay and [³H]TdR uptake, respectively. Relevant immunological mechanisms were chased by assaying cytokines including TGF-β, IL-6, IFN-γ, and TNF-α by ELISA.

Results

The content and peel extracts of SM inhibited the growth of tumor cells in tumor-bearing mice. Especially, average tumor volume of two groups treated with 3 and 30 mg peel extracts per mouse weight (kg) were significantly decreased to 52.32% (p < 0.05) and 68.72% (p < 0.01), respectively. To identify tumor regression mechanism, anti-tumor cytokines measured in Con A-activated splenocytes from tumor-bearing mice. IFN-γ was increased in both of the peel extract-treated groups, while TNF-α, which had been decreased by tumor growth, was rescued to the normal level in SM content and peel extracts-treated groups. However, SM content and peel extracts did not inhibit proliferation and tumor-proliferative cytokines including TGF-β and IL-6 production of tumor cells.

Conclusion

These results indicate that SM content and peel extracts have anti-tumor properties in the tumor-bearing murine model. The mechanism underlying the anti-tumor effects of SM extracts is strongly suggested to be via boosting cytokines such as IFN-γ and TNF-α, enhancing immune-mediated anti-tumor properties.     

Methylene chloride fraction of the leaves of Thuja orientalis inhibits in vitro inflammatory biomarkers by blocking NF-κB and p38 MAPK signaling and protects mice from lethal endotoxemia

Aim of the study

Thuja orientalis (TO) has been a recognized herbal medicine across Northeast Asian countries for thousands of years and used for the treatment of various inflammatory diseases through as yet undefined mechanisms. In this study, we set out to determine whether the anti-inflammatory effects of this plant are mediated to suppress mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) activation in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells.

Materials and methods

RAW 264.7 cells were pretreated with the methylene chloride fraction of TO (MTO) and stimulated with LPS. Nitric oxide (NO) release was determined by the accumulation of nitrite in the culture supernatants and tumor necrosis factor-α (TNF-α) and IL-6 secretion were determined by immunoenzymatic assay. Inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression were evaluated via RT-PCR and Western blotting. NF-κB activation was also evaluated by reporter gene assay and electrophoretic mobility shift assay (EMSA). In addition, the protective effect of MTO was evaluated by use of the LPS-induced endotoxin shock model in mice.

Results

We found that MTO significantly suppressed LPS-stimulated NO and IL-6 production without affecting cell viability. MTO inhibited the expression of LPS-induced iNOS and COX-2 protein and their mRNA expression. Also, TNF-α and IL-6 secretion were decreased by MTO in both PMA and ionomycin-stimulated splenocytes. As a result, MTO inhibited pro-inflammatory cytokines such as TNF-α and IL-6, which is hypothesized as being due to the suppression of LPS-induced p38 MAPK and NF-κB activation. Moreover, MTO improved the survival rate during lethal endotoxemia by inhibiting the production of TNF-α in an animal model and our LC-MS analysis showed that a major component of MTO was pinusolide.

Conclusions

We demonstrate here the evidence that the methylene chloride fraction of Thuja orientalis (MTO) potentially inhibits the biomarkers related to inflammation in vitro and in vivo, and might be provided as a potential candidate for the treatment of inflammatory diseases.