Tristetraprolin (TTP) and let-7 microRNA exhibit suppressive effects on cell growth through down-regulation of oncogenes. Both TTP and let-7 are often repressed in human cancers, thereby promoting oncogenesis by derepressing their target genes. However, the precise mechanism of this repression is unknown. We here demonstrate that p53 stimulated by the DNA-damaging agent doxorubicin (DOX) induced the expression of TTP in cancer cells. TTP in turn increased let-7 levels through down-regulation of Lin28a. Correspondingly, cancer cells with mutations or inhibition of p53 failed to induce the expression of both TTP and let-7 on treatment with DOX. Down-regulation of TTP by small interfering RNAs attenuated the inhibitory effect of DOX on let-7 expression and cell growth. Therefore, TTP provides an important link between p53 activation induced by DNA damage and let-7 biogenesis. These novel findings provide a mechanism for the widespread decrease in TTP and let-7 and chemoresistance observed in human cancers.

PurposeThis study aimed to evaluate the clinicopathological characteristics of pregnancy-associated breast cancer (PABC) in comparison with non-pregnancy associated breast cancer (non-PABC).MethodsA total of 344 eligible patients with PABC were identified in the Korean Breast Cancer Society Registry database. PABC was defined as ductal carcinoma in situ, invasive ductal carcinoma, or invasive lobular carcinoma diagnosed during pregnancy or within 1 year after the birth of a child. Patients with non-PABC were selected from the same database using a 1:2 matching method. The matching variables were operation, age, and initial stage.ResultsPatients with PABC had significantly lower survival rates than patient with non-PABC (10-year survival rate: PABC, 76.4%; non-PABC, 85.1%; p=0.011). PABC patients had higher histologic grade and were more frequently hormone receptor negative than non-PABC patients. Being overweight (body mass index [BMI], ≥23 kg/m2), early menarche (≤13 years), late age at first childbirth (≥30 years), and a family history of breast cancer were more common in the PABC group than in the non-PABC group. Multivariate analysis showed the following factors to be significantly associated with PABC (vs. non-PABC): early menarche (odds ratio [OR], 2.165; 95% confidence interval [CI], 1.566–2.994; p<0.001), late age at first childbirth (OR, 2.446; 95% CI, 1.722–3.473; p<0.001), and being overweight (OR, 1.389; 95% CI, 1.007–1.917; p=0.045).ConclusionEarly menarche, late age at first childbirth, and BMI ≥23 kg/m2 were more associated with PABC than non-PABC.

The aim of this study is to review the characteristics and the survival rate in male breast cancer (MBC) patients in Korea over a 31-year period. Additionally, we analyzed the overall survival (OS) rate of a group of MBC matched to females with breast cancer.We retrospectively analyzed the data from 400 Korean patients who were treated for MBC from 1978 to 2009. Patient demographics and clinical information were routinely documented throughout the study period. Survival and prognostic factors were evaluated. Each MBC patient was matched with 5 female breast cancer (FBC) patients based on 7 characteristics and we compared the OS rates between the 2 groups.For MBC cases, the median follow-up was 72 months and the 5-year OS rate was 85.9%. In univariate analyses, the prognostic factors influencing OS were age (more than 60 years, P <0.001), tumor size (>2 cm, P = 0.007), and having a negative progesterone receptor (PR) status (P = 0.042). Only the age (P = 0.028) and tumor size (P = 0.024) were significant prognostic factors for OS in multivariate analysis. After matching, we had 260 male patients matched to 1300 female patients for analysis. Compared with cases among females, the rate of mastectomy was higher among MBC cases and tumors, which were almost invasive ductal carcinomas (IDCs), were more likely to be located in the central part of the breast. For MBC cases, the percentage of adjuvant radiation therapy was low compared with female cases. The primary hormone therapy agent used was tamoxifen. The 5-year OS rates were similar in MBC compared with FBC (91.0% vs. 92.6%, P = 0.300).We found that only the age (more than 60 years) and tumor size were independent prognostic factors of survival in MBC. The prognosis for MBC is similar to that for FBC given similar stage and hormone-receptor status.