Song YJ, et al. J Breast Cancer. 2011 Sep;14(3):198-203. http://dx.doi.org/10.4048/jbc.2011.14.3.198

Known risk variants explain only a small proportion of breast cancer heritability, particularly in Asian women. To search for additional genetic susceptibility loci for breast cancer, here we perform a meta-analysis of data from genome-wide association studies (GWAS) conducted in Asians (24,206 cases and 24,775 controls) and European descendants (122,977 cases and 105,974 controls). We identified 31 potential novel loci with the lead variant showing an association with breast cancer risk at P < 5 × 10⁻⁸. The associations for 10 of these loci were replicated in an independent sample of 16,787 cases and 16,680 controls of Asian women (P < 0.05). In addition, we replicated the associations for 78 of the 166 known risk variants at P < 0.05 in Asians. These findings improve our understanding of breast cancer genetics and etiology and extend previous findings from studies of European descendants to Asian women.

In this study, we prepared an injectable drug delivery depot system based on a visible light-cured glycol chitosan (GC) hydrogel containing paclitaxel (PTX)-complexed beta-cyclodextrin (β-CD) (GC/CD/PTX) for ovarian cancer (OC) therapy using a tumor-bearing mouse model. The hydrogel depot system had a 23.8 Pa of storage modulus at 100 rad/s after visible light irradiation for 10 s. In addition, GC was swollen as a function of time. However, GC had no degradation with the time change. Eventually, the swollen GC matrix affected the releases of PTX and CD/PTX. GC/PTX and GC/CD/PTX exhibited a controlled release of PTX for 7 days. In addition, GC/CD/PTX had a rapid PTX release for 7 days due to improved water solubility of PTX through CD/PTX complex. In vitro cell viability tests showed that GC/CD/PTX had a lower cell viability percentage than the free PTX solution and GC/PTX. Additionally, GC/CD/PTX resulted in a superior antitumor effect against OC. Consequently, we suggest that the GC/CD system might have clinical potential for OC therapy by improving the water solubility of PTX, as PTX is included into the cavity of β-CD.

Lymphovascular invasion (LVI) has been a predictor of worse survival outcomes in breast cancer. However, the role of LVI compared than pathologic complete response (pCR) following neoadjuvant chemotherapy (NAC) remains unclear. The aim of this study was to examine the association between LVI and survival outcomes and clinicopathological features in patients with breast cancer treated with NAC. We retrospectively analyzed 187 patients with breast cancer treated with NAC and surgery between 2005 and 2013 in our institution. Kaplan–Meier analyses were used to assess recurrence-free survival (RFS) and overall survival (OS). Median follow-up was 57.9 months. Mastectomy (vs breast conserving surgery [BCS]; hazard ratio [HR], 1.791; 95% confidence interval [CI], 1.022–3.139; P = .042), ypN1-3 stage (vs ypN0 stage; HR, 2.561; 95% CI, 1.247–5.261; P = .010), and LVI (vs no LVI; HR, 2.041; 95% CI, 1.170–3.562; P = .012) were associated with worse RFS. Mastectomy (vs BCS; HR, 2.768; 95% CI, 1.173–6.535; P = .020), LVI (vs no LVI; HR, 3.474; 95% CI, 1.646–7.332, P = .001), and human epidermal growth factor receptor 2 overexpression type (vs luminal A type; HR, 11.360; 95% CI, 1.501–85.972; P = .019) were associated with worse OS. Patients with LVI and hormone receptor-negative cancer had the worst RFS (P < .001) and OS (P < .001). LVI more than pCR in surgical breast cancer specimens obtained after NAC was a significant independent prognostic factor. Patients with hormonal receptor-negative cancer and LVI had unfavorable survival outcomes. We suggest that patients with hormone receptor-negative cancer and LVI should receive short-term follow-up and appropriate management.

The association between body mass index (BMI) at the time of breast cancer diagnosis and the prognosis of breast cancer patients remains controversial. Furthermore, the association between BMI and prognosis with respect to different breast cancer subtypes is not clearly defined. We analyzed data from 41,021 invasive breast cancer patients between January 1988 and February 2008 from the Korean Breast Cancer Registry (KBCR) database. Overall survival (OS) and breast cancer-specific survival (BCSS) were analyzed using the Kaplan-Meier method and Cox’s proportional hazard regression model among all patients and specific breast cancer subtypes with respect to BMI categories. A U-shaped association between BMI and mortality was observed in the total cohort. Underweight and obese individuals exhibited worse OS (hazard ratio, 1.23 [95 % confidence interval {CI}, 1.05 to 1.44] and 1.29 [1.13 to 1.48], respectively) and BCSS (1.26 [1.03 to 1.54] and 1.21 [1.02 to 1.43], respectively) than normal-weight individuals. In the estrogen receptor (ER) and/or progesterone receptor (PR)+/human epidermal growth factor receptor 2 (HER2) - subgroup, obese individuals exhibited worse OS (1.48 [1.18 to 1.85]) and BCSS (1.31 [1.13 to 1.52]) than normal-weight individuals. Conversely, in the ER and PR-/HER2+ subgroup, underweight individuals exhibited worse OS (1.68 [1.12 to 2.47]) and BCSS (1.79 [1.11 to 2.90]) than normal-weight individuals. We observed a U-shaped relationship between BMI at diagnosis and poor OS and BCSS among all breast cancer patients. However, obesity in the ER and/or PR+/HER2- subgroup and underweight in the ER and PR-/HER2+ subgroup were poor prognostic factors. Therefore, BMI at diagnosis and breast cancer subtype should be considered simultaneously in various treatment decision processes and surveillance schedules.