Targeted exome sequencing of Korean triple-negative breast cancer reveals homozygous deletions associated with poor prognosis of adjuvant chemotherapy-treated patients.

Triple-negative breast cancer is characterized by the absence of estrogen and progesterone receptors and human epidermal growth factor receptor 2, and is associated with a poorer outcome than other subtypes of breast cancer. Moreover, there are no accurate prognostic genes or effective therapeutic targets, thereby necessitating continued intensive investigation. This study analyzed the genetic mutation landscape in 70 patients with triple-negative breast cancer by targeted exome sequencing of tumor and matched normal samples. Sequencing showed that more than 50% of these patients had deleterious mutations and homozygous deletions of DNA repair genes, such as ATM, BRCA1, BRCA2, WRN, and CHEK2. These findings suggested that a large number of patients with triple-negative breast cancer have impaired DNA repair function and that therefore a poly ADP-ribose polymerase inhibitor may be an effective drug in the treatment of this disease. Notably, homozygous deletion of three genes, EPHA5, MITF, and ACSL3, was significantly associated with an increased risk of recurrence or distant metastasis in adjuvant chemotherapy-treated patients.

Risk factor for axillary lymph node metastases in microinvasive breast cancer.

BACKGROUND: Sentinel lymph node biopsy (SLNB) in patients with ductal carcinoma in situ (DCIS) was controversial. Usually we did not do a SLN biopsy when we performed conserving operations with small-sized DCIS. However, sometimes we find DCIS with microinvasive breast cancer (MIC) after the operation. Must reoperations be performed in all patients? The incidence of axillary metastases in microinvasive breast cancer (MIC) has not been extensively studied. We determined the incidence of positive axillary lymph node (ALN) in patients with MIC and the predictive factors of ALN metastases in these patients. METHODS: Between July 1989 and December 2008, 9635 patients had operation on invasive breast cancer in Asan Medical Center. Among these patients, 319 patients had MIC. The research conducted on the 293 patients (excluded were 26 who did not receive axillary lymph node dissection or SLN biopsy). We retrospectively checked clinical and pathologic variables. RESULTS: There were 22 cases of ALN metastases identified in this group of patients (7.5%). Lymphatic invasion (P < .001) and positive estrogen receptor status (P = 03) were independent significant predictors of axillary metastases. CONCLUSIONS: Microinvasive breast cancer is associated with a low rate of lymph node metastases. Some breast cancer patients with MIC at low likelihood of lymph node metastases may be spared lymph node evaluation.

Impact of omission of axillary lymph node dissection after negative sentinel lymph node biopsy: 70-month follow-up.

BACKGROUND: The objective of this study is to assess the oncologic safety of sentinel lymph node biopsy (SLNB), especially with regard to the axillary recurrence (AR) rate, and to determine the risk factors for AR and disease-free survival (DFS) and overall survival (OS) after negative SLNB. MATERIALS AND METHODS: Between 2003 and 2006, a total of 1626 patients with invasive breast cancer and clinically axillary node-negative tumors underwent SLNB using a radioisotope at the Asan Medical Center. Of these patients, 1196 were negative on SLNB. Among these, 709 underwent SLNB only, and 487 underwent SLNB and axillary lymph node dissection (ALND). We included patients with any size tumors, except for those with inflammatory breast cancer, if patients had clinically negative lymph nodes. RESULTS: Mean follow-up was 70.2 months for the SLNB-only group and 71.5 months for the SLNB and ALND group. The 5-year axillary-free survival rates were 98.91% (95% confidence interval [95% CI] 70.2-71.0) and 99.36% (95% CI 71.3-72.0), respectively; the 5-year DFS rates were 95.17% and 95.18%, respectively (log rank P = .543); and the 5-year OS rates were 98.36% and 98.75%, respectively (log rank P = .380). Univariate analysis showed that negative hormone receptor status (P = .002) and high tumor grade (P = .032) were significant prognostic factors for AR in the SLNB only group. Multifocality and tumor size did not affect the rate of AR. CONCLUSION: SLNB alone is an oncologically safe procedure in clinically node negative patients abrogating the need for further ALND. Negative hormone receptor status and high tumor grade might be risk factors for AR.