Adenoid cystic carcinoma (ACC) of the breast is a rare subtype of breast cancer. Despite its triple-negative status, this tumor has a very good prognosis. Breast-conserving treatment including postoperative radiotherapy seems to be equivalent to mastectomy alone with respect to survival. Routine axillary lymph node staging is not recommended since lymph node metastases are extremely rare. The value of adjuvant systemic therapies is not established. Late relapses can occur, so long-term follow-up is mandatory for these patients.

Background: Apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like (APOBEC) family is known to function in innate immune system that protects against retrovirus by deaminating cytosine to uracil in single-stranded DNA. APOBEC family has emerged as an endogenous mutator to contribute to the mutation burden in many cancers. We aimed to evaluate the expression of APOBEC3A (A3A), 3B (A3B) mRNA and APOBEC3A-3B deletion polymorphism in Korean breast cancer patients and investigate the correlation between their expression and clinicopathological characteristics. Methods: One hundred thirty-eight patients who underwent surgery for breast cancer in Uijeongbu St. Mary's Hospital between January 2013 and December 2016 were evaluated. RNA and DNA were extracted from 138 breast cancer tissues and 10 adjacent normal breast tissues. The levels of A3A and A3B mRNA transcripts were determined using real-time quantitative PCR. Insertion and deletion PCR assays were performed to detect the APOBEC3A-3B deletion allele. Mutation hotspots in exon 2-11 of TP53 and exon 9/20 of PIK3CA were evaluated using direct sequencing method. Results: The expression of A3B was increased in breast cancer tissues than in normal breast tissues. The median A3B mRNA expression levels in both triple-negative breast cancer and human epidermal growth factor 2-positive breast cancer were significantly higher than in hormone receptor-positive breast cancer. Old age and high ki-67 expression were associated with increased expression of A3A and A3B. Advanced stage, presence of lymph node involvement, and high histological grade were associated with increased expression of A3A. The APOBEC3B deletion allele was found in 78 (56%) tumor samples. There was no significant association between A3A, A3B mRNA levels and the presence of APOBEC3B deletion allele. There was no difference in clinicopathological characteristics according to the presence of APOBEC3B deletion allele except histological grade. The frequency of high histological grade was significantly higher in tumors with APOBEC3B deletion allele than tumors without APOBEC3B deletion allele. TP53 mutations were identified in 12 (8.7%) cases and PIK3CA mutations were identified in 31 (22.5%) cases. There were no significant differences in the levels of A3A and A3B mRNA expression by TP53 mutation status. The presence of a PIK3CA mutation was significantly associated with lower A3A expression. Conclusions: The levels of A3B mRNA expression showed a difference according to breast cancer subtype, and triple-negative breast cancer showed the highest levels of A3B mRNA expression. The high levels of A3A and A3B mRNA expression were associated with an aggressive phenotype including high proliferation index. The APOBEC3A-3B deletion polymorphism was found in about half of the patients, but there was no difference in clinicopathological factors according to the presence of APOBEC3B deletion allele except histological grade. Citation Format: Won HS, Sun DS, Ko YH, You SH, Kim YS, Kim JS. Clinical implication of APOBEC3A and 3B in Korean patients with breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-05-03.

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Introduction: Triple positive breast cancer is one of intrinsic subtype in breast cancer that is defined namely, ER/PR/Her2 positive tumors. It has multiple strategies for systemic therapy according to the characteristics of hormonal and anti-HER2 responsiveness. Each targeted therapy plays cross-talks between HER-2 and estrogen receptor signaling pathway resulting in endocrine resistance and anti Her2 resistance. Methods: We compared the triple positive subtype to the other breast cancer intrinsic subtypes to distinguish the uniqueness in their position among other breast cancer subtypes using retrospective analysis of two different cohorts; Korea Breast Cancer Society (KBCS) Breast cancer registry data (N=31266, Jan. 2006 – Dec. 2010) and database from St. Mary`s hospital Breast cancer registry (N=2216, Apr. 2009 – Mar. 2016). Results: Median follow up duration of 76 months in KBCS cohort (2006-2010) showed the overall survival graph of triple positive breast cancer located in the middle in between Luminal A intrinsic subtype and HER2 enriched subtype(P<.001). Also HER2 directed trastuzumab therapy did not improve the overall survival in triple positive breast cancer patients (P=.899) in contrast to the improved overall survival using trastuzumab therapy in HER2 enriched subtype (P=.018). Like the preceding results, CMC breast cancer data showed the similar results in recurrence free survival (P<.001). and no recurrence free survival improvement using trastuzumab therapy in triple positive breast cancer patient during the median follow up of 33 months (P=0.800). Conclusion: 1) Anti-HER2 therapy seems less beneficial in Triple positive breast cancer subtype regardless of breast cancer stage. 2) Triple positive breast cancer may require different therapeutic approaches 3) Other targeted agents (mTOR inhibitor, CDK4/6 inhibitor, PIK3CA inhibitor) can be a substitute option for the Trastuzumab therapy in triple positive breast cancer. Citation Format: Kim JS, Kim YS, You SH. Triple positive breast cancer ; a distictive subtype and consideration of systemic therapeutic approach [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-13-14.