A comparison of an androgenic pathway between development and reoccurrence/progression of triple negative breast cancer patients

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 292-325-Breast & Prostate Cancer
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-299
Keely M McNamara*1, Alif Meem Nurani1, Tomomi Yoda1, Yasuhiro Miki1, Niramol Chanplakorn2, Eriko Abe3, Yang Yang3, Hideko Yamauchi3, Koyu Suzuki3, Hisashi Hirakawa4, Reiki Nishimura5, Nobuyuki Arima5, Takashi Suzuki6, Minoru Miyashita7, Kentaro Tamaki8, Takanori Ishida7, Noriaki Ohuchi7 and Hironobu Sasano1
1Tohoku Univ Sch of Med, Miyagi, Japan, 2Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand, 3St Lukes Hospital, Tokyo, Japan, 4Tohoku Kosai Hospital, Sendai, Japan, 5Kumamoto City Hospital, Kyushu, Japan, 6Tohoku Univ Sch of Hlth Sci, Sendai, Japan, 7Tohoku Univ Sch of Med, Sendai, Japan, 8Nahanishi Clinic, Naha, Japan
Triple negative breast cancer (TNBC) is considered an aggressive breast malignancy due to its poor prognosis and lack of potential therapeutic targets. We have previously demonstrated in a Japanese TNBC cohort that 25% of all invasive ductal carcinomas express androgen receptor (AR) and that its presence alone or in combination with 5αR1 was associated with a significantly lower Ki67 LI. Therefore, in this study, we explored the roles of androgenic pathways in the development and progression of TNBC by evaluating the immunoreactivity (IR) of AR, 5αR1 and 17βHSD5 in a large cohort of triple negative precursor lesions (ductal carcinoma in situ, (DCIS), n= 42) and a smaller cohort of paired primary and recurrent TNBC (pIDC, rIDC, n= 16 pairs).

We studied cases from three different Japanese hospitals (DCIS: St Lukes Hospital Tokyo, Tohoku Kosai Hospital Sendai, pIDC/rIDC: Kumamoto City Hospital, Kyushu) with appropriate IRB approval. Immunoreactivity was quantified using H score for nuclear staining (AR) and a semi-quantative score for cytoplasmic staining (5αR1, 17βHSD5) with 10% IR(nuclear) and >50% IR (cytoplasmic) being used to dichotomise the results.

AR LIs were significantly higher in DCIS compared to those in historical IDC cases (AR H Score; DCIS:182, IDC:23, p<0.001). Levels of AR and enzymes demonstrated concordance in 49% of DCIS cases which was correlated well with the 48% concordance reported in our historical IDC data. These findings suggest TNBC DCIS lesions had higher levels of AR but similar levels of concordance between the enzymes and AR to TNBC IDC samples.

In recurrent disease, the status of AR LI between pIDC and rIDC were significantly correlated (p<0.001 RSq=0.79), but not significantly different from that in historical IDC cases.  No significant correlations were detected between AR and the enzyme status in these cases.

These results suggest that the loss of AR may be a non obligate step in the progression of triple negative breast cancer but AR remains in a significant proportion of invasive disease. These finding also indicated that a) androgenic pathways were associated with a less invasive TNBC and b) androgen based therapy may not only be effective against primary TNBC but also may have a therapeutic potential in recurrent disease.

Nothing to Disclose: KMM, AMN, TY, YM, NC, EA, YY, HY, KS, HH, RN, NA, TS, MM, KT, TI, NO, HS

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: KM is supported by a JSPS-AAS postdoctoral fellowship.