Abstract P5-02-11: Triple negative breast cancer: The role of classic histological and prognostic factors on disease free survival
Authors: Elkhanany Ahmed , Suman Vera J , Cafourek Victoria , Gilbert Judith A , Ingle James N , Couch Fergus , Vissscher Daniel W , Goetz Matthew P 
Published: May 2015

Background: Triple negative breast cancer (TNBC) represents 15% of all breast cancers, and is characterized by an aggressive clinical course. While efforts are ongoing to characterize the molecular basis for variation in TNBC, there are conflicting data regarding the impact of prognostic factors such as age and Ki-67 typically used for treatment decisions in other breast cancer subtypes. We identified a retrospective cohort of women with ER- breast cancer with long term follow-up, and performed central confirmation of ER, PR, HER2, Ki-67 and histological classification to assess the association of Ki-67 and histologic subtype on clinical outcome in TNBC pateints (pts).

Methods: 9,836 women who underwent breast cancer surgery at Mayo Clinic Rochester from 1985-2005 were identified. Pts were excluded due to: ER+ disease (7363); prior cancer (553); non-invasive disease (465); bilateral breast cancer (167); metastatic disease [at diagnosis or within 60 days of surgery (110)]; ER- disease treated with neoadjuvant chemotherapy (121) or adjuvant hormonal therapy (112); or tumor block exhausted (94). For all others, centralized ER/PR/HER2 identified the following for exclusion, &gt;1% ER staining (n=76), &gt; 1% PR (n=14) and HER2+ (n=144) by IHC (3+) or FISH amplification. 225 cases are still undergoing review. For the centrally confirmed pts with TNBC (n=392), Ki-67 and histological characterization (WHO subtypes) were assessed.

Results: Patient characteristics are listed in the table. The median age for all TNBC’s was 45 (range 29-88) and nearly all tumors were grade 3 (91%) with high proliferation (63% with Ki-67 &gt; 30%). The median follow-up was &gt;10 years, where 139 pts had a disease event: progression (86) or second primary (53) and 53 died without a disease event. The 10 yr DFS rate was 55.8% (95%CI: 48.8-63.9%) among the 238 pts who did not receive adjuvant chemotherapy (AdjCT) and 58.9% (95% CI: 48.9-70.9%) among the 102 pts administered AdjCT. In pts without adjCT, DFS was found to differ with respect to number of positive LNs (0 vs. 1-4 vs. 4+; log rank p=0.003) and medullary histology (log rank p=0.015) but not with age (&lt; 50 vs. ≥ 50), tumor size (&lt; 2.0 vs. 2-5 vs. ≥ 5.0 cm) or Ki-67 (0-15% vs. 15.1-30% vs. &gt;30 %).

Conclusions: Our findings confirm the poor prognosis of TNBC. The medullary histological subtype is associated with significantly better prognosis than other TNBC subtypes (10 year DFS rate of 78.5%; 95%CI: 59.1-99.9% in pts not treated with adjCT). After central confirmation, neither age nor Ki-67 provide additional prognostic information.

Patient characteristicsMedian Age (range)45(29-88) n%Histology  Apocrine287.1Carcinoma, anaplastic or undiffrentiated9323.7Central scar/necrotizing348.7Clear Cell297.4Infiltrating ductal ca7118.1Large Cell neuroendocrine143.6Medullary and atypical medullary4311.0Metaplastic ca246.1Trabecular ca338.4other histologies235.9Grade  130.82317.9335891.3Tumor Size  0.1-2 cm19650&gt; 2.0 cm19549.6not stated10.3Nodal status  0251641-38220.94-9338.410+225.6not evaluated41.0Ki-67  0-157719.615.1-306516.6&gt;30%24763.3not done20.5Adjuvant Chemotherapy  Yes10226.0No23860.7unknown5213.3

Citation Format: Ahmed Elkhanany, Vera J Suman, Victoria Cafourek, Judith A Gilbert, James N Ingle, Fergus Couch, Daniel W Vissscher, Matthew P Goetz. Triple negative breast cancer: The role of classic histological and prognostic factors on disease free survival [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-02-11.