Chromosome 17 Polysomy and Monosomy as Predictive Markers of Complete Pathological Response (pCR) in Women with Locally Advanced Breast Cancer (LABC)
Leela Elavathil, Priyatharsini Nirmalanantham, Bindi Dhesy, Gabriella Gohla, Odette Boutross-Tadross, Jennifer Ramsay, Tariq Aziz, Anita Bane, Shangguo Tang, Alice Lytwyn. Juravinski Hospital, Hamilton, ON, Canada; Juravinski Cancer Centre, Hamilton, ON, Canada
Background: Fifteen to 22% of LABC patients achieve pCR after neoadjuvant therapy. Carcinomas that are negative for estrogen and progesterone receptor expression (ER-/PR-) and those that show HER-2/neu overexpression (HER-2/neu+) may achieve higher rates of pCR, but study results are not consistent. The HER-2/neu gene is present on chromosome 17 (Ch17). Polysomy or monosomy of Ch17 can occur, but the effect of these aberrations on response to treatment is not clear. We studied whether Ch17 polysomy/monosomy as detected by fluorescent in situ hybridization (FISH) on the pre-treatment breast needle core biopsy (NCB) can predict pCR in LABC patients. Additionally, we examined whether tissue expression of ER/PR and HER-2/neu was associated with pCR.
Design: LABC patients who were treated between 2007 and 2010 were identified. Immunohistochemistry (IHC) and FISH were performed on the NCB specimens to test for ER/PR expression and HER-2/neu expression, respectively. Ch17 polysomy was defined as present when the FISH Ch17 probe (CEP17) signal/nucleus was ≥3, and monosomy when CEP17 signal/nucleus was <2. Two pathologists, who were blinded to all IHC and FISH results, reviewed the slides from each mastectomy case to assess pCR.
Results: A total of 65 LABC patients were identified. Of the 14 patients with polysomy, 4 (29%) achieved pCR compared to 6/46 (13%) with normal Ch17 expression (p= 0.172). pCR was not seen in any of the 5 patients with monosomy. Of the 35 patients with ER- tumors, 9 (26%) achieved pCR, compared to 1/30 (3%) of ER+ patients (P= 0.013). Ten of the 40 (25%) PR- patients achieved pCR, while none of the 25 PR+ patients showed pCR (P= 0.010). pCR was seen in 6/14 (43%) of HER-2/neu+ patients, compared to 4/51 (8%) of HER-2/neu- patients (P=0.001).
Conclusions: Patients with monosomic tumors may display higher resistance to chemotherapy for histologic response. Polysomic tumors may have a higher rate of pCR compared to normal Ch17 expression, but the small sample size prevents definitive conclusion. Our findings agree with others that ER-/PR- and HER-2/neu+ tumours achieve higher frequency of pCR.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 60, Wednesday Morning