Loss of Her-2 expression after neo-adjuvant therapy with dual anti-Her-2 agents (Pertuzumab/Herceptin) with chemotherapy in locally advanced Her-2 positive breast cancer.

Abstract

e12562 Background: Conversion of Her-2 positive to negative after neoadjuvant treatments in Her-2 positive breast cancer has been reported. In most of these reports either chemotherapy alone or in combination with a single Her-2 agent (trastuzumab) was utilized. Use of dual anti-Her-2 agents (Pertzummab/Trastuzumab) along with chemotherapy as the neoadjuvant treatment regimen in Her-2 + breast cancer is a standard of care now. We looked at the loss of Her-2 expression after neo-adjuvant regimen consisting of dual anti-Her-2 agents and chemotherapy in locally advanced Her-2 + breast cancer. Methods: We reviewed the records of Her-2 positive patients with T2 or higher or lymph Node+ Her-2 + breast treated at our institution. Patients who had received neo-adjuvant chemotherapy and dual anti-Her-2 agents, pertuzumab and Trastuzumab were identified for this study. Clinical and pathologic data was collected. Her-2 expression was determined by IHC and FISH. Results: Between Dec 2014 and June 2019, 79 patients for identified. Median age was 47 yrs, range 31-83 yrs. All were females except one. Pre-treatment, 74 pts. were 3 + on IHC and 5 pts. were 2+ on IHC, but positive by FISH. Median Her-2/CEP 17 copy number ratio was 6.2, range 3.6-16.7. Sixty patients were ER positive and 19 were ER negative. Pertuzumab+ TCH was the most common regimen used, 91% of the patients. All patients underwent surgery. Forty five out of 79 patients, 56%, had a pCR. Thirty four pts with residual disease were re-assessed for Her-2 expression. 7/32 (20.5%) patients were Her-2 negative. 6/7 pts. were 0/1+ by IHC and 1 pt. was 2+ by IHC but negative by FISH. Five out of seven pts. (71.5%) converting to Her-2 negative were ER negative at diagnosis and 2/7 (28.5%) converting to Her-2 negative were ER + at diagnosis. All patients converting to Her-2 negative had received Pertuzumab+TCH. Conclusions: Loss of Her-2 expression is observed after neoadjuvant treatments with a dual anti-Her-2 regimen along with chemotherapy. Implications of this change on choosing adjuvant treatments in Her-2 + pts who have had neo-adjuvant therapy and effect on recurrence/survival outcomes needs to be explored in larger studies.