The effect of anthracycline and taxane based chemotherapy on biological features of residual disease after neo-adjuvant therapies in breast cancer patients is poorly described.
PATIENTS AND METHODS: We collected information through the institutional clinical database on all consecutive breast cancer patients treated with neo-adjuvant chemotherapy at INT, Milan, Italy, between January 2010 and March 2015. We selected patients who did not achieve pathological complete response at final surgery. All patients had a pathological evaluation including the shrinking pattern (scattered or concentric); ER, PgR, HER2 and Ki-67 expression were evaluated both at diagnostic biopsy and at final surgery. McNemar's test was used to compare paired proportions.
RESULTS: We identified a total of 325 patients. Median age was 51 yrs (range: 23 - 85 yrs). 304 (93%) pts received anthracycline and taxane containing chemotherapy for a median number of 6 (range 2-18) cycles. Radical modified mastectomy was performed in 68% of cases. Scattered residual disease was diagnosed in 112 (34%) cases. HER2 over-expression in diagnostic biopsy was significantly associated to scattered response (OR 1.94, CI 1.13 – 3.36, p= 0.017). 11/220 pts (5%) with ER-positive diagnostic biopsy had ER-negative residual tumor; 9/54 pts (17%) with initial ER-negative tumors became ER-positive. 34/183 (19%) pts with initial positive PgR at diagnostic biopsy had PgR-negative residual tumor; whereas, 17/86 pts (20%) with negative PgR became positive. The HER2 expression changed from positive to negative in 9/49 (18%) cases and from negative to positive in 7/190 (4%) cases. The Ki-67 expression changed from > or =20% to <20% in 63/175 (36%) cases and vice-versa in 14/54 (26%) cases. Compared to diagnostic biopsy, the rate of PgR-positive tumors decreased from 68 to 62% (p= 0.024) and the rate of Ki67<20% tumors increased from 24 to 45% (p=<0.001) in surgical specimen. Subtype changes at surgery occurred in 37/245 (15%) of cases, i.e. none in triple negative, 8/20 (10%) in HER2 positive, and 29/202 (14%) in luminal tumors. 73% of cases that changed after treatment showed a trend towards luminal differentiation. There was no significant correlation between pre- and post-treatment biological characteristics and the type of tumor shrinkage.
CONCLUSION: Anthracycline and taxane-based neo-adjuvant chemotherapy induces loss of PgR and Ki-67 in breast cancer. These changes are independent of the pattern of tumor shrinkage. The subtype switching toward more luminal phenotype suggest an endocrine effect of chemotherapy and paves the way to possible combinatorial approach of chemo- and hormone-therapy.
Citation Format: Galli G, Porcu L, Baili P, Hade A, Di Salvo F, Bregni G, Agresti R, Gennaro M, De Santis MC, Ferrari B, de Braud F, Di Cosimo S. Neo-adjuvant chemotherapy for the treatment of breast cancer exterts a selection pressure toward luminal phenotype. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-14-22.