Neo-adjuvant doxorubicin and cyclophosphamide followed by paclitaxel in triple-negative breast cancer among BRCA1 mutation carriers and non-carriers.
The purpose of this study was to assess pathological complete response and whether it serves a surrogate for survival among patients receiving neo-adjuvant doxorubicin-cyclophosphamide followed by paclitaxel for triple-negative breast cancer with respect to BRCA1 mutation status. From a neo-adjuvant systemic therapy database of 588 breast cancer cases, 80 triple-negative cases who had undergone BRCA genotyping were identified. Logistic regression model was fitted to examine the association between BRCA1 status and pathological complete response. Survival outcomes were evaluated using Kaplan-Meier method, differences between study groups calculated by log-rank test. Thirty-four BRCA1 carriers and 43 non-carriers were identified. The BRCA1 carriers had pathological complete response rate of 68 % compared with 37 % among non-carriers, p = 0.01. Yet this did not translate into superior survival for BRCA1 carriers compared with non-carriers. No difference in relapse-free survival were noted among those with or without pathological complete response in BRCA1 carriers regardless of pathological complete response status (Log-rank p = 0.25), whereas in the non-carrier cohort, relapse-free survival was superior for those achieving pathological complete response (Log-rank p < 0.0001). Response to neo-adjuvant systemic therapy differed in BRCA1-associated triple-negative breast cancer compared with triple-negative non-carriers, with a higher rate of pathological complete response. However, compared with non-carrier triple-negative breast cancer, pathological complete response was not a surrogate for superior relapse-free survival in BRCA1 patients. Future studies using specific chemotherapy regimens may provide further improvements in outcomes.
Institute of Oncology, The Chaim Sheba Medical Center, 52621, Tel Hashomer, Israel. shani.paluch-shimon@sheba.health.gov.il.|The Dr. Pinchas Borenstein Talpiot Medical Leadership Program, The Chaim Sheba Medical Center, Tel Hashomer, Israel. shani.paluch-shimon@sheba.health.gov.il.|The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. shani.paluch-shimon@sheba.health.gov.il.
Shani
S
Paluch-Shimon
The Suzanne Levy Gertner Oncogenetics Unit, The Chaim Sheba Medical Center, Tel Hashomer, Israel.|The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Eitan
E
Friedman
Institute of Oncology, The Chaim Sheba Medical Center, 52621, Tel Hashomer, Israel.|The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Raanan
R
Berger
The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Moshe
M
Papa
Institute of Oncology, The Chaim Sheba Medical Center, 52621, Tel Hashomer, Israel.
Maya
M
Dadiani
Institute of Oncology, The Chaim Sheba Medical Center, 52621, Tel Hashomer, Israel.
Neil
N
Friedman
Department of Surgery, The Chaim Sheba Medical Center, Tel Hashomer, Israel.|The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Moshe
M
Shabtai
Department of Surgery, The Chaim Sheba Medical Center, Tel Hashomer, Israel.|The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Dov
D
Zippel
Department of Surgery, The Chaim Sheba Medical Center, Tel Hashomer, Israel.|The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Mordechai
M
Gutman
Institute of Oncology, The Chaim Sheba Medical Center, 52621, Tel Hashomer, Israel.|The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Talia
T
Golan
Department of Pathology, The Chaim Sheba Medical Center, Tel Hashomer, Israel.|The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Ady
A
Yosepovich
Institute of Oncology, The Chaim Sheba Medical Center, 52621, Tel Hashomer, Israel.|The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Raphael
R
Catane
Institute of Oncology, The Chaim Sheba Medical Center, 52621, Tel Hashomer, Israel.|The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Tami
T
Modiano
Institute of Oncology, The Chaim Sheba Medical Center, 52621, Tel Hashomer, Israel.|The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Bella
B
Kaufman
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D019313:BRCA1 Protein / Q000235:genetics*; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D020360:Neoadjuvant Therapy; D017239:Paclitaxel / Q000008:administration & dosage* / Q000627:therapeutic use; D016019:Survival Analysis; D016896:Treatment Outcome; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D055815:Young Adult
D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D003520:Cyclophosphamide; D017239:Paclitaxel
BRCA; Neo-adjuvant; Triple negative