title: Response to neo-adjuvant chemotherapy in BRCA1 and BRCA2 related stage III breast cancer.
abstract: Pathological features and consequently, tumor response differ between BRCA1/2 carriers and sporadic breast cancer (BC) cases. It is expected that BRCA1/2 associated tumors will be more vulnerable to DNA damaging agents and irradiation due to their function in DNA repair. In addition, very high pathological complete response (pCR) rate of approximately 40-50% to neo-adjuvant chemotherapy were reported by two studies. We describe the clinical outcome, i.e.; complete response (cCR), major pathological response (more than 80% reduction in tumor mass), pathologiacl CR (pCR) and local control rates in 15 BRCA1 and 7 BRCA2 carriers, all diagnosed at stage III and treated with anthracyclin based chemotherapy, mastectomy, and irradiation. cCR were found in 6/15 carriers and in 1/7 BRCA2 carriers (P = 0.3). Rate of major pathological response were 4/15 (26.6%) in BRCA1 compared with none of BRCA2 carriers (P = 0.3). Of them, pCR was recorded in 2/15 of BRCA1 carriers. Clinical and pathological nodal involvements were lower in BRCA1 carriers. While all BRCA2 carriers remained node positive as compared to 50% of BRCA1 carriers (P = 0.047), overall survival was similar in both groups. However, approximately 1/3 of BRCA1 carriers did not respond to chemotherapy and 4/15 died within 5 years of diagnosis. We found a non-significant higher clinical and pathological response rate among BRCA1 carriers in response to neo-adjuvant chemotherapy compared with BRCA2 carriers. Our results suggest chemoresistance of approximately a 1/3 of BRCA1 associated tumors. Tumors of BRCA2 carriers are resistant to chemotherapy, while the estrogen receptor positive nature of tumors results in better post recurrence survival.
authors.affiliation: Sharett Institute of Oncology, Hebrew University-Hadassah Medical Center, 91120 Jerusalem, Israel.
authors.forename: Ayala
authors.initials: A
authors.lastname: Hubert
authors.forename: Bela
authors.initials: B
authors.lastname: Mali
authors.forename: Tamar
authors.initials: T
authors.lastname: Hamburger
authors.forename: Yakir
authors.initials: Y
authors.lastname: Rottenberg
authors.forename: Beatrice
authors.initials: B
authors.lastname: Uziely
authors.forename: Tamar
authors.initials: T
authors.lastname: Peretz
authors.forename: Luna
authors.initials: L
authors.lastname: Kadouri
mesh_terms: D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D019313:BRCA1 Protein / Q000235:genetics* / Q000502:physiology; D024682:BRCA2 Protein / Q000235:genetics* / Q000502:physiology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D009026:Mortality; D009154:Mutation; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D019313:BRCA1 Protein; D024682:BRCA2 Protein