Response to neo-adjuvant chemotherapy in women with BRCA1-positive breast cancers.
OBJECTIVE
There have been no studies to date which look at the relative effectiveness of different regimens of chemotherapy in women who have breast cancer and who carry a BRCA1 germ-line mutation. We wished to compare rates of response to neo-adjuvant chemotherapy in BRCA1 mutation carriers and non-carrier controls.


METHODS
From a registry of 3,479 patients, we identified 44 Polish women who carried a BRCA1 founder mutation and who had been treated with neo-adjuvant chemotherapy for breast cancer, and 41 age- and hospital-matched controls.


RESULTS
35 of the 44 BRCA1 mutation carriers (80%) experienced a partial or complete response to neo-adjuvant chemotherapy, compared to 39 of the 41 (95%) non-carriers (P=0.05). In the hereditary subgroup, response rates differed depending on whether or not a taxane (docetaxel) was given. Six of the 15 BRCA1 carrier women given docetaxel with doxorubicin responded (complete or partial), compared to 29 of 29 given other (DNA-damaging) therapies (P=0.001). Among the non-carriers, the rates of response to the two categories of chemotherapy were similar.


CONCLUSIONS
Breast cancers among BRCA1 carriers frequently do not exhibit sensitivity to docetaxel in the neo-adjuvant setting. It is likely that normal BRCA1 is required for clinical response to mitotic spindle poisons.
Byrski
T
T
Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
Gronwald
J
J
Huzarski
T
T
Grzybowska
E
E
Budryk
M
M
Stawicka
M
M
Mierzwa
T
T
Szwiec
M
M
Wiśniowski
R
R
Siolek
M
M
Narod
S A
SA
Lubinski
J
J
D000328:Adult; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019313:BRCA1 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D017024:Chemotherapy, Adjuvant; D000077143:Docetaxel; D004317:Doxorubicin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D018579:Patient Selection; D011044:Poland; D012042:Registries; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D050257:Tubulin Modulators / Q000008:administration & dosage
D000903:Antibiotics, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D043823:Taxoids; D050257:Tubulin Modulators; D000077143:Docetaxel; D004317:Doxorubicin