Acute chemotherapy-related toxicity is not increased in BRCA1 and BRCA2 mutation carriers treated for breast cancer in the United Kingdom.
OBJECTIVE
To evaluate acute toxicity induced by chemotherapy for breast cancer in a retrospective study of 62 BRCA1/2 mutation carriers matched 1:1 with women who had treatment for sporadic disease in the United Kingdom between 1983 and 2003.


METHODS
All participants were interviewed by one of two researchers using standardized questionnaires, and their medical records were reviewed by one research nurse. The two main regimens received were cyclophosphamide, methotrexate, and fluorouracil and fluorouracil, epirubicin, and cyclophosphamide. The proportion of cases and controls receiving anthracycline-based treatment was equivalent, but fewer BRCA1 cases received this treatment than did BRCA2 mutation carriers. Toxicity was documented using the Eastern Cooperative Oncology Group Common Toxicity Criteria for hematologic, infective, and gastrointestinal toxicities. No increase in toxicity was seen in BRCA1/2 mutation carriers.


RESULTS
The only significant difference was that neutropenia was less evident in BRCA2 mutation carriers than in either BRCA1 mutation carriers or controls. As a result, there was no requirement for dose reduction among BRCA2 mutation carriers, in contrast to 10 of 39 BRCA1 carriers and 16 of 62 controls (P = 0.02).


CONCLUSIONS
This result has implications for therapy and indicates that women with mutations in BRCA1 and BRCA2 may be given the same doses of chemotherapy as noncarriers.
Shanley
Susan
S
Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Sutton, UK. shanleysusan@hotmail.com
McReynolds
Kate
K
Ardern-Jones
Audrey
A
Ahern
Roger
R
Fernando
Indrajit
I
Yarnold
John
J
Evans
Gareth
G
Eccles
Diana
D
Hodgson
Shirley
S
Ashley
Sue
S
Ashcroft
Linda
L
Tutt
Andrew
A
Bancroft
Elizabeth
E
Short
Susan
S
Smith
Ian
I
Gui
Gerald
G
Barr
Lester
L
Baildam
Andrew
A
Howell
Anthony
A
Royle
Gavin
G
Pierce
Lori
L
Easton
Douglas
D
Eeles
Rosalind
R
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D016022:Case-Control Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D009367:Neoplasm Staging; D011878:Radiotherapy; D012189:Retrospective Studies; D016896:Treatment Outcome; D006113:United Kingdom / Q000453:epidemiology