Response to neo-adjuvant chemotherapy in women with BRCA1-positive breast cancers
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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.
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.
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.
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.
KeywordsTaxane Neo-adjuvant chemotherapy BRCA1 Breast cancer Doxorubicin
This study was funded by the Polish Ministry of Science 04/p05/11. Supported by the Canadian Breast Cancer Research Alliance. We thank William Foulkes for helpful comments.
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