Response to neo-adjuvant chemotherapy in women with BRCA1-positive breast cancers

Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
Breast Cancer Research and Treatment (Impact Factor: 4.2). 04/2008; 108(2):289-96. DOI: 10.1007/s10549-007-9600-1
Source: PubMed

ABSTRACT 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.

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    • "A further explanation may be that even low levels of BRCA1 are sufficient to mediate response to taxanes and perhaps reduced taxane response is confined to patients with complete BRCA1 dysfunction. In support of this, two small studies in hereditary breast cancer have reported resistance to neo-adjuvant taxane based chemotherapy in patients with germline BRCA1 mutations [17] [18]. Another point to consider is the potential dose dependent effects that may occur when both platinums and taxanes are administered in combination. "
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