Sensitivity to first-line chemotherapy for metastatic breast cancer in BRCA1 and BRCA2 mutation carriers.

Abstract

PURPOSE:

Preclinical as well as a few small retrospective, neoadjuvant studies suggest that breast cancer (cells) without functional BRCA1 or BRCA2 protein have an increased sensitivity to some chemotherapeutic agents causing double-strand DNA breaks. In this study we assessed the sensitivity to standard first-line chemotherapy of metastatic BRCA1/2-associated breast cancer, compared with sporadic breast cancer patients.

PATIENTS AND METHODS:

From the Family Cancer Clinic database, we selected 93 BRCA1- and 28 BRCA2-associated breast cancer patients treated with chemotherapy for metastatic disease before January 1, 2007. Objective response (OR), progression-free survival (PFS), and overall survival (OS) after start of first-line chemotherapy were compared with those of sporadic patients, matched for year of birth, age at diagnosis of primary breast cancer, and year of detection of metastatic disease.

RESULTS:

The chemotherapy regimens most frequently used were anthracycline-based (n = 147) and cyclophosphamide, methotrexate, and fluorouracil (CMF)/CMF like (n = 68). As compared to sporadic patients, BRCA2-associated patients had a significantly higher OR (89% v 50%; P = .001), a longer PFS (hazard ratio multivariate [HR(mult)] 0.64; P = .04) and a prolonged OS (HR(mult), 0.53; P = .005) after start of first-line chemotherapy for metastatic breast cancer. For BRCA1-associated patients, a nonsignificant trend for an increased OR (66% v 50%; P = .07), and a longer PFS (HR(mult), 0.79; P = .14) after first-line chemotherapy for metastatic breast cancer was observed, but not for OS.

CONCLUSION:

BRCA2-associated breast cancer is more sensitive to standard first-line chemotherapy for metastatic breast cancer in comparison with sporadic breast cancer, especially to anthracyclines. For BRCA1-associated breast cancer no statistically significant higher sensitivity was observed.

• Authors: Mieke Kriege, Caroline Seynaeve, Hanne Meijers-Heijboer, J Margriet Collee, Marian B E Menke-Pluymers, Carina C M Bartels, Madeleine M A Tilanus-Linthorst, Jannet Blom, Elisabeth Huijskens, Agnes Jager, Ans van den Ouweland, Bert van Geel, Maartje J Hooning, Cecile T M Brekelmans, Jan G M Klijn
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 27 Issue 23 Pg. 3764-71 (Aug 10 2009) ISSN: 1527-7755 [Electronic] United States
• PMID: 19564533 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apoptosis Regulatory Proteins
• BLID protein, human
• BRCA1 Protein
• BRCA1 protein, human
• BRCA2 Protein
• BRCA2 protein, human
• Receptors, Estrogen
• Receptors, Progesterone

Topics

• Adult
• Aged
• Analysis of Variance
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Apoptosis Regulatory Proteins
• BRCA1 Protein (genetics)
• BRCA2 Protein (genetics)
• Breast Neoplasms (chemistry, drug therapy, genetics, pathology)
• Chemotherapy, Adjuvant
• Disease Progression
• Disease-Free Survival
• Female
• Heterozygote
• Humans
• Kaplan-Meier Estimate
• Middle Aged
• Mutation
• Neoplasm Staging
• Receptors, Estrogen (analysis)
• Receptors, Progesterone (analysis)
• Research Design