BRCA1 mRNA EXPRESSION LEVELS PREDICT SURVIVAL IN BREAST CANCER PATIENTS TREATED WITH NEOADJUVANT CHEMOTHERAPY

#The present invention relates to the field of diagnostics and, in particular, to a method for selecting an individual neoadjuvant chemotherapy and for predicting the survival of breast cancer patients, based on the expression level of the BRCA1 gene in a sample from said patient.

#Worldwide, breast cancer is the second most common type of cancer (10.4%; after lung cancer) and the fifth most common cause of cancer death (after lung cancer, stomach cancer, liver cancer, and colon cancer). Among women worldwide, breast cancer is the most common cause of cancer death. In 2005, breast cancer caused 502,000 deaths worldwide (7% of cancer deaths; almost 1% of all deaths). The number of cases worldwide has significantly increased since the 1970s, a phenomenon partly blamed on modern lifestyles in the Western world. North American women have the highest incidence of breast cancer in the world.

#Because the breast is composed of identical tissues in males and females, breast cancer also occurs in males. Incidences of breast cancer in men are approximately 100 times less common than in women, but men with breast cancer are considered to have the same statistical survival rates as women.

#FIG. 1 shows a Kaplan-Meier survival curve representing disease free survival (DFS) for BRCA1 by terciles. Time is represented in months. On the plot, small vertical tick-marks indicate losses, where patient data has been censored. The term “censored” indicates losses from the sample before the final outcome is observed.

#FIG. 2 shows a Kaplan-Meier survival curve representing median survival for BRCA1 by terciles. Time is represented in months. On the plot, small vertical tick-marks indicate losses, where patient data has been censored. The term “censored” indicates losses from the sample before the final outcome is observed.

#FIG. 3 is a graph representing correlation between BRCA1 protein expression measured by immunohistochemistry (values 0, 1, 2, and 3) and BRCA1 mRNA expression measured by quantitative PCR in 41 breast cancer patients treated with FEC neoadjuvant therapy.

#The authors of the present invention have surprisingly found that the clinical response of patients suffering from breast cancer being treated with a neoadjuvant therapy based on a combination of an anti-metabolite, an intercalating agent and an alkylating agent closely correlates with the expression levels of BRCA1.

#This allows the physician to make an informed decision as to the therapeutic regimen most likely to improve survival according to the BRCA1 expression level with appropriate risk and benefit trade off to the patient. Based on these findings they have defined the method of the invention in its different embodiments that will be described now in detail.

#Thus, in a first aspect, the invention provides a novel method for selecting an individual neoadjuvant therapy for a patient suffering from breast cancer which comprises determining the expression levels of BRCA1 gene in a sample from said patient, wherein if expression levels of BRCA1 gene are low when compared with reference values, then the patient is a good candidate for a neoadjuvant therapy based on a combination of an anti-metabolite, an intercalating agent and an alkylating agent.