Predicting breast cancer recurrence

A method of treating a human subject who has been diagnosed with breast cancer and is receiving or has received an initial treatment, the method comprising the steps of:

• measuring or having measured mRNA expression levels of the genes homeobox B13 (HoxB13), interleukin 17 receptor B (IL17BR), budding uninhibited by benzimidazoles 1 beta (Bub1B), centromere protein A, isoform a (CENPA), never in mitosis gene a-related kinase 2 (NEK2), Rac GTPase activating protein 1 (RACGAP1), and ribonucleotide reductase M2 (RRM2) in a sample from the subject comprising breast cancer cells that are estrogen receptor positive (ER+);
• determining or having determined the ratio of expression levels of HoxB13/IL17BR (H:I);
• calculating or having calculated a molecular grade index (MGI) comprising summing the expression levels of Bub1B, CENPA, NEK2, RACGAP1, and RRM2;
• calculating or having calculated a breast cancer index (BCI) value by combining H:I and MGI;
• comparing or having compared the BCI value of the subject to a BCI cutoff;
• and
• classifying or having classified the subject into a two-category scheme of (a) high risk of recurrence if the subject's BCI is higher than the BCI cutoff or (b) low risk of recurrence if the BCI is lower than the BCI cutoff, wherein classification does not include an intermediate risk category;
• and
• treating the subject with an adjuvant therapy selected from an aromatase inhibitor, anti-mTOR therapy, anti-HER2 therapy, and endocrine therapy;
• wherein
• (a) if the subject has a high risk of recurrence, the subject is treated with the adjuvant therapy for more than 5 years after the initial treatment, or
• (b) if the subject has a low risk of recurrence, the subject is treated with the adjuvant therapy for 5 years or less after the initial treatment.

A method of treating a human subject who has been diagnosed with breast cancer and is receiving an initial treatment with a first therapy comprising an aromatase inhibitor, targeted therapy, or endocrine therapy, the method comprising the steps of:

• measuring or having measured mRNA expression levels of the genes homeobox B13 (HoxB13), interleukin 17 receptor B (IL17BR), budding uninhibited by benzimidazoles 1 beta (Bub1B), centromere protein A, isoform a (CENPA), never in mitosis gene a-related kinase 2 (NEK2), Rac GTPase activating protein 1 (RACGAP1), and ribonucleotide reductase M2 (RRM2) in a sample from the subject comprising breast cancer cells that are estrogen receptor positive (ER+);
• determining or having determined the ratio of expression levels of HoxB13/IL17BR (H:I);
• calculating or having calculated a molecular grade index (MGI) comprising summing the expression levels of Bub1B, CENPA, NEK2, RACGAP1, and RRM2;
• calculating or having calculated a breast cancer index (BCI) value by combining H:I and MGI;
• comparing or having compared the BCI value of the subject to a BCI cutoff;
• classifying or having classified the subject into a two-category scheme of (a) high risk of recurrence if the subject's BCI is higher than the BCI cutoff or (b) low risk of recurrence if the BCI is lower than the BCI cutoff, wherein classification does not include an intermediate risk category;
• and
• either
• (a) treating the high-risk subject with a second therapy comprising an aromatase inhibitor or anti-mTOR therapy or anti-HER2 therapy or endocrine therapy, wherein the first therapy and second therapy are different, or
• (b) ceasing the first therapy after 5 years in the low-risk subject.