Post-treatment breast cancer prognosis

A method of treating breast cancer in a subject who has undergone removal of estrogen receptor positive (ER+) breast cancer and has been treated with a first endocrine therapy of a selective estrogen receptor modulator (SERM), a selective estrogen receptor down-regulator (SERD), or an aromatase inhibitor (AI), the method comprising:

• preparing cDNA from nucleic acids in a sample of ER+ breast cancer cells from the subject,
• measuring the expression level of the HoxB13, IL17BR, Bub1B, CENPA, NEK2, RACGAP1, and RRM2 genes from said cDNA,
• calculating a ratio of expression levels of HoxB13:IL17BR (“H:I ratio”) using the subject's expression levels,
• calculating a molecular grade index (“MGI”) comprising summing expression levels of Bub1B, CENPA, NEK2, RACGAP1, and RRM2 using the subject's expression levels,
• building a continuous risk model by combining an H:I ratio and a MGI as continuous variables from a plurality of reference patients,
• establishing a reference breast cancer index (BCI) value for ER+ breast cancer patients that did not have cancer recurrence and/or ER+ breast cancer patients that did have cancer recurrence by combining the H:I ratio and MGI from the plurality of reference patients, wherein the reference BCI value has a cut-off value greater than 6.4,
• calculating the subject's BCI value by combining the subject's H:I ratio and MGI,
• comparing the subject's BCI value to the cut-off value,
• classifying the subject as having recurrence of breast cancer if the subject's BCI value is (a) above 6.4 for the patients that did not have cancer recurrence and/or (b) not below 6.4 for the patients that did have cancer recurrence, wherein risk of cancer recurrence is higher above the cut-off than below the cut-off, and
• treating the subject classified as having a high risk of recurrence with a second endocrine therapy.