Recurrence risk in breast cancer depends on clinical factors such as tumor size and lymph node involvement, as well as pathologic and molecular features that further refine prognosis. Virginia Kaklamani, MD, DSc, reviews how genomic assays can influence chemotherapy decisions, particularly by menopausal status, and summarizes systemic and lifestyle approaches that may reduce early and late recurrence risk.

Clinical risk factors for breast cancer recurrence are related to the size of the tumor, the presence or absence of lymph node metastases, and the age of the patient. When we talk about pathologic risk factors, we are referring to the type of breast cancer (ie, ER, PR, and HER2 status), the degree of proliferation (ie, the grade or Ki-67), and the presence of any other mutation(s) that might place a patient at a higher or lower risk for recurrence. Genomic assays such as Oncotype DX Breast Recurrence Score (Exact Sciences Corporation) and MammaPrint (Agendia) look more deeply into recurrence risk based on other molecular tumor characteristics. Oncotype DX Breast Recurrence Score, for example, provides a continuous score from 0 to 100. The lower the score, the lower the recurrence risk. The MammaPrint index is calculated and then translated into high 2, high 1, low, and ultra-low risk of recurrence.

The risk of recurrence can be reduced by the use of neoadjuvant and adjuvant therapies. For example, for HR+/HER2- early-stage breast cancer, local therapy (ie, radiation therapy) and systemic therapy (ie, chemotherapy, endocrine therapy, and CDK4/6 inhibitor therapy) can decrease the risk of local and systemic recurrence. Further, patients with a BRCA germline mutation may also be eligible for PARP inhibitor therapy. Extended endocrine therapy may be used to decrease the risk of late recurrence. Finally, lifestyle factors can also modify risk, and collective data suggest that maintaining a healthy weight and exercising can decrease the recurrence risk.

Menopausal status can influence the use of adjuvant chemotherapy in patients with HR+/HER2- early-stage breast cancer. For a premenopausal patient who has axillary node-positive breast cancer, standard-of-care adjuvant therapy includes the use of chemotherapy regardless of the patient’s Oncotype DX Breast Recurrence Score. Conversely, in a postmenopausal patient with 1 to 3 positive axillary lymph nodes, the Oncotype DX Breast Recurrence Score assay can be used to determine whether the use of chemotherapy is indicated. If the score is 25 or less, then chemotherapy is not indicated; if the score is 26 or greater, then chemotherapy is considered standard of care.

The type of endocrine therapy also depends on whether the patient is pre- or postmenopausal. In postmenopausal patients, the most commonly used endocrine therapy is an aromatase inhibitor, whereas, in premenopausal patients, tamoxifen can be used. Ovarian suppression in combination with an aromatase inhibitor can also be used in patients with a higher risk of relapse. Finally, the use of CDK4/6 inhibitors has been incorporated into the adjuvant setting based on results from the NATALEE and monarchE trials.