Approach for patients with locally advanced, hormone-positive breast cancer receiving neoadjuvant therapy*

HER2: human epidermal growth factor receptor 2; NACT: neoadjuvant chemotherapy; BCT: breast-conserving therapy.
* Not all patients with locally advanced, hormone-positive breast cancer will need or benefit from neoadjuvant therapy. This algorithm describes the approach for those who warrant neoadjuvant treatment.
¶ Chemotherapy and HER2-directed therapy are discussed separately. Refer to UpToDate topics on neoadjuvant therapy for patients with HER2-positive breast cancer.
Δ An alternative strategy for medically frail patients who cannot tolerate chemotherapy is HER2-directed therapy plus endocrine therapy. However, responses may be less frequent and less durable than when chemotherapy is incorporated. Refer to UpToDate topics on neoadjuvant therapy for HER2-positive breast cancer, section on HER2-targeted therapy without chemotherapy.
◊ Assessment of medically fit versus frail for the purposes of decisions regarding systemic therapy is discussed separately. Refer to UpToDate topics on general principles on the treatment of early-stage and locally advanced breast cancer in older women.
§ For medically fit patients who warrant neoadjuvant treatment, chemotherapy is the standard approach, provided there are no contraindications. However, we offer endocrine therapy as an acceptable alternative for those who would prefer to avoid chemotherapy, particularly for those with multiple features that would predict a good response to endocrine therapy including low/intermediate grade, estrogen receptor (ER) richness (eg, 50% staining for ER or an Allred score of 7 or 8), and Ki67<15%). Further data are needed to establish the optimal biomarkers for response to neoadjuvant treatment. Refer to UpToDate topics on neoadjuvant therapy for newly-diagnosed hormone receptor positive breast cancer.
¥ Tumors should be reassessed by physical exam routinely during treatment. If there is evidence of progression, patients should proceed directly to surgery.
‡ Aromatase inhibitors are preferred over tamoxifen in neoadjuvant endocrine therapy. For patients who decline or are not tolerant of aromatase inhibitors, tamoxifen is an appropriate alternative.
† While assessment after neoadjuvant treatment is typically via physical exam, imaging may be appropriate in certain instances and is discussed elsewhere. Refer to UpToDate topic on general principles of neoadjuvant therapy for breast cancer, section on clinical assessment and indications for imaging.
** Contraindications for BCT: Multicentric disease, large tumor relative to breast, diffuse malignant-appearing calcifications, prior chest radiation, or pregnancy.
¶¶ Many patients treated with neoadjuvant endocrine therapy are not appropriate candidates for chemotherapy. However, for those who are candidates for chemotherapy, it may be considered as another alternative in the context of poor response to neoadjuvant endocrine therapy.