Hope S. Rugo, MD
As reported by Hope S. Rugo, MD, of the University of California San Francisco Comprehensive Cancer Center, and colleagues in the Journal of Clinical Oncology, ASCO has released a clinical practice guideline on endocrine therapy for hormone receptor–positive metastatic breast cancer.1 The recommendations are based on expert panel review of evidence from 2008 to 2015, with outcomes of interest including sequencing of hormonal agents, hormonal agents compared with chemotherapy, targeted biologic therapy, and treatment of premenopausal women. The panel was co-chaired by Dr. Rugo and Harold J. Burstein, MD, PhD, of Dana-Farber Cancer Center. Key recommendations are reproduced here.
Hormone therapy should be offered to patients whose tumors express any level of estrogen and/or progesterone receptors.
Treatment recommendations should be offered on the basis of the type of adjuvant treatment, disease-free interval, and extent of disease at the time of recurrence. A specific hormonal agent may be used again if recurrence occurs > 12 months from the last treatment.
Harold J. Burstein, MD, PhD
Endocrine therapy should be recommended as initial treatment for patients with hormone receptor–positive metastatic breast cancer, except for patients with immediately life-threatening disease or those experiencing rapid visceral recurrence during adjuvant endocrine therapy.
Treatment should be administered until there is unequivocal evidence of disease progression, as documented by imaging, clinical examination, or disease-related symptoms.
The use of combined endocrine therapy and chemotherapy is not recommended.
Patients should be encouraged to consider enrolling in clinical trials, including those receiving treatment in the first-line setting.
Postmenopausal women with hormone receptor–positive metastatic breast cancer should be offered aromatase inhibitors as part of first-line endocrine therapy.
Combination hormone therapy with a nonsteroidal aromatase inhibitor and fulvestrant (Faslodex) at 500 mg and with a loading schedule may be offered for patients with metastatic breast cancer without prior exposure to adjuvant endocrine therapy.
Premenopausal women with hormone receptor–positive metastatic breast cancer should be offered ovarian suppression or ablation and hormone therapy, because contemporary hormonal agents have only been studied among postmenopausal women.
Sequential hormone therapy should be offered to patients with endocrine-responsive disease, except in the case of rapid disease progression with organ dysfunction; no specific order of agents is recommended.
When fulvestrant is administered, it should be administered using the 500-mg dose and with a loading schedule (treatment start, day 15, day 28, then once a month).
A nonsteroidal aromatase inhibitor and palbociclib (Ibrance) may be offered to postmenopausal women with treatment-naive hormone receptor–positive metastatic breast cancer, because progression-free survival—but not overall survival—was improved compared with letrozole alone.
Exemestane and everolimus (Afinitor) may be offered to postmenopausal women with hormone receptor–positive metastatic breast cancer who experienced disease progression during prior treatment with nonsteroidal aromatase inhibitors with or without one line of prior chemotherapy, either before or after treatment with fulvestrant, because progression-free survival—but not overall survival—was improved compared with exemestane alone.
Fulvestrant and palbociclib may be offered to patients who experienced disease progression during prior treatment with aromatase inhibitors with or without one line of prior chemotherapy, because progression-free survival was improved compared with fulvestrant alone. Treatment should be limited to those without prior exposure to cyclin-dependent kinase 4/6 inhibitors.
The addition of HER2-targeted therapy to first-line aromatase inhibitors should be offered to patients with hormone receptor–positive, HER2-positive metastatic breast cancer in whom chemotherapy is not immediately indicated.
Genomic or expression profiling should not be used at this time to select treatment for hormone receptor–positive metastatic breast cancer.
Tumor markers or circulating tumor cells should not be used as the sole criterion for determining disease progression.
Providers should recognize and acknowledge special issues faced by premenopausal women with metastatic breast cancer, including the loss of fertility.
Treatment should take into account the biology of the tumor and the menopausal status of the patient, with careful attention paid to ovarian production of estrogen.
There is more toxicity associated with the combination of exemestane and everolimus compared with other single-agent endocrine options.
There is more toxicity associated with the combination of palbociclib and endocrine therapy compared with other single-agent endocrine options.
Palbociclib should be administered once a day for 21 days every 28 days; the primary toxicity is neutropenia. Blood cell counts should be monitored every 14 days for the first two 28-day cycles, then at the start of each subsequent cycle, with neutropenia managed by dose delays and reductions. Although no data exist at present, any aromatase inhibitor could be substituted depending on individual tolerance. On the basis of the data from PALOMA-3, palbociclib can also be combined with fulvestrant in the second-line setting or later, including after one line of chemotherapy.
Chemotherapy in combination with HER2-targeted therapy is indicated in de novo and visceral-dominant disease, because this treatment offers a survival benefit compared with chemotherapy alone.
There is no routine clinical role for genomic or expression profiling in the selection of treatment for hormone receptor–positive metastatic breast cancer. ■
Disclosure: For full disclosures of the study authors, visit www.jco.ascopubs.org.
1. Rugo HS, Rumble RB, Macrae E, et al: Endocrine therapy for hormone receptor-positive metastatic breast cancer: American Society of Clinical Oncology guideline. J Clin Oncol. May 23, 2016 (early release online).
Endocrine therapy has been a mainstay of breast cancer treatment for over a century, and the prospects are bright that understanding the molecular pathways driving disease progression and resistance to endocrine agents will lead to the rational development of additional agents to...!-->!-->