HR+/HER2– Advanced Breast Cancer Treatment in the First-Line Setting: Expert Review

Katarzyna J. Jerzak (1), Nathaniel Bouganim (2), Christine Brezden-Masley (3), Scott Edwards (4), Karen Gelmon (5), Jan-Willem Henning (6), John F. Hilton (7), Sandeep Sehdev (7)
(1) Odette Cancer Centre, Sunnybrook Health Sciences, Toronto, ON M4N 3M5, Canada
(2) Cedars Cancer Centre, McGill University Health Centre, Montreal, QC H4A 3J1, Canada
(3) Marvelle Koffler Breast Centre, Mount Sinai Hospital, Toronto, ON M5G 1X5, Canada
(4) Dr. H. Bliss Murphy Cancer Center, St. John’s, NL A1B 3V6, Canada
(5) Faculty of Medicine, University of British Columbia, Vancouver, BC V5Z 1M9, Canada
(6) Tom Baker Cancer Centre, Calgary AB T2N 4N2, Canada
(7) The Ottawa Hospital Cancer Centre, ON K1H 8L6, Canada

The approval of CDK4/6 inhibitors has dramatically improved care for the treatment of HR+/HER2– advanced breast cancer, but navigating the rapidly-expanding treatment evidence base is challenging. In this narrative review, we provide best-practice recommendations for the first-line treatment of HR+/HER2– advanced breast cancer in Canada based on relevant literature, clinical guidelines, and our own clinical experience. Due to statistically significant improvements in overall survival and progression-free survival, ribociclib + aromatase inhibitor is our preferred firstline treatment for de novo advanced disease or relapse ≥12 months after completion of adjuvant endocrine therapy and ribociclib or abemaciclib + fulvestrant is our preferred first-line treatment for patients experiencing early relapse. Abemaciclib or palbociclib may be used when alternatives to ribociclib are needed, and endocrine therapy can be used alone in the case of contraindication to CDK4/6 inhibitors or limited life expectancy. Considerations for special populations – including frail and fit elderly patients, as well as those with visceral disease, brain metastases, and oligometastatic disease – are also explored. For monitoring, we recommend an approach across CDK4/6 inhibitors. For mutational testing, we recommend routinely performing ER/PR/HER2 testing to confirm the subtype of advanced disease at the time of progression and to consider ESR1 and PIK3CA testing for select patients. Where possible, engage a multidisciplinary care team to apply evidence in a patient-centric manner.

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