Expert Perspectives in Metastatic Breast Cancer - Episode 8

Treating ER-Positive De Novo Metastatic Breast Cancer

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Moderator Adam Brufsky, MD, PhD, presents a case study focused on the treatment of a 60-year-old woman with estrogen receptor (ER)—positive, metastatic de novo breast cancer. The patient has predominately bone metastases, with 1-2 lymph node metastases, he notes.

The ideal frontline therapy for this patient might be a nonsteroidal aromatase inhibitor, Ruth O’Regan, MD, states. However, the combination of fulvestrant and anastrozole could also be considered, although still investigational. Regardless of the endocrine therapy selected, this patient will likely have a good outcome, O'Regan notes.

If single-agent treatment was decided upon, findings from the phase II FIRST trial could shed light on which therapy to use, O'Regan suggests. In this study, fulvestrant improved overall survival by 5.7 months compared with anastrozole as a frontline treatment for postmenopausal women with HR-positive metastatic breast cancer. The CDK 4/6 inhibitor palbociclib also represents a promising treatment for patients with ER-positive breast cancer, adds O'Regan. Results from a phase III study exploring the drug in combination with letrozole will be presented at the 2015 ASCO Annual Meeting.

The combination of palbociclib and letrozole was approved in February 2015, as a frontline treatment for postmenopausal women with ER-positive, HER2-negative metastatic breast cancer. In the open-label phase II study that led to its approval, treatment with the combination reduced the risk of disease progression by 51% compared with letrozole alone. The median progression-free survival with palbociclib was 20.2 versus 10.2 months for letrozole alone (HR = 0.49; P = .0004).

In patients who have relapsed after a prior therapy, unlike the de novo patient discussed in this case study, it is important to conduct a biopsy to confirm ER status, Lee Schwartzberg, MD, comments. In up to 20% of patients, the phenotype could change between the initial treatment and the development of metastatic disease. Immunohistochemistry tests are known to have many technical difficulties, says Richard Finn, MD, noting that ER testing discordance was reported to be 20% by ASCO/CAP.