A Practice-Changing Study in Breast Cancer Treatment

Hormone-sensitive breast cancer accounts for almost 70% of all patients with breast cancer. British Doctor Beatson demonstrated the benefit of removing women’s ovaries, the first treatment method for this type of breast cancer, through case reports 120 years ago. In 1969, Tamoxifen was first used in patients with metastatic (fourth-stage) hormone-sensitive breast cancer; thereafter hormonal treatments were frequently used in this area and many new hormonal treatment drugs were developed.

The new group of hormonal treatment drugs for hormone-sensitive metastatic breast cancer took treatment success a step beyond Tamoxifen, but the period of benefit from treatment remained at 1-1.5 years. After this period, the average duration of benefit from second-line hormonal treatments could not exceed 4 months. After these treatments, patients necessarily begin chemotherapy.

The most important reason for the reduced duration of benefit from hormonal treatment is the “resistance” mechanisms that cancer cells develop against the drugs we use

In recent years, developments particularly in targeted therapies have also brought about new searches in hormone-sensitive metastatic breast cancer. Particularly with the identification of mechanisms of resistance development, studies combining antihormonal treatment with additional drugs attracted interest. Based on successful studies among these, everolimus (Afinitor), which suppresses an intracellular signaling pathway, in July 2012, and the cell cycle inhibitor drug Palbociclib (Ibrance), in February 2015, received FDA approval and became available for use. Although these agents provide clinical benefits, their side effects limit their use in our daily practice.

Presented at ESMO 2016 and simultaneously published in the respected medical journal New England Journal of Medicine, the MONALEESA-2 study evaluated the use of a cell cycle inhibitor from the same family as Palbociclib, Ribociclib (a CDK4/6 inhibitor), together with the hormone-suppressing drug Letrozole.

The study included 668 newly diagnosed patients with metastatic (fourth-stage) breast cancer who had not yet received any hormonal treatment or chemotherapy. The study showed that using the two drugs significantly increased the time until disease progression compared with Letrozole alone and provided an additional 16% benefit in disease response rate. The clinical benefit rate reached 80% with the Letrozole-Ribociclib combination. While the duration of benefit from treatment was around 14 months in the arm receiving hormonal treatment alone, the duration of benefit in the combined-treatment arm (not yet reached) appears likely to exceed 2 years.

Although a decrease in the number of neutrophils, which are immune cells in the blood, was observed as a side effect, no serious problem related to this side effect occurred in patients. This phase llI study demonstrated that it is a very safe agent in terms of side effects.

The Ribociclib-Letrozole combination, which attracted attention in breast cancer at the ESMO 2016 Congress and was designated a breakthrough therapy by the American drug agency (FDA), has not yet entered clinical use. Ribociclib appears likely to become part of standard treatment for our patients with hormone-sensitive metastatic breast cancer in the near future.

Not all breast cancers are the same. You can find more information about breast cancers in our article entitled “What are the types of breast cancer?”