
Introduction
International guidelines highly recommend adjuvant trastuzumab for breast cancer with HER2+;
- specifically, immunohistochemistry (IHC 3+, over expression) or fluorescence in situ hybridisation (FISH) amplified
- affect 20% of all breast cancer cases
Addition of 1 year of adjuvant trastuzumab to adjuvant chemotherapy significantly improved disease- free survival (DFS) and overall survival (OS) among women with HER2+ breast cancer (non-metastatic).
- Reduces the risk of death by 33%-59% (NCCTH, BCIRG 006, HERA, FinHer)
In Malaysia, public hospitals with oncology services offer 12 months course of adjuvant trastuzumab to suitable breast cancer patients with N+ (nodal positive) and/ or T4 (locally advanced) at minimal cost.
As treatment is expensive and exceed 60k – 80k per patients, quota system is allocation for first-come-first-basis until yearly quota finishes.
Cardiac related side effects (congestive heart failure, contractile dysfunction) are serious side effect that triggers treatment interruption (postponement, stopping treatment).

Trials with treatment de-escalation (reducing duration of trastuzumab treatment), were conducted to see if 6 months treatment could reduce cardiac toxicity and still achieve results as good as 12 months treatment.
Previously, PHARE trial (6 months vs 12 months Herceptin) in 2005, failed to show 6 months treatment with trastuzumab was non-inferior to 12 months of trastuzumab.
- 2-year disease-free survival (DFS) was 93·8% in the 12-month group and 91·1% in the 6-month group.
- 5.7% patients in 12 month treatment group experienced cardiac event vs 1.9% in 6 month treatment group.
Other studies that failed to show non-inferiority of shorter duration trastuzumab were phase 3 trials; Short-HER and SOLD (see below) study.

PERSEPHONE trial was supposed to finally validate the importance of 12 months trastuzumab treatment. However, the results, which was recently announced in large oncology meeting (ASCO 2018) successfully shown non-inferiority of 6 months vs 12 months treatment with trastuzumab.
- 4-year disease-free survival (DFS) were 89.8% with 12 months of trastuzumab compared with 89.4% with the 6 month course.
- Cardiac events halved, 4% vs 8%, for 6 months vs 12 months trastuzumab treatment, respectively.
- Details of overall survival wasn’t reported in detailed, just that results were congruent/ same for both treatment courses.
- Need to read the full paper once it’s made available.

Finally
How will PERSEPHONE trial change my practice?
I will be very cautious to change my practice based on just one paper.
The 6-months course of trastuzumab treatment for highly selected patients who are:
- Early breast cancer (tumor size < 2cm, no nodal involvement/ N0)
- Patients who needed dose interruptions (treatment delay, dose modifications) for cardiac events but not serious enough to warrant stopping treatment altogether.
- Those who might have financial difficulties completing 12 months course