Treatment of small (T1mic, T1a, and T1b) node-negative HER2+ breast cancer – a review of current evidence for and against the use of anti-HER2 treatment regimens

ABSTRACT

Introduction

Since the advent of anti-HER2 therapies, evidence surrounding adjuvant treatment of small (T1mic, T1a, and T1b), node-negative, HER2-positive breast cancer (HER2+ BC) has remained limited. Practices vary widely between institutions with little known regarding the added benefit of systemic therapy, including cytotoxic chemotherapy and HER2-directed treatments. Our group has set out to perform an extensive review of available literature on this topic.

Areas covered

In this review, we examined HER2 biology, anti-HER therapies, outcome definitions, and available prospective and retrospective data surrounding the use of adjuvant therapy in those with small, node-negative, HER2+ BC. For outcomes, we primarily explored breast cancer-specific survival (BCSS), invasive disease-free survival (iDFS), and overall survival (OS). We also investigated the incidence of adverse events with a particular focus on symptomatic and asymptomatic declines in ejection fraction.

Expert opinion

Retrospective data will likely be the main driver for future treatment decisions. Given what we know, high-risk T1b and T1c subgroups derive measurable added benefit from HER2-guided combination therapies but it’s not clear whether these benefits outweigh known risks associated with this combination therapy. For tumors ≤0.5 cm (T1mic and T1a), treatment remains highly controversial with limited evidence available through retrospective analysis that suggest over-treatment may be occurring.

KEYWORDS:

• Adjuvant therapy
• HER2-positive
• N0
• node-negative
• recurrence
• small
• DFS
• t1mic
• t1a
• t1b
• breast cancer

Article highlights

• In T1mic and T1a N0 disease, adjuvant HER2-directed chemotherapy remains controversial and studies point towards potential overtreatment.

• In T1b and T1c N0 disease, current retrospective data suggests added treatment benefit based on improved cancer specific survival outcomes and recurrence rates

• Prospective trials have shown impressive rates of iDFS, but no improvements in OS have been demonstrated to date. Furthermore, prospective trials have used historical controls in place of untreated control arms due to the high patient volume required for enrollment in order to evaluate the presence of any statistically significant benefit.

Acknowledgments

The authors would like to thank investigators, funding bodies, and patients who contributed to the knowledge contained in this review.

Compliance with ethics

This study is solely a review of available literature and did not involve access to patient-specific data.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This work was funded by NIH grant T32 CA247815 given contributions from Dr. Dionisia Quiroga.