Locoregional therapy in breast cancer patients treated with neoadjuvant chemotherapy

ABSTRACT

Introduction: Neoadjuvant chemotherapy (NAC) is increasingly used preoperatively in breast cancer patients to achieve disease downstaging, reduce distant dissemination, and assess chemosensitivity. While NAC indications are expanding, knowledge of its impact on subsequent locoregional treatment with surgery and radiation therapy (RT) decisions is evolving. Radiation oncologists are often called upon to estimate locoregional recurrence (LRR) risks and provide recommendations for adjuvant RT to the breast/chest wall and regional lymph nodes postoperatively. In the non-NAC setting, adjuvant RT decisions are guided by the pathology findings after definitive surgery. In the NAC setting, decisions for or against adjuvant RT are complex, particularly in patients who achieve complete pathologic response (pCR).

Areas covered: This review will examine contemporary data on NAC in patients with breast cancer and discuss its impact on surgical and RT decisions. We will also evaluate controversies in the role of LRRT for these patients, focussing on prognostic factors that include biological subtypes and pCR after NAC.

Expert opinion: Advances in personalized medicine and diagnostic techniques have shifted paradigms and increased complexities in locoregional treatment decisions, particularly in the setting of NAC. Despite the challenges, our goals while we await prospective data remain focused on improving survival, minimizing toxicity, and optimizing function and cosmesis.

KEYWORDS:

• Breast cancer
• complete pathologic response
• locoregional radiotherapy
• locoregional recurrence
• neoadjuvant chemotherapy
• postmastectomy radiotherapy
• surgery

Article highlights

• Retrospective and prospective data guiding LRRT after NAC are limited by a lack of molecular subtype information and contemporary systemic therapy regimens, including targeted therapies.

• Post-NAC surgery is evolving toward breast conservation and sentinel node biopsy in select individuals, and consequently the role of LRRT is expected to increase.

• LRRT is well tolerated, but identifying patients who are unlikely to derive significant benefit from this treatment is important to reduce the incidence of late side effects, particularly in those receiving extensive surgery (i.e., mastectomy, reconstruction, and/or axillary node dissection) who may be at increased risk of such complications.

• Pathologic complete response (pCR) is a well-established prognostic factor in patients treated with NAC, but its impact on locoregional recurrence risk and radiotherapy recommendations remains unclear.

• Among retrospective studies of NAC, it is generally accepted that LRRT has a role if pCR is not achieved, but its benefit in patients who do achieve pCR is controversial.

• Attempts have been made to identify risk factors predicting increased locoregional recurrence, some resulting in the creation of nomograms to guide treatment decisions, which often reference clinical T stage, pathologic stage after NAC, and overall stage.

• As prospective data are required to formulate evidence-based guidelines for patients treated with NAC, the results of ongoing studies including the NSABP B-51/RTOG 1304 and Alliance A11202 trials are eagerly awaited.

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.