Improving Breast Cancer Outcomes Through Neoadjuvant Therapy

Posted on by Peter Rigney

Improving Breast Cancer Outcomes Through Neoadjuvant Therapy:

Insights from the Society of Surgical Oncology and the American Society of Breast Surgeons

Here is a summary of the article, which looked at neoadjuvant therapy over the last 40 years. The article is from Weiss et al. Annals of Surgical Oncology 32:5453–5466

Key Advantages of NST

The article emphasizes three primary benefits of NST for both operable and non-operable breast cancers:

  • De-escalation of surgical interventions: NST can shrink tumors, allowing more patients to undergo breast-conserving surgery instead of mastectomy.
  • Improved understanding of survival based on pathologic complete response (pCR): Achieving a pCR (no residual cancer in the breast and lymph nodes after treatment) is a strong indicator of better long-term outcomes, especially in aggressive subtypes.
  • Ability to tailor adjuvant therapy: The response to NST helps guide subsequent treatment decisions, allowing for either escalation or de-escalation of adjuvant therapies to improve survival.

NST by Breast Cancer Subtype

The review details tailored approaches to NST based on breast cancer subtypes:

HER2-Positive Breast Cancer

  • Historically aggressive HER2+ breast cancer treatment has been revolutionized by targeted therapies like trastuzumab and pertuzumab, significantly increasing pCR rates.
  • The KATHERINE trial demonstrated that patients with residual disease after NST benefit significantly from adjuvant ado-trastuzumab emtansine (T-DM1), reducing recurrence and death risk.
  • NST is now standard for most HER2+ cases, with ongoing research focusing on de-escalation for those with excellent responses and escalation for those with residual disease.

Triple-Negative Breast Cancer (TNBC)

  • TNBC lacks estrogen, progesterone, and HER2 receptors and has been challenging to treat.
  • Adding platinum-based therapies and, more recently, immunotherapy (checkpoint inhibitors like pembrolizumab) to NST has significantly improved pCR rates and event-free survival for TNBC patients.
  • For patients with residual disease after NST, adjuvant capecitabine or olaparib (for BRCA-mutated cases) has shown improved outcomes. Current guidelines recommend NST with immunotherapy for most stage II/III TNBC.

Hormone Receptor-Positive (HR+) Breast Cancer

  • Compared to HER2+ and TNBC, HR+ breast cancer generally has lower pCR rates with chemotherapy, and pCR is less prognostic.
  • Neoadjuvant endocrine therapy (NET) is an effective and less toxic alternative to chemotherapy for post-menopausal HR+ patients, often facilitating breast-conserving surgery.
  • Genomic assays (e.g., Oncotype DX, MammaPrint) are increasingly used to determine the benefit of chemotherapy for HR+ patients, often leading to de-escalation of chemotherapy in lower-risk cases.

Surgical Management After NST

  • NST has led to a notable increase in breast-conserving surgery (BCS) rates and a de-escalation in axillary surgery.
  • Pre-treatment clip placement is recommended for tumor localization. MRI is valuable for assessing residual disease, particularly in HER2+ and TNBC.
  • Current evidence supports applying the “no tumor on ink” margin guideline for BCS after NST, similar to upfront surgery.
  • Excitingly, research explores the omission of surgery in select patients who achieve a complete response to NST, though this requires further robust clinical trials.
  • For lymph nodes, NST can achieve high nodal pCR rates. For clinically node-negative disease, sentinel lymph node biopsy (SLNB) after NST is considered safe.

– Alan Stolier        

Dr. Alan Stolier, MD, FACS, clinical breast oncologist

Dr. Alan Stolier, MD, FACS, clinical breast oncologist, shares his expert medical perspective with a series of educational and scientific articles.

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