Understanding Neoadjuvant Therapy for Breast Cancer: A Comprehensive Patient Guide

Table of Contents

• Summary and Recommendations
• Introduction to Neoadjuvant Therapy
• Goals of Treatment
• Understanding Medical Terminology
• Patient Selection Criteria
• Pretreatment Evaluation Process
• Neoadjuvant Treatment Options
• Post-Treatment Evaluation and Management
• Management of the Axilla (Underarm Area)
• Special Considerations
• Clinical Implications for Patients
• Study Limitations
• Source Information

Introduction to Neoadjuvant Therapy

Neoadjuvant therapy refers to systemic treatment of breast cancer administered before definitive surgical therapy. Typically, this treatment involves chemotherapy, though there's growing interest in using neoadjuvant endocrine therapy for certain patient groups. This approach has evolved from being used primarily for locally advanced cancers to now being considered for many patients with operable breast cancers.

The fundamental purpose of this treatment sequence is to address the cancer systemically before local surgical intervention. This sequencing allows doctors to assess how your cancer responds to treatment, which provides valuable information for planning subsequent therapies. The treatment approach discussed here follows the anatomic staging system from the eighth edition of the American Joint Committee on Cancer (AJCC) Staging Manual.

Goals of Treatment

While all systemic therapy for non-metastatic invasive breast cancer aims to reduce distant recurrence risk, administering it before surgery serves several specific purposes. The primary goals include downstaging the tumor (making it smaller) and providing critical information about treatment response that guides future decisions.

Downstaging tumors may allow for less extensive breast and axillary surgery. This can mean avoiding mastectomy in favor of breast-conserving surgery, improving cosmetic outcomes, and reducing postoperative complications like lymphedema. Research shows neoadjuvant chemotherapy increases breast-conserving therapy rates from 49% to 65% compared to adjuvant approaches.

Neoadjuvant therapy also lets doctors evaluate systemic treatment effectiveness. The presence and extent of residual invasive cancer after treatment strongly predicts recurrence risk, particularly for triple-negative breast cancer (TNBC) and human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Additionally, this approach provides researchers opportunities to obtain tumor specimens and blood samples that may help identify biomarkers of treatment response or resistance.

Despite early hopes that neoadjuvant therapy might improve overall survival by starting systemic treatment earlier, randomized trials show equivalent mortality rates whether similar therapy is given before or after surgery. A major analysis of 4,756 women across 10 trials conducted between 1983-2002 found identical 15-year distant recurrence rates (38% in both groups) and breast cancer mortality rates (34% in both groups).

Understanding Medical Terminology

This discussion uses both clinical and pathological staging in management decisions. Key terminology includes:

• Pathological staging after neoadjuvant therapy uses "y" designation (ycTN for clinical stage, ypTN or ypTNM for pathologic stage)
• Pathological complete response (pCR) requires absence of residual invasive disease in both breast and sampled axillary nodes (ypT0/is ypN0)
• Residual in situ carcinoma doesn't affect distant recurrence risk in patients with no residual invasive cancer

Patient Selection Criteria

Discussions between surgical and medical oncologists are crucial for determining which patients might benefit from neoadjuvant therapy. Potential candidates include:

• Locally advanced breast cancer patients (stage III disease, T3, or T4 lesions) - These cancers often aren't amenable to upfront resection, and their high distant recurrence risk warrants systemic treatment
• Select early-stage breast cancer patients (stage I or II) - Appropriate when breast-conserving surgery isn't possible due to high tumor-to-breast ratio or suboptimal cosmetic outcomes due to tumor location
• Patients with triple-negative or HER2-positive cancers - Even smaller (T1c) cancers may benefit, especially if residual disease identification could guide additional treatments
• Patients with limited clinically node-positive disease (cN1) - Neoadjuvant therapy can downstage axillary nodes, potentially avoiding extensive lymph node dissection
• Patients with temporary surgery contraindications - Such as women diagnosed during pregnancy or those requiring short-term anticoagulation

The role of neoadjuvant therapy in hormone receptor-positive, HER2-negative cancers is less clear. While chemotherapy rarely yields pathological complete response in these cases (typically less than 10-15%), it often induces sufficient tumor shrinkage to allow breast conservation instead of mastectomy.

Pretreatment Evaluation Process

Before starting neoadjuvant therapy, doctors conduct comprehensive evaluations to confirm pathology and document disease extent:

Tumor evaluation requires histopathologic confirmation and receptor status assessment (estrogen receptor, progesterone receptor, and HER2). A radiopaque clip should be placed in the tumor during diagnostic biopsy to mark the site for future surgical guidance and pathological assessment.

Imaging studies document disease extent before treatment. Ultrasound typically suffices for tumor size documentation, but breast MRI may help evaluate multifocal/multicentric disease, especially in patients with dense breast tissue. Routine CT, bone, or PET/CT scans are typically omitted for clinical stage I/II disease but ordered for stage III disease or inflammatory breast cancers.

Node evaluation involves physical axillary exams in all newly diagnosed patients. For palpable nodes, ultrasound-guided fine needle aspiration (FNA) or core needle biopsy (CNB) confirms pathological involvement. For non-palpable nodes, axillary ultrasound is routine. Suspicious nodes on ultrasound undergo FNA or CNB, with false-negative rates of 20-25% for FNA and slightly lower for CNB.

For biopsy-proven involved lymph nodes, doctors favor placing a radiopaque clip or marker to enable identification after neoadjuvant therapy. Removing marked nodes during post-treatment sentinel lymph node biopsy reduces false-negative rates from 10.1% to 1.4% according to prospective studies.

Neoadjuvant Treatment Options

Chemotherapy remains the standard neoadjuvant approach for most patients, including those with locally advanced hormone receptor-positive disease. However, endocrine therapy may be appropriate for certain hormone receptor-positive patients.

Treatment selection depends on cancer subtype:

• HER2-negative cancers receive neoadjuvant chemotherapy regimens tailored to individual circumstances
• HER2-positive cancers receive HER2-targeted agents concurrent with all or part of their chemotherapy

The choice between chemotherapy and endocrine neoadjuvant therapy for hormone receptor-positive patients depends on multiple factors including patient age, comorbidities, clinical stage, tumor grade, hormone-receptor expression intensity, and proliferation indices like Ki-67 or gene expression assay results.

Post-Treatment Evaluation and Management

Definitive surgery should proceed as soon as patients recover from treatment toxicities, typically within 3-6 weeks after completing neoadjuvant therapy. Post-treatment evaluation includes physical examination and imaging studies using the modality that best demonstrated initial disease extent.

The correlation between tumor measurements by physical exam, imaging (mammography, ultrasound, or MRI), and final pathological analysis is modest due to variable tumor response patterns. These range from symmetric shrinkage around a central core to apparent complete resolution despite persistent microscopic cancer foci.

Repeat breast imaging may not be necessary for patients with clear contraindications to breast-conserving therapy or those choosing mastectomy regardless of eligibility. PET scans aren't sufficiently sensitive for routine residual disease assessment after neoadjuvant therapy.

Management of the Axilla (Underarm Area)

Post-neoadjuvant therapy axillary management depends on pre-treatment node status, biopsy results, and post-treatment clinical node status:

Clinically negative axilla before treatment: Patients without lymph node involvement evidence before or during neoadjuvant therapy should undergo post-treatment sentinel lymph node biopsy (SLNB). A meta-analysis of 16 studies (1,456 women) showed a 96% sentinel node identification rate and 6% false-negative rate in this population.

SLNB typically occurs concurrently with breast surgery. Patients should know that axillary lymph node dissection (ALND) might be performed during the same operation if intraoperative analysis shows persistent disease in sampled nodes.

• If post-treatment SLNB is negative (ypN0), no further axillary treatment is needed
• If post-treatment SLNB is positive (ypN+), axillary lymph node dissection is typically recommended

Special Considerations

Patients with SLNB before treatment: While generally discouraged, if sentinel lymph node biopsy was performed before neoadjuvant therapy, results impact post-treatment management. Resection of positive SLNs before therapy means axillary response cannot be fully assessed since the node was removed.

Poor response or progression: Patients showing poor response or disease progression during neoadjuvant therapy require individualized management plans, potentially including switching chemotherapy regimens or proceeding directly to surgery.

COVID-19 pandemic considerations: Treatment protocols may be adjusted during pandemic conditions to balance cancer treatment needs with infection risk mitigation.

Clinical Implications for Patients

Neoadjuvant therapy offers several potential benefits for breast cancer patients:

1. Increased breast conservation rates: Research shows neoadjuvant chemotherapy increases breast-conserving therapy from 49% to 65% compared to adjuvant approaches
2. Reduced axillary surgery complications: Converting clinically node-positive patients to pathologically node-negative status may allow sentinel node biopsy instead of full axillary dissection, reducing lymphedema risk
3. Personalized treatment guidance: Response to neoadjuvant therapy provides valuable prognostic information that helps tailor subsequent treatments
4. Earlier systemic treatment: Addressing potential micrometastases sooner rather than later

However, patients should understand that neoadjuvant therapy is associated with a slightly increased risk of local recurrence (15-year local recurrence rate of 21.4% versus 15.9% with adjuvant therapy), attributed mainly to increased breast-conserving surgery use.

Study Limitations

Several limitations should be considered when interpreting data on neoadjuvant therapy:

• Most cited studies used previous editions of staging systems to define patient populations
• The individual patient data meta-analysis included trials initiated between 1983-2002, before many current treatment advances
• False-negative rates for axillary node assessment methods range from 20-25% for FNA and slightly lower for CNB
• Correlation between imaging measurements and pathological findings is modest due to variable tumor response patterns
• Further randomized trials comparing neoadjuvant versus adjuvant therapy impact on overall survival may not be feasible

Source Information

Original Article Title: General principles of neoadjuvant management of breast cancer
Authors: William M Sikov, MD, FACP, FNCBC; Judy C Boughey, MD, FACS; Zahraa Al-Hilli, MD, FACS, FRCSI
Section Editor: Harold J Burstein, MD, PhD
Deputy Editors: Sadhna R Vora, MD; Wenliang Chen, MD, PhD
Literature Review Current Through: February 2021
Topic Last Updated: February 10, 2021

This patient-friendly article is based on peer-reviewed research from UpToDate, an evidence-based clinical decision support resource. The content is not intended as a substitute for medical advice, diagnosis, or treatment. Always seek advice from your physician regarding any medical questions or conditions.