Breast Cancer
Conditions
Brief summary
This is a prospective, phase 2, single arm trial to evaluate whether Axillary Lymph Node Dissection (ALND) can be safely omitted for patients with cN2 and cN3 breast cancer who achieve a complete clinical response on exam with a complete or partial response by end-of-treatment (EOT) imaging and have either a partial or complete pathologic nodal response after neoadjuvant chemotherapy (NAC) by performing nodal assessment of sentinel lymph node surgery (with or without targeted axillary dissection (TAD) followed by Regional Nodal Irradiation (RNI). This study aims to demonstrate that performing only a sentinel node dissection, which includes the removal of palpably gross disease followed by radiation, will not impact distant disease and thus survival.
Interventions
PROCEDUREAxillary Surgery
Patients who are clinically node negative after neoadjuvant chemotherapy by physical examination will undergo clinically indicated breast surgery (mastectomy or lumpectomy) with sentinel lymph node (SLN) surgery. Sentinel lymph node surgery must be performed within 8 weeks (56 days) after completion of the last dose of neoadjuvant chemotherapy.
Sponsors
University of Kansas Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Ability of participant to understand this study, and participant willingness to sign a written informed consent. NOTE Remote consenting allowed per IRB policy and approval. 2. Stated willingness to comply with all study procedures and lifestyle considerations and availability for the duration of the study 3. Males and/or females age ≥ 18 to 80 years 4. Clinical stage T1-3 N2-3 M0 breast cancer at diagnosis (prior to the start of neoadjuvant chemotherapy). 5. Patients stage T1-3 cN1 (prior to start of neoadjuvant chemotherapy) and pN2-3 breast cancer based on number of positive nodes on final surgical pathology. 6. All patients must have had an axillary ultrasound with FNA or core needle biopsy of axillary lymph nodes documenting axillary metastasis at the time of diagnosis, prior to or at most 14 days after starting neoadjuvant chemotherapy. 7. Patients must have had estrogen receptor, progesterone receptor and HER2 status (by IHC and/or ISH) evaluated on diagnostic core biopsy prior to start of neoadjuvant chemotherapy. Note: If HER2 status has not been clearly determined (i.e. equivocal/indeterminate), then patients should not be enrolled (see
Exclusion criteria
). 8. Patients must have completed planned chemotherapy (neoadjuvant chemotherapy \[NAC\]) prior to surgery. Sandwich chemotherapy is not allowed (i.e. chemotherapy planned to be given after surgery). Adjuvant systemic therapy based on final surgical pathology is allowed and at the discretion of the treating medical oncologist. Note: Delays/dose modifications due to toxicities/adverse events are allowed per the treating medical oncologist. 9. Patients with HER-2 positive tumors must have received neoadjuvant trastuzumab, or trastuzumab + pertuzumab, or other approved anti-HER-2 therapy (either with all or with a portion of the neoadjuvant chemotherapy regimen). Therapy must be FDA-approved targeted anti-HER2 therapy, but additional therapies are allowed as are non-trastuzumab regimens if administered in the context of an IRB-approved clinical trial. 10. Benign breast disease, LCIS or DCIS of contralateral breast is allowed 11. All patients must have a clinically negative axilla (no bulky adenopathy) on physical examination documented at the completion of neoadjuvant chemotherapy. Note: A partial or complete imaging response that includes all lymph nodes measuring ≤ 1cm clinically is required for eligibility. 12. ECOG (Zubrod) Performance Status 0-1 (Appendix A) 13. A minimum of 1 sentinel node must be identified and excised by the surgeon. Patients who do not have an identifiable sentinel lymph node will not proceed to omission of ALND. 14. Patients that have a pathologic complete response (pCR) in the breast and axilla can be considered for discussion at the Breast Multidisciplinary Tumor Conference for omission of radiation. Note: Isolated tumor cells (metastases less than or equal to 0.2 mm) will be treated as node negative disease (N0i+). 15. Breast surgery (lumpectomy or mastectomy) and sentinel lymph node surgery must be completed within 56 days of the completion of the last dose of neoadjuvant chemotherapy. Negative margin (by either breast conservation or mastectomy) on final pathology where negative margin is defined as no tumor on ink. 16. Females of childbearing potential must have a negative serum pregnancy at day of surgery in pre-operative holding prior to initiating treatment. 17. Females of child-bearing potential and males with partners of child-bearing potential must agree not to donate sperm, to practice sexual abstinence or to use the forms of contraception listed in Child-Bearing Potential/Pregnancy section for the duration of study participation and, following the last administration of therapy , for as long as directed per standard or care chemotherapy (investigational regimen allowed) and radiation therapy, whichever is longer. Note: Peri-menopausal women must be amenorrheic for ≥ 12 months to be considered not of childbearing potential. Definition of medically fit for surgery: * ECOG status of 0-1 * NOTE - participants are eligible for surgery if they have nicotine in the blood or high A1c. These values will be monitored per SOC.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Free Survival (DFS) | 5 years | To determine if radiation to the undissected axilla and regional lymph nodes is not inferior to axillary lymph node dissection with regional nodal irradiation (excluding dissected axilla) for DFS after neoadjuvant chemotherapy response. DFS assessed according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v6.0. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Invasive Breast Cancer Recurrence Free Interval (IBC - RFI) | 5 years | To assess if radiation to the undissected axilla and regional nodes is not inferior to axillary dissection plus regional nodal radiation for IBC-RFI, DSS, and LRR in patients with complete or partial response to neoadjuvant chemotherapy. Determined by medical record. |
| Disease Specific Survival (DSS) | 5 years | To assess if radiation to the undissected axilla and regional nodes is not inferior to axillary dissection plus regional nodal radiation for IBC-RFI, DSS, and LRR in patients with complete or partial response to neoadjuvant chemotherapy. Determined by medical record. |
| Locoregional Recurrence (LRR) | 5 years | To assess if radiation to the undissected axilla and regional nodes is not inferior to axillary dissection plus regional nodal radiation for IBC-RFI, DSS, and LRR in patients with complete or partial response to neoadjuvant chemotherapy. Determined by medical record. |
| Lymphedema Incidence | Measured at 9 months, annually, and PRN (as needed) per patient reported symptoms, over a duration of approximately 5 years. | To estimate the incidence of arm lymphedema in participants that undergo SLN with comprehensive RNI. Determined by Bioimpedance Spectroscopy |
| Recurrence Cancer Burden (RCB) Score | Measured at final surgical pathology (up to 21 days after surgery) | To estimate the distribution or Recurrence Cancer Burden (RCB) Score |
| Imaging positive predictive value for extent of nodal disease burden compared to final surgical pathology and lab draws | Measured at final surgical pathology (up to 21 days after surgery) | Assessed by MRI, US, and final surgical pathology. The same imaging modality used to assess nodal adenopathy at baseline must be used throughout. RECIST v 1.1 criteria will be used for assessments. |
Contacts
CONTACTKUCC Navigation
PRINCIPAL_INVESTIGATORJamie Wagner, D.O.
The University of Kansas Cancer Center
Outcome results
None listed