HER2-positive Breast Cancer, Breast Cancer
Conditions
Keywords
HER2-positive Breast Cancer, Breast Cancer, Memorial Sloan Kettering Cancer Center, 26-385
Brief summary
The purpose of this study is to find out whether it is safe to skip (omit) radiation therapy to the breast after lumpectomy in people with low-risk HER2-positive breast cancer who are receiving HER2-targeted therapy.
Interventions
Participants will continue to receive standard HER2-targeted therapy as part of their usual care
DRUGTamoxifen
If participants' cancer is hormone receptor-positive, participants may also receive endocrine therapy as part of their usual care.
RADIATIONNo Radiation Therapy
Participants will not receive radiation therapy to their breast after their lumpectomy.
Sponsors
Memorial Sloan Kettering Cancer Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
A patient cannot be considered eligible for this study unless ALL of the following conditions are met. Please contact the study PI for exceptions, or if uncertainties arise. * The trial is open to female and male patients who have undergone breast conserving surgery and have received neoadjuvant\* or adjuvant systemic therapy with a HER2-targeted therapeutic regimen. * The maximum window between surgery (neoadjuvant cohort) or last chemotherapy (adjuvant cohort) and enrollment is 90 days. * While the standard duration of neoadjuvant or adjuvant systemic therapy is at least 12 weeks, patients will be eligible if they receive a minimum of 8 weeks of systemic therapy. Patients treated with an antibody-drug conjugate (ADC; eg. T-DM1 or T-DXd) must have received at least 6 cycles of this treatment. \*For the neoadjuvant cohort: Patients are eligible if they achieved pCR with HER2-targeted preoperative treatment. Pathologic complete response is defined as ypT0/TisN0 based on surgical pathology. Patients treated with and ADC must have received at least 6 cycles of this treatment. * The patient must be ≥18 years of age. * The patient must have an ECOG performance status of 0, 1, or 2/Karnofsky performance status above 60. * Histologically or cytologically confirmed invasive breast carcinoma. * The tumor must have been determined to be HER2-positive by current ASCO/CAP guidelines based on local testing results. * The tumor must have ER and PgR status assessed. * The following staging criteria must be met according to AJCC 8th edition criteria: Adjuvant cohort * Following resection, the patient's primary tumor must be ≤ 3 cm. * Surgical axillary evaluation via sentinel node biopsy or axillary dissection * Surgical lumpectomy margins must be negative for invasive cancer and ductal carcinoma in situ (no ink on tumor). Neoadjuvant cohort: * Prior to neoadjuvant therapy, the patient's primary tumor must be \<5 cm by imaging studies with negative axillary nodes (cN0) based on axillary U/S, CT, PET or MRI. Physical examination alone is not sufficient documentation of cN0 status. * The patient must have undergone surgical axillary nodal evaluation demonstrating ypN0 (eg. axillary node dissection, sentinel node biopsy with at least 3 sentinel lymph nodes removed, or sentinel node biopsy followed by axillary node dissection). * Must be ypT0/TisN0 at surgery (lumpectomy); patients with residual non invasive disease (DCIS) in the surgical specimen (ypTis), are only eligible if residual DCIS spans ≤1 cm, and surgical margins are negative for DCIS. * Bilateral mammogram or MRI within 52 weeks prior to enrollment.
Exclusion criteria
* Definitive clinical or radiologic evidence of metastatic disease. * On the Adjuvant cohort, patients with a primary tumor \>3 cm on pathologic examination of the surgical specimen. On the Neoadjuvant cohort, patients with a primary tumor \>5 cm or with abnormal or suspicious ipsilateral axillary nodes by pretreatment imaging, unless demonstrated to be negative by cytologic or histologic examination. * Pathologically positive axillary nodes at any time including of pN0(i+) or pN0(mol+) ypN0(i+) or ypN0(mol+) disease. * Patient planning for or status-post mastectomy. * Radiographically suspicious ipsilateral or contralateral axillary, supraclavicular, infraclavicular, or internal mammary lymph nodes, unless there is histological confirmation that these nodes are negative for metastatic disease. * Suspicious microcalcifications, densities, or palpable abnormalities (in the ipsilateral or contralateral breast), or mass or non-mass enhancement on MRI (if performed) aside from the known cancer, unless biopsied and found to be benign. * Non-epithelial breast malignancies such as sarcoma or lymphoma. * Multicentric carcinoma (invasive cancer or DCIS) in more than one quadrant or multifocal disease spanning \>4 cm. If multifocal, all foci should be confined to a maximum summed tumor extent of 3 cm determined by pathological assessment. * Paget's disease of the nipple. * Synchronous contralateral invasive breast cancer or DCIS or synchronous ipsilateral invasive breast cancer of a different histology. (Patients with synchronous and/or previous contralateral LCIS are eligible). * On the Adjuvant cohort, surgical margins that cannot be microscopically assessed or are positive at pathologic evaluation. (If surgical margins are rendered free of disease by re-excision, the patient is eligible). * Treatment plan that includes regional nodal irradiation. * Patients treated for a prior invasive breast malignancy are excluded. Contralateral DCIS ≥10 years prior to enrollment is permissible. * Patients on oral, transdermal, or subdermal estrogen replacement (including all estrogen only and estrogen-progesterone formulas) are not eligible unless discontinued prior to enrollment. * Use of any investigational product within 30 days prior to enrollment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ipsilateral breast recurrence/IBR rate | 5 years | To assess whether omission of adjuvant breast radiotherapy among patients with early-stage, low risk HER2+ breast cancer who undergo breast conserving surgery and receive HER2-directed therapy, results in an acceptable rate of 5 year ipsilateral breast recurrence (IBR). |
Countries
United States
Contacts
CONTACTLior Braunstein, MD
CONTACTDiana Roth O'Brien, MD
PRINCIPAL_INVESTIGATORLior Braunstein, MD
Memorial Sloan Kettering Cancer Center
Outcome results
None listed