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Pre-Operative Window of Endocrine Therapy to Inform Radiation Therapy Decisions in Older Women with Early Stage Estrogen Receptor Positive Breast Cancer, the POWER II Trial
Trial Status: active
This phase III trial compares the effect of adding pre-operative endocrine therapy to lumpectomy to surgery alone in determining treatment with post-operative radiation therapy in older women with early stage estrogen receptor positive (ER+) breast cancer. Historically, women over 65 with early-stage ER+ breast cancer are treated with surgery to remove the mass (lumpectomy) with or without radiation followed by endocrine therapy. Endocrine therapy lowers the amount of estrogen made by the body or blocks the use of estrogen by the tumor cells. This may help stop the growth of tumor cells that need estrogen to grow. Radiation therapy can be used after surgery to treat early-stage breast cancer and uses high-energy rays to kill cancer cells. Current guidelines indicate radiation is not necessary for in women 65 or older with early stage ER+ breast cancer taking endocrine therapy after surgery. However, if a patient does not get radiation therapy and is unable to take the prescribed number of years of endocrine therapy, the risk of recurrence increases. Alternatively, radiation therapy may not be needed if endocrine therapy is tolerable. Pre-operative endocrine therapy with lumpectomy may be effective in determining treatment with post-operative radiation therapy in older women with early stage ER+ breast cancer.
Inclusion Criteria
Diagnosis of ER+, progesterone receptor (PR)+/-, and HER2- (according to American Society of Clinical Oncology [ASCO]/College of American Pathologists [CAP] guidelines for HER2 testing) non amplified invasive breast cancer and clinically negative nodes;
* Histologic subtypes: Any invasive breast cancer histologic subtype may be enrolled
* Tumor size based on diagnostic breast imaging: ≤ 3 cm
** T size ≤ 2.0 cm: any grade (1-3)
** T size 2.1-3.0 cm: grade 1 or 2 and no lymphovascular invasion (LVI)
** Tumor size will be estimated via review of diagnostic imaging. When there is a size discrepancy on different imaging modalities, treating investigator may determine which best estimates actual tumor size and participant eligibility
* Multifocal disease criteria: Primary tumor and satellite lesion are allowed if the primary tumor meets other inclusion criteria and a single lumpectomy is planned.
* Note the following additional guidance on disease specific inclusion criteria:
** Clinically node negative (cN0) may be determined by exam or imaging. Axillary ultrasound is not required; however, if an ultrasound is completed and shows an abnormal node the treating physician must assess it to be clinically negative
** Performing sentinel lymph node biopsy at the time of surgery will be at the discretion of treating physician
** Gene expression profiling of tumor is not required or mandated for eligibility. However, if gene expression profiling is performed on the diagnostic biopsy specimen, this should be completed prior to enrollment and, the result must be consistent with low risk (ex: Oncotype recurrence score of 25 or less, low risk by Mammaprint, Prosigna, Endopredict, etc.)
Eastern Cooperative Oncology Group (ECOG) performance status 0-2
Females, aged ≥ 65 years
Patient is eligible for BCS and opted for BCS
Patient is a candidate for radiation therapy
Patient is a candidate for endocrine therapy (tamoxifen or an aromatase inhibitor)
Ability to take oral medication and be willing to adhere to endocrine therapy for the 3-month period prior to BCS
Agreement to adhere to lifestyle considerations throughout study duration
Provision of signed and dated informed consent form
Stated willingness to comply with all study procedures and availability for the duration of the study
Exclusion Criteria
Bilateral synchronous breast cancer
Multicentric disease
Prior use of tamoxifen or aromatase inhibitors
History of ipsilateral breast radiation therapy
Has a known additional malignancy that is progressing and/or requires active treatment with cytotoxic chemotherapy or radiation therapy. Malignancies deemed stable and low risk for complication per investigator’s judgment may be allowed after discussion with multi-site principal investigator (PI)
Current or planned use of a strong CYP2D6 inhibitor (e.g., fluvoxamine, paroxetine) and is not able to receive an endocrine therapy agent that does not use the CYP2D6 pathway
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT06507618.
I. To determine whether treatment with pre- endocrine therapy (ET) compared to standard of care results in a decrease in treatment with breast conservation surgery (BCS) alone.
II. To determine whether treatment with pre- ET compared to standard of care results in a decrease in treatment with BCS + radiation therapy (RT) + adjuvant endocrine therapy (AET).
SECONDARY OBJECTIVES:
I. To determine whether treatment with pre-ET lessens Decision Conflict and Regret.
II. To assess whether patients’ final treatment correlates with their beliefs about breast cancer.
III. To assess whether treatment with pre-ET leads to improved Health Related Quality of Life compared to those treated with standard of care.
IV. To assess whether early side effects of ET correlate with patient treatment group within study arms.
V. To obtain data on recurrence and survival.
EXPLORATORY OBJECTIVES:
I. To assess long-term adherence to AET.
II. To assess whether patients’ final treatment correlates with their beliefs about breast cancer.
III. To assess whether short-term, patient-derived organoids can be established from larger pieces of surgical tissue of trial participants who have received AET.
IV. To evaluate whether larger pieces of surgical tissue can be cryopreserved for short-term organoid derivation after thawing and dissociation.
V. To evaluate whether patient-derived organoids exhibit short-term responses to endocrine therapy and radiotherapy that are patient-specific.
VI. To explore artificial intelligence algorithms as a means for calculating a prognostic score within breast tumors.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive ET for 90 days then undergo lumpectomy on day 91 with or without post-operative radiation and AET.
ARM II: Patients undergo lumpectomy with or without post-operative radiation and AET.
After completion of study intervention, patients are followed up at 90 days, 6, 12, 18 and 24 months.
Trial PhasePhase III
Trial Typetreatment
Lead OrganizationUniversity of Virginia Cancer Center
