Molecular Analyses to Predict Pathways of Endocrine Resistance Following Short Term Neoadjuvant Endocrine Treatment in Patients With Hormone Receptor-Positive HER2-negative Breast Cancer (MAPPER)
Summary
This is an exploratory phase II interventional study that initiates standard-of-care anti-estrogen treatment preoperatively for 4-12 weeks (+/- 2 weeks).
Detailed description
Patients with HR+ HER2- node-negative breast cancers generally undergo surgical resection upfront, followed by adjuvant chemotherapy, if needed, in addition to adjuvant endocrine therapy. Because endocrine therapy is primarily delivered in the postoperative setting, the ability to assess the tumor response to this treatment modality is lost and very difficult to assess. This study offers the unique opportunity to assess the responsiveness of breast tumors to endocrine therapy while the tumors are still in vivo by treating patients with endocrine therapy before surgery and assessing molecular changes with treatment. By comparing pre- and post-treatment levels of molecular markers with advanced omic analysis in individual tumors, the investigators expect to identify predictors of responsiveness to existing agents and identify new candidate therapeutic targets.
Arms & interventions
- DrugAromatase inhibitors or tamoxifen
Choice of endocrine therapy (aromatase inhibitors or tamoxifen) would be decided by medical oncologist, following a review of the patient's medical history and menstrual status.
Outcome measures
Primary
Change from baseline in the number of subjects with increased HER-1 receptor tyrosine kinases protein expression in tumors.
Pathologists will use immunohistochemistry (IHC) to determine the average count of tumor protein expression. IHC is reported categorically as 0,1, 2 or 3. Any increase between these categories is considered increase.
Time frame: Time of surgery
Change from baseline in the number of subjects with increased HER-2 receptor tyrosine kinases protein expression in tumors.
Pathologists will use immunohistochemistry to determine the average count of tumor protein expression. IHC is reported categorically as 0,1,2 or 3. Any increase between these categories is considered increase.
Time frame: Time of surgery
Change from baseline in the number of subjects with increased HER-3 receptor tyrosine kinases protein expression in tumors.
Pathologists will use immunohistochemistry to determine the average count of tumor protein expression. IHC is reported categorically as 0,1,2 or 3. Any increase between these categories is considered increase.
Time frame: Time of surgery
Change from baseline in the number of subjects with increased HER-4 receptor tyrosine kinases protein expression in tumors.
Pathologists will use immunohistochemistry to determine the average count of tumor protein expression. IHC is reported categorically as 0,1,2 or 3. Any increase between these categories is considered increase.
Time frame: Time of surgery
Eligibility criteria
Study locations (1)
Froedtert Hospital and the Medical College of Wisconsin
Milwaukee, Wisconsin, 53226