Neoadjuvant Endocrine Therapy in Hormone Receptor-Positive HER2-Negative Node-Negative Breast Cancer Patients to Assess Responses and Mechanisms of Endocrine Resistance
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 37
- 试验地点
- 1
- 主要终点
- Change in Baseline of Cancer Cell Protein Levels of Human Epidermal Growth Factor Receptor (HER) Family Members (HER1-4) Following Neoadjuvant Endocrine Therapy.
研究概览
简要总结
This is an exploratory interventional study that initiates standard-of-care anti-estrogen treatment preoperatively for four weeks.
详细描述
STUDY RATIONALE: Patients with hormone receptor (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 in individual tumors, the team expects to identify predictors of responsiveness to existing agents and identify new candidate therapeutic targets.
PRIMARY OBJECTIVE: The primary objective is to determine the frequency of increased HER family of receptor tyrosine kinases protein expression in tumors, following treatment with neoadjuvant endocrine therapy and their correlation with Ki-67 tumor responses. The team will measure cancer cell protein levels of growth factor receptors of the human epidermal growth factor receptor (HER) family before and after neoadjuvant endocrine therapy. The data will be used to inform a future randomized trial of combined endocrine and the most promising anti-HER targeted therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Female; age ≥18 years.
- •Pathologically proven diagnosis of invasive breast cancer, clinically stage I-II.
- •Clinically lymph node negative, confirmed by clinical exam and/or ultrasound imaging.
- •Estrogen- and/or progesterone-receptor-positive tumor, defined ≥1% positively staining cells by immunohistochemistry, according to the current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines.
- •HER2/neu must be negative by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH).
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-
- •Pretreatment evaluations (minimum diagnostic workup) within 28 days prior to study
- •Qualify for anti-endocrine treatment (per medical oncologist).
- •Informed consent provided.
- •If history of contralateral breast cancer, patient completed all treatment two years prior
- •No treatment for this breast cancer or any malignancy within two years (except non-melanomatous skin cancer, carcinoma in situ of the cervix and contralateral breast cancer)
- •Using adequate methods of contraception; negative pregnancy test.
- •No strong CYP2D6 inhibitors.
- •Adequate organ function with baseline lab values.
- •Absolute neutrophil count (ANC) ≥ 1500/µL.
- •Hemoglobin (Hb) ≥ 9g/dL.
- •Platelet count ≥ 100,000/µL.
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3x upper limit of normal (ULN).
- •Serum bilirubin within ≤ 1.5 x ULN.
排除标准
- •American Joint Committee on Cancer (AJCC) clinical T4, N1-3 or M1, breast cancer.
- •Synchronous non-breast malignancy (exceptions include non-melanomatous skin cancer, carcinoma in situ of the cervix).
- •Purely noninvasive breast cancer (i.e., ductal carcinoma in situ, lobular carcinoma in situ).
- •Men with breast cancer.
- •Medical, psychiatric or other condition that would prevent the patient from receiving the protocol therapy or providing informed consent.
- •Pregnant or lactating women.
研究组 & 干预措施
Neoadjuvant endocrine therapy treatment (physician's choice)
Once enrolled, patients would be treated with the current standard-of-care endocrine therapy. 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. The patient would be treated with endocrine therapy in a neoadjuvant setting for four weeks, with dosing continuing until surgery.
干预措施: Anastrozole (Drug)
Neoadjuvant endocrine therapy treatment (physician's choice)
Once enrolled, patients would be treated with the current standard-of-care endocrine therapy. 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. The patient would be treated with endocrine therapy in a neoadjuvant setting for four weeks, with dosing continuing until surgery.
干预措施: Letrozole (Drug)
Neoadjuvant endocrine therapy treatment (physician's choice)
Once enrolled, patients would be treated with the current standard-of-care endocrine therapy. 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. The patient would be treated with endocrine therapy in a neoadjuvant setting for four weeks, with dosing continuing until surgery.
干预措施: Exemestane (Drug)
Neoadjuvant endocrine therapy treatment (physician's choice)
Once enrolled, patients would be treated with the current standard-of-care endocrine therapy. 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. The patient would be treated with endocrine therapy in a neoadjuvant setting for four weeks, with dosing continuing until surgery.
干预措施: Tamoxifen (Drug)
结局指标
主要结局
Change in Baseline of Cancer Cell Protein Levels of Human Epidermal Growth Factor Receptor (HER) Family Members (HER1-4) Following Neoadjuvant Endocrine Therapy.
时间窗: At four weeks.
ImmunoHistoChemistry (IHC) will be used. The IHC test gives a score of 0 to 3+ that measures the amount of HER2 receptor protein on the surface of cells in a breast cancer tissue sample. If the score is 0 to 1+ (up to 25% of cells stained), it's called "HER2 negative." If the score is 2+ (approximately 50% of cells stained), it's called "borderline." A score of 3+ (approximately 75% or more of cells stained) is called "HER2 positive." Upregulation means increased staining from a prior observation; Downregulation means decreased staining from a prior observation; and No Change means similar staining from a prior observation.
次要结局
- Number of Subjects Who Achieve Complete Radiographic Response.(At four weeks.)
- Number of Subjects Who Achieve a Partial Radiographic Response.(At four weeks.)
研究者
Lubna Chaudhary
Associate Professor
Medical College of Wisconsin