A Phase III Clinical Trial Evaluating De-Escalation of Breast Radiation for Conservative Treatment of Stage I, Hormone Sensitive, HER-2 Negative, Oncotype Recurrence Score Less Than or Equal to 18 Breast Cancer
概览
- 阶段
- 3 期
- 干预措施
- Radiation and Endocrine Therapy (Tamoxifen, Anastrozol, Letrozole, Exemestane)
- 疾病 / 适应症
- Stage I Breast Cancer
- 发起方
- NRG Oncology
- 入组人数
- 1670
- 试验地点
- 1589
- 主要终点
- Time to invasive or noninvasive IBTR.
- 状态
- 招募中
- 最后更新
- 17天前
概览
简要总结
This Phase III Trial evaluates whether breast conservation surgery and endocrine therapy results in a non-inferior rate of invasive or non-invasive ipsilateral breast tumor recurrence (IBTR) compared to breast conservation with breast radiation and endocrine therapy.
详细描述
Breast conservation therapy for early stage breast cancer has been an important achievement of oncology practice in the last half century and breast radiotherapy (RT) has been essential in its development. Several seminal randomized clinical trials conducted in the 1980's era demonstrated that breast radiotherapy following lumpectomy yielded overall survival outcomes equivalent to mastectomy for treatment of early stage invasive breast cancer leading to the National Institute of Health (NIH) Consensus Conference statement in 1991 supporting breast conservation treatment.This established lumpectomy with RT as an alternative to mastectomy and subsequently the rate of breast conservation for eligible breast cancer patients rose steadily. Shortly thereafter, investigators recognized that the toxicity, patient burden, and geographic barriers associated with the protracted treatment course for breast RT was a potential barrier to breast conservation utilization. Numerous phase III clinical trials were conducted randomizing women post lumpectomy to RT vs. observation aimed at identifying which cases did not derive a significant RT benefit. No such subsets of breast cancer patients were consistently identified, thereby solidifying the standard that breast conservation required both lumpectomy and RT. Two meta-analyses by the Early Breast Cancer Trialists Collaborative Group (EBCTCG) in 2005 and 2011 further reinforced the value of breast RT post lumpectomy by examining the relationship of local recurrence and breast cancer mortality relative to the use of breast RT post lumpectomy. In each analysis, it found for axillary node negative breast cancer patients undergoing breast conservation a small but consistent increase in breast cancer mortality when breast radiotherapy was omitted. As a result, breast RT after lumpectomy has become an established paradigm for breast conservation for early stage breast cancer and is recommended by the NCCN 2018 guidelines (as it has for nearly two decades) that are commonly used today by clinicians and health systems alike. The landscape of early stage breast cancer has changed dramatically over the past three decades since the establishment of breast conservation. Widespread screening with mammography has led to the diagnosis of smaller and earlier stage disease. All breast cancers are now routinely characterized by their hormone sensitivity based on the presence of estrogen and progesterone receptors on tumor cells within the biopsy or surgical specimen and presence of HER2 (human epidermal growth factor receptor 2) which has provided an additional means of stratifying breast cancer into distinct prognostic groups. Small, node negative invasive breast cancer that is hormone sensitive (HS) and HER2-negative has a lower overall recurrence rate (local, regional, and distant) than breast cancers characterized by more adverse clinical pathologic features. However, other than in a smaller subset of women greater than 70 years old, clinical trials in this HS population still demonstrated unacceptable local recurrence risks long term after lumpectomy alone emphasizing that clinical and pathologic features are insufficient for consistently identifying when RT can safely be omitted.
研究者
入排标准
入选标准
- •• The patient or a legally authorized representative must provide study-specific informed consent prior to pre-entry/Step 1 and, for patients treated in the U.S., authorization permitting release of personal health information.
- •The patient must have an ECOG performance status of 0 or
- •The patient must have undergone a lumpectomy and the margins of the resected specimen or re-excision must be histologically free of invasive tumor and DCIS with no ink on tumor as determined by the local pathologist. If pathologic examination demonstrates tumor at the line of resection, additional excisions may be performed to obtain clear margins. (Patients with margins positive for LCIS are eligible without additional resection.)
- •The tumor must be unilateral invasive adenocarcinoma of the breast on histologic examination.
- •Patient must have undergone axillary staging (sentinel node biopsy and/or axillary node dissection).
- •The following staging criteria must be met postoperatively according to AJCC 8th edition criteria:
- •By pathologic evaluation, primary tumor must be pT1 (less than or equal to 2 cm).
- •By pathologic evaluation, ipsilateral nodes must be pN
- •(Patients with pathologic staging of pN0(i+) or pN0(mol+) are NOT eligible.)
- •Oncotype DX Recurrence Score of less than or equal to 18 on diagnostic core biopsy or resected specimen.
排除标准
- •• Definitive clinical or radiologic evidence of metastatic disease.
- •pT1 mi and pT2 - pT4 tumors including inflammatory breast cancer.
- •Pathologic staging of pN0(i+) or pN0(mol+), pN1, pN2, or pN3 disease.
- •Patient had a mastectomy.
- •Palpable or radiographically suspicious ipsilateral or contralateral axillary, supraclavicular, infraclavicular, or internal mammary nodes, unless there is histologic confirmation that these nodes are negative for tumor.
- •Suspicious microcalcifications, densities, or palpable abnormalities (in the ipsilateral or contralateral breast) unless biopsied and found to be benign.
- •Non-epithelial breast malignancies such as sarcoma or lymphoma.
- •Proven multicentric carcinoma (invasive cancer or DCIS) in more than one quadrant or separated by 4 or more centimeters. (Patients with multifocal carcinoma are eligible.)
- •Paget's disease of the nipple.
- •Any history, not including the index cancer, of ipsilateral invasive breast cancer or ipsilateral DCIS treated or not treated. (Patients with synchronous or previous ipsilateral LCIS are eligible.)
研究组 & 干预措施
Arm 1: Breast Radiation Therapy + Endocrine Therapy
Radiation therapy to the breast and hormonal drug for at least 5 years. Tamoxifen 20 mg daily Anastrozole 1 mg daily Letrozole 2.5 mg daily Exemestane 25 mg daily
干预措施: Radiation and Endocrine Therapy (Tamoxifen, Anastrozol, Letrozole, Exemestane)
Arm 2: No Breast Radiation Therapy + Endocrine Therapy
No radiation therapy, only hormonal drug for at least 5 years. Tamoxifen 20 mg daily Anastrozole 1 mg daily Letrozole 2.5 mg daily Exemestane 25 mg daily
干预措施: Endocrine Therapy (Tamoxifen, Anastrozol, Letrozole, Exemestane)
结局指标
主要结局
Time to invasive or noninvasive IBTR.
时间窗: 5 years
Time from randomization to any invasive or noninvasive IBTR or last follow-up (expressed as % IBTR-free)
次要结局
- Percent of women with an intact index breast at report of the primary endpoint inclusive of salvage second breast conservation procedures.(Through study completion, an average of 15 years.)
- Time from randomization to the first occurrence of invasive ipsilateral breast tumor recurrence.(5 years)
- Time from randomization to diagnosis of a local, regional or distant recurrence as a first cancer event.(5 years)
- Time from randomization to the first distant cancer event (either a recurrence or a secondary primary cancer).(5 years)
- Time from randomization to any death.(5 years)