Prospective Study of Omission of Whole-breast Radiotherapy Following Breast-conserving Surgery in Patients With Very Low Risk Ductal Carcinoma in Situ of the Breast
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- UNICANCER
- 入组人数
- 295
- 试验地点
- 37
- 主要终点
- 5-year cumulative incidence of in-breast cancer recurrences
研究概览
简要总结
Following breast-conserving surgery (BCS) for localized ductal carcinoma in situ (DCIS) of the breast, whole-breast irradiation (WBRT) is a standard of care, reducing the absolute rate of in-breast recurrences (IBR) by more than 15% at 10 years, from 28% without radiotherapy to 13 % with radiotherapy. Half of the recurrences occurred as invasive disease. Whereas in the comparative trials, WBRT did not impact on overall survival, survival of patients who recurred with invasive cancers was impaired in comparison to patients who did not recur, or to patients with DCIS-only recurrences.
Using criteria based on age, tumor size, nuclear grade, and margins status, several trials and cohort studies failed to identify subgroups of patients at low risk, who could be safely spared the need for WBRT. The Radiation Therapy Oncology Group (RTOG) DCIS trial included patients treated with BCS for low- or intermediate grade DCIS revealed by unifocal microcalcifications, size ≤25 mm, margins ≥3 mm, and no residual microcalcifications after surgery. The 5-year rates of IBR were 3.5 % without radiotherapy, versus 0.4 % with radiotherapy, and 6.7 % and 0.9 % at 7 years, respectively (p <0.001). Sixty percent of the patients received tamoxifen in both groups.
Several studies showed that the same molecular classes were identified in DCIS as in invasive cancers. Studies suggested that low proliferation, hormone receptors expression, and lack of ERBB2 amplification were associated with a low risk of IBR in patients not receiving radiotherapy. A combined signature was tested in the Eastern Cooperative Oncology Group (ECOG) trial, showing a 10% IBR rate at ten years in patients with a low-risk.
Identifying very low-risk DCIS, using biological markers in addition to the clinical and histological markers of low-risk DCIS, could help to select patients who could be safely avoided WBRT following BCS. It would avoid over-treatment in these women and could decrease the cost of management.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Woman aged ≥50 years,
- •ECOG performance status ≤2
- •Microcalcifications on pre-biopsy mammography, unifocal, ≤25 mm or opacity without microcalcifications and no clinical palpable tumour
- •Absence of suspicious residual microcalcifications either on post-biopsy/ preoperative localization mammography, or on post-operative mammography Note: if absence of residual microcalcifications on post-biopsy/pre-operative mammography, post-operative mammography is not mandatory;
- •Breast-conserving surgical excision;
- •Histologically proven DCIS of the breast without an invasive component; Note Incidental histological finding of DCIS lesions developed within a benign breast lesion as well as an association with classical lobular carcinoma in situ (LCIS) associated with the DCIS are accepted.
- •Free margins (≥2 mm), or free margins following re-excision;
- •Low or Intermediate nuclear grade; Note: In case of nuclear grade heterogeneity within the same sample or between the biopsy or the surgical specimen, the highest nuclear grade score will prevail.
- •Tumour tissue sample availability; Note: Surgical specimen is mandatory unless no residual disease on the surgical specimen. In this instance, the initial diagnosis biopsy is required.
- •Absence of extensive necrosis (≤30% of the lumen diameter);
- •Immunohistochemical characteristics of luminal A subtype: ER≥10 %, PR ≥20 %, HER2 negative (0/1+) or 2+ not amplified (confirmed by fluorescent in situ hybridization (FISH) or chromogenic in situ hybridization (CISH)), Ki67 <15%.
- •Patient willing and able to comply with the protocol for the duration of the study including undergoing treatment, scheduled visits and examinations and including follow-up;
- •Written informed consent.
- •Affiliation to the French social security.
排除标准
- •Endocrine treatment for breast cancer.
- •Previous invasive breast cancer including contralateral breast cancer, either metachronous or synchronous
- •Previous DCIS except contralateral DCIS in complete and continuous remission for more than 5 years
- •Previous other cancers (except basal-cell, carcinoma in situ of the cervix or endometrium), not in complete and continuous remission for more than 10 years
- •Known breast-cancer predisposing germ-cell mutation;
- •Palpable tumour with a diagnosis of DCIS on biopsy
- •Bloody nipple discharge;
- •Histological size >25 mm in one or multiple foci
- •High nuclear grade, including high nuclear grade in heterogeneous tumours;either on biopsy or on surgical specimen
- •Associated microinvasive or invasive component;
- •Presence of tumour cells in lymph nodes detected using H&E or immunohistochemical examination (if lymph node sentinel biopsy or dissection has been performed);
- •Absolute contra-indication to whole-breast irradiation as determined by the referring physician;
- •Patient unable to comply with study obligations for geographic, social, or physical reasons, or who is unable to understand the purpose and procedures of the study.
- •Pregnant women or breast feeding mothers,
研究组 & 干预措施
Radiotherapy
two fractionation regimens will be allowed for whole-breast irradiation: 50 Gy in 25 fractions over 5 weeks or 40 Gy in 15 fractions over 3 weeks. The delivery of an additional dose to the tumour bed (boost) will be at the referring physician discretion, according to the guidelines
干预措施: Radiotherapy (Radiation)
No Radiotherapy
No Irradiation- Active surveillance
干预措施: No Radiotherapy (Other)
结局指标
主要结局
5-year cumulative incidence of in-breast cancer recurrences
时间窗: 5 years
Incidence of breast recurrence is determined from the date of last surgery to the date of breast recurrence.
次要结局
- Rate of in-breast recurrences (IBR).(10 years)
- Long term toxicities(Throughout study completion, up to 10 years.)
- Relapse-free survival (RFS)(10 years)
- Quality of life of the patients using EORTC-QLQ-BR23(3 years)
- Cosmetics Evaluation(3 years)
- Overall survival (OS)(10 years)
- Quality of life of the patients using EORTC-QLQ-C 30(3 years)
- Breast cancer-specific survival (BCSS)(10 years)
- Rate of Contralateral breast(10 years)