Patient case: 45-year-old female with cervical cancer; genetic feature: ERBB2 (S310Y)

Clinical trial: Radiotherapy Omission in Low Risk Ductal in Situ Carcinoma Breast

Summary: 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 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 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.


Eligibility: Inclusion Criteria:
  1. Woman aged >50 years,
  2. Postmenopausal Status; Note: Note: woman is considered post-menopausal if she has had amenorrhea for 12 months or more or has undergone surgical oophorectomy.
  3. ECOG performance status ≤2
  4. Microcalcifications on pre-operative mammography, unifocal, ≤25 mm;
  5. Absence of residual microcalcifications on post-operative mammography;
  6. Breast-conserving surgical excision;
  7. Histologically proven DCIS of the breast without an invasive component; Note: histological finding of DCIS lesions associated with or developed in a benign breast lesion or in case of a classical LCIS associated with the DCIS are accepted.
  8. Free margins (≥2 mm), or free margins following re-excision;
  9. Low or Intermediate nuclear grade; Note: In case of nuclear grade heterogeneity, the higher -grade score will prevail.
  10. 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.
  11. Absence of extensive necrosis;
  12. Immunohistochemical characteristics of luminal A subtype: ER ≥10 %, PR ≥20 %, HER2 negative (0/1+) or 2+ not amplified (confirmed by FISH or CISH), Ki67 <15%.
  13. 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;
  14. Written informed consent;
  15. Affiliation to the French social security.
  Exclusion Criteria:
  1. Endocrine treatment for breast cancer;
  2. Previous diagnosis of DCIS or invasive cancer, (except basal-cell, carcinoma in situ of the cervix or endometrium);
  3. Synchronous bilateral DCIS;
  4. Known breast-cancer predisposing germ-cell mutation;
  5. Palpable tumour opacity or bloody nipple discharge;
  6. Histological evidence of multifocality (defined as having more than one distinct focus of DCIS with >5 mm of intervening benign breast tissue in one quadrant of the breast);
  7. High nuclear grade, including high nuclear grade in heterogeneous tumours;
  8. Associated microinvasive component;
  9. Presence of tumour cells in lymph nodes detected using H&E or immunohistochemical examination (if lymph node sentinel biopsy or dissection has been performed);
  10. Absolute contra-indication to whole-breast irradiation as determined by the referring physician;
  11. 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.

Relevance to patient case: not relevant