Patient case: 70-year-old female with breast cancer; genetic feature: AURKA amplification

Clinical trial: Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction

Summary: Overall rationale: Prophylactic NAC irradiation after nipple-areola sparing mastectomy and immediate reconstruction for patient with ductal carcinoma in-situ or invasive breast cancer will allow better cosmesis and patient's satisfaction:
  -  The use of NAC-sparing mastectomy followed by postoperative NAC (nipple-areola complex) external beam radiotherapy for selected patient with early stage invasive or in-situ breast cancers will be technically feasible and with acceptable complication rates.
  -  The cosmetic results after NAC-sparing mastectomy followed by postoperative external beam radiotherapy to the NAC will be better comparable with Skin Sparing Mastectomy.
  -  The local control rate in the NAC will be more than expected for a NAC sparing mastectomy without postoperative radiotherapy.
  -  The patient's satisfaction after NAC-sparing mastectomy followed by postoperative NAC external beam radiotherapy will be better than after Skin Sparing Mastectomy.

Detailed description: Study design: Phase I trial assessing the safety, feasibility and toxicity of prophylactic NAC irradiation after nipple-areola sparing mastectomy and immediate reconstruction in patients with ductal carcinoma in-situ or invasive breast cancer.
  Primary objective: To determine the recommended phase I dose of post-operative prophylactic NAC irradiation.
  Secondary objectives: To provide extensive descriptive data regarding NAC-sparing surgery with reconstruction, including both surgeon experience and patient evaluation of cosmetic results. Survival and recurrence will be assessed.
  Study size: Between 12 and 18 patients will be enrolled in the dose-escalation/deescalation part of this phase I study. An additional expansion cohort of 12 patients will be enrolled at the "potential" recommended phase II dose (RP2D) over an expected accrual period of 2 years.

Eligibility: Inclusion Criteria:
  -  Patients must have histologically confirmed in-situ or invasive breast carcinoma.
  -  Tis, T1, T2 invasive or non-invasive carcinoma of the breast; lesion less than 4 cm.
  -  Unifocal, multifocal or multicentric breast cancers that can be removed by nipple sparing mastectomy with negative surgical margins.
  -  No extensive intraductal component or patient with distant metastases.
  -  Patients must be > 18 years of age.
  -  No concomitant or history of nipple discharge or skin involvement.
  -  No prior history of malignancy (less than 5 years prior to study entry), except non-melanomatous skin cancer.
  -  No prior history of radiation to the chest.
  -  No collagenous disease (systemic lupus erythematosis, scleroderma, dermatomyositis)No previous non-hormonal therapy including radiation or chemotherapy for current breast cancer.
  -  No patients with Paget's disease of the nipple.
  -  No patients with co-existing medical conditions with life expectancy < 2 years.
  -  No pregnant or lactating women.
  -  Eastern Cooperative Oncology Group (ECOG) 0 - 2.
  -  Signed study-specific informed consent form prior to the study entry.
  Exclusion Criteria:
  -  Retroareolar breast cancer lesions within one cm, depth from the skin surface.
  -  Concomitant or history of nipple discharge or skin involvement.
  -  Patient with distant metastases.
  -  Patient with extensive intraductal carcinoma.
  -  Any previously irradiated ipsilateral breast cancer.
  -  Patients with Paget's disease of the nipple.
  -  Patients with collagenous diseases, as systemic lupus erythematosis, scleroderma or dermatomyositis.
  -  Other malignancy, except nonmelanomatous skin cancer, less than 5 years prior to participation in this study.
  -  Patients who are pregnant or lactating due to potential exposure of the fetus to RT and unknown effects of RT to lactating females.
  -  Positive surgical margins following nipple sparing mastectomy.

Relevance to patient case: not relevant