Successful case of breast conservation radiotherapy in a patient with type III Ehlers‐Danlos syndrome

To the Editor: Ehlers-Danlos syndrome (EDS) is an inherited connective tissue disorder with defective or deficient collagen. There is extremely limited literature on radiotherapy tolerance in EDS patients but concerns exist due to anecdotal evidence of fatal cerebrovascular aneurysm rupture in a patient with suspected EDS. Greater evidence exists for severe toxicities associated with collagen vascular diseases (CVD), which are generally considered a relative contraindication for radiotherapy. We present a 42 year old premenopausal woman with diagnosed type III EDS whose screening mammogram found a circumscribed 1.6 cm mass in the upper outer quadrant of the right breast. After further evaluation, core needle biopsy showed estrogen receptor (ER) and progesterone receptor (PR) positive, HER2/neu negative mucinous carcinoma . After counseling on breast conservation therapy versus mastectomy, the patient elected to undergo lumpectomy with axillary node dissection. Final pathology report showed a 2 cm Nottingham Grade II mucinous/colloid carcinoma with clear surgical margins and no lymphatic invasion, perineural or lymph node involvement. Because her tumor tested as low risk by Oncotype DX, Tamoxifen was recommended instead of adjuvant chemotherapy. Given that EDS is associated with impaired connective tissue function and potentially fatal complication, serious concern was raised regarding her risk of severe thoracic injuries and poor cosmetic outcome. After extensive discussion, the patient elected to undergo post-lumpectomy breast radiotherapy. Over 45 calendar days, she received 4680 centigray (cGy) in 26 daily fractions to the right breast with two tangential fields using mixed 6 and 16 MV photons. The lumpectomy tumor bed and incision scar received an additional 1400 cGy in seven fractions with enface electron therapy using 12 MeV electrons. The radiation course was completed without interruption. Acutely, the patient experienced fatigue and a maximum of Radiation Therapy Oncology Group (RTOG) and Common Toxicity Criteria for Adverse Events (CTCAE) grade III radiation dermatitis (Table 1). She developed right breast fold tenderness and edema 3 weeks into radiotherapy which became grade II dermatitis consisting of a 1.5-2 cm focus of wet desquamation by 5 weeks. The affected area further progressed to grade III toward the end of radiotherapy (Figure 1). During this time, the patient endorsed breast pain, discomfort, and feeling distressed. She received supportive care with topical skin moisturizers, antibiotics ointment, wound dressings and oral nonsteroid anti-inflammatory drugs. Hypermobility type III EDS is a milder variant which exhibits less impaired wound healing relative to classical type I and II, whereas vascular type IV features severe aneurysm, arterial dissection, and visceral rupture. Few cases of radiotherapy in EDS patients have been reported and no clear recommendations currently exist. A 62 year old woman with presumptive type III EDS who received whole brain irradiation for metastatic breast ductal carcinoma suffered a delayed, fatal basilar artery aneurysm rupture. In contrast, a 50 year old man with type IV EDS received radiation therapy for mediastinal hemangioendothelioma without significant toxicities. In addition, a 71 year old woman with type IV EDS underwent uncomplicated frontal lobe stereotactic radiosurgery for lung TABLE 1 Radiation Therapy Oncology Group (RTOG) and National Cancer Institute’s Common Toxicity Criteria for Adverse Events (CTCAE) Scoring System