Key findings:

The abstract highlights the occurrence of radiation recall dermatitis (RRD), an acute skin reaction induced by certain agents post-radiotherapy, with tamoxifen being reported as a triggering factor. This case underscores the potential of tamoxifen, commonly used in breast cancer treatment, to induce RRD, expanding the understanding of adverse reactions in cancer therapy.

What is known and what is new?

The abstract outlines the established knowledge that radiation recall dermatitis (RRD) can occur following the administration of certain agents post-radiotherapy. However, the novelty lies in reporting a case of RRD specifically induced by tamoxifen, expanding the understanding of potential triggers for this acute skin inflammatory reaction in patients undergoing breast cancer treatment.

What is the implication, and what should change now?

The occurrence of radiation recall dermatitis induced by tamoxifen highlights the need for careful monitoring and management of patients undergoing breast cancer treatment. Clinicians should be aware of this potential side effect when prescribing tamoxifen, especially in patients who have previously undergone radiotherapy. Close surveillance and prompt intervention are essential to mitigate the impact of this adverse reaction on patient well-being.

Despite using modern and safer methods of oncological treatment, patients receiving radiotherapy as part of treatment for cancer are still exposed to post-radiation adverse effects within the irradiated skin or mucous membranes [3]. Irradiation has a high risk of early and late adverse reactions [4]. The frequency and severity of radiation-induced skin changes depend on many factors: location and schedule of radiotherapy, radiation dose, and individual sensitivity of the skin [5]. Skin areas particularly predisposed to radiation-induced reactions are the armpits, nipples and folds under the breasts [6]. Tamoxifen and radiotherapy are used in breast cancer treatment all over the world. Herein, we report a case of radiation recall dermatitis induced by tamoxifen.

A 43 years old woman was diagnosed with cancer of the right breast in March 2019. The patient underwent Modified Radical Mastectomy with axillary lymph node dissection. The histopathological analysis revealed a 3x4.5-cm invasive ductal carcinoma with 2/15 lymph node metastasis. On IHC, the patient was positive for estrogen and progesterone receptor while the human epidermal growth factor receptor 2 was negative (by FISH). The patient received four cycles of doxorubicin and cyclophosphamide every 21 days, followed by four cycles of taxanes as adjuvant treatment. The patient received hypofractionated radiation treatment (45 Gy in 15 fractions) to the right chest wall, axillary and supraclavicular lymph node. Patient was then started on hormonal treatment (Tamoxifen 20 mg/day).

In February 2021, the patient developed a heating sensation, tenderness, edema, and redness at the irradiated area of the right breast with well-bordered erythematous-infiltrative-oedematous lesions located on the skin of the right arm and shoulder and the anterior and posterior chest wall on the right side that matched the radiation field. As per patient, the appearance of skin lesions was preceded by flu-like symptoms (musculoskeletal pain – joint pain, fever to 39°C, weakness – 5 days before hospitalization). Complete blood count demonstrated that the TLC was 5,300/µl (normal range, 4,000–8,600/µl), indicating that there was no inflammatory response, and all other measurements were within normal ranges. Breast ultrasonography detected skin hypertrophy in the area of redness. Despite erythema on the skin of the affected breast initially suggesting the presence of inflammatory breast cancer, the patient did not exhibit any signs of inflammation (burning sensations or pain). As there was no dilation seen in the lymphatic vessels, it was unlikely that the patient had inflammatory breast cancer. Furthermore, a PET scan was performed confirming that there was no breast cancer recurrence. The symptoms were consistent with RRD. As the patient was only taking tamoxifen at that time, Tamoxifen was immediately stopped and the patient started on prednisolone and NSAIDS.

Radiation recall dermatitis is a condition triggered by drug administration following radiation therapy, and is characterized by an inflammatory response localized to the irradiated body area [7-11]. Although the precise mechanism underlying radiation recall dermatitis is unknown, it has been proposed that increased local vascular permeability, transforming growth factor β1 (TGF-β1) overexpression or the expression of inflammatory cytokines may cause this condition [7, 8]. It has also been hypothesized that the condition is triggered by specific drugs that are administered days to years after exposure to ionizing radiation [9].

Tamoxifen is used worldwide as a standard endocrine therapy for HR-positive breast cancer [12]. In Western countries, cases of tamoxifen (TAM)-induced radiation recall dermatitis have been reported in which the condition was triggered by the administration of anti oestrogen following radiation therapy for breast cancer. In prior reports, based on the following clinical findings the diagnosis of tamoxifen-induced RRD was confirmed: 1) localized symptoms of an acute inflammatory skin reaction at previously irradiated areas, 2) symptom development and worsening during tamoxifen treatment, 3) no other therapy provoking RRD, and 4) negative test results for infection and/or breast cancer recurrence or other malignancy [7, 8].

The patient in our study also experienced localized acute inflammatory symptoms in the irradiated area of her right chest wall without any evidence of infection during tamoxifen treatment. The possibility of breast cancer recurrence was excluded on PET scan and on spontaneous resolving of skin lesion after stopping Tamoxifen.

Funding: No funding sources.

Conflict of interest: None declared.

Ethical approval: The study was approved by the Institutional Ethics Committee of Dr. Rajendra Prasad Government Medical College.

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