Bloom syndrome is defined by a number of characteristics, including growth retardation, immunodeficiency, early development of age-related comorbidities, a predisposition to early and varied cancers, and increased sensitivity to drug toxicity [8]. In general, leukemia and lymphoma are the most prevalent neoplasms in individuals with BS. Among solid tumors, colorectal and other gastrointestinal cancers are common, but cancer of almost all organ systems has been observed [9]. In a prospective study by Sugranes TA et al., among the 290 individuals with BS, 155 developed cancer, with 100 (65%) diagnosed with a single cancer. The remaining 55 patients (35%) developed multiple cancers, with an average interval of 6 years between the first and second malignancies. Among 251 neoplasms, 83 (33%) were hematologic and 168 (67%) were solid tumors. Hematologic malignancies were more prevalent than any of the solid tumors. The most frequently observed solid tumors were colorectal, breast, and oropharyngeal. The second most common malignancies were leukemia and breast cancer, each present in 10 patients (18%). The observed cases of acute myeloid leukemia occurred subsequently to chemotherapy treatments for the primary cancer and were typically preceded by myelodysplastic syndrome. The cumulative incidence of any malignancy by age 40 was 83%. The median survival for all participants was 36.2 years [10]. Similarly, the patient with BS developed both breast cancer and MDS-EB2 during the follow-up period, with an overall survival of 33 years. In contrast, the time to the development of a secondary malignancy was remarkably brief, with a median of only 8 months.

In the literature review, case reports of malignancies accompanying BS are usually related to hematological malignancies or solid cancers [11, 12]. A single case report exists in which hematological and solid cancers were observed in the same individual [13]. This case report represents the second such instance.

The oncogenic potential of CT and radiation exposure constitute a challenge for cancer treatment among patients with BS. However, due to the rarity of BS, the existing literature is limited. The paucity of data concerning cancer treatment in patients with BS, coupled with the absence of clear guidelines for their management and treatment adjustment, represents a significant challenge for physicians tasked with their care. A recent published article by several patient societies emphasized the importance of a BS-adapted approach for the BS community [14]. Despite the lack of systematic studies on the treatment of malignancies in BS, most treating physicians have employed reduced or omitted (weight-based) doses of CT and RT to avoid excessive toxicity.

Although there are no evidence-based data linking specific chemotherapeutic agents to an increased risk of secondary malignancies, most treating clinicians recommend against the use of alkylating agents, particularly busulfan, cyclophosphamide, or melphalan, due to their direct interaction with DNA. Only in vitro studies have demonstrated that the introduction of 5‑fluorouracil into DNA results in greater DNA fragmentation in cells with pathogenic variants of BLM compared to control cells. A comparable concern pertains to radiation exposure in the diagnosis and treatment of patients with BS. Irradiated Blm-deficient mice (Blmm3/m3) exhibited an increased risk for tumors, particularly hematological malignancies [15, 16].

Individuals with DNA repair disorders are at an increased risk of developing malignant tumors and of hypersensitivity to radiotherapy. These tumors commonly appear at an early age and have a poor prognosis [17]. Similarly, there is a lack of evidence-based data on the use of chemotherapeutic agents in conjunction with RT. In the international medical literature, radiotherapy (RT) in patients with BS and solid cancers is only rarely described in case reports [18,19,20,21]. Between the 1950s and 1970s, a total of 14 patients with acute leukemia were identified in the German registry. Seven of these patients developed severe treatment reactions, including fatal bone marrow suppression, interstitial pneumonitis and hepatitis, mucositis leading to severe intestinal hemorrhage, candidiasis, and neurological toxicity. Some of these reactions occurred despite reduced doses of chemotherapy. The remaining patients did not exhibit any unusual reactions, although the data for some patients are limited, and only two survived their disease and treatment [22]. In contrast to these studies, our patient did not develop any serious complications during RT. The data indicate that there is no definitive evidence to suggest that CT or RT can be linked to an increased risk of malignancy. However, case reports suggest that these treatments have the potential to induce malignant transformation, a possibility that should be kept in mind when assessing individual cases.

Our patient had an aggressive triple-negative histology and was diagnosed at an early age. We therefore predicted that she would have a poor prognosis, as in a study by Kanyılmaz et al. involving 559 patients, the 5‑year overall survival rate of patients with triple-negative breast cancer was significantly lower than that of patients with hormone receptor-positive and HER2-positive breast cancer. In addition, patients with triple-negative disease had a 2.64 times increased risk of death compared to other groups (hazard ratio: 2.64, 95% confidence interval [1.36–5.12]; p = 0.004), [23]. We had to use alkylating agents and RT, which are recommended in current guidelines for the triple-negative subtype. After a multidisciplinary tumor board discussion, we planned adjuvant CT followed by RT with no dose reduction. Although dose reduction is recommended in the literature based on case reports rather than evidence-based randomized treatments, we treated at standard doses and achieved an oncological response.