A severe case of NF1 is reported in this report. Despite the well-established association between NF1 and breast cancer, an early detection program was not followed, resulting in an advanced-stage diagnosis. Nonetheless, surgery and medical treatment were administered properly, and the patient did not have any recurrence to date.
In this case, due to the large size of the tumor, chemotherapy was administered prior to surgery resulting in a complete response. Systemic chemotherapy administered before or after surgery does not significantly differ from each other in long-term outcomes according to randomized clinical trials [9, 10]. Systemic therapy has traditionally been beneficial for improving surgical outcomes before surgery. In addition, preoperative systemic therapy may provide valuable prognostic information based on response. While neoadjuvant therapy is most commonly indicated for HER2-positive and triple-negative breast cancer subtypes, it may also be considered in select hormone receptor–positive cases, particularly when tumor burden is high or breast-conserving surgery is desired. A pathologic complete response (pCR) to neoadjuvant therapy can lead to a favorable disease-free and overall survival rate.
Various types of breast malignancies have been reported in the literature, in association with Von Recklinghausen’s disease (NF1); with most available studies on this association were case reports [11,12,13,14,15,16]. A common feature shared between our case and those previously reported is the late presentation to medical care, often due to patients mistakenly identifying the breast tumor as benign manifestations of NF1, such as neurofibromas. The majority of reported cases involve postmenopausal women between the ages of 50 and 75. A summary of these cases is presented in Table 1. A study by Evans et al. of 142 patients with NF-1 and breast cancer showed a higher incidence of contralateral breast cancer and a shorter survival [17].
Mutations within the NF1 gene on chromosome 17q11.2 result in NF1. The NF1 gene encodes a tumor suppressor protein called neurofibromin. The NF1 gene is autosomal-dominant and exhibits complete penetration but a variable expression pattern. 30 to 50% of people with NF1 have unaffected relatives and acquire the germline mutation during embryogenesis de novo [18]. Genetic testing was not performed on the patient in this case because it is not available in public hospitals or covered by insurance. However, genetic testing is not necessary to diagnose NF1.
There is a notable discrepancy in tumor size as measured by mammography/ultrasound versus CT imaging in the current study. This variation is likely due to differences in imaging modality resolution, measurement planes, and tissue contrast characteristics. Ultrasound and mammography, which are breast-specific modalities, are more reliable for primary tumor sizing. It should be noted that, due to resource constraints, no pre-treatment fine-needle aspiration was performed for the enlarged axillary lymph node; therefore, the preoperative axillary lymph nodal status cannot be definitively confirmed as N1. Additionally, some pathological tests were not performed in the current case, including Ki-67 testing, so the tumor could not be classified according to its molecular subtypes (luminal A or luminal B). In this case, initial preoperative treatment consisted of four cycles of chemotherapy. Despite achieving a complete pathological response, adjuvant chemotherapy with four additional cycles of paclitaxel was administered. However, current guidelines suggest that completing the full course of standard neoadjuvant chemotherapy prior to surgery is preferable [19].
In conclusion, this case report illustrates the complex interplay between NF1 (Von Recklinghausen’s disease) and breast cancer. The inclusion of NF1 patients in national high-risk breast cancer screening programs is warranted and may substantially improve early detection and survival outcomes in these individuals. Furthermore, improving access to specialized healthcare services and enhancing surveillance in this high-risk population could positively affect prognosis and long-term outcomes.