Unusual Presentation of Triple-Negative Breast Cancer in a Young Woman with Xeroderma Pigmentosum: A Case Report

Xeroderma pigmentosum (XP) is a rare autosomal recessive DNA repair disorder, resulting from defects in nucleotide excision repair, that predisposes affected individuals to multiple cancers, particularly skin malignancies. Internal tumors including breast cancer are uncommon. Triple-negative breast cancer (TNBC) is an aggressive subtype that presents unique therapeutic challenges, particularly in XP patients where radiotherapy is contraindicated.

We report a 34-year-old woman with XP who presented with a 6-cm right breast mass. Histopathology revealed grade III invasive carcinoma of no special type (NST) ER-negative, PR low positivity (1-2% of cells), HER2-negative (score 0), Ki-67 >80%. BRCA1/2 testing was negative. She underwent four cycles of neoadjuvant doxorubicin/cyclophosphamide with limited response, followed by modified radical mastectomy with axillary lymph node dissection. Pathology confirmed residual 60 mm tumor with negative surgical margins and fifteen negative lymph nodes. Pathological stage: pT3pN0M0 (AJCC 8th edition). She subsequently received adjuvant paclitaxel plus carboplatin. Radiotherapy was omitted due to XP-related radiosensitivity. At 12 months, the patient remained disease-free.

TNBC in XP is exceedingly rare and presents complex management challenges. Platinum-based chemotherapy is biologically rational given the underlying NER defect and may be particularly effective given underlying DNA repair defects, while radiotherapy avoidance necessitates surgical prioritization and PARP inhibitors may represent promising future strategies.