A Case of Late-Onset Li-Fraumeni-like Syndrome with Unilateral Breast Cancer
A 47-yr-old woman presented to a local hospital with a painless lump in the right breast that had been present for 1 month. She had no history of other breast complaints or surgeries. Her menarche occurred at age 14 yr and she gave birth to 3 children. There was no family history of breast or ovarian cancer, but 2 of her family members died from late-onset cancers (). On physical examination, a poorly defined, firm mass was noted in the medial upper portion of her right breast, measuring approximately 3 cm, and no axillary or cervical lymphadenopathy was detected. Mammography demonstrated a lesion highly suspicious of cancer, and histological examination of the core needle biopsy of the lesion revealed invasive ductal carcinoma (IDC) of the breast. The patient was then transferred to our hospital for further evaluation and management of the cancer. Results for complete cell count, blood chemistry, and tumor markers (carcinoembryonic antigen; 0.8 ng/mL, cancer antigen 15-3; 5.3 U/mL) were all within reference intervals. Screening for metastatic disease by computed tomography and positron emission tomography showed no evidence of adjacent lymphatic, pulmonary, bone, or hepatic metastases.\nA pathologist reviewed slides from the other hospital and confirmed the diagnosis of IDC. The patient then underwent a partial mastectomy of the right breast with ipsilateral, axillary sentinel lymph node biopsies. The final pathology of the tumor was IDC, and the cancer was staged as pT2N0M0. The specimen showed comedo-type necrosis with calcification and had a maximum diameter of 2.2 cm. The Nottingham classification [] was II (moderately differentiated), and the total point score was 7 (2-3-2). The tumor cells stained positive for p53, and results for Ki67 were positive in 5% of the tumor cells. The carcinoma displayed no nuclear reactivity for estrogen receptors, progesterone receptors, or HER-2. Biopsy findings for 7 sentinel lymph nodes were all negative. Although frozen sections, removed during the surgery, were negative for malignancy, final pathology revealed malignant infiltrations in the deep layers of the inferior and medial margins.\nGiven the extensive family history of cancer, samples of peripheral blood (PB) lymphocytes and tumor tissue were assessed for TP53 mutation. Briefly, DNA was extracted from breast cancer tissue and mononuclear cells from PB, and 5 to 9 TP53 exons and intron-exon boundaries were studied. Analysis of PB revealed a germline heterozygotic A189V mutation that was homozygous in the IDC specimen (). Later, her 3 offsprings underwent genetic screening, and 2 daughters (aged 20 and 16 yr) were found to carry the mutation ( and ) despite absence of signs or symptoms of cancer. Patients (or their parents, if younger than 14 yr) gave informed consent for all molecular testing.\nAfter confirmation of the patient's TP53 mutation status, an interdisciplinary panel met to determine the utility of localized radiotherapy, based on the suspected radiosensitivity of individuals harboring a deleterious mutation in the TP53 gene [, ]. As partial mastectomy is generally followed by radiotherapy to increase the probability of tumor-free resection margins, risk of cancer relapse was determined to be greater than the risk of secondary carcinogenesis due to radiation. The patient has completed 4 cycles of adjuvant chemotherapy consisting of doxorubicin (60 mg, 32.8 mg/m2) and cyclophosphamide (500 mg, 273.2 mg/m2), and 6,400 cGy of adjuvant radiotherapy is planned. The patient is currently well, without any signs or symptoms of cancer recurrence.