Department of Breast and Endocrine Surgery, Kumamoto University Graduate School of Medical Science, 1-1-1, Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
World J Surg Oncol. 2022 Sep 3;20(1):279. doi: 10.1186/s12957-022-02745-5.
Cowden syndrome is a rare autosomal-dominant disease with a high risk of malignant tumors of the breast, commonly caused by germline mutations in the PTEN gene. Most breast cancers related to Cowden syndrome showed typically a slow-growing and favorable clinical course. Here, we report a progressive case of triple-negative breast cancer in a patient who was diagnosed with Cowden syndrome.
A 35-year-old female with breast cancer was referred to our hospital. Histopathological examination of the tumor showed that it was triple-negative breast cancer with high proliferation marker. Preoperative positron emission tomography-computed tomography showed abnormal uptake in the left cerebellar hemisphere in addition to the right breast and axillary lymph node. Brain T2-weighted magnetic resonance imaging revealed hyperintense bands in the left cerebellar hemisphere lesion, which demonstrated a "tiger-stripe" appearance. The patient's mother had died of endometrial cancer. Subsequently, she underwent genetic testing, leading to a diagnosis of Cowden syndrome with a pathogenic variant c.823_840del.18 at exon 8 in PTEN. She was treated with neoadjuvant chemotherapy of eribulin and cyclophosphamide followed by adriamycin and cyclophosphamide. However, her tumors increased after these treatments. She was immediately surgically treated and received adjuvant chemotherapy of capecitabine. Unfortunately, the cancer recurred in the lung nine months after surgery. We then administered paclitaxel and bevacizumab therapy, but the disease rapidly progressed. Consequently, the patient died due to breast cancer about three months after recurrence.
We report an aggressive case of cancer with Cowden syndrome which was resistant to standard chemotherapy. Alteration of the phosphatidylinositol-3 kinase/Akt/mammalian target of rapamycin pathway due to inactivating PTEN protein may be associated with chemoresistance and serves as a candidate for therapeutic intervention in PTEN-related cancers.
考登综合征（Cowden syndrome）是一种罕见的常染色体显性遗传病，具有较高的乳腺癌恶性肿瘤风险，通常由 PTEN 基因突变引起。大多数与考登综合征相关的乳腺癌表现为生长缓慢、临床预后良好。本研究报告了一例携带 PTEN 基因致病性变异 c.823_840del.18 的考登综合征患者发生三阴性乳腺癌的进展性病例。
一位 35 岁女性因乳腺癌就诊。肿瘤的组织病理学检查显示为三阴性乳腺癌，增殖标志物高。术前正电子发射断层扫描-计算机断层扫描（PET-CT）显示，除右乳腺和腋窝淋巴结外，左侧小脑半球也有异常摄取。脑 T2 加权磁共振成像显示左侧小脑半球病变呈高信号带，表现出“虎纹”样外观。患者的母亲因子宫内膜癌去世。随后，患者接受了基因检测，诊断为考登综合征，PTEN 基因第 8 外显子存在致病性变异 c.823_840del.18。患者接受了表柔比星和环磷酰胺联合艾日布林的新辅助化疗，随后是多柔比星和环磷酰胺。然而，这些治疗后肿瘤增大。她立即接受了手术治疗，并接受了卡培他滨辅助化疗。不幸的是，手术后 9 个月癌症复发。随后给予紫杉醇和贝伐珠单抗治疗，但疾病迅速进展。因此，患者在复发后约 3 个月因乳腺癌死亡。
我们报告了一例考登综合征相关侵袭性癌症病例，该病例对标准化疗耐药。PTEN 蛋白失活导致的磷脂酰肌醇 3 激酶/蛋白激酶 B/哺乳动物雷帕霉素靶蛋白通路改变可能与化疗耐药相关，是 PTEN 相关癌症治疗干预的候选靶点。
