A progressive and refractory case of breast cancer with Cowden syndrome.

BACKGROUND: 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. CASE PRESENTATION: 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. CONCLUSION: 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.

Neoadjuvant endocrine therapy for estrogen receptor-positive primary breast cancer.

Neoadjuvant endocrine treatment (NAE) for estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative primary breast cancer improves the surgical outcome, and its therapeutic response is useful for predicting prognosis. The indication for NAE is patients who have highly hormone-sensitive breast cancer. The optimal treatment duration depends on the required endpoint. In the case of tumor reduction or introduction to breast-conserving surgery (BCS), a treatment period of at least 6 months is required. Several clinical trials are underway to develop treatment strategies based on shortterm responsiveness to NAE to improve the prognosis of hormone receptor (HR)-positive/HER2-negative breast cancer. This article outlines the current status of NAE and new treatment strategies based on the responsiveness during NAE or clinical and biological feature on residual tumor after NAE.