Pembrolizumab response in stage IV luminal-type breast cancer with high microsatellite instability: a case report.

BACKGROUND: Pembrolizumab (PEM), an immune checkpoint inhibitor (ICI), is often used for triple-negative breast cancer, but can also be used to treat solid tumors that exhibit high microsatellite instability (MSI-High). However, patients with breast cancer rarely have MSI-High, the use of PEM in such cases in clinical practice is uncertain due to lack of sufficient supporting data. Here, we report the case of a premenopausal woman in who received PEM for MSI-High luminal-type breast cancer. CASE PRESENTATION: A 40-year-old premenopausal Asian woman was diagnosed with stage IIA (T2N0M0) breast cancer and had an Oncotype DX recurrence score of 38. After surgery, she received 4 courses of chemotherapy with docetaxel and cyclophosphamide. After 3 months of tamoxifen therapy, the patient complained of abdominal pain due to right iliac metastasis, and biopsy of the metastatic lesion showed of luminal type; she was sequentially treated with fulvestrant, a CDK4/6 inhibitor, and an anticancer drug (TS1), but over the next year, metastasis to the bone and para-aortic lymph nodes increased. Tumor was MSI-High; PEM was started, and after three courses, bone metastases were reduced, para-aortic lymph node metastases resolved, opioids were discontinued, and the patient returned to society; PEM was administered for 1 year with no worsening of bone metastases on imaging. Asymptomatic brain metastasis less than 1 cm was detected and gamma knife was performed. Six months after completion of PEM, the patient is working with no new lesions. CONCLUSION: We report a case of luminal-type breast cancer with bone metastases and MSI-High, which was treated with PEM and showed a rapid therapeutic response.

Response-Guided Omission of Anthracycline in Patients with HER2-Positive Early Breast Cancer Treated with Neoadjuvant Taxane and Trastuzumab: 5-Year Follow-Up of Prognostic Study Using Propensity Score Matching.

BACKGROUND: De-escalation therapy omitting anthracycline has been generally adopted for patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer in the adjuvant setting, but not in the neoadjuvant chemotherapy (NAC) setting. We investigated whether anthracycline can be omitted in HER2-positive early breast cancer patients receiving neoadjuvant taxane plus trastuzumab with clinical response. METHODS: HER2-positive primary breast cancer patients treated using NAC containing trastuzumab were enrolled between September 2006 and July 2018 at Osaka Breast Clinic. The primary outcome was disease-free survival (DFS). The secondary outcome was overall survival (OS). We investigated survival with or without fluorouracil, epirubicin, and cyclophosphamide (FEC) using the log-rank test and propensity score matching (PSM). RESULTS: In total, 142 patients were retrospectively included and median follow-up was 61 months. There was no significant difference in DFS (p = 0.93) and OS (p = 0.46) between the FEC-omitted group and the FEC-added group. The 5-year DFS was 91% and 88% and OS was 100% and 100%, respectively. After PSM, the FEC-omitted group and the FEC-added group had no significant differences in DFS (p = 0.459) and there were no death events in either group. The 5-year DFS was 90% and 88% and OS was 100% and 100%, respectively. CONCLUSIONS: Using PSM, the 5-year DFS of HER2-positive early breast cancer was not different with or without anthracycline. Response-guided omission of anthracycline may be an option for HER2-positive early breast cancer patients receiving neoadjuvant taxane and trastuzumab with good response in order to avoid overtreatment.

Prognostic Factors in HER2-Positive Primary Breast Cancer Patients Treated Using Neoadjuvant Chemotherapy Plus Trastuzumab.

BACKGROUND: It is unclear for whom new anti-human epidermal growth factor receptor 2 (anti-HER2) agents, such as pertuzumab and T-DM1, should be considered. We investigated prognostic factors before neoadjuvant chemotherapy (NAC) among HER2-positive invasive breast cancer patients and those after NAC among patients who did not achieve pathological complete response (pCR) using conventional adjuvant trastuzumab. METHODS: HER2-positive primary breast cancer patients treated using NAC containing trastuzumab were enrolled between September 2006 and June 2017 at the Osaka Breast Clinic. Patients with distant metastasis or using NAC containing pertuzumab were excluded. The main outcome was disease-free survival (DFS). We investigated pre- and post-NAC prognostic factors using the log-rank test and Cox proportional hazards model. RESULTS: In total, 157 patients were included. Among the pre-NAC prognostic factors, younger age (under 40 years old) and positive clinical nodal status were significantly poorer prognostic factors (hazard ratio [HR] 3.47, 95% CI 1.06-10.12, p = 0.041 and HR 3.32, 95% CI 1.03-14.78, p = 0.045) by multivariate analysis. Among the post-NAC prognostic factors, patients with non-pCR (3-year DFS; 85 vs. 96%, p = 0.022) had a poorer DFS than patients with pCR. DFS was assessed for non-pCR patients (n = 64). High post-NAC Ki-67 status (≥20%; HR 6.73, 95% CI 1.82-31.93, p = 0.004) was a significant and large post-NAC tumor size (≥2 cm; HR 3.65, 95% CI 0.97-14.71, p = 0.056) was a marginally significant prognostic factor by multivariate analysis. After having combined them, high post-NAC Ki-67 status or large post-NAC tumor size was also a significant prognostic factor (HR 5.75, 95% CI 1.32-16.12, p = 0.017). CONCLUSIONS: Positive clinical nodal status and young age were found to be prognostic factors before NAC in HER2-postive invasive breast cancer patients. A high post-NAC Ki-67 status and large post-NAC tumor size were significant and marginally significant prognostic factors, respectively, after NAC in patients who did not achieve pCR. New anti-HER2 agents, such as pertuzumab and T-DM1, should be considered for the patients with those prognostic factors.

Strategy for the accurate preoperative evaluation of the number of metastatic axillary lymph nodes in breast cancer.

BACKGROUND: After the ACOSOG Z0011 trial, it became important to evaluate the number of metastatic axillary lymph nodes (LNs) preoperatively. The purpose of this paper is to confirm whether the number of metastases can be accurately diagnosed by preoperative computed tomography (CT), ultrasound sonography (US), and US-guided fine-needle aspiration cytology (FNAC). METHODS: We retrospectively analyzed the axillary LNs finding of preoperative CT/US of 470 breast cancer patients. Metastasis was suspected based on the following findings: LNs with a long-axis diameter of ≥10 mm or a short-axis diameter of ≥5 mm on CT, and LNs with the absence of a fatty hilum, focal cortical thickness or a cortical thickness ≥2 mm on US. We also examined the results of FNAC making a rapid bedside diagnosis (bedside-FNAC) of 162 LNs that were suspected to metastatic based on the US findings. RESULTS: On CT, all cases with ≥3 LNs with a long-axis diameter of ≥10 mm and a short-axis diameter of ≥5 mm had metastasis. However, there was no relationship between the number of detected LNs and the number of metastases. On US, 75.7% of LNs with the absence of a fatty hilum and all LNs with cortical thickness ≥6 mm had metastasis. The accuracy of bedside-FNAC for suspicious LNs was 100%. CONCLUSIONS: Although we can pick up LNs that are likely to have metastasis on CT/US, it was impossible to accurately predict the number of metastases on CT/US. However, bedside-FNAC of suspicious LNs could accurately predict the number of metastases.