The effect of low HER2 expression on treatment outcomes in metastatic hormone receptor positive breast cancer patients treated with a combination of a CDK4/6 inhibitor and endocrine therapy: A multicentric retrospective study.

BACKGROUND: CDK4/6 inhibitors combined with endocrine therapy have significantly improved treatment outcomes for metastatic hormone receptor-positive (HR+) breast cancer patients. However, the impact of low HER2 expression on treatment response and progression-free survival (PFS) remains unclear. METHODS: This multicenter retrospective study included 204 HR+ breast cancer patients treated with a combination of CDK4/6 inhibitor and endocrine therapy. HER2-zero disease was detected in 138 (68%) and HER2-low disease in 66 (32%) patients. Treatment-related characteristics and clinical outcomes were analyzed, with a median follow-up of 22 months. RESULTS: The objective response rate (ORR) was 72.7% in the HER2 low group and 66.6% in the HER2 zero group (p = 0.54). Median PFS was not significantly different between the HER2-low and HER2 zero groups (19 months vs.18 months, p = 0.89), although there was a trend toward longer PFS in the HER2-low group for first-line treatment (24 months progression-free survival rate 63% vs 49%). In recurrent disease, the median PFS was 25 months in the HER2-low group and 12 months in the HER2-zero group (p = 0.08), while in de novo metastatic disease, the median PFS was 18 months in the HER2-low group and 27 months in the HER2-zero group (p = 0.16). The order of CDK4/6 inhibitor use and the presence of visceral metastasis were identified as independent variables affecting PFS. CONCLUSION: Low HER2 expression did not significantly impact treatment response or PFS in HR+ breast cancer patients treated with a CDK4/6 inhibitor and endocrine therapy. Because of the conflicting results in the literature, further prospective studies are needed to evaluate the clinical significance of HER2 expression in HR+ breast cancer.

The effectiveness and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early-stage human epidermal growth factor receptor 2-positive breast cancer: Turkish Oncology Group study.

In our study, we aimed to evaluate the pathological response rates and side effect profile of adding pertuzumab to the treatment of HER2+ locally advanced, inflammatory, or early-stage breast cancer. This study was conducted by the Turkish Oncology Group (TOG) with data collected from 32 centers. Our study was multicentric, and a total of 364 patients were included. The median age of the patients was 49 years (18-85 years). Two hundred fifteen (60%) of the cases were hormone receptor/HER2+ positive(ER+ or PR+, or both), and 149 (40%) of them were HER2-rich (ER and PR negative). The number of complete responses was 124 (54%) in the docetaxel+trastuzumab+pertuzumab arm and 102 (45%) in the paclitaxel+trastuzumab+pertuzumab arm, and there was no difference between the groups in terms of complete response. In 226 (62%) patients with complete response, a significant correlation was found with DCIS, tumor focality, removed lymph node, and ER status P < 0.05. Anemia, nausea, vomiting, myalgia, alopecia, and mucosal inflammation were significantly higher in the docetaxel arm, P < 0.05. In our study, no statistical difference was found between the before-after echocardiography values. DCIS positivity in biopsy before neoadjuvant chemotherapy, tumor focality; the number of lymph nodes removed and ER status were found to be associated with pCR. In conclusion, we think that studies evaluating pCR-related clinicopathological variables and radiological imaging features will play a critical role in the development of nonsurgical treatment approaches.

Deficient Mismatch Repair and Lymphocytic Response to Tumor as Prognostic Markers in Stage II Colon Cancer Patients.

OBJECTIVE: To investigate the relationship between colon cancer (CC) subtypes defined by the status of tumor-infiltrating lymphocytes (TIL) and mismatch repair (MMR) combination with clinicopathological features and survival. STUDY DESIGN: Observational study. PLACE AND DURATION OF STUDY: Department of Medical Oncology, Haydarpasa Numune Research and Training Hospital, Istanbul, Turkey, from July 2010 to March 2020. METHODOLOGY: Eighty-three patients with operated stage II colon cancer were included in the study. Pathology, surgery and oncological treatment and follow-up information were obtained from patient files; and statistical analyses were performed on overall survival (OS). Tumor-infiltrating lymphocytes and mismatch repair status was determined with the help of immunohistochemistry. RESULTS: TIL-high and deficient MMR (dMMR) status were detected in 26 patients (31.3%) and 21 patients (25.3%), respectively. Tumors were divided into four subgroups according to TIL and MMR status. TIL-high/dMMR tumors had the most favourable prognosis, while TIL-low/proficient MMR tumors exhibited poor OS. CONCLUSION: The combination of TIL and MMR could enable us to differentiate patients' survival outcomes in more details. Therefore, considering that the TIL and MMR status, evaluated by IHC, may be a cost-effective and effective option for risk classification in patients with stage II colon cancer. Key Word: Lymphocytic response, Mismatch repair, Prognosis, Tumor-infiltrating lymphocytes, Stage II cancer, Colon cancer.

The Effect of FDG-PET/CT on Clinical Prognostic Staging of Breast Cancer Patients being Planned Neoadjuvant Treatment.

OBJECTIVE: To evaluate the effect of FDG-PET/CT in the radiological imaging of breast cancer (BC) patients planned for neoadjuvant treatment (NAT), on the clinical prognostic stage (CPS). STUDY DESIGN: A descriptive study. PLACE AND DURATION OF STUDY: Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey, between June 2014 and September 2020. METHODOLOGY: Consecutive patients with stage I-III breast cancer (BC) who were planned for neoadjuvant treatment (NAT). The distribution of CPS detected by both conventional radiological methods (c-CPS) and FDG-PET/CT (PET-CPS) were compared. RESULTS: Significant upstaging on CPS was detected with the addition of FDG-PET/CT to conventional imaging methods in 25/121 (20.7%) patients (p <0.001). In the c-CPS stage, IB, IIA, IIB, IIIA, IIIB patients, the stage change rate was 22.7%, 28.6%, 37.5%, 50%, and 9.1%, respectively. There was no change in patients with c-CPS stage IA and IIIC. There was a significant change in the cN stages (p <0.001), while no significant change was detected in the cT stages of the patients (p = 0.180). Upstaging was detected in 5/16 (6.3%, p=0.034), 14/71 (19.7%, p <0.01), 15 / 30 (50%, p <0.01) of initially cN 0, 1, 2 patients, respectively (p<0.001). CONCLUSION: The change in CPS was due to nodal upstaging. The effectiveness of including FDG-PET/CT in the initial radiological imaging in patients planned for NAT should be evaluated with prospective studies evaluating treatment choices to be used in NAT. Key Words: PET scan, Breast cancer, Positron emission tomography, Neoadjuvant treatment, Cancer staging, Staging system, TNM.

Efficacy and safety profile of COVID-19 vaccine in cancer patients: a prospective, multicenter cohort study.

Aim: To compare the seropositivity rate of cancer patients with noncancer controls after inactive SARS-CoV-2 vaccination and evaluate the factors affecting seropositivity. Method: Spike IgG antibodies against SARS-CoV-2 were measured in blood samples of 776 cancer patients and 715 noncancer volunteers. An IgG level ≥50 AU/ml is accepted as seropositive. Results: The seropositivity rate was 85.2% in the patient group and 97.5% in the control group. The seropositivity rate and antibody levels were significantly lower in the patient group (p < 0.001). Age and chemotherapy were associated with lower seropositivity in cancer patients (p < 0.001). Conclusion: This study highlighted the efficacy and safety of the inactivated vaccine in cancer patients. Clinical Trials Registration: NCT04771559 (ClinicalTrials.gov).

Cancer patients are at high risk for infection with SARS-CoV-2 and of developing the associated disease, COVID-19, which therefore puts them in the priority group for vaccination. This study evaluated the efficacy and safety of inactive SARSCoV-2 vaccination, an inactivated virus vaccine, in cancer patients. The immune response rate, defined as seropositivity, was 85.2% in the cancer patient group and 97.5% in the control group. The levels of antibodies, which are blood markers of immune response to the vaccine, were also significantly lower in the patient group, especially in those older than 60 years and receiving chemotherapy. These results highlight the importance of determining the effective vaccine type and dose in cancer patients to protect them from COVID-19 without disrupting their cancer treatment.

The Role of FDG PET/CT to Evaluation of Axillary Lymph Nodes after Neoadjuvant Chemotherapy in Breast Cancer.

OBJECTIVE: To determine the diagnostic value of breast and axillary maximum standard uptake (SUVmax) values for predicting ypT0 and ypN0 separately. STUDY DESIGN: A descriptive study. PLACE AND DURATION OF STUDY: Department of Medical Oncology, Haydarpasa Numune Training and Research Hospital, between May 2017 and September 2020.  Methodology: Consecutive patients with operated breast cancer (BC) after neoadjuvant chemotherapy (NAC) were evaluated. SUVmax on FDG-PET/CT after NAC at both primary tumour (postSUVmax-T) and axillary lymph nodes (postSUVmax-N) were assessed to predict the ypT0 and the ypN0, respectively.  Results: Clinically meaningful correlation was detected between postSUVmax-N with ypN0 in patients with human epidermal receptor-positive (Her2+) and triple-negative (TN) BC (in Her2+ BC: r=0.596, p <0.001, in TN BC: r=0.782, p = 0.001). The postSUVmax-N predicted ypN0 with 90.5% positive predictive value (PPV) and 85.7% negative predictive value (NPV) in patients with Her2+ and TN BC. The postSUVmax-T predicted ypT0 with 87.5% PPV and 100% NPV in patients with TN BC (AUC: 0.938, P <0.01) Conclusion: According to this study's findings, the FDG-PET/CT may be an alternative to sentinel lymph node biopsy (SNB) to protect patients from axillary lymph node dissection when the expected FNR of the SNB is high in patients with Her+ and TN BC. Key Words: Breast cancer, FDG PET/CT, Neoadjuvant therapy.

Usefulness of serum M30 and M65 levels to predict response to neoadjuvant chemotherapy in patients with breast cancer.

OBJECTIVE: M30 and M65 levels reflect tumor cell activity in patients with epithelial cancer. Cytokeratin 18 is one of the cell skeletal elements. M30 is a apoptotic marker of cytokeratin 18. M65 levels are both an apoptosis and a necrosis marker. The aim of our study was to determine the predictive value of M30 and M65 levels in neoadjuvant treatment of breast cancer. MATERIALS AND METHODS: In this prospective study, 41 patients with breast cancer who underwent neoadjuvant chemotherapy were included. Following 4 cycles of chemotherapy with anthracycline containing regimen, patients received paclitaxel treatment for 12 weeks. Blood was collected from the patients before chemotherapy and on day 21, after the 2nd, 4th, and 8th cycles. M30 and M65 levels were measured with the ELISA method. RESULTS: While there was an increase in M30 and M65 levels at the 4th cycle (P < 0.05), levels were decreased after the 8th cycle. In addition, there was no significant relationship among M30, M65 levels, and prognostic factors such as ER, PR, c-Erb-2, Ki-67, pathologic-T, pathologic-N, and chemotherapy responses. CONCLUSION: M30 and M65 levels are not of predictive values of response to breast cancer patients receiving neoadjuvant chemotherapy. Nevertheless, M30 and M65 levels increased when patients kept receiving anthracycline containing chemotherapy.

Role of Urotensin-2 in 5-Fluorouracil-Related Arterial Vasoconstriction in Cancer Patients.

BACKGROUND: The aim of this study was to identify the possible relationship of 5-fluorouracil (5-FU)-related arterial vasoconstriction with urotensin-2 (UT-2), which has a high potential as an endogenic vasoconstrictor. METHODS: We assigned the patients to 1 of 3 groups. Patients in group 1 received a bolus of 5-FU, those in group 2 a continuous infusion (CI) of 5-FU, and those in group 3 no 5-FU, which was also a control group. Pre- and post-treatment UT-2 levels and brachial arterial diameters were measured and recorded in all patients. RESULTS: 132 patients were included in the study. Pre- and post-treatment brachial artery diameters were similar in all groups: in group 1 (3.28 ± 0.52 vs. 3.25 ± 0.44 mm, p = 0.740), in group 2 (3.57 ± 0.47 vs. 3.46 ± 0.45 mm, p = 0.441) and in the control group (3.51 ± 0.52 vs. 3.25 ± 0.44 mm, p = 0.818). Pre- and post-treatment UT-2 levels were significantly different in each group: in group 1 (39.5 ± 30.9 vs. 56.7 ± 27.1 ng/ml, p = 0.0001), in group 2 (37.7 ± 33.7 vs. 62.5 ± 37.7 ng/ml, p = 0.0001) and in the control group (52.9 ± 40.2 vs. 60.8 ± 40.7 ng/ml, p = 0.006). CONCLUSION: Our findings suggest that UT-2 has a high potential as a vasoconstrictor agent in our bodies and its level increases through a bolus or CI 5-FU. Increased UT-2 levels are likely to play a role in 5-FU-related cardiac toxicity pathogenesis.