The evaluation of miR-1181 and miR-4314 as serum microRNA biomarkers for epithelial ovarian cancer diagnosis and prognosis.

AIM: Epithelial ovarian cancer (EOC) is the most ominous tumor of gynecological cancers due to its poor early detection rate and unfavorable prognosis. To date, there is no reliable screening method for the diagnosis of ovarian cancer at an early stage. MiRNAs are small non-coding RNA molecules, and their main function is to regulate gene expression. The present study compared the serum miR-1181 and miR-4314 levels in patients with EOC and healthy controls to measure the diagnostic and prognostic value as candidate biomarkers. MATERIALS AND METHODS: We collected serum samples from a total of 135 participants (69 patients with EOC and 66 healthy controls). Relative expressions of miR-1181 and miR-4314 were measured by quantitative real-time polymerase chain reaction assay (qPCR). RESULTS: The present study revealed that both serum miR-1181 and miR-4314 levels in patients with EOC were significantly increased compared to healthy controls for each marker. In addition, there was a significant relationship between miR-1181 and miR-4314 overexpressions and the stage and prognosis of the disease. Finally, patients with high expression levels of miR-1181 and miR-4314 had significantly shorter survival rates than those with low expression levels. CONCLUSION: The current study proposed that serum miR-1181 and miR-4314 could discriminate the EOC patients from healthy controls. In addition, both miR-1181 and miR-4314 may be predictive biomarkers for ovarian cancer prognosis. Further studies are needed to confirm the findings of the present study.

Outcomes of reconstructive techniques in breast cancer using BCCT. core software.

BACKGROUND: Surgery remains a priority for breast cancer treatment. This study aimed to compare the cosmetic outcomes of oncoplastic patients who had undergone breast-conserving surgery, mini-LDF (latissimus dorsi flap), and immediate implant reconstruction using both the Japanese scale and the BCCT.core (The Breast Cancer Conservative Treatment cosmetic results software) program and to validate this program. PATIENTS AND METHODS: Patients who underwent surgery for breast cancer between 1997 and 2021 were retrospectively studied. Patients were divided into three groups: 1-those who had undergone breast-conserving surgery (245 patients, 71.3%), 2-those who had undergone mini-LDF after lumpectomy (38 patients, 11.02%), and 3- those who underwent reconstruction with implants after nipple-sparing mastectomy (61 patients, 17.68%). The patients were called for a follow-up examination, and their photos were taken. The photographs were shown to an independent breast surgeon and a plastic surgeon who was not included in the surgeries, and they were asked to evaluate and rate them according to the Japanese cosmetic evaluation scale. The same images were transferred to the computer and scored using BCCT.core. RESULTS: The plastic and breast surgeon evaluation results showed no significant difference between the three cosmetic techniques (p = 0.99, 0.98). The results of BCCT.core software measurements were similar to the results of plastic and breast surgeons (p: 0.43). CONCLUSION: Patients are more knowledgeable about cosmetic outcomes and expect more objective data. In this study, we used 3 different cosmetic evaluation scales. We found that these techniques give results that are compatible with each other in terms of evaluating the work done in a more concrete way. For this reason, we recommend the use of such software, which offers objective results in a subjective field such as aesthetics and is very easy to apply.

The effect of parity, breastfeeding history, and duration on clinical and pathological characteristics of breast cancer patients.

Background/aim: The study is aimed to determine the relationship between the delivery and breastfeeding history of the patients and the clinicopathological properties of breast cancer. Materials and methods: A questionnaire was utilized for the study, which included the age of diagnosis, the number of children at the time of diagnosis, the age of the children, and the breastfeeding period of each child. Results: The study included 828 patients. The median age at diagnosis was 47 years for parous women and 42 years for nonparous women (p < 0.001). The tumor size of the patients diagnosed within the breastfeeding period was significantly larger compared to the other patients. Estrogen and progesterone receptor positivity were lower in patients diagnosed during breastfeeding. Additionally, the mean number of positive lymph nodes, dissected lymph nodes, and positive lymph node/dissected lymph node ratio in parous and breastfed patients with a nonmetastatic disease were statistically significantly higher in multivariable analysis than those patients who were nulliparous and have not breastfed. Conclusion: Breast cancer is seen at a later age in patients who are parous than those who have never given birth. Patients who are parous and have breastfed tend to present with a higher stage of the disease.

Real-world data on efficacy and safety of first-line alectinib treatment in advanced-stage, ALK-positive non-small-cell lung cancer patients: a Turkish Oncology Group study.

Aims: In this multicenter study, the authors aimed to determine the real-life efficacy and safety of first-line alectinib. Materials & methods: This retrospective trial included advanced-stage, ALK-positive non-small-cell lung cancer patients who were treated with first-line alectinib in terms of ALK-tyrosine kinase inhibitors, regardless of previous chemotherapy. The co-primary end points were progression-free survival both for all patients and for the treatment-naive population. The secondary end points were overall response rate, overall survival, rate of CNS progression and safety. Results & conclusion: A total of 274 patients (n = 177 for treatment-naive patients) were enrolled in the study. The median progression-free survival was 26 and 28.8 months for all patients and the treatment-naive group, respectively. The overall response rate, CNS progression rate and 1-year overall survival ratio were 77.9, 12.4 and 77%. Alectinib is a highly effective therapy with a favorable safety profile.

The advancements in cancer treatment, particularly in the last two decades, have been promising. Non-small-cell lung cancer (NSCLC) is one of the most important diseases experiencing these promising developments. ALK positivity, which is caused by the rearrangement of different gene fragments between two chromosomes, affects about 5% of NSCLC patients. This provides a target for next-generation therapies. One of these targeted therapy drugs is alectinib. The authors examined the outcomes of 271 patients with body-disseminated NSCLC who received alectinib as initial targeted therapy. These patients were not chosen to participate in a clinical phase study. They were treated with an approved drug; the study also included 97 patients who had previously received chemotherapy. The median duration of survival without disease worsening was 26 months for all patients receiving alectinib treatment. This value was 28.8 months in 177 patients who had not received any treatment before alectinib. Regardless of disease status, 77% of all patients were found to be alive at the end of the first year. Alectinib treatment resulted in a significant improvement of the disease in approximately four out of five patients. The treatment's side effects were generally tolerable or manageable. Only four patients were reported to have discontinued their medication due to treatment-related side effects. These real-world findings are compatible with previous clinical research. Alectinib is an important first-line treatment option for patients with advanced, ALK-positive NSCLC.

Prolongation of Neoadjuvant Chemotherapy before Surgery: Seeking the Optimal Number of Cycles in Serous Ovarian Cancer.

AIM: The optimal number of neoadjuvant chemotherapy (NACT) cycles is unclear in epithelial ovarian cancer. Our study aimed to evaluate the effect of the number of NACT cycles before interval debulking surgery on survival. METHODS: Data of 221 patients with advanced-stage serous epithelial ovarian cancer (EOC) were retrospectively evaluated. The patients were divided into groups as who received 3 cycles of NACT (group A), 4-5 cycles of NACT (group B), and 6 cycles of NACT (group C). RESULTS: There were 67 (30%) patients in group A, 70 (32%) in group B, and 84 (38%) in group C. Median overall survival (OS) was 61 (range 43-79) months for group A, 44 (range 36-52) months for group B, and 39 (range 27-50) months for group C. In addition, median disease-free survival (DFS) was 23.1 (range 8.5-32.1) months for group A, 19.2 (range 10.1-28.4) months for group B, and 21.5 (range 16-27) months for group C. Patients receiving >3 NACT cycles had worse OS than patients who received 3 NACT cycles (for group A vs. B, p = 0.018; for group A vs. C, p = 0.049). However, in terms of DFS, patients receiving 3 NACT cycles had no statistically significant difference compared to patients who received >3 NACT cycles. CONCLUSIONS: Patients with advanced-stage serous EOC who received more than 3 cycles of NACT had poor OS. However, there was no statistical difference in terms of DFS. In addition, >3 cycles of NACT did not increase the probability of achieving complete cytoreduction at the time of surgery.

Does nutritional status affect treatment tolerability, chemotherapy response and survival in metastatic gastric cancer patients? Results of a prospective multicenter study in Turkey.

BACKGROUND: The possible impact of malnutrition on the efficacy and tolerability of modern chemotherapy for metastatic gastic adenocarcinoma (mGC) patients is unclear. With this study, we aimed to represent the possible impact of malnutrition on the efficacy and tolerability of chemotherapy, and also on the overall survival of mGC patients. METHODS: In this prospective multicenter study, we collected demographic, oncological and nutritional data of our mGC patients. The nutritional status of patients were assessed with the Nutritional Risk Index (NRI), Body Mass Index (BMI) and weight loss percentage within 21-day period, between the chemotherapy cycles. All of these parameters along with toxicity assessment were evaluated after each courses of chemotherapy in order to determine inter-treatment weight loss. NRIs were calculated with a formula as follows; [1.519 × serum albumin level(g/L) + 41.7 × current weight/basic weight]. Patients were classified as having 'no malnutrition' (NRI > 97.5), 'moderate malnutrition' (97.5 ≥ NRI ≥ 83.5) or 'severe malnutrition' (NRI < 83.5). Drug-induced toxicities and treatment responses were evaluated via National Cancer Institute CTCAE version 4.0 and RECIST Criteria 1.1, respectively. RESULTS: One hundred and sixteen mGC patients were enrolled into the study. Median age was 60 years with range 32-83. Primary location of the tumor was antrum in 40% of the patients and of which 24% had undergone primary tumor resection. Ninety-eight percent of the patients had WHO performance status 0 or 1. Malnutrition was diagnosed in 67% of the patients and was severe in 31% of them. All patients received chemotherapy as first-line setting. Severe malnutrition was not associated with chemotherapy responses (p = 0.57). Moderate/severe malnutrition was associated with more cytopenia, nausea/vomiting, diarrhea, neuropathy, (p < 0.05 for all parameters). Moderate/severe malnutrition is associated with worser non-hematological toxicities (p = 0.038). Forty-one percent of patients died during the follow up period (Median: 138 days, range: 21-378). Malnutritional level was associated with significantly reduced overall survival. Severe malnutrition was associated with shorter median overall survival (74 days (95% CI, 20.7-111.0) vs. 237 (95% CI, 148.4-325.6) in none/moderate groups, p = 0.007). CONCLUSIONS: In mGC patients, moderate/severe malnutrition is associated with worse non-hematological toxicities. Severe malnutrition is also associated with reduced overall survival.

Multidrug refractory aggressive metastatic TFE3 (+) renal cell carcinoma: A case report.

BACKGROUND: Transcription factor E3 (TFE3) related renal cell carcinomas constitute a very small percent of all renal tumors in adults. Prognosis mainly depends on the stage of the disease at the time of diagnosis which is often poor. There is yet to be a standardized treatment protocol. Treatment options include agents identical to TFE3(-) cell renal carcinoma treatment. We present a case of a young woman with a rapidly progressing metastatic TFE3 (+) renal cell carcinoma. CASE REPORT: A 31 year old female presented with abdominal mass, distension, nausea. Initial tests and tumor markers found to be normal. Abdominal CT scan revealed a left retroperitoneal mass along with three other neighboring masses in liver manifesting as metastases. Trucut biopsy and immunohistochemical staining confirmed the retroperitoneal mass as TFE3 (+) renal cell carcinoma.Management and outcome: Sunitinib, pazopanib, nivolumab, axitinib treatments are consecutively given after surgery. It is noteworthy that rapid progression was observed under nivolumab treatment. DISCUSSION: During surveillance, rapid progression is noted under consecutive immunotherapy which was unexpected. Thus, there is a need for more standardized treatment protocols and invention of new agents for management of TFE3 (+) renal cell carcinoma.

Efficacy and Safety of Trastuzumab Emtansine in Her2 Positive Metastatic Breast Cancer: Real-World Experience.

AIM: The aim of this study is to evaluate the efficacy and toxicity of trastuzumab emtansine (T-DM1) in cases with metastatic breast cancer (mBC) in different lines of treatment. METHOD: Retrospective analysis of T-DM1 results of human epidermal growth factor receptor 2 (Her2) positive 414 cases with mBC from 31 centers in Turkey. FINDINGS: Except 2, all of the cases were female with a median age of 47. T-DM1 had been used as second-line therapy in 37.7% of the cases and the median number of T-DM1 cycles was 9. Progression-free survival (PFS) and overall survival (OS) times were different according to the line of treatment. The median OS was found as 43, 41, 46, 23 and 17 months for 1st, 2nd, 3rd, 4th and 5th line, respectively (p = 0.032) while the median PFS was found as 37, 12, 8, 8 and 8 months, respectively (p = 0.0001). Treatment was well tolerated by the patients. The most common grade 3-4 adverse effects were thrombocytopenia (2.7%) and increased serum gamma-glutamyl transferase (2%). DISCUSSION: The best of our knowledge this is the largest real-life experience about the safety and efficacy of T-DM1 use in cases with mBC after progression of Her2 targeted treatment. This study suggests and supports that T-DM1 is more effective in earlier lines of treatment and is a reliable option for mBC.

Skeletal system as a rare metastatic site in patients with ovarian carcinoma.

OBJECTIVE: To evaluate the frequency and predictors of bone metastasis in patients with ovarian cancer and to determine prognostic factors associated with this finding. METHODS: Patients diagnosed with ovarian cancer between January 2009 and December 2019 were evaluated. Patients with radiologically or pathologically confirmed bone metastasis were included in the study. Survival was analyzed using Kaplan-Meier curves and compared using the log-rank test. Multivariate analysis of prognostic factors related to survival was performed using the Cox proportional hazards model. RESULTS: Nineteen (2.6%) of 736 patients had bone metastases. Patients with clear cell histology had a higher risk of bone metastases than patients with the other epithelial histology groups (12.3% vs 2.1%, p<0.001). Overall survival was significantly lower in patients diagnosed with bone metastasis at the time of cancer diagnosis than in those diagnosed with bone metastasis during the course of the disease (median 63 vs 6.1 months, p<0.001). However, when the survival time after the development of bone metastasis was examined, no difference was found between patients with metastasis at the time of diagnosis and at the time of first or later progression (median 13.6 vs 4 months, p=0.09). In addition, the median survival of patients with clear cell histology after bone metastasis did not differ statistically from that of patients with other epithelial histology (median 22 vs 7.5 months; p=0.13). In the clear cell subgroup, bone metastasis was an independent prognostic factor for survival after multivariate analysis. For all patients, the stage at diagnosis and serum CA125 and alkaline phosphatase levels at the time of bone metastasis were prognostic factors for survival. DISCUSSION: Bone metastasis is rare in patients with ovarian cancer. However, the risk of bone metastasis is highest in patients with clear cell histology.

Nivolumab treatment for metastatic thymic epithelial tumors.

BACKGROUND: Metastatic and unresectable thymoma (T) or thymic carcinoma (TC) have limited treatment options, especially after first line. METHODS: Patients with unresectable or recurrent thymic tumors who used minimum one dose of nivolumab at any line of treatment were evaluated retrospectively. Even though nivolumab was administered 3mg/kg dosage in PRIMER study, due to toxicity and financial concerns, we used low dose regimen mostly. RESULTS: Among 46 unresectable and recurrent thymic epithelial tumors; 8 patients with TC (n = 3), T (n = 4) and mixt histology (n = 1) were reviewed. Three patients had myasthenia gravis history that had to be controlled before treatment. Four patients showed moderate (n = 2) or severe (n = 2) adverse events with nivolumab treatment. Interestingly, two severe adverse events were occurred at first dose even with 40 mg nivolumab and required cessation of treatment permanently. The median number of nivolumab received was four (range: 1-18). Best response was partial response. Two patients progressed at the 3rd and 5th month of treatment. Best duration of response for one patient with TC and one patient with T-B2 were 9 and 14 months, respectively. Median survival time after nivolumab was 7.4 months (range: 2-22.1). CONCLUSIONS: After the results of the previous study could be supported by randomized prospective studies with more number of patients, nivolumab may be considered as an option in patients with thymic epithelial tumors who have received multiple line treatments. However, given the high rate of severe toxicities, there is need to find out a reliable marker to prediction patients who will derive benefit or exhibit toxicity.

Dramatic response to single-agent atezolizumab in a patient with MSI-H serous ovarian cancer.

WHAT IS KNOWN AND OBJECTIVE: Patients with ovarian cancer have not benefited substantially from immunotherapy. We report a case of ovarian cancer, however, that responded well to the programmed cell death-ligand 1 inhibitor atezolizumab. CASE SUMMARY: A 64-year-old woman with recurrent ovarian carcinoma, not responsive to platinum/taxane and bevacizumab therapy, was BRCA normal but showed loss of MLH1 and PMS2 proteins. She was treated with atezolizumab. After the third cycle, her CA 125 levels decreased to normal. Radiologic evaluation showed a near-complete response. WHAT IS NEW AND CONCLUSION: Identifying response markers is important when choosing therapy for ovarian cancer patients.

Clinical impact of PD-L1 expression in triple-negative breast cancer patients with residual tumor burden after neoadjuvant chemotherapy.

BACKGROUND: Studies on PD-L1 expression in breast cancer have gained importance in recent years, especially in triple-negative breast cancer (TNBC). Our aim was to analyze the differential expression of PD-L1 to explore its correlation with response to neoadjuvant chemotherapy (NACT) and patient survival. METHODS: PD-L1 expression was evaluated immunohistochemically (Ventana SP263 clone kit) by staining tumor specimen. PD-L1 positivity was defined as membranous staining > 1%, > 5%, > 10%, and > 20% on either tumor cell (TC) and /or immune cell (IC). RESULTS: Fifty patients with locally advanced TNBC, who had a partial response to NACT, were included in the study. PD-L1 staining was observed in TCs in 25 patients (50%) and in ICs in 23 patients (46%) when PD-L1 > 1% was considered positive. Patients with PD-L1 positivity on ICs were more likely to respond to chemotherapy as measured by "MD Anderson Cancer Center Residual Cancer Burden Index" (14/22, 63.6% vs. 10/27, 37%, p = 0.064). The 5-year disease-free survival (DFS) and disease-specific survival (DSS) rates were 46.3% and 51.4%, respectively. A high (> 20%) tumoral PD-L1 positivity was associated with a better DFS and DSS. CONCLUSIONS: Studies in the literature mostly focused on PD-L1 expression in inflammatory cells. However, our results suggest that patients with a high PD-L1 expression on TCs were more likely to have a better outcome. Since patients with residual tumor burden who express PD-L1 on TILs were more likely to respond to NACT, an immune checkpoint inhibitor therapy in addition to NACT would be an important option for TNBC with locally advanced disease.

Does visceral adiposity have an effect on the survival outcomes of the patients with endometrial cancer?

AIM: Endometrial cancer is the most common cancer of the female reproductive tract in the developed countries. There are many risk factors defined for the development of endometrial cancer, including obesity. We aimed to evaluate the significance of adiposity on the survival outcomes of the patients with endometrial cancer. METHODS: The patients diagnosed with endometrial cancer and underwent surgery between April 2009 and October 2017 were retrospectively reviewed. The visceral adipose tissue and subcutaneous adipose tissue volumes were measured at the level of umbilicus on single-slice magnetic resonance imaging. Visceral adiposity index was calculated. Patients were compared regarding their clinical, demographical, pathologic and survival characteristics. Patients divided into low visceral adiposity (≤0.265, group 1) and high visceral adiposity (>0.265, group 2). RESULTS: A total of 186 patients were included in this retrospective study. There was no significant difference in terms of the demographical, clinical and tumor characteristics of the patients, except age, menopausal status, subcutaneous adipose tissue and visceral adipose tissue. Although no significant difference in progression-free survival and disease-specific survival was noted between groups (P = 0.181), more patients in group 2 died because of endometrial cancer as statistically significant (P = 0.024). Disease-specific survival showed a significant difference between groups according to the log-rank test. CONCLUSION: Visceral adiposity tissue is a significant and reliable prognostic indicator for endometrial cancer prognosis. Women diagnosed with endometrial cancer should be informed about the deleterious effects of visceral adiposity on disease-specific survival.

"Door to Treatment" Outcomes of Cancer Patients during the COVID-19 Pandemic.

BACKGROUND: The novel coronavirus disease 2019 has become a worldwide threat. We aimed to explore reflections of these unexpected changes to newly diagnosed cancer patients. METHOD: We searched the 2 months after the index case of our country. The first admission day and the first day of intravenous treatment of newly diagnosed patients were recorded. RESULTS: In the 60 days measured during the pandemic, the total number of patients on polyclinics was 159/weekdays, and the total applied chemotherapy cycles were 276/week. For comparison, the total numbers in the previous year were 267/weekday and 363/week for polyclinic and applied chemotherapy cycles, respectively. The total number of newly admitted patients in 2020 was 283. For comparison, the number of new patients in the same 60-day period in 2019 was 495. Patients who were admitted for adjuvant treatment required a median of 8 days for the first course, those who were admitted for neoadjuvant treatment required 12 days, and metastatic patients required 14 days; there were no significant differences between treatment types (p = 0.233). However, the median treatment time was 11.5 and 17 days, in 2020 and in 2019, respectively. A significant difference was observed between the 2 groups (p < 0.001). CONCLUSION: The effective shift of workers and accurate regulations have not resulted in apparent delays in patient care. While a decrease in the number of patients has detected, faster healthcare service was introduced to newly diagnosed patients. The reason for the decrease in the number of patients should be investigated with new studies.

Worse patient-physician relationship is associated with more fear of cancer recurrence (Deimos Study): A study of the Palliative Care Working Committee of the Turkish Oncology Group (TOG).

OBJECTIVE: Fear of cancer recurrence (FCR) is an important psychological trauma associated with reduction in the quality of life, disruptions in the level of adjustment, emotional distress and anxiety. The purpose of the study was to evaluate the impact of patient-physician relationship on FCR. METHODS: The study was designed as a multicentre survey study. The cancer survivors, who were under remission, were evaluated with structured questionnaires. Patient-physician relationship (PPR) scale in which higher scores indicate better relationship and FCR inventory was used. RESULTS: Between January and April 2019, 1,580 patients were evaluated. The median age was 57.0 (19-88), and 66% were female. There was high level of FCR scores in 51% of participants. There was a negative correlation between PPR and FCR scores (r = -.134, p < .001). In multivariate analysis, young age, female gender, history of metastasectomy and worse PPR were associated with high levels of FCR. CONCLUSION: It is the first data showing the adverse impact of worse PPR on FCR. The strategies to improve the PPR should be practised. In addition, the cancer survivors, who are under the risk of FCR, should be evaluated and managed.

The Relationship of Pathological Response and Visceral Muscle and Fat Volume in Women With Breast Cancer Who Received Neoadjuvant Chemotherapy.

Objective: Differences in individual muscle/fat volumes may change the effectiveness of chemotherapy. In this study, the relationship between trunkal muscle and fat volume and body mass index (BMI) obtained before receiving neoadjuvant chemotherapy (NCT) in patients with breast cancer and complete pathological response (pCR) was investigated. Materials and Methods: The volumes of psoas, abdominal and paraspinal muscles, and trunkal subcutaneous and visceral fat were calculated using CoreSlicer AI 2.0 opensource program from the F-18 fluorodeoxyglucose positron emission tomography/computed tomography (CT) and CT images before NCT and postoperative pCR rates to NCT were recorded. Muscle/fat volumes and BMI prior to NCT were compared in terms of pathological pCR rates. Patients were followed up regularly for recurrence and survival. Results: Ninety-three patients were included with median (range) values for age, BMI, and body weights of 48 (28-72) years, 27 (16.8-51.6) kg/m2, and 71.94 (43-137) kg, respectively. The median follow-up time was 18.6 (6.7-59.6) months. No significant correlation was found between total muscle or fat volumes of patients with and without pCR. BMI [26.2 (16.8-51.6) kg/m2 vs. 24.6 (20.3-34.3) kg/m2, p = 0.03] and pCR rates in patients with low right-psoas muscle volume [11.74 (7.03-18.51) vs. 10.2 (6.71-13.36), p = 0.025] were significantly greater. A significant relationship was found between right psoas muscle volume and disease-free survival (DFS) (11.74 cm3 (7.03-18.51) vs. 10.2 cm3 (6.71-13.36), p = 0.025). However, no significant relationship was detected between total muscle-fat volume, BMI and overall survival and DFS (p>0.05). Conclusion: This is the first published study investigating the relationship between the pCR ratio and body muscle and fat volume measured by CoreSlicer AI 2.0 in patients with breast cancer who received NCT. No correlation was found between the pCR ratio and total muscle plus fat volume. However, these results need to be validated with larger patient series.

Real-world data on the efficacy and safety of trastuzumab emtansine in patients with metastatic breast cancer previously treated with pertuzumab: Turkish oncology group multicenter study.

We aimed to evaluate the efficacy and safety of trastuzumab emtansine in patients with metastatic breast cancer previously treated with pertuzumab plus trastuzumab and taxane. We reviewed the medical records of patients who were diagnosed with Human Epidermal Growth Factor Receptor 2 (HER-2) positive metastatic breast cancer and received pertuzumab and then TDM-1 between January 2014 and January 2021 from twenty- five cancer centers. The Kaplan- Meier method estimated progression-free survival (PFS) and overall survival (OS). Additionally, objective response rate (ORR), clinical benefit rate (CBR), and safety were evaluated. One hundred fifty-three patients were included,79.1% of the patients received TDM-1 in the second line, 90.8% had visceral metastasis, and 30.7% had central nervous system involvement. The PFS and OS of TDM-1 were evaluated according to the number of previous lines (on the 2nd line or more than two lines) metastatic sites (visceral and non-visceral) and the presence of central nervous metastasis. In TDM-1 therapy, PFS in second line therapy was ten months (95% CI: 7.7 - 12.2); this was statistically higher than later-line PFS, which was six months (95% CI: 3.3 to 8.6) (p = 0.004). The median OS time was 25 months (95% CI: 21.0 to 28.9) in patients treated with TDM-1 in the second line and 19 months (95% CI: 12.3 to 25.6) in patients who received later than the second line(p = 0.175). There were no significant differences in PFS time of patients with and without visceral and central nervous metastases. Our study showed that TDM-1 was also effective in patients using pertuzumab, contributes significantly to PFS when used in the second line compared to its use in the later line, and does not make any difference in OS.

Prognostic Factors Influencing Progression-Free Survival in HER2-Positive Metastatic Breast Cancer Patients Who Were Treated With A Combination of Lapatinib and Capecitabine.

Objective: The aim was to assess the prognostic variables in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer patients receiving lapatinib plus capecitabine. Materials and Methods: Retrospective data on HER2-positive metastatic breast cancer patients who received lapatinib and capecitabine were analyzed. Survival outcome was obtained with Cox regression analysis and the Kaplan-Meier method. Results: The study included 102 patients. Forty-four (43.1%) patients had de novo metastatic disease. The most frequent metastatic sites were, in order, bone (61.8%), brain (57.8%), liver (35.3%), and lung (34.3%). All of the patients had previously received chemotherapy based on trastuzumab. With combined lapatinib and capecitabine, complete response was observed in 7.8%, partial response in 30.4%, and stable disease in 24.5%. Progression-free survival was 8 (95% confidence interval, 5.1-10.8) months. In multivariable analysis, endocrine therapy (p = 0.02), de novo metastatic disease (p = 0.02), and age (p = 0.02) were prognostic factors for progression-free survival. However, the number of chemotherapy cycles with trastuzumab, palliative radiotherapy, history of breast surgery, and the number of metastatic sites were not significant in this respect. Conclusion: These results have demonstrated the effectiveness of lapatinib plus capecitabine in metastatic HER2-positive breast cancer patients. Furthermore, unfavorable prognostic factors for progression-free survival were shown to be hormone-negative tumor, de novo metastatic disease, and young age.