Primary Operable Breast Cancer Research Articles

Abstract PO3-01-04: Neoadjuvant compared to adjuvant chemotherapy combined with trastuzumab in patients with HER2-positive breast cancer: a register-based cohort study

Abstract Introduction Neoadjuvant therapy (NAT) is considered the standard of care in patients with HER2-positive breast cancer mainly due to the possibility to adjust the post-neoadjuvant treatment based on the tumor response to NAT. However, there is no convincing evidence on a survival benefit with NAT compared to adjuvant therapy (AT) for HER2-positive breast cancer. The aim of the present study was to compare the two therapeutic strategies in a register-based cohort of Swedish patients with primary operable HER2-positive breast cancer. Method The research database BCBaSe 3.0, which is based on the Swedish National Quality breast cancer register, was used to identify patients with primary operable HER2-positive breast cancer that diagnosed between 2008 and 2020 and received either NAT or AT including chemotherapy and trastuzumab. To mitigate confounding by indication bias, propensity score matching (PSM) with 1:1 matching was applied. The effectiveness of the two therapeutic strategies was investigated through analyzing distant disease-free survival (DDFS), breast-cancer specific survival (BCSS), and overall survival (OS). Multivariate Cox regression analyses were performed for the outcomes of interest to provide Hazard Ratios (HR) and corresponding 95% Confidence Intervals (CI). Results In total, 7258 patients with primary operable HER2-positive breast cancer treated with either NAT or AT were identified, 1789 (24.6%) received NAT and 5469 (75.4%) AT. After 1:1 PSM, 1258 patients in each therapeutic strategy were available for comparisons. After a median follow-up of 63 months, no statistically significant differences between NAT and AT were observed in either outcome (HR for DDFS: 0.97; 95% CI: 0.72 – 1.30; HR for BCSS: 0.69; 95% CI: 0.45 – 1.07; HR for OS: 0.72; 95% CI: 0.50 – 1.05). In subgroup analyses, estrogen-receptor status did not impact the results that remained statistically non-significant between NAT and AT whereas in patients with clinically positive lymph node status, NAT resulted in better BCSS (HR: 0.44; 95% CI: 0.22 – 0.89) and OS (HR: 0.49; 95% CI: 0.29 – 0.90). The latter trend was not evident in patients with clinically negative lymph node status. Conclusion Our study results confirm the equivalence of NAT and AT in terms of prognosis for patients with operable HER2-positive disease and imply a potential benefit of NAT compared to AT in patients with clinically positive lymph node status. Considering the emerging treatment strategies in HER2-positive breast cancer patients treated with NAT (pertuzumab as a part of NAT, T-DM1 as post-neoadjuvant therapy) that have been shown to improve survival but are not reflected in the study cohort, NAT should be considered as the strategy with the higher possibility to improve long-term prognosis for patients with HER2-positive disease. Citation Format: Servah Hosseini-Mellner, Åsa Wickberg, Antonis Valachis, Andreas Karakatsanis. Neoadjuvant compared to adjuvant chemotherapy combined with trastuzumab in patients with HER2-positive breast cancer: a register-based cohort study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-01-04.

Reliability of predicting low-burden (≤ 2) positive axillary lymph nodes indicating sentinel lymph node biopsy in primary operable breast cancer — a retrospective comparative study with PET/CT and breast MRI

BackgroundSentinel lymph node biopsy (SLNB) is the standard of care for axillary staging in early breast cancer patients with low-burden axillary metastasis (≤ 2 positive nodes). This study aimed to determine the diagnostic performances of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and breast magnetic resonance imaging in detecting axillary lymph node (ALN) metastases and the reliability to predict ALN burden.MethodsA total of 275 patients with primary operable breast cancer receiving preoperative PET/CT and upfront surgery from January 2001 to December 2022 in a single institution were enrolled. A total of 244 (88.7%) of them also received breast MRI. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET/CT and breast MRI were assessed. The predictive values to determine ALN burden were evaluated using radio-histopathological concordance.ResultsPET/CT demonstrated a sensitivity of 53.4%, specificity of 82.1%, PPV of 65.5%, NPV of 73.5%, and accuracy of 70.9% for detecting ALN metastasis, and the corresponding values for MRI were 71.8%, 67.8%, 56%, 80.8%, and 69.2%, respectively. Combining PET/CT and MRI showed a significantly higher PPV than MRI (72.7% vs 56% for MRI alone, p = 0.037) and a significantly higher NPV than PET/CT (84% vs 73.5% for PET/CT alone, p = 0.041). For predicting low-burden axillary metastasis (1–2 positive nodes), the PPVs were 35.9% for PET/CT, 36.7% for MRI, and 55% for combined PET/CT and MRI. Regarding patients with 0–2 positive ALNs in imaging, who were indicated for SLNB, the predictive correctness was 96.1% for combined PET/CT and MRI, 95.7% for MRI alone, and 88.6% for PET/CT alone.ConclusionsPET/CT and breast MRI exhibit high predictive values for identifying low-burden axillary metastasis in patients with operable breast cancer with ≦ 2 positive ALNs on imaging.

Практические рекомендации по лекарственному лечению первично операбельного рака молочной железы

Breast cancer (BC) treatment implies an integrated approach that involves inclusion of surgical techniques, radiation therapy, chemotherapy, endocrine therapy, targeted therapy, and in some cases immunotherapy in the treatment plan, while selection of treatment tactics depends on the tumor biological subtype, neoplastic process extension, and somatic status of the patient. The paper provides analysis of Russian clinical guidelines and advanced treatment regimens for primary operable BC that are based on the principle of case-by-case selection in each clinical situation considering the disease stage, tumor molecular subtype and the goals set by an expert specialist.

Correlation of SUV on Early Interim PET with Recurrence-Free Survival and Overall Survival in Primary Operable HER2-Positive Breast Cancer (the TBCRC026 Trial).

Predictive biomarkers of response to human epidermal growth factor receptor 2 (HER2)-directed therapy are essential to inform treatment decisions. The TBCRC026 trial reported that early declines in tumor SUVs corrected for lean body mass (SULmax) on 18F-FDG PET/CT predicted a pathologic complete response (pCR) to HER2 therapy with neoadjuvant trastuzumab and pertuzumab (HP) without chemotherapy in estrogen receptor (ER)-negative, HER2-positive breast cancer. We hypothesized that 18F-FDG PET/CT SULmax parameters would predict recurrence-free survival (RFS) and overall survival (OS). Methods: Patients with stage II/III ER-negative, HER2-positive breast cancer received neoadjuvant HP (n = 88). pCR after HP alone was 22% (18/83), additional nonstudy neoadjuvant therapy was administered in 28% (25/88), and the majority received adjuvant therapy per physician discretion. 18F-FDG PET/CT was performed at baseline and at cycle 1, day 15 (C1D15). RFS and OS were summarized using the Kaplan-Meier method and compared between subgroups using logrank tests. Associations between 18F-FDG PET/CT (≥40% decline in SULmax between baseline and C1D15, or C1D15 SULmax ≤ 3) and pCR were evaluated using Cox regressions, where likelihood ratio CIs were reported because of the small numbers of events. Results: Median follow-up was 53.7 mo (83/88 evaluable), with 6 deaths and 14 RFS events. Estimated RFS and OS at 3 y was 84% (95% CI, 76%-92%) and 92% (95% CI, 87%-98%), respectively. A C1D15 SULmax of 3 or less was associated with improved RFS (hazard ratio [HR], 0.36; 95% CI, 0.11-1.05; P = 0.06) and OS (HR, 0.14; 95% CI, 0.01-0.85; P = 0.03), the latter statistically significant. The association of an SULmax decline of at least 40% (achieved in 59%) with RFS and OS did not reach statistical significance. pCR was associated with improved RFS (HR, 0.25; 95% CI, 0.01-1.24; P = 0.10) but did not reach statistical significance. Conclusion: For the first time, we report a potential association between a C1D15 SULmax of 3 or less on 18F-FDG PET/CT and RFS and OS outcomes in patients with ER-negative, HER2-positive breast cancer receiving neoadjuvant HP alone. If confirmed in future studies, this imaging-based biomarker may facilitate early individualization of therapy.

Diagnostic accuracy of pre-operative breast magnetic resonance imaging (MRI) in predicting axillary lymph node metastasis: variations in intrinsic subtypes, and strategy to improve negative predictive value—an analysis of 2473 invasive breast cancer patients

BackgroundThe value and utility of axillary lymph node (ALN) evaluation with MRI in breast cancer were not clear for various intrinsic subtypes. The aim of the current study is to test the potential of combining breast MRI and clinicopathologic factors to identify low-risk groups of ALN metastasis and improve diagnostic performance.Material and methodsPatients with primary operable invasive breast cancer with pre-operative breast MRI and post-operative pathologic reports were retrospectively collected from January 2009 to December 2021 in a single institute. The concordance of MRI and pathology of ALN status were determined, and also analyzed in different intrinsic subtypes. A stepwise strategy was designed to improve MRI-negative predictive value (NPV) on ALN metastasis.Results2473 patients were enrolled. The diagnostic performance of MRI in detecting metastatic ALN was significantly different between intrinsic subtypes (p = 0.007). Multivariate analysis identified tumor size and histologic type as independent predictive factors of ALN metastases. Patients with HER-2 (MRI tumor size ≤ 2 cm), or TNBC (MRI tumor size ≤ 2 cm) were found to have MRI–ALN-NPV higher than 90%, and these false cases were limited to low axillary tumor burden.ConclusionThe diagnostic performance of MRI to predict ALN metastasis varied according to the intrinsic subtype. Combined pre-operative clinicopathologic factors and intrinsic subtypes may increase ALN MRI NPV, and further identify some groups of patients with low risks of ALN metastasis, high NPV, and low burdens of axillary disease even in false-negative cases.

Perspectives and possibilities of preserving reproductive function in patients receiving antitumor treatment. Clinical observation

Currently, treatment of patients with early primary operable BRCA mutation-associated breast cancer requires integrative approach. A mutation in BRCA1/2 genes is a prognostically unfavorable factor increasing the risk of cancer of the contralateral breast, as well as ovaries, pancreas, fallopian tubes, and primary peritoneal cancer. In this clinical observation, an integrative multidisciplinary approach to treatment of a young patient with luminal B breast cancer is described which allowed to preserve the patient’s fertility and achieve pregnancy using assisted reproductive technologies.High effectiveness of the chosen treatment tactics in the framework of integrative approach in a specialized medical facility with experience in treatment of oncological diseases and preservation of reproductive function confirmed by clinical data and results of laboratory and instrumental exams is demonstrated.

Patritumab deruxtecan in untreated hormone receptor-positive/HER2-negative early breast cancer: final results from part A of the window-of-opportunity SOLTI TOT-HER3 pre-operative study

Patritumab deruxtecan (HER3-DXd) is a HER3-directed antibody-drug conjugate composed of a fully human anti-HER3 monoclonal antibody (patritumab) covalently linked to a topoisomerase I inhibitor payload via a stable, tumor-selective, tetrapeptide-based cleavable linker. TOT-HER3 is a window-of-opportunity study designed to assess the biological activity, measured by CelTIL score [ = -.8 × tumor cellularity (in %) + 1.3 × TILs (in %)], and clinical activity of HER3-DXd during short-term (21 days) pre-operative treatment in patients with primary operable HER2-negative early breast cancer. Patients with previously untreated hormone receptor (HR)-positive/HER2-negative tumors were allocated to one of four cohorts according to baseline ERBB3 mRNA expression. All patients received one dose of HER3-DXd 6.4 mg/kg. The primary objective was to evaluate change from baseline in CelTIL score. Seventy-seven patients were evaluated for efficacy. A significant change in CelTIL score was observed, with a median increase from baseline of 3.5 (interquartile range, -3.8 to 12.7; P=.003). Among patients evaluable for clinical response (n=62), an overall response rate of 45% was observed (tumor measurement by caliper), with a trend toward an increase in CelTIL score among responders compared with non-responders (mean difference, +11.9 vs +1.9). Change in CelTIL score was independent of baseline ERBB3 mRNA and HER3 protein levels. Genomic changes occurred, including switching toward a less proliferative tumor phenotype based on PAM50 subtypes, suppression of cell proliferation genes, and induction of genes associated with immunity. Treatment-emergent adverse events were observed in 96% of patients (14% grade ≥3); most common were nausea, fatigue, alopecia, diarrhea, vomiting, abdominal pain, and neutrophil count decrease. A single dose of HER3-DXd was associated with clinical response, increased immune infiltration, suppression of proliferation in HR-positive/HER2-negative early breast cancer, and a tolerable safety profile consistent with previously reported results. These findings support further study of HER3-DXd in early breast cancer.

124O Patritumab deruxtecan (HER3-DXd) in hormonal receptor-positive/HER2-negative (HR+/HER2-) and triple-negative breast cancer (TNBC): Results of part B of SOLTI TOT-HER3 window of opportunity trial

We previously reported the biologic and clinical activity of HER3-DXd in Part A of SOLTI TOT-HER3 in patients (pts) with HR+/HER2- early breast cancer (BC) after a single dose of 6.4 mg/kg (Prat A. et al, ESMO BREAST 2022). Here, we present the main efficacy and safety results of TOT-HER3 Part B. In Part B of this window of opportunity trial, 2 cohorts of pts with treatment-naïve HER2- primary operable BC, ≥1 cm by US or MRI were recruited. Pts received a single dose of HER3-DXd 5.6 mg/kg. Primary objective was the variation in tumor cellularity and tumor-infiltrating lymphocytes (CelTIL) score between pre- and post-treatment tumors. Associations of baseline clinical and biological features with CelTIL changes and overall response rate (ORR) by US were explored. Thirty-seven pts with HER2- BC were recruited (HR+ n=20; TNBC n=17). Mean age was 53 (30-81); 20 (54%) were pre-menopausal; mean tumor size was 21 mm (range 10-81 mm); and median Ki67 was 30% (12-95%). In response to treatment with HER3-DXd CelTIL score increased and decreased in 21 (57%) and 16 (43%) pts, respectively. Overall, a statistically significant change in CelTIL was observed between paired samples overall (p=0.046) and in TNBC (p=0.016), but not in HR+ (p=0.793). ORR by US in all patients was 32% (35% in TNBC and 30% in HR+). The absolute change in CelTIL was associated with ORR (AUC=0.693; p=0.049). Baseline ERBB3 levels were not associated with CelTIL change or ORR. HER3-DXd induced high expression of immune-related genes (e.g., PD1, CD8 and CD19), and suppressed proliferation-related genes. Thirty-one (84%) patients reported AEs at any grade. Most common AEs were nausea, fatigue, alopecia, diarrhea, constipation and vomiting. Grade 3 treatment-related nausea occurred in 1 patient. No ILD events were reported. A single dose of HER3-DXd was associated with clinical response and significant biological changes in HER2- tumors, irrespective of baseline ERBB3 levels. The safety profile was consistent with that previously reported. Additional correlative analysis will be presented on site.

Effect of preoperative chemotherapy on the outcome of women with operable breast cancer.

To determine, in women with primary operable breast cancer, if preoperative doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan; AC) therapy yields a better outcome than postoperative AC therapy, if a relationship exists between outcome and tumor response to preoperative chemotherapy, and if such therapy results in the performance of more lumpectomies. Women (1,523) enrolled onto National Surgical Adjuvant Breast and Bowel Project (NSABP) B-18 were randomly assigned to preoperative or postoperative AC therapy. Clinical tumor response to preoperative therapy was graded as complete (cCR), partial (cPR), or no response (cNR). Tumors with a cCR were further categorized as either pathologic complete response (pCR) or invasive cells (pINV). Disease-free survival (DFS), distant disease-free survival (DDFS), and survival were estimated through 5 years and compared between treatment groups. In the preoperative arm, proportional-hazards models were used to investigate the relationship between outcome and tumor response. There was no significant difference in DFS, DDFS, or survival (P = .99, .70, and .83, respectively) among patients in either group. More patients treated preoperatively than postoperatively underwent lumpectomy and radiation therapy (67.8% v 59.8%, respectively). Rates of ipsilateral breast tumor recurrence (IBTR) after lumpectomy were similar in both groups (7.9% and 5.8%, respectively; P = .23). Outcome was better in women whose tumors showed a pCR than in those with a pINV, cPR, or cNR (relapse-free survival [RFS] rates, 85.7%, 76.9%, 68.1%, and 63.9%, respectively; P < .0001), even when baseline prognostic variables were controlled. When prognostic models were compared for each treatment group, the preoperative model, which included breast tumor response as a variable, discriminated outcome among patients to about the same degree as the postoperative model. Preoperative chemotherapy is as effective as postoperative chemotherapy, permits more lumpectomies, is appropriate for the treatment of certain patients with stages I and II disease, and can be used to study breast cancer biology. Tumor response to preoperative chemotherapy correlates with outcome and could be a surrogate for evaluating the effect of chemotherapy on micrometastases; however, knowledge of such a response provided little prognostic information beyond that which resulted from postoperative therapy.

Efficacy and Safety of Nanosomal Docetaxel Lipid Suspension (NDLS) versus Conventional Docetaxel as Neoadjuvant and Adjuvant Therapy for Primary Operable Breast Cancer.

Nanosomal docetaxel lipid suspension (NDLS) is a novel formulation developed to overcome toxicity issues caused by excipients (polysorbate 80 and ethanol) present in commercially available docetaxel formulation. We conducted a prospective, observational study to compare the outcomes of nanosomal docetaxel lipid suspension (NDLS)-based versus conventional docetaxel-based chemotherapy in primary operable breast cancer. Sixty adult women with newly diagnosed stage IIb-III breast cancer were included. Patients received NDLS-based (n=30) or docetaxel-based (n=30) chemotherapy. Patients received (1) four cycles of preoperative doxorubicin and cyclophosphamide (AC) followed by four cycles of NDLS or docetaxel (T) and surgery (neoadjuvant AC→NDLS [n=9], or neoadjuvant AC→T [n=10]), or (2) four cycles of preoperative AC followed by surgery and postoperative NDLS or T (neoadjuvant AC→adjuvant NDLS [n=14], or neoadjuvant AC→adjuvant T [n=15]), or (3) surgery followed by postoperative AC→NDLS or T (adjuvant AC→NDLS [n=7], or adjuvant AC→T [n=5]) regimens. The study outcomes were pathological complete response (pCR) rates, clinical overall response rates (ORR), disease-free survival (DFS), overall survival (OS), and adverse event (AE) profile. For neoadjuvant AC→T (n=10) vs neoadjuvant AC→NDLS (n=9), the pCR rates were 100% each, and the ORR were 100% vs 88.9% (p=1.0). All patients were alive at 6 months, and the median OS was not reached. Three patients had progressive disease (T: n=2, NDLS: n=1) with a DFS of 12 weeks in all three patients. Grade 3 infusion-related reactions were seen in five patients (16.7%) in T vs none in NDLS arms. NDLS-based neo/adjuvant chemotherapy was efficacious in the treatment of primary operable breast cancer and showed comparable pCR, ORR, DFS and OS rates versus conventional docetaxel. NDLS was better tolerated than conventional docetaxel.

The Association Between Medication Use in Older Women with Early-Stage Operable Primary Breast Cancer and Decision Regarding Primary Treatment.

Polypharmacy is one factor contributing to increased mortality, hospitalization, and adverse drug reactions in older adults. The aim of this study was to measure the prevalence of polypharmacy in a cohort of older women with early-stage operable primary breast cancer and the relationship of polypharmacy to primary treatment decision and functional status. A total of 139 patients with a new diagnosis of early-stage operable primary breast cancer proven histologically were recruited as part of a prospective study. The average age was 77 years. Assessment using a cancer-specific Comprehensive Geriatric Assessment (CGA) tool was conducted within 6 weeks of diagnosis of breast cancer. Association was determined between number of medications and treatment decision and physical status as measured by the CGA outcomes. Additional analysis was performed to determine the associations above with polypharmacy defined by ≥5 daily medications, and if cardiovascular-related diseases have a role in the treatment decision. Polypharmacy was present in 48% of patients (n = 139). CGA determined that polypharmacy was associated with greater comorbidity (P < .001), reduced physical status rated by physicians (P = .009) and patients (P = .019), and reduced ability to perform activities of instrumental ADLs (P = .008). Similar findings were present in the analysis of cardiovascular-related diseases. This work suggests that patients with polypharmacy are more likely to be frail. The number of medications could help us screen patients who should go on to receive full CGA.

The Evaluation of a Cost-Effective Method for Tumour Marking Prior to Neo-Adjuvant Chemotherapy Using Silver Rods.

The lack of objective documentation of pre-neoadjuvant chemotherapy (NAC) tumour margins is a major constraint in performing safe breast conserving surgery (BCS) in patients with breast cancer. Using a novel method of marking pre-NACT tumour margins with indigenous silver wire markers, this retrospective observational study attempted to assess the feasibility of safe BCS in breast cancer patients by performing excision wide of the marked pre-NACT margins. This retrospective observational study was conducted on breast cancer patients who were attending our oncology centre between May, 2015 and April, 2022. All patients had received NAC followed by surgery as recommended by our multidisciplinary team. All the patients had a primary operable solitary breast cancer. We used radiopaque metallic rods made from silver to localize tumour margins prior to NAC. Sixty-four breast cancer patients were included; none had marker-related complications. Following NAC, BCS could be easily performed in 60 patients guided by the silver markers, which were used as temporary implants and removed during surgery. Only 2 patients were seen with positive margins and were converted to mastectomy. Breast cancer localization using sterile silver markers before the initiation of NAC is safe, easy, inexpensive, and effective, causing no morbidity or significant pain to the patients.

191P Correlation of early change in standardized uptake value (SUV) on positron emission tomography (PET/CT) with recurrence-free survival (RFS) and overall survival (OS) in patients with primary operable HER2-positive breast cancer (TBCRC026)

Predictive biomarkers of response to HER2-directed therapy are essential to inform treatment decisions. The TBCRC026 trial reported that early changes in tumor standardized uptake values corrected for lean body mass (SULmax) on FDG-PET/CT predicted pathologic complete response (pCR) to neoadjuvant trastuzumab and pertuzumab (HP) in HER2-positive breast cancer (PMID:33999652). We hypothesized that early changes on FDG-PET/CT will predict RFS/OS.

Evaluation of the results of neoadjuvant treatment in patients with HER2 positive breast cancer subtype

Background. In women, breast cancer is the most common malignant tumor. Based on current clinical guidelines for HER2 positive tumor growth, it is possible to carry out preoperative chemotherapy for further organ-preserving operations. However, a prognostic scale for assessing neoadjuvant treatment has not yet been developed.&#x0D; Aim. To create a mathematical model on the basis of which a computer program was developed to determine the likelihood of the neoadjuvant treatment effectiveness in patients diagnosed with HER2 positive breast cancer for further organ-preserving operations.&#x0D; Material and methods. A planned retrospective study was performed at the Samara Regional Clinical Oncology Dispensary to assess the results of combined treatment of 93 patients diagnosed with breast cancer with HER2-positive tumor growth subtype with organ-preserving operations. The age of the patients was from 31 to 62 years, the mean age was 47.119.78 years. Three (15.53%) patients were diagnosed with stage I of the disease according to the TNM system, and 90 (84.47%) with stage II. A search for statistically significant predictors of achieving morphological regression as a result of preoperative chemotherapy was carried out.&#x0D; Results. The mathematical model was created in the logistic regression module according to Wald's algorithm. Using SPSS 10.0, stepwise exclusion of predictors was performed. As a result of the multivariate analysis, a mathematical model and the corresponding program for the electronic computer Calculation of the achievement of complete morphological regression in patients diagnosed with primary operable breast cancer with epidermal growth factor receptors after neoadjuvant chemotherapy were created. In the future, the evaluation of the effectiveness of this program was compared with the results of 206 patients treatment.&#x0D; Conclusion. The creation of a mathematical model and a computer program made it possible to personalize the most effective treatment regimen for patients diagnosed with HER2 positive breast cancer, depending on the initial characteristics of the tumor.

РЕКОНСТРУКТИВНО-ПЛАСТИЧЕСКИЕ ОПЕРАЦИИ С ИСПОЛЬЗОВАНИЕМ ЭНДОПРОТЕЗА В СОЧЕТАНИИ С ЛУЧЕВОЙ ТЕРАПИЕЙ У БОЛЬНЫХ ПЕРВИЧНО-ОПЕРАБЕЛЬНЫМ РАКОМ МОЛОЧНОЙ ЖЕЛЕЗЫ (СT1-2N0-1M0)

Purpose: indications for determination of radiation therapy in patients with primary operable breast cancer (сT1-2N0-1M0) after skin-sparing/nipple-sparring mastectomy with immediate breast reconstruction. Material and methods: The study analyzed 203 patients who underwent skin-sparing (58 cases (28.6%)) or nipple-sparring (145 cases (71.4%)) mastectomy with immediate breast reconstruction as part of combined or complex treatment from January 2008 to March 2018. Radiation therapy was performed in 98 (48,2 %) cases on the reconstructed breast and the area of regional lymph nodes. Results: The presence of metastatic axillary lymph nodes (p=0.008) and lymphovascular invasion (p=0.048) correlates with deterioration in deseese-free survival. There were no significant differences in the rates of recurrence (p=0.734) and progression (p=0.432) in groups of patients with and without RT. However, due to the inclusion of an initially favorable group of patients and a small number of adverse outcomes, it was found that RT changes the risk of developing a relapse of the disease by no more than 3-4 times. Conclusions: Additional RT allowed to obtain the same results in the group цшер poor prognosis as in the group цшер favorable prognosis. The preliminary conclusion that RT does not affect treatment outcomes in the group with favorable prognosis should be validated in a study with larger number of observations.

Five-year survival in luminal breast cancer patients: relation with intratumoral activity of proteasomes.

The purpose of the study was to analyze the relationship between the caspase-like (CL) and chymotrypsin-like (ChTL) activities of proteasomes and the 5-year overall and metastasis-free survival rates in patients with luminal breast cancer. The study included 117 patients with primary operable invasive breast cancer (T1-2N0-1M0). Tissue samples from breast cancer patients were obtained as a result of the radical mastectomy or breast conserving surgery, which was a first line of therapy. The ChTL and CL proteasomes activities in the tumor tissue and in the surrounding adjacent breast tissues were assessed using the fluorometric method. The coefficients of ChTL (cChTL) and CL (cCL) proteasomes activities were also determined. The coefficients were calculated as the ratio of the corresponding proteasomes activity in the tumor tissue to the surrounding adjacent breast tissues. Within 5 years of follow-up, hematogenous metastases occurred in 14% of patients with luminal A breast cancer, in 31% of patients with luminal B human epidermal growth factor receptor-2 (HER-2) negative and in 23% of patients with luminal B HER-2 positive breast cancers. The study protocol was approved by the Local Ethics Committee of the Cancer Research Institute of Tomsk National Research Medical Center. Written informed consent was obtained from all patients. An increase in the ChTL and CL proteasomes activities was shown in all studied molecular subtypes of breast cancer compared to adjacent tissues. It was found that the cChTL of >35.9 U/mg protein and the cCL of >2.21 in breast cancer patients were associated with the development of distant metastases. In patients with luminal A breast cancer, the 5-year metastasis-free survival rates were associated only with the value of cCL of proteasomes (log-rank test: P=0.008). In patients with luminal B HER-2 negative breast cancer, the 5-year metastasis-free survival rates were associated with the levels of ChTL and cCL proteasomes activities (log-rank test: P=0.02 and P=0.04, respectively). The data obtained on the correlation of 5-year metastasis-free survival rates with the level of proteasomes activities indicate the possibility of their use as additional prognostic criteria for breast cancer.

Influence of alcohol sensitivity on bone metastases and skeletal-related events in primary operable breast cancer: A retrospective cohort study.

BackgroundBone metastases in breast cancer patients are a common concern for medical doctors and dentists. Bone-modifying agents, which are necessary to prevent skeletal-related events (SREs), are associated with osteonecrosis of the jaw as an adverse side effect. Hypersensitivity to alcohol is an unfavorable response caused by deficiency of aldehyde dehydrogenase-2 (ALDH2) activity. Inactive ALDH2 is associated with osteoporosis, but its influence on bone metastases is unclear. The aim of our study was to evaluate the effects of alcohol sensitivity on bone metastases and SREs in primary operable breast cancer patients.MethodsWe retrospectively analyzed patients who were administered docetaxel, an anti-tumor agent, for histologically diagnosed breast cancer between April 2004 and September 2015. Alcohol sensitivity was assessed based on medical records of hypersensitivity to alcohol. The primary endpoint was time to bone metastases and the secondary endpoint was time to first SRE from the initial docetaxel administration. Data were stratified by alcohol sensitivity and tumor stages, and differences were estimated by the Kaplan-Meier method. Prognostic risk factors were analyzed by the multivariate Cox proportional hazards model.ResultsThe median follow-up period of patients with high sensitivity to alcohol (n = 45) was 54 months and that for those with low sensitivity (n = 287) was 64 months. Stratification by alcohol sensitivity revealed that tumor stage exhibited significant correlations with the cumulative incidence of bone metastases in low-sensitivity patients; however, no differences were found in high-sensitivity patients. In multivariate analysis, alcohol sensitivity was a significant prognostic risk factor for bone metastases (HR 2.721, 95% CI 1.268–5.841, P = 0.010).ConclusionAlcohol sensitivity may be a prognostic risk factor for bone metastases. More detailed genetic investigations and metabolic analyses are needed.

Prognostic Factors and Models for Elderly (≥70 Years Old) Primary Operable Triple-Negative Breast Cancer: Analysis From the National Cancer Database.

BackgroundTriple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer. In the elderly (≥70 years old) primary operable (T1-3N0-1M0) TNBC, individualized treatment modalities for this population are pivotal and important, but limited studies are explored.MethodsThe clinicopathological features of elderly primary operable TNBC patients were retrospectively selected from the Surveillance, Epidemiology, and End Results (SEER) database between January 2010 and December 2015. Kaplan–Meier curves were used to show the survival patterns in the different subgroups. Multivariate Cox analysis was used to identify independent risk factors in the 3-, 5-, and 7- year overall survival (OS) and cancer-specific survival (CSS) in this subpopulation. The predictive model was further developed and validated for clinical use.ResultBetween 2010 and 2015 years, a total of 4,761 elderly primary operable TNBC patients were enrolled for the study, with a mean age of 76 years and a median follow-up of 56 months. The multivariate Cox analysis showed that age (increased per year: hazard ratio (HR) = 1.05), race (Asian/Pacific Islander and American Indian/Alaska Native, HR = 0.73), differentiation grade (grade II: HR = 2.01; grade III/IV: HR = 2.67), larger tumor size (T1c: HR = 1.83; T2: HR = 2.78; T3: HR = 4.93), positive N stage (N1mi: HR = 1.60; N1: HR = 1.54), receiving radiation therapy (HR = 0.66), and receiving adjuvant chemotherapy (HR = 0.61) were the independent prognostic factors for OS, and a similar prognostic pattern was also determined in CSS. Besides, two nomograms for predicting the 3-, 5-, and 7-year OS and CSS in this population were developed with a favorable concordance index of 0.716 and 0.746, respectively.ConclusionThe results highlight that both radiation and adjuvant chemotherapy are significantly associated with favorable long-term OS and CSS probability in elderly primary operable TNBC patients. Based on the determined independent prognostic factors, the novel nomograms could assist the oncologists to make individualized clinical decisions for the subpopulation at different risks.

Evaluation of KISS1 Receptor Gene Expression in Egyptian Female Patients with Breast Cancer.

Objective:Breast cancer is the second most common cancer in the world. Many metastasis suppressor genes were identified, including the KISS1 gene which encodes for a 145 amino acid protein (kisspeptin-145), which undergoes proteolytic cleavage resulting in kisspeptin-14, -13 and -10. All of these proteins can activate KISS1 receptor (KISS1R). The role of KP/KISS1R signaling in breast cancer remains controversial. The present study aimed to measure mRNA gene expression of KISS1 receptor in healthy and cancerous breast tissue and to evaluate the association of its level with the available molecular subtypes and the traditional clinico-pathological variables. Methods:The study was done on 41 operable primary breast cancer patients. Biopsies from both tumor tissue and surrounding healthy mammary tissue were taken from all patients. KISS1R mRNA expression level was measured using a quantitative real time PCR. Results:KISS1R mRNA expression was significantly higher in stage III patients compared to stage II patients. At a cut-off value for KISS1R mRNA expression of 1.75, stage II was discriminated from stage III. A significant positive correlation was found between KISS1R mRNA expression and tumor size as well as lymph nodes metastasis. KISS1R mRNA was highly expressed in ER negative cases compared to ER positive ones, and in PR negative cases compared to PR positive ones. There was a statistically significant difference in KISS1R mRNA expression levels and different molecular subtypes being over-expressed in HER2 and triple negative cancer cases. Conclusion:This study supports other studies suggesting that KISS1/KISS1R may not be acting as a metastasis suppressor in breast cancer. KISS1R mRNA is over expressed in advanced stages of breast cancer and hence it can be used as a prognostic marker for aggressiveness of breast cancer. Also being over expressed in triple negative patients, KISS1R could represent a promising therapeutic target in triple negative cases.

Comparative analysis of the CYP2D6 metabolic activity and its effect on its effect on the treatment results of primary breast cancer

Background. Standard treatment for hormone receptor-positive breast cancer includes long-term hormone therapy. However, treatment efficacy varies even in homogeneous groups of patients. Tamoxifen is metabolized in the liver, resulting in the production of endoxifen, its active metabolite. Cytochromes P450 (CYP2D6, etc.) play a major role in converting tamoxifen to endoxifen. The CYP2D6 gene is extremely polymorphic and has more than 100 alleles that can encode normal, high, and low metabolic activity or be inactive. Thus, patients can be divided into three groups according to the presence or absence of CYP2D6 gene polymorphisms, namely slow, intermediate, and rapid metabolizers. Objective – to analyze the long-term results of complex treatment of patients with early breast cancer depending on the variability of the polymorphism of the CYP2D6 gene. Materials and methods. We analyzed the frequency of 3 main polymorphisms in the CYP2D6 gene among 89 patients with hormone receptor-positive stage I–II breast cancer who received tamoxifen at a dose of 20 mg/day as adjuvant hormone therapy for 6 months to 9 years. Homozygous carriers of wild-type CYP2D6 allele were assigned to the group of patients with unchanged (normal) metabolism (Group 1) (wt CYP2D6) (n = 64), whereas homozygous and heterozygous carriers of non-functional CYP2D6 alleles were included into the group of patients with slow metabolism (Group 2) (n = 25). Results. Disease progression was observed in 21 (23.6 %) patients with primary operable hormone receptor-positive breast cancer, including 10 women from Group 1 (15.6 %) and 11 women from Group 2 (44 %); the difference between them was statistically significant (p &lt;0.05). Disease progression after combination therapy without chemotherapy was registered in 8 (22.9 %) patients, including 2 (5.8 %) patients with normal metabolism and 6 patients (17.1 %) with slow metabolism (р &lt;0.05). Ten-year relapse-free survival rate was 85.9 % in Group 1 and 63.6 % in Group 2 (р = 0.02). We found no significant difference in overall survival rates between the two groups, which confirmed the results of other studies. Conclusion. The assessment of metabolic activity and its impact on the efficacy of combination treatment for breast cancer is a promising method; however, it requires further research in this area.