Local Recurrence Of Breast Cancer Research Articles

Impact of semaglutide and tirzepatide administration on weight in women with stage I-III breast cancer.

e24140 Background: Weight gain and obesity are significant problems for women receiving adjuvant therapy for breast cancer and obesity is associated with adverse breast cancer outcomes. In addition, obesity is associated with negative impact on overall physical and mental health. The GLP-1 agonists, semaglutide (S) and tirzepatide (T), are effective in achieving weight loss and have been associated with decreased incidence of diabetes, stroke and overall mortality in the non-diabetic as well as diabetic populations. There are limited data on the efficacy and safety of GLP1 agonists in women with breast cancer. Methods: We performed a retrospective analysis of the association of S and T use with weight loss in patients with stage I-III breast cancer diagnosed and treated at the Yale Cancer Center/Yale New Haven Health Network between 2017 and 2022. After institutional review board approval, a database including 7149 patients including 92,989 office visits was constructed. Maximal weight loss after S/T prescription as well as mean weight loss were calculated. S and T treated patient’s stage distribution and rates of recurrence were compared to untreated patients. For patients without metastatic disease, repeated measures regression analysis was utilized to evaluate changes in weight and BMI. Results: Of the 5430 evaluable patients with non-metastatic disease, 70 (1.3%) were prescribed S or T. Mean age was 58 (41-78). 74% received endocrine therapy. Mean pretreatment weight was 95.8 kg and BMI was 35.9 kg/m2. Mean weight loss for S/T treated patients was 3.03 kg (3.9-2.13, p < .0001) corresponding to reduction in BMI of 1.1 kg/m2 (0.7-1.5 p < .0001). We also calculated maximal weight loss after S/T prescription. Mean maximal weight loss was 8.89 kg (6.71-10.98 P < .0001) corresponding to a mean maximal reduction in BMI of 3.2 kg/m2 (2.3-4.2 P < .0001). Rates of local, locoregional, and distant breast cancer recurrence were 1.5%, 0%, 1.5% in the S/T treated patients and 1.3%, 4.7% and 3.3% in the untreated patients. None of these differences were statistically significant. Conclusions: In this retrospective analysis, GLP-1 agonist are associated with clinically meaningful weight loss in overweight and obese women with early breast cancer. Recurrence risk did not appear to be preliminarily impacted by treatment. Additional research is needed on long term safety as well as weight loss maintenance with these drugs in breast cancer survivors.

Breast Cancer Local Recurrence Risk in Implant-Based Breast Reconstruction with Macrotexturized and Microtexturized Prosthesis: A Multicentric Retrospective Cohort Study

Breast Cancer Local Recurrence Risk in Implant-Based Breast Reconstruction with Macrotexturized and Microtexturized Prosthesis: A Multicentric Retrospective Cohort Study

Recurrence in lobular carcinoma of the breast: A 14-year review.

The two most common types of breast cancer are invasive or infiltrating ductal carcinoma (IDC) and invasive or infiltrating lobular carcinoma (ILC) (Pestalozzi etal., J. Clin. Oncol., 26, 2008, 3006). Between 5% and 15% of invasive breast carcinomas are lobular carcinomas (Pestalozzi etal., J. Clin. Oncol., 26, 2008, 3006; Dossus and Benusiglio, Breast Cancer Res., 17, 2015, 37; Braunstein etal., Breast Cancer Res. Treat., 149, 2015, 555). The paucity of data relating to recurrence rates of lobular cancers prompted this study. A retrospective cohort study of all cases of lobular breast carcinoma reported to the Western Australia Cancer Registry with the clinical and pathological details between 2000 and 2014. Overall, 2463 subjects with a total of 2526 events of invasive lobular carcinoma of the breast. 11/2463 (0.45%) subjects met criteria for local recurrence of invasive lobular breast cancer, with an incidence of 1 in 224. There are clinical implications for the management and follow-up for patients with a diagnosis of lobular cancer of the breast. Due to the low recurrence rate, now, the standard practice in our institution does not offer magnetic resonance imaging (MRI) as part of the follow-up for ILC patients. Other centres should establish local recurrence rates to aid development of appropriate management protocols.

Abstract PO2-11-03: A long-term follow-up of patients who interrupted endocrine therapy to become pregnant following breast cancer surgery

Abstract Introduction: Regarding discontinue adjuvant endocrine therapy to attempt pregnancy, Pregnancy Outcome and Safety of Interrupting Therapy for Women with Endocrine Responsive Breast Cancer (POSITIVE) clinical trials have revealed temporary interruption of endocrine therapy to attempt pregnancy did not confer short-term risk of breast cancer events. However, that report involved a short observation period, longer-term follow-up is required. This study was aimed to evaluate the safety of endocrine therapy interruption with long-term followed-up data base. Methods: This was a retrospective study using surveying of medical chart data between June 2007 and November 2015 at St. Luke’s International Hospital. The subjects were 65 patients with estrogen-receptor positive primary breast cancer (clinical stage I-III) who had been performed fertility preservation prior to starting breast cancer treatment. Adjuvant endocrine therapy completion was defined as 120 months (10 years) and discontinuation was defined as < 120 months. Using the definition, we classified the patients into an endocrine therapy interruption-group and a continuation-group. The primary outcome was the breast cancer free interval (BCFI). We defined breast cancer events as local, regional, or distant recurrence of invasive breast cancer or new contralateral invasive breast cancer during follow-up. Results: Median follow-up period was 110 (range, 36–181) months. The number of adjuvant endocrine therapy interruption-group was 30 and continuation-group was 35. Among 65 patient, the mean patient age in the interruption vs. continuation groups were as follows: 38(range, 26-48) years vs. 36.5 (range, 26–45) years at breast cancer diagnosis and HER2 positive breast cancer was identified in 4 (11.4%) vs 4 (13.3%) patients. Clinical stages were Stage I, 9 (30%) vs. 11 (31.4%) patients; Stage II, 18 (60%) vs. 18 (51.4%) patients; and Stage III, 3 (10%) vs. 6 (17.1%) patients. Chemotherapy was administered in 17 (56.7%) and 23 (65.7%) patients, respectively. The median duration of endocrine therapy before interruption was 25.5 months: 3 (10%) patients received endocrine therapy for 0–18 months, 16 (53.3%) for 18–30 months, and 11 (36.7%) for >30 months. The BCFI was 124 and 119 months in the interruption and continuation groups, respectively (p = 0.16). There were 6 (20%) and 9 (25.7%) breast cancer events in the interruption-group and continuation-group, respectively (p = 0.4). All the pregnancies were in the endocrine therapy interruption group (17 pregnancies, 16 deliveries), with one pregnancy involving the delivery of twins. Three pregnancies were spontaneous. Endocrine therapy was resumed in 16 (59.3%) patients in the interruption-group (median time to resumption, 20.5 months). One patient developed distant metastasis during endocrine therapy interruption period. Conclusion: Among patients who performed fertility preservation prior to starting breast cancer treatment, our long-term follow-up data, almost 9 years, suggested that the BCFI was not statistically different between endocrine therapy interruption-group and continuation-group. A limitation of this study is that only three cases of Stage III breast cancer were included in the interruption group. Therefore, we consider that careful decisions should be made regarding interruption of endocrine therapy. Citation Format: Risa Kasahara, Atsuko Kitano, Fumi Akitani, Kyoko Shiota, Kumiko Kida, Junko Takei, Atsushi Yoshida. A long-term follow-up of patients who interrupted endocrine therapy to become pregnant following breast cancer surgery [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 PO2-11-03.

Abstract ED02-02: The Challenges of Lobular Carcinoma

Abstract Infiltrating lobular carcinoma (ILC) and lobular carcinoma in situ (LCIS) were first described in the1940s by two Memorial Hospital pathologists, Foote and Stewart. They were most intrigued by the infiltrative appearance of these lobular cancers which they described as demonstrating large numbers of isolated, loose or dyscohesive cells of rather uniform size but of varying shape. We now recognize that this dyscohesive growth pattern is the result of loss of a functional e-cadherin protein; a distinguishing feature between ILC and invasive ductal carcinoma (IDC). Several studies comparing clinical features and outcomes between ILC and IDC have generated consistent findings. Lobular cancers are more likely to be ER+, larger, lower grade, less likely to be detected on MMG and more likely to have positive margins at breast conserving surgery (BCS), or to require mastectomy. Yet importantly, if BCS is successful, local recurrence and rates of contralateral breast cancer are equal for ILC and IDC. Although lobular cancers represents only 5-15% of all breast cancer, numerically, if ILC was an independent cancer in women, it would rank as the 6th most common cancer in women. Notably the incidence of ILC rose sharply in the late 80s throughout the 90s, and it has become clear that there is a strong relationship between ILC and hormone replacement therapy. Perhaps the “strongest” risk factor for ILC, is LCIS. Classic LCIS is an incidental finding – there are no pathnogmonic features on breast imaging or gross examination of tissue. On microscopic examination it is often multicentric and bilateral. Although originally considered a precursor to ILC and treated with mastectomy, over the years it was realized that rates of ipsilateral cancer in women who were not treated for LCIS were lower than expected and were quite similar to rates of contralateral breast cancer – and this combined with the fact that only 50% of the cancers were of the lobular phenotype led to a movement to consider LCIS as a high risk lesion. Contemporary data continue to support this management approach as rates of cancer development in women with a diagnosis of LCIS are consistently reported at 1-2% per year and the risk is conferred bilaterally, with a slightly higher representation of ILC in the ipsilateral breast. In this presentation we will review areas of clinical controversy, including the use of MRI, the safety of breast conservation, the role of neoadjuvant chemotherapy and the utility of genomic assays in patients with ILC. Citation Format: T. King. The Challenges of Lobular Carcinoma [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 ED02-02.

Abstract PS06-06: Analysis of ctDNA for the detection of minimal residual disease (MRD) using a tissue-free, multiomic assay in patients with early-stage breast cancer

Abstract Background: The detection of ctDNA in patients with early-stage breast cancer after completion of adjuvant therapy is associated with a high risk of recurrence. Current clinical guidelines do not recommend routine screening for metastatic disease unless there are clinical signs and symptoms in patients who completed adjuvant therapy. However, ctDNA may serve as an early biomarker of recurrence which may allow effective identification of patients with asymptomatic distant metastases or molecular relapse only, who could benefit from early treatment intervention. Herein, we utilized a tissue-free, multiomic assay for the sensitive and specific detection of MRD in patients with early-stage breast cancer. Methods: Plasma samples were collected from patients with stage I-III breast cancer who were enrolled in the SUCCESS-A phase 3 clinical trial (NCT02181101) between 2006 and 2007. All patients received adjuvant chemotherapy +/- endocrine therapy and/or anti-HER2 therapy. Samples were collected approximately two years after completion of adjuvant chemotherapy, and plasma samples selected for analysis were from patients without evidence of disease recurrence prior to sample collection. Presence of MRD was assessed using Guardant Reveal powered by Infinity, which evaluates the epigenomic signals associated with cancer versus normal DNA for the detection of ctDNA. Samples with the presence of ctDNA are characterized for somatic alterations with common sources of interference such as clonal hematopoiesis excluded. An analytically validated bioinformatics pipeline was used for the detection of breast cancer ctDNA. Samples were analyzed blinded to the clinical data. Median survival times were estimated using the Kaplan-Meier method and hazard ratios were calculated based on univariable cox regression models. Results: A total of 311 plasma samples from 311 patients were evaluable. ctDNA was detected in 34% (13/38) of patients who subsequently developed distant recurrence and in none (0/7) of the patients who had local or contralateral breast cancer recurrence. ctDNA was detected in 60% (9/15) of samples that were collected within one year before recurrence. In the ctDNA detected samples from patients who had disease recurrence, the median time from sample collection to recurrence was 7.9 months (range, 1.4-28.6 months). ctDNA was detected in 6 patients who did not have a documented disease recurrence, resulting in a specificity of 97.7% (260/266). In the overall cohort, ctDNA detection was prognostic for recurrence-free survival (RFS; HR 11.0, 95% CI 2.28-53.6; p< 0.0001), distant recurrence-free survival (D-RFS; HR 13.7, 95% CI 2.52-74.9; p< 0.0001), and overall survival (OS; HR 17.4, 95% CI 1.33-227; p< 0.0001). Conclusion: Detection of ctDNA after adjuvant chemotherapy was highly prognostic and demonstrated high specificity in an early-stage breast cancer cohort. Larger, prospective studies are needed to confirm the prognostic value of ctDNA in the post-treatment setting and assess the clinical utility of MRD detection in this population. Citation Format: Wolfgang Janni, Thomas Friedl, Brigitte Rack, Peter A. Fasching, Andreas Hartkopf, Hans Tesch, Ralf Lorenz, Georg Heinrich, Jens-Uwe Blohmer, Tanja Fehm, Volkmar Müller, Andreas Schneeweiss, Matthias Beckmann, Matthias Ruebner, Nadia Harbeck, Klaus Pantel, Derek Dustin, Mingyang Cai. Analysis of ctDNA for the detection of minimal residual disease (MRD) using a tissue-free, multiomic assay in patients with early-stage breast cancer [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 PS06-06.

Imaging for local recurrence of breast cancer

PurposeIsolated locoregional recurrence of breast cancer (ILRR) and contralateral breast cancer (CBC) affect up to 20% of all breast cancer (BC) patients in the first 20 years after primary diagnosis. Treatment options comprise surgical interventions and further systemic therapies depending on the histological subtype. Patients with hereditary breast or ovarian cancer (HBOC) undergo MRI, mammography, and ultrasound in the aftercare of BC, while non-HBOC (nHBOC) patients do not regularly receive MRI. Since early detection is crucial for morbidity and mortality, the evaluation and constant improvement of imaging methods of the breast is necessary.MethodsWe retrospectively analyzed the data of 1499 former BC patients that received imaging of the breast at a tertiary-care university hospital between 2015 and 2020. The analysis comprised various patient characteristics, such as breast density, age, tumor size and subtype, and their influence on BC detection rates by the different imaging methods.ResultsWithin the patient sample, 176 individuals (11.7% of former BC patients) were diagnosed with either ILRR or CBC. CBC was observed in 32.4% of patients, while both ILRR and secondary breast cancer occurred in 20.5% and 23.9% of all patients. Sensitivity of MRI, mammography, and ultrasound for recurrent malignancy was 97.9%, 66.3%, and 67.8%, respectively. ILRR and CBC detection rates were similar for patients with and without HBOC history. Lower breast density and larger tumor size increased the detection rates of all imaging modalities.ConclusionIn breast cancer survivors, MRI might improve the early detection of ILRR and CBC in both HBOC and nHBOC patients.

Triplane technique for breast reconstruction after breast cancer surgery: A case series report.

Implant-based breast reconstruction is an important method for post-mastectomy breast reconstruction. Currently, the most commonly used technique is the biplane technique. However, the high rate of postoperative complications, the inability of pockets to accommodate larger implants, and the expensive costs of biological mesh make the development of new surgical methods urgent. The triplane technique for breast reconstruction is an ideal candidate method. The main local symptoms were breast lump, abnormal breast skin, nipple discharge, and abnormal nipple or areola in 24 patients. The study included 24 female patients who underwent breast reconstruction using the triplane technique after radical breast cancer surgery. The surgical procedure involved measuring the dimensions of the breast, designing the incision, and creating a pocket for the implant using the triplane technique, which includes the pectoralis major muscle, the pectoralis major fascia continuing to the rectus abdominis fascia, and the latissimus dorsa muscle fascia continuing to the rectus abdominis fascia. Postoperative follow-up included regular assessments of pain and evaluation of breast appearance. No cases of postoperative infection were observed in all patients. During the 1-year follow-up period after surgery, 5 patients (20.8%) who needed radiotherapy after mastectomy for cancer showed slight darkening of skin flap pigment after using the triplane technique implant. No cases of exposure or infection of the expanders were reported, and 1 patient underwent expander replacement with a permanent prosthesis. All patients expressed satisfaction with the reconstructed breast shape. The 10 patients (41.7%) experiencing postoperative swelling and pain. However, the pain gradually subsided during the postoperative recovery period. No cases of local recurrence or distant metastasis of breast cancer were observed during the 1-year-follow-up period. The triplane technique for breast reconstruction after breast cancer surgery provides good implant coverage, reduces the risk of complications, and is cost-effective.

Competing risk analysis of cardiovascular disease risk in breast cancer patients receiving a radiation boost

BackgroundThoracic radiotherapy may damage the myocardium and arteries, increasing cardiovascular disease (CVD) risk. Women with a high local breast cancer (BC) recurrence risk may receive an additional radiation boost to the tumor bed.ObjectiveWe aimed to evaluate the CVD risk and specifically ischemic heart disease (IHD) in BC patients treated with a radiation boost, and investigated whether this was modified by age.MethodsWe identified 5260 BC patients receiving radiotherapy between 2005 and 2016 without a history of CVD. Boost data were derived from hospital records and the national cancer registry. Follow-up data on CVD events were obtained from Statistics Netherlands until December 31, 2018. The relation between CVD and boost was evaluated with competing risk survival analysis.Results1917 (36.4%) received a boost. Mean follow-up was 80.3 months (SD37.1) and the mean age 57.8 years (SD10.7). Interaction between boost and age was observed for IHD: a boost was significantly associated with IHD incidence in patients younger than 40 years but not in patients over 40 years. The subdistribution hazard ratio (sHR) was calculated for ages from 25 to 75 years, showing a sHR range from 5.1 (95%CI 1.2–22.6) for 25-year old patients to sHR 0.5 (95%CI 0.2–1.02) for 75-year old patients.ConclusionIn patients younger than 40, a radiation boost is significantly associated with an increased risk of CVD. In absolute terms, the increased risk was low. In older patients, there was no association between boost and CVD risk, which is likely a reflection of appropriate patient selection.

Long-Term Impact of Various Endocrine Therapy Regimens on Mortality, Local Recurrence, and Metastasis in Breast Cancer: A 25-Year Retrospective Study

Background: This retrospective cohort study explores the long-term effects of different endocrine therapy regimens on mortality, local recurrence, and metastasis in breast cancer patients. Methods: Data from the Referral Cancer Research Center of Shahid Beheshti University of Medical Sciences were analyzed. Records of 2,262 histologically confirmed breast cancer patients, with 25 years of follow-up were included. We collected patient data, including treatment modalities, and details of the endocrine therapy, and conducted statistical analysis to assess treatment-outcome associations. Results: Patients had an average age of 49.45 years, and 99.1% were female. The average tumor size was 2.8 cm, with a 12.3% mortality rate. Positive expression of human epidermal growth factor receptor 2, progesterone receptor, and estrogen receptor was found in 17.3%, 71.8%, and 70.6% of patients, respectively. Tamoxifen was administered to 1,700 patients, letrozole to 715, and exemestane to 540, with an average endocrine therapy duration of 5.2 years. Letrozole treatment duration (P = 0.001) and lymph node involvement (P = 0.028) were independent predictive variables for local recurrence, with longer letrozole therapy associated with lower recurrence. Conclusion: Estrogen receptor expression and endocrine therapy duration are independent predictive markers for recurrence and mortality. Longer letrozole therapy predicts lower local recurrence. Endocrine therapy duration inversely relates to mortality, recurrence, and local recurrence.

Matrix Metalloproteinase as Predictors of Local Recurrence in Early-Stage Breast Cancer After Mastectomy and Chemotherapy A Cross-Sectional Study in Single Centre

Introduction: The prognosis for early-stage breast cancer is generally favourable. However, in cases when a recurrence manifests after therapy, the prognosis becomes significantly poor. To determine early breast cancer recurrence risk, a marker is needed. Currently, previous tumour markers are used to predict general breast cancer, lacking specificity in the context of early breast cancer. Matrix Metalloproteinase1 (MMP1) is already acquainted with the local recurrence process of invasive ductal carcinoma (IDC). MMP1 expression may better predict early recurrence in early-stage IDC than other approaches. This research examined the potential predictive value of MMP1 expression in early-stage IDC for early local recurrence and its correlation with clinicopathological factors. Methods: This study was a cross-sectional analysis of a single center's medical records. The sample size was 25 subjects for the group without recurrence and 25 subjects with recurrence. Mastectomy and chemotherapy were performed from January 2014 through December 2019. Using immunohistochemistry, paraffin blocks of surgical specimens were examined for MMP1. The data processing was done utilising the trial version of IBM SPSS 25. and Openepi 3.0 programs and analysed using Bivariate, which is performed using the Chi-square test or Fisher's exact test. Result: The statistic test showed a significant difference (p < 0.000) in the average expression of MMP1 for non-recurrence cases (3,95±5,36) compared to recurrence cases (14,95±5,36). We also found a statistically significant correlation between recurrence and high expression of MMP1 (odd ratio [OR]= 60.38, 95% confidence interval [CI]=10.01-364.3, p<0.001). Clinicopathological variables and MMP1 expression did not have a significant correlation. Conclusions: In early-stage IDC, MMP1 expression had the potential to predict and could be an independent prognostic factor for early recurrence.

Predictive factors of axillary lymph node involvement in Tunisian women with early breast cancer

Background: Axillary lymph node involvement (ALNI) is associated with an increased risk of local recurrence and poor prognosis in early breast cancer. The determination of the risk of positive axillary lymph node contributes to therapeutic decisions.Objectives: The aim of this study was to identify clinicopathological predictive factors of axillary lymph node metastases in patients with early breast cancer.Methods: We included patients with clinical T0, T1 andT2 invasive breast carcinoma who underwent resection of the primary tumor and axillary staging by sentinel lymph node biopsy and/or axillar lymph node dissection between 2012 and 2018.Results: Of the 135patients included, 41.5% had ALNI. Regarding univariate analysis, clinical factors correlated with positive ALNM were clinical tumour size>30mm, clinical tumour stage, clinical number of tumours, clinical axillary nodal status and nodal status on ultrasound. Pathologic factors associated with nodal involvement were pathologic tumour stage, tumour grade SBR, number of foci, lymphovascular invasion, perineural invasion and Ki67>20%.In multivariate logistic regression, clinical axillary nodal status, pathologic tumour stage and lymphovascular invasion (LVI) remained as independent predictors of ALNI.Conclusions: Based on these results, we suggest that clinical axillary nodal status, pathologic tumour stage and LVI are predictive factors for ALNM in Tunisian women with early breast cancer.

Protocol of the HISTOTHERM study: assessing the response to hyperthermia and hypofractionated radiotherapy in recurrent breast cancer.

Breast cancer is globally the leading cancer in women, and despite the high 5-year survival rate the most frequent cause of cancer related deaths. Surgery, systemic therapy and radiotherapy are the three pillars of curative breast cancer treatment. However, locoregional recurrences frequently occur after initial treatment and are often challenging to treat, amongst others due to high doses of previous radiotherapy treatments. Radiotherapy can be combined with local hyperthermia to sensitize tumor cells to radiation and thereby significantly reduce the required radiation dose. Therefore, the combination treatment of mild local hyperthermia, i.e. locally heating of the tissue to 39-43°C, and re-irradiation with a reduced total dose is a relevant treatment option for previously irradiated patients. The mechanisms of this effect in the course of the therapy are to date not well understood and will be investigated in the HISTOTHERM study. Patients with local or (loco)regional recurrent breast cancer with macroscopic tumors are included in the study. Local tumor control is evaluated clinically and histologically during the course of a combination treatment of 60 minutes mild superficial hyperthermia (39 - 43°C) using water-filtered infrared A (wIRA) irradiation, immediately followed by hypofractionated re-irradiation with a total dose of 20-24 Gy, administered in weekly doses of 4 Gy. Tumor and tumor stroma biopsies as well as blood samples will be collected prior to treatment, during therapy (at a dose of 12 Gy) and in the follow-up to monitor therapy response. The treatment represents the standard operating procedure for hyperthermia plus re-irradiation. Various tissue and blood-based markers are analyzed. We aim at pinpointing key mechanisms and markers for therapy response which may help guiding treatment decisions in future. In addition, quality of life in the course of treatment will be assessed and survival data will be evaluated. The study is registered at the German Clinical Trials Register, Deutsches Register Klinischer Studien (DRKS00029221).

Adjuvant Auger Electron-Emitting Radioimmunotherapy with [111In]In-DOTA-Panitumumab in a Mouse Model of Local Recurrence and Metastatic Progression of Human Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) has a high risk for recurrence and metastasis. We studied the effectiveness of Auger electron (AE) radioimmunotherapy (RIT) with antiepidermal growth factor receptor (EGFR) panitumumab conjugated with DOTA complexed to 111In ([111In]In-DOTA-panitumumab) for preventing metastatic progression after local treatment of 231/LM2-4 Luc+ human TNBC tumors in the mammary fat pad of NRG mice. Prior to RIT, the primary tumor was resected, and tumor margins were treated with X-irradiation (XRT; 5 days × 6 Gy/d). RIT was administered 1 day post-XRT by intravenous injection of 26 MBq (15 μg) or 2 × 10 MBq (15 μg each) separated by 7 d. These treatments were compared to tumor resection with or without XRT combined with DOTA-panitumumab (15 μg) or irrelevant [111In]In-DOTA-IgG2 (24 MBq; 15 μg), and efficacy was evaluated by Kaplan-Meier survival curves. The effect of [111In]In-DOTA-panitumumab (23 MBq; 15 μg) after tumor resection without local XRT was also studied. Tumor resection followed by XRT and RIT with 26 MBq [111In]In-DOTA-panitumumab significantly increased the median survival to 35 d compared to tumor resection with or without XRT (23-24 d; P < 0.0001). Local treatment with tumor resection and XRT followed by 2 × 10 MBq of [111In]In-DOTA-panitumumab, DOTA-panitumumab, or [111In]In-DOTA-IgG2 did not significantly improve median survival (26 days for all treatments). RIT alone with [111In]In-DOTA-panitumumab postresection of the tumor without XRT increased median survival to 29 days, though this was not significant. Despite significantly improved survival in mice treated with tumor resection, XRT, and RIT with [111In]In-DOTA-panitumumab, all mice eventually succumbed to advanced metastatic disease by 45 d post-tumor resection. SPECT/CT with [111In]In-DOTA-panitumumab, PET/MRI with [64Cu]Cu-DOTA-panitumumab F(ab')2, and PET/CT with [18F]FDG were used to detect recurrent and metastatic disease. Uptake of [111In]In-DOTA-panitumumab at 4 d p.i. in the MFP tumor was 26.8 ± 9.7% ID/g and in metastatic lymph nodes (LN), lungs, and liver was 34.2 ± 26.9% ID/g, 17.5 ± 6.0% ID/g, and 9.4 ± 2.4%ID/g, respectively, while uptake in the lungs (6.0 ± 0.9% ID/g) and liver (5.2 ± 2.9% ID/g) of non-tumor-bearing NRG was significantly lower (P < 0.05). Radiation-absorbed doses in metastatic LN, lungs, and liver were 9.7 ± 6.1, 6.4 ± 2.1, and 10.9 ± 2.7 Gy, respectively. In conclusion, we demonstrated that RIT with [111In]In-DOTA-panitumumab combined with tumor resection and XRT significantly improved the survival of mice with recurrent TNBC. However, the aggressive nature of 231/LM2-4 Luc+ tumors in NRG mice may have contributed to the tumor recurrence and progression observed.

Repeat sentinel lymph node surgery for locally recurrent breast cancer after prior mastectomy.

Current NCCN guidelines discourage repeat sentinel lymph node (SLN) surgery in patients with local recurrence (LR) of breast cancer following prior mastectomy. This study addresses the feasibility and therapeutic impact of this approach. We identified 73 patients managed with repeat SLN surgery for post-mastectomy isolated LR. Lymphatic mapping was performed using radioisotope with or without lymphoscintigraphy and/or blue dye. Successful SLN surgery was defined as retrieval of ≥1 SLN. SLN surgery was successful in 65/73 (89%), identifying a median of 2 (range 1-4) SLNs, with 10/65 (15%) SLN-positive. Among these, 5/10 (50%) proceeded to ALND. In unsuccessful cases, 1/8 (13%) proceeded to ALND. Seven of 10 SLN-positive patients and 50/55 SLN-negative patients received adjuvant radiotherapy. Chemotherapy was administered in 31 (42%) and endocrine therapy in 50 of 57 HR+ patients (88%). After 28 months median follow-up, eight patients relapsed with the first site local in two, distant in five, and synchronous local/distant in one. No nodal recurrences were observed. SLN surgery for patients with LR post-mastectomy is feasible and informative. This approach appears oncologically sound, decreases axillary dissection rates and may be used to tailor adjuvant radiation target volumes and systemic therapies.

Extensive intraductal component as a factor determining local recurrence of breast cancer: a systematic review and meta-analysis.

Breast-conserving surgery and mastectomy are standard surgical options for breast cancer. However, some patients experience a local recurrence after the operation. Many factors have been identified as a risk of local recurrence. Extensive intraductal component (EIC) was found as one of the major risks of the recurrence. Nevertheless, there were neither any systematic reviews nor controlled trials focused on EIC. This study aims to identify the impact of EIC on the local recurrence of breast cancer. We searched all relevant studies published between the inception to December 2020. All electronic data from PubMed and Scopus databases were extracted for evaluation of EIC as a factor of the recurrence. Local recurrence was a primary outcome between EIC-positive group and EIC-negative group. Margin status and adjuvant radiation were focused as a subgroup analysis. The Newcastle Ottawa Scale was applied for quality assessment of included studies and RevMan 5.3 program was used to estimate the effect of the results. The odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. A total of 32 studies, comprising 4,290 and 15,143 patients in the EIC-positive and EIC-negative groups respectively, were retrieved and met selection criteria. All included studies were at low to intermediate risk of bias. There was a statistically significant difference in local recurrence between EIC-positive patients and EIC-negative patients (OR =2.73; 95% CI: 2.42-3.07; P<0.00001). However, there was not any significant difference in patients who had negative margin (OR =1.97; 95% CI: 0.92-4.19; P=0.36) or received any adjuvant irradiation (OR =1.58; 95% CI: 0.55-4.54; P=0.24). EIC increases the risk of local recurrence, especially in breast-conserving surgery patients. However, there are a limited number of populations to analyze in subgroup analysis, the rate of local recurrence between two groups is not different in patients who had negative margin or received postoperative irradiation.

Differentiated approach to adjuvant neutron therapy in patients with locally advanced breast cancer, taking into account signifcant prognostic factors

The purpose of the study was to assess the risk of developing local recurrence in patients with locally advanced breast cancer, taking into account unfavorable prognostic factors, and to determine the indications for adjuvant neutron therapy. Material and Methods. The treatment outcomes in 155 patients with stage T2–4N0–3M0 locally advanced breast cancer were analyzed. The patients received adjuvant radiation therapy delivered to soft tissues of the anterior chest wall (the area of the postoperative scar). The study group (n=89) received neutron therapy, and the control group received photon therapy. The main clinical and morphological prognostic factors: age, menstrual function, size of the primary tumor, invasion of the lymphatic vessels, tumor invasion into the dermis, multicentric tumor growth, tumor grade, presence of absence of edematous-infltrative form of the tumor, receptor status (RP, RE, Her2-neu), and Ki67 were studied in all patients with locally advanced breast cancer. Results. A probabilistic mathematical model that made it possible to predict the development of local recurrence in the postoperative period was created. The model was highly informative (χ2 =43.7; p&lt;0.001). The sensitivity of the model was 87.1 %, the specifcity was 85.7 %, and the diagnostic accuracy was 86.4 %. We present a clinical case with an estimated risk of developing local recurrence of breast cancer of 99 %. A patient received adjuvant neutron therapy, which made it possible to avoid the development of recurrence. At 5 years of follow-up after combined treatment modality including neutron therapy to the postoperative scar area, no evidence of local recurrence was found. Conclusion. Based on the data obtained, the approach to indications for adjuvant neutron therapy, namely: stage III B-C breast cancer, tumor invasion into the dermis, angiolymphatic invasion, grade 3 tumor, triple-negative tumor subtype and overexpression Her2-neu subtype.

Diagnostic value of preoperative examination for evaluating margin status in breast cancer.

A positive resection margin is a major risk factor for local breast cancer recurrence after breast-conserving surgery (BCS). Preoperative imaging examinations are frequently employed to assess the surgical margin. To investigate the role and value of preoperative imaging examinations [magnetic resonance imaging (MRI), molybdenum target, and ultrasound] in evaluating margins for BCS. A retrospective study was conducted on 323 breast cancer patients who met the criteria for BCS and consented to the procedure from January 2014 to July 2021. The study gathered preoperative imaging data (MRI, ultrasound, and molybdenum target examination) and intraoperative and postoperative pathological information. Based on their BCS outcomes, patients were categorized into positive and negative margin groups. Subsequently, the patients were randomly split into a training set (226 patients, approximately 70%) and a validation set (97 patients, approximately 30%). The imaging and pathological information was analyzed and summarized using R software. Non-conditional logistic regression and LASSO regression were conducted in the validation set to identify factors that might influence the failure of BCS. A column chart was generated and applied to the validation set to examine the relationship between pathological margin range and prognosis. This study aims to identify the risk factors associated with failure in BCS. The multivariate non-conditional logistic regression analysis demonstrated that various factors raise the risk of positive margins following BCS. These factors comprise non-mass enhancement (NME) on dynamic contrast-enhanced MRI, multiple focal vascular signs around the lesion on MRI, tumor size exceeding 2 cm, type III time-signal intensity curve, indistinct margins on molybdenum target examination, unclear margins on ultrasound examination, and estrogen receptor (ER) positivity in immunohistochemistry. LASSO regression was additionally employed in this study to identify four predictive factors for the model: ER, molybdenum target tumor type (MT Xmd Shape), maximum intensity projection imaging feature, and lesion type on MRI. The model constructed with these predictive factors exhibited strong consistency with the real-world scenario in both the training set and validation set. Particularly, the outcomes of the column chart model accurately predicted the likelihood of positive margins in BCS. The proposed column chart model effectively predicts the success of BCS for breast cancer. The model utilizes preoperative ultrasound, molybdenum target, MRI, and core needle biopsy pathology evaluation results, all of which align with the real-world scenario. Hence, our model can offer dependable guidance for clinical decision-making concerning BCS.

Second Conservative Treatment for Local Recurrence Breast Cancer: A GEC-ESTRO Oncological Outcome and Prognostic Factor Analysis

For second ipsilateral breast tumor event (2nd IBTE), second conservative treatment (2nd CT) combining lumpectomy plus accelerated partial breast reirradiation (APBrI) represents a curative option. The aim of this study was to analyze oncological prognostic factors for patients with a 2nd IBTE treated with 2nd CT. An analysis of clinical practices was conducted across 7 academic hospitals/cancer centers in 6 European countries based on the GEC-ESTRO database. Patients presenting a 2nd IBTE occurring after conservative surgery (lumpectomy+axillary evaluation) and irradiation performed for the primary tumor underwent a 2nd CT with brachytherapy-based APBrI. The main outcome was 5-year cumulative incidence (CI) rate of second local relapse. All analyzed patients were classified according to risk groups for Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) accelerated partial breast irradiation (APBI) and molecular classification and time interval between first and second breast surgery (TIS1S2). Finally, we combined GEC-ESTRO APBI, molecular, and TIS1S2 risk groups, leading to the definition of a new score (named TAM: score based on the combination of time interval [T] between first and second surgery and APBI [A] and molecular [M] classifications) specifically designed for 2nd IBTE oncological outcome analysis. From July 1994 to January 2021, a total of 508 patients received a 2nd CT. At the time of 2nd IBTE, median age was 64.6 years (range, 56.2-72.6). With a median follow-up of 60.9 months (56.2-72.6), the 5-year second local relapse CI rate was 4% (95% confidence interval [95% CI], 2%-6%). The 5-year distant metastasis disease CI rate was 7% (95% CI, 4%-10%). Five-year disease-free and overall survival rates were 89% (95% CI, 86%-93%) and 91% (95% CI, 88%-94%), respectively. In multivariate analysis, TAM score was an independent prognostic factor for all the oncological items (P < .001) except disease-specific survival (P=.07) and overall survival (P=.09). The grade ≥3 late toxicity rate was 12.1%. This analysis of 2nd CT combining lumpectomy with APBrI for 2nd IBTE confirmed the excellent oncological results obtained after 2nd CT. Furthermore, the GEC-ESTRO TAM score appears to be an important prognostic factor, assisting patients and physicians in the decision-making process.

Breast conserving surgery combined with radiation therapy offers improved survival over mastectomy in early-stage breast cancer

IntroductionLandmark trials established equivalent survival regardless of extent of breast surgery in early-stage breast cancer. However, recent studies suggest a survival advantage for breast conserving surgery (BCS) with radiotherapy (BCT). This study assesses the impact of type of surgery on overall survival (OS), breast cancer specific survival (BCSS) and local recurrence (LR) in a modern population-based cohort. MethodsFemale patients aged ≥18, pT1-2pN0, who had surgery between 2006 and 2016 were identified from Breast Cancer Outcome Unit prospective database. Neoadjuvant chemotherapy patients were excluded. Multivariable Cox regression was used to assess the effect of surgical procedure on OS, BCSS, and LR on cohort with complete data. ResultsBCT was performed in 8422 patients and TM in 4034 patients. The baseline characteristics differed between the groups. Mean follow up was 8.3 years. BCT was associated with increased OS HR 1.37, p < 0.001, BCSS survival HR 1.49, p < 0.001, and similar LR HR 1.00, p > 0.90. ConclusionThis study supports that in early-stage breast cancer, BCT has improved BCSS compared to TM without an increased risk of LR.