Locoregional Recurrence Of Breast Cancer Research Articles

Abstract PO4-23-07: Impact of distance between tumor and nipple on locoregional recurrence in breast cancer

Abstract Introduction: Mastectomy is usually recommended for centrally located tumors due to the risk of nipple invasion. While it is well known that there is no significant difference in survival outcomes according to tumor location, central tumors have a higher likelihood of main lactiferous duct invasion, which can result in the migration of tumor cells to the periphery. Therefore, we conducted an investigation specifically focusing on locoregional recurrence (LRR) rates based on the tumor-to-nipple distance (TND). Method: We retrospectively collected the data of patients who underwent breast cancer surgery between 2004-2018 from two institutions. Patients who underwent neoadjuvant chemotherapy were excluded. TND information was obtained from preoperative MRI records. Results: A total of 9,014 patients were included in the study, and the median tumor-to-nipple distance (TND) was 3.4 (0.0-15.0) cm. For all patients, the restricted cubic spline curve analysis showed that the hazard risk of LRR increased with shorter TND. The pattern was more pronounced in the breast-conserving surgery (BCS) group, whereas the mastectomy group showed a relatively constant risk regardless of TND. Thus, we conducted survival analysis for 5,455 patients who underwent BCS. We set the cutoff for TND as 2.5cm as it showed the lowest p-value for LRR rate. Compared to those with TND >2.5cm, patients with TND≤2.5cm showed significantly lower LRR (HR,1.83;95%CI,[1.37-2.46],p< 0.001) and distant metastasis(DM) (HR,1.53;95%CI,[1.16-2.02],p=0.002) rates. Overall survival was not different between two groups (p=0.405). Cox-regression analysis revealed that TND still impacts LRR (HR,1.52;95%CI,[1.11-2.09],p=0.010) but not DM. Importantly, TND still remained significant factor affecting LRR when analyzed as continuous variable (HR,1.04; 95%CI,[1.02-1.06],p< 0.001). The prognostic impact of TND was particularly evident in patients with high mammographic density. Discussion: BCS can be performed for centrally located tumors, as it offers considerable oncologic safety compared to mastectomy. However, for patients who have a fear of recurrence and are reluctant to undergo re-operation, mastectomy would be a good choice. Citation Format: Jong-Ho Cheun, Eunhye Kang, Hong-Kyu Kim, Han-Byoel Lee, Hyeong-Gon Moon, Wonshik Han, Ki-Tae Hwang. Impact of distance between tumor and nipple on locoregional recurrence in 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 PO4-23-07.

Abstract PO5-20-04: A Phase II Study of Ribociclib and Endocrine Treatment of Physician’s Choice for Locoregional Recurrent, Resected Hormone Receptor Positive HER2 Negative Breast Cancer (RaPhLRR Study)

Abstract Background Hormone receptor positive (HR+) breast cancer (BC) is the most common subtype of BC (70-80%). This subset tends to have good prognosis, therefore most patients with localized disease have excellent long-term survival, approaching 100% 5-year relative survival. However, 10% of patients experience loco-regional recurrence (LRR) within 5 year of final surgical management of the primary disease-well within the typical treatment window of adjuvant endocrine therapy. Few studies exists to guide the systemic treatment of patients who have suffered LRR of HR+ HER2 - BC. The randomized controlled CALOR trial demonstrated no benefit to systemic cytotoxic chemotherapy for this subgroup of patients and persistent high rate of subsequent recurrences (50% within 10 years on LRR event). There is no standard of care for managing this patient population. The combination of ribociclib and endocrine therapy (ET) (fulvestrant and aromatase inhibitors) is FDA approved for management of unresectable recurrences and metastatic HR+HER- BC (MONALEESA trials). CDK4/6 inhibitors have been investigated in early BC setting too, several trials showing positive results (monarchE, NATALEE). Data is needed to investigate their use in patients with LRR. Trial design This is a multicenter, single arm phase II study to evaluate efficacy and safety of ribociclib and ET in patients with LRR of HR+HER2- BC. Treatment includes ribociclib for 36 months, 600 mg daily for 21 days, 28-day cycle plus physician’s choice ET for 60 months (fulvestrant or AIs). Ribociclib dose was chosen based on approved dose in metastatic BC. Eligibility Criteria Patients ≥ 18 of age, with LRR of BC (ipsilateral breast, axilla, regional lymph nodes, chest wall), histologically confirmed estrogen receptor positive and/or progesterone receptor positive, HER 2 negative. Patients must have adequate local treatment for LRR (surgery and/or radiation) with negative microscopic margins, no evidence of distant metastatic disease. Prior treatment with neo-adjuvant and adjuvant chemotherapy and ET is allowed, no prior CDK 4/6 inhibitor in the last 12 months. Pre and post-menopausal women are allowed. Patient must enroll within 6 months of the last local therapy. Specific aims Primary objective: to estimate subsequent recurrence-free survival (RFS) at 3 years for ribociclib when administered with ET in patients with HR + HER2- BC with adequately resected local recurrence. Secondary objectives: to estimate distant metastasis-free survival and overall survival, to evaluate safety and tolerability, to identify predictors of LRR. Correlative analysis will explore prognostic and predictive biomarkers of treatment with ribociclib and ET and potential molecular mechanisms of resistance to treatment. Statistical Methods From previous published data (J Clin Oncol. 2018 Apr 10;36(11):1073-1079), we assume that patients receiving standard of-care management following recurrence would have a recurrence free survival (RFS) rate of 80% at 3 years and that treatment with ribociclib + ET will increase it by 7%. We wish to have at least 80% power at that significance level of 0.0487 to correctly detect that improvement in RFS rate at 3 years from 80 to 87%. Because only an improvement in RFS rate is of clinical interest, we have a directional hypothesis, and have used a 1-sided alpha. Using a one-sample survival study design, with assumed accrual duration of 3-years and additional follow-up time of 3 years, the minimum sample size requirement is N=180 patients. Target accrual The minimum sample size requirement is N=180 patients. A bigger sample size of N=200 patients will achieve a power of at least 84%. Current accrual is 6/200. This study will be open at up to 35 sites. Contact information The study is being administered through the HCRN, it can be identified as BRE20-468, NCT05467891, ocdanciu@uic.edu Citation Format: Oana Danciu, Nancy Chan, Kari Wisinski, Trish Millard, Kathleen Kemmer, Sneha Phadke, Zhengjia Chen, Ana Cuesta Fernandez, Melanie Clark, Alison Conlin, Coral Omene, Sima Ehsani, Stephanie Dublis, Vijayakrishna K. Gadi. A Phase II Study of Ribociclib and Endocrine Treatment of Physician’s Choice for Locoregional Recurrent, Resected Hormone Receptor Positive HER2 Negative Breast Cancer (RaPhLRR 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 PO5-20-04.

Abstract PO4-27-11: Fat grafting is oncologically safe during implant-based breast reconstruction and mastectomy after radiotherapy for breast cancer or Hodgkin Lymphoma: results of a multicentric study

Abstract Background. Fat grafting during or after mastectomy could promote the regeneration of irradiated tissues, thus improving tissue softness, increasing patient comfort and ameliorating quality of life. However, there are no conclusive data about the oncological safety of fat grafting, especially in terms of risk of tumor recurrences. The most appropriate timing of adipose tissue transplant is also debated, especially in patients with locoregional breast cancer (BC) recurrence undergoing salvage mastectomy and implant-based breast reconstruction after breast conserving surgery and radiotherapy. Methods. We conducted a prospective, multicentric Italian study to investigate the oncological safety of fat grafting between June 2007 and March 2022. One hundred sixty-three patients who had previously received radiotherapy, either as adjuvant treatment after breast conservative surgery (N=154), or as a treatment of Hodgkin Lymphoma (N=9), underwent mastectomy (simple mastectomy, NAC-sparing and skin-sparing mastectomy) and implant-based, two-stage breast reconstruction. Inclusion criteria were: age between 25 and 75 years, absence of concomitant malignancies, grade 2 or 3 of Breast post Radiotherapy Reconstruction with ExpAnder Score Test (B.R.R.E.A.S.T. score) (Tab 1). Patient BMI, hypertension, smoking history, diabetes and having received neoadjuvant chemotherapy were not considered as exclusion criteria. Contextual mastectomy and expander positioning were performed during first stage (stage I), while substitution of the expander with definitive implant occurred during second stage (stage II). Fat grafting could be performed during stage I, between stage I and II surgery, or during stage II. Results. One hundred sixty-nine mastectomy procedures (six bilateral) and first-stage implant-based reconstructions with expander were performed either as prophylactic surgery (N=23) or for the treatment of primary or recurrent BC (N=146). Thirty-four patients had ductal carcinoma in situ, whereas 112 patients had invasive disease, including: 17 patients with Luminal A BC, 67 patients with Luminal B HER2-negative BC, 3 patients with Luminal B HER-2 positive BC, 7 patients with HER-2 positive BC and 18 patients had triple-negative BC. One hundred thirty-six (80.5%) patients received at least one fat grafting. Eighty-six patients (52.8%) have received second-stage definitive implant. With a median time of observation of 25.1 months, we observed four locoregional cancer recurrences (2.4%), one of which in axillary lymph nodes. All tumor recurrences occurred in patients who had received fat grafting. Eight patients (4.9%) developed distant metastases (liver, lung, lymph nodes, and bone metastases); of these, four patients (50%) had received fat grafting. No death events occurred. Conclusion. Fat grafting after radiotherapy of the breast is associated with a low incidence of locoregional tumor recurrences and distant metastases. Although our findings need to be confirmed in larger, multicentric clinical studies, fat grafting is a safe and useful technique that can be proposed for breast reconstruction after irradiation. Table. Breast post Radiotherapy Reconstruction with ExpAnder Score Test, B.R.R.E.A.S.T score. Based on our experience, we thought to include two tissue characteristics (Pinch test ≥ 0.5 cm and presence/absence of skin teleangectasia or severe dyscromia) in a pre-operative, clinically useful, and ready-to-use score to assess soft tissue adequacy as recommended by NCCN guidelines, that we called Breast post Radiotherapy Reconstruction with ExpAnder Score Test (B.R.R.E.A.S.T. score). In our study, two-stage implant-based breast reconstruction and adipose tissue transplant with regenerative intent were performed in patients with Pinch test ≥ 0.5 cm but moderate skin teleangectasia or dyscromia (B.R.R.E.A.S.T. score 2) and in patients with Pinch test ≥ 0.5 cm and absence of skin teleangectasia or severe dyscromia (B.R.R.E.A.S.T. score 3). Patients with skin teleangectasia or dyscromia and Pinch test < 0.5 cm (B.R.R.E.A.S.T. score 1) were not enrolled in our study as they did not undergo alloplastic breast reconstruction but they underwent autologous reconstruction (data not shown). Citation Format: Chiara Listorti, Claudio Vernieri, Francesco Barretta, Chiara Osio, Ilaria Maugeri, Federica Pilotta, Cristina Ferraris, Massimiliano Gennaro, Gabriele Martelli, Marco Visaggio, Giulia Valeria Bianchi, Serena Di Cosimo, Gianfranco Scaperrotta, Maria Carmen De Santis, Daniela Tognali, Antonino Romeo, Matteo Mingozzi, Francesco Marongiu, Annalisa Curcio, Secondo Folli. Fat grafting is oncologically safe during implant-based breast reconstruction and mastectomy after radiotherapy for breast cancer or Hodgkin Lymphoma: results of a multicentric 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 PO4-27-11.

Abstract PO1-19-12: VERITAC-2: a phase 3 study of vepdegestrant, a PROteolysis TArgeting Chimera (PROTAC) estrogen receptor (ER) degrader, vs fulvestrant in ER–positive/human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer

Abstract Background: Vepdegestrant (ARV-471) is an oral PROTAC ER degrader that binds to and degrades wild-type ER and clinically relevant mutants. Vepdegestrant directly recruits the ubiquitin-proteasome system to degrade ER, whereas selective ER degraders (SERDs) indirectly cause ER degradation. In a first-in-human phase 1/2 study (NCT04072952), vepdegestrant monotherapy was well tolerated and showed clinical activity in heavily pretreated patients with ER+/HER2- advanced breast cancer. The phase 3 monotherapy dose (200 mg once daily [QD]) was chosen due to comparable efficacy and favorable tolerability relative to 500 mg QD and robust ER degradation in paired tumor biopsies. The global, randomized phase 3 VERITAC-2 study (NCT05654623) will compare efficacy and safety of vepdegestrant vs the SERD fulvestrant in patients with ER+/HER2- advanced breast cancer after prior combination cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor therapy and endocrine therapy (ET). Trial design: Eligible patients (aged ≥18 years) have a confirmed diagnosis of ER+/HER2- locoregional recurrent or metastatic breast cancer not amenable to surgical resection or radiation; 1 prior line of combination CDK4/6 inhibitor therapy and ET; ≤1 additional line of ET; most recent ET given for ≥6 months before disease progression; and radiological disease progression during or after the last line of therapy. Prior chemotherapy in the locally advanced or metastatic setting and prior fulvestrant are not permitted. Patients (N≈560) are randomized 1:1 to receive vepdegestrant 200 mg orally QD continuously or fulvestrant intramuscularly on days 1 and 15 in the first 28-day cycle and on day 1 in subsequent cycles; patients are stratified by ESR1 mutation status and presence of visceral disease. The primary endpoint, progression-free survival, will be assessed by blinded independent central review in the intention-to-treat population and the ESR1 mutation subpopulation. Secondary outcome measures include overall survival, antitumor activity (objective response rate, duration of response, and clinical benefit rate), safety, and quality of life assessments. Citation Format: Mario Campone, Cynthia Ma, Michelino de Laurentiis, Hiroji Iwata, Sara Hurvitz, Seth Wander, Michael Danso, Dongrui Lu, Julia Perkins Smith, Yuan Liu, Lana Tran, Sibyl Anderson, Erika Hamilton. VERITAC-2: a phase 3 study of vepdegestrant, a PROteolysis TArgeting Chimera (PROTAC) estrogen receptor (ER) degrader, vs fulvestrant in ER–positive/human epidermal growth factor receptor 2 (HER2)–negative advanced 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 PO1-19-12.

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.

Abstract 3474: Racial disparities in receipt of surveillance mammography after breast cancer diagnosis

Abstract Background: The 5-year survival rate for breast cancer (BC) stands at an estimated 91%, with approximately 3.8 million BC survivors in the U.S. This large population of breast cancer survivors remains at risk of loco-regional recurrence, with variations noted across racial groups. White survivors face a locoregional breast cancer recurrence rate of 1.8%, whereas Black, Asian, and Hispanic survivors experience higher rates of 3.9%, 3.6%, and 3.1%, respectively. Notably, Black BC survivors with recurrent breast cancer exhibit a median survival time of 1.8 years compared with 3.6 years observed for White BC survivors. Current recommendations from the U.S. Preventative Services Task Force and the American College of Radiology advocate for surveillance through annual mammography and routine clinical visits following breast-conserving surgery and lumpectomies. However, there are gaps in the data available regarding disparities in the utilization of surveillance mammography by race/ethnicity. Thus, the goal of this study is to estimate race/ethnic disparities in surveillance mammography utilization and its impact on survival among breast cancer survivors at a large comprehensive cancer center. Methods: A retrospective cohort study of female breast cancer survivors ≥19 years diagnosed and/or treated at the Duke Cancer Institute (DCI) between 2014 and 2022 was conducted. Data was abstracted on patient socio-demographics, cancer type (invasive ductal and ductal in situ carcinomas) and utilization of surveillance mammography within 2-5 years post initial breast cancer diagnosis. Chi-squared testing will be used to analyze rates of mammography surveillance receipt among different races presenting with BC at DCI. Kaplan-Meier estimates will be used for analysis on survival. Results: A total of 10,904 women with a mean age of 43.7 years were included in the study. The study cohort is comprised of 69% non-Hispanic (NH) White, 24% NH Black, 2.2% Hispanic, 0.5% NH Native American, 1% NH other, and 3.2% NH Asian women. There were 1,791 cases of ductal in situ carcinomas and 9,113 invasive ductal carcinoma cases. NH Black women had the lowest 5-year relative survival rate (81.5%) of all represented racial groups: NH White 89.1%, Hispanic 95.3%, NH Native 87.8%, Asian 97.9%, and NH Other 88.0%. Ongoing analysis will be completed to estimate disparities in the use of post-treatment surveillance mammography amongst breast cancer survivors. Conclusions: This study will inform efforts to increase post-treatment surveillance and improve adherence to survivorship guidelines with the ultimate goal of reducing mortality disparities among breast cancer survivors. Citation Format: Jasmine G. Wilkerson, Frances Wang, Yadurshini Raveendran, Tomi Akinyemiju. Racial disparities in receipt of surveillance mammography after breast cancer diagnosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3474.

The MARECA (national study of management of breast cancer locoregional recurrence and oncological outcomes) study: protocol for a prospective, multicentre cohort study.

Despite a UK 5-year breast cancer survival rate of 86.6%, patients may develop breast cancer recurrence within the same breast after breast conserving surgery, as well as in the remaining skin or chest wall after mastectomy or in the ipsilateral lymph glands. These recurrences, collectively termed locoregional recurrence (LRR), occur in around 8% of patients within 10 years of their original diagnosis. Currently, there is a lack of robust information on the presentation and prevalence of LRR with no UK-specific clinical guidelines available for the optimal management of this patient group. Additionally, there is a need to identify patterns of LRR presentation and their progression, which will enable prognostic factors to be determined. This will subsequently enable the tailoring of treatment and improve patient outcome. The MARECA study is a prospective, multicentre cohort study recruiting patients diagnosed with breast cancer LRR +/- associated distant metastases. Over 50 UK breast units are participating in the study with the aim of recruiting at least 500 patients over a recruitment period of 24 months. The data collected will detail the tumour pathology, imaging results, surgical treatment, radiotherapy and systemic therapy of the primary and recurrent breast cancer. Study follow-up will be for up to 5 years following LRR diagnosis to determine subsequent oncological outcomes and evaluate potential prognostic factors. This study will address the current knowledge gap and identify subgroups of patients who have less successful treatment outcomes. The results will determine the current management of LRR and the prognosis of patients diagnosed with breast cancer LRR +/- distant metastases in the UK, with the aim of establishing best practice and informing future national guidelines. The results will direct future research and inform the design of additional interventional trials and translational studies.

95 (PB-095) Poster - The INFLUENCE 3.0 model: time-dependent risks of locoregional recurrence and contralateral breast cancer, now also including patients treated with neoadjuvant systemic therapy

95 (PB-095) Poster - The INFLUENCE 3.0 model: time-dependent risks of locoregional recurrence and contralateral breast cancer, now also including patients treated with neoadjuvant systemic therapy

157 (PB-064) Poster - The continuous thermal dose-effect relationship in locoregional recurrent breast cancer patients treated with postoperative reirradiation combined with hyperthermia

157 (PB-064) Poster - The continuous thermal dose-effect relationship in locoregional recurrent breast cancer patients treated with postoperative reirradiation combined with hyperthermia

Locoregional Breast Cancer Recurrence in the European Organisation for Research and Treatment of Cancer 10041/BIG 03-04 MINDACT Trial: Analysis of Risk Factors Including the 70-Gene Signature.

A number of studies are currently investigating de-escalation of radiation therapy in patients with a low risk of in-breast relapses on the basis of clinicopathologic factors and molecular tests. We evaluated whether 70-gene risk score is associated with risk of locoregional recurrence (LRR) and estimated 8-year cumulative incidences for LRR in patients with early-stage breast cancer treated with breast conservation. In this exploratory substudy of European Organisation for Research and Treatment of Cancer 10041/BIG 03-04 MINDACT trial, we evaluated women with a known clinical and genomic 70-gene risk score test result and who had breast-conserving surgery (BCS). The primary end point was LRR at 8 years, estimated by cumulative incidences. Distant metastasis and death were considered competing risks. Among 6,693 enrolled patients, 5,470 (81.7%) underwent BCS, of whom 98% received radiotherapy. At 8-year follow-up, 189 patients experienced a LRR, resulting in an 8-year cumulative incidence of 3.2% (95% CI, 2.7 to 3.7). In patients with a low-risk 70-gene signature, the 8-year LRR incidence was 2.7% (95% CI, 2.1 to 3.3). In univariable analysis, adjusted for chemotherapy, five of 12 variables were associated with LRR, including the 70-gene signature. In multivariable modeling, adjuvant endocrine therapy and to a lesser extent tumor size and grade remained significantly associated with LRR. This exploratory analysis of the MINDACT trial estimated an 8-year low LRR rate of 3.2% after BCS. The 70-gene signature was not independently predictive of LRR perhaps because of the low number of events observed and currently cannot be used in clinical decision making regarding LRR. The overall low number of events does provide an opportunity to design trials toward de-escalation of local therapy.

Locoregional recurrences of breast cancer after reconstructive plastic and organ-preserving surgery

Objective. To analyze locoregional relapses (LRR) after reconstructive plastic and organ-preserving operations in breast cancer (BC)Materials and methods. A retrospective analysis of the results of the treatment of 303 patients with BC who underwent reconstructive plastic and organ-preserving operations in the period from 2014 to 2019 in the Oncological Department of General Oncology and Rehabilitation of Gomel Regional Clinical Oncological Dispensary was carried out. The median age was 44 years (25-70 years). Statistical data processing was carried out using the application software package “Statistica”, 10.0. To characterize the surveyed groups, a standard methodological approach based on the calculation of descriptive statistics data was used. In order to statistically assess the relationship between the frequency of relapses depending on the stage and the molecular biological type of neoplasm, the Spearman correlation coeffi cient was used. The accepted level of statistical signifi cance (p) was 0.05.Results. Locoregional relapses were recorded in 11 (3.6%) patients, of which local — in 8 (2.6%), regional — in 3 (1.0%). The minimum period of development of LRR was 15 months, the maximum was 74 months; the median period of occurrence of LRR was 47 months. Depending on the stage of breast cancer, relapses developed: at stage I — in 4 (3.7%) cases, II — 5 (3.5%), III — 2 (4.2%). Depending on the molecular biological subtype of the neoplasm, LRR were distributed as follows: with luminal A — 1 (1.3%) case, luminal In HER2-negative — 1 (0.9%), luminal In HER2-positive — 6 (9.7%), non-luminal HER2-positive 1 (6.3%), three times negative — 2 (5.6%). Discordance of the receptor status was detected in 8 (72.7%) patients with recurrent tumor, most often due to the loss or decrease in the number of progesterone receptors (PR). The level of tumor-infi ltrating lymphocytes (TILs) in primary neoplasm ranged from 4 to 12%, in recurrent tumors it remained low: 5-10%.Conclusion. Given the heterogeneity of BC, the risk of developing LRR depends on many factors. LRR developed in luminal HER2-positive cancer in 9.7% of cases (p 0.05), stage III breast cancer — 4.2% (p 0.05). One of the important predictive factors is the evaluation of TILs. We noted a low level of TILs in both primary and recurrent tumors. There is a high discordance in the receptor status — 72.7%, which is important to take into account when prescribing systemic therapy.

Omission of axillary lymph node dissection in breast cancer patients with micrometastasis or isolated tumor cells in sentinel lymph nodes: a 12-year experience in a tertiary breast unit.

After the IBCSG 23-01 trial, our breast center no longer performed axillary lymph node dissection (ALND) after detection of isolated tumor cells (ITC) or micrometastasis in the sentinel lymph nodes (SLN). A recent study suggested that up to half of the patients with micrometastasis in the SLN could benefit from ALND in terms of disease-free survival (DFS) and overall survival (OS). This retrospective, unicentric, study analyzed 261 consecutive cT1-3 cN0 breast cancer patients with ITC or micrometastasis in their SLN. Primary objective was comparison of ALND vs. SLN biopsy (SLNB) with regard to DFS and OS. Secondary objectives included analysis of factors associated with an increased rate of locoregional recurrence (LRR), distant metastasis (DM) and metachronous contralateral breast cancer (MCBC). DFS events occurred in 19 patients (7.3%) and 14 patients died (5.4%). Median follow-up time was 78months. 251 patients (96.2%) had micrometastasis in their SLN. There was no difference in the OS or DFS of ALND vs. SLNB patients. History of previous contralateral breast cancer and WBI were associated with an increased and decreased rate of LRR, respectively. Larger tumor size was associated with an increased rate of DM. Non-ductal histological types were associated with an increased rate of MCBC. Avoiding ALND may be safe in pN1mi/pN0(i+) patients. Besides, we strongly encourage clinicians to develop their own follow-up protocols based on the best available evidence, to rapidly identify and treat breast cancer recurrence.

Immune cells within tertiary lymphoid structures are associated with progression-free survival in patients with locoregional recurrent breast cancer.

Locoregional recurrent breast cancers have a poor prognosis. Little is known about the prognostic impact of immune microenvironment, and tertiary lymphoid structures (TLSs) in particular have not been reported. Thus, we aimed to characterize the immune microenvironment in locoregional recurrent breast tumors and to investigate its relationship with prognosis. We retrospectively included 112 patients with locoregional recurrent breast cancer, and hematoxylin-eosin staining and immunohistochemical staining (CD3, CD4, CD8, CD19, CD38, and CD68) were performed on locoregional recurrent tumor samples. The association of immune cells and TLSs with progression-free survival (PFS) were analyzed by survival analysis. We found more immune cells in the peritumor than stroma. After grouping according to estrogen receptor (ER) status, a low level of peritumoral CD3+ cells in ER+ subgroup (p = 0.015) and a low level of stromal CD68+ cells in ER- subgroup (p = 0.047) were both associated with longer PFS. TLSs were present in 68% of recurrent tumors, and CD68+ cells within TLSs were significantly associated with PFS as an independent prognostic factor (p = 0.035). TLSs and immune cells (CD3, CD38, and CD68) within TLSs were associated with longer PFS in ER- recurrent tumors (p = 0.044, p = 0.012, p = 0.050, p < 0.001, respectively), whereas CD38+ cells within TLSs were associated with shorter PFS in ER+ recurrent tumors (p = 0.037). Our study proposes potential predictors for the clinical prognosis of patients with locoregional recurrent breast cancer, emphasizing the prognostic value of immune cells within TLSs, especially CD68+ cells.

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).

Proton Re-Irradiation with Concurrent Hyperthermia in Patients with Recurrent Breast Cancer

The aim of this study is to evaluate the safety and effectiveness of proton re-irradiation with concurrent hyperthermia in the treatment of recurrent breast cancer. We retrospectively identified patients previously treated with photon whole breast or chest wall irradiation for a primary breast cancer at our institution, who subsequently developed a histologically-confirmed locoregional recurrence or new ipsilateral primary breast cancer and underwent proton chest wall re-irradiation with concurrent hyperthermia as part of definitive treatment. Acute toxicity was evaluated once weekly while on-treatment and at 2 weeks and 3 months post-treatment. Toxicities were graded according to CTCAE v4.0. Fifteen patients received proton re-irradiation with concurrent superficial hyperthermia at our institution from August 2018 to December 2022. Median interval between radiation treatment courses was 7.7 years (range 1-30 years). Four patients (26%) had gross, unresected disease at the time of re-treatment. The median initial radiation dose, re-irradiation dose, and cumulative EQD2 was 60.4 Gy (50.6-61.2 Gy), 60 Gy (RBE) (45-66 Gy (RBE)), and 120 Gy (RBE) (103-126 Gy (RBE)), respectively. Patients received a median of 9 (3-14) concurrent hyperthermia treatments delivered twice weekly, and 13 patients (87%) received seven or more hyperthermia treatments. Median toxicity follow-up was 9 months (0-36 months). Acute grade 3 toxicities included two patients (13%) with grade 3 dermatitis, both of which resolved with conservative management within 3 months of treatment completion. Chronic grade 2 or higher toxicities included two grade 2 hyperpigmentation, one grade 3 induration, one grade 2 telangiectasia, and one grade 2 rib fracture. There were no grade 4-5 acute or late toxicities. There was one in-field local recurrence and one regional recurrence outside of the re-irradiation field. Both patients had gross, unresected disease at the time of re-irradiation. Two patients (13%) developed distant disease. Proton re-irradiation with concurrent hyperthermia is feasible and well-tolerated in the re-treatment of breast cancer. Further studies are warranted to determine long-term toxicity and oncologic outcomes.

Efficient synergistic combination effect of curcumin with piperine by polymeric magnetic nanoparticles for breast cancer treatment

Although it has been reported that the co-delivery of drugs can be beneficial to patients to kill breast cancer cells, the delivery methods could only be employed to effectively encapsulate individual curcumin (CUR) or piperine (PIP) molecules due to their different molecular polarities. Therefore, in the current research, an attempt was made to overcome the limitation of the co-delivery of CUR and PIP nanoparticles for breast cancer therapy. To manage locoregional breast cancer recurrence, a magnetic co-delivery system of CUR and PIP against MCF-7 breast cancer cells was examined. CUR and PIP demonstrated synergistic effects for breast cancer therapy when utilized together. However, due to the different polarities of CUR and PIP, it was difficult to co-encapsulate them in conventional delivery systems. Moreover, their low bioavailability, hydrophobic nature, and low cellular uptake limit its usage for cancer therapy. In the current study, to overcome the issues and improves its therapeutic efficacy, CUR and PIP-loaded zein/chitosan-coated iron oxide (Chit-PIP/[email protected]3O4) were prepared via a combination of anti-solvent precipitation and layer-by-layer deposition. X-ray diffraction (XRD) analysis revealed magnetite cores and also showed that the binding process did not change the Fe3O4 phase. A vibrational sample magnetometer confirmed that the saturation of sample magnetization was 60 and 40 emu/g for pure Fe3O4 and nanocomposite, respectively. Nanoparticles with an average size of 20 nm were prepared. The drug-loading content of CUR and PIP was approximately 18% and 16%, respectively. CUR and PIP release from Chit-PIP/[email protected]3O4 was faster at the extracellular pH of around tumors (6.5) than in normal tissues (7.4), an interesting degree of pH sensitivity. The MTT assay exhibited that PIP/CUR-loaded polymeric magnetic nanoparticles had significant synergistic cytotoxicity against MCF-7 cells compared with other groups. These results demonstrate that the combination of dual-drug loaded polymeric magnetic nanoparticles holds promise for the targeted treatment of cancer cells.

Comparison of Digital Mammography with Tomosynthesis and Ultrasound to Magnetic Resonance Imaging in Assessment of Post Operative Scarring and Locoregional Recurrence of Breast Cancer

Background Breast cancer is the most common type of cancer and the second cause of cancer associated death in women. It is the most common type of cancer in women and the third cause of cancer associated death in Egypt. Aim of the Study Our study aims to evaluate the role of digital breast tomosynthesis with complementary ultrasound compared to magnetic resonance imaging in assessment of post-operative changes and loco regional recurrence of breast cancer. Patients and Methods A Cross sectional study was approved by the ethics review board of Ain Shams University Hospitals. All MR imaging were conducted at the Department of Radiology at Ain-Shams University. Thirty patients who were surgically treated by conservative breast surgery were included in our study from March2021 to September 2021 according to the regulations of the ASU ethical committee. The resultant BIRADS were subsequently correlated with the final results by histopathology. Results In our study DBT with complementary US showed greater sensitivity (100 %) than MRI (80 %), yet it revealed lower specificity(96%) than MRI (100%). DBT with complementary ultrasound show a higher NPV (100%)but lower PPV (83. 3%) than MRI (96.1%) (100%) respectively. However, both of them revealed comparable accuracy: DBT with us (96.6%) and MRI (96.6%). Conclusion MRI has a lot of technical errors that limit its results and increase its numerous pitfalls. DBT with complementary ultrasound are a powerful imaging modalities that can be used to detect any recurrence in patients who are surgically treated for breast cancer with higher sensitivity and higher NPV than MRI and both of them revealed comparable accuracy.So, the use of these modalities enhance diagnosis of surgically treated breast cancer for early detection of recurrence.

Locoregional Treatment for Early-Stage Breast Cancer: Current Status and Future Perspectives.

The locoregional recurrence of breast cancer has been reduced due to the multidisciplinary approach of breast surgery, systemic therapy and radiation. Early detection and better surgical techniques contribute to an improvement in breast cancer outcomes. The purpose of this review is to have an overview and summary of the current evidence behind the current approaches to the locoregional treatment of breast cancer and to discuss its future direction. With improved surgical techniques and the use of a more effective neoadjuvant systemic therapy, including checkpoint inhibitors and dual HER2-directed therapies that lead to a higher frequency of pathologic complete responses and advances in adjuvant radiation therapy, breast cancer patients are experiencing better locoregional control and reduced local and systemic recurrence. De-escalation in surgery has not only improved the quality of life in the majority of breast cancer patients, but also maintained the low risk of recurrence. There are ongoing clinical trials to optimize radiation therapy in breast cancer. More modern radiation technologies are evolving to improve the patient outcome and reduce radiation toxicities.

A three-gene signature marks the time to locoregional recurrence in luminal-like breast cancer

Gene expression profiling (GEP)-based prognostic signatures are being rapidly integrated into clinical decision making for systemic management of breast cancer patients. However, GEP remains relatively underdeveloped for locoregional risk assessment. Yet, locoregional recurrence (LRR), especially early after surgery, is associated with poor survival. GEP was carried out on two independent luminal-like breast cancer cohorts of patients developing early (≤5 years after surgery) or late (>5 years) LRR and used, by a training and testing approach, to build a gene signature able to intercept women at risk of developing early LRR. The GEP data of two in silico datasets and of a third independent cohort were used to explore its prognostic value. Analysis of the first two cohorts led to the identification of three genes, CSTB, CCDC91 and ITGB1, whose expression, derived by principal component analysis, generated a three-gene signature significantly associated with early LRR in both cohorts (P value <0.001 and 0.005, respectively), overcoming the discriminatory capability of age, hormone receptor status and therapy. Remarkably, the integration of the signature with these clinical variables led to an area under the curve of 0.878 [95% confidence interval (CI) 0.810-0.945]. In in silico datasets we found that the three-gene signature retained its association, showing higher values in the early relapsed patients. Moreover, in the third additional cohort, the signature significantly associated with relapse-free survival (hazard ratio 1.56, 95% CI 1.04-2.35). Our three-gene signature represents a new exploitable tool to aid treatment choice in patients with luminal-like breast cancer at risk of developing early recurrence.

Biomarker status conversion in locoregional breast cancer recurrence in a patient who had achieved pathologic complete response: a case report

Biomarker status conversion in locoregional breast cancer recurrence in a patient who had achieved pathologic complete response: a case report