Treatment Of Primary Breast Cancer Research Articles

Development and Characterization of a Peptide-Bisphosphonate Nanoparticle for the Treatment of Breast Cancer.

In women, breast cancer (BC) is the most common cancer, and despite advancements in diagnosis and treatment, 20-30% of early stage BC patients develop metastatic disease. Metastatic BC is deemed an incurable disease, which accounts for 90% of BC related deaths, with only 26% of metastatic patients reaching a 5 year survival rate. Therefore, there is an unmet need for the prevention or treatment of metastasis in early stage breast cancer patients. Bisphosphonates (BPs) are potent inhibitors of bone resorption and are extensively used for the prevention of osteoporosis and other skeletal disorders, as well as for the treatment of secondary bone cancer in BC patients. Furthermore, the direct anticancer activity of BPs has been established in primary tumor models. However, these studies were limited by the need for dosages far above the clinical range to overcome BPs' high affinity for bones and poor accumulation in the tumor itself, which leads to toxicity, including osteonecrosis of the jaw. To decrease BP dosage, increase bioavailability, and direct anticancer activity, we used the RALA (R-) peptide delivery system to form highly stable NPs with the nitrogen containing BP, risedronate (R-RIS). In vitro studies showed that, in comparison to RIS, R-RIS nanoparticles increased cytotoxicity and reduced metastatic features such as proliferation, migration, invasion, and adhesion of metastatic BC cells to bones. Furthermore, in an in vivo model, R-RIS had increased tumor accumulation while still maintaining similar bone accumulation to RIS alone. This increase in tumor accumulation corresponded with decreased tumor volume and lungs metastasis. R-RIS has great potential to be used in combination with standard of care chemotherapy for the treatment of primary BC and its metastasis while still having its bone resorption inhibiting properties.

Impact of Diet Modifications on Body Weight, Body Composition, Treatment Outcomes, and Quality of Life During Primary Treatment for Breast Cancer: A Systematic Review.

Breast cancer is a significant public health challenge, with 290 000 new cases annually and significant healthcare costs. Treatment advancements have led to improvements in survival, but common adverse effects include weight gain, fatigue, nausea, and taste changes, decreasing quality of life. This review aims to assess the impact of diet and lifestyle interventions during primary treatment for breast cancer and their effects on body weight, body composition, treatment-related adverse outcomes, and patient-reported quality of life. A search of PubMed, CINAHL, and EMBASE conducted through May 10, 2023, identified 31 publications describing 27 interventions including diet or diet plus exercise. The Cochrane Risk of Bias tool assessed the quality of publications. The findings suggest that whole foods, aerobic and strength-training exercises, and intermittent fasting during treatment may improve body weight and composition, treatment-related outcomes, and quality of life. Limitations include variation in study duration, small sample sizes, and limited sociodemographic data. Improvements seen with increased diet quality and reduced caloric intake, with or without exercise, challenge current standard-of-care recommendations during treatment for breast cancer. While there is a need for additional research, healthcare teams can confidently promote healthy diets and exercise during primary treatment for breast cancer to manage weight and improve treatment-related side effects and quality of life. PROSPERO registration no. 42023425613.

Lipid-coated gold nanorods for photoimmunotherapy of primary breast cancer and the prevention of metastasis

Nanomedicines hold promise for the treatment of various diseases. However, treating cancer metastasis remains highly challenging. In this study, we synthesized gold nanorods (AuNRs) containing (α-GC), an immune stimulator, for the treatment of primary cancer, metastasis, and recurrence of the cancer. Therefore, the AuNR were coated with lipid bilayers loaded with α-GC (α-LA). Upon irradiation with 808 nm light, α-LA showed a temperature increase. Intra-tumoral injection of α-LA in mice and local irradiation of the 4T1 breast cancer tumor effectively eliminated tumor growth. We found that the presence of α-GC in α-LA activated dendritic cells and T cells in the spleen, which completely blocked the development of lung metastasis. In mice injected with α-LA for primary breast cancer treatment, we observed antigen-specific T cell responses and increased cytotoxicity against 4T1 cells. We conclude that α-LA is promising for the treatment of both primary breast cancer and its metastasis.

Distress, Pain, and Nausea on Postoperative Days 1 and 14 in Women Recovering From Breast-Conserving Surgery: A Repeated-Measures Study.

To determine the incidence and trajectory of distress, pain, and nausea and vomiting at postoperative day (POD) 1 and at POD 14 following breast-conserving surgery. 75 women aged 18 years or older receiving breast-conserving surgery with sentinel lymph node biopsy for treatment of early-stage primary breast cancer at an ambulatory surgery center. This prospective, repeated-measures study assessed distress, pain, and nausea and vomiting using the National Comprehensive Cancer Network Distress Thermometer and Problem List on POD 1 and POD 14. Pain and distress scores were highest on POD 1. The number of women who reported depression increased from POD 1 to POD 14. Thematic analysis revealed that family concerns, fears and worries, and postoperative issues contributed to pain and distress. Women experience pain and distress during recovery at home after breast-conserving surgery. Nurses can use these results to apply evidence-based practice to reduce this symptom burden. Future nursing research should focus on targeted interventions outside of the hospital setting.

CT-Guided Percutaneous Cryoablation of Breast Cancer: A Single-Center Experience.

This study shall retrospectively evaluate the efficacy and safety of liquid-nitrogen based CT-guided cryoablation (CA) as a minimal-invasive technique for the curative treatment of primary breast cancer. A total of 45 female patients with 56 tumors were treated by CT-guided CA in analgosedation as an outpatient procedure. We used a liquid-nitrogen based system with a single cryoprobe and performed two freeze cycles with an intermediate thawing. The mean tumor diameter was 1.6 ± 0.7 cm. Follow-up was conducted via contrast-enhanced MR images of the breast. No complications were observed in all 56 ablations. Initial complete ablation was achieved in 100% of cases. Four cases of local tumor progression were reported, resulting in a rate of 8.9%, and 6 cases of intramammary distant recurrence at a rate of 13.3%. The extramammary tumor progression was observed in 7 patients at a rate of 15.6%. The mean overall survival was 4.13 years (95% CI: 3.7-4.5). The mean overall progression-free survival was 2.5 years (95% CI: 1.8-3.2) and the mean local progression-free survival was 2.9 years (95% CI: 2.3-3.6). Cryoablation is a safe and effective treatment for primary breast cancer tumors, which can be performed in analgosedation and as an outpatient procedure. However, potential for improvement exists and further evidence is necessary.

Molecular subtype and risk of local recurrence after nipple‑sparing mastectomy for breast cancer.

The present study aimed to investigate whether local recurrence (LR) after nipple-sparing mastectomy (NSM) and reconstruction was associated with i) Ki67 values and molecular subtypes of the initial lesions, and ii) the size of the initial tumor and the size of the implant. A total of 156 patients with breast cancer with a mean age of 51.58 years (age range, 26-75 years) who underwent NSM with primary implant breast reconstruction were analyzed. After surgery, the mean follow-up time was 59.26 months (range, 17-85 months). Molecular subtypes, Ki67 values, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status were recorded for each patient. Additionally, information regarding the size of the implant and the initial tumor size were collected. The information was used to assess LR. For univariate analyses of risk factors, χ2 test, Fisher's exact test, Mann-Whitney U test and Student's t-test for independent samples were used. For multivariate analyses, a Cox proportional-hazards model was used. NSM was the primary treatment for breast cancer in 34/156 patients (21.8%), while 122/156 (78.2%) of patients received neoadjuvant chemotherapy followed by surgery. Luminal B was the most frequent molecular subtype, detected in 82/156 patients (52.6%), whereas the luminal A subtype was detected in 37 patients (23.7%) and the HER2-enriched subtype was detected in 17/156 patients (10.9%). Ki67 expression was low in 13/156 patients (8.3%), while medium expression was detected in 78/156 patients (50.0%) and high expression was present in 58/156 patients (37.2%). LR was noted in 17/156 patients (10.9%). As determined by univariate analysis, lower ER (P=0.010) and PR (P=0.008) expression were indicated to be significant risk factors for LR. In conclusion, in the present patient cohort, low ER and PR expression were risk factors for LR of breast cancer, whereas Ki67 status and molecular subtype were not statistically significant risk factors for LR. Additionally, the size of the initial tumor and the size of the implant were not risk factors for LR. These findings are consistent with the current literature, and should be utilized when discussing treatment options and potential clinical outcomes with patients prior to surgical management.

Association of childhood trauma with choice of bilateral mastectomy for the treatment of unilateral breast cancer.

e24096 Background: Patients are increasingly choosing bilateral mastectomy (BMX) for the treatment of primary breast cancer (BC) despite minimal survival benefits and potential for adverse medical and psychosocial consequences. Exposure to childhood trauma is associated with dysregulation of stress response systems, threat perception alterations, increased risk-taking behaviors, and body dissatisfaction. We examined childhood trauma in relation to treatment decision-making in adulthood within a sample of breast cancer patients undergoing either BMX or more conservative BC treatment. Methods: Secondary analyses of a case-control study of the neurobiological and affective determinants of BMX choice were conducted. Cross-sectional data from the baseline survey were analyzed. Participants were recruited via institutional clinic practices, social media, and patient advocacy groups. Patients completed a medical status questionnaire and the Childhood Trauma Questionnaire (CTQ). Chi-square and Mann-Whitney U tests examined differences in treatment decision-making by childhood trauma exposure and type. Results: The sample included 137 patients with unilateral stages 0-III BC (mean age 49.2; SD = 11.2; 76.6% White; 10.9% Hispanic/Latina; 68.6% married). Seven tested positive for a BRCA gene mutation. Patients were divided between BMX (n = 66) and non-BMX (n = 71) treatment groups. On average, patients in the non-BMX group reported higher levels of childhood trauma severity (Median = 7; IQR = 0-12.5) compared to patients in the BMX group (Median = 4; IQR = 0-11.75; Mann Whitney U = 4728; small effect size; SRD = -0.11; p = .26). Patients who reported a major parental upheaval (e.g., divorce, separation) were significantly more likely to pursue non-BMX compared to BMX (small effect size; SRD = -.16; p = .047). Patients who reported any uncategorized major upheaval were more likely to choose non-BMX than BMX (small effect size; SRD = -.14), but group differences did not reach significance (p = .093) . No other statistically significant relationships were observed. Conclusions: Contrary to hypotheses, preliminary results suggest BC patients who were exposed to traumatic events in childhood may be more likely to elect conservative BC surgical treatments. Trauma-related hypervigilance to threats may cause patients to exercise more caution regarding treatment choice. More research exploring the effects of adverse childhood experiences in the BC population is warranted. [Table: see text]

Effect of timing of recurrence on outcomes in patients with metastatic breast cancer treated with CDK4/6 inhibitors.

e13067 Background: CDK4/6 inhibitors (CDKi) + endocrine therapy (ET) comprise the standard 1st line treatment for ER+ HER2- metastatic breast cancer (MBC). However, there is a gap in understanding how timing of MBC recurrence affects clinical outcomes on CDKi. We conducted a study to compare clinical outcomes of MBC patients on CDKi based on timing of MBC recurrence. Methods: This retrospective study enrolled ER+ HER2- MBC patients diagnosed from Jan 2015 to Jan 2023, who received CDKi + ET as 1st line treatment for MBC. Patients were categorized as de novo MBC (dMBC), if they had 1. Stage 4 disease at initial diagnosis or 2. MBC diagnosed < 6 months of the primary breast cancer (PBC) diagnosis and before starting any systemic treatment for PBC. Patients with distant recurrence occurring < 5 years, 5-10 years, and >10 years from PBC were categorized as early, intermediate, and late MBCs (eMBC, iMBC, laMBC). Endpoints were Progression-Free Survival (PFS) and Overall Survival (OS) from MBC diagnosis. Baseline variables were compared using t-tests (continuous) and Chi-square tests (categorical). Endpoint analyses were conducted using Kaplan-Meier method and compared using Log rank test. Multivariate analyses were performed using Cox models. Results: Out of 280 patients enrolled, 67 were dMBC, 75 eMBC, 56 iMBC, and 82 laMBC. The laMBC group had a higher mean age (years) compared to other groups (71 vs. 62 in dMBC+ eMBC + iMBC, p<0.001). 64.5% of laMBC had visceral disease compared to 50.5% of dMBC + eMBC + iMBC (p=0.031). 65.7% of dMBC patients were treated with palbociclib compared to 80.8% of eMBC + iMBC + laMBC (p=0.010). Higher % of eMBC were PR- vs other cohorts (41.3 vs 23.9 dMBC + iMBC + laMBC, p<0.001). Among the 3 non dMBC groups, prior ET sensitivity (no recurrence for 2 years on adjuvant ET) was lower in eMBC (45.3%) compared to iMBC + laMBC (81.9%, p<0.001). 61.3% of eMBC patients were on adjuvant ET at recurrence compared to 17.4% of iMBC + laMBC (p<0.001). Other variables were similar. Table shows unadjusted endpoint analyses. In multivariate analyses, the risk of PFS events were not significantly different among cohorts (age<=65, ECOG performance status (PS) >=2 and PR- were independently associated with shorter PFS); risk of death was higher in eMBC vs laMBC (HR 1.73, p=0.047). Conclusions: In this retrospective study of ER+ HER2- MBC patients treated with 1st line CDKi + ET, timing of MBC recurrence was not associated with PFS differences after adjusting for other variables. However, patients with MBC recurring < 5 years of PBC had the higher likelihood of death compared to those recurring >10 years of PBC. [Table: see text]

Abstract PO3-11-10: Second primary non-breast cancers in young breast cancer survivors

Abstract Adolescent and young adults (AYAs) (15-39 years) have a heightened risk of developing a second primary malignancy due to extended periods of survivorship, higher incidence of germline cancer predisposing variants, and increased susceptibility to treatment-induced malignancies. Research on survivors of specific AYA cancer types, including breast cancer (BC) survivors, is limited. Among BC survivors, while much survivorship research focuses on risk of locoregional recurrence or contralateral BC, little is known about overall risk, and risk factors, of developing second non-breast primaries. This prospective cohort study examined women diagnosed with BC from 2006-2016 at age ≤40 years enrolled in the Young Women’s BC Study (YWS) (N=1297). Women were excluded from the analytic cohort if initially diagnosed with Stage IV breast cancer (N=64). To enable investigation of how BC treatments may impact second primary risk, women were also excluded if they reported another cancer before primary BC diagnosis (N=3). Patient characteristics, treatment information, and clinical events were collected via serial surveys. Tumor characteristics and detailed treatment data were obtained from medical record review. Five- and 10-year risk of second non-breast primary was estimated via the cumulative incidence function after applying the Fine-Gray competing risks model with time starting at primary BC diagnosis. Death, metastasis, or diagnosis with a second primary BC were considered as competing events. Univariate and multivariate Fine-Gray sub-distribution models were used to estimate sub-distribution hazard ratios (sHRs) and 95% confidence intervals (CI) for second non-breast primary cancer risk. Risk factors considered included age, race, body mass index, smoking, alcohol use, income, family history of cancer, germline pathogenic variant (PV) carrier status, tumor stage, grade, and ER status, primary surgery type, and receipt of radiation, chemotherapy, or endocrine therapy (yes/no). Multivariate models tested individual associations with additional adjustment for radiation therapy and PV carrier status, as both are consistently associated with second primary in the literature. Over a median follow-up of 10.1 years (inter-quartile range (IQR) =7.9-12.1 y), 47 patients (4%) developed a second non-breast primary cancer. Median age at second non-breast primary was 43 years (IQR=39-46), and median time between primary BC and second non-breast primary was 7.3 years (IQR=4.1-9.3). Second primary types included melanoma (n=10), thyroid (n=10), ovarian (n=4), sarcoma (n=4), uterine (n=3), rectal (n=3), bladder (n=2), cervical (n=2), head and neck (n=2), lung (n=2), lymphoma (n=2), pancreatic (n=2), and kidney (n=1). During the study, 22 patients (2%) developed a second primary BC, 167 (19%) developed metastasis, and 15 (1%) died from causes other than BC. Among the patients who developed a second primary BC, two later developed another non-breast cancer (ovarian and brain cancer). When incorporating competing risks, five and 10-year cumulative incidence of second non-breast primary was 1.4% and 3.2%, respectively. No patient or treatment factors were statistically significantly associated with second non-breast primary in univariate or multivariate models, including radiation and PV carrier status. In this population of young BC survivors, 10-year cumulative incidence of second non-breast primary cancer was 3.2%, with the most common second cancers being melanoma and thyroid cancer. Incidence rates of all second primary cancer types in this cohort were higher than population-based incidence rates for healthy women under 50 years of age, highlighting the importance of long-term surveillance for other cancer events in this young population. While risk of second non-breast primary was not associated with primary BC treatment in this study, cases were limited, and the follow-up interval was relatively short. Citation Format: Bessie Zhang, Kristen Brantley, Shoshana Rosenberg, Gregory Kirkner, Laura Collins, Kathryn Ruddy, Rulla Tamimi, Lidia Schapira, Virginia Borges, Ellen Warner, Steven Come, Eric Winer, Ann Partridge. Second primary non-breast cancers in young breast cancer survivors [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 PO3-11-10.

Information and communication priorities of patients and healthcare professionals in shared decision making regarding adjuvant systemic breast cancer treatment: A survey study

PurposeTo assess information and communication priorities of patients and healthcare professionals in Shared Decision Making about adjuvant systemic treatment of primary breast cancer and identify key decision-relevant information accordingly. MethodsPatients (N = 122) and professionals working with breast cancer patients (N = 118), of whom 38 were nurse practitioners and 32 nurses, were recruited using convenience sampling, and surveyed about information/communication aspects key to decision-making, using ranking assignments. We further posed a simple open question, questions about receiving population-based statistics versus personalized statistics concerning treatment outcomes, and their attitude and experience concerning Shared Decision Making. Data were analyzed using descriptive analysis and a qualitative analysis. ResultsBoth patients and professionals prioritized information about treatment outcomes (i.e., survival, recurrence) as key decision-relevant information for patients. Patients prioritized information about relatively severe treatment side-effects and late effects (e.g., blood clot, stroke), whilst professionals prioritized information about effects that occur relatively often (e.g., hair loss, fatigue). Patients specifically wanted to know if the benefit of treatment is worth the negative impact. Both groups prioritized personalized statistics over population-based statistics. ConclusionsSome differences between patients and professionals were found in information and communication priorities, specifically related to the different side-effects. It seems worthwhile to precisely address these side-effects in Shared Decision Making concerning adjuvant systemic treatment. Furthermore, it seems important to deliberate together on the question if expected benefit of treatment is worth the potential negative impact for the individual patient.

Role of Interventional Radiology in Managing Primary and Metastatic Breast Cancer.

Percutaneous image-guided locoregional therapies are emerging in the treatment of primary and metastatic breast cancer. Cryoablation has emerged as the dominant ablative approach as an alternative to surgery for primary breast cancer in patients who do not wish to have surgery or are poor surgical candidates. Cryoablation is well tolerated and provides excellent local control and cosmesis. Thermal ablation may also be used in the treatment of oligometastatic breast cancer, allowing patients to achieve long disease-free intervals. Transarterial therapies have been studied in the treatment of oligoprogressive hepatic metastasis, though further supportive data would be helpful to demonstrate its efficacy.

Comparison Between Erector Spinae Plane Block versus Serratus Anterior Plane Block Regarding Analgesia and Stress Response After Modified Radical Mastectomy: Randomized Controlled Trial.

Modified radical mastectomy (MRM) is the primary surgical treatment for breast cancer, yet it leads to significant postoperative pain. This randomized controlled trial evaluates the effects of an erector spinae plane block (ESPB) versus a serratus anterior plane block (SAPB) on post-MRM pain management and stress response reduction. Sixty individuals scheduled for unilateral MRM under general anesthesia from October 2021 to October 2022 were divided into three groups. Group A comprised 20 patients who received ultrasound-guided ESPB (20 mL of 0.25% bupivacaine). Group B included 20 patients who received ultrasound-guided SAPB (20 mL of 0.25% bupivacaine). Group C was treated with intravenous morphine based on pain scores. Anesthesia was induced using 2 μg/kg of fentanyl and 2 - 3 mg/kg of propofol. The study compared the three groups regarding pain scores using a numerical rating scale, serum cortisol levels, total fentanyl, and morphine consumption, changes in mean arterial blood pressure (MAP) and heart rate (HR) during surgery, and the occurrence of postoperative complications. Statistically significant reductions in pain scores were observed in group A compared to groups B and C. Moreover, group A exhibited a significant decrease in postoperative morphine consumption, serum cortisol levels 1 hour post-surgery (P = 0.021), MAP, and postoperative vomiting and nausea compared to group B. Furthermore, groups A and B showed statistically significant improvements in all parameters compared to group C. The study demonstrates that ESPB provides superior analgesic effects compared to SAPB in patients undergoing MRM, with reduced morphine use and lower postoperative cortisol levels. Both blocks offer more effective pain control than intravenous morphine alone.

Symptoms and need for individualised support during the first year after primary treatment for breast cancer-A qualitative study.

The survival rate among patients with breast cancer is high. It is well described that after primary treatment patients may experience symptoms and concerns but the needs and resources during the first year to manage everyday life are not well described. To describe experiences of symptom distress, needs and support during the first year after primary treatment for breast cancer from the perspectives of patients and healthcare professionals. Qualitative descriptive. Data collection through individual interviews with patients (n = 17) and a focus group interview with healthcare professionals (n = 7). Data was analysed using thematic analysis and resulted in three themes. The first theme, 'Struggling with symptoms and changes in everyday life' shows how symptoms and concerns interfered with the everyday life of patients and in some situations even impeded them. Patients try to adapt to their new situation by creating new routines and managing symptoms through self-care. The second theme, 'Adaption in a period of uncertainty' describes thoughts about cancer recurrence and doubts about continuing with the endocrine therapy if symptoms prolong. In the third theme, 'Support and need for individualized follow-up care' healthcare professionals described that they provide support by being available and by giving both verbal and written information. Patients expressed that the information could be too general and voiced a need for more individually tailored support. During the first year after primary treatment, patients with breast cancer describe how they try to manage by themselves, but express both unmet needs and a wish for extended and more individually tailored support. The healthcare professionals recognised that patients lack a structured plan for the first year and the need for continued support. This stresses a need for development of care models with special consideration towards individualised support after breast cancer treatment. There was no patient or public involvement in the design or conduct of the study. The interview study was not considered to benefit from involving patients or healthcare professionals when designing the interview guides as they were developed through literature and previous research of patients treated for breast cancer.

Stereotactic body radiation therapy (SBRT) for the treatment of primary breast cancer in patients not undergoing surgery

PurposeThe purpose was to explore the role of stereotactic body radiation therapy (SBRT) in providing local control (LC) for primary breast cancer in patients unable to undergo surgery. Materials/methodsBetween 2015 and 2019, 13 non-surgical candidates with 14 lesions were treated with SBRT for primary breast cancer. In 4 cases, SBRT was used after whole breast radiation therapy (WBRT; 40–50 Gy/20–25 fractions). SBRT dose was 30–40 ​Gy in 5 fractions for patients treated with SBRT alone and 25–32 ​Gy in 4–5 fractions for those treated with SBRT ​+ ​WBRT. LC and overall survival (OS) were estimated using Kaplan-Meier curves. Response was also assessed using RECIST guidelines. ResultsMedian follow-up was 32 (range: 3.4–70.4) months. Imaging at median 2.2 (0.6–8.1) months post-SBRT showed median 43.2 ​% (range: 2–100 ​%) decrease in the largest diameter and median 68.7 ​% (range: 27.9–100 ​%) SUV reduction. There were 3 cases of local progression at 8.7–10.6 months. Estimated LC was 100 ​% at 6 months and 71.6 ​% at 12, 24 and 36 months.Estimated median OS was 100 ​% at 6 months, 76.9 ​% at 12 months, and 61.5 ​% at 24 and 36 months. Acute toxicity (n ​= ​13; 92.9 ​%) included grade (G)1 (n ​= ​8), G2 (n ​= ​4), and G4 (necrosis; n ​= ​1). Late toxicity included G2 edema (n ​= ​1) and G4 necrosis (n ​= ​2, including 1 consequential late effect). Only patients treated with SBRT ​+ ​WBRT experienced acute/late G4 toxicity, managed with resection or steroids. ConclusionsSBRT to primary breast cancer resulted in good LC in non-surgical/metastatic patients. Although necrosis (n ​= ​2) occurred in the SBRT ​+ ​WBRT group, it was successfully salvaged.

Locoregional Therapies for Primary and Metastatic Breast Cancer: AJR Expert Panel Narrative Review.

Minimally invasive locoregional therapies have a growing role in the multidisciplinary treatment of primary and metastatic breast cancer. Factors contributing to the expanding role of ablation for primary breast cancer include earlier diagnosis, when tumors are small, and increased longevity of patients whose condition precludes surgery. Cryoablation has emerged as the leading ablative modality for primary breast cancer owing to its wide availability, the lack of need for sedation, and the ability to monitor the ablation zone. Emerging evidence suggests that in patients with oligometastatic breast cancer, use of locoregional therapies to eradicate all disease sites may confer a survival advantage. Evidence also suggests that transarterial therapies-including chemoembolization, chemoperfusion, and radioembolization-may be helpful to some patients with advanced liver metastases from breast cancer, such as those with hepatic oligoprogression or those who cannot tolerate systemic therapy. However, the optimal modalities for treatment of oligometastatic and advanced metastatic disease remain unknown. Finally, locoregional therapies may produce tumor antigens that in combination with immunotherapy drive anti-tumor immunity. Although key trials are ongoing, additional prospective studies are needed to establish the inclusion of interventional oncology in societal breast cancer guidelines to support further clinical adoption and improved patient outcomes.

RETRACTED ARTICLE: Tumor microenvironment and immune system preservation in early-stage breast cancer: routes for early recurrence after mastectomy and treatment for lobular and ductal forms of disease

BackgroundIntra-ductal cancer (IDC) is the most common type of breast cancer, with intra-lobular cancer (ILC) coming in second. Surgery is the primary treatment for early stage breast cancer. There are now irrefutable data demonstrating that the immune context of breast tumors can influence growth and metastasis. Adjuvant chemotherapy may be administered in patients who are at a high risk of recurrence. Our goal was to identify the processes underlying both types of early local recurrences.MethodsThis was a case-control observational study. Within 2 years of receiving adjuvant taxan and anthracycline-based chemotherapy, as well as modified radical mastectomy (MRM), early stage IDC and ILC recurred. Vimentin, α-smooth muscle actin (SMA), platelet-derived growth factor (PDGF), matrix metalloproteinase (MMP1), and clustered differentiation (CD95) were investigated.ResultsOf the samples in the ductal type group, 25 showed local recurrence, and 25 did not. Six individuals in the lobular-type group did not experience recurrence, whereas seven did. Vimentin (p = 0.000 and 0.021), PDGF (p = 0.000 and 0.002), and CD95 (p = 0.000 and 0.045) expressions were significantly different in ductal and lobular carcinoma types, respectively. Measurement of ductal type was the sole significant difference found in MMP1 (p = 0.000) and α-SMA (p = 0.000). α-SMA and CD95 were two variables that helped the recurrence mechanism in the ductal type according to the pathway analysis. In contrast, the CD95 route is a recurrent mechanism for the lobular form.ConclusionsWhile the immune system plays a larger role in ILC, the tumor microenvironment and immune system both influence the recurrence of IDC. According to this study, improving the immune system may be a viable cancer treatment option.

DNAJC12 causes breast cancer chemotherapy resistance by repressing doxorubicin-induced ferroptosis and apoptosis via activation of AKT

BackgroundChemotherapy is a primary treatment for breast cancer (BC), yet many patients develop resistance over time. This study aims to identify critical factors contributing to chemoresistance and their underlying molecular mechanisms, with a focus on reversing this resistance. MethodsWe utilized samples from the Gene Expression Omnibus (GEO) and West China Hospital to identify and validate genes associated with chemoresistance. Functional studies were conducted using MDA-MB-231 and MCF-7 cell lines, involving gain-of-function and loss-of-function approaches. RNA sequencing (RNA-seq) identified potential mechanisms. We examined interactions between DNAJC12, HSP70, and AKT using co-immunoprecipitation (Co-IP) assays and established cell line-derived xenograft (CDX) models for in vivo validations. ResultsBoruta analysis of four GEO datasets identified DNAJC12 as highly significant. Patients with high DNAJC12 expression showed an 8 % pathological complete response (pCR) rate, compared to 38 % in the low expression group. DNAJC12 inhibited doxorubicin (DOX)-induced cell death through both ferroptosis and apoptosis. Combining apoptosis and ferroptosis inhibitors completely reversed DOX resistance caused by DNAJC12 overexpression. RNA-seq suggested that DNAJC12 overexpression activated the PI3K-AKT pathway. Inhibition of AKT reversed the DOX resistance induced by DNAJC12, including reduced apoptosis and ferroptosis, restoration of cleaved caspase 3, and decreased GPX4 and SLC7A11 levels. Additionally, DNAJC12 was found to increase AKT phosphorylation in an HSP70-dependent manner, and inhibiting HSP70 also reversed the DOX resistance. In vivo studies confirmed that AKT inhibition reversed DNAJC12-induced DOX resistance in the CDX model. ConclusionDNAJC12 expression is closely linked to chemoresistance in BC. The DNAJC12-HSP70-AKT signaling axis is crucial in mediating resistance to chemotherapy by suppressing DOX-induced ferroptosis and apoptosis. Our findings suggest that targeting AKT and HSP70 activities may offer new therapeutic strategies to overcome chemoresistance in BC.

Axillary Lymphadenectomy: Safe Dissection Through a Correct Technique.

The primary treatment of breast cancer in sentinel-positive ganglia includes axillary lymphatic nodal dissection. The LAD (lymphatic axillary dissection) has decreased in overall numbers but due to the increasing incidence of breast cancer, it is practised on a daily basis, even though there is a myriad of complications such as numbness of the upper limb and chest wall, movement restriction of the upper limb, and chronic painwhich appear due to trauma to the nerves which pass through the axilla. However, the utility in the overall survival or DFS (disease-free survival) of the patient is unquestionable. In our study, through the dissection of cadavers, we exposed the vital structures and theanatomical relations of this region. We aimed to offer a map or technique for the surgeon to followto decrease the overall morbidity of this procedure.

Risk and prognosis of second cutaneous melanoma after radiotherapy for breast cancer: A population-based analysis.

Radiation therapy (RT), a primary treatment for breast cancer (BC), may be associated with increased non-BC tumor risk. We aimed to examine second cutaneous melanoma (SCM) risk in BC patients who underwent RT and to assess their survival outcomes. Data from 520,977 BC patients diagnosed between 1973-2018 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Cumulative SCM incidence was estimated using the Fine-Gray competing risk model. Poisson regression analysis was conducted to calculate the standardized incidence ratio (SIR) and estimate the SCM relative risk in patients who underwent RT compared to those who did not. Overall survival (OS) and cancer-specific survival (CSS) were assessed using the Kaplan‒Meier method. Among the 520,977 BC patients, 243,676 (46.8%) underwent surgery and RT, while 277,301 (53.2%) only underwent surgery. Our results suggest that BC patients receiving RT had a higher SCM risk than those who did not (hazard ratio [HR] 1.40; 95% confidence interval [CI] 1.30-1.51; P < 0.001). SCM incidence was also higher in BC patients treated with RT than in the general US population (SIR 1.12; 95% CI 1.05-1.19; P < 0.05). However, SCM patients who received RT had a significantly higher 10-year survival rate than those who did not receive RT (14.90% vs 5.94%; P < 0.001). No significant difference was found in 10-year OS or 5-year CSS between SCM following RT and only primary cutaneous melanoma (OPCM), but SCM patients who did not receive RT had a significantly lower 10-year OS, with no significant difference in CSS. This study suggests an increased SCM likelihood in BC patients due to RT, although the overall risk is minimal.

Mini-AFTERc: a controlled pilot trial of a nurse-led psychological intervention for fear of breast cancer recurrence

ObjectivesTo determine the feasibility and acceptability of implementing the Mini-AFTERc intervention.DesignNon-randomised cluster-controlled pilot trial.SettingFour NHS out-patient breast cancer centres in Scotland.ParticipantsNinety-two women who had successfully completed primary treatment for breast cancer were screened for moderate levels of fear of cancer recurrence (FCR). Forty-five were eligible (17 intervention and 28 control) and 34 completed 3-month follow-up (15 intervention and 21 control).InterventionMini-AFTERc, a single brief (30 min) structured telephone discussion with a specialist breast cancer nurse (SBCN) trained to target the antecedents of FCR.OutcomesFeasibility and acceptability of Mini-AFTERc and the study design were assessed via recruitment, consent, retention rates, patient outcomes (measured at baseline, 2, 4, and 12 weeks), and post-study interviews with participants and SBCNs, which were guided by Normalisation Process Theory.ResultsMini-AFTERc was acceptable to patients and SBCNs. SBCNs believe the implementation of Mini-AFTERc to be feasible and an extension of discussions that already happen routinely. SBCNs believe delivery, however, at the scale required would be challenging given current competing demands for their time. Recruitment was impacted by variability in the follow-up practices of cancer centres and COVID-19 lockdown. Consent and follow-up procedures worked well, and retention rates were high.ConclusionsThe study provided invaluable information about the potential challenges and solutions for testing the Mini-AFTERc intervention more widely where limiting high FCR levels is an important goal following recovery from primary breast cancer treatment.Trial registrationClinicalTrials.gov, NCT0376382. Registered on 4 December 2018.