Correction of the Tuberous Breast with Fat Grafting and Implant: Techniques, Evaluation with BREAST-Q, and Preliminary Results.

BACKGROUND: The correction of tuberous breast deformity with fat grafting has gained popularity in recent years, but it remains unclear whether this new technique can produce patient satisfaction levels comparable to those achieved with implant-based correction. METHODS: This study aimed to compare patients' satisfaction and quality of life using the BREAST-Q questionnaire after correction of tuberous breast deformity with fat grafting and implants. Twenty-four patients (36 breasts) were included in our study. Thirteen patients (15 breasts) had a correction with lipofilling (mean 2.67 interventions) and 11 patients (21 breasts) had an implant-based correction (mean 1 intervention). RESULTS: Both fat and implant treatments showed statistically significant improvements in breast satisfaction (p value=0.001, 0.002, respectively), psychosocial (p value=0.003, 0.003, respectively), and sexual satisfaction (p value=0.008, 0.002, respectively) between the pre-treatment and post-treatment stages. However, the only statistically significant differences between the treatments were observed in the physical condition pre-treatment (p value=0.008) and sexual condition post-treatment (p value=0.030). The outcome of both treatments was not statistically different. Furthermore, the outcome exhibited a statistically significant positive linear relationship with breast satisfaction for both treatments. CONCLUSIONS: This study suggests that lipofilling can achieve breast and outcome satisfaction comparable to that of implants, although this parity in results comes at the cost of more interventions. These preliminary results lend support to the notion that, as surgeons have access to two equally effective techniques, it is crucial to provide appropriate guidance to patients to ensure their satisfaction. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Extracellular vesicle-associated tyrosine kinase-like orphan receptors ROR1 and ROR2 promote breast cancer progression.

BACKGROUND: Extracellular vesicles (EVs) harbor a plethora of different biomolecules, which they can transport across cells. In cancer, tumor-derived EVs thereby support the creation of a favorable tumor microenvironment. So far, EV uptake and cargo delivery into target cells have been regarded as the main mechanisms for the pro-tumoral function of EVs. To test this hypothesis, we investigated the fate of the oncogenic transmembrane Wnt tyrosine kinase-like orphan receptor 1 and 2 (ROR1, ROR2) delivered via distinct EV subpopulations to breast cancer cells and aimed to unravel their impact on tumor progression. METHODS: EVs were isolated by differential ultracentrifugation from cell culture supernatant as well as plasma samples from healthy individuals (n = 27) and breast cancer patients (n = 41). EVs were thoroughly characterized by electron microscopy, nanoparticle tracking analysis, immunoblot, and flow cytometry. ROR transfer to target cells was observed using microscopy-based assays and biodistribution experiments were conducted in syngeneic mice. EV impact on cancer cell migration and invasion was tested in functional assays. RESULTS: We observed that the supernatant of ROR-overexpressing cells was sufficient for transferring the receptors to ROR-negative cells. Analyzing the secretome of the ROR-overexpressing cells, we detected a high enrichment of ROR1/2 on large and small EVs, but not on large oncosomes. Interestingly, the majority of ROR-positive EVs remained attached to the target cell surface after 24 h of stimulation and was quickly removed by treatment with trypsin. Nonetheless, ROR-positive EVs increased migration and invasion of breast cancer cells, even after chemically inhibiting EV uptake, in dependence of RhoA downstream signaling. In vivo, ROR-depleted EVs tended to distribute less into organs prone for the formation of breast cancer metastases. ROR-positive EVs were also significantly elevated in the plasma of breast cancer patients and allowed to separate them from healthy controls. CONCLUSIONS: The oncogenic Wnt receptors ROR1/2 are transferred via EVs to the surface of ROR-negative cancer cells, in which they induce an aggressive phenotype supporting tumor progression. Video Abstract.

Simultaneous FAPI PET/MRI Targeting the Fibroblast-Activation Protein for Breast Cancer.

Background Integrated PET/MRI is a promising modality for breast assessment. The most frequently used tracer, fluorine 18 (18F) fluorodeoxyglucose (FDG), is applied for whole-body staging in advanced breast cancer but has limited accuracy in evaluating primary breast lesions. The fibroblast-activation protein (FAP) is abundantly expressed in invasive breast cancer. FAP-directed PET tracers have recently become available, but results in primary breast tumors remain lacking. Purpose To evaluate the use of FAP inhibitor (FAPI) breast PET/MRI in assessing breast lesions and of FAPI whole-body scanning for lymph node (LN) and distant staging using the ligand gallium 68 (68Ga)-FAPI-46. Materials and Methods In women with histologically confirmed invasive breast cancer, all primary 68Ga-FAPI-46 breast and whole-body PET/MRI and PET/CT examinations conducted at the authors' center between October 2019 and December 2020 were retrospectively analyzed. MRI lesion characteristics and standardized uptake values (SUVs) were quantified with dedicated software. Mann-Whitney U tests were used to compare tumor SUVs across different tumor types. The Pearson correlation coefficient was calculated between SUV and measures of MRI morphologic characteristics. Results Nineteen women (mean age, 49 years ± 9 [standard deviation]) were evaluated-18 to complement initial staging and one for restaging after therapy for distant metastases. Strong tracer accumulation was observed in all 18 untreated primary breast malignancies (mean maximum SUV [SUVmax] = 13.9 [range, 7.9-29.9]; median lesion diameter = 26 mm [range, 9-155 mm]), resulting in clear tumor delineation across different gradings, receptors, and histologic types. All preoperatively verified LN metastases in 13 women showed strong tracer accumulation (mean SUVmax= 12.2 [range, 3.3-22.4]; mean diameter = 21 mm [range, 14-35 mm]). Tracer uptake established or supported extra-axillary LN involvement in seven women and affected therapy decisions in three women. Conclusion This retrospective analysis indicates use of 68Ga fibroblast-activation protein inhibitor tracers for breast cancer diagnosis and staging. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Mankoff and Sellmyer in this issue.

Treating Pain and Fat Necrosis after Breast Cancer Surgery with Fat Grafting: Is one Session Enough?

BACKGROUND: Chronic pain after breast cancer surgery is affecting up to 60% of patients, causing significant morbidity to patients. Lately, fat grafting has been applied as a therapy for chronic neuropathic pain. METHODS: We report a series of eighteen patients, who were treated for pain after breast cancer surgery. Twelve patients had a breast conserving therapy, two a mastectomy and four an autologous flap-based reconstruction. While most presented with neuropathic pain, six patients had fat necrosis in their history. Most patients presented with severe pain (77%) and were treated with fat grafting sessions, performed by water-assisted liposuction. RESULTS: All patients responded to the interventions; the median number of fat grafting sessions was 2, the median duration of the interventions was 4 months, and the median follow-up period was 56.5 months. The median pain prior to the fat grafting procedure had an intensity of 8 (range 7-9) numeric rating scale points; after the first intervention, this was reduced to 4 (range 2.3-5.8); and after the second intervention, it was down to 2 (range 0.8-3.3). Patients with pain intensities of 4-5 had a good chance of achieving analgesia after one session. CONCLUSIONS: Fat grafting could be a new treatment modality for symptomatic fat necrosis: complete or partial suction of the necrosis and/or fat grafting around the necrosis to reduce inflammation and pain. Fat grafting proved a valuable tool, reducing pain or even achieving analgesia after breast cancer surgery presenting with a highly favorable risk-benefit ratio. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Treating Anisomastia and Tuberous Breast with Fat Grafting: Technique and Evaluation of Outcomes Using BREAST-Q Surveys.

BACKGROUND: In the surgical correction of tuberous breast deformity, implants and regional flaps play a prominent role. Lately, fat grafting has been used as an alternative, but there is evidence that patient satisfaction is higher after correction with implants compared with lipofilling. METHODS: We report a tuberous breasts correction series of ten cases, enrolled between 2015 and 2018. Percutaneous fasciotomies and fat grafting were performed by the Body-Jet technique. Analysis of outcomes was undertaken with BREAST-Q surveys. RESULTS: The breast satisfaction scores increased from 0 to 75 (p < 0.01), the psychological well-being scores from 20 to 70 (p < 0.01) and the sexual well-being scores from 18.5 to 58 (p = 0.02), while the physical well-being scores remained stable (from 68 to 63, p = 0.2). The median outcome satisfaction score was 86. CONCLUSION: Scores of patient-reported outcomes after lipofilling can reach and even exceed those of patients corrected with implants, at the cost of more interventions. Fat grafting is beginning to establish itself as a true alternative in the treatment of tuberous breast deformity in patients with the appropriate fat deposits. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine Ratings, please refer to Table of Contents or online Instructions to Authors www.springer.com/00266 .

Fat Grafting and Auto-Augmentation Mastopexy After Breast Implant Removal: Technique and Evaluation of Outcomes Using BREAST-Q.

BACKGROUND: Auto-augmentation mastopexy after implant removal has been described as a possible alternative for women who do not opt for implant replacement and decline major reconstructive surgery. OBJECTIVES: This study aimed to evaluate patient satisfaction after auto-augmentation mastopexy relative to the final breast volume and to assess the role of fat grafting on patients' satisfaction and quality of life according to the BREAST-Q questionnaire. METHODS: Forty-seven breasts from 28 patients who underwent implant removal and auto-augmentation mastopexy were reviewed; 9 patients (group 1) were primarily treated with several fat grafting sessions with subsequent auto-augmentation, 5 (group 2) were treated primarily with auto-augmentation, but subsequently expressed a wish for breast augmentation by lipofilling, and 14 patients (group 3, control) had only auto-augmentation. RESULTS: Group 1 patients maintained their breast volume, and showed significant improvements in breast satisfaction, psychosocial well-being, and contentment with breast surgery outcomes (P = 0.01, ˂0.01, and ˂0.01, respectively). However, the physical well-being of this group, as well as response to final cup size or interaction parameters, did not improve (P = 0.06). In group 2, all except 1 patient had breast volume reduction to A cup, as was the case with one-third of the patients in control group 3 (group 3A, n = 5) who scored lower, and thus were less satisfied with the breast auto-augmentation than group 3B, who achieved final bigger cup sizes (P ˂ 0.01). CONCLUSIONS: Auto-augmentation mastopexy resulted in substantial improvements in the parameters measured by BREAST-Q. Thus, combined auto-augmentation mastopexy and lipofilling provided a better alternative treatment after breast implant removal.

Correlation between SFRP1 expression and clinicopathological parameters in patients with triple-negative breast cancer.

Aim: Breast cancer is a heterogeneous disease with distinct molecular and clinical behavior demanding reliable biomarkers, especially in triple-negative breast cancer (TNBC). This study seeks to improve the understanding of SFRP1 as a potential biomarker in breast cancer focusing on TNBC. Materials & methods: SFRP1 expression was investigated via immunohistochemistry with two anti-SFRP1-antibodies on tissue-microarrays of 376 invasive breast cancers. Results: Statistical analysis revealed a highly significant association between TNBC (n = 36) and SFRP1 expression (p < 0.001). SFRP1 expression was significantly associated with younger age, higher tumor stage, size and grade. Conclusion: SFRP1 expression is strongly correlated with TNBC on protein level. Associations with age and tumor grade support the role of SFRP1 as a biomarker for chemotherapy response in TNBC.

The need for harmonized structured documentation and chances of secondary use - results of a systematic analysis with automated form comparison for prostate and breast cancer.

INTRODUCTION: Medical documentation is a time-consuming task and there is a growing number of documentation requirements. In order to improve documentation, harmonization and standardization based on existing forms and medical concepts are needed. Systematic analysis of forms can contribute to standardization building upon new methods for automated comparison of forms. Objectives of this research are quantification and comparison of data elements for breast and prostate cancer to discover similarities, differences and reuse potential between documentation sets. In addition, common data elements for each entity should be identified by automated comparison of forms. MATERIALS AND METHODS: A collection of 57 forms regarding prostate and breast cancer from quality management, registries, clinical documentation of two university hospitals (Erlangen, Münster), research datasets, certification requirements and trial documentation were transformed into the Operational Data Model (ODM). These ODM-files were semantically enriched with concept codes and analyzed with the compareODM algorithm. Comparison results were aggregated and lists of common concepts were generated. Grid images, dendrograms and spider charts were used for illustration. RESULTS: Overall, 1008 data elements for prostate cancer and 1232 data elements for breast cancer were analyzed. Average routine documentation consists of 390 data elements per disease entity and site. Comparisons of forms identified up to 20 comparable data elements in cancer conference forms from both hospitals. Urology forms contain up to 53 comparable data elements with quality management and up to 21 with registry forms. Urology documentation of both hospitals contains up to 34 comparable items with international common data elements. Clinical documentation sets share up to 24 comparable data elements with trial documentation. Within clinical documentation administrative items are most common comparable items. Selected common medical concepts are contained in up to 16 forms. DISCUSSION: The amount of documentation for cancer patients is enormous. There is an urgent need for standardized structured single source documentation. Semantic annotation is time-consuming, but enables automated comparison between different form types, hospital sites and even languages. This approach can help to identify common data elements in medical documentation. Standardization of forms and building up forms on the basis of coding systems is desirable. Several comparable data elements within the analyzed forms demonstrate the harmonization potential, which would enable better data reuse. CONCLUSION: Identifying common data elements in medical forms from different settings with systematic and automated form comparison is feasible.

App-based support for breast cancer patients to reduce psychological distress during therapy and survivorship - a multicentric randomized controlled trial.

Introduction: The negative impact of unmanaged psychological distress on quality of life and outcome in breast cancer survivors has been demonstrated. Fortunately, studies indicate that distress can effectively be addressed and even prevented using evidence-based interventions. In Germany prescription-based mobile health apps, known as DiGAs (digital health applications), that are fully reimbursed by health insurances, were introduced in 2020. In this study, the effectiveness of an approved breast cancer DiGA was investigated: The personalized coaching app PINK! Coach supports and accompanies breast cancer patients during therapy and follow-up. Methods: PINK! Coach was specifically designed for breast cancer (BC) patients from the day of diagnosis to the time of Follow-up (aftercare). The app offers individualized, evidence-based therapy and side-effect management, mindfulness-based stress reduction, nutritional and psychological education, physical activity tracking, and motivational exercises to implement lifestyle changes sustainably in daily routine. A prospective, intraindividual RCT (DRKS00028699) was performed with n = 434 patients recruited in 7 German breast cancer centers from September 2022 until January 2023. Patients with BC were included independent of their stage of diseases, type of therapy and molecular characteristics of the tumor. Patients were randomized into one of two groups: The intervention group got access to PINK! over 12 weeks; the control group served as a waiting-list comparison to "standard of care." The primary endpoint was psychological distress objectified by means of Patient Health Questionnaire-9 (PHQ-9). Subgroups were defined to investigate the app's effect on several patient groups such as MBC vs. EBC patients, patients on therapy vs. in aftercare, patients who received a chemotherapy vs. patients who did not. Results: Efficacy analysis of the primary endpoint revealed a significant reduction in psychological distress (least squares estimate -1.62, 95% confidence interval [1.03; 2.21]; p<0.001) among intervention group patients from baseline to T3 vs, control group. Subgroup analysis also suggested improvements across all clinical situations. Conclusion: Patients with breast cancer suffer from psychological problems including anxiety and depression during and after therapy. Personalized, supportive care with the app PINK! Coach turned out as a promising opportunity to significantly improve psychological distress in a convenient, accessible, and low-threshold manner for breast cancer patients independent of their stage of disease (EBC/MBC), therapy phase (aftercare or therapy) or therapy itself (chemotherapy/other therapy options). The app is routinely available in Germany as a DiGA. Clinical Trial Registration: DRKS Trial Registry (DRKS00028699).

The Safety and Efficacy of the Combination of Sacituzumab Govitecan and Palliative Radiotherapy-A Retrospective Multi-Center Cohort Study.

Sacituzumab govitecan (SG) is a new treatment option for patients with metastatic triple-negative and hormone receptor-positive, HER2-negative breast cancer. This antibody-drug conjugate is currently approved as monotherapy. Palliative radiotherapy is frequently used to treat symptomatic metastases locally. Concurrent use of SG and irradiation was excluded in clinical trials of SG, and there are currently limited published data. We report here a systematic review, as well as a retrospective multi-center study of 17 patients with triple-negative breast cancer who received concurrent SG and radiotherapy. In these patients, concurrent use was found to be efficient, safe and well tolerated. There were no apparent differences in moderate or severe acute toxicity according to the timing of SG administration.

Low RNA disruption during neoadjuvant chemotherapy predicts pathologic complete response absence in patients with breast cancer.

In previously reported retrospective studies, high tumor RNA disruption during neoadjuvant chemotherapy predicted for post-treatment pathologic complete response (pCR) and improved disease-free survival at definitive surgery for primary early breast cancer. The BREVITY (Breast Cancer Response Evaluation for Individualized Therapy) prospective clinical trial (NCT03524430) seeks to validate these prior findings. Here we report training set (Phase I) findings, including determination of RNA disruption index (RDI) cut points for outcome prediction in the subsequent validation set (Phase II; 454 patients). In 80 patients of the training set, maximum tumor RDI values for biopsies obtained during neoadjuvant chemotherapy were significantly higher in pCR responders than in patients without pCR post-treatment (P = .008). Moreover, maximum tumor RDI values ≤3.7 during treatment predicted for a lack of pCR at surgery (negative predictive value = 93.3%). These findings support the prospect that on-treatment tumor RNA disruption assessments may effectively predict post-surgery outcome, possibly permitting treatment optimization.

Establishment of a 3D co-culture model to investigate the role of primary fibroblasts in ductal carcinoma in situ of the breast.

BACKGROUND: Ductal carcinoma in situ (DCIS) is a precursor form of breast cancer. 13%-50% of these lesions will progress to invasive breast cancer, but the individual progression risk cannot be estimated. Therefore, all patients receive the same therapy, resulting in potential overtreatment of a large proportion of patients. AIMS: The role of the tumor microenvironment (TME) and especially of fibroblasts appears to be critical in DCIS development and a better understanding of their role may aid individualized treatment. METHODS AND RESULTS: Primary fibroblasts isolated from benign or malignant punch biopsies of the breast and MCF10DCIS.com cells were seeded in a 3D cell culture system. The fibroblasts were cultured in a type I collagen layer beneath a Matrigel layer with MCF10DCIS.com cells. Dye-quenched (DQ) fluorescent collagen I and IV were used in collagen and Matrigel layer respectively to demonstrate proteolysis. Confocal microscopy was performed on day 2, 7, and 14 to reveal morphological changes, which could indicate the transition to an invasive phenotype. MCF10DCIS.com cells form smooth, round spheroids in co-culture with non-cancer associated fibroblasts (NAFs). Spheroids in co-culture with tumor-associated fibroblasts (TAFs) appear irregularly shaped and with an uneven surface; similar to spheroids formed from invasive cells. Therefore, these morphological changes represent the progression of an in situ to an invasive phenotype. In addition, TAFs show a higher proteolytic activity compared to NAFs. The distance between DCIS cells and fibroblasts decreases over time. CONCLUSION: The TAFs seem to play an important role in the progression of DCIS to invasive breast cancer. The better characterization of the TME could lead to the identification of DCIS lesions with high or low risk of progression. This could enable personalized oncological therapy, prevention of overtreatment and individualized hormone replacement therapy after DCIS.

Initial Results of 68Ga-FAPI-46 PET/MRI to Assess Response to Neoadjuvant Chemotherapy in Breast Cancer.

Improving imaging-based response after neoadjuvant chemotherapy (NAC) in breast cancer assessment could obviate histologic confirmation of pathologic complete response (pCR) and facilitate deescalation of chemotherapy or surgery. Fibroblast activation protein inhibitor (FAPI) PET/MRI is a promising novel molecular imaging agent for the tumor microenvironment with intense uptake in breast cancer. We assessed the diagnostic performance of follow-up breast 68Ga-FAPI-46 (68Ga-FAPI) PET/MRI in classifying the response status of local breast cancer and lymph node metastases after completion of NAC and validated this approach immunohistochemically. Methods: In women who completed NAC for invasive breast cancer, follow-up 68Ga-FAPI PET/MRI and corresponding fibroblast activation protein (FAP) immunostainings were retrospectively analyzed. Metrics of 68Ga-FAPI uptake and FAP immunoreactivity in women with or without pCR were compared using the Mann-Whitney U test. Diagnostic performance to detect remnant invasive cancer was calculated for tracer uptake metrics using receiver-operating-characteristic curves and for masked readers' visual assessment categories of PET/MRI and MRI alone. Results: Thirteen women (mean age ± SD, 47 ± 9 y) were evaluated. Seven of the 13 achieved pCR in the breast and 6 in the axilla. FAP immunoreactivity was significantly associated with response status. The 68Ga-FAPI PET/MRI mean breast tumor-to-background ratio was 0.9 (range, 0.6-1.2) for pCR and 2.1 (range, 1.4-3.1) for no pCR (P = 0.001). Integrated PET/MRI could classify breast response correctly in all 13 women based on readers' visual assessment or tumor-to-background ratio. Evaluation of MRI alone resulted in at least 2 false-positives. For lymph nodes, PET/MRI readers had at least 2 false-negative classifications, whereas MRI alone resulted in 2 false-negatives and 1 false-positive. Conclusion: To our knowledge, this was the first analysis of 68Ga-FAPI PET/MRI for response assessment after NAC for breast cancer. The diagnostic performance of PET/MRI in a small study sample trended toward a gain over MRI alone, clearly supporting future prospective studies.

De-Escalated Neoadjuvant Trastuzumab-Emtansine With or Without Endocrine Therapy Versus Trastuzumab With Endocrine Therapy in HR+/HER2+ Early Breast Cancer: 5-Year Survival in the WSG-ADAPT-TP Trial.

PURPOSE: Neoadjuvant chemotherapy is standard of care in human epidermal growth factor receptor 2-positive (HER2+) early breast cancer (EBC), irrespective of the hormone receptor status. Trastuzumab-emtansine (T-DM1), antibody-drug conjugate, is highly effective in HER2+ EBC; however, no survival data are available for de-escalated antibody-drug conjugate-based neoadjuvant therapy without conventional chemotherapy. PATIENTS AND METHODS: In the WSG-ADAPT-TP (ClinicalTrials.gov identifier: NCT01779206) phase II trial, 375 centrally reviewed patients with hormone receptor-positive (HR+)/HER2+ EBC (clinical stage I-III) were randomly assigned to 12 weeks of T-DM1 with or without endocrine therapy (ET) or trastuzumab + ET once every 3 weeks (ratio 1:1:1). Adjuvant chemotherapy (ACT) omission was allowed in patients with pathologic complete response (pCR). In this study, we report the secondary survival end points and biomarker analysis. Patients who received at least one dose of study treatment were analyzed. Survival was analyzed using the Kaplan-Meier method, two-sided log-rank statistics, and Cox regression models stratified for nodal and menopausal status. P values < .05 were considered statistically significant. RESULTS: T-DM1, T-DM1 + ET, and trastuzumab + ET induced similar 5-year invasive disease-free survival (iDFS; 88.9%, 85.3%, 84.6%; Plog-rank = .608) and overall survival rates (97.2%, 96.4%, 96.3%; Plog-rank = .534). Patients with pCR versus non-pCR had improved 5-year iDFS rates (92.7% v 82.7%; hazard ratio, 0.40 [95% CI, 0.18 to 0.85]). Among the 117 patients with pCR, 41 did not receive ACT; 5-year iDFS rates were similar in those with (93.0% [95% CI, 84.0 to 97.0]) and without ACT (92.1% [95% CI, 77.5 to 97.4]; Plog-rank = .848). Translational research revealed that tumors with PIK3CA wild type, high immune marker expression, and luminal-A tumors (by PAM50) had an excellent prognosis with de-escalated anti-HER2 therapy. CONCLUSION: The WSG-ADAPT-TP trial demonstrated that pCR after 12 weeks of chemotherapy-free de-escalated neoadjuvant therapy was associated with excellent survival in HR+/HER2+ EBC without further ACT. Despite higher pCR rates for T-DM1 ± ET versus trastuzumab + ET, all trial arms had similar outcomes because of mandatory standard chemotherapy after non-pCR. WSG-ADAPT-TP demonstrated that such de-escalation trials in HER2+ EBC are feasible and safe for patients. Patient selection on the basis of biomarkers or molecular subtypes may increase the efficacy of systemic chemotherapy-free HER2-targeted approaches.

Efficacy and Tolerance of IMRT Boost Compared to IORT Boost in Early Breast Cancer: A German Monocenter Study.

The aim of this retrospective study is to compare the two boost subgroups, IORT or IMRT, in terms of overall survival (OS), progression-free survival (PFS), cosmesis, and acute and late toxicity. It shall be shown whether and which of the boost techniques offers better results with respect to the facial points, since there are already many studies on applying boost to the tumor bed after/during breast conserving surgery, and there are few which compare the different techniques. For this comparison, two subgroups of 76 patients each (n = 152), treated between 2002 and 2015, were enrolled in the study. In one subgroup, the 9 Gy boost was intraoperatively administered after complete removal of the primary tumor, while the other subgroup received the boost of 8.4 Gy percutaneously and simultaneously integrated into the tumor bed after breast conserving surgery. Both subgroups have subsequently undergone whole breast irradiation (WBI) of 50.4/50 Gy in 1.8−2 Gy per fraction. OS and the incidence of late toxicity did not differ between the two subgroups and no risk factor was found regarding PFS. Acute toxicities initially occurred significantly less (p < 0.001) in the IORT subgroup; however, after WBI took place, this difference vanished. Therefore, boost application by means of IORT or IMRT can be considered equivalent.

Are there sustained psychological impacts in women diagnosed with in-situ or early invasive breast cancers?

Purpose: The detection of a ductal carcinoma in-situ (DCIS) or an early invasive breast cancer (EIBC), particularly by population-wide mammography-screening-programs, is controversial as an unknown proportion of these cases may be due to overdiagnosis. We investigated whether women with such potentially overdiagnosed breast cancers suffer from sustained adverse psycho-social consequences. Methods: Standardized questionnaires were mailed to 900 survivors, diagnosed with either DCIS or EIBC, requesting self-reports on quality of life using EORTC Quality of Life Questionnaire C-30. Levels of anxiety and depression were assessed using the HADS questionnaires. Item score values in the study group were compared to reference data obtained from normative studies in the German female reference population. Results: The 577 women who returned completed questionnaires had a mean age of 65.1 years, 387 (67%) had been diagnosed by mammography screening. Median time since diagnosis was 5.9 years. There were no substantial differences between the study sample and the reference population for most of the items. While most score values were even slightly more favorable in the study group, the scores for cognitive function were moderately lower, especially among younger patients. Score values for anxiety were generally higher among younger women (50 to 59 years) from the study group, while depression scores were lower irrespective of age. Conclusions: This study indicates that the diagnosis of DCIS or EIBC, which is predominantly a result of screening, does not seem to induce sustained, adverse psychological impacts in affected women when compared with the respective general female population. Only anxiety levels remained elevated among younger women.

Protroca: A Noninterventional Study on Prophylactic Lipegfilgrastim against Chemotherapy-Induced Neutropenia in Nonselected Breast Cancer Patients.

BACKGROUND: Protroca evaluated the efficacy and safety of primary and secondary prophylaxis of neutropenia with lipegfilgrastim (Lonquex®) in breast cancer patients receiving neoadjuvant or adjuvant chemotherapy (CT). PATIENTS AND METHODS: Of the 255 patients enrolled, 248 patients were evaluable for the intent-to-treat (ITT) and 194 patients for the per-protocol set. Primary and secondary end points after lipegfilgrastim treatment were assessed. RESULTS: Nine patients of the ITT set receiving lipegfilgrastim as primary prophylaxis (n = 222) had febrile neutropenia of grade 3-4 (5 patients) or infection of grade 3-4 (4 patients); 1/26 of those receiving secondary prophylaxis had an event. Dose reductions were performed in 9.5% of the patients. Postponement of cancer CT cycles for >3 days occurred in <15% of patients; 10.8% (92/851 AEs) and 8% (2/25 SAEs) of documented adverse events and serious adverse events, respectively, were related to lipegfilgrastim. CONCLUSIONS: Application of lipegfilgrastim was effective as primary and secondary prophylaxis in the prevention of CT-induced neutropenia in breast cancer.

Immune Markers and Tumor-Related Processes Predict Neoadjuvant Therapy Response in the WSG-ADAPT HER2-Positive/Hormone Receptor-Positive Trial in Early Breast Cancer.

Prognostic or predictive biomarkers in HER2-positive early breast cancer (EBC) may inform treatment optimization. The ADAPT HER2-positive/hormone receptor-positive phase II trial (NCT01779206) demonstrated pathological complete response (pCR) rates of ~40% following de-escalated treatment with 12 weeks neoadjuvant ado-trastuzumab emtansine (T-DM1) ± endocrine therapy. In this exploratory analysis, we evaluated potential early predictors of response to neoadjuvant therapy. The effects of PIK3CA mutations and immune (CD8 and PD-L1) and apoptotic markers (BCL2 and MCL1) on pCR rates were assessed, along with intrinsic BC subtypes. Immune response and pCR were lower in PIK3CA-mutated tumors compared with wildtype. Increased BCL2 at baseline in all patients and at Cycle 2 in the T-DM1 arms was associated with lower pCR. In the T-DM1 arms only, the HER2-enriched subtype was associated with increased pCR rate (54% vs. 28%). These findings support further prospective pCR-driven de-escalation studies in patients with HER2-positive EBC.

Ribociclib in Breast Cancer Brain Metastases: A Case Report.

INTRODUCTION: Breast cancer is the most common cancer in women. It frequently metastasizes to the lung, liver, and bones. Due to the improvement of therapeutic strategies and therefore longer patient survival, brain metastases have become more frequent. However, evidence-based therapeutic options of systemic treatment are limited because patients with breast cancer brain metastases are often excluded from clinical trials. CASE PRESENTATION: Here, we show a patient with brain and orbital metastases from a hormone receptor-positive, Her2neu-negative breast cancer that led to one-sided blindness. She was treated with a combination therapy of the CDK4/6 inhibitor ribociclib and the aromatase inhibitor anastrozole and showed a fast and durable response for 9 months with good tolerability of the treatment. CONCLUSION: Systemic treatment with a CDK4/6 inhibitor and endocrine therapy can be considered in breast cancer brain metastases.