Intact Breast Research Articles

Abstract PO4-22-03: Intensity Modulated Proton Therapy (IMPT) for the Definitive Adjuvant Management of Women with Breast Cancer: A Single Institutional Experience of 5-Year Oncologic Outcomes

Abstract Purpose: There is limited data reporting the oncologic outcomes of breast cancer patients treated definitively with adjuvant proton beam therapy. Here we report a single institutional experience of oncologic outcomes, treating a predominantly vulnerable breast cancer patient population and compare these to historical standards primarily utilizing photon therapy. Materials and Methods: Unver IRB approval, we retrospectively reviewed 453 definitively treated breast cancer patients from 2016 – 2023 using adjuvant IMPT as part of their cancer care. Patients with recurrent disease, receiving re-irradiation, and those with less than 1-year of follow up were excluded from this analysis. Patients were treated with surgery and systemic therapies as per standards of care. Radiation therapy was administered using pencil beam scanning IMPT with daily image guidance. χ2 and Mann-Whitney U tests were performed to determine differences between select variables. Kaplan-Meier analysis and Cox proportional hazard models were used to analyze overall survival (OS). Results: With a median follow up of 22 months for the entire cohort, 453 patients were treated at XXXX as part of definitive adjuvant management for their breast cancer. Nearly 30% of patients self-identified as black (n=135), average patient age was 54 and 56% (n=255) self-identified as being married with approximately 25% (n=109) of patients having Medicare/Medicaid insurance. 198 patients (43.8%) had an intact breast and the remainder mastectomy of which 37.4% had reconstruction at the time of their radiation. 229 patients (50.7%) received neoadjuvant chemotherapy while 55 patients (12%) received concurrent chemotherapy which was either her2+ directed or Xeloda. The number of patients (%) corresponding to the AJCC 8th edition anatomical staging is as follows: Stage 0: 12 (2.7%); Stage I: 91 (20.1%); Stage 2: 197 (43.6%); Stage 3: 152 (33.6%). Median RT dose delivered for patients receiving comprehensive treatment was 50.4 Gy with 81% of patients receiving a boost to either scar, lumpectomy cavity and/or LN regions. Median RT dose delivered for patients receiving whole breast radiation was 42.56 Gy with a 10 Gy lumpectomy cavity boost. 5-yr OS by stage was 0: 100%; stage I: 98.8%; stage 2: 93.5%; stage 3: 90.8%. Five-year OS for black, white and other race patients were 85.3%, 95.8% and 96%, respectively (White as Ref: HR 3.176, 95% CI: 1.313-7.681, p=0.010 for black patients). For the entire cohort, patients with triple negative disease had a 5-yr OS of 80.4% (HR: 4.33, 95% CI 1.87-10.04, p< 0.001) and there was no difference in OS when insurance status was considered (p=0.378). Conclusions: To the best of our knowledge this represents the largest series of definitively treated breast cancer patients utilizing adjuvant proton therapy and the 5-year OS rates in our analysis coincide with published standards1. Results from the on-going randomized RADCOMP study will provide further guidance as to which patients benefit the most from proton therapy and will further support equivalent oncological outcomes when compared to photon therapy. 1. Weiss A, Chavez-MacGregor M, Lichtensztajn DY, et al. Validation study of the American Joint Committee on Cancer eighth edition prognostic stage compared with the anatomic stage in breast cancer. JAMA Oncol. 4(2):203-209, 2018. Citation Format: Elizabeth Nichols, Gurbani Singh, Desiree Lejano, Sarah McAvoy, Mark Mishra, Melissa Vyfhuis. Intensity Modulated Proton Therapy (IMPT) for the Definitive Adjuvant Management of Women with Breast Cancer: A Single Institutional Experience of 5-Year Oncologic Outcomes [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 PO4-22-03.

Abstract 4723: Target engagement sheds light on difference in drug efficacy in breast cancer cell lines

Abstract Breast cancer is a serious disease that affects millions of women worldwide, and 700,000 people succumb to the disease annually. Breast cancers are divided into several functional subgroups based on molecular characteristics and growth pattern: Luminal A and B, HER2 positive (HER2+) and triple negative. The subgroups are important from a clinical perspective as they partially guide treatment strategies. In this study we wanted to investigate the difference in target engagement with four drugs indicated for treatment of different types of breast cancer: Alpelisib, Neratinib, Vinorelbine, and Docetaxel. Five different human breast cancer cell lines were included, representing Luminal A (MCF-7, T-47D), HER2+ (SK-BR-3, BT-474), and triple negative (BT-20). We used CETSA® (CEllular Thermal Shift Assay) coupled to mass spectrometry detection to assess proteome wide changes in protein thermal stability in intact breast cancer cell lines. CETSA is unique as a target engagement detection modality as it allows for target engagement assessment in intact cells with unaltered drug molecules. Also, as biology is intact in live cells it is possible to follow compound induced downstream signaling or phenotypic events that result in changed thermal stability of proteins. In addition to assessing protein thermal stability with CETSA, which is a short treatment of 1 h, we also subjected cells in culture to prolonged drug exposures, ≤72 h, in order to measure viability. This was done to correlate early changes in protein thermal stability to the viability phenotype that manifested later. In general, responses both in protein thermal stability and cell viability was heterogenous among the cell lines. The most homogenous response in viability was observed for the Phosphatidyl Inositol 3’ kinase inhibitor Alpelisib, which reduced viability to 20 - 40% in all cell lines. In contrast, partial resistance was shown to the other drugs by at least one of the cell lines. For Alpelisib, the amount and type of proteins that were thermally shifted correlated with the effect on viability. The covalent HER2 inhibitor Neratinib was most effective in inhibiting viability in HER2+ cells and proteins of the HER2 pathway were thermally shifted in these cells, which was not observed for the other cell lines. Viability of the other cell lines were also affected by Neratinib, but only at higher concentrations. Both microtubule inhibitors induced thermal stabilization of tubulins, but that did not always translate into efficacy in the viability assay. However, sensitive cell lines showed thermal shifts of tubulins at lower concentrations of compound. In oncology drug development it is important that effects on viability are driven by on-target efficacy and not by off-target effects. Here we show the benefit of connecting knowledge of target engagement and phenotypic readouts; what targets are engaged, at which concentrations, and what is the corresponding phenotype. Citation Format: Tomas Friman, Tuomas Tolvanen, Merve Kacal, Victoria Brehmer, Stina Lundgren, Laurence Arnold, Daniel Martinez Molina. Target engagement sheds light on difference in drug efficacy in breast cancer cell lines [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 4723.

Upgrade Rates and Breast Cancer Development Among Germline Pathogenic Variant Carriers with High-Risk Breast Lesions.

High-risk lesions (HRL) of the breast are risk factors for future breast cancer development and may be associated with a concurrent underlying malignancy when identified on needle biopsy; however, there are few data evaluating HRLs in carriers of germline pathogenic variants (PVs) in breast cancer predisposition genes. We identified patients from two institutions with germline PVs in high- and moderate-penetrance breast cancer predisposition genes and an HRL in an intact breast, including atypical ductal hyperplasia (ADH), flat epithelial atypia (FEA), and lobular neoplasia (LN). We calculated upgrade rates at surgical excision and used Kaplan-Meier methods to characterize 3-year breast cancer risk in patients without upgrade. Of 117 lesions in 105 patients, 65 (55.6%) were ADH, 48 (41.0%) were LN, and 4 (3.4%) were FEA. Most PVs (83.8%) were in the BRCA1/2, CHEK2 and ATM genes. ADH and FEA were excised in most cases (87.1%), with upgrade rates of 11.8% (95% confidence interval [CI] 5.5-23.4%) and 0%, respectively. LN was selectively excised (53.8%); upgrade rate in the excision group was 4.8% (95% CI 0.8-22.7%), and with 20 months of median follow-up, no same-site cancers developed in the observation group. Among those not upgraded, the 3-year risk of breast cancer development was 13.1% (95% CI 6.3-26.3%), mostly estrogen receptor-positive (ER +) disease (89.5%). Upgrade rates for HRLs in patients with PVs in breast cancer predisposition genes appear similar to non-carriers. HRLs may be associated with increased short-term ER+ breast cancer risk in PV carriers, warranting strong consideration of surgical or chemoprevention therapies in this population.

Dosimetric evaluation of VMAT automated breast treatment plans: Towards the establishment of an institutional plan acceptability criteria

Abstract Introduction: To evaluate the clinical suitability of the current facility-based treatment plan protocol in establishing acceptability criteria. Material and methods: Automated Volumetric Arc Therapy (VMAT) treatment plans were retrospectively evaluated for intact breast and chest-wall cancer patients from January 2021 to January 2023. Results: A total of 94 patients were planned and treated using automated contouring and VMAT planning technique. The number of patients planned and treated for intact breast and chest-wall were 41 (43.6%) and 53 (56.4%), respectively. The mean intact breast volumes for optimization (Brst_opt) receiving 95% and 105% of the prescribed doses were 92.80% ± 1.11 and 1.54% ± 1.02, respectively. Their corresponding mean chest-wall volumes for optimization (Chst_opt) were 90.65% ± 3.19 and 2.28% ± 2.99, respectively. For left-sided cases, the mean heart dose received was 4.61 Gy ± 1.76 and 5.18 Gy ± 1.55 for intact breast plans and that for chest-wall plans, respectively. The mean ipsilateral lung volume receiving 20 Gy of the prescribed dose was 12.22% ± 3.86 and 13.19% ± 3.74 for intact breast plans and chest-wall plans, respectively. For the Brst_opt and Chst_opt dose metrics were calculated; the mean homogeneity index (HI) was 0.14 ± 0.03 and 0.15 ± 0.04, mean uniformity index (UI) was 1.09 ± 0.03 and 1.11 ± 0.03, and mean conformity index (CI) were 0.92 ± 0.04 and 0.91 ± 0.04, respectively. Conclusions: The dosimetric evaluation shows a good dose distribution in the target volumes with minimal doses to the organs at risk (OAR). Assessment of the current data affirms the clinical usefulness of the facility-adopted protocol in achieving quality treatment plans for intact breast and chest-wall irradiations. The establishment of plan acceptability criteria will help achieve improved overall treatment outcomes.

Combined Bilateral Salpingo-oophorectomy and Cesarean Delivery in BRCA1/2 Alteration Carriers : A Case Series.

The cumulative lifetime risk of ovarian cancer is 16-68% and 11-30% in female BRCA1 and BRCA2 gene alteration carriers, respectively. Risk-reducing bilateral salpingo-oophorectomy (RRSO) is the only proven way to reduce ovarian cancer mortality. We report a series of patients who underwent risk-reducing surgery at the time of planned obstetric-indicated cesarean delivery. This is a case series of four women carrying a pathogenic germline BRCA1 or BRCA2 gene alteration who underwent RRSO at the time of cesarean delivery between March 1, 2018, and March 31, 2022. All women were referred during pregnancy to the University College London Hospitals Familial Cancer Clinic for consideration of RRSO at the time of obstetric-indicated cesarean delivery. Women were considered eligible for RRSO if they had a proven pathogenic germline alteration, would have completed childbearing after the cesarean delivery, and were older than age 35 or 40 years with BRCA1 or BRCA2 alterations, respectively. Operating time, blood loss, transfusion requirements, length of hospital stay, complications, and ability to breastfeed were assessed and, where possible, compared with the institutional means for similar patients who underwent cesarean delivery only, to determine whether RRSO was associated with increased morbidity. Women were contacted 11-59 months postprocedure to assess satisfaction. The mean blood loss was 687 mL (range 400-1,000 mL), mean operating time was 68 minutes, mean length of hospital stay was 3 days, and mean change in hemoglobin was -1 g/dL. No patient required a transfusion, had internal organ damage, returned to the operating room, or was readmitted. One of two women with intact breast tissue successfully breastfed, and the other chose to bottle feed. The mean contemporaneous institutional blood loss for cesarean delivery was not significantly different at 681 mL for singleton pregnancies and 872 mL for twin pregnancies. All four women reported a high level of satisfaction with the combined procedure. Our results show that RRSO can be performed at the time of cesarean delivery with high patient satisfaction. This approach can be offered to appropriately counseled individuals, with the benefit of avoiding the need for two separate procedures, with potentially reduced patient morbidity and health care costs.

Dosimetric and Clinical Results of a Volumetric-Based Skin-Sparing Planning Technique for Patients Treated to the Breast and Chest Wall with Pencil Beam Scanning Proton Therapy

Given clinical concerns for more brisk acute skin toxicity with proton compared with photon RT due to differences in the energy deposition properties, our institution implemented a novel volumetric skin-sparing planning technique (SSPT) for intensity modulated proton therapy (IMPT) for patients treated to the breast or chest wall (CW). This study evaluates SSPT dosimetry and the hypothesis that a SSPT will reduce acute dermatitis during IMPT to the breast and CW. Prior to the development of a consensus technique, skin dose evaluation in IMPT plans was limited to mitigation of skin hot spots and cropping off the skin surface by 3mm for CW and 5mm for intact breast targets (except indications for deliberate skin dosing). In January 2022 our center added volumetric-based skin sparing objectives in addition to hot-spot evaluation as a SSPT. A skin evaluation structure (skin-eval) was defined as a skin rind of 3 mm for CW and 5 mm for intact breast within 5mm of the CTV, bound by the patient's surface. The SSPT incorporated an objective to limit the volume of skin-eval receiving 95% of the prescription dose or more (V95%Rx) to ideally <50% (goal<60%) while still prioritizing CTV coverage and robustness. We compared target coverage, robustness, and skin-eval dosimetry as well as acute on-treatment skin toxicity in patients treated with and without incorporation of this SSPT. Patients with skin/dermal lymphatic invasion or inflammatory breast cancer were excluded. 84 patients who were planned to receive breast or CW IMPT were included (43 planned without and 41 with the SSPT). There was no difference in percentages of patients treated to the intact breast/CW/immediate CW reconstruction between the groups (37%/23%/40% without and 34%/27%/39% with SSPT, p>0.05). Mean skin-evalV95%Rx was 72% vs. 30%, p<0.0001, for those treated without vs. with a SSPT. Maximum %Rx to the skin volume of 0.03 cc, 0.3cc, and 1cc, was higher in patients treated without compared to those with a SSPT (103.1% vs. 101.5%; 101.3% vs. 100.4%; and 101.8% vs. 99.7% (all p=<0.0001)), respectively. There was a small statistical difference in the mean CTV V97.5%Rx in patients treated without vs. with the SSPT (97.8% vs. 96.5%, p=0.0003). Patients planned utilizing the SSPT demonstrated reduced rates of Grade 1 breast pain at Week 2 (12% vs. 33%, p=0.0424) and Grade 2 and 3 dermatitis at Week 5 (grade 2 38% vs. 42%; grade 3, 0% vs. 11%, p=0.0016). There were numerically more patients requiring a treatment break or not completing full intended prescription (4 vs. 1) in the pre-SSPT cohort. A volumetric-based SSPT appears to reduce the frequency of brisk onset dermatitis and near-end of RT significant dermatitis while still maintaining acceptable target coverage and robustness in patients receiving IMPT to the breast and CW.

Lateral wedge with medial only cardiac shielding (LEMONADE) technique in left breast radiotherapy

This dosimetric study analyzed the lateral wedge with medial only cardiac shielding (LEMONADE) technique for left breast radiotherapy (LBRT) against three other commonly used techniques which is a follow-up from our earlier publication of LEMONADE technique in left chest wall (LCW) radiotherapy.&#x0D; Dosimetric parameters of 30 consecutive patients who underwent LBRT with LEMONADE technique (P1) after breast conserving surgery (BCS) were compared with 3 other virtually reconstructed plans: no cardiac shielding with paired wedges; P2 (paired wedges and medial only Y-direction shielding) and P3 (paired wedges and bilateral Y-direction shielding).&#x0D; P1 had target volume (TV) coverage [mean 90% isodose coverage of 89.00% ± 3.96 vs 86.28% ± 4.80 and 84.43% ± 5.70 for P2 and P3, respectively]. While there is 3.07% drop in TV coverage compared to no cardiac shielding, the V26Gy of heart dropped from 5.26% to a negligible 0.56% for P1. Low dose region (TV receiving &lt; 30Gy) is also significantly lesser for P1 compared to P2 and P3 (1.50% vs 3.61% and 5.65%).&#x0D; The earlier positive LEMONADE dosimetric study of LCW radiotherapy has been replicated in this study with much better dose volume parametres likely due to the physical properties of intact breast. LEMONADE is an easily re-producible and simple radiotherapy technique that can be implemented in most radiotherapy centres. Further study is needed on the use of LEMONADE technique in extreme hypofractionation.

Phase 2 Study of Preoperative SABR for Early-Stage Breast Cancer: Introduction of a Novel Form of Accelerated Partial Breast Radiation Therapy

Pre-operative delivery of partial breast irradiation (PBI) facilitates smaller target volumes and reduced dose to normal tissues. We hypothesized that pre-operative stereotactic ablative radiotherapy (SABR) delivered to intact breast tumor would achieve pathological complete response (pCR) in 25% of patients while preserving low rates of toxicity and good cosmesis. Eligible patients had hormone receptor-positive, clinically node-negative breast cancer measuring ≤2cm on magnetic resonance imaging (MRI). Patients received SABR to 28.5 Gy in three fractions of 9.5 Gy to the tumor defined on MRI and computed tomography in the prone position. Lumpectomy was performed 6-8 weeks later. Tumor pathologic response was assessed and adverse events (AEs) were rated on the Common Terminology Criteria for AEs version 4.0 scale. Physician-rated cosmesis are also reported. Twenty patients were enrolled and completed treatment; the study was terminated prior to full accrual due to pre-specified stopping rules. Median follow-up was 14 months. Median patient age was 65 years (range 54-78) and median tumor size on MRI was 10.5mm (range 5-22). All patients had negative surgical margins. Four patients (20%) required post-operative whole breast and axillary radiation due to positive sentinel lymph nodes. No pCR were observed, although the median percent residual tumor cellularity was 30% (range 10-80) and 90% had ≤50% residual cellularity. Three patients had late grade 3 AEs, including 2 of the 4 patients who received post-operative RT. Cosmesis was good in 85% of cases, fair in 10%, and poor in 5%. We observed a 0% incidence of pCR with pre-operative SABR for early-stage BrCa as evaluated 6-8 weeks following treatment. Evolution of pCR may require longer than 6-8 weeks. Patients requiring post-operative whole breast radiotherapy after pre-operative SABR may be at increased risk for high-grade soft tissue toxicity. Further studies are needed to determine optimal patient selection, treatment methodology and timing of pathologic response evaluation.

The function of forward planned intensity-modulated radiotherapy technique in radiotherapy of the intact breast dose distribution optimization

The function of forward planned intensity-modulated radiotherapy technique in radiotherapy of the intact breast dose distribution optimization

The MR mammography of phyllodes tumors of different histological grades

Purpose: to evaluate retrospectively the MR data of the breast phyllodes tumors and to perform comparative analysis of the MR signs and the histological grade of the phyllodes tumors.Materials and methods. The analyses enrolled 27 pathologically confirmed phyllodes tumors (mean age of patient 37.8 y.o.). Following features were evaluated: tumor shape and structure, margins, size, type of contrast enhancement, foci of high signal intensity on the T1-WI, foci of hypo- or isointense signal on the T2-WI comparing with intact breast tissue, presence of cystic inclusions and the type of their margins.Results. The study included 18 benign, 4 borderline and 5 malignant phyllodes tumors. The following features showed significant correlation with the tumor grade: irregular margins of the cystic foci (p = 0.003), foci of hypoor isointense signal on the T2-WI compared with intact breast tissue (p = 0.005). Foci of high signal intensity on the T1-WI were often revealed in the malignant (3/5) and borderline tumors (2/4), but this dependence was not significant (p = 0.021). According to pathomorphological correlation the foci of the high signal intensity on the T1-WI corresponded to hemorrhages, while cystic foci with irregular margins were revealed to be foci of necrosis. The foci of hypo- or isointense signal on the T2-WI compared with intact breast tissue corresponded to the hypercellular stroma.Conclusion. Specific features of phyllodes tumors are useful in differentiation of their histological types; furthermore the MR mammography provides accurate data for planning the point of biopsy.

Clinical Introduction of a Volumetric-Based Skin-Sparing Planning Technique for Breast and Chest Wall Patients Treated with PBS Proton Therapy: A Review on Feasibility and Impact on Target Coverage and Robustness

<h3>Purpose/Objective(s)</h3> Acute and late skin toxicities are common and bothersome for patients undergoing breast or chest wall (CW) irradiation. There is clinical concern that acute skin toxicity may be higher with proton radiation compared with photon radiation because of differences in their energy deposition properties. Limited literature exists on dosimetric strategies to mitigate skin toxicity for patients treated with intensity modulated proton therapy (IMPT). We characterize the outcomes of a volumetric-based skin-sparing planning technique for IMPT treated breast and CW patients. <h3>Materials/Methods</h3> Prior to a consensus strategy, skin dose evaluation in IMPT Breast and CW plans was heterogeneous across physicians and dosimetrists. Uniformly, clinical targets were delineated by cropping off the skin surface by 3 mm for CW and 5 mm for intact breast; however, further skin-sparing strategies were previously restricted to limiting hot spots. In January 2022 our center established a consensus strategy to mitigate skin toxicity that added volumetric-based skin sparing objectives in addition to hot-spot evaluation. To start, a consistent skin evaluation structure (skin-eval) was defined within 5 mm of the CTV and included a rind of 3 mm for CW and 5 mm for intact breast, bound by the patient's surface. IMPT planning incorporated an objective to limit the volume of skin-eval receiving 95% of the prescription dose or more (V95%) to ideally less than 40% (goal of less than 50%) of the volume of the skin-eval structure, Skin-eval V95%Rx<40% (goal 50%), while still prioritizing CTV coverage and robustness. We report the early dosimetric experience with this volumetric-based objective. Boost plans were not included in this study. <h3>Results</h3> Ten patients underwent IMPT planning incorporating the described skin-eval objective, including 6 with intact breasts and 4 CW. Median skin-eval V95%Rx=36.4% (range, 20.3-49.9%). Median skin-eval max dose to 0.03cc, 0.3cc, and 1cc was 102.8% (range 101.4%-103.9%), 101.8% (range 100.5%-102.9%), and 101.1% (range 99.5%-102.3%), respectively. Median CTV V97.5%Rx was 98.2% (range, 94.9%-99.5%). 9 of the 10 plans passed all robust evaluation scenarios at V95%Rx receiving at least 95% (median 97.7%, range 96.1%-98.5%). Only 1 plan did not meet CTV goal coverage in all robust scenarios, failing only 1 scenario. This plan uniquely incorporated a couch kick to address atypical setup challenges. <h3>Conclusion</h3> A volumetric-based objective of skin-eval V95%Rx<50% appears consistently achievable while still maintaining excellent nominal and robustly optimized target coverage in patients receiving IMPT to the breast and CW. Future studies with both retrospective and prospective designs can validate dose constraints that may be more relevant for toxicity mitigation with IMPT.

Patient-derived breast model repository, a tool for hyperthermia treatment planning and applicator design

Objective The addition of hyperthermia in the treatment of intact breast cancer with the aim to improve local response is currently in a research phase. First, optimal hyperthermia devices need to be developed, for which a diverse, anatomically and pathologically accurate set of patient models is necessary. Methods To investigate the effects of inter-subject variations on hyperthermia treatment plans, we generated a repository of 22 anatomically and pathologically diverse patient models based on MR images of breast cancer patients. Hyperthermia treatment plans were generated for the 22 models using a generic theoretical phased array hyperthermia applicator. Results Good temperature coverage was achieved in the vast majority of the models, with median values for T 10 = 43.5°C (41.9–43.8°C), T 50 = 42.5°C (41.3–43.3°C), and T 90 = 41.3°C (39.8–42.6°C) under the condition that the maximum temperature increase in the patient is limited to 44°C. Conclusions For future development of hyperthermia devices and treatment methods, a repository with a sufficiently large number of representative patient models, such as the one provided in this study, should be used to ensure applicability to a wide variety of patients. This repository is therefore made publicly available.

Planning and Treatment Recommendations for Breast Proton Therapy From a Single Center's Experience

PurposeProton therapy use for breast cancer has grown due to advantages in coverage and potentially reduced late toxicities compared with conventional radiation therapy. We aimed to provide recommendations for robustness criteria, daily imaging, and quality assurance computed tomography (QA CT) frequency for these patients. Methods and MaterialsAll patients treated for localized breast cancer at the Johns Hopkins Proton Center between November 2019 and February 2022 were eligible for inclusion. Daily shift information was extracted and examined through control charts. If an adaptive plan was used, the time to replan was recorded. Three and 5 mm setup uncertainty was used to calculate robustness. Robust evaluation of QA CTs was compared with initial robustness range for breast/chest wall and lymph node target coverage. ResultsSixty-six patients were included: 19 with intact breast, 25 with non-reconstructed chest wall, and 22 with chest wall plus expanders or implants. Sixteen percent, 13%, and 41% of breast, chest wall, and expander/implant patients had a replan. Only patients with expanders or implants required 2 adaptive plans. Daily shift data showed large variation and did not correlate with plan adaptation. Patients without adaptive plans had QA CTs with dose-volume histogram metrics within robustness more frequently than those with adaptive plans. Using 3 mm robustness for patients who did not require an adaptive plan, 91% to 100% of patients had QA CTs within robustness, while 55% to 60% of patients with an adaptive plan had QA CTs within robustness for the axilla, internal mammary nodes, and supraclavicular nodes. Five millimeter setup uncertainty did not significantly improve this. ConclusionsWe recommend using daily cone beam CT because of the large variation in daily setup with 3 mm setup uncertainty in robustness analysis. If daily cone beam CT imaging is not available, then larger setup uncertainty should be used. Two QA CTs should be conducted during treatment if the patient has expanders or implants; otherwise, one QA CT is sufficient.

Radiation therapy in breast cancer: a narrative review on current standards and future perspectives

: Mastectomy and reconstructive procedures have been refined over the decades, allowing for aesthetic outcomes close to the native breast shape and in symmetry with the contralateral intact breast or even to improve breasts appearance and symmetry. Similarly, improvements in radiation oncology can help reduce treatment related toxicity and improve outcomes. However, postmastectomy radiation therapy (PMRT) is associated with poor cosmetic outcomes and increased rate complications in patients who undergo breast reconstruction. Radiation therapy planning should be guided by disease stage, risk of recurrence, correct definition of the target volumes and treatment objectives. Currently, there are guidelines endorsed by European Society for Radiotherapy and Oncology (ESTRO) for target volume delineation for breast cancer and elective nodal volumes, including after immediate reconstruction. Correct target volume delineation, along with meticulous radiation planning, total dose and fractionation, dose homogeneity, and organs at risk (OAR) doses are significant for reducing radiation-induced toxicity. Currently, tremendous efforts are done by different groups to improve aesthetic outcomes without compromising disease outcomes in breast cancer patients who are candidates for mastectomy and radiation therapy. The current paper summarizes key principles in PMRT, considering new surgical techniques for immediate breast reconstruction and new, partly experimental radiation techniques including future trials and proton beam irradiation.

Abstract P3-19-10: Subcutaneous layer dosimetry of the breast and chest wall at clinical beam energies without bolus: A Monte Carlo and analytical anisotropic algorithm (AAA) calculation study

Abstract PURPOSE: Breast skin thickness is 3 mm (1). The subcutaneous layer (SL) lies immediately beneath the skin and is at risk for local recurrence after breast cancer surgery and adjuvant radiotherapy. As the SL lies within the buildup region for megavoltage radiation treatment, placement of bolus for patients receiving chest wall (CW) radiotherapy (RT) is routine at many centers. The dermal toxicity of bolus is well known: in 12 studies of CW RT, the pooled risk of Grade 3 acute toxicity is 9.6% with bolus and 1.2% without bolus (2). Meanwhile, bolus is rarely used after breast-conserving surgery (BCS) RT for patients with similar cancers. This study examines variation in tangential RT dose coverage of the SL in the intact breast and bolus-free CW with clinically relevant photon beam energies using Monte Carlo (MC) calculations and a commercial treatment planning system (TPS). METHODS: Thirty CT datasets from patients without skin involvement were identified. There were two groups of patients: 15 treated with BCS RT and 15 treated with CW RT. In each group, 5-patient subgroups had tangent-beam RT planned without bolus with 6, 10, and 15 MV photons, respectively, using the Analytical Anisotropic Algorithm (AAA) algorithm (v.13.6.23) in Eclipse v.15.6 (Varian Medical Systems Inc., Palo Alto, CA). On each CT, the SL was segmented as a high-resolution shell from 3 to 5 mm below the body contour in the Eclipse TPS v.15.6 (Varian Medical Systems Inc., Palo Alto, CA). A 1x1x1 mm MC dose simulation was performed using EGSnrc code (BEAMnrc/DOSXYZnrc). The MC dose distributions were imported back into the TPS for comparison with AAA calculations. The V95% and V90% for the SL were calculated for each case and the mean V95% and V90% were reported for each subgroup. A t-test was used with a two-sided alpha = 0.05 for statistical analysis. RESULTS: The mean separation increased with use of higher energies for both BCS and CW RT. The MC-calculated mean SL V90% and V95% were higher for CW RT than for BCS RT at each energy. The V90% coverage was 91.5% for CW and 74.4 % for BCS at 6 MV (p&amp;lt;0.001), 89.3% for CW and 61.3% for BCS (p&amp;lt;0.001) at 10 MV and 87.1% for CW and 60.9% for BCS (p&amp;lt;0.001) at 15 MV (Table 1). For SL V95% the CW coverage was higher than the BCS coverage for every energy. For SL V90% at 6 MV, the AAA and MC calculations agreed within 2.5%, with the MC being slightly higher. The agreement between AAA and MC decreased for higher energies with MC reporting higher SL V90% coverage by up to 16.3%. The higher MC-calculated dose to the SL is consistent with the literature (3). CONCLUSION: MC and AAA SL dose calculations agreed well for 6 MV, but AAA underestimated the dose for 10 and 15 MV. For 6-15 MV photons, the MC-calculated dosimetric coverage of the SL is higher for CW RT than BCS RT. Since radiation oncologists are satisfied with the SL coverage by BCS RT, bolus is not needed for CW RT, because, without bolus, CW RT delivers a higher SL dose than BCS RT. REFERENCES:. 1.Pope TL Jr, et al.J Can Assoc Radiol. 1984 Dec;35(4):365-8. PMID: 6526847. 2.Dahn HM, et al. Crit Rev Oncol Hematol. 2021 Jun 5;163:10339. PMID: 34102286. 3.Panettieri V, et al., Radiother Oncol 2009; 93: 94-101 Table 1.Monte Carlo calculated mean V90% and V95% for Breast and Chest Wall for each energyV95%V95%V95%V90%V90%V90%Energy(MV)Chest Wall(Mean)Breast. (Mean)p-valueChest Wall(Mean)Breast. (Mean)p-value661.9%35.1%&amp;lt;0.00191.5%74.4%&amp;lt;0.0011065.2%39.7%&amp;lt;0.00189.3%61.3%&amp;lt;0.0011561.7%38.9%0.01287.1%60.9%&amp;lt;0.001 Citation Format: Dylan Narinesingh, Alan Nichol, Alanah Bergman, Tony Popescu. Subcutaneous layer dosimetry of the breast and chest wall at clinical beam energies without bolus: A Monte Carlo and analytical anisotropic algorithm (AAA) calculation study [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-10.

Sensing for intact breast cancer-related small extracellular vesicles

Sensing for intact breast cancer-related small extracellular vesicles

The Expression of Prolactin Receptors in Benign Breast Tumors Is Not Associated with Serum Prolactin Level.

The role of prolactin (PRL) and its receptors in the initiation and development of benign breast tumors (BBT) has not been sufficiently studied. An imbalance in the system of hormone homeostasis is crucial in the development of BBT. In particular, an association between elevated prolactin levels and the development of BBT has been reported. Our study showed no significant differences between PRL receptor (PRL-R) expression in BBT tissue under normal and elevated serum PRL levels. There was also no significant correlation between age, PRL-R expression in BBT tissue, intact tissue, and PRL level in the serum. There was a strong significant correlation (p < 0.01; r = 0.92) between PRL-R expression in BBT samples and intact breast tissue, which did not depend on the serum PRL level. There was also no significant difference in the expression of the proliferative marker Ki-67 in BBT tissues from women with normal and elevated levels of serum PRL (p > 0.05). No signs of PRL and its receptors were detected in the BBT cystic fluid women with elevated serum PRL levels. In summary, our prospective study showed that the expression of PRL-R in the tissue of BBT and physiological breast tissue does not depend on the level of serum PRL.

Tangential Volumetric Modulated Arc Therapy for Locally Advanced Breast Cancer

Cardiovascular toxicity from breast radiation therapy (RT) is a concern to patients and providers. Herein, we present a cardiac-sparing strategy using tangential volumetric modulated arc therapy (tVMAT) in comparison with standard 3-dimensional conformal RT. Ten patients with left-sided breast cancer previously treated with adjuvant RT covering the breast, as well as the axillary and supraclavicular nodal regions, were selected for the study. For each patient, 2 plans were created: a dual-isocenter 3-field 3-dimensional conformal RT plan and a monoisocentric tVMAT plan. The prescription for both techniques was 50 Gy in 25 fractions to the breast and nodal target volumes. Compared with 3-dimensional conformal RT, tVMAT provided more uniform coverage to the breast and regional lymph nodes (mean conformity index: 1.42 for tVMAT vs 2.42 for 3-dimensional conformal RT; P < .01), and the maximum point dose for tVMAT was lower on average (112.8% for tVMAT vs 121.5% for 3-dimensional conformal RT; P < .001). Coverage to the lymph nodes was superior for tVMAT (average minimum coverage to 95% of entire nodal target volumes: 99.5% of prescribed dose for tVMAT vs 94.9% for 3-dimensional conformal RT; P < .001). Organ-at-risk sparing was improved with tVMAT, with a lower average V20Gy for the left lung (15.0% for tVMAT vs 24.6% for 3-dimensional conformal RT; P < .01) and lower mean heart dose (156 cGy for tVMAT vs 200 cGy for 3-dimensional conformal RT; P < .01). Tangential volumetric modulated arc therapy is a promising technique for the treatment of intact breast and regional lymphatics, and it may improve target coverage and organ-at-risk avoidance compared with 3-dimensional conformal techniques.

OL105 - Gold nanoparticles and SABR for treatment planning of intact breast tumor

OL105 - Gold nanoparticles and SABR for treatment planning of intact breast tumor

Breast cancer surveillance following ovarian cancer in BRCA mutation carriers

ObjectivesBRCA 1 or 2 mutation carriers have increased risk of developing breast cancer (BC) and serous epithelial ovarian cancer (EOC). The incidence of BC over time after EOC is unknown. Optimal BC surveillance for BRCA mutation carriers following EOC has not been defined. MethodsA multi-institutional retrospective chart review was performed. Patients with BRCA -associated EOC diagnosed between 1996 and 2016 were followed for an average of 80 months. Women with previous bilateral mastectomy were excluded; women with prior BC and an intact breast were included. Descriptive statistics, Chi Square, and univariate survival analysis were performed. Results184 patients with BRCA -associated EOC were identified. Eighteen (10%) were diagnosed with BC a median of 48 months following EOC. Two (1%) with prior BC developed contralateral BC and 16 (9%) developed primary BC. The majority of BC (55%) was diagnosed 3 years following EOC. The 3-, 5- and 10-year incidence of BC was 5.6%, 9.5% and 33.3%. Annual mammography was performed in 43% and MRI in 34%. Twenty-eight (15%) women underwent risk-reducing mastectomy (RRM). There was no statistically significant difference in BC screening between women with, and without, a prior BC. BC was most commonly detected on mammogram. Three (17%) women had occult BC at the time of RRM. Nine (50%) had DCIS, and 8 (44%) had stage I/II BC. Median 5- and 10-year survival was 68% and 43% and was comparable between groups. ConclusionsTen percent of women developed BC after EOC. The incidence of BC following EOC in BRCA carriers increases over time, and surveillance is recommended given their enhanced survival of EOC. Timely genetic testing for women with EOC is imperative to better triage BC screening resources and treatment.