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In inflammatory breast cancer, radiation therapy intensification is considered a standard of care by some teams, although the level of evidence remains low. We sought to analyze the impact of radiation therapy modalities on the risk of loco-regional and distant relapse. This retrospective multicenter study included patients with localized inflammatory breast cancer treated between 2010 and 2017. Standard postmastectomy radiation therapy consisted of daily fractions to a total dose of 50 Gy equivalent without a boost or bolus, while intensified radiation therapy referred to the use of a boost or bolus. The cumulative incidence curves of locoregional and distant recurrence were displayed using the competing risk method. Of the 241 included patients, 165 were treated with standard and 76 with intensified radiation therapy. There was significantly more nodal involvement in the intensified group. With a median follow-up of 40 months postradiation therapy, there was no difference between standard versus intensified radiation therapy regarding the cumulative incidence of locoregional (P =.68) or distant recurrence (P =.29). At 5 years, the risks of locoregional and distant recurrence were 12.1% (95% CI, 7.5; 17.7) and 29.4% (95% CI, 21.8; 37.3) for patients treated with standard radiation therapy and 10.4% (95% CI, 4.4; 19.3) and 21.4% (95% CI, 12.6; 31.9) for those treated with intensified radiation therapy. In multivariate analyses, triple-negative subtype and absence of complete pathologic response were associated with a higher risk of loco-regional recurrence. Radiation therapy intensification had no significant impact on locoregional and distant recurrence. For patients with a non-complete pathologic response (n = 172, 71.7%), no significant differences were observed between the 2 groups for loco-regional (P =.80) and distant (P =.39) recurrence. Severe toxicity rates were similar in both groups. Contrary to other important series, this large retrospective multicentric study did not show a locoregional or distant control benefit of intensified radiation therapy. Pooled prospective studies and meta-analyses of intensified radiation therapy are warranted to endorse this approach. [ABSTRACT FROM AUTHOR]

There is new data in the fractionation modalities and these are the really the practice-changing trials of last years: can we use hypo fractionated whole breast radiotherapy in patients presented with ductal carcinoma in situ? Can we realize hypofractionated whole breast radiotherapy with simultaneous integrated boost? What about hypofractionated irradiation after mastectomy with reconstruction? Can we do hypofractionation to lymph nodes without risk of increased toxicity? The purpose of this work is to respond with the last evidence-based recently presented or published data. [ABSTRACT FROM AUTHOR]

• Interobserver reproducibility for boost delineation in breast cancer is mostly poor. • The presence of clips and fluid in the surgical bed improves this reproducibility. • Pre-operative imaging is useful to improve the accuracy of tumour bed delineation. • Boost delineation has become even more challenging since oncoplastic surgery exists. • Guidelines involving surgeon, pathologist, radiologist and oncologist are essential. Several randomized controlled trials have demonstrated the benefit of a boost to the tumor bed (TB) to reduce the risk of ipsilateral breast tumor recurrence. Recent technological progress has facilitated improved conformation of isodoses around the target volume. The accuracy and reproducibility of TB delineation have become even more essential. The purpose of this study is to review the extant knowledge on the boost delineation in breast cancer, focusing on interobserver variability (IOV) and the influence of various factors, such as the presence of clips or different imaging modalities to improve IOV. Most studies investigating IOV for boost delineation have shown poor reproducibility (with comparison indices such as the dice similarity index around 0.5). Clips in the lumpectomy cavity (LC), postoperative fluid accumulation in the LC and/or high cavity visualization score appeared to be associated with improved IOV. Likewise, the use of preoperative imaging (CT and/or MRI) may also be useful in improving the accuracy of TB definition but without any real gain in terms of IOV. Moreover, the delineation of boost has become even more challenging since the development of oncoplastic surgery. To improve the reproducibility and the accuracy of boost delineation, this review suggests that within each center, a group of multidisciplinary experts, including surgeons, radiation oncologists, pathologists, and radiologists, should convene to develop local guidelines, which may include the choice of preoperative imaging, the number and location of surgical clips, pathological margins, and orientation. The elaboration of contouring atlas is certainly of great assistance. [ABSTRACT FROM AUTHOR]

• ERT was commonly performed in dnMBC patients despite the absence of guidelines. • This is the largest study evaluating the impact of ERT on OS in dnMBC patients. • ERT and BMT were associated with reductions in the hazard of death compared with no LRT. • ERT could be an appropriate locoregional treatment in selected dnMBC patients. The impact of locoregional treatment (LRT) on overall survival (OS) in de novo metastatic breast cancer (dnMBC) is still under debate, with very few data available regarding exclusive radiotherapy (ERT) as a therapeutic modality. We evaluated the impact of ERT, exclusive surgery, or a combination of surgery plus radiotherapy (bimodality therapy, BMT) on survival outcomes in a national real-life dnMBC cohort. The primary and secondary end points were OS and progression free survival (PFS) according to LRT (ERT, exclusive surgery, BMT) and no LRT. Sensitivity analyses were performed using propensity score matched analyses. From 2008 to 2014, 4507 dnMBC patients were identified. Only patients alive and free from progression under systemic therapy at least 1 year after diagnosis were included (n = 1965). Forty-five percent of patients (891/1965) underwent LRT: 41.1% (n = 366) ERT, 13.7% (n = 122) exclusive surgery, and 45.2% (n = 403) BMT. OS adjusted for major prognostic factors was significantly longer in the ERT and BMT group compared with no-LRT group, but not exclusive surgery (hazard ratio (HR) = 0.63, 95% confidence interval (CI) [0.49, 0.80], p < 0.001, HR = 0.61, 95%CI [0.47, 0.78], p < 0.001 and HR = 0.87, 95%CI [0.61, 1.26], p = 0.466 respectively). Results were similar after matching on a propensity score. ERT, surgery and BMT were all associated with a significantly better PFS in multivariable analysis. ERT was significantly associated with better OS in dnMBC, in the same magnitude as BMT, compared with no-LRT. However, even with statistical models adjusted for known prognostic factors and propensity score analysis, selection biases cannot be eliminated from observational studies. [ABSTRACT FROM AUTHOR]

Secondary breast cancer is a frequent late adverse event of mediastinal Hodgkin lymphoma radiotherapy. Secondary breast cancers overwhelmingly correspond to ductal carcinoma and develop from the glandular mammary tissue. In addition, during childhood, radiation overexposure of the glandular tissue may lead to a late breast hypotrophy at adult age. The aim of this study was to evaluate the radiation exposure to the glandular tissue in patients treated for mediastinal Hodgkin lymphoma with intensity-modulated proton therapy, in order to evaluate the potential dosimetric usefulness of its delineation for breast sparing. Sixteen consecutive intermediate-risk mediastinal female patients with Hodgkin lymphoma treated with consolidation radiation with deep inspiration breath hold intensity-modulated proton therapy to the total dose of 30 Gy were included. Breasts were delineated according to the European Society for Radiotherapy and Oncology guidelines for treatment optimization ("clinical organ at risk"). The glandular tissue ("glandular organ at risk") was retrospectively contoured on the initial simulation CT scans based on Hounsfield unit (HU) values, using a range between −80 HU and 500 HU. The mean and maximum doses delivered to the glandular organ at risk were significantly lower than the mean and maximum doses delivered to the clinical organ at risk, but were statistically correlated. Glandular organ at risk volumes were significantly smaller. Optimizing the treatment plans on the clinical breast contours will systematically lead to overestimation of the dose received to the glandular tissue and, consequently, to an indistinct and involuntary improved glandular tissue sparing. As such, our findings do not support the consideration of the glandular tissue as an additional organ at risk when planning intensity-modulated proton therapy for mediastinal Hodgkin lymphoma in female patients. [ABSTRACT FROM AUTHOR]

Introduction. Mean heart dose (MHD) is the most widely used dosimetric parameter for cardiac sparing during treatment planning. Specific cardiac substructure exposure could be more clinically important, but MHD cannot provide the radiation oncologist with precise insight at the substructural level. Materials. We propose a straightforward method for estimating cardiac substructure exposure based on linear regressions between mean dose delivered to cardiac substructures and MHD. We focused on breast irradiation with intensity modulated radiation therapy as an application example. Correlations between mean dose to cardiac substructures and MHD were statistically significant and usually moderate (r > 0.5) or strong (r > 0.7), allowing the use of such linear regression models to estimate cardiac substructure exposure from MHD for clinical practice. Conclusion. This method can be extrapolated to other clinical situations for daily practice, albeit with some restrictions. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To evaluate whole breast 3D-conformal radiotherapy (RT) delivered in the lateral decubitus position (isocentric lateral decubitus [ILD]) and to report the acute toxicity of a series of consecutive patients treated with ILD. Materials and methods: From January to December 2010, 56 consecutive patients with large breasts and early-stage breast cancer treated by breast conserving surgery underwent 3D-conformal whole breast RT in the lateral decubitus position. A dose of 50Gy in 25 fractions via two opposed isocentric beams was prescribed to whole breast, with or without a 16Gy photon tumor bed boost. Dosimetry of all patients was reviewed, and the acute toxicity of treatment, evaluated weekly using the NCI CTC v3.0 scale, was analyzed. Results: Median age was 57years (range: 33–71). 85% of patients had a breast circumference of at least 95cm and 80% had at least a C cup size. Average breast volume was 991cm3 (range: 225–2791cm3). Median dose to the breast was 50Gy, while median dose to the tumor bed was 16Gy. Grade 1, 2 and 3 dermatitis developed in 37.5%, 58.9% and 1.8% of patients, respectively. From a dosimetric point of view, doses to the ipsilateral lung were extremely low: average V1Gy, V2Gy and V5Gy were 26.6%, 9.3% and 0.7%, respectively. Average mean lung dose was 0.96Gy. For the 26 patients with left-sided tumors, heart doses were also extremely low: average V1Gy, V2Gy and V5Gy were 58.8%, 14.2% and 0.7%, respectively. Average mean heart dose was 1.35Gy. Conclusion: Whole breast radiotherapy in the lateral decubitus position for patients with large breasts and early-stage breast cancer provides an excellent dosimetric profile, with low doses to the heart and ipsilateral lung. It is also very well tolerated, with a good acute toxicity profile. [Copyright &y& Elsevier]

Background. We investigated the feasibility of helical tomotherapy (HT) for inoperable large breast tumors, after failing to achieve adequate treatment planning with conformal radiation techniques. Material and Methods. Five consecutive patients with locally advanced breast cancer (LABC) were treated by preoperative HT. All patients received up-front chemotherapy before HT. Irradiated volumes included breast and nodal areas (45-50 Gy) in 4 patients. One patient received a simultaneous integrated boost (55 Gy) to gross tumor volume (GTV) without lymph node irradiation. Acute toxicity was assessed with Common Toxicity Criteria for Adverse Events v. 4. Patients were evaluated for surgery at the end of treatment. Results. Patients were staged IIB to IIIC (according to the AJCC staging system 2010). HT was associated in 4 patients with concomitant chemotherapy (5-fluorouracil and vinorelbine). Two patients were scored with grade 3 skin toxicity (had not completed HT) and one with grade 3 febrile neutropenia. One patient stopped HT with grade 2 skin toxicity. All patients were able to undergo mastectomy at a median interval of 43 days (31-52) from HT. Pathological partial response was seen in all patients. Conclusions. HT is feasible with acceptable toxicity profiles, potentially increased by chemotherapy. These preliminary results prompt us to consider a phase II study. [ABSTRACT FROM AUTHOR]

Kaposi's sarcoma (KS) most often affect the skin but occasionally affect the mucosa of different anatomic sites. The management of mucosal KS is seldom described in the literature. Data from 15 eligible patients with mucosal KS treated between 1994 and 2008 in five institutions within three countries of the Rare Cancer Network group were collected. The inclusion criteria were as follows: age >16 years, confirmed pathological diagnosis, mucosal stages I and II, and a minimum of 6 months' follow-up after treatment. Head and neck sites were the most common (66%). Eleven cases were HIV-positive. CD4 counts correlated with disease stage. Twelve patients had biopsy only while three patients underwent local resection. Radiotherapy (RT) was delivered whatever their CD4 status was. Median total radiation dose was 16.2 Gy (0-45) delivered in median 17 days (0-40) with four patients receiving no RT. Six patients underwent chemotherapy and received from 1 to 11 cycles of various regimens namely vinblastin, caelyx, bleomycine, or interferon, whatever their CD4 counts was. Five-year disease free survival were 81.6% and 75.0% in patients undergoing RT or not, respectively. Median survival was 66.9 months. Radiation-induced toxicity was at worse grade 1-2 and was manageable whatever patients' HIV status. This small series of mucosal KSs revealed that relatively low-dose RT is overall safe and efficient in HIV-positive and negative patients. Since there are distant relapses either in multicentric cutaneous or visceral forms in head and neck cases, the role of systemic treatments may be worth investigations in addition to RT of localized disease. Surgery may be used for symptomatic lesions, with caution given the risk of bleeding. [ABSTRACT FROM AUTHOR]

Abstract: We wanted to evaluate a simplified “field-in-field” technique (SFF) that was implemented in our department of Radiation Oncology for breast treatment. This study evaluated 15 consecutive patients treated with a simplified field in field technique after breast-conserving surgery for early-stage breast cancer. Radiotherapy consisted of whole-breast irradiation to the total dose of 50 Gy in 25 fractions, and a boost of 16 Gy in 8 fractions to the tumor bed. We compared dosimetric outcomes of SFF to state-of-the-art electronic surface compensation (ESC) with dynamic leaves. An analysis of early skin toxicity of a population of 15 patients was performed. The median volume receiving at least 95% of the prescribed dose was 763 mL (range, 347–1472) for SFF vs. 779 mL (range, 349–1494) for ESC. The median residual 107% isodose was 0.1 mL (range, 0–63) for SFF and 1.9 mL (range, 0–57) for ESC. Monitor units were on average 25% higher in ESC plans compared with SFF. No patient treated with SFF had acute side effects superior to grade 1-NCI scale. SFF created homogenous 3D dose distributions equivalent to electronic surface compensation with dynamic leaves. It allowed the integration of a forward planned concomitant tumor bed boost as an additional multileaf collimator subfield of the tangential fields. Compared with electronic surface compensation with dynamic leaves, shorter treatment times allowed better radiation protection to the patient. Low-grade acute toxicity evaluated weekly during treatment and 2 months after treatment completion justified the pursuit of this technique for all breast patients in our department. [Copyright &y& Elsevier]

Abstract: Purpose: Radio-induced early skin reactions still remain a clinical challenge. Preliminary results with Hyaluronic acid, one of the most recent topical products used in this indication are proving interesting. To evaluate the efficacy of Hyaluronic acid compared to placebo. Material and methods: Breast cancer patients with grade 1–2 radio-induced dermatitis during postoperative radiotherapy were eligible. They were randomised to receive either hyaluronic acid (A) or a simple emollient (B). The primary endpoint was the clinical evaluation of the erythema (success versus failure). Secondary endpoints were the evaluation of skin colorimetry, pain, and quality of life. Results: Two-hundred patients were enroled (A =99, B =101). Ninety-five patients per treatment arm could be evaluated. Failures occurred in 23 patients (24%) in the hyaluronic acid arm, and 32 (34%) in the emollient arm (p =0.15). Seventy-three patients (36.5%) prematurely stopped the treatment without any ensuing difference between the two arms. Body mass index and the size of the epithelitis were both independently associated with the failure of the local treatment. The relative reduction of colorimetric levels was 20% in the hyaluronic acid group, and 13% in the emollient group (p =0.46). Concerning the quality of life assessment, there was a trend towards a lower level of pain in patients receiving hyaluronic acid (p =0.053). Conclusions: The present study showed no significant difference between hyaluronic acid and simple emollient in the treatment of acute radio-induced dermatitis. There was however a trend towards an improvement in both pain level and skin colorimetry. [Copyright &y& Elsevier]

Background: To evaluate the skin and heart toxicity of a concurrent adjuvant trastuzumab-radiotherapy for breast cancer (BC), especially in the case of internal mammary chain (IMC) irradiation. Material and methods: Prospective study of 106 patients treated between 06/2003 and 03/2007 by concurrent trastuzumab-radiotherapy for non-metastatic BC. Left ventricular ejection fractions (LVEF) was assessed at baseline, before and after radiotherapy and then every 4–6months. All toxicities were evaluated using CTCAEV3. Results: Median age was 52years (25–76). Chemotherapy with anthracycline was administered in 92% of patients. All patients received trastuzumab every three weeks (8mg/kg followed by 6mg/kg) for a median duration of 12months (3-40). The IMC was irradiated in 83% of patients. There were: 87 grade 1, 14 grade 2 and 2 grade 3 skin reactions. There were 13 oesophagitis: 9 grade 1; 3 grade 2, and 1 grade 3. Out of 101 patients with assessments after 6months, late telangiectasia grade 1 occurred in 5 patients, local pain grade 1 in 19 patients and grade 2 in 3 patients, fibrosis grade 1 in 16 patients. A reversible grade ⩾2 left ventricular systolic dysfunction occurred in 6 patients. Conclusion: In this prospective study of breast cancer patients treated with trastuzumab-radiotherapy with, in most cases, anthracycline-based chemotherapy and IMC irradiation, both the rate of abnormal LVEF after concurrent trastuzumab-radiotherapy and the skin toxicity were deemed acceptable. Further follow-up is needed. [Copyright &y& Elsevier]

Purpose: To evaluate the accuracy of a boost technique. Methods and Materials: Twenty-two patients underwent tumorectomy with placement of two or more clips in the surgical cavity before breast remodeling. Preoperative and postoperative computed tomography scans, with match-point registration, were performed on all patients. The relationship between the location of the gross tumor volume (GTV), defined on the preoperative scan, and clip clinical target volume (CTV) (clips with a 5-mm margin on the postoperative scan) was then studied, by use of commercial volume analysis software. Results: Of the patients, 4 had two clips, 2 had three clips, 8 had four clips, and 8 had five clips. The median GTV was 1.06 mL (range, 0.2–5.3 mL); clip CTV ranged from 2.4 to 21.5 mL. Volumetric analysis showed that in 7 cases (32%), there was no intersection between the GTV and the clip CTV, with the following distribution: 4 patients with two clips, 1 patient with three clips, 1 patient with four clips, and 1 patient with five clips. The common contoured volume was defined as the percent ratio between the intersection of the GTV and clip CTV and the GTV. It was found to be significantly increased if three or more clips were used vs. only two clips (common contoured volume, 35.45% vs. 0.73%; p = 0.028). Finally, the GTV and clip CTV volume relationship can be presented as follows: 12.5% to 33% overlap in 8 patients (36.4%), 50% to 75% in 5 patients (22.7%), and greater than 90% in 2 patients (9%). Conclusions: The use of three or more clips during tumorectomy increases the accuracy of tumor bed delineation. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the long-term cause-specific survival (CSS), locoregional recurrence-free survival (LRFS), and metastases-free survival (MFS) in elderly breast cancer patients receiving adjuvant normofractionated (NF) or hypofractionated (HF) radiotherapy (RT). Methods and Materials: Between 1995 and 1999, 367 women aged ≥70 years with nonmetastatic Stage T1 or T2 tumors were treated by breast-conserving surgery and adjuvant RT at the Institut Curie. They underwent wide tumor excision with or without lymph node dissection followed by RT. They received either a NF-RT schedule, which delivered a total dose of 50 Gy (25 fractions, 5 fractions weekly) to the whole breast, followed by a boost to the tumor bed when indicated, or a HF-RT schedule, which delivered a total dose of 32.5 Gy (five fractions of 6.5 Gy, once weekly) with no subsequent boost. The HF-RT schedule was indicated for the more elderly patients. Results: A total of 317 patients were in the NF-RT group, with 50 in the HF-RT group. The median follow-up was 93 months (range, 9–140). The 5- and 7-year CSS, LRFS, and MFS rates were similar in both groups. The 5-year NF-RT and HF-RT rate was 96% and 95% for CSS, 95% and 94% for LRFS, and 94% and 95% for MFS, respectively. The 7-year NF-RT and HF-RT rate was 93% and 87% for CSS, 93% and 91% for LRFS, and 92% and 93% for MFS, respectively. Conclusion: According to the findings from this retrospective study, the HF-RT schedule is an acceptable alternative to NF-RT for elderly patients. However, large-scale prospective randomized trials are needed to confirm these results. [Copyright &y& Elsevier]

Purpose: Helical tomotherapy (HT) was assessed in two patients with paramedullar solitary bone plasmocytoma. We compared doses delivered to critical organs, according HT plan or tridimensional conformal plan. Methods and materials: One male (patient no. 1), 67 yr-old and one female (patient no. 2), 37-yr-old, with histologically, biologically and radiological confirmed paramedullar solitary plasmocytoma have been treated in our department between November 2007 and February 2008 using HT. The prescription dose was 40 Gy in 20 fractions. This HT treatment planning was compared with a routine dosimetric work that was executed for a standard conformal radiotherapy treatment planning. Results: Treatment tolerance was excellent, without any side effects. Both patients achieved 9-month complete remission. HT resulted in substantial critical organs sparing. For patient no. 1, dose delivered to 20% of the total intestine volume was reduced from 28 Gy for conformal radiotherapy to 13 Gy for HT. Radiation dose delivered to 20% of the left kidney was reduced from 25 Gy to 7 Gy. For patient no. 2, volume of left lung that received at least 20 Gy was 12% for conformal radiotherapy vs. 6% for HT. Conclusions: For paramedullar solitary plasmocytoma, HT has the potential to significantly improve the quality of the dose distribution both in terms of better dose homogeneity within the planning target volume and more efficient sparing of critical organs. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article “Breast Reconstruction After Surgery for Breast Cancer,” by P.G. Cordeiro in a previous issue.

Purpose: To describe a new procedure for breast radiotherapy that will improve tumor bed localization and radiotherapy treatment using a multidisciplinary approach. Patients and Methods: This pilot study was conducted by departments of radiation oncology, surgery, and radiology. A new procedure has been implemented, summarized as eight steps: from pre-surgery contrast CT to surgery, tumor bed planning target volume (PTV) determination, and finally breast and tumor bed irradiation. Results: Twenty patients presenting with T1N0M0 tumors were enrolled in the study. All patients underwent lumpectomy with the placement of surgical clips in the tumor bed region. During surgery, 1 to 5 clips were placed in the lumpectomy cavity before the plastic procedure. All patients underwent pre- and postoperative CT scans in the treatment position. The two sets of images were registered with a match-point registration. All volumes were contoured and the results evaluated. The PTV included the clips region, the gross tumor volume, and the surgical scar, with an overall margin of 5–10 mm in all directions, corresponding to localization and setup uncertainties. For each patient the boost PTV was discussed and compared with our standard forward-planned PTV. Conclusions: We demonstrate the feasibility of a tumor bed localization and treatment procedure that seems adaptable to routine practice. Our study shows the advantages of a multidisciplinary approach for tumor bed localization and treatment. The use of more than 1 clip associated with pre- to postoperative CT image registration allows better definition of the PTV boost volume. [Copyright &y& Elsevier]

Abstract: Introduction: This study aimed to evaluate responses and outcome of hormone-therapy (HT) and radiotherapy (RT) given concurrently for large breast cancers in post-menopausal women. Material and methods: Forty-two breast carcinomas in 41 women were treated with HT and concurrent RT to the breast ± lymph node bearing areas. For 30 tumours this was followed by breast surgery (with axillary lymph node dissection when the axilla had not been irradiated). RT delivered a median dose to the tumour of 50 Gy (48–66) and 75 Gy (65–84) for, respectively, preoperative and exclusive RT–HT. Median follow-up was 64 months. Results: Out of 42 clinically assessable tumours (after a mean dose of 50 Gy), 9 tumours (21%) had complete clinical responses, 24 (57%) partial responses, 9 (21%) stable disease. Breast-conserving surgery or exclusive RT–HT was possible in 74% of tumours. For 29 patients who underwent breast surgery, the rate of pathological complete responses was 17%. At 50 Gy no skin toxicity higher than grade 2 occurred. Five year OS, RFS and local control were, respectively, 85%, 84% and 97%. Lymphoedema occurred in one patient. Conclusion: Concurrent association of RT–HT demonstrated good efficacy, both in terms of clinical and pathological complete responses. It allowed breast conservation with acceptable tolerance and good 5-year local control. [Copyright &y& Elsevier]

Purpose: Electron beam radiotherapy of the chest wall with or without lymph node irradiation has been used at the Institut Curie for >20 years. The purpose of this report was to show the latest improvements of our technique developed to avoid hot spots and improve the homogeneity. Methods and Materials: The study was split into two parts. A new electron irradiation technique was designed and compared with the standard one (dosimetric study). The dose distributions were calculated using our treatment planning software ISIS (Technologie Diffusion). The dose calculation was performed using the same calculation parameters for the new and standard techniques. Next, the early skin toxicity of our new technique was evaluated prospectively in the first 25 patients using Radiation Therapy Oncology Group criteria (clinical study). Results: The maximal dose found on the five slices was 53.4 ± 1.1 Gy for the new technique and 59.1 ± 2.3 Gy for the standard technique. The hot spots of the standard technique plans were situated at the overlap between the internal mammary chain and chest wall fields. The use of one unique field that included both chest wall and internal mammary chain volumes solved the problem of junction. To date, 25 patients have been treated with the new technique. Of these patients, 12% developed Grade 0, 48% Grade 1, 32% Grade 2, and 8% Grade 3 toxicity. Conclusions: This report describes an improvement in the standard postmastectomy electron beam technique of the chest wall. This new technique provides improved target homogeneity and conformality compared with the standard technique. This treatment was well tolerated, with a low rate of early toxicity events. [Copyright &y& Elsevier]

Purpose: The aim of this study was to estimate the risk of second malignancies (SM) after radiation therapy (RT) for breast cancer (BC) in a large, institutional, homogeneous cohort of patients. Methods and Materials: We retrospectively studied 16,705 patients with nonmetastatic BC treated at the Institut Curie in Paris between 1981 and 1997. Adjuvant RT was given to 13,472 of these patients, and no RT was given to 3,233. The SM included all first nonBCs occurring during follow-up. Cumulative risks for each group were calculated using Kaplan-Meier estimates, censoring for contralateral cancer or death. Results: Median patient age at diagnosis of BC was 55 years for the whole population, and 53 and 60 years for patients who had and had not undergone irradiation, respectively. At the 10.5-year median follow-up, 709 patients were diagnosed with SM (113 in the non-RT and 596 in the RT group). There was a significant increase in the rate of sarcomas and lung cancers in the RT group compared with non-RT group (p 0.02). Treatment with RT was not found to increase the risk of other types of cancers such as thyroid cancer, malignant melanoma, gastrointestinal or genitourinary, and hematologic SM. Conclusions: This study suggests that adjuvant RT increased the rate of sarcomas and lung cancers, whereas it did not increase the rate of other malignancies. [Copyright &y& Elsevier]

The article presents a study which examined prophylactic salpingo-oophorectomy (SO) in women carrying BRCA1/2 mutation genes. The study employed 89 BRCA1/BRCA2 mutation carriers who underwent SO between 1994 and 2004. Occult ovarian carcinomas were found in four patients, one experienced recurrence and two are disease-free. The study concluded that prophylactic SO remains an important option for BRCA1/2 mutation carriers as asymptomatic ovarian/fallopian cancers were found in 4.5% of patients.

Abstract: Background and purpose: To evaluate the influence of the position and the exact localizations of supra clavicular nodes (SCN) and internal mammary chain (IMC) and their variability among patients in order to improve treatment planning in breast cancer (BC) patients. Patients and methods: A total of 46 CT scans of the chest were examined. All patients were female treated with breast conserving surgery and radiotherapy. The study was divided into two phases. The first consisted of measurements on 20 diagnostic CT scans, performed in the supine position with both arms over the head. All patients received contrast. This first phase was performed as a training program for radiologist and radiation oncologist to prepare for the second phase of the study: 26 CT scans in treatment position on angled board without injection. For this second group, patients had one arm raised above the head (treated side) and the other kept by the side (contralateral side). Measurements were performed on both sides to evaluate the influence of the arm position. The depths of IM- and SC vessels were measured at five points: (1) the origin of the internal mammary artery, (2) the sterno-clavicular articulation, (3–5) the first, second and third rib interspaces (RI). Measurements of the depth and of the distance between the internal mammary vessels and the middle axis of the sternum were obtained using electronic calipers on a PACS workstation. Results: There were important individual variations of the depth of SCN, as follows: 20–84mm (diagnostic) and 19–64 (treatment position). No differences in the depth of the IMC were found between treated and contralateral side at the region of the I, II, and III rib interspaces. The lateral margin of the IMC was never more than 40mm from the middle axis of the sternum (I, II, III rib interspaces). There was no difference in the lateral limits of IMC (the distance between the IM vessels and the middle axis of the sternum) between the two sides: treated and contralateral. Conclusions: This study shows the importance of the patients'' individual anatomy, their position and the large variability in the depth of SCN. It is important to visualize these regions to permit individual dosimetric optimization. [Copyright &y& Elsevier]

Abstract: BRCA1 and BRCA2 germline mutations are associated with a strong risk of breast cancer, which may preclude breast-conserving treatment in carriers. This study examined whether mutation status influenced the rate of breast cancer recurrence following breast-conserving treatment. BRCA1 and BRCA2 genes were screened for germline mutations in 131 patients with a family history of breast and/or ovarian cancer, who had been treated with breast-conserving surgery and radiotherapy. The 131 patients with familial history were matched to 261 patients without, according to age at diagnosis and year of treatment. The follow-up of controls was at least equal to the time-interval between diagnosis and genetic testing in familial cases. Matched cohorts were compared according to rates of breast cancer recurrence as first event and contralateral breast cancer using log-rank tests. BRCA1/2 mutations were found in 20.6% patients with a family history. Nineteen patients had a BRCA1 mutation and 8 had a BRCA2 mutation. Breast cancers in mutation carriers were more often grade III (p <10-4) and oestrogen receptor negative (p =0.005) than tumours in both non-carriers and controls. Median follow-up for all 392 patients was 8.75 years. No significant differences in breast cancer recurrence as first event were seen between BRCA1/2 tumours and controls (p =0.47), carriers and non-carriers with a family history (p =0.96), or non-carriers and controls (p =0.10). On multivariate analysis, age was the most important factor significantly predicting for breast cancer recurrence. The rate of contralateral breast cancer was significantly increased in all patients with a family history: BRCA1/2 carriers versus controls (p =0.0003), non-carriers versus controls (p =0.0034) and carriers versus non-carriers (p =0.02). At a 9-year median follow-up, the rate of ipsilateral breast cancer recurrence was not higher in BRCA1 and BRCA2 mutation carriers than in non-carriers with a family history or sporadic cases. These results support the hypothesis that breast tumours in BRCA carriers are more sensitive to radiation. Therefore, breast-conserving treatment can be offered to these patients. However, longer follow-up is needed to ensure that the rate of new primary cancer in the treated breast does not increase in the long-term. [Copyright &y& Elsevier]

Purpose: To present an original technique for breast radiotherapy, with the aim of limiting lung and heart irradiation, satisfying quality assurance criteria. Methods and Material: An original radiotherapy technique for breast irradiation has been developed at the Institute Curie in January 1996. It consists of isocentric breast irradiation in the lateral decubitus position (isocentric lateral decubitus [ILD]). This technique is indicated for voluminous or pendulous breasts needing breast irradiation only. Thin carbon fiber supports and special patient positioning devices have been developed especially for this technique. In vivo measurements were performed to check the dose distribution before the routine use of the technique. Results: ILD has been successfully implemented in routine practice, and 500 patients have been already treated. Breast radiotherapy is performed using a dose of 50 Gy at ICRU point in 25 fractions. ILD shows good homogeneity of the dose in breast treatment volume, treatment fields are perpendicular to the skin ensuring its protection, and extremely low dose is delivered to the underlying lung and heart. Conclusion: In cases of voluminous breasts or patients with a history of lung and heart disease, our technique provides several advantages over the conventional technique with opposing tangential fields. This technique improves the dose homogeneity according to the ICRU recommendations. [ABSTRACT FROM AUTHOR]

Simple Summary: Skin toxicity is the main complication during irradiation in the management of early-stage breast cancer. In some cases, it may cause treatment to stop. These toxicities may be acute (mainly radiodermatitis) and/or late (mainly fibrosis). Their understandings, their mechanisms of occurrence, as well as their management is indispensable in order to improve the management of these patients. Through this study we propose to provide a clear picture of these toxicities in relation to the modalities of radiotherapy, advances in their quantification, and management to help practitioners improve their knowledge and clinical practices on this topic. Background: Radiation therapy has been progressively improved in order to maintain a satisfactory tumour response, while reducing toxicity. We will review the incidence of radiodermatitis and fibrosis according to the various radiation and fractionation techniques. We will then focus on the various methods used to manage, prevent, and quantify this toxicity. Method: More than 1753 articles were identified using the various search terms. We selected 53 articles to answer the questions addressed in this study according to criteria set in advance. Result: The literature reports lower acute toxicity with IMRT compared to 3DCRT, but no significant differences in terms of late toxicities. Partial breast irradiation appears to be less effective in terms of local control with a higher rate of late toxicity. Intra operative radiation therapy appears to provide good results in terms of both local control and late toxicity. The hypofractionation has equivalent efficacy and safety to the normofractionated regimen, but with lower rates of radiodermatitis and fibrosis. The adddition of a boost, particularly a sequential boost, increases the risk of fibrosis and radiodermatitis during treatment. Conclusion: The development of IMRT has significantly reduced acute toxicity and has improved tolerability during treatment. Modified fractionation has reduced treatment time, as well as adverse effects. [ABSTRACT FROM AUTHOR]

Breast-conserving surgery followed by adjuvant radiation to reduce the risk of ipsilateral breast tumor recurrence is the mainstay of treatment for early-stage breast cancer (ESBC). However, improved understanding of the heterogeneity of the clinical and molecular characteristics of ESBC has led to greater efforts to personalize approaches to treatment. Furthermore, advances in the understanding of the radiobiology of breast cancer have led to several practice-changing trials on the effectiveness and tolerability of moderate and ultrahypofractionated radiation. Here, we review the recent evidence and ongoing research in the radiotherapeutic management of ESBC, including the use of boost for high-risk disease and opportunities for accelerated fractionation, partial breast irradiation, and radiation omission for low-risk disease. We also discuss how molecular profiling can inform decision-making and new opportunities for primary radiation therapy and reirradiation. [ABSTRACT FROM AUTHOR]

Electron radiotherapy has long been preferred to photons for the treatment of superficial lesions because of its physical characteristics (high dose at the surface, rapid decrease in depth). Other characteristics (penumbra, heterogeneity on an oblique or irregular surface) make them difficult to use. In most indications (skin cancers, head and neck, medulloblastoma), with technical progress, in some cases they have been replaced by intensity-modulated conformal radiotherapy, brachytherapy and contact therapy. Other indications (drainage of mesotheliomas or irradiation of benign lesions) have disappeared. The low frequency of use leads to problems of safety and cost-effectiveness. However, modern photon radiotherapy techniques are still less effective than electrons in specific indications such as total skin irradiation (mycosis fungoides) or certain thin chest wall irradiations after total mastectomy, reirradiation or paediatric treatments without protons. Flash therapy, initiated by electrons, has been developed over the last 10 years, providing high-dose irradiation in an extremely short time. Initial results show good efficacy, with fewer side effects than with conventional radiotherapy. These results are leading to clinical technological developments on a larger scale. Although it has been replaced in most indications by more modern techniques, electron radiotherapy remains essential for targeted indications in specialised centres. The emergence of flash therapy will lead to new indications, on machines equipped with this new technology, which have yet to be defined and are currently the responsibility of specialised teams. [ABSTRACT FROM AUTHOR]

Simple Summary: Local radiation treatment of the main tumors in patients with synchronous metastatic illness has traditionally only been used for palliative purposes. The management of patients with de novo metastatic cancer is undergoing a revolution with the advent of new systemic therapies enabling longer overall survival with enhanced quality of life. Numerous studies have looked into the potential survival advantage of treating localized primary tumors at the oligometastatic or oligopersistent stage. In the case of synchronous metastatic disease, the local treatment of primary tumors by radiotherapy has long been reserved for palliative indications. The emergence of the concept of oligometastatic and oligopersistent diseases, the advent of new systemic therapies enabling longer overall survival with an enhanced quality of life, a better understanding of the biologic history of metastatic spread, and technical advances in radiation therapy are revolutionizing the management of patients with de novo metastatic cancer. The prognosis of these patients has been markedly improved and many studies have investigated the survival benefits from the local treatment of various primary tumors in cases of advanced disease at the time of diagnosis or in the case of oligopersistence. This article provides an update on the place of irradiation of the primary tumor in cancer with synchronous metastases, and discusses its interest through published or ongoing trials. [ABSTRACT FROM AUTHOR]

Simple Summary: Inflammatory breast cancer is a rare entity associated with a poor prognosis, especially for the triple-negative subtype. This study investigates the independent prognostic value of tumour and nodal responses after neoadjuvant chemotherapy. It shows that tumour and lymph node responses did not have the same prognostic value regarding HR and HER2 statuses. We identified a subgroup of patients with triple-negative inflammatory breast cancer with residual lymph node disease for whom adjuvant treatment intensification may be worth investigating. Inflammatory breast cancer (IBC) is a rare entity with a poor prognosis. We analysed the survival outcomes of patients with nonmetastatic IBC and the prognostic value of tumour or nodal responses to assess their individual prognostic impact across IBC subtypes. This retrospective multicentre study included patients diagnosed with IBC between 2010 and 2017 to account for advances in neoadjuvant systemic therapies and modern radiotherapy at seven oncology centres in France. Three hundred and seventeen patients were included and analysed. After a median follow-up of 52 months, the 5-year DFS was lower for triple-negative (TN) (50.1% vs. 63.6%; p < 0.0001). After multivariate analyses, incomplete nodal response was the only significant prognostic factor in the triple-negative group (HR:6.06). The poor prognosis of TN-IBC was reversed in the case of nodal response after neoadjuvant chemotherapy. Breast response does not appear to be a decisive prognostic factor in patients with TN-IBC compared to lymph node response. Despite improvements in neoadjuvant treatments, IBC remains associated with a poor prognosis. In TN-IBC patients, lack of pathological complete node response was associated with poorer survival than any other group. Treatment intensification strategies are worth investigating. [ABSTRACT FROM AUTHOR]

Abstract: To assess clinical outcome of patients with pacemaker treated with thoracic radiation therapy for T8-T9 paravertebral chloroma. A 92-year-old male patient with chloroma presenting as paravertebral painful and compressive (T8-T9) mass was referred for radiotherapy in the Department of Radiation Oncology, Institut Curie. The patient presented with cardiac dysfunction and a permanent pacemaker that had been implanted prior. The decision of Multidisciplinary Meeting was to deliver 30 Gy in 10 fractions for reducing the symptoms and controlling the tumor growth. The patient received a total dose of 30 Gy in 10 fractions using 4-field conformal radiotherapy with 20-MV photons. The dose to pacemaker was 0.1 Gy but a part of the pacing leads was in the irradiation fields. The patient was treated the first time in the presence of his radiation oncologist and an intensive care unit doctor. Moreover, the function of his pacemaker was monitored during the entire radiotherapy course. No change in pacemaker function was observed during any of the radiotherapy fractions. The radiotherapy was very well tolerated without any side effects. The function of the pacemaker was checked before and after the radiotherapy treatment by the cardiologist and no pacemaker dysfunction was observed. Although updated guidelines are needed with acceptable dose criteria for implantable cardiac devices, it is possible to treat patients with these devices and parts encroaching on the radiation field. This case report shows we were able to safely treat our patient through a multidisciplinary approach, monitoring the patient during each step of the treatment. [Copyright &y& Elsevier]

Simple Summary: Of the worldwide population, 0.5 to 1% of people are carrying a heterozygous mutation of Ataxia–Telangiectasia Mutated (ATM) gene. While the clinical radiosensitivity of carriers of germline biallelic inactivation of the ATM gene is well described, controversies are observed for monoallelic carriers of ATM mutation. The aim of this study is to evaluate acute and late toxicities after adjuvant breast radiation therapy in ATM pathogenic variant carriers. This observational retrospective study showed an absence of significative acute and late toxicities after breast radiation therapy among patients carrying a heterozygous rare variant of the ATM gene. Single nucleotide polymorphism rs1801516 (G/A), described as associated with late subcutaneous fibrosis, was not associated with this late adverse event in our study. The Ataxia–Telangiectasia Mutated (ATM) gene is implicated in DNA double-strand break repair. Controversies in clinical radiosensitivity remain known for monoallelic carriers of the ATM pathogenic variant (PV). An evaluation of the single-nucleotide polymorphism (SNP) rs1801516 (G-A) showed different results regarding late subcutaneous fibrosis after breast radiation therapy (RT). The main objective of this study was to evaluate acute and late toxicities in carriers of a rare ATM PV or predicted PV and in carriers of minor allele A of rs1801516 facing breast RT. Fifty women with localized breast cancer treated with adjuvant RT between 2000 and 2014 at Institut Curie were selected. Acute and late toxicities in carriers of a rare PV or predicted PV (n= 9), in noncarriers (n = 41) and in carriers of SNP rs1801516 (G-A) (n = 8), were examined. The median age at diagnosis was 53 years old and 82% of patients had an invasive ductal carcinoma and 84% were at clinical stage I–IIB. With a median follow-up of 13 years, no significant difference between carriers and noncarriers was found for acute toxicities (p > 0.05). The same results were observed for late toxicities without an effect from the rs1801516 genotype on toxicities. No significant difference in acute or late toxicities was observed between rare ATM variant carriers and noncarriers after breast RT for localized breast cancer. [ABSTRACT FROM AUTHOR]

Background: For decades, conventional fractionated whole breast irradiation (CF-WBI) was used after breast conserving surgery (BCS). Pivotal phase-3 trials on hypofractionated-WBI (HF-WBI) showed its non-inferiority as compared to CF-WBI. However, younger patients are often not treated with HF-WBI. The aim of this multi-centre comparative study is to confirm the safety of HF-WBI in a real-life series of younger patients. Material and methods: Between 2010 and 2016, a total of 786 patients aged less than 60 years old with early-stage breast cancer were treated with postoperative WBI after BCS in three breast cancer centres: 340 underwent HF-WBI while 446 were treated with CF-WBI. Acute toxicity was evaluated at the end of WBI. Late toxicity was evaluated at 6, 12, 24 and 36 months. Results: At univariate logistic analysis, hypofractionation showed a significant protective effect in terms of acute oedema, acute wet desquamation, chronic oedema, chronic erythema/pigmentation and breast fibrosis. At multivariate logistic analysis, hypofractionation was an independent significant factor for acute oedema, acute wet desquamation, and chronic oedema. There were not differences in tumour-related outcomes. Conclusions: HF-WBI showed significantly improved outcomes in terms of acute skin oedema, wet desquamation and chronic skin oedema. HF-WBI after BCS should be strongly encouraged to replace CF-WBI independently of age. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Modern breast cancer care is a complex multidisciplinary undertaking in which the integrated function of multiple constituent parts is critical, and where changes to one therapeutic component may profoundly influence the delivery and outcomes of another. Oncoplastic and reconstructive breast surgery has evolved in the era of longer survival rates for women with breast cancer and aims to enhance oncological and cosmetic outcomes. However, concurrently there has been an expansion in the indications for post-mastectomy radiation therapy (Abdulkarim et al., 2011 ; Early Breast Cancer Trialists' Collaborative Group (EBCTCG), 2014; Poortmans et al., 2015 ; Wang et al., 2011), the recognition of several biologically distinct breast cancer subtypes (Perou et al., 2000 ; Sørlie et al., 2001 , 2003 ; Cheang et al., 2008 , 2009 ; Sotiriou et al., 2003 ; Millar et al., 2011 ; Blows et al., 2010 ; Schnitt, 2010 ; Haque et al., 2012 ; Dai et al., 2015) and the development of recommendations for prophylactic surgery for high-risk women, including BRCA-mutation carriers (James et al., 2006 ; Domchek et al., 2010). Primary systemic therapy is increasingly utilised yet has varying efficacy depending on tumour biology (Cortazar et al., 2014). In this paper we review the evidence which informs the multidisciplinary team opinion in the era of oncoplastic and reconstructive breast surgery. We aim to describe an optimal multidisciplinary approach which balances competing risks of multimodal therapies to optimise oncological and cosmetic outcomes. [ABSTRACT FROM AUTHOR]

Presents mammograms which identified breast lipoma in a 37-year-old woman.

Ultra-hypofractionation breast radiotherapy is a safe alternative to moderate hypofractionation. This study reports the results of two ultrahypofractionated regimens used in clinical practice in a high-volume radiotherapy center in terms of efficacy and of tolerance. we included all patients treated in an adjuvant setting with five fractions after breast conserving surgery (BCS), for a histologically-confirmed invasive or in situ breast carcinoma. Radiotherapy regimens after BCS were either a 5-week schedule with 5 weekly fractions of 5,7 Gy or a one-week schedule with 5 daily fractions of 5,2 Gy. Adverse events were recorded and local-relapse free survival (LRFS), locoregional-relapse free survival (LRRFS), metastasis-free survival (MFS), for breast-cancer specific survival (BCSS) and overall survival (OS) were evaluated. Between December 2014 and December 2022, 396 patients (400 breasts) were treated with ultrahypofractionated radiotherapy. Five-year LRFS was 98.8% (95% confidence interval: 97.1%–100%), and 5-year OS was 96.0% (95%CI: 92.6–99.5%). Age was statistically associated with OS in univariate analysis (HR: 1.16, 95%CI: 1.04–1.42, p =.01). Four patients (1.0%) experienced acute grade 3 radiation-induced adverse events, and 8 patients (2.3%) acute grade 2 toxicities. Twenty-three patients (5.8%) experienced late toxicity, all of them being graded as grade 1. The use of the 5.7 Gy-weekly-fraction regimen and the delivery of a tumor bed boost were significantly associated with acute radiodermatitis (p <.01; p =.02; respectively) and late fibrosis (p <.01; p =.049; respectively). ultrahypofractionated radiotherapy was associated with an excellent tumor control rate in our 'real-life' cohort with low-risk breast cancer patients. However, delivery of a tumor bed boost and using weekly 5.7-Gy fractions were associated with an increased risk of acute and late cutaneous toxicities. [ABSTRACT FROM AUTHOR]

Simple Summary: Breast reirradiation could represent a valuable option for local recurrence of breast cancer in previously irradiated sites. We aimed to report on the efficacy and tolerability of this treatment in our institution. The results of this series combined with those available in the literature indicate that breast/chest wall reirradiation is feasible with good oncological results and low toxicity rates. Background: The management of cancer relapse in previously irradiated tissues is a challenging therapeutic issue. The aim of this work was to report our experience with breast reirradiation for locoregionally recurrent breast cancer. Methods: All patients who underwent breast or chest wall in-field reirradiation at the Institut Curie, Paris, France, between 2003 and 2019, were identified. Efficacy outcomes and physician-reported toxicities were retrospectively assessed. Results: A total of 21,372 patients underwent breast irradiation in our institution. Of these, 28 received a second course of radiotherapy to the homolateral breast/chest wall. A total of 18 (64%) patients were treated with a curative intent, and 10 (36%) were treated for palliative purposes. Only one acute and one late grade 3 adverse events were reported. One patient with major cardiovascular risk factors died of myocardial infarction 13 months after left breast reirradiation. The 2-year LRFS, OS, DSS, PFS and MFS were 59%, 79%, 82%, 46% and 75%, respectively, in the whole cohort. The 2-year LRFS (72% vs. 31%, p = 0.02), OS (94% vs. 50%, p < 0.01), DSS (94% vs. 56%, p < 0.01) and PFS (61% vs. 20%, p = 0.02) differed significantly between patients treated with curative or palliative intent but not the MFS (78% vs. 69%, p = 0.77). Among the patients, eight (29%) remained relapse-free 5 years after reirradiation. Conclusion: Breast/chest wall reirradiation appears to be feasible with good disease control, especially in patients treated with a curative intent, and presents acceptable toxicity rates. [ABSTRACT FROM AUTHOR]

Background. We investigated the feasibility of helical tomotherapy (HT) for inoperable large breast tumors, after failing to achieve adequate treatment planning with conformal radiation techniques. Material and Methods. Five consecutive patients with locally advanced breast cancer (LABC) were treated by preoperative HT. All patients received up-front chemotherapy before HT. Irradiated volumes included breast and nodal areas (45-50 Gy) in 4 patients. One patient received a simultaneous integrated boost (55 Gy) to gross tumor volume (GTV) without lymph node irradiation. Acute toxicity was assessed with Common Toxicity Criteria for Adverse Events v. 4. Patients were evaluated for surgery at the end of treatment. Results. Patients were staged IIB to IIIC (according to the AJCC staging system 2010). HT was associated in 4 patients with concomitant chemotherapy (5-fluorouracil and vinorelbine). Two patients were scored with grade 3 skin toxicity (had not completed HT) and one with grade 3 febrile neutropenia. One patient stopped HT with grade 2 skin toxicity. All patients were able to undergo mastectomy at a median interval of 43 days (31-52) from HT. Pathological partial response was seen in all patients. Conclusions. HT is feasible with acceptable toxicity profiles, potentially increased by chemotherapy. These preliminary results prompt us to consider a phase II study. [ABSTRACT FROM AUTHOR]

Aims: High‐grade metaplastic breast carcinoma (HG‐MBC) is a rare subtype of invasive breast carcinoma, mostly triple‐negative. Metaplastic carcinomas are less responsive to neoadjuvant chemotherapy and are associated with a worse outcome than invasive carcinomas of no special type. Methods: Clinicopathological characteristics and immunophenotype were retrospectively assessed in a series of 65 patients diagnosed with HG‐MBC between 2005 and 2017 at the Curie Institute (antibody panel: oestrogen receptor [ER], progesterone receptor [PR], androgen receptor [AR], human epidermal growth factor receptor 2 [HER2], programmed death ligand‐1 [PD‐L1], and trophoblast cell surface antigen 2 [TROP2]). Results: The median age at diagnosis was 59.5 years. Six (9%) patients had metastatic disease at diagnosis. Among the nonmetastatic patients receiving neoadjuvant therapy, 26% (5/19) achieved pathological complete response. Most tumours were pT1/pT2 (77%) and 12% were pN+. Histological subtypes (mixed, squamous, mesenchymal, and spindle cell) were 40%, 35.5%, 15.5%, and 9%, respectively. Tumour‐infiltrating lymphocytes were low or moderate except when squamous differentiation was present. Most tumours were triple‐negative (92%). AR and TROP2 were positive in 34% and 85% of the cases, respectively. PD‐L1 was positive in tumour cells in 18% (cutoff: 1% of positive tumour cells) of the cases and in tumour‐infiltrating immune cells in 40% (cutoff: 1% of tumour area) of the cases. Notably, spindle cell and mesenchymal metaplastic breast carcinomas were mostly PDL1‐negative. Lastly, 21 (32.3%) cases were HER2‐low, all being HER2 1+, with no HER2 2+. Conclusion: Metaplastic breast carcinoma could benefit from tailored therapeutic strategies adapted to the phenotypic specificities of histological subtypes. [ABSTRACT FROM AUTHOR]