Radiation for inflammatory breast cancer: Updates.

Inflammatory breast cancer (IBC) is a diagnosis based on a constellation of clinical features of edema (peau d'orange) of a third or more of the skin of the breast with a palpable border and a rapid onset of breast erythema. Incidence of IBC has increased over time, although it still makes up only 1-4% of all breast cancer diagnoses. Despite recent encouraging data on clinical outcomes, the published local-regional control rates remain consistently lower than the rates for non-IBC. In this review, we focus on radiotherapy, provide a framework for multi-disciplinary care for IBC, describe local-regional treatment techniques for IBC; highlight new directions in the management of patients with metastatic IBC and offer an introduction to future directions regarding the optimal treatment and management of IBC.

Preoperative Radiation Therapy for Chemorefractory Localized Inflammatory Breast Cancer.

PURPOSE: Inflammatory breast cancer (IBC) is a rare breast cancer subtype. Chemorefractory nonmetastatic IBC, defined by locoregional progression under neoadjuvant chemotherapy, is a rare situation with few therapeutic options. Owing to the rarity of this clinical presentation and the lack of specific data, no specific management guidelines exist. We evaluated whether preoperative radiation therapy/chemoradiotherapy could achieve locoregional control after first-line neoadjuvant chemotherapy in patients with IBC. METHODS AND MATERIALS: Patients with chemorefractory disease receiving preoperative radiation therapy were identified from a retrospective multicenter cohort of consecutive patients with IBC diagnosed between 2010 and 2017 at 7 oncology centers in France. RESULTS: Overall, 18 patients among the 364 patients (5%) treated for IBC had progressive disease during neoadjuvant chemotherapy. These patients had aggressive tumors with lymph node involvement at diagnosis (n = 17; 94.4%), triple-negative subtype (n = 11; 61.1%), Scarff Bloom and Richardson grade 3 (n = 10; 55.6%), and high Ki67 (median, 56.0%). After preoperative radiation therapy, all patients had a complete (n = 1; 5.6%) or partial (n = 17; 94.4%) locoregional response. One patient (5.6%) experienced acute grade 3 dermatitis. Twelve (66.7%) patients underwent surgery as planned. The estimated median follow-up was 31 months. The median overall survival, disease-free survival, distant metastases-free survival, and locoregional recurrence-free survival were 19 months, 4.5 months, 5 months, and 6 months, respectively. Ultimate locoregional control was obtained for 11 patients (61.1%), and 13 patients (72.2%) experienced metastatic progression. Triple-negative subtype (hazard ratio [HR], 15.54; P = .011) and surgery (HR, 0.23; P = .030) were significantly associated with overall survival in the univariate analysis. In multivariate analyses, the triple-negative subtype remained a significant prognostic factor (HR, 13.04; P = .021) for overall survival. CONCLUSIONS: Preoperative radiation therapy is a feasible approach with acceptable toxicities. It allowed surgery and ultimate locoregional control in a majority of patients. The lack of translation into better survival has been a challenge, in part owing to the metastatic propensity of patients with chemorefractory IBC, especially in the overrepresented triple-negative population in this series.

Clinical outcomes of curative-intent multimodal management of chemorefractory nonmetastatic inflammatory breast cancer.

INTRODUCTION: Chemorefractory nonmetastatic inflammatory breast cancer (IBC) which progresses under neoadjuvant chemotherapy poses specific therapeutic challenges: either pursuing a curative-intent treatment with a salvage combination of radiotherapy and surgery or switching to second-line systemic treatments despite the absence of metastasis. Due to the rarity of this situation, no specific management guidelines exist and the outcomes of these patients remain uncertain. In this retrospective observational study, we aimed to report the clinical outcomes of patients treated in a curative intent for chemorefractory nonmetastatic IBC, with a multimodal salvage treatment combining radiotherapy and surgery. MATERIALS AND METHODS: This single-center retrospective observational study included all chemorefractory nonmetastatic IBC treated at the Institut Curie (Paris, France). Overall survival (OS), disease-free survival (DFS), and locoregional relapse-free survival (LRRFS) were calculated from the time of diagnosis and from the time of neoadjuvant chemotherapy interruption. RESULTS: Between January 2010 and January 2018, 7 patients presented with chemorefractory nonmetastatic IBC with a progressive disease during neoadjuvant chemotherapy. Overall, chemorefractory IBC patients were young (median age of 50 years), had a good performance status, and usually presented with node-positive tumors characterized by a combination of adverse histological factors such as triple-negative breast cancer (TNBC), grade III, and high proliferation index. From the date of pathological diagnosis, 1­year OS, DFS, and LRRFS were 64.3%, 53.6%, and 71.4%, respectively. From the date of neoadjuvant chemotherapy interruption, 1­year OS, DFS, and LRRFS were 47.6%, 19.0%, and 45.7%, respectively, and median OS, DFS, and LRRFS were 8.3, 5.0, and 5.0 months, respectively. CONCLUSION: The prognosis of chemorefractory nonmetastatic IBC treated with a multimodal approach combining surgery and radiotherapy is particularly reserved, despite the curative intent of the salvage treatment and the lack of distant metastasis at the time of treatment. Optimal treatment modalities are still to be defined in this rare but critical presentation of IBC.

Proton therapy for the treatment of inflammatory breast cancer.

PURPOSE: Inflammatory breast cancer (IBC) poses a radiotherapeutic challenge due to dermal lymphatic involvement, which often necessitates larger target volumes and chest wall boosts, making advanced planning techniques attractive to reduce exposure to nearby organs. We report our experience with intensity modulated proton therapy (IMPT) for the treatment of IBC. METHODS: Between 2016 and 2020, all IBC patients treated with adjuvant IMPT at our institution were identified. Overall survival (OS) and distant metastasis-free survival (DMFS) were estimated using the Kaplan-Meier method. Adverse events (AEs) were assessed using CTCAE version 5.0. RESULTS: Nineteen patients were identified with median 24-month follow-up. CTVs included skin, chest wall, and regional lymph nodes. Median dose was 50 Gy in 25 fractions, with fifteen receiving chest wall boost (median 56.25 Gy in 25 fractions). During treatment, plan re-optimization was required in 9 (47%). Acute grade 3 dermatitis occurred in 2 (11%). Rib facture occurred in 4 (21%). One patient with pre-existing surgical seroma experienced a grade 3 fistula. Mean heart, left anterior descending artery, and right coronary artery doses were 0.7 Gy, 2.3 Gy, and 0.1 Gy, respectively. Mean ipsilateral lung V20Gy was 14.9%. At 2 years, there were no locoregional recurrences, and OS and DMFS were 89% and 82%, respectively. CONCLUSION: IMPT for IBC is well-tolerated with excellent dosimetry, low rates of AEs, and favorable early locoregional control outcomes. Follow-up for long-term outcomes is ongoing. Our findings suggest that IMPT is feasible and an attractive modality worthy of further investigation in patients with IBC.

Symptom palliation of hypofractionated radiotherapy for patients with incurable inflammatory breast cancer.

BACKGROUND: Incurable inflammatory breast cancer (IBC) patients occasionally suffer from general symptoms such as breast pain, bleeding, ulceration, and discharge, and thus require palliative radiotherapy (RT). Hypofractionated RT has many advantages in palliative settings, but very few studies on IBC have been conducted. This study was conducted to evaluate the effects of hypofractionated RT on symptomatic IBC patients. METHODS: Twenty-two patients with IBC who underwent hypofractionated palliative RT between 2010 and 2016 were retrospectively analyzed. RT was performed at a total dose of 42.5-55 Gy with 2.5-3 Gy per fraction. The treatment effects were evaluated with respect to symptom improvement, tumor response, and treatment-related toxicity. RESULTS: The main symptoms that the patients complained of before RT were pain, bleeding, and discharge. According to the percentage of symptom relief compared with pre-RT symptoms, the number of patients with < 30, 30-70%, and ≥ 70% were 2 (9.1%), 7 (31.8%), and 13 (59.1%), respectively. Eighteen (81.8%) patients showed tumor response. No patient experienced grade 3 or higher acute or chronic toxicity during a median follow-up period of 13 months. In univariate analysis, symptom type was a significant factor for predicting the degree of symptom relief. Meanwhile, RT field and C-reactive protein increase were significant factors for predicting the incidence of radiation-induced skin toxicity. CONCLUSIONS: Hypofractionated RT could safely and effectively relieve symptoms among incurable symptomatic IBC patients.

Pathologic Complete Response (pCR) and Survival of Women with Inflammatory Breast Cancer (IBC): An Analysis Based on Biologic Subtypes and Demographic Characteristics.

In this US-based study of the National Cancer Database (NCDB), we examined 8550 patients diagnosed with non-metastatic, invasive inflammatory breast cancer (IBC) who received surgery from 2004⁻2013. Patients were grouped into four biologic subtypes (HR⁺/HER2-, HR⁺/HER2⁺, HR-/HER2⁺, HR-/HER2-). On average, women were 56 years of age at diagnosis and were followed for a median of 3.7 years. The majority were white (80%), had private health insurance (50%), and presented with poorly differentiated tumors (57%). Approximately 46% of the cancers were >5 cm. Most patients underwent mastectomy (94%) and received radiotherapy (71%). Differences by biologic subtypes were observed for grade, lymph node invasion, race, and tumor size (p < 0.0001). Patients experiencing pathologic complete response (pCR, 12%) vs. non-pCR had superior 5-year overall survival (OS) (77% vs. 54%) (p < 0.0001). Survival was poor for triple-negative (TN) tumors (37%) vs. other biologic subtypes (60%) (p < 0.0001). On multivariable analysis, TN-IBC, positive margins, and not receiving either chemotherapy, hormonal therapy or radiotherapy were independently associated with poor 5-year survival (p < 0.0001). In this analysis of IBC, categorized by biologic subtypes, we observed significant differential tumor, patient and treatment characteristics, and OS.

Radiation therapy for inflammatory breast cancer.

Inflammatory Breast Cancer (IBC) is a rare and very aggressive breast cancer, still associated with poor prognosis. Therefore, management of IBC requires carefully integrated care, and ideally, patients should be evaluated in a multidisciplinary team from the beginning, to identify the best treatment strategy. IBC is usually unresectable at presentation, and neo-adjuvant systemic therapy is considered the standard of care. Response to the primary treatment, especially pathological complete response (pCR), is important to move forward to definitive local therapy with the goal to improve survival. In any case, regardless the response to neo-adjuvant therapy, surgery and radiotherapy should administered to ensure a better loco-regional tumor control. Mastectomy with axillary lymph node dissection followed by chest wall and regional nodal radiotherapy is the most frequent approach, and whether breast-conserving surgery could be preferable in some selected groups of patients with clinical complete response is still a debated question. Radiotherapy alone has recommended only in cases of persistent unresectability. To date, the approach remains as established in the current recommendations, with the best option for trimodality treatment, and further studies clearly warranted.

Blocking Interleukin (IL)4- and IL13-Mediated Phosphorylation of STAT6 (Tyr641) Decreases M2 Polarization of Macrophages and Protects Against Macrophage-Mediated Radioresistance of Inflammatory Breast Cancer.

PURPOSE: To determine the role of macrophage polarization on the response of inflammatory breast cancer (IBC) cells to radiation and whether modulation of macrophage plasticity can alter radiation response. METHODS AND MATERIALS: The human THP-1 monocyte cell line and primary human monocytes isolated from peripheral blood mononuclear cells were differentiated into macrophages and polarized to either an "antitumor" (M1) or a "protumor" (M2) phenotype. These polarized macrophages were co-cultured with IBC cells (SUM149, KPL4, MDA-IBC3, or SUM190) without direct contact for 24 hours, then subjected to irradiation (0, 2, 4, or 6 Gy). Interleukin (IL)4/IL13-induced activation of STAT6 signaling was measured by Western blotting of phospho-STAT6 (Tyr641), and expression of M2 polarization gene markers (CD206, fibronectin, and CCL22) was measured by quantitative polymerase chain reaction. RESULTS: Expression of M2 polarization markers was higher in M2-polarized macrophages after IL4/IL13 treatment than in control (M0) or M1-polarized macrophages. Co-culture of IBC cell lines with M1-polarized THP-1 macrophages mediated radiosensitivity of IBC cells, whereas co-culture with M2-polarized macrophages mediated radioresistance. Phosphopeptide mimetic PM37, targeting the SH2 domain of STAT6, prevented and reversed IL4/IL13-mediated STAT6 phosphorylation (Tyr641) and decreased the expression of M2 polarization markers. Pretreatment of M2-THP1 macrophages with PM37 reduced the radioresistance they induced in IBC cells after co-culture. Targeted proteomics analysis of IBC KPL4 cells using a kinase antibody array revealed induction of protein kinase C zeta (PRKCZ) in these cells only after co-culture with M2-THP1 macrophages, which was prevented by PM37 pretreatment. KPL4 cells with stable short hairpin RNA knockdown of PRKCZ exhibited lower radioresistance after M2-THP1 co-culture. CONCLUSIONS: These data suggest that inhibition of M2 polarization of macrophages by PM37 can prevent radioresistance of IBC by down-regulating PRKCZ.

[Radiation therapy in inflammatory breast cancer]. / Radiothérapie des cancers du sein inflammatoires.

BACKGROUND: Inflammatory breast cancer accounts for 1-5% of all breast cancers. It is associated with a poor prognosis, because of an increased risk to develop metastases in comparison with all breast malignancies. The treatment is multimodal. We have evaluated the role of radiotherapy: indications, techniques and impact for local control and overall survival. METHOD: The series of the literature with more than 40 patients irradiated for inflammatory breast cancer published since 1995 were analyzed. RESULTS: Chemotherapy was always delivered first. Adjuvant radiotherapy was associated with local control and overall survival at 10 years of 63-92% and 51-64 respectively. Without surgery, local control was 65% and overal survival 38% at 10years. Results of concomitant radiochemotherapy were reported: the studies were heterogenous. Modalities of radiotherapy were detailed with respect to dose and fractionation, target-volumes and technical considerations (including bolus). CONCLUSION: The multimodal strategy comprises systematically radiotherapy with an evaluation of tumor response to maximise resecability.

Multi-isocenter hybrid electron and rapid arc photon treatment for reirradiation of extensive recurrent inflammatory breast cancer.

Delivering an adequate and homogenous dose to a large volume of recurrent cutaneous disease can be challenging even with modern techniques. Here, the authors describe a 3-isocenter hybrid electron and rapid arc photon radiation treatment plan to provide optimal tumor coverage to an extensive recurrence of inflammatory breast carcinoma. This approach allowed for homogeneous treatment of a large volume while effectively modulating dose to previously irradiated tissue and minimizing dose to the underlying heart, lungs and brachial plexus.

Disparities in the Use of Postmastectomy Radiation Therapy for Inflammatory Breast Cancer.

PURPOSE: Although radiation therapy improves locoregional control and survival for inflammatory breast cancer (IBC), it is underused in this population. The purpose of this study was to identify variables associated with the underuse of postmastectomy radiation therapy (PMRT) for IBC. METHODS AND MATERIALS: Using the 1998 to 2011 National Cancer Data Base, we identified 8273 women who underwent mastectomy for nonmetastatic IBC. We used logistic regression modeling to determine the demographic, tumor, and treatment variables associated with the underuse of PMRT. RESULTS: Although the use of PMRT increased over time, a total of 30.3% of our cohort did not receive PMRT. On multivariate analysis, variables associated with the underuse of PMRT for IBC included the following (all P<.05): Medicare insurance (odds ratio [OR] = 0.70), annual income <$34,999 (<$30,000: OR=0.79; $30,000-$34,999: OR=0.82), cN2 and cN0 disease (cN2: OR=0.71; cN0: OR=0.63), failure to receive chemotherapy and hormone therapy (chemotherapy: OR=0.15; hormone therapy: OR=0.35), treatment at lower-volume centers (OR=0.83), and treatment in the South and West (South: OR=0.73; West: OR=0.80). Greater distance between patient's residence and radiation facility was also associated with the underuse of PMRT (P=.0001). CONCLUSIONS: Although the use of PMRT for IBC has increased over time, it continues to be underused. Disparities related to a variety of variables impact which IBC patients receive PMRT. A concerted effort must be made to address these disparities in order to optimize the outcomes for IBC.

MiR-33a Decreases High-Density Lipoprotein-Induced Radiation Sensitivity in Breast Cancer.

PURPOSE: We previously showed that high-density lipoprotein (HDL) radiosensitizes inflammatory breast cancer (IBC) cells in vitro and is associated with better local control after radiation therapy in IBC patients. The microRNA miR-33 family negatively regulates the adenosine triphosphate binding cassette transporter subfamily A member 1. We hypothesized that variations in miR-33a expression in IBC cancer cells versus non-IBC cells would correlate with radiation sensitivity following exposure to HDL in vitro. METHODS AND MATERIALS: MiR-33a expression was analyzed by reverse transcriptase-polymerase chain reaction in 4 cell lines representing common clinical breast cancer subtypes. Overexpression and knockdown of miR-33a was demonstrated via transfection of an miR-33a mimic or an anti-miR-33a construct in high- and low-expressing miR-33a cell lines. Clonogenic survival in vitro in these cells was quantified at baseline and following HDL treatment. MiR-33a expression on distant relapse-free survival (DRFS) of 210 cases downloaded from the Oxford breast cancer dataset was determined. RESULTS: Expression levels of miR-33a were lower in IBC cell lines and IBC tumor samples than in non-IBC cell lines and normal breast tissue. Cholesterol concentrations in the cell membranes were higher in IBC cells than in non-IBC cells. Clonogenic survival following 24 hours of HDL treatment was decreased in response to irradiation in the low-miR-33a-expressing cell lines SUM149 and KPL4, but survival following HDL treatment decreased in the high-miR-33a-expressing cell lines MDA-MB-231 and SUM159. In the high-miR-33a-expressing cell lines, anti-miR-33a transfection decreased radiation resistance in clonogenic assays. Conversely, in the low-miR-33a-expressing cell lines, the miR-33a mimic reversed the HDL-induced radiation sensitization. Breast cancer patients in the top quartile based on miR-33a expression had markedly lower rates of DRFS than the bottom quartile (P=.0228, log-rank test). For breast cancer patients treated with radiation, high miR-33a expression predicted worse overall survival (P=.06). CONCLUSIONS: Our results reveal miR-33a negatively regulates HDL-induced radiation sensitivity in breast cancer.

High-density and very-low-density lipoprotein have opposing roles in regulating tumor-initiating cells and sensitivity to radiation in inflammatory breast cancer.

PURPOSE: We previously demonstrated that cholesterol-lowering agents regulate radiation sensitivity of inflammatory breast cancer (IBC) cell lines in vitro and are associated with less radiation resistance among IBC patients who undergo postmastectomy radiation. We hypothesized that decreasing IBC cellular cholesterol induced by treatment with lipoproteins would increase radiation sensitivity. Here, we examined the impact of specific transporters of cholesterol (ie lipoproteins) on the responses of IBC cells to self-renewal and to radiation in vitro and on clinical outcomes in IBC patients. METHODS AND MATERIALS: Two patient-derived IBC cell lines, SUM 149 and KPL4, were incubated with low-density lipoproteins (LDL), very-low-density lipoproteins (VLDL), or high-density lipoproteins (HDL) for 24 hours prior to irradiation (0-6 Gy) and mammosphere formation assay. Cholesterol panels were examined in a cohort of patients with primary IBC diagnosed between 1995 and 2011 at MD Anderson Cancer Center. Lipoprotein levels were then correlated to patient outcome, using the log rank statistical model, and examined in multivariate analysis using Cox regression. RESULTS: VLDL increased and HDL decreased mammosphere formation compared to untreated SUM 149 and KPL4 cells. Survival curves showed enhancement of survival in both of the IBC cell lines when pretreated with VLDL and, conversely, radiation sensitization in all cell lines when pretreated with HDL. In IBC patients, higher VLDL values (>30 mg/dL) predicted a lower 5-year overall survival rate than normal values (hazard ratio [HR] = 1.9 [95% confidence interval [CI]: 1.05-3.45], P=.035). Lower-than-normal patient HDL values (<60 mg/dL) predicted a lower 5-year overall survival rate than values higher than 60 mg/dL (HR = 3.21 [95% CI: 1.25-8.27], P=.015). CONCLUSIONS: This study discovered a relationship among the plasma levels of lipoproteins, overall patient response, and radiation resistance in IBC patients and IBC patient-derived cell lines. A more expansive study is needed to verify these observations.

Challenging a traditional paradigm: 12-year experience with autologous free flap breast reconstruction for inflammatory breast cancer.

BACKGROUND: Inflammatory breast cancer is a rare but aggressive breast cancer with an overall poor prognosis. Traditionally, reconstruction has not been offered, because of poor long-term survival, the need for multimodality treatment, and complex treatment sequencing. The authors examined the safety and feasibility of free flap breast reconstruction for inflammatory breast cancer. METHODS: A retrospective analysis of all patients who underwent reconstruction for inflammatory breast cancer from January of 2000 to December of 2012 was conducted. RESULTS: Of 830 inflammatory breast cancer patients, 59 (7.1 percent; median age, 48 years; range, 27 to 65 years) underwent free flap reconstruction. All patients received chemotherapy and radiation therapy. Most patients (n = 52) underwent delayed reconstruction. Five patients with a history of prior partial mastectomy and irradiation developed inflammatory breast cancer and underwent immediate reconstruction following completion mastectomy. Two others underwent immediate chest wall and breast reconstruction following resection. Thirteen patients underwent bilateral reconstruction, and seven required a bipedicled abdominal flap for the unilateral mastectomy defect. Thirty-seven patients (62.7 percent) required revision of the reconstructed breast, and 29 (49.2 percent) had a contralateral balancing procedure to optimize symmetry. Complications occurred in 21 patients (35.6 percent), with one total flap loss (1.7 percent). The median length of follow-up was 43.9 months; 49 patients (83.1 percent) were alive without evidence of recurrent disease. CONCLUSIONS: Autologous free flap breast reconstruction can be performed safely in inflammatory breast cancer patients, with acceptable complication rates and without an increased risk for flap loss. Inflammatory breast cancer should not preclude free flap breast reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Long-term follow-up of breast-conserving therapy in patients with inflammatory breast cancer treated with neoadjuvant chemotherapy.

Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer. Currently, multimodality treatment is recommended, but the optimal surgical management has not been fully elucidated. In this study, we investigated the long-term outcomes of using breast-conserving therapy in patients with IBC undergoing neoadjuvant chemotherapy (NAC). Twenty-four patients with IBC were treated from 2002 to 2006. NAC was initiated with doxorubicin and cyclophosphamide followed by paclitaxel. In addition, HER2/neu-positive patients received trastuzumab, whereas HER2/neu-negative patients received bevacizumab. Clinical response was assessed by dynamic contrast-enhanced magnetic resonance imaging before surgery and pathologic response after surgery. A partial mastectomy with sentinel lymph node biopsy and/or axillary lymph node dissection or a modified radical mastectomy was performed based on the surgeon's recommendations and patient's preference. All patients received adjuvant radiation. Of the 24 patients, seven (29%) underwent a partial mastectomy and 17 (71%) underwent a mastectomy. The overall survival rate for partial mastectomy and for mastectomy patients was 59 and 57 per cent (P = 0.49), respectively, at a median follow-up of 60 months (range, 48 to 92 months). Breast-conserving therapy can be considered in a selected group of patients who demonstrate a good response to NAC.

EZH2 expression correlates with locoregional recurrence after radiation in inflammatory breast cancer.

BACKGROUND: Enhancer of zeste homolog 2 (EZH2), a member of the polycomb group proteins, has been shown to promote cancer progression and breast cancer stem cell (CSC) expansion. Breast CSCs are associated with resistance to radiation in inflammatory breast cancer (IBC), a rare but aggressive variant of breast cancer. In this retrospective study, we examined the clinical role of EZH2 in locoregional recurrence (LRR) of IBC patients treated with radiation. PATIENTS AND METHODS: 62 IBC patients who received radiation (7 pre-operative, 55 post-operative) and had adequate follow up to assess LRR were the subject of this study. Positive EZH2 status was defined as nuclear immunohistochemical staining in at least 10% of invasive cancer cells. Association of EZH2 expression with clinicopathologic features were evaluated using the Chi-square statistic and actuarial LRR free survival (LRFS) was determined using the Kaplan-Meier method. RESULTS: The median follow-up for this cohort was 33.7 months, and the 5-year overall LRFS rate was 69%. Of the 62 patients, 16 (25.8%) had LRR, and 15 out of 16 LRR occurred in EZH2 expressing cases. Univariate analysis indicated that patients who had EZH2-positive IBC had a significantly lower 5-year locoregional free survival (LRFS) rate than patients who had EZH2-negative IBC (93.3% vs. 59.1%; P = 0.01). Positive EZH2 expression was associated significantly with negative ER status (97.1% in ER- vs 48.1% in ER+; P < 0.0001) and triple-negative receptor status (P = 0.0001) and all triple-negative tumors were EZH2-positive. In multivariate analysis, only triple negative status remained an independent predictor of worse LRFS (hazard ratio 5.64, 95% CI 2.19 - 14.49, P < 0.0001). CONCLUSIONS: EZH2 correlates with locoregional recurrence in IBC patients who received radiation treatment. EZH2 expression status may be used in addition to receptor status to identify a subset of patients with IBC who recur locally in spite of radiation and may benefit from enrollment in clinical trials testing radiosensitizers.

Inflammatory breast cancer: a single centre analysis.

BACKGROUND: Inflammatory breast cancer (IBC) is an aggressive form of locally advanced breast cancer characterized by rapidly progressive breast erythema, pain and tenderness, oedema and paeu d'orange appearance. It accounts for 1-3% of all newly diagnosed cases of breast cancer in the west. Data on IBC from India are lacking. The aim of our study was to assess the clinical-pathological parameters and outcome of IBC at, All India Institute of Medical Sciences, a large tertiary care centre. MATERIALS AND METHODS: We screened 3,650 breast cancer cases registered from January 2004 to December 2012 and found 41 cases of IBC. Data included demographics as well as clinical, radiological and histopathological characteristics, and were collected from clinical case records using the International Classification of Diseases code (C-50). Patients who presented with IBC as a recurrence, or who had a neglected and advanced breast cancer that simulated an IBC were excluded from this study. RESULTS: The median age was 45 years (range 23-66). The median duration of symptoms was 5 months. The American Joint Committee on Cancer stage (AJCC) distribution was Stage III - 26 and IV - 15 patients. Estrogen receptor (ER), progesterone receptor (PR) positivity and human epidermal growth factor receptor 2 (HER2/neu) positivity were 50%, 46% and 60%, respectively. Triple negativity was found in 15% of the cases. All the non metastatic IBC patients received anthracycline and/ or taxane based chemotherapy followed by modified radical mastectomy , radiotherapy and hormonal therapy as indicated. Pathological complete remission rate was 15%. At a median follow-up of 30 months, the 3 year relapse free survival and overall survival were 30% and 40%respectively. CONCLUSION: IBC constituted 1.1% of all breast cancer patients at our centre. One third of these had metastatic disease at presentation. Hormone positivity and Her2 neu positivity were found in 50% and 60% of the cases, respectively.

[Safety and efficacy of whole breast irradiation with a concomitant boost: analysis of 121 cases treated at the Institute of Cancerology of Lorraine]. / Efficacité et sécurité de la technique de radiothérapie mammaire avec complément d'irradiation concomitant : analyse de 121 cas traités à l'institut de cancérologie de Lorraine.

PURPOSE: To evaluate the safety and efficacy of whole breast irradiation with a concomitant boost. PATIENTS AND MATERIALS: This is a retrospective study of 121 patients with node negative T1-T2 breast tumors inferior to 3 cm in diameter, previously treated by conservative surgery without chemotherapy. A dose of 50 Gy was delivered to the whole breast in 2 Gy daily fractions with 5 weekly treatments. A concomitant boost to the lumpectomy site delivered a total of 10 Gy in 1 Gy fractions twice a week. This would result in an equivalent tumour bed dose (assuming an α/ß of 4) of approximately 65 Gy in 2 Gy fractions. RESULTS: Over 7 years, 121 patients were treated. The median age was 67 years (range, 46-86 years). Stage distribution was: 115 T1, 6 T2; 116 tumors had positive hormonal receptors, 6 grade SBR3. With a median follow-up of 6 years (range, 1.4-11.4 years), 5-year overall survival was 98.2% (95% confidence interval [CI] 0.95-1), disease-free survival was 100% and local recurrence-free survival 100%. The maximum acute skin toxicity by the end of treatment was grade 2. Cosmetic outcomes were good on the long term. One spontaneous rib fracture was observed 1 year after radiotherapy among 76 patients. CONCLUSIONS: The study shows that whole breast radiation therapy with a concomitant boost is safe and effective for selected patients with low risk of relapse, and gives excellent long term results. This protocol represents a good alternative to longer standard whole breast radiation therapy with sequential boost to the lumpectomy bed.

Once-daily radiation therapy for inflammatory breast cancer.

PURPOSE: Inflammatory breast cancer (IBC) is a rare and aggressive breast cancer variant treated with multimodality therapy. A variety of approaches intended to escalate the intensity and efficacy of radiation therapy have been reported, including twice-daily radiation therapy, dose escalation, and aggressive use of bolus. Herein, we examine our outcomes for patients treated with once-daily radiation therapy with aggressive bolus utilization, focusing on treatment technique. METHODS AND MATERIALS: A retrospective review of patients with nonmetastatic IBC treated from January 1, 2000, through December 31, 2010, was performed. Locoregional control (LRC), disease-free survival (DFS), overall survival (OS) and predictors thereof were assessed. RESULTS: Fifty-two women with IBC were identified, 49 (94%) of whom were treated with neoadjuvant chemotherapy. All underwent mastectomy followed by adjuvant radiation therapy. Radiation was delivered in once-daily fractions of 1.8 to 2.25 Gy (median, 2 Gy). Patients were typically treated with daily 1-cm bolus throughout treatment, and 33 (63%) received a subsequent boost to the mastectomy scar. Five-year Kaplan Meier survival estimates for LRC, DFS, and OS were 81%, 56%, and 64%, respectively. Locoregional recurrence was associated with poorer OS (P<.001; hazard ratio [HR], 4.1). Extracapsular extension was associated with worse LRC (P=.02), DFS (P=.007), and OS (P=.002). Age greater than 50 years was associated with better DFS (P=.03). Pathologic complete response was associated with a trend toward improved LRC (P=.06). CONCLUSIONS: Once-daily radiation therapy with aggressive use of bolus for IBC results in outcomes consistent with previous reports using various intensified radiation therapy regimens. LRC remains a challenge despite modern systemic therapy. Extracapsular extension, age ≤50 years, and lack of complete response to chemotherapy appear to be associated with worse outcomes. Novel strategies are needed in IBC, particularly among these subsets of patients.