De novo metastatic breast cancer represents 5 to 8% of all breast cancers (2500 new cases per year in France). Systemic treatment is the cornerstone of treatment, whereas radiation therapy usually has a palliative intent. Advances in systemic and local treatments (surgery and radiation therapy) have substantially improved overall survival. In the recent breast cancer statistics in the United States, the 5-year relative survival for patients diagnosed during 2012-2018 was 29% for stage IV (Breast Cancer Statistics). Thus, an increasing proportion of metastatic breast cancers present a prolonged complete response to systemic therapy, which raises the question of the impact of local treatment on patient survival. Radiation therapy has shown its value for early breast cancer, but its place in the local management of the primary tumour or oligometastatic sites for de novo metastatic breast cancer remains under debate. This article is a literature review assessing the role of radiation therapy directed to the primary tumour and oligometastatic sites of breast cancer in patients with synchronous metastases, in order to highlight clinicians in their therapeutic decision. (c) 2023 Societe francaise de radiotherapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.

In 1st-line trials, the relative Progression Free Survival (PFS) benefit of adding CDK4/6 inhibitors to AI was consistent across all subgroups of patients (pts), including those with lower ER expression. However, little is known about the absolute PFS obtained under CDK4/6i and AI in pts with low ER expression and whether PR and HER2 expression impact PFS in this setting. PADA-1 is a phase III trial (NCT03079011) testing the clinical utility of ESR1mut detection in blood in ER ≥ 10% HER2- MBC pts receiving 1st- line Pal + AI. We investigated the association of locally-assessed ER (%), PR (%) and HER2 (0,1+,2+) IHC expression on the most recent tumor sample with PFS under Pal + AI. Of 1017 pts, 12 (1.2%), 34 (3.5%), 181 (18.5%) & 751 (76.8%) had an ER% expression of [10-20%], [21-50%], [51-80%] & [81-100%], respectively. N=249 pts (29.2%), 148 (17.3%), 186 (21.8%) & 270 (31.6%) had a PR% of [0-20%], [21-50%], [51-80%] & [81-100%], respectively (Allred scores will be presented). Available HER2 IHC scores were 0 & 1+/2+ in 357 (54.6%) & 296 (45.4%) pts, respectively. In univariate analysis, after a mFU of 28.1 months and 527 PFS events (51.8%) under Pal + AI, mPFS in pts with [10-50%], [51-80%] & [81-100%] ER IHC were 14.1, 21.6 & 30.1 months, respectively. mPFS in pts with [0-50%], [51-80%] & [81-100%] PR IHC were 20.6, 27.1 and 42.6 months, respectively. Longer PFS were observed in HER2(1/2+) vs (0) MBC (HR=0.79 [0.64;0.98]). In multivariate analysis, aside standard prognostic factors (PS, age, visceral disease, number of metastatic site, DMFI), both ER% and PR% had an independent prognostic impact: each +10% gain in ER% was associated with a reduced 10% risk of PFS event under Pal + AI (HR=0.90, 95%CI [0.84;0.96], p=0.002); each +10% gain in PR% was associated with a reduced 8% risk of PFS event under Pal + AI (HR=0.92, 95%CI [0.90;0.95], p<0.001). ER and PR IHC % have significant, independent and similar impact on PFS achieved under 1st line by Pal + AI. The 14.1 months absolute mPFS obtained among pts with ER IHC <50% suggests that CDK4/6i + AI remains a good treatment option in this patient population.

Anti-PD-1/L1 therapy alone has limited activity in ovarian cancer. We hypothesised that blockade of VEGF and prostaglandin E2 (PGE2) can reverse the endothelial barrier allowing T cell infiltration and subsequent T cell activation by PD-L1 blockade. This is the first trial combining an anti-PD-L1 antibody, atezolizumab (ATE), with bevacizumab (BEV) and the irreversible COX1/2 inhibitor acetylsalicylic acid (ASA).

L’élévation progressive du taux sérique d’antigène spécifique prostatique (PSA) survenant en cas de cancer de la prostate après prostatectomie totale est désignée comme une récidive biologique. Étant donné que le sulforaphane, substance naturelle, a été beaucoup étudié en tant qu’agent anticancéreux, nous avons effectué une étude en double insu, randomisée, multicentrique, contre placebo, en administrant du sulforaphane à 78 patients (âge moyen : 69 ± 6 ans) présentant une élévation du taux de PSA après prostatectomie totale. Le traitement comprenait une administration orale quotidienne de 60 mg de sulforaphane libre stabilisé pendant six mois (M0–M6) suivie de deux mois sans traitement (M6–M8). L’étude a été conçue pour détecter une diminution de 0,012 log (ng/ml)/mois de la pente logarithmique du PSA dans le groupe sulforaphane de M0 à M6. Ce critère d’évaluation primaire n’a pas été atteint. Concernant les critères d’évaluation secondaires, les courbes logarithmiques médianes de PSA étaient constamment inférieures chez les hommes traités par sulforaphane. Les variations moyennes du taux de PSA entre M6 et M0 étaient inférieures dans le groupe sulforaphane (+0,099 ± 0,341 ng/ml) par rapport au groupe placebo (+0,620 ± 1,417 ng/ml ; p = 0,0433). Le temps de doublement du PSA était 86 % plus long dans le groupe sulforaphane par rapport au groupe placebo (respectivement 28,9 et 15,5 mois). Les augmentations de PSA supérieures à 20 % à M6 étaient significativement supérieures dans le groupe placebo (71,8 %) par rapport au groupe sulforaphane (44,4 %) ; p = 0,0163. La compliance et la tolérance au traitement étaient très bonnes. Les effets du sulforaphane étaient remarquables dès trois mois de traitement (M3–M6). Après traitement, l’évolution des courbes du PSA de M6 à M8 est comparable dans les deux bras. Une administration quotidienne de sulforaphane libre semble prometteuse dans la prise en charge des récidives biologiques du cancer de la prostate après prostatectomie totale.

BACKGROUNDTo improve the therapeutic index of whole-brain radiation therapy (WBRT) in the treatment of brain metastases (BM) from breast cancer, we investigated the efficacy and safety of WBRT combined with temozolomide (TMZ) in this population.PATIENTS AND METHODSThis phase II multicenter prospective randomized study included patients with newly diagnosed intraparenchymal BMs from breast cancer, unsuitable for surgery or radiosurgery. All patients received conformal WBRT (3 Gy × 10-30 Gy), with or without concomitant TMZ administered at a dosage of 75 mg/m(2)/day during the irradiation period. The primary end point was objective response rate (ORR) 6 weeks after the end of treatment, defined as a partial or complete response on systematic brain MRI (modified WHO criteria). Secondary end points were progression-free survival (PFS) and overall survival (OS), neurologic symptoms, and tolerability.RESULTSBetween February 2008 and November 2010, 100 patients were enrolled in the study (50 in the WBRT + TMZ arm, 50 in the WBRT arm). Median age was 55 years (29-79). Median follow-up was 9.4 months [1.0-68.1]. ORRs at 6 weeks were 36% in the WBRT arm and 30% in the WBRT + TMZ arm (NS). In the WBRT arm, median PFS was 7.4 months and median OS was 11.1 months. In the WBRT + TMZ arm, median PFS was 6.9 months and median OS was 9.4 months. Treatment was well tolerated in this arm: the most common ≥grade 2 acute toxicity was reversible lymphopenia.CONCLUSIONWBRT combined with TMZ did not significantly improve local control and survival in patients with BMs from breast cancer. CLINICALTRIALS.GOV: NCT00875355.

Le sulforaphane (SF) est un composé naturel extrait du brocoli. Il agit au niveau de plusieurs cibles moléculaires mais est instable sous sa forme libre bioactive. Nous avons étudié l’efficacité d’un SF libre stabilisé. Essai multicentrique, 81 patients, 69 ± 6 ans, avec un taux de PSA en augmentation > 0,2 ng/ml (et < 5 ng/ml) après prostatectomie totale ± radiothérapie externe, un score de Gleason ≤ 7, un temps de doublement du PSA (PSA DT) > 5 et < 36 mois (M) ont participé à une étude randomisée, contrôlée en double insu versus placebo (P). Le traitement : 60 mg de SF per os quotidien, pendant 6 mois (M0–M6) suivi de deux mois sans traitement (M6–M8). Une baisse de 0,012 log (ng/ml)/mois de la pente de Log (PSA) dans le bras SF était attendue par rapport au P. Soixante-dix-huit patients (en ITT) ont été évalués entre M0 et M6. La pente log (PSA) médiane était de 0,0248 dans le bras SF et 0,042 dans le bras P (p = 0,11, du fait d’une variabilité inattendue du PSA à M1). L’effet traitement, d = –0,0162 log (ng/ml)/mois (95 % CI = –0,0374, +0,0031) était significatif. La différence des valeurs PSA entre M6 et M0 était plus importante dans le bras SF par rapport au P (+0,099 ± 0,341 vs +0,620 ± 1,417 ng/ml ; p = 0,03). Une augmentation de 86 % du PSA-DT (28,9 vs 15,5 mois) a été observée chez les patients SF. La testostéronémie n’a pas varié. L’observance et la tolérance ont été très bonnes. En étude exploratoire, les pentes de log (PSA) du bras SF sont moindres entre M0–M3–M6 (p = 0,0439), M0–M6 (p = 0,0397), M3–M6 (p = 0,011). Le sulforaphane stabilisé, utilisé dans cette première étude preuve de concept, semble ralentir la progression du PSA chez les patients en échappement biologique après prostatectomie totale ± radiothérapie externe adjuvante ou de rattrapage. Son efficacité clinique doit être confirmée.

Indications for adjuvant radiotherapy in breast cancer are defined from the clinical data and the pathological extent of disease in the surgical specimen. Neoadjuvant chemotherapy could modify the pathological characteristics of the tumour, inducing a pathologic complete response in 15 to 50% of cases, challenging the classical indications of adjuvant radiotherapy. The benefit of adjuvant radiotherapy after neoadjuvant chemotherapy was not prospectively evaluated. Nonetheless, from retrospective series, some recommendations with a low level of proof could be given: (i) after lumpectomy, radiotherapy of the mammary gland must be performed even in case of pathologic complete response; (H) after mastectomy, postoperative radiotherapy is recommended in case of cT3-T4, cN1-3 (clinical or radiological) or pathologically involved nodes; (Hi) irradiation of the lymph nodes areas is more questionable, but could be also proposed in case of cN1 or pN1. These recommendations are in accordance with those recently published by the National Cancer Institute and the French National Cancer Institute. (C) 2014 Societe francaise de radiotherapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.

Purpose. To evaluate the prognostic value of Ki67 expression, breast cancer molecular subtypes and the impact of postmastectomy radiotherapy in breast cancer patients with pathologic negative lymph nodes (pNO) after modified radical mastectomy.Patients and methods. - Six hundred and ninety-nine breast cancer patients with pN0 status after modified radical mastectomy, treated between 2001 and 2008, were identified from a prospective database in a single institution. Tumours were classified by intrinsic molecular subtype as luminal A or B, HER2+, and triple-negative using estrogen, progesterone, and HER2 receptors. Multivariate Cox analysis was used to determine the risk of locoregional recurrence associated with intrinsic subtypes and Ki67 expression, adjusting for known prognostic factors.Results. - At a median follow-up of 56 months, 17 patients developed locoregional recurrence. Five-year locoregional recurrence-free survival and overall survival in the entire population were 97%, and 94.7%, respectively, with no difference between the postmastectomy radiotherapy (n = 191) and no-postmastectomy radiotherapy (n = 508) subgroups. No constructed subtype was associated with an increased risk of locoregional recurrence. A Ki67 above 20% was the only independent prognostic factor associated with increased locoregional recurrence (hazard ratio, 4.18; 95% CI, 1.11 to 15.77; P < 0.0215). However, postmastectomy radiotherapy was not associated with better locoregional control in patients with proliferative tumours.Conclusion. - Ki67 expression but not molecular subtypes are predictors of locoregional recurrence in breast cancer patients with negative lymph nodes after modified radical mastectomy. The benefit of adjuvant radiotherapy in patients with proliferative tumours should be further investigated in prospective studies. (C) 2013 Societe francaise de radiotherapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.

5032 Background: Sulforaphane (SF) is a natural compound present in cruciferous vegetables. It has demonstrated molecular targets. Its main problem is its instability in its free form. We have assessed the efficacy of a natural, stabilized SF in recurrent prostate cancer patients (pts) after radical prostatectomy (RP) ± adjuvant or salvage external radiotherapy (RT). Methods: In this multicenter trial, 81 pts, mean age 69 ± 6 years with a rising prostate-specific antigen (PSA) >0.2 ng/ml (and <5 ng/ml) after RP ± RT, without metastasis, a Gleason score ≤7, a PSA doubling time (PSADT) >5 and <36 months (M) participated in a double-blind, randomized, placebo (P) controlled study. Treatment consisted in 60 mg daily SF during six-months (M0-M6). A two months washout period (M6 to M8) followed. Clinical and biological assessments were performed at M0, M1, M3, M6 and M8. The study was designed to detect a 0.012 log(ng/ml)/month decrease in Log PSA slope in the SF arm compared to P. Results: Baseline parameters did not differ between the 2 groups considering pathological stage and Gleason score, PSA, PSADT, Log PSA slope and serum testosterone. Three non-complying pts were excluded. The ITT population was 78 patients (40 P and 38 SF). Log PSA slope in the SF group (0.0298±0.0096) was significantly lower between M0 and M6 (p=0.036, 0.0285 log(ng/ml)/month =-49%) than in the P group (0.0583±0.0093) and most particularly (-83%) between M3 and M6 (p=0.011). The difference in PSA levels observed at M6 between the two groups was preserved during the washout period. A 78 % PSA DT increase was observed in the SF group (21.9 vs 12.1 months) compared to P. The mean change in PSA levels between M6 and M0 was significantly lower in the SF group compared to P (0.099±0.341 vs 0.620±1.417 ng/ml; p=0.03). Testosterone levels did not differ between the two groups. Observance was excellent (96% in each group). Safety was very good with a few more GI tract side effects in the SF arm (17 vs 10). Conclusions: The stabilized SF used in this study was shown to significantly delay PSA progression after RP ± RT. These encouraging results both on efficacy and safety indicate more extensive studies of this SF. Clinical trial information: ID-RCB: 2011- A00347-34.

Breast cancer brain metastases (BM) incidence increases with diagnosis and systemic therapeutics progresses. New strategies are needed to improve these patients' prognosis. Temozolomide (TMZ) is an oral alkylating agent with well-known radiosensitizing properties. The association of TMZ with whole-brain radiation therapy (WBRT) showed interesting brain control rates in previous phase 2 studies. However, patients with brain metastases from breast cancer were underrepresented. The purpose of this trial was to assess the efficacy and safety of WBRT combined with TMZ specifically in the treatment of brain metastases from breast cancer. Eligibility criteria for this prospective randomized multicenter phase II study were newly diagnosed intraparenchymal brain metastases from breast cancer, not suitable for surgery or radiosurgery. Patients were randomly assigned to receive WBRT (3 Gy x 10 to 30 Gy) with or without concomitant TMZ administered 75 mg/m2/day during radiation period. The primary end point was radiologic objective response at six weeks after the end of treatment, defined as a partial or complete response on systematic brain MRI (WHO modified criteria). Secondary endpoints were local progression free survival (PFS) and overall survival (OS), neurologic symptoms, and tolerability. A longer clinical-brain MRI follow-up was planned each three months during a two-year period. All patients gave an informed written consent. The study was approved by the ethical research committee. Between February 2008 and December 2010, 100 patients were enrolled (50 in the WBRT + TMZ arm, 50 in the WBRT arm). Median age was 55 (range, 29-79). Fifteen patients in the WBRT alone arm and 18 patients in the association arm had a triple negative breast cancer subtype. Twelve and 7 patients had HER2 positive tumors, respectively. Median time to brain metastases diagnosis was 45 months (range, 0-274). Sixteen patients had metastatic breast cancer at initial diagnosis. Median follow-up was 53.1 months (range, 1-68). The objective response rate at six weeks was 36% in the WBRT arm, and 30% in the WBRT + TMZ arm (NS). There was no complete response. In the WBRT arm, median PFS was 7.4 months and median OS 11.1 months. In the WBRT + TMZ arm, median PFS was 6.9 months and median OS 9.4 months. No improvement in neurologic symptoms was noticed compared to standard arm. Tolerance was good in the association arm. The most frequent upper grade 2 acute toxicity was reversible lymphopenia in this group. Time to brain metastases diagnosis between 6 to 24 months was negatively associated with PFS in multivariate analysis. Whole-brain radiation therapy combined with oral temozolomide did not improve brain control or survival among patients with brain metastases from breast cancer.

Approximately 20 to 40 % of patients with metastatic cancer will develop brain metastases (BM) during the disease course. Whole-brain radiation therapy (WBRT) is considered the standard treatment for most patients, particularly those with extensive intracranial disease, providing symptom relief and increasing median and overall survival. Despite WBRT, the prognosis for the general population of patients with BM remains poor, with a median survival time of approximately five months. Several studies have examined the relative contribution of patient characteristics to survival and have attempted to identify subgroups of patients with substantially different outcomes in order to tailor therapy and to influence the design, stratification and interpretation of future clinical trials. Here, we review the main prognostic factors and prognostic scores in patients with BM and the value and limits of these prognostic scores in clinical practice.

Environ 20 % à 40 % des patients pris en charge pour un cancer en phase métastatique présenteront des métastases cérébrales (MC) au cours de leur maladie. L’irradiation panencéphalique (IPE) est considérée comme le traitement de référence pour la plupart des patients, notamment ceux présentant une évolution intracérébrale diffuse, permettant une amélioration des symptômes neurologiques et une augmentation de la médiane de survie. Malgré l’utilisation de cette IPE, le pronostic général de cette population reste sombre avec des médianes de survie de l’ordre de cinq à six mois. Plusieurs études ont été menées ces dernières années afin de mettre en évidence les principaux facteurs pronostiques de survie après survenue de MC. Ces résultats ont permis d’établir des scores pronostiques afin d’identifier des sous-groupes de patients de pronostics différents, dans le but d’influencer la stratification et l’interprétation des essais thérapeutiques et d’assurer une meilleure sélection des patients qui pourraient se voir proposer de nouvelles stratégies thérapeutiques. Cette revue de la littérature a pour but de résumer les principaux facteurs et scores pronostiques publiés à ce jour, ainsi que l’intérêt et les limites potentielles de tels scores dans la pratique clinique.

Abstract Background: Despite of therapeutics progress in advanced breast cancer, brain metastases occurrence remain a frequent and delicate situation. The efficacy of whole-brain radiation therapy (WBRT), still considered as the standard local treatment in case of multiple brain metastases, is limited. Recently, several phase II studies have shown some efficacy of the association of WBRT and temozolomide (TMZ), an oral alkylating agent already known as a radiosensitizer, with improved brain control rate (44 to 96%). Patients with breast cancer were underrepresented and none of these trials have studied this combined treatment issue in this specific population. The aim of this study was to assess the efficacy and safety of WBRT combined with temozolomide in the treatment of brain metastases from breast cancer. Materials and Methods: A prospective randomized multicenter phase II study was developed, using a modified two-stage Fleming design. Patients with newly diagnosed intraparenchymal brain metastases from breast cancer, not suitable for surgery nor radiosurgery, were included. All patients received conformational WBRT (3 Gy x 10 to 30 Gy). They were randomized to WBRT plus concomitant TMZ administered 75 mg/m2/day during radiation period versus WBRT alone. The primary endpoint was radiologic objective response at six weeks after the end of treatment, defined as a partial or complete response on systematic brain MRI (WHO modified criteria). We also evaluated neurologic symptoms, tolerance, safety, progression free survival (PFS) and overall survival (OS) as secondary endpoints. A longer clinical-brain MRI follow-up was planned, each three months during a two-year period. All of the patients gave their written informed consent to be part of the study, which was approved by the local committee. Results: One hundred patients were enrolled between February 2008 and December 2010 (50 in the WBRT + TMZ arm, 50 in the WBRT arm). The median age was 55 [29 -79]. Eighty (80) patients had brain metastases as single secondary localization. About one third of patients had a triple negative breast cancer subtype (38,3% in the association arm and 35,71% in the WBRT alone arm). There were 26,7% and 14,6% of HER2 positive subtype respectively. The median follow-up was 30 months [range 6-60]. At six months from brain metastases diagnosis (three months after the end of the treatment), objective response rate seems better in the WBRT + TMZ arm: 52% versus 40% in the arm WBRT alone but was not statistically significant (p = 0,54). No complete response was observed. In the WBRT + TMZ group, median PFS and OS at six-months were respectively 55,6% [range 46-7 – 66,0] and 67,7% [range 59,1 – 77,6]. No improvement in neurologic symptoms was noticed. In multivariate analysis, initial TNM status was significantly correlated with PFS and OS. The concurrent use of TMZ with WBRT was well-tolerated. The most frequent upper grade II acute toxicity was reversible leucopenia in the association arm. Conclusion: The addition of temozolomide to WBRT in patients with brain metastases from breast cancer did not improve local control or survival at six months follow-up. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-11-01.

PURPOSE:To report characteristics and outcome of breast cancer after irradiation for Hodgkin lymphoma with special focus on breast conservation surgery. PATIENTS AND METHODS:Medical records of 72 women who developed either ductal carcinoma in situ or stage I-III invasive carcinoma of the breast after Hodgkin lymphoma between 1978 and 2009 were retrospectively reviewed. RESULTS:Median age at Hodgkin lymphoma diagnosis was 23 years old. Median total dose received by the mediastinum was 40 Gy, mostly by a mantle field technique. Breast cancer occurred after a median time interval of 21 years. Ductal invasive carcinoma and ductal carcinoma in situ represented respectively 71% and 19% of the cases. Locoregional treatment for breast cancer consisted of mastectomy with or without radiotherapy in 39 patients and of lumpectomy with or without adjuvant radiotherapy in 32 patients. The isocentric lateral decubitus radiation technique was used in 17 patients after breast conserving surgery (57%). With a median follow-up of 7 years, 5-year overall survival rate and locoregional control rate were respectively 74.5% and 82% for invasive carcinoma and 100% and 92% for in situ carcinoma. Thirteen patients died of progressive breast cancer and contralateral breast cancer was diagnosed in ten patients (14%). CONCLUSIONS:Breast conserving treatment can be an option for breast cancers that occur after Hodgkin lymphoma despite prior thoracic irradiation. It should consist of lumpectomy and adjuvant breast radiotherapy with use of adequate techniques, such as the lateral decubitus isocentric position.

Triple-negative breast cancer (TNBC) is a subgroup of breast cancer that is negative for estrogen and progesterone receptor and ERBB2 protein expression. It is characterized by its aggressive behavior and by the lack of targeted therapies. To identify new therapeutic targets in TNBC, we used real-time quantitative RT-PCR to analyze 63 TNBC samples in terms of their mRNA expression of 26 genes coding for the major proteins currently targeted by drugs used to treat other cancers or undergoing clinical trials in breast cancer. Six of the 26 genes tested (VEGFA, SRC, PARP1, PTK2, RAF1, and FGFR3) were significantly upregulated in 13% to 46% of the TNBCs. None of the 6 genes was specifically upregulated in the TNBCs compared with 3 other classical breast tumor subtypes. No association was observed between overexpression of these 6 genes (except for FGFR3) and PIK3CA mutation status. These results confirm the interest of targeting VEGFA and PARP1 in ongoing clinical trials in TNBC patients and also identify new target genes (SRC, PTK2, RAF1, and FGFR3). Clinical trials could be initiated easily with existing drugs. Our results also suggest that these target genes might serve as predictive biomarkers of the TNBC treatment response.

Purpose: To determine whether Ki67 expression and breast cancer subtypes could predict locoregional recurrence (LRR) and influence the postmastectomy radiotherapy (PMRT) decision in breast cancer (BC) patients with pathologic negative lymph nodes (pN0) after modified radical mastectomy (MRM).Methods and Materials: A total of 699 BC patients with pN0 status after MRM, treated between 2001 and 2008, were identified from a prospective database in a single institution. Tumors were classified by intrinsic molecular subtype as luminal A or B, HER2+, and triple-negative (TN) using estrogen, progesterone, and HER2 receptors. Multivariate Cox analysis was used to determine the risk of LRR associated with intrinsic subtypes and Ki67 expression, adjusting for known prognostic factors.Results: At a median follow-up of 56 months, 17 patients developed LRR. Five-year LRR-free survival and overall survival in the entire population were 97%, and 94.7%, respectively, with no difference between the PMRT (nZ191) and no-PMRT (n=508) subgroups. No constructed subtype was associated with an increased risk of LRR. Ki67 >20% was the only independent prognostic factor associated with increased LRR (hazard ratio, 4.18; 95% CI, 1.11-15.77; P<.0215). However, PMRT was not associated with better locoregional control in patients with proliferative tumors.Conclusions: Ki67 expression but not molecular subtypes are predictors of locoregional recurrence in breast cancer patients with negative lymph nodes after MRM. The benefit of adjuvant RT in patients with proliferative tumors should be further investigated in prospective studies. (C) 2012 Elsevier Inc.