ACO ASSO

Neoadjuvant

Ann Surg Oncol. 2012 Apr 3. [Epub ahead of print]

Evaluation of Tumor Stiffness by Elastography Is Predictive for Pathologic Complete Response to Neoadjuvant Chemotherapy in Patients with Breast Cancer.

Hayashi M, Yamamoto Y, Ibusuki M, Fujiwara S, Yamamoto S, Tomita S, Nakano M, Murakami K, Iyama KI, Iwase H.

Source

Department of Breast and Endocrine Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.

Abstract

BACKGROUND: Breast elastography (EG), which can objectively evaluate tumor stiffness, has been useful for differentiation of benign and malignant breast lesions. However, the value of EG for prediction of response to systemic therapy is poorly understood.

METHODS: The baseline evaluations of EG in 55 patients who received neoadjuvant chemotherapy were reviewed. We investigated the correlation between tumor stiffness and response to neoadjuvant chemotherapy. Tumor stiffness was evaluated by the Tsukuba elasticity scoring system.

RESULTS: The mean EG scores were significant lower for the clinical and pathologic complete response (pCR) groups than for the others. When we categorized patients into two groups according to tumor stiffness, 26 patients were assigned to the low EG group (soft, scores from 1 to 3) and 29 patients were assigned to the high EG group (hard, score 4 and 5). The low EG group had significantly higher clinical complete response and pCR rates than the high EG group (clinical complete response, low EG group 38 % vs. high EG group 10 %, P = 0.024; pCR, low EG group 50 % vs. high EG group 14 %, P = 0.003, respectively). Furthermore, multivariate analysis indicated that estrogen receptor, human epidermal growth factor receptor 2, and low EG (odds ratio 13.04, 95 % confidence interval 1.19-458.28, P = 0.035) were independent predictive factors of pCR.

CONCLUSIONS: Tumor stiffness evaluated by EG bears predictive potential for response to neoadjuvant chemotherapy. Stiffness evaluated by EG may be recognized as a clinically significant tumor characteristic, comparable to other data obtained by functional imaging techniques.

J Clin Oncol. 2012 Apr 16. [Epub ahead of print]

Definition and Impact of Pathologic Complete Response on Prognosis After Neoadjuvant Chemotherapy in Various Intrinsic Breast Cancer Subtypes.

von Minckwitz G, Untch M, Blohmer JU, Costa SD, Eidtmann H, Fasching PA, Gerber B, Eiermann W, Hilfrich J, Huober J, Jackisch C,Kaufmann M, Konecny GE, Denkert C, Nekljudova V, Mehta K, Loibl S.

Source

Gunter von Minckwitz, Valentina Nekljudova, Keyur Mehta, and Sibylle Loibl, German Breast Group, Neu-Isenburg; Michael Untch, Helios-Klinikum; Jens-Uwe Blohmer, St Gertrauden Krankenhaus; Carsten Denkert, Institute for Pathology, Charité, Berlin; Serban D. Costa, Universitäts-Frauenklinik, Magdeburg; Holger Eidtmann, Universitäts-Frauenklink, Kiel; Peter A. Fasching, Frauenklinik des Universitätsklinikums Erlangen, Erlangen; Bernd Gerber, Universitäts-Frauenklinik, Rostock; Wolfgang Eiermann, Klinikum zum Roten Kreuz, München; Jörn Hilfrich, Henrietten-Stiftung, Hannover; Christian Jackisch, Städtische Kliniken, Offenbach; Manfred Kaufmann, Universitäts-Frauenklinik, Frankfurt; Jens Huober, Kantonsspital, St Gallen, Switzerland; and Gottfried E. Konecny, University of California Los Angeles, Los Angeles, CA.

Abstract

PURPOSE: The exact definition of pathologic complete response (pCR) and its prognostic impact on survival in intrinsic breast cancer subtypes is uncertain.

METHODS: Tumor response at surgery and its association with long-term outcome of 6,377 patients with primary breast cancer receiving neoadjuvant anthracycline-taxane-based chemotherapy in seven randomized trials were analyzed.ResultsDisease-free survival (DFS) was significantly superior in patients with no invasive and no in situ residuals in breast or nodes (n = 955) compared with patients with residual ductal carcinoma in situ only (n = 309), no invasive residuals in breast but involved nodes (n = 186), only focal-invasive disease in the breast (n = 478), and gross invasive residual disease (n = 4,449; P < .001). Hazard ratios for DFS comparing patients with or without pCR were lowest when defined as no invasive and no in situ residuals (0.446) and increased monotonously when in situ residuals (0.523), no invasive breast residuals but involved nodes (0.623), and focal-invasive disease (0.727) were included in the definition. pCR was associated with improved DFS in luminal B/human epidermal growth factor receptor 2 (HER2) -positive (P = .013), HER2-positive/nonluminal (P < .001), and triple-negative (P < .001) tumors but not in luminal A (P = .39) or luminal B/HER2-positive (P = .45) breast cancer. pCR in HER2-positive (nonluminal) and triple-negative tumors was associated with excellent prognosis.

CONCLUSION: pCR defined as no invasive and no in situ residuals in breast and nodes can best discriminate between patients with favorable and unfavorable outcomes. Patients with noninvasive or focal-invasive residues or involved lymph nodes should not be considered as having achieved pCR. pCR is a suitable surrogate end point for patients with luminal B/HER2-negative, HER2-positive (nonluminal), and triple-negative disease but not for those with luminal B/HER2-positive or luminal A tumors.

J Clin Oncol. 2012 Apr 9. [Epub ahead of print]

Preoperative Chemotherapy Plus Trastuzumab, Lapatinib, or Both in Human Epidermal Growth Factor Receptor 2-Positive Operable Breast Cancer: Results of the Randomized Phase II CHER-LOB Study.

Guarneri V, Frassoldati A, Bottini A, Cagossi K, Bisagni G, Sarti S, Ravaioli A, Cavanna L, Giardina G, Musolino A, Untch M, Orlando L,Artioli F, Boni C, Generali DG, Serra P, Bagnalasta M, Marini L, Piacentini F, D’Amico R, Conte P.

Source

Valentina Guarneri, Antonio Frassoldati, Federico Piacentini, Roberto D’Amico, and PierFranco, Modena University Hospital, Modena; Alberto Bottini and Daniele Giulio Generali, AO Istituti Ospitalieri di Cremona, Cremona; Katia Cagossi and Fabrizio Artioli, Ramazzini Hospital, Carpi; Giancarlo Bisagni and Corrado Boni, Arcispedale Santa Maria Nuova, Reggio Emilia; Samanta Sarti and Patrizia Serra, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola; Alberto Ravaioli, Ospedale Infermi, Rimini; Luigi Cavanna, Hospital of Piacenza, Piacenza; Giovanni Giardina, Ospedale di Circolo e Fondazione Macchi, Varese; Antonino Musolino, University Hospital of Parma, Parma; Laura Orlando, Antonio Perrino Hospital, Brindisi; Michela Bagnalasta and Luca Marini, GlaxoSmithKline, Verona, Italy; and Michael Untch, Helios Klinikum Berlin-Buch, Berlin, Germany.

Abstract

PURPOSE: This is a noncomparative, randomized, phase II trial of preoperative taxane-anthracycline in combination with trastuzumab, lapatinib, or combined trastuzumab plus lapatinib in patients with human epidermal growth factor receptor 2 (HER2) -positive, stage II to IIIA operable breast cancer. The primary aim was to estimate the percentage of pathologic complete response (pCR; no invasive tumor in breast and axillary nodes).

PATIENTS AND METHODS: In the three arms, chemotherapy consisted of weekly paclitaxel (80 mg/m(2)) for 12 weeks followed by fluorouracil, epirubicin, and cyclophosphamide for four courses every 3 weeks. The patients randomly assigned to arm A received a 4-mg loading dose of trastuzumab followed by 2 mg weekly; in arm B patients received lapatinib 1,500 mg orally (PO) daily; and in arm C, patients received trastuzumab and lapatinib 1,000 mg PO daily.ResultsA total of 121 patients were randomly assigned. Diarrhea and dermatologic and hepatic toxicities were observed more frequently in patients receiving lapatinib. No episodes of congestive heart failure were observed. The rates of breast-conserving surgery were 66.7%, 57.9%, and 68.9% in arms A, B and C, respectively. The pCR rates were 25% (90% CI, 13.1% to 36.9%) in arm A, 26.3% (90% CI, 14.5% to 38.1%) in arm B, and 46.7% (90% CI, 34.4% to 58.9%) in arm C (exploratory P = .019).

CONCLUSION: The primary end point of the study was met, with a relative increase of 80% in the pCR rate achieved with chemotherapy plus trastuzumab and lapatinib compared with chemotherapy plus either trastuzumab or lapatinib. These data add further evidence supporting the superiority of a dual-HER2 inhibition for the treatment of HER2-positive breast cancer.

Chirurgie

Eur J Cancer. 2012 Mar 23. [Epub ahead of print]

Locoregional recurrence after breast-conserving therapy remains an independent prognostic factor even after an event free interval of 10years in early stage breast cancer.

Tanis E, van de Velde CJ, Bartelink H, van de Vijver MJ, Putter H, van der Hage JA.

Source

Department of Surgery, The Netherlands Cancer Institute, The Netherlands.

Abstract

INTRODUCTION: Locoregional recurrence (LRR) after breast-conserving therapy is a well-known independent risk factor associated with unfavourable long-term outcome. Controversy exists concerning the prognostic impact of a LRR after a very long event-free interval.

METHOD: Patients who underwent breast-conserving therapy for early stage breast cancer were pooled from four European Organisation for Research and Treatment of Cancer (EORTC) Breast Group trials. Only LRR as a first event was taken into account. Risk factors such as tumour size, nodal status, young age and chemotherapy were assessed in multivariate Cox regression analysis. LRR was used as a time-dependent variable in the landmark analysis for distant disease-free survival (DFS) and overall survival (OS). Patients were categorised as having at least 0, 5 or 10years event-free survival.

RESULTS: In total, 7751 early stage breast cancer patients were included with a median follow-up of 10.9years. Tumour size, nodal status, young age and chemotherapy are strong independent prognostic factors with a significant impact on long-term outcome, but lose their power and significance over time. Including all patients, LRR was the strongest prognostic factor for OS and distant DFS (resp. HR 5.01 and HR 5.31, p<0.001). In the subgroup of patients developing a LRR after at least 5 or 10years, LRR remained the strongest independent prognostic factor for OS (resp. HR 3.98, HR 4.96, p⩽0.001) and distant DFS (HR 4.42, HR 7.57 p<0.001).

CONCLUSION: This is the first study which shows LRR after breast-conserving therapy is a very strong, time-independent prognostic factor for long term outcome in early stage breast cancer patients. These findings suggest that a LRR after a long event-free interval seems to be an indicator rather than an instigator of subsequent distant disease.

Copyright © 2012 Elsevier Ltd. All rights reserved.

Eur J Cancer. 2012 Apr 4. [Epub ahead of print]

Mastectomy trends for early-stage breast cancer: A report from the EUSOMA multi-institutional European database.

Garcia-Etienne CA, Tomatis M, Heil J, Friedrichs K, Kreienberg R, Denk A, Kiechle M, Lorenz-Salehi F, Kimmig R, Emons G, Danaei M,Heyl V, Heindrichs U, Rageth CJ, Janni W, Marotti L, Turco MR, Ponti A.

Source

Breast Unit, Humanitas Cancer Center, Milan, Rozzano, Italy; EUSOMA Data Centre, Turin, Italy.

Abstract

INTRODUCTION: Recent single-institution reports have shown increased mastectomy rates during the last decade. Further studies aiming to determine if these reports could be reflecting a national trend in the United States of America (US) have shown conflicting results. We report these trends from a multi-institutional European database.

PATIENTS AND METHODS: Our source of data was the eusomaDB, a central data warehouse of prospectively collected information of the European Society of Breast Cancer Specialists (EUSOMA). We identified patients with newly diagnosed unilateral early-stage breast cancer (stages 0, I or II) to examine rates and trends in surgical treatment.

RESULTS: A total of 15,369 early-stage breast cancer cases underwent surgery in 13 Breast Units from 2003 to 2010. Breast conservation was successful in 11,263 cases (73.3%). Adjusted trend by year showed a statistically significant decrease in mastectomy rates from 2005 to 2010 (p=0.003) with a progressive reduction of 4.24% per year. A multivariate model showed a statistically significant association of the following factors with mastectomy: age <40 or ⩾70years, pTis, pT1mi, positive axillary nodes, lobular histology, tumour grade II and III, negative progesterone receptors and multiple lesions.

CONCLUSION: Our study demonstrates that a high proportion of patients with newly diagnosed unilateral early-stage breast cancer from the eusomaDB underwent breast-conserving surgery. It also shows a significant trend of decreasing mastectomy rates from 2005 to 2010. Moreover, our study suggests mastectomy rates in the population from the eusomaDB are lower than those reported in the US.

Ann Oncol. 2012 Apr 12. [Epub ahead of print]

Long-term cosmetic changes after breast-conserving treatment of patients with stage I-II breast cancer and included in the EORTC ‘boost versus no boost’ trial.

Immink JM, Putter H, Bartelink H, Cardoso JS, Cardoso MJ, van der Hulst-Vijgen MH, Noordijk EM, Poortmans PM, Rodenhuis CC,Struikmans H.

Source

Department of Radiotherapy, Medical Center, Reinier de Graaf Groep, Delft.

Abstract

BACKGROUND: In breast cancer treated with breast-conserving radiotherapy, the influence of the boost dose on cosmetic outcome after long-term follow-up is unknown.

PATIENTS AND METHODS: We included 348 patients participating in the EORTC ‘boost versus no boost’ mega trial with a minimum follow-up of 6 years. Digitalised pictures were analysed using specific software, enabling quantification of seven relative asymmetry features associated with different aspects of fibrosis.

RESULTS: After 3 years, we noted a statistically significantly poorer outcome for the boost patients for six features compared with those of the no boost patients. Up to 9 years of follow-up, results continued to worsen in the same magnitude for the both patient groups. We noted the following determinants for poorer outcome: (i) boost treatment, (ii) larger excision volumes, (iii) younger age, (iv) tumours located in the central lower quadrants of the breast and (v) a boost dose administered with photons.

CONCLUSIONS: A boost dose worsens the change in breast appearance in the first 3 years. Moreover, the development of fibrosis associated with whole-breast irradiation, as estimated with the relative asymmetry features, is an ongoing process until (at least) 9 years after irradiation.

Her2neu

Breast Cancer Res Treat. 2012 Apr 4. [Epub ahead of print]

Final results of a multicenter phase II clinical trial evaluating the activity of single-agent lapatinib in patients with HER2-negative metastatic breast cancer and HER2-positive circulating tumor cells. A proof-of-concept study.

Pestrin M, Bessi S, Puglisi F, Minisini AM, Masci G, Battelli N, Ravaioli A, Gianni L, Di Marsico R, Tondini C, Gori S, Coombes CR,Stebbing J, Biganzoli L, Buyse M, Di Leo A.

Source

Medical Oncology Unit, Hospital of Prato, Prato, Italy.

Abstract

This multicenter phase II trial was designed to evaluate the activity of lapatinib in metastatic breast cancer patients with HER2-negative primary tumors and HER2-positive circulating tumor cells (CTCs). In this study MBC patients with HER2-negative primary tumors and HER2-positive CTCs previously treated with at least a first-line therapy for metastatic disease received lapatinib 1500 mg/day. The CellSearch System(®) was used for CTCs isolation and bio-characterization. HER2 status was assessed on CTCs by immunofluorescence. A case was defined as CTCs positive if ≥2 CTC/7.5 ml of blood were isolated and HER2-positive if ≥50 % of CTCs were HER2-positive. 139 HER2-negative patients were screened, 96 patients were positive for CTCs (mean number of CTCs: 85; median number of CTCs: 19; range 2-1637). Seven of the 96 patients (7 %) had ≥50 % HER2-positive CTCs and were eligible for treatment with lapatinib. No objective tumor responses occurred in this population. In one patient, disease stabilization lasting 254 days (8.5 months) was observed. From the findings of this study, we concluded that a subset of patients with a HER2-negative primary tumor presents HER2-positive CTCs during disease progression, although the HER2 shift rate seems to be lower than previously reported. Despite the lack of objective response, the durable disease stabilization observed in one patient cannot rule out the hypothesis that lapatinib may have some activity in this patient population. However, considering that only 1/139 screened patients may potentially have derived benefit from this approach, future trials designed according to the presented strategy cannot be recommended.

Screening

JAMA. 2012 Apr 4;307(13):1394-404.

Detection of breast cancer with addition of annual screening ultrasound or a single screening MRI to mammography in women with elevated breast cancer risk.

Berg WA, Zhang Z, Lehrer D, Jong RA, Pisano ED, Barr RG, Böhm-Vélez M, Mahoney MC, Evans WP 3rd, Larsen LH, Morton MJ,Mendelson EB, Farria DM, Cormack JB, Marques HS, Adams A, Yeh NM, Gabrielli G; ACRIN 6666 Investigators.

Collaborators (43)