Alberto Luini

Publications (140)635.47 Total impact

• Article: Axillary dissection versus no axillary dissection in patients with sentinel-node micrometastases (IBCSG 23-01): a phase 3 randomised controlled trial.

  Viviana Galimberti, Bernard F Cole, Stefano Zurrida, Giuseppe Viale, Alberto Luini, Paolo Veronesi, Paola Baratella, Camelia Chifu, Manuela Sargenti, Mattia Intra, [......], Angelo Recalcati, David Littlejohn, Monika Bamert, Marco Colleoni, Karen N Price, Meredith M Regan, Aron Goldhirsch, Alan S Coates, Richard D Gelber, Umberto Veronesi
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  ABSTRACT: BACKGROUND: For patients with breast cancer and metastases in the sentinel nodes, axillary dissection has been standard treatment. However, for patients with limited sentinel-node involvement, axillary dissection might be overtreatment. We designed IBCSG trial 23-01 to determine whether no axillary dissection was non-inferior to axillary dissection in patients with one or more micrometastatic (≤2 mm) sentinel nodes and tumour of maximum 5 cm. METHODS: In this multicentre, randomised, non-inferiority, phase 3 trial, patients were eligible if they had clinically non-palpable axillary lymph node(s) and a primary tumour of 5 cm or less and who, after sentinel-node biopsy, had one or more micrometastatic (≤2 mm) sentinel lymph nodes with no extracapsular extension. Patients were randomly assigned (in a 1:1 ratio) to either undergo axillary dissection or not to undergo axillary dissection. Randomisation was stratified by centre and menopausal status. Treatment assignment was not masked. The primary endpoint was disease-free survival. Non-inferiority was defined as a hazard ratio (HR) of less than 1·25 for no axillary dissection versus axillary dissection. The analysis was by intention to treat. Per protocol, disease and survival information continues to be collected yearly. This trial is registered with ClinicalTrials.gov, NCT00072293. FINDINGS: Between April 1, 2001, and Feb 28, 2010, 465 patients were randomly assigned to axillary dissection and 469 to no axillary dissection. After the exclusion of three patients, 464 patients were in the axillary dissection group and 467 patients were in the no axillary dissection group. After a median follow-up of 5·0 (IQR 3·6-7·3) years, we recorded 69 disease-free survival events in the axillary dissection group and 55 events in the no axillary dissection group. Breast-cancer-related events were recorded in 48 patients in the axillary dissection group and 47 in the no axillary dissection group (ten local recurrences in the axillary dissection group and eight in the no axillary dissection group; three and nine contralateral breast cancers; one and nine regional recurrences; and 34 and 25 distant relapses). Other non-breast cancer events were recorded in 21 patients in the axillary dissection group and eight in the no axillary dissection group (20 and six second non-breast malignancies; and one and two deaths not due to a cancer event). 5-year disease-free survival was 87·8% (95% CI 84·4-91·2) in the group without axillary dissection and 84·4% (80·7-88·1) in the group with axillary dissection (log-rank p=0·16; HR for no axillary dissection vs axillary dissection was 0·78, 95% CI 0·55-1·11, non-inferiority p=0·0042). Patients with reported long-term surgical events (grade 3-4) included one sensory neuropathy (grade 3), three lymphoedema (two grade 3 and one grade 4), and three motor neuropathy (grade 3), all in the group that underwent axillary dissection, and one grade 3 motor neuropathy in the group without axillary dissection. One serious adverse event was reported, a postoperative infection in the axilla in the group with axillary dissection. INTERPRETATION: Axillary dissection could be avoided in patients with early breast cancer and limited sentinel-node involvement, thus eliminating complications of axillary surgery with no adverse effect on survival. FUNDING: None.
  The lancet oncology 03/2013; · 14.47 Impact Factor
• Article: Immunohistochemically Defined Subtypes and Outcome of Apocrine Breast Cancer.

  Silvia Dellapasqua, Patrick Maisonneuve, Giuseppe Viale, Giancarlo Pruneri, Giovanni Mazzarol, Raffaella Ghisini, Manuelita Mazza, Monica Iorfida, Nicole Rotmensz, Paolo Veronesi, Alberto Luini, Aron Goldhirsch, Marco Colleoni
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  ABSTRACT: BACKGROUND: Conflicting data are available in the literature on the outcome of invasive apocrine carcinoma (IAC), possibly related to a heterogeneous classification of these tumors. PATIENTS AND METHODS: A series of 6899 consecutive patients with invasive ductal carcinoma (IDC) not otherwise specified and 72 patients with immunohistochemically defined IAC who received surgery at the European Institute of Oncology between 1997 and 2005 were included. We then explored patterns of recurrence of IAC according to 2 immunohistochemically defined tumor subtypes: pure apocrine carcinoma (estrogen [ER] and progesterone [PgR] receptor negative, and AR positive) and apocrine-like carcinoma (ER or PgR positive and AR negative). RESULTS: The diagnosis of pure apocrine carcinoma was correlated with a worse outcome in terms of DFS (hazard ratio [HR] 1.7; 95% confidence interval [CI], 1.01-2.86; P = .0010) if compared with IDC, whereas IDC and apocrine-like breast cancers showed a similar outcome in terms of DFS and overall survival. Patients with pure apocrine carcinoma had an increased risk in contralateral breast cancer (HR, 4.12; 95% CI, 1.22-14; P = .02). CONCLUSION: Pure apocrine carcinoma represents a distinct subtype of breast cancer with a significantly worse DFS as compared with IDC. AR determination might have an important prognostic implication in IAC. Moreover, AR-targeted therapy should be further explored within these tumors.
  Clinical Breast Cancer 12/2012; · 2.38 Impact Factor
• Article: Accelerated partial breast irradiation with intraoperative electrons: Using GEC-ESTRO recommendations as guidance for patient selection.

  Maria Cristina Leonardi, Patrick Maisonneuve, Mauro Giuseppe Mastropasqua, Anna Morra, Roberta Lazzari, Veronica Dell'acqua, Annamaria Ferrari, Nicole Rotmensz, Claudia Sangalli, Alberto Luini, Umberto Veronesi, Roberto Orecchia
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  ABSTRACT: PURPOSE: To evaluate outcomes among early-stage breast cancer patients after conservative surgery and full-dose intraoperative radiotherapy electrons (ELIOT) by applying the Groupe Européen de Curiethérapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) recommendations for partial breast irradiation (APBI). MATERIALS AND METHODS: One-thousand eight-hundred and twenty-two patients were stratified into the three GEC-ESTRO categories of "good candidates", "possible candidates" and "contraindication" in order to assess outcomes. RESULTS: All the 1822 cases except 7 could be classified according to GEC-ESTRO groups: 573 patients met the criteria to be included in the "good candidates" group, 468 patients in the "possible candidates" group and 767 patients in the "contraindication" group. Median and mean follow-up length was 3.5years (range 0-10.5years) and 3.8years (SD 2.2), respectively. The 5-year rate of in-breast tumor reappearances for "good candidates", "possible candidates" and "contraindication" groups were 1.9%, 7.4% and 7.7%, respectively (p 0.001). While the regional node relapse showed no difference, the rate of distant metastases was significantly different in the "contraindication" group compared to the other two categories, having a significant impact on survival. CONCLUSIONS: Among the ELIOT population, the GEC-ESTRO recommendations enabled the selection of the good candidates with a low rate of local recurrence, but failed to differentiate the "possible candidates" and the "contraindication" groups.
  Radiotherapy and Oncology 12/2012; · 5.58 Impact Factor
• Article: Second malignancies following breast cancer treatment: a case-control study based on the Peridose methodology. Allegro project (task 5.4).

  Roberto Orecchia, Barbara A Jereczek-Fossa, Elena Rondi, Isa Bossi-Zanetti, Ilaria Meaglia, Rosa Luraschi, Maria Cristina Leonardi, Nicole Rotmensz, Edoardo Botteri, Cristiana Fodor, [......], Alberto Luini, Paolo Veronesi, Stefano Zurrida, Stefano Magrini, Wolfgang Doerr, Nicole Humble, Klaus R Trott, Andrea Ottolenghi, Vere Smyth, Umberto Veronesi
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  ABSTRACT: Aims and background. To calculate peripheral radiation dose to the second primary site in patients who have developed a second malignancy after breast cancer radiotherapy (index cases) and to compare it with dose in the analogous anatomical site in radiotherapy-treated breast cancer patients who did not experience a second malignancy (controls). To evaluate the feasibility of Peridose-software peripheral dose calculation in retrospective case-control studies. Material and study design. A case-control study on 12,630 patients who underwent adjuvant breast radiotherapy was performed. Minimum 5-year follow-up was required. Each index case was matched with 5 controls by 1) year of birth, 2) year of radiotherapy and 3) follow-up duration. Peridose-software was used to calculate peripheral dose. Results. 195 second cancers were registered (0.019% of all patients treated with adjuvant irradiation). Several methodological limitations of the Peridose calculation were encountered including impossibility to calculate the peripheral dose in the patients treated with intraoperative or external electron beam radiotherapy, in case of second tumors located at <15 cm from the radiotherapy field etc. Moreover, Peridose requires full radiotherapy data and the distance between radiotherapy field and second primary site. Due to these intrinsic limitations, only 6 index cases were eligible for dose calculation. Calculated doses at the second cancer site in index cases and in an analogous site in controls ranged between 7.5 and 145 cGy. The mean index-control dose difference was -3.15 cGy (range, -15.8 cGy and +2.7 cGy).Conclusions. The calculated peripheral doses were low and the index-control differences were small. However, the small number of eligible patients precludes a reliable analysis of a potential dose-response relationship. Large patient series followed for a long period and further improvement in the methodology of the peripheral dose calculation are necessary in order to overcome the methodological challenges of the study.
  Tumori. 11/2012; 98(6):715-21.
• Article: Heterogeneity of Triple-Negative Breast Cancer: Histologic Subtyping to Inform the Outcome.

  Emilia Montagna, Patrick Maisonneuve, Nicole Rotmensz, Giuseppe Cancello, Monica Iorfida, Alessandra Balduzzi, Viviana Galimberti, Paolo Veronesi, Alberto Luini, Giancarlo Pruneri, Luca Bottiglieri, Mauro G Mastropasqua, Aron Goldhirsch, Giuseppe Viale, Marco Colleoni
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  ABSTRACT: BACKGROUND: This study assesses outcome in terms of disease-free survival (DFS) and overall survival (OS) of special types of triple-negative breast cancer (TNBC). PATIENTS AND METHODS: We identified 8801 women with first primary nonmetastatic breast cancer operated on at the European Institute of Oncology between 1997 and 2005. Of these patients, 781 consecutive patients with immunohistochemically defined TNBC were selected for the analyses. We explored patterns of recurrence by histologic type. Median follow-up was 5.7 years (range 0-13 years). RESULTS: The 5-year DFS was 77% for TNBC, 68% for human epidermal growth factor receptor 2 (HER2)-positive breast cancer, and 84% and 95% for luminal B and luminal A breast cancer, respectively. From 781 TNBC subtypes, 693 cases (89%) were classified as ductal not otherwise specified (NOS) (invasive ductal carcinoma [IDC]), 29 were classified as apocrine (3.7%), 18 (2.3%) were classified as lobular, 10 (1.2%) were classified as adenoid cystic, and 10 (1.2%) were classified as metaplastic. Five-year DFS and OS were 77% and 84% for patients with ductal carcinoma, 56% and 89% for patients with metaplastic carcinoma, and both 5-year DFS and OS were 100% for patients with adenoid cystic and medullary carcinomas, respectively. CONCLUSION: Distinct prognostic implications may derive from the specific histotype of TNBC. The identification of these special types has a significant clinical utility and should be considered in therapeutic algorithms.
  Clinical Breast Cancer 10/2012; · 2.38 Impact Factor
• Article: Do Early Breast Cancer Patients with Only Sentinel Lymph Node Biopsy Experience Lower Psychological Morbidity Over Time?

  Florence Didier, Davide Radice, Andrea Maldifassi, Giovanna Gatti, Alberto Luini, Christina Leonardi, Francesca Lupo, Nicole Rotmensz, Barbara Santillo, Vivana Galimberti, Aron Goldhirsch
  The Breast Journal 10/2012; · 1.64 Impact Factor
• Article: Sarcoma of the Breast: Outcome and Reconstructive Options.

  Antonio Toesca, Gianluca Spitaleri, Tommaso De Pas, Edoardo Botteri, Oreste Gentilini, Luca Bottiglieri, Nicole Rotmentsz, Claudia Sangalli, Emilia Marrazzo, Enrico Cassano, Paolo Veronesi, Mario Rietjens, Alberto Luini
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  ABSTRACT: INTRODUCTION: Surgery is the mainstay of treatment for all breast sarcomas. The role of adjuvant chemotherapy and radiation therapy has not been clearly defined. The aim of this single-center retrospective study was to analyze prognostic factors, outcome, and recent advances. MATERIALS AND METHODS: Data from 203 patients with all breast sarcomas treated in a single center were collected from 1996 to 2010. Phyllodes tumors and metastatic disease at presentation were excluded from the population. Thirty-six women and 1 man were included in the analysis. Local recurrence, metastatic disease, survival, and reconstructive outcome were evaluated. RESULTS: Thirty-four patients out of 37 (91.9%) had an angiosarcoma and 3 had a stromal sarcoma (8.1%). Twenty-one patients (56.8%) had previously undergone breast radiation therapy for breast carcinoma or lymphoma. Twenty-six patients (70.3%) underwent mastectomy, 14 of whom (53.8%) with breast reconstruction. Thirty-six patients (97.3%) had free margins, 1 (2.7%) had a microscopically focally involved margin after surgery. Five patients received adjuvant chemotherapy and 6 received adjuvant radiation therapy. Median follow-up was 58 months (range, 4-146 months). Twelve sarcoma-related deaths were observed with a 5-year cumulative incidence of 43.4%. Twenty-four sarcoma-related events were observed with a 5-year cumulative incidence of 70.8%. The same figure was 49.7% in patients affected by primary sarcoma and 85.7% in patients with secondary sarcoma (P = .06). CONCLUSION: Secondary sarcomas were associated with a higher risk of events. Patients undergoing breast conservative surgery or reconstruction after mastectomy did not show a worse prognosis compared with patients undergoing mastectomy.
  Clinical Breast Cancer 10/2012; · 2.38 Impact Factor
• Article: Predictors of invasive breast cancer and lymph node involvement in ductal carcinoma in situ initially diagnosed by vacuum-assisted breast biopsy: Experience of 733 cases.

  Chiara Trentin, Valeria Dominelli, Patrick Maisonneuve, Simona Menna, Barbara Bazolli, Alberto Luini, Enrico Cassano
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  ABSTRACT: To predict presence of invasive component and nodal involvement in women diagnosed preoperatively with ductal carcinoma in situ (DCIS) by vacuum-assisted breast biopsy (VABB). We retrospectively analyzed 733 patients with preoperatively diagnosed DCIS, investigating the association of clinical-radiological variables with invasive component and nodal involvement. Mammographic size >20 mm and residual lesion on post-VABB mammogram were related to invasive component (both p < 0.0001) and nodal involvement (p = 0.001, p = 0.03). Age <40 years was associated with presence of invasive component (p = 0.003). By multivariate analysis residual disease was associated with invasive component, and mammographic tumor size >20 mm with nodal involvement, both highly significant. Older age, lesion <20 mm, and no residual lesion predict absence of invasion and no nodal involvement in VABB-diagnosed DCIS. However it would be imprudent to routinely forego sentinel node biopsy in such patients as non-negligible proportions of them have invasive disease.
  Breast (Edinburgh, Scotland) 07/2012; 21(5):635-40. · 2.09 Impact Factor
• Article: Repeating conservative surgery after ipsilateral breast tumor reappearance: criteria for selecting the best candidates.

  Oreste Gentilini, Edoardo Botteri, Paolo Veronesi, Claudia Sangalli, Andres Del Castillo, Bettina Ballardini, Viviana Galimberti, Mario Rietjens, Marco Colleoni, Alberto Luini, Umberto Veronesi
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  ABSTRACT: Mastectomy is still considered the treatment of first choice in patients with ipsilateral breast tumor recurrence (IBTR) after breast-conserving surgery (BCS) and whole-breast radiotherapy. We retrospectively evaluated 161 patients with invasive IBTR who underwent a second BCS in order to describe prognosis, determine predictive factors of outcome, and select the subset of patients with the best local control. Median follow-up after IBTR was 81 months. Median age at IBTR was 53 years. Five-year overall survival after IBTR was 84 % (95 % confidence interval [CI] 78-89). Five-year cumulative incidence of a second local event after IBTR was 29 % (95 % CI 22-37). At the multivariate analysis, IBTR size >2 cm and time to relapse ≤48 months significantly increased the risk of local reappearance (hazard ratio [HR] 3.3, 95 % CI 1.6-7.0; and HR 1.9, 95 % CI 1.1-3.5). The 5-year cumulative incidence of a further local reappearance of the tumor after repeating BCS was 15.2 % in the patients with IBTR ≤2 cm and time to IBTR >48 months, 31.2 % in the patients with IBTR ≤2 cm and time to IBTR ≤48 months, and 71.2 % in patients with IBTR >2 cm (P < 0.001). The best candidates for a second BCS are those with small (≤2 cm) and late (>48 months) IBTR. The information about the risk of a further local reappearance after repeating BCS should be shared with the patients in the decision making process.
  Annals of Surgical Oncology 05/2012; 19(12):3771-6. · 4.17 Impact Factor
• Article: Dual effect of metformin on breast cancer proliferation in a randomized presurgical trial.

  Bernardo Bonanni, Matteo Puntoni, Massimiliano Cazzaniga, Giancarlo Pruneri, Davide Serrano, Aliana Guerrieri-Gonzaga, Alessandra Gennari, Maria Stella Trabacca, Viviana Galimberti, Paolo Veronesi, Harriet Johansson, Valentina Aristarco, Fabio Bassi, Alberto Luini, Matteo Lazzeroni, Clara Varricchio, Giuseppe Viale, Paolo Bruzzi, Andrea Decensi
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  ABSTRACT: Metformin is associated with reduced breast cancer risk in observational studies in patients with diabetes, but clinical evidence for antitumor activity is unclear. The change in Ki-67 between pretreatment biopsy and post-treatment surgical specimen has prognostic value and may predict antitumor activity in breast cancer. After tumor biopsy, we randomly allocated 200 nondiabetic women with operable breast cancer to either metformin 850 mg/twice per day (n = 100) or placebo (n = 100). The primary outcome measure was the difference between arms in Ki-67 after 4 weeks adjusted for baseline values. Overall, the metformin effect on Ki-67 change relative to placebo was not statistically significant, with a mean proportional increase of 4.0% (95% CI, -5.6% to 14.4%) 4 weeks apart. However, there was a different drug effect depending on insulin resistance (homeostasis model assessment [HOMA] index > 2.8, fasting glucose [mmol/L] × insulin [mU/L]/22.5; P(interaction) = .045), with a nonsignificant mean proportional decrease in Ki-67 of 10.5% (95% CI, -26.1% to 8.4%) in women with HOMA more than 2.8 and a nonsignificant increase of 11.1% (95% CI, -0.6% to 24.2%) with HOMA less than or equal to 2.8. A different effect of metformin according to HOMA index was noted also in luminal B tumors (P(interaction) = .05). Similar trends to drug effect modifications were observed according to body mass index (P = .143), waist/hip girth-ratio (P = .058), moderate alcohol consumption (P = .005), and C-reactive protein (P = .080). Metformin before surgery did not significantly affect Ki-67 overall, but showed significantly different effects according to insulin resistance, particularly in luminal B tumors. Our findings warrant further studies of metformin in breast cancer with careful consideration to the metabolic characteristics of the study population.
  Journal of Clinical Oncology 05/2012; 30(21):2593-600. · 18.37 Impact Factor
• Article: Long-term side effects and cosmetic outcome in a pool of breast cancer patients treated with intraoperative radiotherapy with electrons as sole treatment.

  Maria Cristina Leonardi, Giovanni Battista Ivaldi, Luigi Santoro, Roberta Lazzari, Annamaria Ferrari, Anna Morra, Pietro Caldarella, Loredana Burgoa, Fabio Domenico Bassi, Claudia Sangalli, Nicole Rotmensz, Alberto Luini, Umberto Veronesi, Roberto Orecchia
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  ABSTRACT: To evaluate late toxicity and cosmetic outcome after intraoperative radiotherapy using electrons (ELIOT) as sole treatment modality in early breast cancer patients. A total of 119 patients selected randomly among 1200 cases was analyzed. Late toxicities were documented using the LENT-SOMA scoring system, cosmesis was evaluated with the Harvard scale, and a numeric rating scale was used to assess symptoms. After a median follow-up of 71 months, grade II fibrosis was observed in 38 patients (31.9%) and grade III fibrosis in 7 patients (5.9%). Postoperative complications (12.6%) did not correlate with late toxicity. Physicians and patients scored cosmesis as excellent or good in 84% and 77.3% of the cases, respectively. Patient satisfaction was higher than 90%. In the study, ELIOT gives low and acceptable long-term toxicity. A longer follow-up and a larger number of patients are needed to confirm these promising results.
  Tumori. 05/2012; 98(3):324-30.
• Article: Intraoperative avidination for radionuclide treatment as a radiotherapy boost in breast cancer: results of a phase II study with 90Y-labeled biotin

  Giovanni Paganelli, Concetta De Cicco, Mahila E. Ferrari, Giuseppe Carbone, Gianmatteo Pagani, Maria Cristina Leonardi, Marta Cremonesi, Annamaria Ferrari, Monica Pacifici, Amalia Di Dia, Rita De Santis, Viviana Galimberti, Alberto Luini, Roberto Orecchia, Stefano Zurrida, Umberto Veronesi
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  ABSTRACT: PurposeExternal beam radiotherapy (EBRT) after conservative surgery for early breast cancer requires 5–7weeks. For elderly patients and those distant from an RT center, attending for EBRT may be difficult or impossible. We investigated local toxicity, cosmetic outcomes, and quality of life in a new breast irradiation technique—intraoperative avidination for radionuclide therapy (IART)—in which avidin is administered to the tumor bed and 90Y-labelled biotin later administered intravenously to bind the avidin and provide irradiation. Reduced duration EBRT (40Gy) is given subsequently. MethodsAfter surgery, 50 (ten patients), 100 (15 patients) or 150mg (ten patients) of avidin was injected into the tumor bed. After 12-24 h, 3.7GBq 90Y-biotin (beta source for therapeutic effect) plus 185MBq 111In-biotin (gamma source for imaging and dosimetry) was infused slowly. Whole-body scintigraphy and SPECT/CT images were taken for up to 30 h. Shortened EBRT started 4weeks later. Local toxicity was assessed by RTOG scale; quality of life was assessed by EORTC QOL-30. ResultsOf 35 patients recruited (mean age 63years; range 42–74) 32 received IART plus EBRT. 100mg avidin provided 19.5 ± 4.0Gy to the tumor bed and was considered the optimum dose. No side-effects of avidin or 90Y-biotin occurred, with no hematological or local toxicity. Local G3 toxicity occurred in 3/32 patients during EBRT. IART plus EBRT was well accepted, with good cosmetic outcomes and maintained quality of life. ConclusionsIART plus reduced EBRT can accelerate irradiation after conservative breast surgery.
  European journal of nuclear medicine and molecular imaging 04/2012; 37(2):203-211. · 4.99 Impact Factor
• Article: Radioguided Sentinel Node Biopsy to Avoid Axillary Dissection in Breast Cancer

  Stefano Zurrida, Viviana Galimberti, Enrico Orvieto, Chris Robertson, Bettina Ballardini, Marta Cremonesi, Concetta De Cicco, Alberto Luini
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  ABSTRACT: Background: Sentinel node (SN) biopsy may predict axillary status in breast cancer. We retrospectively analyzed more than 500 SN cases, to suggest more precise indications for the technique.Methods99mTc-labeled colloid was injected close to the tumor; lymphoscintigraphy was then performed to reveal the SN. The next day, during surgery, the SN was removed by using a gamma probe. Complete axillary dissection followed, except in later cases recruited to a randomized trial. The SN was examined intraoperatively by conventional frozen section, in later cases by sampling the entire node and using immunocytochemistry.Results: In the first series, the SN was identified in 98.7% of cases; in 6.7%, the SN was negative but other axillary nodes were positive; in 32.1%, the SN was negative by intraoperative frozen section but metastatic by definitive histology, prompting introduction of the exhaustive method. In the randomized trial, the SN was identified in all cases so far, the false-negative rate is approximately 6.5%, and in 15 cases, internal mammary chain nodes were biopsied.Conclusions: SN biopsy can reliably assess axillary status in selected patients. The problems are the SN detection rate, false negatives, and the intraoperative examination, which can miss 30% of SN metastases. Our exhaustive method overcomes the latter problem, but it is time consuming.
  Annals of Surgical Oncology 04/2012; 7(1):28-31. · 4.17 Impact Factor
• Article: Metronomic chemotherapy combined with bevacizumab and erlotinib in patients with metastatic HER2-negative breast cancer: clinical and biological activity.

  Emilia Montagna, Giuseppe Cancello, Vincenzo Bagnardi, Davide Pastrello, Silvia Dellapasqua, Gino Perri, Giuseppe Viale, Paolo Veronesi, Alberto Luini, Mattia Intra, Angelica Calleri, Cristiano Rampinelli, Aron Goldhirsch, Francesco Bertolini, Marco Colleoni
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  ABSTRACT: The aim of this study was to determine the safety and efficacy of metronomic chemotherapy combined with targeted drugs in patients with metastatic breast cancer (MBC). We included 26 untreated patients with HER2-negative (HER-) MBC and poor hormone receptor expression. The analysis of the results suggests that the metronomic chemotherapy combined with bevacizumab and erlotinib is effective and well tolerated. The object of this study was to evaluate the safety and efficacy of metronomic chemotherapy in combination with bevacizumab and erlotinib in patients with HER2-negative (HER2(-)) metastatic breast cancer (MBC) and poor hormone receptor expression. Patients with untreated MBC were candidates to receive metronomic oral capecitabine (500 mg thrice daily) and cyclophosphamide (50 mg daily) plus bevacizumab (15 mg/kg every 3 weeks) and erlotinib (100 mg daily). Of 24 patients assessable for response, we observed 1 complete response (CR, 4%), 14 partial responses (58%), 5 patients with stable disease greater than 9 weeks' duration (SD, 21%), and 1 patient (4%) with early progression of disease. The overall clinical benefit (CB) (CR + partial response + SD > 24 weeks) was 75% (95% confidence interval [CI], 53%-90%). Median time to progression was 43 weeks (95% CI, 21-69). Patients with low levels of circulating endothelial progenitors (CEPs) at baseline had a significantly improved progression-free survival (PFS). Toxicity was generally mild. Grade 3 toxicity included diarrhea (n = 1), thrombosis (n = 1), and hypertension (n = 2). Grade 2 adverse events included diarrhea (n = 5), hand-foot syndrome (n = 13), and hypertension (n = 4). Treatment with metronomic chemotherapy in combination with bevacizumab and erlotinib was effective in HER2(-), estrogen receptor (ER)- and progesterone receptor (PR)-poor advanced breast cancer.
  Clinical Breast Cancer 04/2012; 12(3):207-14. · 2.38 Impact Factor
• Article: Axillary radiotherapy instead of axillary dissection: A randomized trial

  Stefano Zurrida, Roberto Orecchia, Viviana Galimberti, Alberto Luini, Irene Giannetti, Bettina Ballardini, Andrea Amadori, Giulia Veronesi, Umberto Veronesi, Italian Oncological Senology Group
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  ABSTRACT: BackgroundSurgical dissection of the axilla is a standard part of the treatment of breast cancer but, by itself, does not improve prognosis; furthermore, most patients with small-sized breast cancer and a clinically uninvolved axilla never develop axillary metastases. We evaluated disease-free and overall survival in patients with early breast cancer treated by breast-conservation surgery without dissection of acillary lymph nodes, receiving or not receiving axillary radiotherapy (RT). MethodsFrom 1995 to 1998, 435 patients older than 45 years with breast cancer up to 1.2 cm were randomized, 214 to breast conservation without axillary treatment and 221 to breast conservation plus axillary RT. ResultsAfter a follow-up of 28 to 68 months (median, 42 months), two women (1%) in the no axillary treatment group and one (.5%) in the axillary RT group developed axillary metastases. Rates of distant metastases and local treatment failure were also very low, and 5-year overall survival was 99%. ConclusionsAfter a mean of 46 months of follow-up, our results indicate that axillary dissection can be safely avoided in patients with very small invasive carcinomas and a clinically negative axilla. Whether axillary RT should be added can be assessed only by longer follow-up.
  Annals of Surgical Oncology 04/2012; 9(2):156-160. · 4.17 Impact Factor
• Article: Invasive lobular breast cancer: subtypes and outcome.

  Monica Iorfida, Eugenio Maiorano, Enrico Orvieto, Patrick Maisonneuve, Luca Bottiglieri, Nicole Rotmensz, Emilia Montagna, Silvia Dellapasqua, Paolo Veronesi, Viviana Galimberti, Alberto Luini, Aron Goldhirsch, Marco Colleoni, Giuseppe Viale
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  ABSTRACT: Invasive lobular carcinoma (ILC) is the most common "special type" of breast cancer. Although conflicting literature data are available on the outcome of ILC, recently reported data indicate that ILC carries a poorer prognosis if compared to invasive ductal carcinomas. We evaluated clinical and biological features of 981 consecutive patients with pT1-3, pN1-3 M0 ILC. Median follow-up was 7.4 years for survival. A total of 541 patients were classified as classic (55.8%), 146 alveolar (14.9%), 145 mixed non-classic (14.8%), 104 solid (10.6%), and 38 trabecular (3.9%). A statistically significant difference in the outcome was observed at multivariate analysis for patients with solid (HR 2.44, 95% CI 1.39-4.29 for OS; HR 1.92, 95% CI 1.29-2.88 for DFS) and mixed non-classic (HR 1.99, 95% CI 1.12-3.53 for OS) versus patients with classical ILC. A statistically significant difference in the risk of distant metastases was observed at multivariate analysis for patients with Luminal B (HR 2.56, 95% CI 1.38-4.76), HER2 positive (HR 7.80, 95% CI 1.55-39.3), and triple negative (HR 7.61, 95% CI 2.63-22.1) subtypes versus patients with Luminal A ILC. Age ≥70 years, tumor size and degree of nodal involvement were additional independent predictors of reduced overall survival. The outcome of ILC significantly correlated with histological and immunohistochemically defined molecular subtypes. New tailored strategies should be explored in these subgroups of patients with poor outcome.
  Breast Cancer Research and Treatment 03/2012; 133(2):713-23. · 4.43 Impact Factor
• Article: Increased mean corpuscular volume of red blood cells predicts response to metronomic capecitabine and cyclophosphamide in combination with bevacizumab.

  Silvia Dellapasqua, Vincenzo Bagnardi, Francesco Bertolini, Maria Teresa Sandri, Davide Pastrello, Giuseppe Cancello, Emilia Montagna, Alessandra Balduzzi, Patrizia Mancuso, Alberto Luini, Aron Goldhirsch, Marco Colleoni
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  ABSTRACT: There is an urgent need for the identification of commonly assessable predictive factors in the treatment of patients with metastatic breast cancer. During the course of a treatment including low dose metronomic oral cyclophosphamide and capecitabine plus i.v. bevacizumab (plus erlotinib in one third of the patients) for metastatic breast cancer, we observed that a relevant number of patients developed repeatedly elevated levels of mean corpuscular volume (MCV) of red blood cells without a significant fall in hemoglobin levels. We conducted a retrospective analysis on these 69 patients to evaluate if the increase in MCV could be associated to tumor response. During the course of treatment 42 out of 69 patients (61%) developed macrocytosis. Using Cox proportional hazards modeling that incorporated macrocytosis (MCV ≥ 100 fl) as a time-dependent covariate, macrocytosis resulted in a halved risk of disease progression (HR 0.45; 95% CI, 0.22-0.92, p-value 0.028). In a landmark analysis limited to patients with no sign of progression after 24 weeks of treatment, median time to progression was 72 weeks (48 weeks after landmark) in patients who had developed macrocytosis, and 43 weeks (19 weeks after landmark) in patients who had not (p=0.023). Macrocytosis inversely related to risk of disease progression in patients treated with metronomic capecitabine plus cyclophosphamide and bevacizumab for metastatic breast cancer. This finding may be explained through thymidylate synthase inhibition by capecitabine. Whether bevacizumab has a role in determining macrocytosis, similarly to what happens with sunitinib, has to be further investigated. If other studies will confirm our findings, macrocytosis might be used as an early marker of response during metronomic treatment with capecitabine and cyclophosphamide with or without bevacizumab.
  Breast (Edinburgh, Scotland) 02/2012; 21(3):309-13. · 2.09 Impact Factor
• Article: How do the ASTRO consensus statement guidelines for the application of accelerated partial breast irradiation fit intraoperative radiotherapy? A retrospective analysis of patients treated at the European Institute of Oncology.

  Maria Cristina Leonardi, Patrick Maisonneuve, Mauro Giuseppe Mastropasqua, Anna Morra, Roberta Lazzari, Nicole Rotmensz, Claudia Sangalli, Alberto Luini, Umberto Veronesi, Roberto Orecchia
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  ABSTRACT: To verify how the classification according to the American Society for Therapeutic Radiation Oncology (ASTRO) consensus statement (CS) for the application of accelerated partial breast irradiation (APBI) fits patients treated with intraoperative radiotherapy with electrons (ELIOT) at a single institution. The study included 1,822 patients treated with ELIOT as the sole radiation modality outside of a clinical trial at the European Institute of Oncology after breast-conserving surgery for invasive breast cancer, who were classified into CS groups of suitable, cautionary, and unsuitable. The outcome in terms of ipsilateral breast recurrence, regional node relapse, distant metastases, progression free-survival, cause-specific survival, and overall survival were assessed. All the 1,822 cases except for 25 could be classified according to ASTRO CS: 294 patients met the criteria for inclusion into the suitable group, 691 patients into the cautionary group, and 812 patients into the unsuitable group. The 5-year rate of ipsilateral breast recurrence for suitable, cautionary, and unsuitable groups were 1.5%, 4.4%, and 8.8%, respectively (p = 0.0003). Whereas the regional node relapse showed no difference, the rate of distant metastases was significantly different in the unsuitable group compared with the suitable and cautionary groups, having a significant impact on survival. In the context of patients treated with ELIOT, the ASTRO guidelines identify well the groups for whom APBI might be considered as an effective alternative to whole breast radiotherapy and also identify groups for whom APBI is not indicated.
  International journal of radiation oncology, biology, physics 01/2012; 83(3):806-13. · 4.59 Impact Factor
• Article: Breast cancer: from "maximum tolerable" to "minimum effective" treatment.

  Umberto Veronesi, Vaia Stafyla, Alberto Luini, Paolo Veronesi
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  ABSTRACT: Randomized trials have played a fundamental role in identifying better treatments for most type of diseases, especially in the oncological field. In breast cancer, the shift from "maximum tolerable" to "minimum effective" treatment has been evident since the 1970s and has been based on the results of international randomized trials. The progress of breast surgery represents an excellent model of the evolution of science and the aim of this article is to review the main randomized studies that changed everyday practice in breast surgery.
  Frontiers in oncology. 01/2012; 2:125.
• Article: Primary and secondary angiosarcomas of the breast: a single institution experience.

  Conceição Fraga-Guedes, Helenice Gobbi, Mauro Giuseppe Mastropasqua, Edoardo Botteri, Alberto Luini, Giuseppe Viale
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  ABSTRACT: Angiosarcomas of the breast (ASB) are rare, representing <1% of breast malignancies. They can develop as a primary or secondary malignancy, also called post-radiation angiosarcoma. The aim of the this study is to discuss diagnosis, treatment, and outcome of primary and secondary ASB patients, diagnosed and treated in a single institution, over a 10-year period and to further compare the two conditions. We retrieved 28 consecutive cases of ASB, diagnosed from 1999 to 2009 at the European Institute of Oncology. Clinical and pathologic findings and survival analyses were performed. Of the 28 cases (27 women and 1 man), eight were primary breast angiosarcomas (PBA) and 20 were secondary breast angiosarcomas (SBA). Median follow-up was 23 months (range 1-112 months). Type of treatment (conservative or radical surgery) did not affect survival in both types of angiosarcomas. The clinical course observed was characterized by a high rate of local recurrence rather than distant metastasis or death from disease. There was a correlation between histological grade and prognosis of angiosarcomas with high-grade tumors presenting worse prognosis. SBA had a poorer prognosis compared to PBA. Our data indicate that primary and secondary ASB are distinct clinical and pathological features. SBA showed worse prognosis and was more often diagnosed in the study period compared to PBA. Physicians who care for patients who have been treated with radiation must be aware of its potential to induce angiosarcoma and stay vigilant in its detection.
  Breast Cancer Research and Treatment 12/2011; 132(3):1081-8. · 4.43 Impact Factor